Colitis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

OLITIS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES J AMES N. P AR...

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OLITIS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2003 by ICON Group International, Inc. Copyright ©2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Colitis: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83833-X 1. Colitis-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on colitis. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON COLITIS ...................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Colitis.......................................................................................... 27 E-Journals: PubMed Central ....................................................................................................... 87 The National Library of Medicine: PubMed ................................................................................ 92 CHAPTER 2. NUTRITION AND COLITIS .......................................................................................... 137 Overview.................................................................................................................................... 137 Finding Nutrition Studies on Colitis......................................................................................... 137 Federal Resources on Nutrition ................................................................................................. 152 Additional Web Resources ......................................................................................................... 152 CHAPTER 3. ALTERNATIVE MEDICINE AND COLITIS.................................................................... 155 Overview.................................................................................................................................... 155 National Center for Complementary and Alternative Medicine................................................ 155 Additional Web Resources ......................................................................................................... 183 General References ..................................................................................................................... 192 CHAPTER 4. DISSERTATIONS ON COLITIS...................................................................................... 193 Overview.................................................................................................................................... 193 Dissertations on Colitis.............................................................................................................. 193 Keeping Current ........................................................................................................................ 194 CHAPTER 5. CLINICAL TRIALS AND COLITIS ................................................................................ 195 Overview.................................................................................................................................... 195 Recent Trials on Colitis.............................................................................................................. 195 Keeping Current on Clinical Trials ........................................................................................... 205 CHAPTER 6. PATENTS ON COLITIS ................................................................................................ 207 Overview.................................................................................................................................... 207 Patents on Colitis....................................................................................................................... 207 Patent Applications on Colitis ................................................................................................... 228 Keeping Current ........................................................................................................................ 260 CHAPTER 7. BOOKS ON COLITIS .................................................................................................... 261 Overview.................................................................................................................................... 261 Book Summaries: Federal Agencies............................................................................................ 261 Book Summaries: Online Booksellers......................................................................................... 263 The National Library of Medicine Book Index ........................................................................... 267 Chapters on Colitis..................................................................................................................... 269 Directories.................................................................................................................................. 286 CHAPTER 8. MULTIMEDIA ON COLITIS ......................................................................................... 289 Overview.................................................................................................................................... 289 Video Recordings ....................................................................................................................... 289 Bibliography: Multimedia on Colitis ......................................................................................... 290 CHAPTER 9. PERIODICALS AND NEWS ON COLITIS ...................................................................... 293 Overview.................................................................................................................................... 293 News Services and Press Releases.............................................................................................. 293 Newsletters on Colitis ................................................................................................................ 296 Newsletter Articles .................................................................................................................... 298 Academic Periodicals covering Colitis ....................................................................................... 299 CHAPTER 10. RESEARCHING MEDICATIONS ................................................................................. 301 Overview.................................................................................................................................... 301 U.S. Pharmacopeia..................................................................................................................... 301 Commercial Databases ............................................................................................................... 303

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Researching Orphan Drugs ....................................................................................................... 303 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 307 Overview.................................................................................................................................... 307 NIH Guidelines.......................................................................................................................... 307 NIH Databases........................................................................................................................... 309 Other Commercial Databases..................................................................................................... 312 The Genome Project and Colitis................................................................................................. 312 APPENDIX B. PATIENT RESOURCES ............................................................................................... 317 Overview.................................................................................................................................... 317 Patient Guideline Sources.......................................................................................................... 317 Associations and Colitis............................................................................................................. 329 Finding Associations.................................................................................................................. 332 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 335 Overview.................................................................................................................................... 335 Preparation................................................................................................................................. 335 Finding a Local Medical Library................................................................................................ 335 Medical Libraries in the U.S. and Canada ................................................................................. 335 ONLINE GLOSSARIES................................................................................................................ 341 Online Dictionary Directories ................................................................................................... 342 COLITIS DICTIONARY............................................................................................................... 343 INDEX .............................................................................................................................................. 455

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with colitis is indexed in search engines, such as www.google.com or others, a nonsystematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about colitis, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to colitis, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on colitis. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to colitis, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on colitis. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON COLITIS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on colitis.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and colitis, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “colitis” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Medical Treatment of Severe Ulcerative Colitis Source: Alimentary Pharmacology and Therapeutics. 16(Supplement 4): 7-12. July 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Approximately 15 percent of patients with ulcerative colitis (UC, a type of inflammatory bowel disease, or IBD) have a severe attack requiring hospitalization at some time during their illness. This article reviews the medical treatment of severe UC. The authors note that hospitalization leads to a remission in 60 to 80 percent of patients. However, nonresponders may require a total colectomy. Mortality (death) in severe episodes of UC decreased from 31 to 61 percent in the 1950s to 5 to 9 percent in the

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1960s, thanks to the introduction of steroids and to a policy of early colectomy. Recently, some new drugs have been shown to be effective in the treatment of severe steroidrefractory (resistant) UC. This review article concludes on the clinical evaluation, prognostic factors, and new developments in medical therapy in severe UC. The authors also report on a retrospective evaluation of a consecutive series of patients with severe UC who were admitted to a Gastroenterology Department in Torino, Italy. 1 figure. 3 tables. 37 references. •

Prevalence of Celiac Disease in Collagenous and Lymphocytic Colitis Source: Canadian Journal of Gastroenterology. 14(11): 919-921. December 2000. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail: [email protected]. Summary: Both collagenous and lymphocytic colitis (inflammation of the colon) have been described in patients with celiac disease, suggesting an association between the conditions. Over the past few years, the availability, sensitivity, and specificity of serological (blood) markers for celiac disease have improved; the most recent advancement is the description of tissue transglutaminase as the major antigen for endomysium antibody. This article describes how a quantitative ELISA test was used to measure titres of immunoglobulin A (IgA) antibody to tissue transglutaminase (tTG) along with an immunofluorescent technique for IgA endomysium antibody (EmA) in 15 patients with lymphocytic colitis and 8 with collagenous colitis to determine whether celiac disease latency could be detected. One patient with lymphocytic colitis demonstrated both elevated titres of tTG antibody and positive EmA, and small bowel biopsy confirmed celiac disease. One patients with collagenous colitis had a slightly elevated titre of tTG antibody with a negative EmA, and results of a small bowel biopsy were normal. Three other patients with lymphocytic colitis were already treated for previously diagnosed celiac disease. The prevalence of celiac disease occurring in lymphocytic colitis was found to be 27 percent, but no cases of celiac disease in association with collagenous colitis were found. 1 figure. 1 table. 23 references.

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Pseudomembranous Colitis: An Update Source: Canadian Journal of Gastroenterology. 14(1): 51-56. January 2000. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail: [email protected]. Summary: Clostridium difficile is the most common nosocomial infection of the gastrointestinal tract. Most cases are associated with antibiotic therapy that alters the fecal flora, allowing overgrowth of C. difficile with production of its toxins. This article focuses on the diagnosis and therapy for C. difficile associated disease, as well as on illness complicated by ileus, toxic megacolon, or recurrences. Diagnosis is made by detection of the organism or toxin in the stools. A variety of different tests can be used, but none is ideal. A stool culture can be positive in someone without diarrhea (i.e., a carrier). While the cytotoxin is the gold standard, it is expensive, and there is a delay before results are available. Thus, many laboratories use the enzyme linked immunoassay tests to detect toxin of C. difficile because they are a more rapid screen. First line therapy for C. difficile disease should be metronidazole 250 mg four times a day for 10 days. Vancomycin should be reserved for severe cases where metronidazole has failed or where metronidazole cannot be tolerated or is contraindicated. Recurrent C. difficile disease is a particularly vexing clinical problem. A variety of biotherapeutic approaches have been used. The authors caution that retreatment with antibiotics is

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almost always necessary. In addition, the nonpathogenic yeast Saccharomyces boulardii has been shown to be of benefit as an adjunct in preventing further recurrences. 2 tables. 48 references. •

Budesonide Treatment for Collagenous Colitis: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial Source: Gastroenterology. 123(4): 978-984. October 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: Collagenous colitis is an idiopathic (of unknown cause) microscopic colitis characterized by chronic watery diarrhea, a typical subepithelial collagen layer, and lymphoplasmacellular infiltration. This article reports on a randomized, double-blind, placebo-controlled multicenter study that investigated the effect of budesonide on symptoms and histology in patients with collagenous colitis. Patients with chronic diarrhea and histologically proven collagenous colitis were randomized to receive either oral budesonide 9 milligrams per day for 6 weeks, or placebo; 45 patients were available for per protocol analysis. The rate of clinical remission was significantly higher in the budesonide group than in the placebo group. Histologic improvement was observed in 14 patients of the budesonide group (60. 9 percent) and in 1 patient of the placebo group (4.5 percent). Two patients in the budesonide group (7.7 percent) and 1 patient in the placebo group (4.0 percent) discontinued treatment prematurely because of side effects. The authors conclude that oral budesonide (Entocort capsules) is an effective and safe treatment modality for patients with collagenous colitis. Long-term follow up of these patients is necessary to investigate whether clinical and histologic remission is sustained. 2 figures. 5 tables. 34 references.

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Microscopic Colitis Source: Gastroenterology Nursing. 22(4): 167-169. July-August 1999. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (410) 528-8555. Summary: Endoscopy nurses and associates occasionally find themselves assisting with colonoscopies in which biopsy specimens are obtained from normal appearing mucosa to rule out microscopic colitis. This article reports on a review of the literature that was undertaken to learn more about this uncommon but troublesome cause of chronic diarrhea in patients. The author notes that the few studies completed have been small and have yielded some conflicting and controversial data regarding many aspects of the two forms of microscopic colitis. Some findings, however, have been consistent and may help to provide a better understanding of this challenging syndrome for gastroenterology nurses. Several authors have described similar clinical features in microscopic colitis, typically chronic watery, nonbloody diarrhea with 5 to 10 (but as many as 30) stools per day. The lack of alternating constipation helps to distinguish the disease from irritable bowel syndrome (IBS). Colorectal biopsies are needed to make a diagnosis, regardless of the appearance of the colonic mucosa on colonoscopy. The inflammatory changes seen in collagenous colitis, ulcerative colitis (UC), and Crohn's disease differ from one another. A few patients improve initially with symptomatic treatment such as avoidance of lactose containing food, NSAIDs (nonsteroidal antiinflammatory drugs), and caffeine; use of antimotility and bulking agents; and ingestion of a low fat diet if steatorrhea (fatty stools) is present. Usually, however, it is necessary to treat these patients with antiinflammatory agents such as sulfasalazine or

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5ASA. Corticosteroids may be added if there is no response to these medications. The author concludes that gastroenterology and endoscopy nurses and associates who familiarize themselves with these diseases improve the quality of care delivered to their patients, especially in the form of patient education. 7 references. •

Nutritional Therapies for Ulcerative Colitis: Literature Review, Chart Review Study, and Future Research Source: Alternative Therapies in Health and Medicine. 6(1): 55-63. January 2000. Contact: Available from Innovision Communications. 101 Columbia, Aliso Viejo, CA 92656. (800) 899-1712. Fax (949) 362-2022. E-mail: [email protected]. Website: www.healthonline.com/altther.htm. Summary: Few clinical studies suggest a significant influence of diet or nutritional supplementation on ulcerative colitis (UC). One reason is that UC, like many chronic diseases, is multifactorial. This article describes and reviews the relevant literature on UC, including studies of diet and intravenous therapy; nutritional status and nutritional supplementation; and bowel flora and immune function and their influences. Also, results of a retrospective chart review study that was done at a complementary medicine office are presented. Finally, suggestions for future research are discussed based on a nutritional model of UC. The authors hope that, taken together, these areas will clarify the current status of UC research and promote the types of investigations that are necessary to establish the validity of nutritional influences on UC, as well as the mechanisms that are involved. The authors conclude that their retrospective chart review study suggests that a dietary and nutritional supplementation regimen may significantly benefit UC patients. The study finding is based on significant improvements in symptoms and medication dosage needed to control symptoms. One figure offers a multifactorial model of the use of nutritional therapy in UC. 3 figures. 4 tables. 65 references.

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Crohn's Disease and Ulcerative Colitis Are Associated with the DNA Repair Gene MLH1 Source: Annals of Surgery. 225(6): 718-725. June 1997. Contact: Available from Lippincott-Raven Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030. Summary: Identification of genes involved in the etiology of inflammatory bowel disease (IBD) may lead to the development of markers that objectively can define disease and permit therapy. The treatment of Crohn's disease of the colon and ulcerative colitis also is complicated by difficulties in differentiating the two conditions. This article reports on a study undertaken to determine whether there is an association between Crohn's disease and ulcerative colitis (two types of IBD) with MLH1, a DNA repair gene. The DNA and clinical data were obtained on 126 unrelated individuals (45 with Crohn's disease, 36 with ulcerative colitis, and 45 control subjects without intestinal disease). Polymerase chain reaction (PCR) products were analyzed. The association between single haplotypes and disease was expressed as relative odds. The authors found that novel associations exist between IBD and two genetic markers within, and one nearby, the DNA mismatch repair gene MLH1. Two categories of haplotypes were associated with the family history of Crohn's disease or ulcerative colitis. The significant association of MLH1 exon 15/D3S1611 haplotype with colonic Crohn's disease, as opposed to ulcerative colitis, may prove to be useful in distinguishing these two diseases. This information may also be helpful in the identification of individuals who

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are at high risk of developing IBD. Appended to the article is a discussion by three specialists in the field. 2 figures. 3 tables. 24 references. •

Is Ileal Pouch-Anal Anastomosis Really the Procedure of Choice for Patients with Ulcerative Colitis? Source: Diseases of the Colon and Rectum. 41(1): 41-45. January 1998. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-6423 or (410) 528-8555. Summary: Ileal pouch-anal anastomosis is widely claimed to have replaced total proctocolecotomy with ileostomy as the 'procedure of choice' for ulcerative colitis (UC), largely on the basis of a perceived improved quality of life (QOL). There exists relatively little support for this assertion in the literature. This article reports on a study undertaken to determine if informed patients choosing total proctocolectomy with ileostomy have a similar QOL to those who choose ileal pouch-anal anastomosis. All patients with UC referred to a single surgeon and deemed an appropriate surgical candidate were educated about the available surgical options, and then offered a choice between the two options. Age, gender, and complications (including pouchitis) were recorded prospectively, and all patients were questioned regarding functional outcome and level of satisfaction. They were then asked to complete a slightly modified Inflammatory Bowel Disease Questionnaire, which was analyzed by categoric and overall scores. Sixty-seven patients underwent elective surgery for UC during the study period: 55 patients chose ileal pouch-anal anastomosis and 12 had total proctocolectomy with ileostomy. The groups were similar except for younger age and longer followup in the ileal pouch-anal anastomosis group. Patients undergoing the ileal pouch procedure had significantly more short term or long term complications (49 versus 8 percent), with pouchitis being the most frequent complication. There was no difference in level of satisfaction between the two groups, and no patients in either group wished they had undergone the other procedure. Patients who undergo ileal pouch-anal anastomosis can expect a high level of satisfaction, with a good QOL. However, educated patients choosing an ileostomy can achieve the same quality of life, without the higher complication rate associated with a pelvic pouch. 2 figures. 4 tables. 10 references. (AAM).

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Management Strategies for C. Difficile Colitis Source: IM. Internal Medicine. 20(8): 26-29. August 1999. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Summary: Infections caused by Clostridium difficile are very common, especially in hospitalized patients. In this article, the author reviews the pathophysiology of C. difficile, the clinical features of infections, appropriate diagnostic testing, and treatment regimens for this pathogen. There are two patient populations that appear to be particularly vulnerable to C. difficile infection: patients receiving antibiotics who are exposed to an environmental source of C. difficile (in the hospital, for example); and carriers of C. difficile who are subsequently treated with an antibiotic that allows the bacteria to proliferate. Specific antibiotics that put patients at risk for infection with C. difficile include ampicillin, amoxicillin, clindamycin, and cephalosporins. A wide range of conditions are associated with C. difficile infection: asymptomatic carrier state, antibiotic associated diarrhea without colitis, antibiotic associated colitis without pseudomembrane formation, pseudomembranous colitis, fulminant colitis with toxic

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megacolon, C. difficile complicating inflammatory bowel disease (IBD), and nonantibiotic associated C. difficile colitis. The gold standard laboratory test for C. difficile colitis is the tissue culture bioassay for toxin B performed on the patient's stool. The goal of therapy in C. difficile infection is to eliminate the organism from the feces. Oral metronidazole (250 mg four times per day) is the drug of choice for treating C. difficile infection because of the drug's comparable efficacy and lower cost compared to vancomycin. The author concludes by reviewing the treatment of recurrent infection and summarizing the key points of patient care management. 1 figure. 2 tables. 18 references. •

When to Suspect Ischemic Colitis: Why Is This Condition So Often Missed or Misdiagnosed? Source: Postgraduate Medicine. 105(4): 177-180, 183-184, 187. April 1999. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: Ischemic colitis is the most common ischemic injury (injury due to deficiency of blood, usually from constriction or obstruction of blood vessels) of the gastrointestinal tract and one of the most common disorders of the large bowel in the elderly. In this article, the authors review predisposing and identifying factors, the usual course of the disease, and diagnostic and management measures. A sudden drop in the colonic blood supply is key to its development, but in most patients, no specific cause can be identified. Presentation can range from acute abdominal cramping, distention, and bloody diarrhea to mild pain, but typically patients are otherwise well. Diagnosis is challenging because of the wide disparity between symptoms and objective findings. Common predisposing factors are atherosclerosis, shock, and congestive heart failure, but often, elderly patients have no obvious predisposing or precipitating factors. Common early radiographic signs are bowel wall thickening with thumbprinting, and later, ulceration and strictures may be found. Endoscopy is valuable in revealing the sharp demarcation between viable and necrotic colonic mucosa that is a strong indicator of ischemia. Within 48 hours, most patients show favorable response to conservative measures consisting of intravenous hydration, bowel rest, antibiotic therapy, and correction of precipitating processes. Vasoconstricting drugs and corticosteroids are contraindicated. When surgical intervention is indicated, it usually consists of resection of the ischemic segment and exteriorization of the remaining ends of the bowel. 3 figures. 1 table. 10 references. (AA-M).

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Prevalence of Appendectomy Among Ulcerative Colitis Patients and Their Relatives Source: European Journal of Gastroenterology and Hepatology. 13(10): 1231-1233. October 2001. Contact: Available from Lippincott Williams and Wilkins. 241 Borough High Street, London SE1 1GB, UK 44(0)20-7940-7502. Fax: 44(0)20-7940-7574. Website: http://www.eurojgh.com/. Summary: It has been suggested that appendectomy (removal of the appendix) may protect against ulcerative colitis (UC). However, the incidences of appendectomy and UC in developed countries have diverged over the last 50 years, possibly as a consequence of environmental factors. This study was undertaken to determine whether the incidence of appendectomy is lower in patients with UC than in the general population. Patients with UC (n = 153), their relatives (n = 116), and members of the general population (n = 306) that had been matched for age, sex, and educational status

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were studied. Six percent of UC patients had undergone appendectomy. The corresponding figure for non family controls was 20 percent. The rate of appendectomy within families (cases plus siblings) was 17 of 269 patients (6.3 percent) and was similar to that for UC patients alone. A negative association between appendectomy and UC exists in our patients with UC. In addition, the appendectomy rate in families of UC patients was lower than that in the general population, possibly implying that common environmental and genetic factors could play an important role in the divergent incidences of appendicitis and UC over the last 50 years. 2 tables. 18 references. •

Critical Approach to New Forms of Treatment of Crohn's Disease and Ulcerative Colitis Source: Alimentary Pharmacology and Therapeutics. 16 (Supplement 4): 53-58. July 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Most patient with inflammatory bowel disease (IBD) can be managed with conventional immunosuppressive therapy. However, the recent increase in knowledge of inflammatory mechanisms and the high incidence of toxicity with prolonged steroid use, together with the fact that controlled trials have clearly shown that glucocorticosteroids do not maintain remission, warrants a rational approach to the choice of newer and less well tested therapeutic approaches in those patients who are not responding effectively to the standard treatment. In this review article, the authors offer a critical approach to the newer forms of treatment in the management of severe cases of IBD. 45 references.

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Surgical Therapy for Ulcerative Colitis and Crohn's Disease Source: Gastroenterology Clinics of North America. 28(2): 371-390. June 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Over the past two decades, there has been considerable progress in the surgical management of inflammatory bowel disease (IBD). This article reviews the surgical therapy for ulcerative colitis (UC) and Crohn's disease (CD). Crohn's disease is a chronic, nonspecific inflammatory disease of the gastrointestinal tract of unknown cause. It involves mainly the ileum, colon, and rectum, most often producing symptoms of obstruction or localized perforation with fistula. Although surgical treatment is palliative, operative excision in combination with strictureplasty, where appropriate, provides effective symptomatic relief and reasonable long term benefit. Chronic ulcerative colitis is a diffuse inflammatory disease of the mucosal lining of the colon and rectum. Total removal of the colon and rectum provides a complete cure. Newer surgical alternatives have eliminated the need for a permanent ileostomy following definitive resection of the involved colon and rectum. 7 figures. 2 tables. 42 references. (AA-M).

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Screening and Surveillance of Ulcerative Colitis Source: Gastrointestinal Endoscopy Clinics of North America. 7(1): 129-145. January 1997.

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Contact: Available from W.B. Saunders Company. Periodicals Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 654-2452. Summary: Patients with longstanding ulcerative colitis (UC) are at a higher risk of developing cancer than the normal population. In this article, the author reviews guidelines for the screening and surveillance of cancer risk in people with UC. The relative risk is difficult to assess because published figures vary markedly. A number of centers have instituted annual colonoscopy screening for patients in the at-risk group. No randomized controlled clinical trials have been undertaken using mortality as end point and power calculations suggest that to obtain a useful answer it is necessary to randomize over 4,000. This number is 10 times larger than the largest surveillance study reported to date and it is unlikely that it will ever be undertaken. A critical analysis of the descriptive studies published to date suggests that there may be some benefit from surveillance, but if so it amounts to a saving of perhaps one life for every 200 to 400 colonoscopies. The author concludes that it is better to adopt a flexible and pragmatic approach to the surveillance of patients with UC, providing patients themselves with the information that is available and drawing attention to the advantages and disadvantages of longterm regular colonoscopy. 1 figure. 66 references. (AA-M). •

Ulcerative Colitis of the Appendix ('Ulcerative Appendicitis') Mimicking Acute Appendicitis Source: Canadian Journal of Gastroenterology. 15(3): 201-204. March 2001. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail: [email protected]. Summary: The appendix may be involved in ulcerative colitis (UC, a type of inflammatory bowel disease), in the setting of either diffuse or distal disease, and is usually diagnosed incidentally at the time of proctocolectomy (surgery to treat the UC). This article describes a patient in whom a rare case of 'ulcerative appendicitis' occurring on a background of clinically quiescent (no active symptoms) UC presented with the signs and symptoms of acute appendicitis. Prior to this presentation, the patient's UC was in remission for over 2 years. The patient was treated with laparotomy and the appendix was removed. Pathology showed acute inflammation confined to the mucosa, with neutrophilic crypt epithelial infiltration (cryptitis) and crypt abscesses consistent with appendix involvement by UC. Following appendectomy, the patient made a rapid and uneventful recovery; he was asymptomatic one day after the operation and was discharged home on day 2. Six months later, the colitis remained in complete clinical remission, and there has been no recurrence of right lower quadrant symptoms. The authors suggest that this patient's acute appendiceal pain syndrome derived from a complex interplay of mucosal immune, vascular, and neurogenic factors, driven by a localized, active focus of UC. Appendectomy provided both the diagnosis and the cure of this acute illness. The authors conclude that although rare (and perhaps underrecognized), acute right lower quadrant pain in the setting of clinically quiescent UC may herald active ulcerative appendicitis, rather than typical suppurative appendicitis. 1 figure. 24 references.

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Sensorineural Hearing Loss and Ulcerative Colitis Source: Journal of Laryngology and Otology. 111(3): 277-278. March 1997. Contact: Available from Headley Brothers Ltd. The Invicta Press, Ashford, Kent, England TN24 8HH. Fax 01483-451874.

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Summary: The association of sensorineural hearing loss and ulcerative colitis is well documented and it is speculated that this is autoimmune in origin. This article reports the case of a 12 year old boy who developed acute onset asymmetrical hearing loss, at the same time as a diagnosis of ulcerative colitis (UC) was made. He was treated with olsalazine and prednisolone for three months; his bowel symptoms were controlled and his hearing improved almost immediately. Four years after the onset of disease, he experienced bilateral, profound sensorineural hearing loss in spite of good control of his bowel disease. Tests of immune function showed a raised IgA suggestive of chronic immune response, positive anti-nuclear antibodies, and an ESR of 35 mm per hour. The patient's hearing thresholds did not improve following maximal steroid therapy. Treatment with immunosuppressive drugs was offered to the patient but he refused this line of treatment after the potential side effects were explained to him. Immunological tests may provide a clue as to the etiology of suspected cases of autoimmune inner ear disease. The authors stress that immediate treatment with steroids, with or without immunosuppressive therapy, is essential since delay may lead to irreversible hearing loss. 3 figures. 11 references. (AA-M). •

Is Maintenance Therapy Always Necessary for Patients with Ulcerative Colitis in Remission? Source: Alimentary Pharmacology and Therapeutics. 13(3): 373-379. March 1999. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: The efficacy of sulfasalazine and mesalazine in preventing relapse in patients with ulcerative colitis (UC) is well known. It is less clear how long such maintenance should be continued, and if the duration of disease remission is a factor that affects the risk of recurrence. This article reports on a study undertaken to determine whether the duration of remission affects the relapse rate by comparing the efficacy of a delayed release mesalazine against placebo in patients with UC and whose remission is of short or long duration. The study included 112 patients (66 men, 46 women, mean age 35 years) whose intermittent chronic UC in clinical, endoscopic and histologic remission with sulfasalazine or mesalazine for at least 1 year. Patients were stratified according to the length of their remission, prior to randomization into group A (in remission from 1 to 2 years) or group B (in remission for over 2 years, median 4 years). Patients were treated daily with 1.2 grams of oral mesalazine, for a followup period of 1 year. In group A, while no difference was found between the two treatments after 6 months, mesalazine was significantly more effective than placebo in preventing relapse at 12 months. By contrast, in group B, no statistically significant difference was observed between the two treatments, either at 6 or 12 months. Patients in group B were older, and the disease and remission had lasted longer in their case. The authors conclude that mesalazine prophylaxis is necessary for the prevention of relapse by patients with UC in remission for less than 2 years. This study casts doubt on whether continuous maintenance treatment is necessary in patients with prolonged clinical, endoscopic, and histologic remission, and who are at very low risk of relapse. 2 figures. 1 table. 20 references. (AA-M).

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Induction and Maintenance of Clinical Remission by Interferon-B in Patients with Steroid-Refractory Active Ulcerative Colitis: An Open Long-term Pilot Trial Source: Alimentary Pharmacology and Therapeutics. 16(7): 1233-1239. July 2002.

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Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: The imbalance of pro and anti-inflammatory cytokines plays an important role in the pathogenesis (development) of inflammatory bowel disease (IBD). Shifting this disturbed ratio by means of TNF antibodies or interferon has been shown to be helpful in treating Crohn's disease (a type of IBD) and multiple sclerosis, respectively. This article reports on a pilot study that investigated whether interferon beta can induce clinical remission in patients with corticoid-refractory ulcerative colitis (UC, another type of IBD, n = 25). Twenty-two of the 25 patients (88 percent) went into remission during induction treatment. Mean time to response was 3.0 weeks (plus or minus 1.3 weeks); mean length of remission was 13.0 months (plus or minus 19.7 months). Only eight of 22 patients in remission relapsed during maintenance treatment. Five of these went into remission again after increasing the dose. Adverse events consisted of slight to moderate flu-like symptoms and slight to moderate hair loss in five of 15 female patients. The authors conclude that, although this open pilot study included only a small number of patients, the high response rate suggests that interferon beta may be a safe and effective treatment for steroid refractory active UC. 31 figure. 4 tables. 33 references. •

Clinical Evaluation and Management of Acute Severe Colitis Source: Inflammatory Bowel Diseases. 6(3): 214-227. August 2000. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030. Fax (301) 824-7390. Summary: The patient with acute severe colitis usually presents with frequent diarrheas that are more or less bloody. Fever and abdominal pain occur, but not always. This review article concentrates on the clinical evaluation, imaging, therapy, and prognostic factors in acute severe colitis of idiopathic (unknown) as well as infectious origin. The authors note that an immediate rigid rectosigmoidoscopy is essential for diagnosis and quick fecal sampling for cultivation of fecal pathogens, including Clostridium difficile toxin if there is suspicion of such an infection. The medical history and rectosigmoidoscopic appearance is usually sufficient to make a preliminary diagnosis of ulcerative colitis (UC). The next step is to evaluate the severity of the attack, extent of inflammation in the colon, and prognostic factors. Plain abdominal x-ray is often sufficient for a preliminary opinion about the extent of disease if the lumen is outlined by gas. The authors describe the superiority of colonoscopy performed at an early state, compared to other imaging modalities. Colonoscopy is the most adequate technique to evaluate both the extent and degree of inflammation, and the degree of ulceration. The introduction of early stage surgery resulted in a dramatic decrease in mortality due to severe attacks of UC. However, intensive medical treatment (rather than surgery) of a severe or moderately severe attack of UC may be followed by longstanding remission. This intensive treatment is based on corticosteroids, total parenteral nutrition (TPN), bowel rest, and antibiotics. Other treatments discussed include cyclosporine A, tacrolimus, anti tumor necrosis factor (TNF) alpha; the authors also discuss factors predicting outcome. A short section on Crohn's disease is followed by a section on acute infectious colitis, including the role of various pathogens, including Campylobacter jejuni, Yersinia enterocolitica, Escherichia coli, Salmonella, Shigella, Aeromonas, Clostridium difficile, Entamoeba histolytica, and cytomegalovirus. 188 references.

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Update in Medical Therapy of Ulcerative Colitis: A Practical Approach Source: Journal of Clinical Gastroenterology. 34(4): 397-407. April 2002. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: The vast array of medications use in the therapy of inflammatory bowel disease (IBD) often confounds the clinician in the choice of specific agents regarding the balance between safety and efficacy. This review article surveys and evaluates the currently available IBD therapies as well as those used in clinical trials of ulcerative colitis (UC). The author provides the busy clinician with a practical guide to the use of established and newly emerging medical therapies of IBD. The approach to therapy is divided into categories for the treatment of mild to moderate, moderate to severe, and severe disease; maintenance strategies; and pouchitis. The author stresses that the key is to design an individualized program geared to each patient's specific needs. The practitioner must evaluate the patient's response to treatment with each visit, weighing the risks of drug toxicity, cancer surveillance, long-term debility, and surgical candidacy. 9 tables. 129 references.

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Long-Term Aminosalicylate Therapy is Under-used in Patients With Ulcerative Colitis: A Cross-Sectional Survey Source: Alimentary Pharmacology and Therapeutics. 16(11): 1889-1893. November 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: There is evidence from case-control studies that aminosalicylates drugs can reduce colorectal cancer risk by 75 to 81 percent in patients with ulcerative colitis. Patients may fail to comply with long-term therapies, however, or may have been advised to discontinue treatment once in remission. This article reports on a study undertaken to describe the usage of long-term aminosalicylates therapy in patients with ulcerative colitis (UC). The cross-sectional study was performed using data extracted from general practitioner clinical records on demographic features, extent and duration of disease, use of aminosalicylates therapy, and specialist care. The study included 363 people who had UC and no history of colorectal surgery. Ninety-five of 175 patients (54 percent) with proctitis, 78 of 123 patients (63 percent) with left-sided colitis, and 28 of 45 patients (62 percent) with extensive colitis were currently taking an aminosalicylate drug. Those doing so were more likely to be under specialist care than to be definitely or possibly discharged. The likelihood of current aminosalicylates therapy was not related to gender or the extent of disease, but was negatively related to the duration of disease. The authors conclude that a substantial minority of patients with ulcerative colitis does not take long-term aminosalicylates therapy. Those who do are more likely to be under specialist care, to be older, or to have disease of shorter duration. 2 tables. 23 references.

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Review Article: Insurance Risks for Patients With Ulcerative Colitis or Crohn's Disease Source: Alimentary Pharmacology and Therapeutics. 11(1): 51-59. February 1997. Contact: Available from Mercury Airfreight International, Ltd. 2323 EF, Randolph Avenue, Avenel, NJ 07001. E-mail: [email protected].

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Summary: This article addresses the issue of insurance risks for patients with ulcerative colitis (UC) or Crohn's disease. Prospective population-based studies have allowed a reevaluation of the risks of insuring patients with UC or Crohn's disease. Life expectancy, the risk of cancer, and working capacity are very much better than previously recognized and are normal for many patients. Three population-based studies in UC have shown a mortality similar to or slightly less than the general population except in the first year after diagnosis, while two have shown a slightly higher mortality, except for those with proctitis. In Crohn's disease, two populationbased studies have also shown an increased mortality that is similar to that of unskilled manual laborers from all causes of death. Three other studies have shown no increase in overall mortality, except in the first 5 years after diagnosis, in those with proximal small intestinal disease, and in some patients needing multiple operations. Insurance risks should be evaluated on an individual basis, after details of the extent and pattern of disease have been obtained. Although the 'standard life' in insurance terms differs from that of the general population, because people who seek life insurance are self-selected from a more affluent section of society, many patients can be identified who have a particularly good prognosis. These include patients with ulcerative proctitis, those with leftsided colitis in extended remission (more than 12 months), and patients more than 30 years old with localized ileal or ileocecal Crohn's disease that has responded to treatment. The author concludes that, from the published data, it is difficult to justify increasing the insurance premium in such patients. 6 tables. 23 references. (AA-M). •

Rare Case of Ulcerative Colitis Complicating Wilson's Disease: Possible Association Between the Two Diseases Source: Journal of Clinical Gastroenterology. 35(1): 43-45. July 2002. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: This article describes a rare case of ulcerative colitis (UC, a type of inflammatory bowel disease, or IBD) complicated by Wilson's disease. Wilson's disease is a genetic disorder in which failure of copper excretion causes accumulation of copper in the liver and other organs. In this case, a 24 year old Japanese man, UC occurred 12 years after the diagnosis of Wilson's disease, and the colitis was intractable to prednisolone and salazosulfapyridine. Because copper is one of the trace elements necessary for antioxidant defenses during the inflammatory process, altered copper metabolism may have contributed to the intractability of the UC in this case. 2 figures. 31 references.

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Collagenous Colitis and Lymphocytic Colitis Source: Journal of Clinical Gastroenterology. 30(3): 245-249. April 2000. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: This article discusses the most recently recognized and least understood forms of inflammatory bowel disease (IBD), two types of idiopathic microscopic colitis: collagenous colitis and lymphocytic colitis. Collagenous and lymphocytic colitis are the two recognized presentations of microscopic colitis, a syndrome of chronic watery diarrhea with a chronic inflammatory infiltrate in the colonic mucosa and without specific endoscopic abnormalities. These disorders share many clinical and histologic features, but they have a few notable differences. Whether these are two distinct entities or different presentations of the same disease remains controversial. Bismuth salicylate

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is effective in some patients and treatment is symptomatic and empirical in others. Unlike ulcerative colitis (UC) and Crohn's disease (CD), these forms of inflammatory bowel disease rarely require surgery. Ileostomy with or without colectomy is curative for the rare patient with severe symptoms that are refractory to medical measures. Collagenous and lymphocytic colitis are not associated with an increased risk of malignancy. 4 figure. 48 references. •

Surgical Options in Ulcerative Colitis Source: Surgical Clinics of North America. 77(1): 85-94. February 1997. Contact: Available from W.B. Saunders Company. Periodicals Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 654-2452. Summary: This article outlines controversies in surgical options for ulcerative colitis (UC). The authors review the current literature concerning pouch design, the need for a defunctioning ileostomy after the ileal pouch-anal anastomosis, whether a mucosectomy should be performed, and whether a pouch is safe in the setting of cancer. The J configuration appears to be satisfactory if sufficient length of terminal ileum is used. Functional outcome does not appear to be affected if a mucosectomy is performed. The need for defunction should be based on technical and patient-related considerations. Early cancer does not contraindicate ileal pouch-anal anastomosis. 4 tables. 40 references. (AA).

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Modern Medical Management of Acute, Severe Ulcerative Colitis Source: European Journal of Gastroenterology and Hepatology. 9(9): 831-835. July 1997. Contact: Available from Rapid Science Publishers. 400 Market Street, Suite 750, Philadelphia, PA 19106. (800) 552-5866 or (215) 574-2210. Summary: This article outlines the medical management indicated for patients with acute, severe ulcerative colitis (UC), a condition that the authors stress requires careful in-hospital assessment of the patient and the coordinated treatment of a team of experienced gastroenterologists and surgeons. Complete understanding of the potential complications and their management, especially toxic megacolon, is essential. The authors review the current medical arsenal and advocate a standardized approach to management that includes continuous, high dose intravenous hydrocortisone, more aggressive use of topical steroids as well as feeding the patients and continuing (but not initiating) oral 5-aminosalicylic acid (5-ASA) agents. For those patients whose disease proves refractory to intravenous steroids, intravenous cyclosporin (with an acute response rate of 82 percent) is an essential component of medical management. Antibiotics should be used only when specifically indicated. Total parenteral nutrition has not been shown to be helpful in the acute setting. Air contrast barium enema and colonoscopy have been used to predict response but may be dangerous diagnostic modalities in these acutely ill patients and are no better than good clinical judgment. The authors review and advocate long term management of acute response using 6mercaptopurine or azathioprine. The surgical experience and the postoperative complications of the ileal pouch anal anastomosis, which include acute pouchitis in 50 to 60 percent, chronic pouchitis in 5 to 10 percent, and recent reports of dysplasia among patients with chronic pouchitis, must be considered before colectomy is advised. The authors conclude that more than 80 percent of patients with acute severe colitis can be spared colectomy using the current arsenal of drug therapies. 27 references (20 annotated). (AA-M).

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Transient Ischemic Colitis in Young Adults Source: American Family Physician. 56(4): 1103-1108. September 15, 1997. Summary: This article presents and describes three cases in young adults of transient ischemic colitis, a benign, self-limited form of colitis. The authors note that this disorder should be included in the differential diagnosis in patients presenting with abdominal pain and hematochezia or bloody diarrhea. Estrogen or oral contraceptive therapy is associated with transient ischemic colitis, so its use should further raise suspicion. The effectiveness of discontinuation of estrogen therapy is controversial, but this measure should be considered. Conservative management includes repeated careful assessment, pain management, and fluid replacement. Complications are rare and the prognosis is excellent. A potential long term complication of transient ischemic colitis is colonic stricture formation from mucosal scarring. Occasionally, patients have recurrences. 3 figures. 2 tables. 22 references. (AA-M).

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Guidelines for the Diagnosis and Management of Clostridium Difficile-Associated Diarrhea and Colitis Source: American Journal of Gastroenterology. 92(5): 739-750. May 1997. Summary: This article presents guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis in adults. Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research, derived from extensive review of published literature. C. difficile causes a spectrum of diarrheal syndromes that vary widely in severity and merge with one another. The author considers the pathophysiology and epidemiology of C. difficile diarrhea, the clinical manifestations, diagnostic guidelines, primary treatment, management of relapses or recurrences of C. difficile diarrhea or colitis, and guidelines for prevention. The typical symptoms of C. difficile diarrhea are cramping abdominal pain, profuse diarrhea consisting of mucoid, greenish, smelling, water stools, low grade fever, and leukocytosis. These can start a few days after antibiotic therapy is begun or up to 8 weeks after its discontinuation. The differential diagnosis of C. difficile diarrhea includes benign or simple antibiotic-associated diarrhea, acute and chronic diarrhea caused by other enteric pathogens, adverse reactions to various medications other than antibiotics, ischemic colitis, idiopathic inflammatory bowel diseases, and intraabdominal sepsis. One table presents guidelines for preventing C. difficile diarrhea; these include limiting the use of antimicrobial drugs, washing hands between contact with all patients, using stool isolation precautions for patients with C. difficile diarrhea, and educating the medical, nursing, and other appropriate staff members about the disease and its epidemiology. 4 tables. 63 references. (AA-M).

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Ulcerative Colitis Practice Guidelines in Adults Source: American Journal of Gastroenterology. 92(2): 204-211. February 1997. Summary: This article presents the ulcerative colitis (UC) practice guidelines in adults from the American College of Gastroenterology. Guidelines for clinical practice are intended to indicate preferred approaches to medical problems as established by scientifically valid research. Guidelines are intended to be flexible and must be distinguished from standards of care, which are inflexible and rarely violated. Ulcerative colitis recommendations are presented for diagnosis and assessment, for management of mild-moderate distal colitis, for maintenance of remission in distal disease, for management of mild-moderate extensive colitis, for management of severe

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colitis, for surgery, and for cancer surveillance. In a patient presenting with persistent bloody diarrhea, rectal urgency, or tenesmus, stool examinations and sigmoidoscopy and biopsy should be performed to confirm the presence of a colitis and to rule out infectious causes. Characteristic endoscopic and histologic findings with negative evaluation for infectious causes will suggest the diagnosis of UC. Patients with mild to moderate distal colitis may be treated with either oral aminosalicylates, topical mesalamine, or topical steroids. When the acute attack is controlled, a maintenance regimen is usually required, especially in patients with severe, extensive, or relapsing disease. The patient with severe colitis refractory to maximal oral treatment with prednisone, oral aminosalicylate drugs, and topical medications, or the patient who presents with toxicity, should be treated for 7 to 10 days with intravenous steroids. Failure to demonstrate significant improvement within 7 to 10 days is an indication for either colectomy or treatment with intravenous cyclosporine in specialized centers. After 8 to 10 years of colitis, annual surveillance colonoscopy with multiple biopsies at regular intervals should be performed. 119 references. (AA-M). •

Lower Gastrointestinal Bleeding and Ischemic Colitis Source: Canadian Journal of Gastroenterology. 16(9): 597-600. September 2002. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail: [email protected]. Summary: This article reports on a study that compared the incidence and clinical characteristics of lower gastrointestinal (LGI) bleeding due to ischemic colitis with those with LGI bleeding of other causes. A chart review was performed of patients admitted with LGI bleeding to Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, between July 1, 1997 and January 31, 2000. Of 124 patients with LGI bleeding, 24 cases were due to ischemic colitis, 62 to diverticulosis, 11 to inflammatory bowel disease (IBD), and 27 to all other causes ('others'). The average ages of patients in each group were 66.5, 76.5, 40.5, and 77.5 years, respectively. Patients with ischemic colitis were statistically younger than those with diverticular bleeding and 'others.' Patients with IBD were younger than those in the other three groups. The only statistical difference for vascular disease risks was hypertension, because of its absence from the IBD group. Three patients with ischemic colitis underwent blood transfusions, while 23 with diverticulosis, 15 'others' and none with IBD received blood. Three patients with ischemic colitis and one patient from the 'others' group died. More women (75) than men (49) had LGI bleeding, in total and within each subgroup. Of women with LGI bleeding, many more with ischemic colitis (44.4 percent) than with diverticulosis (3.0 percent), IBD (0 percent) or 'others' (5.6 percent) were taking estrogen. 16 references.

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Transdermal Nicotine for Mildly to Moderately Active Ulcerative Colitis: A Randomized, Double-Blind, Placebo-Controlled Trial Source: Annals of Internal Medicine. 126(5): 364-371. March 1, 1997. Summary: This article reports on a study undertaken to determine the efficacy of transdermal nicotine for controlling clinical disease activity in active ulcerative colitis (UC), a type of inflammatory bowel disease (IBD). The doubleblind, placebo controlled design studied 64 nonsmoking patients with mildly to moderately active UC despite the use of medication. Patients were stratified on the basis of smoking history, extent of disease, and concomitant medical therapy. After stratification, patients were randomly assigned to daily treatment with transdermal nicotine (n = 31) at the highest tolerated dose (11 mg for 1 week and then less than 22 mg for 3 weeks) or placebo (n = 33).

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Clinical features were assessed at baseline and at 4 weeks by endoscopy, physician assessment, and a patient diary of daily symptoms. At 4 weeks, 12 of 31 patients (39 percent) who received nicotine showed clinical improvement compared with 3 of 33 patients (9 percent) who received placebo. Four patients receiving nicotine discontinued therapy because of side effects (contact dermatitis, nausea, acute pancreatitis). The authors conclude that transdermal nicotine administered at the highest tolerated dosage for 4 weeks is efficacious for controlling clinical manifestations of mildly to moderately active UC. The authors briefly consider the phenomenon of 'opposite effects' wherein smoking adversely affects Crohn's disease (another type of IBD). 2 figures. 4 tables. 21 references. (AA-M). •

Surgery for Ulcerative Colitis: Historical Perspective, A Century of Surgical Innovations and Refinements Source: Diseases of the Colon and Rectum. 42(3): 299-306. March 1999. Contact: Available from Williams and Wilkins. 352 West Camden Street, Baltimore, MD 21201-2436. Summary: This article reviews a century of surgical innovations and refinements in the treatment for ulcerative colitis (UC). The authors begin with a discussion of the early role of surgery (1890s) and the Brooke ileostomy, then discuss ileorectal anastomosis, Kock's continent ileostomy, the ileoanal anastomosis, and the evolution and refinements of these techniques. In the early 20th century, UC as a disease entity was largely unknown and almost never resected. Initially, surgeons used cecostomies or appendicostomies to irrigate and put the bowel at rest. Diversion of the fecal stream by ileostomy or colostomy had some proponents, but the inadequacies of stomas and stoma appliances and the risk of surgery limited its use. It was not until Brooke devised and successfully used the everted ileostomy that complete removal of the disease began to be practiced more widely and that surgery became an integral part of therapy. It was the advent of Kock's continent ileostomy that revolutionized the entire surgical approach to UC by eliminating the need for an external appliance and still curing the disease. The ileal pouch anal anastomosis provided patients with a curative resection and a functional outcome that gave them an even better quality of life, without the need for a permanent external appliance or a stoma. 4 figures. 64 references.

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Microscopic Colitis: Collagenous Colitis and Lymphocytic Colitis Source: Practical Gastroenterology. 26(9): 41-42, 44, 46, 48. September 2002. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: This article reviews collagenous colitis and lymphocytic colitis are chronic relapsing diarrheal illnesses, which are often referred to together as microscopic colitis. Microscopic colitis most commonly occurs in women in their fifth to sixth decade. The symptoms usually include profuse watery diarrhea and crampy abdominal pain. Laboratory and endoscopic studies are generally normal but microscopic inflammation is seen when colonic biopsies are performed. In collagenous colitis there is a subepithelial collagen band in addition to chronic inflammation in the lamina propria (the layer of connective tissue just below the epithelium). The etiology (cause) is not known, but multiple theories exist including autoimmune, infectious, and medicationinduced. Although the course is generally benign, patients may have multiple relapses over many years. Treatment regimens vary and have included anti-diarrheals,

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antibiotics, 5-aminosalicylates, steroids, and immunosuppressive agents. 2 figures. 3 tables. 32 references. •

Maintenance of Remission in Ulcerative Colitis Source: Alimentary Pharmacology and Therapeutics. 16(Supplement 4): 21-24. July 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: This article reviews strategies undertaken to maintain remission in patients with ulcerative colitis (UC, a type of inflammatory bowel disease, or IBD). The author notes that 70 percent of patients with UC can expect to experience a relapse over a 12 month period. Sulfasalazine was the first drug demonstrated to reduce this relapse rate to 21 percent. Subsequent studies have demonstrated that 5 aminosalicylic acid (5ASA) is the main active component and preparations containing only 5ASA have similar efficacy to sulfasalazine. 5ASA is readily absorbed from the small intestine; special release formulations are indicated. A variety of 5ASA preparations is available, differing in their release mechanisms, efficacy, and side effect profile. Most patients can be maintained in remission using oral 5ASA medication. For patients with distal or left sided disease, the use of rectal 5ASA is also of proven benefit in maintaining remission. Some patients with frequent or severe relapses require stronger immunosuppression, and in those patients, azathioprine or 6 mercaptopurine (6MP) are of proven benefit. Azathioprine is also of great use for maintaining remission in patients who have been treated with cyclosporine for a fulminant acute episode of colitis. The author concludes by commenting that the area of natural therapies (probiotics) deserves further exploration. 14 references.

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Colitis: Key Components of the Evaluation Source: Consultant. 38(2): 375-378, 381-383. February 1998. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: This article reviews the key components of the evaluation of colitis. Colitis is a nonspecific condition that has a variety of causes, including inflammatory bowel disease, infections, ischemia, radiation, and antibiotic therapy. The mainstays of evaluating patients who have colitis include the history and physical examination, sigmoidoscopy with mucosal biopsy, stool examination, and barium radiography. These tools are used to determine if colitis is present, how severe it is, the cause of the colitis, and the anatomic extent of the disease. In addition to the typical symptoms of colitis (diarrhea, abdominal pain, and tenesmus), the authors recommend that physicians look for signs of more severe disease, such as orthostasis, pallor, fever, fatigue, and tachycardia. Also, physicians should be alert for extraintestinal manifestations of chronic inflammatory bowel disease (IBD), such as mouth ulcers, erythema nodosum, and arthritis. Laboratory findings that may suggest severe colitis include a low hemoglobin level, leukocytosis, an elevated erythrocyte sedimentation rate, and hypoalbuminemia. After confirming the presence of colitis with proctosigmoidoscopy or flexible sigmoidoscopy, stool cultures and parasite testing should be ordered to identify the specific cause. Complications of colitis include toxic megacolon, perforation, hemorrhage, and obstruction in ischemic disease. 4 figures. 3 tables. 16 references. (AAM).

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Review Article: The Management of Severe Ulcerative Colitis Source: Alimentary Pharmacology and Therapeutics. 11(3): 419-424. June 1997. Contact: Available from Mercury Airfreight International, Ltd. 2323 EF, Randolph Avenue, Avenel, NJ 07001. E-mail: [email protected]. Summary: This article reviews the management of severe ulcerative colitis (UC), a potentially life threatening condition. The authors note that the mortality has fallen dramatically over the past 4 decades to less than 2 percent, including surgical mortality. Early recognition of the severity of the colitis, intensive medical therapy, close liaison between physician and surgeon, and prompt surgery when necessary have all contributed to this improved outcome. Despite the use of high-dose intravenous corticosteroids, 20 to 30 percent of patients will make a poor response and will require urgent surgery. The use of intravenous cyclosporin has proved effective at reducing the immediate surgical rate in this group of unresponsive patients and appears safe. Whether cyclosporin reduces the need for surgery in the longer term is much less uncertain. The authors describe how clinical, radiological, endoscopic, and laboratory parameters can now be used to predict the course of a severe attack. These help in the timing of urgent surgery and are potentially helpful in determining when to begin other therapies such as cyclosporin. 1 table. 36 references. (AA-M).

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Ulcerative Colitis: Surgical Indications and Treatment Source: Alimentary Pharmacology and Therapeutics. 16(Supplement 4): 25-28. July 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: This article reviews the treatment options for ulcerative colitis (UC, a type of inflammatory bowel disease, or IBD), including the surgical indications. The author notes that the indication for surgery is a balance between the severity of the disease despite full medical treatment and the potential disadvantages of surgery. The decision requires cooperation between the gastroenterologist and surgeon. Colectomy with ileostomy and preservation of the rectum in the emergency setting is the accepted procedure and can rapidly restore the patient to normal health, allowing withdrawal of anti-inflammatory medication. After recovery, all surgical possibilities are then open for the future. The elective indications for surgery include failure of medical treatment, retardation of growth in a child or adolescent, and neoplastic (precancerous) transformation. The choice of operation includes conventional proctocolectomy, restorative proctocolectomy (RPC), and colectomy with ileo-rectal anastomosis. Causes of failure include sepsis (50 percent), dysfunction (30 percent), and pouchitis (10 percent). In selected cases, salvage surgery to avoid failure can be successful with rates of around 70 percent for outlet obstruction and fistulation and 50 percent for pelvic sepsis. 26 references.

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Monitoring Activity in Ulcerative Colitis Source: Alimentary Pharmacology and Therapeutics. 16(Supplement 4): 3-6. July 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com.

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Summary: This article reviews therapeutic strategies and the monitoring of patients with ulcerative colitis (UC, a type of inflammatory bowel disease, or IBD). The authors note that monitoring is easier in these patients than in patients with Crohn's disease (another type of IBD) for several reasons. The severity of symptoms and activity of inflammation tend to run parallel in UC when involvement of the large bowel is more extensive. The easy accessibility of the colonic mucosa by endoscopic and histologic examination provides further information concerning the degree of inflammation. In severe attacks, the patients must be admitted to the hospital and monitored carefully. Clinical and laboratory parameters (such as daily stools, CRP, fever, hemoglobin, albumin, etc) and plain abdominal x-ray are useful in monitoring the activity of the disease and to predict the outcome. In mild to moderate attacks, endoscopic and histologic evaluation are the best methods for choosing the appropriate treatment and for assessing response. 2 tables. 18 references. •

Is the Appendix a Vestigial Organ? Its Role in Ulcerative Colitis Source: Gastroenterology 121(3): 730-737. September 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: This article summarizes a research study that considers the role of the appendix in ulcerative colitis (UC, a type of inflammatory bowel disease), including the possible role of appendectomy (removal of the appendix) in protecting against UC. The author briefly reviews the research in this area, then focuses on one particular study that was reported in the New England Journal of Medicine in 2001 (Andersson, R.E., et al, Volume 344). The investigators in that study conclude that the inflammatory response leading to an appendectomy rather than the removal of the appendix was the significant clinical factor negatively associated with developing UC at a later date. The absence of this protective effect in older patients with appendicitis also suggests that the immune mechanisms resulting in appendicitis in these patients may differ from those resulting in appendicitis before the third decade. The author then appends a lengthy commentary exploring the ramifications of these results. The author concludes that in the absence of evidence supporting a more causal role for the appendix, adoption of therapeutic appendectomy as a strategy to affect the incidence or clinical course of UC is premature, despite recent case reports suggesting clinical improvement and reduction in mucosal inflammatory mediators after appendectomy. Numerous studies are referred to in the text of this article.

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Ulcerative Colitis in Adults: Summary of the Latest Practice Guidelines Source: Consultant. 37(4): 1085-1086. April 1997. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: This article summarizes the latest practice guidelines (developed by the American College of Gastroenterology) for the assessment and treatment of ulcerative colitis (UC) in adults. Stool examinations, sigmoidoscopy, and biopsy are indicated to confirm the presence of colitis and to rule out infectious causes in patients who have persistent bloody diarrhea, rectal urgency, or tenesmus. The mucosal changes characteristic of UC, as detected by proctosigmoidoscopy or colonoscopy, include loss of the typical vascular pattern, granularity, friability, and ulceration. Once the diagnosis is confirmed, it is necessary to establish whether the inflammation is distal or extensive. Oral aminosalicylates, topical mesalamine, or topical corticosteroids are appropriate for

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patients with mild to moderate distal colitis. Oral corticosteroids should be reserved for patients whose disease is refractory to oral aminosalicylates. Mercaptopurine or azathioprine is effective in patients who do not respond to oral prednisone, provided they are not so acutely ill that they require intravenous therapy. A maintenance regimen is usually required for patients with mild to moderate extensive colitis, particularly those who have severe or relapsing disease. In adults with UC, the absolute indications for surgery are exsanguinating hemorrhage, perforation, and documented or strongly suggested carcinoma. Surgery is also indicated in patients with severe colitis (with or without toxic megacolon) that is unresponsive to conventional maximal medical therapy and in patients with less severe but medically intractable symptoms or intolerable corticosteroid side effects. Annual cancer surveillance colonoscopy with multiple biopsies at regular intervals is warranted after 8 to 10 years of colitis. 1 table. 4 references. •

Surgical Outcomes in Ulcerative Colitis and Crohn's Disease Source: Canadian Journal of Gastroenterology. 13(10): 804-805. December 1999. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail: [email protected]. Summary: This article summarizes two descriptive studies that provide information on the postoperative aspects of patients who have undergone colonic resective surgery for ulcerative colitis (UC) or Crohn's disease (the two types of inflammatory bowel disease, or IBD). For UC, colonic resection usually results in amelioration of the morbid effects of the disease and substantially eliminates the risk of later malignancy. For Crohn's disease, especially with extensive colonic involvement, resection of the colon and rectum may also be required. For most patients, the early short term results of these surgical therapies have been generally quite satisfactory, with the goal being that the patient may return to a normal life as soon as possible following treatment. For patients with UC, operative treatment is performed during the most sexually active and reproductive years. Thus, most patients faced with restorative proctocolectomy (removal of the colon) may have significant concerns related to sexual function and fertility following surgical treatment. Sexual dysfunction may develop in males, but with variable frequency. In the second study, of Crohn's disease patients undergoing total colectomy and ileostomy, preoperative steroid therapy and associated perforating disease were associated with a high incidence of postoperative complications. The author stresses that convincing data on the effectiveness of antibiotic regimens, immunosuppressive agents or biological therapies (e.g., antitumor necrosis factor) are simply not available, particularly data that may demonstrate a more transient benefit. Until truly effective medical therapies for anorectal disease becomes available, proctocolectomy may well be the surgical treatment of choice.

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Ulcerative Duodenitis with Ulcerative Colitis: Is It Crohn's Disease Or Really Ulcerative Colitis? (editorial) Source: Journal of Clinical Gastroenterology. 32(2): 97. February 2001. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: This editorial comments on an accompanying article in which two patients present the dilemma in differentiating between Crohn's disease and ulcerative colitis (the two subtypes of inflammatory bowel disease, IBD). The first case was that of a man, 31, with a history of left sided colitis who subsequently developed erosive duodenitis

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responsive to methylprednisolone. The second case was that of a woman, 30, with pancolitis who was admitted for closure of an ileostomy after a staged subtotal proctocolectomy with ileoproctostomy and diverting ileostomy. Her hospital course was complicated by the development of ulcerative duodenitis, again responsive to methylprednisolone. Crohn's disease may involve the stomach, the duodenum, or both, usually in conjunction with a more distal disease, although this is not always the case. Ulcerative colitis, on the other hand, is a disease of the colon almost always involving the rectum. The authors conclude that upper gastrointestinal tract inflammation (such as duodenitis) warrants further observation and maximum documentation to sustain the issue of whether ulcerative colitis can involve the upper gastrointestinal tract. They note that there might be a third type of IBD, whether occurring from a separate origin or arising from conversion of one type of IBD to the other. 8 references. •

Explaining Ulcerative Colitis to Friends and Family Source: Insights and Answers. 7-8. Summer 1999. Contact: Available from Insights and Answers. P.O. Box 3217, Cincinnati, OH 452738266. (800) 663-6698. Website: www.living-better.com. Summary: This newsletter article, written by a man with ulcerative colitis (UC, one of the types of inflammatory bowel disease) considers the issues involved in explaining UC to friends and family members. The author underscores the need of letting family and friends be supportive, help the patient through everyday trials and tribulations, comply with the recommended treatment schedule, and stay focused on recovery. The author lists the benefits of telling loved ones about UC, and then offers strategies for exactly how to go about telling them about the disease. These strategies include gather general information, practice what is going to be said, pick out an appropriate time and place to talk, and explain why it is important for them to learn about the disease. The author concludes by reminding readers that even the smallest efforts of support and words of encouragement can go a long way toward helping others who are coping with inflammatory bowel disease.

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Under the Microscope: Research News Bulletin from the Crohn's and Colitis Foundation of America Source: Under the Microscope. Summer 2001. p. 1-6. Contact: Available from Crohn's and Colitis Foundation of America (CCFA). 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 932-2423. E-mail: [email protected]. Website: www.ccfa.org. PRICE: Single copy free. Summary: This newsletter offers a summary of research news that may be of interest to people with Crohn's disease or colitis. The articles review current research activities, focusing on those projects supported by the Crohn's and Colitis Foundation of America (CCFA). For example, this issue includes a report on a recent breakthrough in the genetic understanding of Crohn's disease, a report on the Digestive Disease Week conference (the major medical conference of the year for everyone who plays a role in studying and treating inflammatory bowel disease, IBD), and sidebars about current research projects in which readers may wish to participate. The news report from Digestive Disease Week covers clinical trials of IBS medications, including entanercept, infliximab, Budesonide, and natalizumab; adolescents in transition; cancer surveillance in IBD; animal models of IBD; and a burden of disease (economic) study. 2 figures.

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Surveillance Issues in Inflammatory Bowel Disease: Ulcerative Colitis Source: Journal of Clinical Gastroenterology. 32(2): 99-105. February 2001. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: This review article on the surveillance of patients with ulcerative colitis (UC) provides an overview of the criteria for evaluating screening and surveillance programs and applies the criteria to the available evidence to determine the effectiveness of the surveillance of patients with UC. The authors examine the clinical outcomes associated with surveillance, the additional clinical time required to confirm the diagnosis of dysplasia and cancer, compliance with surveillance and followup, and the effectiveness of the individual components of a surveillance program, including colonoscopy and pathologist's interpretation. The disability associated with colectomy is considered, as are the cost and acceptability of surveillance programs. Patients with longstanding UC are at risk for developing colorectal cancer, therefore recommended surveillance colonoscopy should be supported. The diagnosis of cancer at an early stage in this group is associated with a good prognosis. The authors conclude that new endoscopic and histopathologic techniques used to improve the identification of high risk patients may enhance the effectiveness and cost effectiveness of surveillance practices. 2 figures. 5 tables. 44 references.

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Therapy for Ulcerative Colitis Source: Current Opinion in Gastroenterology. 14(4): 312-316. July 1998. Contact: Available from Lippincott-Raven Publishers. 227 East Washington Square, Philadelphia, PA 19106. (800) 638-3030. Summary: This review article presents the 1997 literature on the medical therapy of ulcerative colitis (UC). Several recent studies have addressed aspects of this topic, including optimization of current therapies, pilot studies, definitive placebo-controlled trials of newer novel therapies, and reports of associated complications. Combination therapy with rectal and oral 5-aminosalicylate may be more effective than either formulation alone, and the renal safety of high-dose oral 5-aminosalicylate has been confirmed. Rectal 5-aminosalicylate is more effective than conventional rectal corticosteroids, and delayed release oral budesonide may also be beneficial for patients with active UC. Treatment with intravenous cyclosporine is only required in 22 percent of patients with severe UC, and cyclosporine may be associated with severe toxicity, including death. Transdermal nicotine is effective in treating active UC but results in side effects, which may be overcome by administering nicotine directly to the colon. Preliminary studies suggest that both anti-tumor necrosis factor-alpha antibody and heparin may benefit patients with UC. Also, 5-Lipoxygenase inhibitors, short chain fatty-acid enemas, olestra, and ciprofloxacin are not effective therapies for UC. Oral therapy with a probiotic bacterial preparation may maintain remission in patients with UC. Finally, folate or folinic acid may decrease rectal cell proliferation and subsequent development of neoplasia (cancer) in patients with longstanding UC. 60 references (13 annotated). (AA).

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Surgical Therapy for Ulcerative Colitis Source: Ostomy Quarterly. 34(1): 36-40. January 1997. Contact: Available from Ostomy Quarterly. 36 Executive Park, Suite 120, Irvine, CA 92614-6744. (800) 826-0826 or (714) 660-8624. Fax (714) 660-9262.

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Summary: Ulcerative colitis (UC) is a disease that involves the inner lining (mucosa) of the colon and rectum. While the cause of UC remains elusive, surgical removal of the entire colon and rectum is curative. The authors of this article describe surgical therapy for UC. They note that the indications for surgery can be divided into three categories: immediately life threatening, chronically disabling, and an increased cancer risk. They discuss each of these indications and then describe the advantages and disadvantages of each of five surgical alternatives for managing UC. Those alternatives are subtotal colectomy with ileostomy, colectomy with ileorectal anastomosis, proctocolectomy with Brooke ileostomy, proctocolectomy with continent ileostomy, and proctocolectomy with ileal pouch anal anastomosis. The authors stress that, as in all operations, the risks of surgical therapy must be balanced against the benefits to the patient. The risks of surgery include the morbidity and mortality associated with the procedure itself and the alteration in lifestyle resulting from the removal and reconstruction of the colon and rectum. The benefits include a cure of UC if the entire colon and rectal mucosa is removed, removing the risk of developing cancer, and improving an individual's lifestyle. Limitations in social activities such as work, as well as the lack of well-being and a reduced energy level, are often significantly improved after surgery. 5 figures. 2 tables. 9 references. •

Avoiding Common Errors in Maintenance Therapy for Ulcerative Colitis Source: Practical Gastroenterology. 22(4): 49-50, 52, 54-56, 58. April 1998. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. E-Mail: [email protected]. Summary: Ulcerative colitis (UC) is a medically incurable chronic disease in which the mucosal lining of the colon becomes inflamed. The goal of medical therapy is to quickly induce remission and maintain it for as long as possible, without creating side effects or adversely affecting quality of life. This article outlines strategies to avoid common errors in maintenance therapy for UC. The authors note that, since therapy is often lifelong, the chance for treatment errors is greatly increased. Aminosalicylates are usually the best choice for long term maintenance of mild to moderate disease. Corticosteroids can quell acute flares in moderate to severe disease, but are contraindicated as maintenance therapy. Immunomodulators are safe and effective as maintenance therapy in more severe cases of steroid resistance and steroid dependence. All of these drugs are safe during pregnancy. Antibiotics are rarely helpful, but resumption of cigarette smoking may sometimes be recommended in lieu of surgery (the potentially life threatening adverse effects associated with smoking must be weighed heavily against the benefits). The only cure for UC is colectomy, which can significantly increase the quality of life for patients who have chronically active symptoms despite optimal medical management. 3 tables. 31 references. (AA-M).

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Ulcerative Colitis in Young Adults: Complexities of Diagnosis and Management Source: Postgraduate Medicine. 103(1): 45-49, 53-54, 56, 59. January 1998. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: Ulcerative colitis (UC) is difficult to differentiate from other inflammatory bowel diseases or to treat with precision. This article discusses the characteristics of UC, the medications used to treat it, and the challenge of recognizing and managing UC. The intestinal inflammation associated with UC may involve the entire colon (36 percent of the patients), or be limited to distal areas such as the left colon (17 percent) or rectum (46

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percent). Patients with active disease commonly present with bloody diarrhea, abdominal pain, and rectal urgency. However, symptoms may differ depending on the extent of the colonic inflammation. The diagnosis of UC depends on a combination of findings from the history, physical examination, laboratory evaluation, and endoscopic and histopathologic studies, as well as exclusion of other causes of colitis. Response to therapy and continued observation of the patient over time help to confirm the diagnosis. The author reviews the medical treatment of ulcerative colitis and summarizes factors related to ulcerative colitis, including smoking status, nutritional therapy, and cancer. The mainstays of treatment are sulfasalazine for mild to moderate disease and corticosteroids for moderate to severe disease. Side effects of sulfasalazine limit its use in some patients. Refractory UC is best treated surgically. 1 figure. 2 tables. 23 references. (AA-M). •

Ulcerative Colitis: A Rational Approach to Management Source: Consultant. 41(4): 541-548. April 1, 2001. Contact: Available from Cliggott Publishing Company. 330 Boston Post Road, Darien, CT 06820-4027. (203) 661-0600. Summary: Ulcerative colitis (UC), a type of inflammatory bowel disease can manifest as proctitis or proctosigmoiditis, left sided colitoss, or pancolitis. This article offers a rational approach to the management of patients with UC. Frequent low volume bowel movements, urgency, rectal bleeding, and tenesmus (ineffective spasms of the rectum) alone suggest proctitis. Prostration, fever, tachycardia (racing heartbeat), dehydration, and complications of blood loss (which may or may not be accompanied by symptoms of proctitis) suggest more severe disease or more extensive bowel involvement. For patients with mild to moderate disease, mesalamine is recommended to induce and maintain remission. Systemic corticosteroids can induce remission in patients with moderate to severe disease but are not useful for maintenance therapy. Azathioprine or 6 mercaptopurine can be used to wean patients with moderate to severe colitis from corticosteroids and to maintain remission. If severe colitis does not respond to corticosteroids, immunosuppressive therapy or colectomy may be needed. Other indications for surgery include development of acute complications related to disease activity and chronic complications, such as dysplasia, carcinoma, recurrent hemorrhage, or growth retardation in children. Annual surveillance colonoscopy with biopsy is recommended for patients with pancolitis and left sided colitis.

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Increase in Colorectal Epithelial Apoptotic Cells in Patients with Ulcerative Colitis Ultimately Requiring Surgery Source: Journal of Gastroenterology and Hepatology. 17(7): 758-764. July 2002. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Up to one-third of patients with ulcerative colitis (UC) need to undergo surgery, but the factors that exacerbate inflammation (and thus lead to surgery) remain unclear. The authors of this study hypothesize that excessive apoptosis (sloughing of skin crust) reported in active UC may disrupt epithelial defenses and exacerbate the disease. The present study was undertaken to clarify whether apoptotic epithelial cells and histiocytes engulfing them increased in patients with active UC who ultimately require surgery (UC-S) rather than those receiving medication alone (UC-M). The study included 29 patients with UC-S, 35 patients with UC-M, 18 with infectious colitis, and 16

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healthy controls. The apoptotic indices in UC-M patients were significantly higher than those in controls but almost equal to those in infectious colitis patients. In the upper and lower halves of the mucosa, both apoptotic indices and histiocyte densities were significantly higher for UC-S than in UC-M. The results suggest that epithelial apoptosis is a non-specific phenomenon and that an increased number of apoptotic cells exceeding histiocyte phagocytic capacity may play a part in the disruption of epithelial defenses and further accelerate mucosal inflammation. 2 figures. 2 tables. 38 references.

Federally Funded Research on Colitis The U.S. Government supports a variety of research studies relating to colitis. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to colitis. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore colitis. The following is typical of the type of information found when searching the CRISP database for colitis: •

Project Title: AGING AND INTESTINAL NEURO-IMMUNE REGULATION IN COLITIS Principal Investigator & Institution: Javed, Najma H.; Physiology and Health Science; Ball State University Muncie, in 47306 Timing: Fiscal Year 2000; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: The long term goal of the proposed project is to elucidate the role of intestinal immune system in modulating the activity of the enteric nervous system in inflammatory bowel disease (IBD) in our aging population. There is much evidence which indicates functional decline in systemic immune responses with aging. However there is no clear evidence suggesting specific effects of aging on gastrointestinal associated immune system and enteric nervous system. The fact that gastrointestinal tract is the largest immune organ in the body, has been ignored and much less attention has been given to the role of lamina propria T cells and intraepithelial lymphocytes (IEL), and antibody producing B cells. The changes may be related to quantitative and qualitative release of cytokines and inflammatory mediators and their interaction with secretory neurons within the wall of the gut. With the use of Lewis rat colitis model (chemical induction), we will pursue the following specific aims: 1) To ascertain if colonic tissues from rats have altered neurosecretory responsiveness associated with age during experimental colitis; 2) To ascertain the immunohistological distribution pattern, quantitation and phenotypic localization of T and B cells in intestinal compartment of

2

Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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Lewis rats of various age groups; 3) To isolate and ascertain the activity of isolated intestinal T cells to proliferate by in vitro proliferative assay; 4) To analyze cytokine profiles of the immune T cells such as IL-1, IL-2, IL- 4, IL-6, IL-8, IFN-gamma among others which accompany the induction of inflammatory response in-he gut; 5) To study the histological and ultra structural changes within the intestine during inflammatory phase in different age groups. The results of this study will contribute significantly to our knowledge of neuroimmune interactions and their role in IBD in aging rats. It will also provide insight into etiology, pathogenesis and strategies for management and basis for future development and selection of therapeutic measures for different age groups for intestinal inflammatory conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTI-INFLAMMATORY INFLAMMATION

LIPIDS

IN

ACUTE

MUCOSAL

Principal Investigator & Institution: Gronert, Karsten; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-DEC-2004 Summary: (provided by applicant) Inflammatory bowel diseases (IBD) that are associate with a dramatic increase in colorectal cancer occur throughout the world with an annual incidence of approximately 12/100,000 people. Aberrant activation of neutrophils and a profound increase in lipid and peptide mediators are cardinal signs of these inflammatory diseases as well as for ischemia reperfusion injury, a known complication of surgical procedures. How acute inflammatory responses switch from vital host defense to aberrant inflammation and neutrophil mediated tissue injury remains to be completely elucidated. Therefore, endogenous mechanisms that disrupt proinflammatory circuits are of interest. Aspirin and omega-3 polyunsaturated fatty acids (PUFA) are therapeutic agents that demonstrate benefits in inflammatory diseases as well as prevention of colon cancer. However, their mechanisms of action still needs to be clearly defined but targets the formation of lipid mediators namely eicosanoids. Both therapeutic agents trigger the formation of novel classes of anti-inflammatory lipids, namely 15R-lipoxins and omega-3 PUFA derived 15R-and 18R-series eicosanoids. This study shall test the hypothesis that acute inflammation induces a regulated and temporal generation of anti-inflammatory lipid signals and that omega-3 fatty acid and aspirin augment these protective lipid mediator circuits. The specific aims of this application will employ a combined approach of structural elucidation, molecular biology and transgenics to delineate three main aspect of the role of lipid signals in neutrophil mediated intestinal injury: i) Establish the temporal relationship of pro- and anti-inflammatory eicosanoids. ii) Determine the impact of aspirin and omega-3 PUFA on eicosanoid profiles and elucidate novel protective lipid mediators. iii) Determine if novel aspirin and omega-3 PUFA triggered lipid mediators are protective against aberrant PMN activation and if changes in expression of receptors for lipid mediators are markers for aberrant intestinal inflammation. The broad and long-term objectives of this application are to elucidate endogenous pathways that block PMN mediated injury to promote resolution of inflammation. Results from this project may provide novel anti-inflammatory tools for controlling inflammatory diseases such as Ulcerative Colitis and Chron's Disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AUTOIMMUNE MECHANISM IN ULCERATIVE COLITIS Principal Investigator & Institution: Das, Kiron M.; Professor; Medicine; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, Nj 08854 Timing: Fiscal Year 2001; Project Start 30-SEP-1993; Project End 31-AUG-2003 Summary: The overall hypothesis for this proposal is that in patients with ulcerative colitis (UC) the colonic epithelium expresses autoantigen(s) which ma drive the immune destruction of the epithelial cells. We earlier identified a putative colonic autoantigen, p40, that belongs to cytoskeletal tropomyosin (TM) family, and majority of UC sera react with p40/TM. Utilizing recombinant hTM isoforms (hTM-5) and isoform specific monoclinal antibodies (mAb) developed by us, we have observed that the normal colon epithelial cells (CEC) contain mostly hTM5 and hTM4 and not hTM1-3. We demonstrated autoantibody response in UC against hTM5 and hTM1. We will examine if there is any qualitative and/or quantitative differences in hTM isoform expression I CEC from UC compared. Using the hTM5 isoform, we identified two HLA DR2-binding peptides. We will focus on T cell responses against hTM5 and the peptides. We will also examine I cells responses against hTM4 and other hTM isoforms. For T cell responses, we will use both peripheral blood mononuclear cells (PBMC) and lamina propria lymphocytes (LPL). We have shown both in UC mucosa as well as in selected colon cancer cells that UC associated autoantibodies bind at the same site as the 7E12H12 mAb (developed by us earlier using highly enriched p40) does. This mAb has unique organ distribution such as colon, biliary tract, skin, eyes and joints. Recently we identified that 7E12H12 mAb reacts with unioval colonic epithelial protein (CEP) of Mr>200K. Preliminary experiments suggest that CEP may act as a "shuttle" to externus hTM5. We will critically examine the relationship between hTMs and CEP. Using purified CEP, we will also be cloned. Human colon cDNA expression libraries from normal and UC colon mucosa and cDNA libraries from two colon cancer cell lines are developed and will be utilized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHWAYS

BACTERIAL

MODULATION

OF

EPITHELIAL

SIGNALING

Principal Investigator & Institution: Neish, Andrew S.; Pathology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: (adapted from the application) Salmonella typhimurium is a common cause of food-borne enterocolitis in this country and the developing world. The clinical manifestations of Salmonella typhimurium infection result from inflammatory cells that are recruited to, and accumulate in, the intestinal mucosa. The intestinal inflammatory response is mediated in large part by synthetic upregulation of secreted cytokines and other inflammatory effector molecules. These inflammatory mediators are activated at the transcriptional level by the action of DNA binding transcription factors such as NFkappaB. Experiments with cultured intestinal epithelial cells have shown that S. typhimurim associated with inflammatory intestinal disease activate NF-kappaB via a calcium dependant activation pathway, while other, non-pathogenic Salmonella strains repress activation of this key regulator. Our overall hypothesis is that Salmonella (and potentially other enteric bacteria) have evolved novel mechanisms to modulate epithelial signaling pathways that may serve to establish either a pathologic or a commensal state. Elucidation of these influences will increase our understanding of the

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epithelial and bacterial factors involved in human enterocolitis, as well as the microbiology of this class of enteric infections. This application describes a variety of experimental methods to study the host inflammatory response including pathogen induced calcium dependant activation of the NF-kappaB pathway. These methods will be applied to signals elicited by S. typhimurium, a series of Salmonella mutants and variety of other enteric pathogens. Secondly, similar assays will be used to study the mechanism by which some bacteria repress host immune and inflammatory reactions by modulation of the NF-kappaB signaling cascade. These studies will be supported using well characterized murine models of intestinal inflammation to correlate the antiinflammatory properties of these bacteria in vivo. Finally, a novel electroporation based method to introduce purified proteins into intact model epithelia will be used to dissect the cellular responses to internalization of a variety of bacterial effector proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BACTERIOPHAGE THERAPY IN C DIFFICILE INTESTINAL DISEASE Principal Investigator & Institution: Rolfe, Rial D.; Microbiology and Immunology; Texas Tech University Health Scis Center Health Sciences Center Lubbock, Tx 79430 Timing: Fiscal Year 2001; Project Start 15-FEB-1999; Project End 31-JAN-2004 Summary: Toxigenic Clostridium difficile is the cause of essentially all cases of antibiotic-induced pseudomembranous colitis, a life-threatening disease, and the cause of approximately 40 percent of cases of antibiotic-induced diarrhea without intestinal inflammation. The present therapy for patients with C. difficile-associated intestinal disease is the administration of an antibiotic directed against C. difficile. However, there are problems with this current therapy including disease relapse, normal flora disruption, and antibiotic resistance. An alternative to antibiotic therapy of C. difficileinduced intestinal disease is the therapeutic use of bacteriophage. Recent studies indicate that bacteriophage can persist and multiply in tissue, blood and the intestinal tracts of animals and can be effective therapeutic and prophylactic agents. Preliminary experiments demonstrate that administration of bacteriophage to hamsters, treated with clindamycin and a toxigenic strain of C. difficile, prevents development of a fatal ileocecitis. It is the purpose of this research application to more rigorously examine these bacteriophage. Specific Aim number 1 will isolate and characterize a collection of C. difficile bacteriophage with respect to their virulence and host-range so that the most effective phages for use in in vivo studies will be identified. Specific Aim number 2 will examine in vivo properties of C. difficile bacteriophage and their efficacy in the treatment and prevention of C. difficile-associated intestinal disease employing a hamster animal model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BLOOD BASED IBD DIAGNOSIS USING MICROARRAY GENE PROFILES Principal Investigator & Institution: Dervieux, Thierry; Prometheus Laboratories, Inc. 5739 Pacific Center Blvd San Diego, Ca 921214203 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD) has been the focus of an intense research effort to improve diagnostic accuracy, shorten the time to confirmed diagnosis, identify new therapeutic agents, and predict responses to therapeutic agents. Inflammatory bowel disease (IBD)

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continues to present monumental challenges to the basic understanding of the onset and control of inflammatory processes. However, the new science of microarray gene expression profiling provides an incomparably powerful technique to 1. identify the molecular participants of the inflammatory process and 2. differentiate the mechanisms of these IBD diseases at the molecular level. Microarray technology allows the simultaneous study of thousands of expressed genes and the comparison of diseased versus control gene expression profiles. The goal of this project is to apply microarray gene expression technology to patient matched peripheral blood and biopsy samples and directly compare over-expressed and under-expressed genes in CD and UC versus non-IBD controls. From the thousands of genes studied, this project seeks to identify a very small number of genes (a Focused Gene Expression Profile) that will allow development of an accurate, non-invasive blood test for IBD diagnosis and definitive stratification of Crohn's disease and ulcerative colitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BOVINE SPECIFIC VIRULENCE FACTORS OF S.TYPHIMURIUM Principal Investigator & Institution: Baumler, Andreas J.; Associate Professor; Medical Microbiol & Immunology; Texas A&M University Health Science Ctr College Station, Tx 778433578 Timing: Fiscal Year 2003; Project Start 01-DEC-1998; Project End 31-MAY-2007 Summary: (provided by applicant): Salmonella serotypes are the leading cause of foodborne infections with lethal outcome in the United States. The pathogenesis of this diarrheal disease has not been intensively studied in Salmonella since diarrhea does not develop in rodent models. In contrast, calves infected with S. Typhimurium develop similar signs of disease and pathology as observed in humans. Our long-range goal is to elucidate the molecular mechanisms involved in the pathogenesis of S. Typhimuriuminduced enterocolitis. The objectives of this application are to study how the invasion associated type III secretion system (TTSS-1) of S. Typhimurium directs migration of neutrophils into the intestinal mucosa and to determine the role of neutrophils in causing fluid accumulation and intestinal pathology in the calf. Our central hypothesis is that upregulation of CXC chemokines in the bovine intestinal mucosa induced by TTSS-1 secreted effector proteins elicits a neutrophil influx, which is the main mechanism leading to tissue injury and diarrhea during S. Typhimurium-induced enterocolitis. The rationale for the proposed research is that a better understanding of the complex series of events leading to inflammation and fluid accumulation during the interaction of S. Typhimurium with host tissue in vivo will be required for the development of new and innovative approaches for treatment and prevention. We will test different aspects of our hypothesis by pursuing the following four specific aims: (1) Determine the role of TTSS-1 in inducing the production of CXC chemokines in the intestinal mucosa; (2) Investigate CXC chemokine expression in bovine tissue on the cellular level; (3) Determine the contribution of CXC chemokines to neutrophil recruitment during S. Typhimurium induced enterocolitis; (4) Determine the role of neutrophils in S. Typhimurium induced fluid accumulation. We are particularly well prepared to perform the proposed studies because we have established the calf model of human enterocolitis and have identified S. Typhimurium virulence factors, which are essential for causing this disease syndrome. It is our expectation that our approach will establish the complex series of events leading to fluid accumulation during enterocolitis. This outcome will be significant because identification of the key events during S Typhimurium interaction with host tissue in vivo will have a considerable impact on the design of in vitro models used by other investigators in the field.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CENTER FOR THE STUDY OF INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Podolsky, Daniel K.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 05-FEB-1991; Project End 31-DEC-2005 Summary: (Adapted from the application) The Center for the Study of Inflammatory Bowel Disease (CSIBD) is a multidisciplinary program to define fundamental mechanisms underlying Crohn?s disease and ulcerative colitis. This Center encompasses sixty-seven investigators at the Massachusetts General Hospital (MGH) and allied institutions pursuing research in a broad spectrum of basic science relevant to IBD. Since its formation eight years ago, the CSIBD has served as a vehicle to achieve advances in our understanding of these diseases through the study of relevant basic biological processes and the directed study of the diseases themselves. The research program of this Center is organized around the central hypothesis that IBD results from activation by luminal antigens (dietary or microbial in origin) of an upregulated chronic immune response due to genetically determined alterations of epithelial cell or immune function including, a lack of appropriate downregulatory functions. Major advances made possible by the CSIBD in the nine years since its inception include the development and characterization of new genetic mouse models of IBD, delineation of mechanisms of lymphocyte activation and leukocyte recruitment to sites of inflammation, identification of key peptides involved in sustaining mucosal integrity, characterization of the mechanisms of mucosal healing following injury, and improved understanding of the regulation of mucosal immune responses and the complex network of regulatory peptides (cytokines) that modulate mucosal immune and epithelial cell function. Over the next five years, the CSIBD will promote further progress in the study of basic aspects of mucosal biology with translation to the study and treatment of IBD using the tools of molecular and cellular biology. A major focus of CSIBD research in the next five years will be the coordinated multi-disciplinary study of mechanisms leading to chronic intestinal inflammation in the available murine genetic models of "IBD". Experiments will delineate interactions between environmental factors and different genetic loci. The overall goal of advancing our knowledge of IBD will continue to be carried out through five Biomedical Cores. These include Molecular Biology, Morphology and Immunology Cores to provide access to advanced technologies. The Genetic Animal Models and Clinical/Tissue Cores will provide access to relevant animal models and patient tissues for study. In addition to advancing the understanding of IBD per se, the goals of this Center will continue to include the recruitment of established investigators to the study of IBD, enhancing collaboration among Center investigators and encouraging the development of young investigators committed to pursuing IBD research. These goals are fostered by Pilot/Feasibility Study awards which support new research initiatives as well as an enrichment program of seminars, workshops and symposia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHEMOKINE SIGNALING AND COLITIS IN GIA2 DEFICIENT MICE Principal Investigator & Institution: Edwards, Robert A.; Pathology; University of California Irvine Campus Dr Irvine, Ca 92697 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007

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Summary: (provided by applicant): Following MSTP-funded MD/ PhD training, residency and board certification in combined Anatomic and Clinical Pathology at Baylor College of Medicine, Dr. Edwards is currently conducting a year-long research fellowship at the University of Michigan. This revised application has been developed in the course of research performed at these two institutions. It address the role of Gprotein coupled chemokine signaling in T-cell activation, trafficking, and polarized cytokine production in the Gia2-deficient mouse model of inflammatory bowel disease. Deletion of the G-protein alpha subunit Gia2 in mice produces diffuse colitis which can progress to invasive adenocarcinoma, mimicking human ulcerative colitis. Much evidence suggests a central role for G-protein coupled chemokine signaling in mucosal immunity. Before clincial disease is present, T-cells from Gia2 (-/-) mice spontaneously develop a Th1 phenotype, producing elevated levels of Th1-type cytokines (TNFa, IFNg, and IL12). Two new lines of transgenic mice expressing Gia2 only in CD4+ T-cells or colon epthelium are currently being produced and will be used to investigate the mechanisms whereby Gi alpha subunit- dependent signaling contribute to maintaining balanced T-cell responses to environmental antigen. T-lymphocyte subsets from wildtype, Gia2 (-/-), and transgenic mice as described above will be studied to identify whether they respond normally to Th1- or Th2- skewing conditions. These cells will also be used to determine whether particular Gi alpha subunits selectively couple with chemokine receptors known to be involved in T-cell activation and differentiation. Finally, these cells will be screened for changes in chemokine and chemokine receptor expression patterns using gene array, TagMan, and RPA analysis. The responses seen in vitro will be correlated with the development of disease in the strains of mice. These experiments will provide insight into the specificity with which chemokine receptors couple with individual G-protein alpha subunits, and how the loss of Gia2 may lead to alterations in chemokine signaling that predispose to colitis. This application has the support of outstanding mentors at two institutions, and funding of this application will foster Dr Edwards' continued development as a physician-scientist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMOKINES IN HOST DEFENSE TO CAMPYLOBACTER JEJUNI Principal Investigator & Institution: Dwinell, Michael B.; Microbiol & Molecular Genetics; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): This R21 research proposal, submitted in response to "Biodefense and Emerging Infectious Diseases Research Opportunities", NOT-AI-02023, has two specific aims designed to increase our understanding of the pathogenesis of Campylobacter jejuni enterocolitis. The intestinal epithelium comprises a dynamic physical barrier that maintains an active repertoire of innate host defense responses to limit entry of clinically significant food- and water-borne pathogens. These mechanisms include the regulated production of chemokines to coordinate the appropriate innate and adaptive immune effector response. C. jejuni is a leading cause of bacterial diarrheal disease in the world. However, while relatively little is known of the pathophysiologic mechanisms employed to infect the human intestinal tract and elicit disease, interaction at the intestinal epithelium is the most common pathogenic feature of infection. The overall objective of this research proposal is to obtain novel information on the mechanisms of pathogenesis to C. jejuni enterocolitis and will, as an important first step, focus on the coordinated production of chemokines by the cells of the intestinal epithelium as a significant host defense mechanism. Studies in Aim 1 will test the hypothesis that C. jejuni infection of human intestinal epithelial cells stimulates

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production of chemokines for neutrophils, dendritic cells and T lymphocytes, effectors cells that we postulate act in concert to limit C. jejuni entry in vivo. A culture model intestinal epithelium will be infected with C. jejuni and the signaling mechanisms regulating epithelial chemokine production assessed. To define bacterial pathogenicity, studies in Aim 2 will utilize C. jejuni mutants to test the hypothesis that specific Campylobacter virulence factors induce host epithelial cell chemokine expression. Induction of epithelial chemokine expression will be tested in C. jejuni flagella mutants, as well as mutants selected from candidates revealed from a promoter trap-based approach to define novel virulence factors. Together, these studies will provide new insights into the cellular signaling mechanisms and bacterial gene products regulating intestinal epithelial chemokine production as a central host defense function to C. jejuni. Understanding the cellular and biochemical mechanisms of intestinal epithelial host defense to human C. jejuni infection are central to the development of preventative therapeutic strategies to modulate host-pathogen interactions to favor the host. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL COMPONENT Principal Investigator & Institution: Plevy, Scott E.; Associate Professor of Medicine; Children's Hosp Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 15213 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: The clinical component of the University of Pittsburgh Autoimmune Center of Excellence proposes three clinical trials targeting autoimmune disorders involving three different organ systems. In the first trial, a non-Fc receptor-binding anti-CD3 humanized monoclonal antibody will be studied in patients with moderate to severe corticosteroid-refractory ulcerative colitis (UC). The specific immunomodulatory agent is Visilizumab, developed and manufactured by Protein Design Laboratories, Inc. This is a humanized IgG2 monoclonal antibody with amino acid substitutions in the CH2 domain of the Fc region, designed to reduce binding to the FcR and minimize toxicities associated with conventional anti-CD3 monoclonal antibodies. This study is based on preliminary data derived from a Phase I dose escalation trial of anti-CD3 in patients with UC led by investigators at the University of Pittsburgh. In the Phase I trial, five of five patients treated at the lowest proposed dose (15 mcg/kg on two consecutive days) were in clinical remission by day 30. In the new study, the investigators propose to enroll a total of 100 subjects who will be randomly assigned to two treatment groups at a 1:1 ratio. Group 1 will receive a placebo infusion and Group 2 will receive anti-CD3 mAb as a single IV injection. The primary end-point will be the proportion of patients with a clinical remission at week 4. No mechanistic studies are proposed in the context of this clinical trial. The second clinical trial is a Phase I dose escalation study of Visilizumab in patients with rheumatoid arthritis (RA). The study design is derived from the ongoing Phase I dose escalation study in UC at the University of Pittsburgh that served as the basis for the first clinical trial in this component. Twenty patients with active RA will be enrolled in the study. Eligible patients will receive Visilizumab at one of four dose levels (15, 45, 90, and 120 mcg/kg) administered as a single IV injection on each of two consecutive days. Five patients will be treated at each dose level. The primary objective of the study is to evaluate the safety and tolerability of Visilizumab when administered to patients with severe RA. The secondary objective is to obtain preliminary evidence of biologic activity in RA and document clinical responses, as defined by the ACR20 Response Criteria for Improvement. Clinical Trial 3 proposes to develop and test a microsphere-based vaccine for Type I diabetes mellitus (T1DM). The

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rationale for this trial is indirectly derived from data developed by the investigators in the NOD mouse using a dendritic cell-based approach to induce immune hyporesponsiveness to autoantigens involved in the pathogenesis of DM. In those studies, dendritic cells (DC) were modified with antisense oligonucleotides or decoys to modulate expression of CD40, CD80, CD86, and/or NF kappa B transcription factor. Because of appropriate concerns about the logistical and regulatory issues associated with the development of a cell-based therapy, the investigators propose to develop a microsphere-based vaccine consisting of dendritic and Langerhans cell (LC) mobilizing factors and immunoregulatory oligonucleotides that will arrest the deterioration of residual beta cell mass in new onset T1DM. The investigators postulate that injection of microspheres releasing chemokines into the skin will recruit DC and LC to the injection site. Immunoregulatory oligonucleotides incorporated into the microsphere will be taken up by the antigen presenting cells, converting them to a tolerizing phenotype. No pre-clinical data supporting the activity of these microspheres in the NOD model are provided. The proposed clinical trial is a safety trial of a vaccine for T1DM that will involve sequential administration of water-based microspheres containing LC and DC attractive chemokines, followed by injection of a second microsphere containing either NF kappa B oligonucleotides decoys or antisense oligonucleotides to CD40, CD80, and CD86. In Specific Aim 1, the investigators will assess the safety of single and multiple administrations of microsphere encapsulated combinations of DC/LC attracting chemokines and immunoregulators in normal volunteers and recent onset T1DM. In Aim 2, the investigators propose to examine the clinical efficacy of single and multiple administrations of microspheres in recent onset T1DM. In Aim 3, the investigators will evaluate immune responses in microsphere-treated individuals and correlate the results with clinical remission or improvement. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTRACTILE SIGNAL TRANSDUCTION IN ULCERATIVE COLITIS Principal Investigator & Institution: Cao, Weibiao; Rhode Island Hospital (Providence, Ri) Providence, Ri 02903 Timing: Fiscal Year 2003; Project Start 10-JAN-2003; Project End 31-DEC-2004 Summary: (provided by applicant): Ulcerative colitis is a chronic inflammatory condition affecting the large bowel: Although it is most frequent in the rectosigrnoid area, it may involve the whole colon. Inflammation in ulcerative colitis is histologically limited to the mucosa, and its effects have been better characterized in the superficial than in the deeper layers such as muscularis propria. Inflammation, however, may affect the muscle layer, leading to motor dysfunction, which contributes to key clinical symptoms, including diarrhea, constipation, and crampy abdominal pain. To define inflammation, associated changes in motor function we will examine the circular muscle from the sigmoid colon from patient with active ulcerative colitis and compare it with muscle from disease-free margins of histologically normal colon tissue from cancer resections. The sigmoid is most often involved and frequently resected, and this avoids variations associated with different anatomical locations of the disease. In preliminary experiments, we find that inflammatory mediators such as interleukin-1beta and hydrogen peroxide are present in the muscularis propria. Our central hypothesis is that inflammatory mediators, first produced by inflammatory cells in the mucosa, may induce production of additional mediators by the target cells themselves, and that in time the muscularis propria becomes affected leading to motor disturbances. We therefore propose to: A) Define inflammation-induced changes in contractile signal

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transduction pathways of human sigmoid colon. B) Test the effect of selected inflammatory mediators, known to be present in ulcerative colitis mucosa, to determine their individual contribution to the observed changes in colonic motor function. C) Determine whether inhibition of selected inflammatory mediators may reverse inflammation-mediated changes in colonic motor function. Examining the relationship between inflammatory mechanisms and changes in motor function may help in understanding the functional disturbances associated with ulcerative colitis and identifying new targets for therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTROL OF COLONIC MOTILITY IN HEALTH AND DISEASE Principal Investigator & Institution: Sarna, Sushil K.; Professor; Surgery; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2001; Project Start 01-APR-1984; Project End 31-DEC-2001 Summary: Abnormal colonic motility in idiopathic human ulcerative colitis as well as in animal models of colonic inflammation is characterized by the suppression of rhythmic phasic contractions, decrease n tone and increase in the frequency of giant migrating contraction (GMCs). These motility abnormalities play a key role in producing the symptoms of diarrhea, urgency of defecation and abdominal cramping. The cellular mechanisms for the generation of tone, phasic contractions and GMCs in the colon are not known. The first aim of this proposal is to investigate the roles of specific signal transduction pathways in the generation of tone and stimulation of phasic contractions in the colon. The second aim is to determine how these signal transduction pathways are modulated by the inflammatory response to suppress the tone and phasic contractions. Key intracellular messengers including cytosolic free Ca2+, Ca2+ efflux from intracellular stores, IP3, DAG and PKC, will be measured to support the physiological and pharmacological observations. Patch clamp studies will be done on freshly dissociated cells and circular muscle strips taken from normal and inflamed canine colon. Extensive in vivo and in vitro data are available from this species to help in the interpretation of our data and relating it to clinical diseases. Mucosal exposure to ethanol and acetic acid will be used to induce inflammation. The motility abnormalities in this model are similar to those reported in human ulcerative colitis. An understanding of the differences n signal transduction pathways that generate tone and stimulate phasic contractions may present the opportunity to regulate each type of contraction separately from the other. In inflammatory bowel disease and other forms of gut inflammation it would be desirable to selectively stimulation phasic contractions and tone to minimize diarrhea, urgency of defecation and abdominal discomfort. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--GENETIC ANIMAL MODEL FACILITY Principal Investigator & Institution: Terhorst, Cox; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 05-FEB-1991; Project End 31-DEC-2005 Summary: (Adapted from the application) The Genetic Animal Core represents one of the centerpieces of the CSIBD's research program for the next proposed funding period. The availability of powerful murine models of IBD offers the opportunity to assess key aspects of the hypotheses underlying the development of the research program of the CSIBD. In addition, these models will allow defining mechanisms contributing to the expression of chronic intestinal inflammation. Overall, the availability of these murine

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models allows for a rapid analysis of the contributions of genetic mutations or novel therapeutic agents to the pathogenesis of colitis. Moreover, this Core has the ability to compare and crosscheck the influence of mutations or of therapeutic agents that may illuminate underlying mechanisms in the onset of disease. The genetic mouse models used in this Core are subdivided into three categories: 1) spontaneous chronic colitis; 2) colitis induced by adoptive transfer of wt or mutant T cells into immunodeficient mice; and 3) colitis induced by bone marrow transplantation into immunodeficient mice. In addition, the Core's mandate has been expanded over the past two years in response to the needs of CSIBD investigators to include two additional services: 4) chemicallyinduced colitis in mutant mice (DSS or TNBS); and 5) isolation of intestinal epithelial lymphocytes and lamina propria lymphocytes from wt and mutant mice. Thus, the overall goals of this Core include provision of these genetic murine models to CSIBD investigators and continued development and refinement of the models themselves. The core currently has a large "menu" of mice available to center investigators, which is listed in Tables 10 and 11 in the grant application. The core will also, in collaboration with the morphology core, characterize the genetic profile of the experimental animals and parallel documentation of IBD, primarily using PCR and histology. The core will also facilitate obtaining samples from animals and finally will play a role in developing new genetic models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COX GENE REGULATION IN INTESTINAL MYOFIBROBLASTS Principal Investigator & Institution: Powell, Don W.; Professor of Medicine; Internal Medicine; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: The general hypothesis of this grant proposal is that intestinal subepithelial myofibroblasts (ISEMF) are the source of soluble factors that modulate epithelial growth, differentiation, and repair and play a pivotal role in mucosal immunophysiology and cancer. Located at the interface between the epithelium and lamina propria, ISEMF modulate information transfer between these tissue compartments. Through elaboration of basement membrane components, prostaglandins (PGs). and growth factors, ISEMF modulate processes of epithelial cell growth, differentiation, and wound repair. One major pathway by which ISEMF influence epithelial and lamina propria cells is through the production of PGs by cyclooxygenase-2 (COX-2). Data indicate that the bulk of mucosal PG synthesis occurs in the lamina propria, possibly in ISEMF. Because COX-2 regulation appears to be different in the various cell types thus far studied, this proposed research will test the hypothesis that ISEMF are major sites of COX-2 expression and that pro- and antiinflammatory agents act in part by inducing or inhibiting COX-2 expression in ISEMF. Specific Aims: 1. Determine the mechanisms by which proinflammatory cytokines (IFN-gamma, TNFalpha, IL-1) and eicosanoids (arachidonic acid, various HETEs) induce COX-2 gene expression in ISEMF, 2. Analyze the mechanisms responsible for inhibition of COX-2 gene expression in ISEMF by antiinflammatory cytokines (IL-4, IL-13) and therapeutic corticosteroids, and 3. Characterize COX-2 expression in human ISEMF in situ and in primary ISEMF cultures from normal small intestine and colon and from various inflammatory diseases such as ulcerative colitis, Crohn's disease, and collagenous colitis and various neoplastic states such as adenomatous and hamartomatous polyps and both sporadic and familial adenomatous polyposis colon cancers. We will use an ISEMF cell line (18Co) isolated from human colon, reporter gene constructs containing

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full length and mutant COX-2 regulatory elements, gel shift assays, in vitro and in vivo promoter footprinting to determine the role of NF-kappaB/cRel, cEBP/NF-IL6, CREB/ATF, and other transcription factors in the induction and inhibition of COX-2 expression in ISEMF. Key findings from studies with 18Co will be confirmed in primary cultures of ISEMF from normal and various disease states. Using immunohistocytochemistry and in situ hybridization techniques we will identify the cellular sites of COX-2 gene expression in normal and diseased tissue and thus shed light on the role of ISEMF in gastrointestinal disease. These studies should define the processes which mediate signalling between intestinal subepithelial myofibroblasts and other immune and non-immune cells, and how these processes are disrupted in pathological states such as IBD, fibrotic disorders, and cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CYTOKINES AND COMPLEMENT IN NEPHRITIS AND COLITIS Principal Investigator & Institution: Lin, Feng; Pathology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-JAN-2006 Summary: (provided by applicant):This proposal is for a three year training program at Case Western Reserve University (CWRU) for the development of a career in academic experimental immunology. The principal investigator, a Ph.D. in molecular biology who is now completing postdoctoral training in molecular immunology, will expand upon his skills and transition to independent research through an integrated program involving further work with his mentor and other investigators.The program will expand knowledge in the interplay of complement activation and cytokine generation in the settings of digestive and particularly renal diseases and in therapeutics in animal models. Dr. Edward Medof will mentor the PI's scientific development. He is a recognized leader in complement regulatory proteins that protect self tissues from complement attack, and pioneered research in the decay accelerating factor (DAF), the first of these to be described. He is a Professor in Pathology, is Associate Director of the CWRU Immunology Postdoctoral and Predoctoral Training Programs, and has trained numerous postdoctoral fellows and graduate students. To enhance the training, the program will include Dr. Steven Emancipator, Professor of Pathology, an authority in immunological diseases of the kidney, Dr. Alan Levine, Associate Professor of Medicine, a recognized expert in cytokines and inflammatory bowel disease, Dr. David Salant, Chief of Nephrology at Boston University, a world renowned expert in antibodyinduced renal diseases, and Dr. Peter Heeger, an expert of cellular immune mechanisms. Additional faculty will provide scientific and career advice.Research will focus on inflammatory mediators that are generated in experimental models of inflammatory bowel disease and particularly nephritis. The applicant has generated a DAF knockout mouse and shown that in the absence of DAF, tissue injury is greatly enhanced in nephrotoxic serum-induced nephritis and dextran sulfate sodium-induced colitis and in delayed, possibly NK cell-mediated allograft rejection. Specific aims are to 1) define the patterns and site(s) of cytokine production in the two disorders and characterize the mechanism of allograft rejection, 2) investigate these issues in related diseases, and 3) explore the effects of targeted recombinant DAF modules on disease pathogenesis. The results will constitute the first in vivo analysis of the interplay between complement activation and cytokine production, and could have therapeutic benefits.The integrated research activities at CWRU encompassing Pathology, Medicine, and the Biomedical Sciences Training Program incorporate diverse expertise and a full range of state-of-theart facilities that provide an ideal setting for training in specific programs. It should

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maximize the opportunity for a promising young scientist to develop a niche for an independent career. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CYTOPROTECTIVE ROLE OF HEAT SHOCK PROTEINS IN IBD Principal Investigator & Institution: Chang, Eugene B,.; Martin Boyer Professor of Medicine; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 30-SEP-1993; Project End 31-JAN-2008 Summary: (provided by applicant): This revised renewal application proposes studies aimed at defining the regulation and mechanisms of action of two intestinal epithelial heat shock proteins (hsp), hsp25/27 and hsp72, both exhibiting epithelial- and colonspecific expression in the gut. Both hsps have essential roles protecting the gut epithelium against many forms of stress, particularly those associated with inflammation such as oxidants. From new studies of IBD and of acute and chronic experimental colitis, the expression of both hsps is significantly impaired in areas of active inflammation, a finding that would likely render the mucosa highly susceptible to extensive and severe injury. Three specific aims are proposed: (1) to further characterize the relative deficiency of hsp25/27 and hsp72 expression in areas of active mucosal inflammation, determine if perturbed expression alters the course of DSS-induced colitis, and identify potential mechanisms for selective hsp downregulation, (2) to define the determinants of normal colon- and epithelial-specific expression of hsp25 and hsp72, with particular attention to the role of colonic flora and mucosal immune cells, and (3) to understand how hsps protect four vital cell functions of intestinal epithelial cells (IEC). For the first specific aim, hsp27 and hsp72 expression and localization in normal and inflamed colons will be assessed. Unique mouse models expressing high or negligible colonic hsps will be studied to determine if the course of DSS induced colitis is mitigated by hsp presence. Potential "hsp-suppressive" cytokines will be identified. Next, we will determine what aspects of enteric flora and mucosal immunocytes maintain the in vivo expression of hsp25 and hsp72. Specific luminal and lamina propria signals that maintain hsp expression will be determined by a combination of in vitro and in vivo approaches. Finally, we will determine how oxidants, major mediators of inflammation-associated stress and injury, impair specific and vital IEC functions, e.g. (1) Na absorption mediated by the Na-H exchanger, NHE3, (2) Na, K-ATPase function and basolateral-restricted expression, (3) mitochondrial and microtubular interaction and function, and (4) tight junction-mediated barrier function. How hsps limit the extent of oxidant-induced impairment of these functions will also be examined. A better understanding of natural defense mechanisms of the gut can be exploited to develop novel therapies aimed at restoring or augmenting the impaired hsp response in areas of active inflammation to limit the extent and severity of mucosal injury in IBD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIAGNOSIS OF DYSPLASIA BY FLUORESCENCE SPECTROSCOPY Principal Investigator & Institution: Van Dam, Jacques; Associate Professor; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 25-SEP-2000; Project End 31-AUG-2005 Summary: (Applicant's Description) The goal of this research proposal is to provide salary support to facilitate the advancement and completion of an NCl-funded clinical research proposal. The Principal Investigator, a clinically active physician scientist, is a collaborator on NCI R01 CA 53717 "Real Time In Vivo Diagnosis of Dysplasia by

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Fluorescence." The goal of the R01 is, in part, to develop endoscope-compatible, fluorescence spectroscopy systems for the real time detection of precancerous (dysplastic) alterations in the luminal gastrointestinal tract. Both fiber optic-based contact probe techniques for localized detection and fluorescence spectral endoscope systems for wide area imaging of disease will be developed and applied clinically. Multi-wavelength excitation fluorescence and reflectance system will be used to characterize the optical/spectroscopic properties of relevant tissue types. The results of this study will be used to select optimal excitation wavelength(s) and design fiber probes with controllable sampling depth for targeting detection of superficial lesions. By combining this information with tissue optical parameters, models of colon and esophageal fluorescence measured at colonoscopy and gastroscopy respectively, will be developed. Inverse modeling will be developed for extracting histopathological information from the clinical spectra. The existing fluorescence imaging colonoscope will be modified for additional clinical studies, including application in patients with Barrett's esophagus. The techniques developed in this program will be clinically tested for rapid detection of colorectal dysplasia/carcinoma in chronic ulcerative colitis and dysplasia in Barrett's esophagus and as such are "translational" in nature. Based on extremely successful preliminary data, light (white light) scattering spectroscopy (LSS) will be used to determine the size and degree of "crowding" of nuclei of superficial mucosal cells in the columnar-lined (Barrett's) esophagus. LSS will be used to guide the endoscopic detection (and pathological grading) of mucosal dysplasia. The Principal Investigator is devoted to training clinical researchers and will continue the formalized instruction and mentoring of young clinicians so that they may successfully engage in meaningful clinical research. In this way, the Principal Investigator will help mentor the next generation of physician scientists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DNA MICROARRAY FOR GASTROENTEROLOGY RESEARCH Principal Investigator & Institution: Curto, Ernest V.; Integriderm, Llc. 2800 Milan Ct Birmingham, Al 35211 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-OCT-2002 Summary: We propose to create a highly informative DNA microarray specifically for gastrointestinal (GI) research with an emphasis on genes associated with inflammatory bowel disease (IBD). RNAs will be harvested from pertinent GI tissues and cell types and screened for genes of high differential expression ("signature biomarker genes") utilizing currently available human DNA microarrays. Gene expression of GI tissues will be profiled against available sequence-validated human cDNAs (ca. 40,000). The 4400 most differentially expressed genes will be selected for inclusion on the array, providing an eight-to-ten fold enrichment of important genes over housekeeping genes. From the selected set of genes we will choose a very informative subset of 384 genes to be triplicated on the array. This triplicate subset will provide statistical validation for what we believe will be some of the most important genes in GI research. Our patentpending method will drive the selection criteria with a bias toward those genes deemed of particular interest to gastroenterology researchers. The GI array will provide researchers with a cost-effective tool to study gene expression in GI tissues. PROPOSED COMMERCIAL APPLICATIONS: The success of the human genome project has sparked growing interest into the genetics of the GI tract. Our GI array will fill a niche in this market, providing a highly informative and cost effective DNA array for researchers eager to pursue this new technology to develop new clinical diagnostics and in vitro

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assays for drug therapies. This timely product will complement our best selling dermatology array DermArray(TM). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EARLY EVENTS IN COLITIS-ASSOCIATED COLORECTAL CANCER Principal Investigator & Institution: Chang, Wen-Chi; Fox Chase Cancer Center Philadelphia, Pa 19111 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Ulcerative colitis is associated with an increased risk of colonic dysplasia and progression to invasive colorectal cancer (CRC). Although the molecular events required for tumor formation remain to be established, recent data suggest that this pathway differs from that of sporadic CRC. In particular, mutation of the p53 gene appears to be an early event in colitis-associated CRC as is evident from the presence of p53 mutations in the non-tumor inflamed colon tissue. In addition, 70-80% of colitis-associated CRCs have p53 mutations, but only 27% of them have APC mutations. However, there are no mouse models that recapitulate the genetic and histopathological changes that accompany human colitis-associated CRC. The dextran sulfate sodium (DSS) model of induced colitis provides a unique opportunity to evaluate the spectrum of histological changes that lead to the development of colitis and subsequent dysplasia similar to ulcerative colitis in humans. Induction of colitis in p53 mice with DSS should lead to the establishment of an excellent model with which to examine the hypothesis that inflammation-related p53 mutation is an initiating event in CRC associated with colitis. Colitis will be induced in heterozygous p53 mice (p53) by administration 4 cycles of DSS (4 days of 4% DSS followed by 17 days of plain water). The gatekeeper function of the p53 and APC genes in colitis-associated CRC will be determined by mutational analysis of these genes in microdissected inflamed noncancerous colonic epithelial cells. Microarray-based techniques will be utilized to identity early changes in the expression of genes within the inflamed noncancerous colonic epithelium that may serve as molecular targets for chemopreventivc intervention. The effect of a p53 deficiency on both the formation of colitis-associated colorectal dysplasias/cancers and the pathological characteristics of these lesions will be assessed in this mouse model by allowing animals to live for an extended period of time following DSS exposure. Establishment of the first clinically relevant model for ulcerative colitis-associated CRC is anticipated to facilitate the elucidation of the molecular mechanisms of colitis-associated colon tumor formation and the identification of cellular targets for early chemopreventive intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECT OF MUCOSAL BARRIER ON SHIGA TOXIN ABSORPTION Principal Investigator & Institution: Morgan, Timothy W.; Veterinary Pathology; Iowa State University of Science & Tech Ames, Ia 500112207 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (provided by applicant): Diarrheal diseases caused by enteropathogenic Gram-negative bacteria are a risk factor for morbidity and mortality in people who live in both underdeveloped and developed countries including the United States. E. coli 0157:H7 has increasingly been recognized as a cause of hemorrhagic colitis and the associated complicating condition, hemolytic uremic syndrome. E. coli 0157:H7 colonizes the intestine, intimately attaches to the intestinal mucosa in a process that requires intimin (an adhesion factor), induces hemorrhage and acute inflammation, and

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releases Shiga toxins (Stx) that are absorbed systemically and cause vascular damage. The process by which Stx enters the systemic circulation is poorly understood. Studies in rabbits and our preliminary data suggest that reduction of leukocyte (i.e. neutrophil) adherence by adhesion molecule inhibitors reduces the clinical severity of disease and reduces death caused by E. coli 0157:H7. It is our hypothesis that damage to the intestinal mucosa enhances passive absorption and systemic spread of Stx, resulting in enhanced Stx-induced lesions in brain and blood vessels. This damage may be caused by the bacteria, the host inflammatory response, or a combination of the two. A 3-day old pig model of E. coli 0157:H7 enteritis produced by a wild type (Stx positive, intimin positive strain) will be developed. This model will be used to determine if infection by an intimin positive, Stx negative strain of E. coli 0157:H7 or if chemically induced mucosal ulceration enhance absorption of exogenous Stx. In each of these studies, one group of pigs will be treated with a selectin inhibitor, TBC 1269, to reduce neutrophil infiltration and the results wilt be compared to the non-treated control groups to determine the contribution of neutrophils to mucosal damage and Stx absorption in a 3day old pig model of E. coli 0157:H7 enteritis. The results of these studies will help define the mechanistic basis of Stx absorption, potentially leading to new therapeutic approaches to treating E. coli 0157:H7 enteritis and the associated systemic lesions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOGENOUS LIGANDS: ROLE IN NEUROLOGICAL DISORDERS Principal Investigator & Institution: Mechoulam, Raphael; Hewbrew University of Jerusalem Timing: Fiscal Year 2002; Project Start 15-SEP-1995; Project End 31-MAR-2007 Summary: (provided by applicant): Anandamide and 2-arachidonyl-glycerol (2-AG) which we isolated from porcine brain in 1992 and from canine gut in 1995 respectively are the major endogenous cannabinoids identified so far. We have strong indications based on chromatographic separations monitored by receptor binding studies that additional endocannabinoids are present in brain. We shall try to isolate and identify them. We have indications that 2-AG is released in brain on closed head injury and that 2-AG reduces edema and neurological consequences of the injury. We aim at solidifying the data which could show that endocannabinoids play a neuroprotective role. We have found that 2-AG reduces the formation of TNF-alpha, a multipotential cytokine. We plan to look at the activity of 2-AG with other cytokines. We plan to synthesize 2-AGtype compounds which will parallel 2-AG in its actions but will not be hydrolyzed in vivo and could thus serve as lead compounds for novel drugs with neuroprotective and anti-inflammatory activity. We have synthesized major cannabidiol (CBD) metabolites. As CBD is a potent anti-arthritic cannabinoid, with no psychotropic effects, we shall investigate the activities of these metabolites on the production of several cytokines as well as in models of multiple sclerosis and experimental colitis. We shall attempt to synthesize CB1 agonists which act outside the brain only. (Added, May 2001) 1. We have now isolated and identified a new endocannabinoid 2. We have shown that 2-AG reduces brain infarct volume and hippocampal cell death due to closed head injury. An antagonist blocks these 2-AG actions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENTEROHEMORRHAGIC E COLI ALTER INTESTINAL FUNCTION Principal Investigator & Institution: Hecht, Gail A.; Professor of Medicine; Medicine; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612

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Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: Infection with enterohemorrhagic E. coli (EHEC), acquired from contaminated food or water, represents a major health problem worldwide with EHEC being the fourth most costly foodborne pathogen in the USA. Although many EHEC strains produce Shiga toxin (Stx), its role in pathogenesis is not understood. In some species, the presence of attaching and effacing (A/E) lesions correlate more closely with intestinal symptoms than does the expression of Stx. While the formation of A/E lesions may be sufficient to induce diarrhea, the production of Stx may be a prerequisite for hemorrhagic colitis. These findings underscore the lack of understanding of the pathogenesis of EHEC. While much effort has been focused on the extraintestinal manifestations of EHEC, the effects of this important pathogen on the intestine have been grossly understudied. The hypothesis of this proposal is that EHEC has direct effects on its initial host target tissue, the intestinal epithelium, which contribute to the associated symptoms. The studies proposed here will utilize two separate models to investigate the effects of EHEC infection on intestinal epithelial function, a reductionist model of cultured human intestinal epithelia and a murine model. Preliminary data show that two major physiological processes, tight junction (TJ) barrier function and the epithelial-initiated inflammatory cascade, are altered in both of these models following infection with EHEC. It is likely that both of these alterations contribute to EHECassociated diarrhea. The impact of EHEC infection on these physiological functions and the underlying mechanisms will be explored by three Specific Aims. The first Specific Aim is to characterize the effect of EHEC on intestinal epithelial tight junction barrier function. The mechanisms by which EHEC perturbs the TJ barrier will be addressed focusing on the role of cytoskeletal contraction and changes in key TJ-associated proteins. Specific Aim 2 is to define the signaling pathways by which EHEC activates the inflammatory response within intestinal epithelial cells. The events that lead to the activation of NF-kappaB, the upregulation of proinflammatory cytokines, such as IL-8, and neutrophil transmigration will be explored. The studies outlined in Specific Aims l and 2 will use the established in vitro cell culture model. Specific Aim 3 is to establish and characterize a murine model of intestinal EHEC infection, The effects of EHEC infection on TJ barrier function as well as epithelial-initiated inflammation will be explored. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENVIRONMENTAL FACTORS AND INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Higuchi, Leslie M.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This K08 award application is designed to enrich the candidate's career development in the epidemiology of gastrointestinal diseases. The program integrates mentored "hands on" experience in the proposed research plan on inflammatory bowel disease (IBD), didactic coursework to advance the knowledge and skills of the candidate, and enhanced interactions with other investigators through seminars, conferences, and scientific meetings. In the later years of the 5-year proposed program, the candidate plans to expand her work in the epidemiology of pediatric gastrointestinal illnesses. The candidate's sponsor is Dr. Richard J. Grand, an accomplished pediatric gastroenterologist with significant established experience in the field of IBD. Her co-sponsor is Dr. Graham A. Colditz, the Principal Investigator of the Nurses' Health Study at the Channing Laboratory. The program combines the

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institutional resources of the Children's Hospital, Boston and the Channing Laboratory of the Brigham and Women's Hospital, Harvard medical School. The Research proposal is a prospective cohort study to examine the association of environmental factors and the two types of IBD, Crohn's disease (CD) and ulcerative colitis (UC). The study base population will be composed of the Nurses' Health Study (NHS I) and the Nurses' Health Study II (NHS II) cohorts. Specific Aim 1 is to establish a database of confirmed cases of CD and UC in the NHS I and NHS II cohorts. Specific aims 2 through 4 will examine the association of specific dietary factors, smoking, and exogenous estrogen therapy and the development of CD or UC. Since the establishment of the NHS I in 1976 and the NHS II in 1989, information pertaining to participants' dietary intake and lifestyle factors has been updated at regular intervals, prior to the onset of CD or UC. Cases of CD and UC will be identified by biennial questionnaires and confirmed by medical chart review using established criteria. Analyses will compare age-specific incidence rates of CD and UC within different exposure categories, multivariate analyses, using the Cox proportional hazards model, will be performed. The proposed study will establish a unique database of repeated dietary and lifestyle assessments over several decades and will provide the opportunity to examine the influence of nutritional and lifestyle risk factors on IBD risk, improve our understanding of IBD pathogenesis, and define potential methods of prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EOSINOPHIL PROTEINS AND GASTROINTESTINAL DISEASE Principal Investigator & Institution: Furuta, Glenn T.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 31-AUG-2003 Summary: (taken from application) The candidate: Dr. Furuta began working in a basic science laboratory during his GI fellowship. This experience led him to choose a career path that would allow him to become a basic scientist. He received a National Research Service Award and a Career Development Award from the Crohn's Colitis Foundation. He has demonstrated the sustained productivity necessary to become an independent investigator. He now seeks to develop skills in molecular gene regulation and epithelial physiology that will permit him to study the role of the eosinophil in GI disease. He is committed to a career in academic medicine and basic science research. The environment: The candidate will work under the close supervision of expert's in gene regulation, epithelial ion secretion, eosinophil biology and gastrointestinal immunology. Dr. Tenen will serve as the primary mentor and Drs. Colgan, Ackerman and Wershil as co-mentors. Dr. Furuta has worked with each of his mentors previously and has established solid working relationships. The Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, and Harvard Medical School are committed to providing nurturing scientific environments. These environments provided both the physical plant necessary to complete the proposed studies and the training activities necessary of his development into an independent investigator. His division is committed to providing the protected time and salary support to completed the studies detailed in this proposal. The research: A number of gastrointestinal disease are characterize by the infiltration of eosinophils into the tissue layers, but the precise participation of the eosinophil in GI disease has not been defined. In preliminary data, we show that eosinophil-derived major basic protein can 1. induce the production of IL8 from intestinal fibroblasts, 2. potentiate chloride secretion from colonic monolayers, and 3. induce tissue swelling and neutrophil infiltration in a murine model of inflammation. These findings suggest new mechanisms by which eosinophils may

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participate in the in [sic] GI diseases. We hypothesize that eosinophil derived granule proteins (EDGPs) participate in GI disease by stimulating pro-inflammatory cytokine/chemokine production and epithelial chloride secretion. We will determine the mechanisms of: 1. EDGP stimulated IL-8 production in intestinal fibroblasts and EDGP stimulated neutrophil transmigration across intestinal epithelium, 2. EDGP stimulated epithelial cell chloride ion secretion and 3. EDGP stimulated neutrophil infiltration, changes in vascular permeability and fluid secretion in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXCELLENCE IN CLINICAL RESEARCH IN CHILDREN'S SURGERY Principal Investigator & Institution: Moss, R Lawrence.; Surgery; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): This application seeks five years of support to allow R. Lawrence Moss, MD, to make major contributions to the level of Children's Surgery by achieving his career objectives in patient-oriented clinical research. His foremost professional objective is to introduce scientific rigor and established clinical research techniques into the manner in which surgical treatments in children are evaluated. Dr. Moss is an active clinical Pediatric Surgeon and an internationally recognized and established clinical investigator. He is the principal investigator for the first ever multicenter clinical trial in Children's Surgery ROl HD 38462. He serves as Stanford Site Director and only surgeon of the first multi-disciplinary patient-oriented research network in Pediatrics. He holds multiple national leadership positions in Pediatric Surgery, and is recognized as a leader in clinical research in the field. He has mentored twelve postdoctoral fellows in clinical research of whom the past five have each obtained extramural funding based on their outstanding productivity. Stanford University is an exceptionally rich environment for patient-oriented research, and has identified clinical investigation as a major focus of the Medical School for the next decade. Dr. Moss' work is an integral component of this institutional mission in clinical research. Examples of work to be conducted during the training period include; 1) leading a twelve-center trial of peritoneal drainage versus laparotomy for infants with perforated necrotizing enterocolitis; 2) establishment of the first multi-center neonatal surgical database for children with congenital anomalies; and 3) development of a multiinstitutional consortium to study biliary atresia. With the support of this award, the awardee's underlying objectives are three-fold: 1) to make substantive contributions to the field Children' s Surgery that will directly impact the health and well-being of children; 2) to conduct multiple clinical research projects that change the shape of the discipline of academic Pediatric Surgery; and 3) to mentor the next generation of physician scientists in Children's Surgery to be critical thinkers who are well versed in clinical research techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GASTROINTESTINAL CANCER SCREENING AND SURVEILLANCE Principal Investigator & Institution: Provenzale, Dawn T.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 29-SEP-2000; Project End 31-MAR-2005 Summary: (Applicant's Description) My research plan focuses on gastrointestinal cancer screening and surveillance. The integrated research approach targets three clinical areas (screening for colorectal cancer, and surveillance of patients with Barrett's esophagus

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and ulcerative colitis). The study methods link decision modeling with clinical research to answer important clinical questions regarding screening and surveillance. The integrated research process includes: 1) Identifying the relevant screening and surveillance questions for study, 2) structuring a decision analytic model (using published literature) to answer the study questions, 3) identifying the optimal strategy given the available data, 4) targeting critical parameters in the model for which there are incomplete data, 5) designing and implementing observational studies for primary collection of these data, and 6) integrating the results of the clinical studies into decision models to provide clinicians and policy makers with new, patient specific data about the optimal management strategy. Research projects focus on the development of the acceptable and cost-effective colon cancer screening strategies for veterans. Future projects will determine the costs and resource needs to implement these preferred strategies. Another study evaluates risk factors for presentation with late stage colorectal cancer. If modifiable factors such as access to screening, or physician delay in follow-up of positive screening tests are identified, then interventions can be made to improve access and reduce delay with the aim of reducing colorectal cancer mortality. Ongoing and future studies will examine the health related quality of life of patients with Barrett's esophagus and ulcerative colitis using standardized measures (SIP, SF-36, RFIPC, TTO). The results will be summarized and incorporated into the decision models to determine their effect on surveillance strategies. The other critical component of my career plan is the structured mentoring program for gastroenterology/health services research fellows. The program integrates coursework leading to a Master of Science in Clinical Research with a mentoring program that provides the fellow with the opportunity for patient centered research experience. There is a gradual increase in his/her research independence under my supervision, leading to the design and execution of his/her own research project, including data analysis, abstract and manuscript preparation and presentation of the study results at a national meeting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC STUDIES IN INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Cho, Judy H.; Assistant Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2001; Project Start 15-MAR-1998; Project End 31-JAN-2003 Summary: The research project involves identifying susceptibility loci for IBD through genome-wide screening of affected relative pairs using non- parametric linkage analysis and gene identification through a variety of approaches. Unique aspects of the genetics of inflammatory bowel disease include the overlap between Crohn's disease and ulcerative colitis and its high prevalence in Ashkenazi Jews. Data on putative loci on chromosomes 16 and 12 are provided. Strategies for fine localization of loci, including fine-mapping by linkage disequilibrium, are proposed. alternative approaches to gene identification and mutation detection are discussed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GI INFLAMMATION

NEMATODES

AND

FUNCTIONAL

RESPONSES

TO

Principal Investigator & Institution: Shea-Donohue, Terez; Professor; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, Md 20852 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007

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Summary: (provided by the applicant): The overall hypothesis of the proposed studies is that the gastrointestinal tract contributes to host defense through stereotypic functional responses that are orchestrated by the profile of cytokines present. Crohn's disease and most murine models of colitis are linked to exaggerated production of Th1 cytokines. In contrast, the host defense to enteric nematode infection is dependent primarily on the type 2 cytokines, IL-4 and IL- 13. Of the type 2 cytokines, IL-4 is most important for the establishment of the Th2 profile and for the down regulation of Th1 pathway, yet there are few studies of IL-4, or other type 2 cytokines, in vivo. In addition, IL-13 shares many biological activities with IL-4 by acting at a common receptor chain. The central premise of this proposal is that colitis-induced changes in the smooth muscle and epithelial cell function will be improved by administration of exogenous IL-4 or IL-l3, or by upregulation of their endogenous production via nematode infection. We propose that the mechanism by which cytokines alter gut function involves receptor-mediated activation of Stat6 signaling pathways, mast cells and mast cell mediators, and enteric nerves. There are 3 specific aims. 1.) Determine that the profile of cytokines present in the gut controls epithelial cell and smooth muscle function in colitis and nematode infection; 2.) Determine the role of altered Th2 cytokines in colitis-induced alterations in epithelial cell and smooth muscle function; 3.) Determine the mechanisms of altered epithelial cell and smooth muscle function in mice with and without colitis and treated with IL-4, IL13, or nematode infection. Based on our preliminary data, we expect that type 2 cytokines have significant region-specific actions on the small and large bowel, and that restoration of the balance of type 1/type 2 profiles will be of therapeutic benefit to the impaired secretomotor function in IBD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GIF REGULATION OF B CELLS AND CD4 CELLS Principal Investigator & Institution: Sugie, Katsuji; La Jolla Allergy/Immunolgy Allergy and Immunology San Diego, Ca 921211118

Institute

for

Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): GIF is a 13-kDa cytokine discovered in the course of the study on IgE synthesis. It is encoded by a single gene in the genome and its nucleotide sequence is identical is that published for macrophage migration inhibitory factor (MIF). MIF(GIF)-/- mice show enhanced susceptibility to Leishmania major. These mice are incapable of developing the experimental colitis. These findings support the notion that GIF is involved inactivating the innate immune system. GIF protein is expressed in the cytosol of hematopoietic and nonhematopoietic cells. GIF secreted from T cells is cysteinylated at C60, whereas that contained in the cytosol of the same cells is unmodified. The modification at C60 is required for the capability of this cytokine to bind to target cells, to inhibit BCR-mediated uptake of antigen, and to inhibit IL-4 secretion from CD4 cells. Binding assays demonstrated that GIF receptors are expressed on T and B cells after these cells are activated, but not on macrophage and dendritic cell lines. Chemical crosslinking experiments suggest that GIF binds to a 50-52 kDa cell surface protein. GIF-/- mice show enhanced antibody responses to T-dependent antigens. GIF-/- CD4 cells were polarized toward a Th2 phenotype as compared with wild type cells. To clarify the role of this cytokine in T-dependent and -independent humoral responses, GIF+/+ and -/- mice crossed to BALB/c and those to B6 will be immunized with various antigens and adjuvants. The role of GIF in cognate T-B interaction will be analyzed in vitro and in vivo using TCR Tg mice and BCR Tg mice on GIF+/+ and -/- backgrounds. The biochemical mechanisms by which GIF regulates BCR-mediated antigen presentation will be analyzed. TCR Tg GIF+/+ and -/- mice will

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be compared for the signals that regulate Th differentiation. These mice will also be used to determine the involvement of the innate immunity in the regulation of Th differentiation. The functional relevance of GIF-dependent Th development will be addressed in the mouse model of allergic airway inflammation. Finally, using C60modified rGIF, GIF receptor will be molecularly characterized. These experiments will be useful to determine whether this cytokine directly regulates innate immunity or antigen-specific immunity and whether the form secreted from T cells or that contained in the cytosol plays an important role in its function. This project will fill a critical gap in our knowledge in cytokine biology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GROWTH FACTORS AND INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Lund, Pauline K.; Professor in Physiology, Pediatrics And; Cellular/Molecular Physiology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-SEP-1995; Project End 31-MAY-2007 Summary: (provided by applicant): Major objectives of this research are to gain a better understanding of positive and negative mediators of inflammation induced intestinal fibrosis, an incurable complication of Crohn's disease (CD). Findings in animal models of acute colitis and in patients with CD indicate benefits of growth hormone (GH) therapy in CD but the documented fibrogenic effects of GH and insulin-like growth factor-I (IGF-I) which is induced by GH, support a hypothesis that GH therapy may exacerbate fibrosis in CD. Locally expressed IGF-I is up-regulated in myofibroblasts at sites fibrosis in CD and animal models of chronic intestinal inflammation implicating IGF-I as an endogenous mediator of fibrosis. Preliminary data support a hypothesis that suppressors of cytokine signaling (SOCS), may limit the fibrogenic actions of therapeutic or endogenous cytokines and growth factors in the inflamed intestine. Other data support a hypothesis that IGF-I interacts with another key cytokine, TNF-alpha to mediate collagen synthesis or proliferation in intestinal myofibroblasts, key cellular mediators of fibrosis in CD. Specific aims are as follows:Aim 1 will define if systemic GH increases fibrosis, circulating or locally expressed IGF-I during PG-PS induced enterocolitis. Cellular sites and levels of SOCS expression will be assessed to verify that SOCS2 or SOCS3 are expressed at in vivo sites that would permit them to limit fibrosis.Aim 2 will define if IGF-I mediates GH action on collagen synthesis or proliferation in intestinal myofibroblasts and test whether SOCS limit GH or IGF-I action.Aim 3 will define if mice with absolute or mesenchyme-specific SOCS2 deficiency show altered fibrosis, JGF-I induction or GH action during TNBS-colitis.Aim 4 will define mechanisms if TNF-alpha has additive or synergistic effects with IGF-I, to induce collagen synthesis in intestinal myofibroblasts and if SOCS limit these effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GUT PEPTIDES IN INTESTINAL PERISTALSIS Principal Investigator & Institution: Grider, John R.; Professor; Physiology; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2001; Project Start 01-JUL-1984; Project End 31-AUG-2004 Summary: The objective of this proposal is to characterize the neuronal circuits that mediate the peristaltic reflex in normal and inflamed colon, and determine the effect of inflammatory cytokines (IL-1beta and IL-6) and neurotrophins (GDNF and BDNF) on neurotransmitter expression and neuronal remodeling. Previous studies and

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preliminary experiments have lead us to identify neuronal circuits within the myenteric plexus consisting of modulatory neurons coupled to motor neurons that mediate the reciprocal activity of circular and longitudinal muscle. The experimental approach exploits novel preparations that enable identification of the neural pathways: (1) compartmented intestinal segments to measure release of sensory (CGRP), modulatory neural pathways: (1) compartmented intestinal segments to measure release of sensory (CGRP), modulatory (somatostatin, GABA, [Met]enkephalin], and excitatory (ACh and SP) or inhibitory (IP, PACAP and NO) motor neurotransmitters in animals and humans; (2) longitudinal muscle strips with adherent myenteric plexus to identify the coupling of interneurons to each other and to excitatory motor neurons; (3) circular muscle strips with axonal remnants, and synaptosomes derived from these strips to identify presynaptic regulation of neurotransmitter release; (4) freshly dispersed and cultured myentric ganglia to examine feedback regulation of somatostatin interneurons and neuronal remodeling by neurotrophins; (5) organotypic cultures of smooth muscle to identify the interplay of cytokines and neurotrophins; (5) organotypic cultures of smooth muscle to identify the interplay of cytokines and neurotrophins in normal and TNBS-induced colitis. The Specific Aims of the proposal are: (1) to characterized the modulatory roles of somatostatin, GRP and NPY in the ascending and descending phases of the peristaltic reflex, and identify the presynaptic interactions between motor neurons; (2) to characterize the sensory pathways activated by chemical stimuli and identify the 5-HT4 receptor splice variant mediating desensitization of the reflex; (3) to characterize the roles of the cytokines, IL-1beta and IL-6, and trophic (GDNF) and antitrophic (BDNF) neurotrophins in mediating changes in peristaltic neurotransmission and neuronal remodeling in TNBS-induced colitis. The aims are supported by preliminary studies and will provide a deeper understanding of neurotransmission in health and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HELMINTHIC CONDITIONING OF THE MUCOSAL IMMUNE RESPONSE Principal Investigator & Institution: Weinstock, Joel V.; Professor; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2004 Summary: (Adapted from the Applicant's Abstract): The frequency of Crohn's disease (CD) has increased substantially in industrialized countries over the last 40 years. CD is an overly exuberant Th1 response probably directed at normal constituents of the intestinal flora. Helminthes live within the human gut interacting with the mucosal immune system. The host mounts a mucosal Th2-type reaction to limit helminthic colonization. Helminthic worms and their eggs are potent stimulators of mucosal Th2 and suppressors of Th1 responses. Th2-type reaction to a helminth can modulate the immune response to other concomitant parasitic, bacterial and viral infections. Many people live in increasingly hygienic environments and acquire fewer helminthes. The major hypothesis of this proposal is that helminthic colonization conditions our mucosal immune system to appropriately respond to stimuli without excessive release of strong tissue-destructive, Th1 cytokines. Failure to undergo helminthic colonization and to experience this mucosal conditioning predisposes people to Crohn's disease, which is an overly exuberant Th1 reaction. To test this hypothesis, the investigator is using normal mice exposed to TNBS and IL-10 mutant mice that develop IBD spontaneously to show if exposure to a murine intestinal helminth affords protection against the subsequent aberrant intestinal Th1-type inflammation. The project has three specific aims. Aim 1

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will determine if helminthes protect mice from acute TNBS colitis and determine the role of T cells and cytokine pathways in mediating this protective process. Aim 2 will evaluate the effect of helminthic conditioning on the natural development of chronic mucosal inflammation in the IL-10-/- mouse. The investigator will determine if exposure to helminthes can prevent or down-modulate ongoing spontaneous Th1-type colitis. Also, the investigator will identify mechanisms through which this exposure affords protection. Aim 3 will determine if immune dysregulation or various agents used to treat IBD alter the host/helminth interaction. These experiments are important, since it must determined how patients with dysregulated immunity may respond to docile live helminthes used as therapy. This investigation could provide new insight into the pathogenesis of CD. The results may lead to novel therapies for disease prevention and treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOST CELLULAR RECEPTORS AND HUS Principal Investigator & Institution: Newburg, David S.; Eunice Kennedy Shriver Center; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2001; Project Start 01-JAN-1997; Project End 31-DEC-2002 Summary: Enterocolitis caused by enterohemorrhagic Escherichia coli (EHEC), i.e., E. coli that produce Shiga-like toxins (SLTs), usually precedes HUS, but fewer than 10% of children with EHEC infection progress to HUS. We hypothesize that individual differences in toxin receptors of the host account for some of this differential susceptibility to HUS, and that these receptors are essential determinants of HUS pathogenesis. Following EHEC infection, SLT may enter the circulation and bind to host cell globotriaosylceramide (Gb3) toxin receptors; such binding in the endothelium is thought to be central to HUS pathology. Globotriaosylceramide is one of the major glycolipids that binds to SLTs in solid-phase assays, and Gb3 is accepted as a major functional receptor for SLT toxicity to cultured cells. Different molecular species of Gb3 that differ in their specific fatty acid moieties have different binding affinities to SLT. Variation of specific species of glycolipids among tissues is not known; such variations may underlie SLT sensitivity. The relative affinities of individual Gb3s for SLT differ greatly under different assay conditions; therefore, large, well defined and carefully studied human populations will be used to relate individual levels of specific species of Gb3 with susceptibility to HUS. We propose that an underlying genetically based predisposition toward HUS will be revealed by erythrocyte glycolipid analyses. The relationship between incidence of HUS, blood group type, and erythrocyte Gb3 profiles will be studied retrospectively in a genetically homogeneous population with unusually high HUS susceptibility, and prospectively in EHEC-infected Canadian children, with emphasis on defining the roles of different species of Gb3 in the etiology of HUS. The relationship between endothelial Gb3 profiles and erythrocyte Gb3 profiles will be studied in blood and human endothelial cells derived from the same umbilical cords. The relationship between endothelial cell Gb3 and susceptibility to SLT will be studied in cultured human endothelial cells. Thus, this project addresses the role of specific toxin receptors in the pathobiology of HUS, the relationship between regulation of host cell receptors and HUS susceptibility, and genetic differences in human glycolipid metabolism that relate to susceptibility to vascular endothelial injury. Such information may identify aspects of HUS pathobiology that are amenable to therapeutic intervention and may aid in identifying patients at high risk for HUS who could be targeted for increased vigilance and prophylactic measures.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HUMAN INTESTINAL ANION EXCHANGERS: FUNCTION & REGULATION Principal Investigator & Institution: Dudeja, Pradeep K.; Associate Professor; Medicine; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 01-JUN-1998; Project End 31-MAY-2006 Summary: (Adapted from the Investigator's Abstract): The short chain fatty acids (SCFA) are the main energy-yielding substrates for the mammalian colonic mucosa and are known to play a pivotal role as regulators of fluid and electrolyte absorption as well as cellular differentiation in the colonic epithelia. Recent studies from the PI's laboratory, utilizing purified membrane vesicles from organ donor colons, have demonstrated the presence of SCFA/HCO3 exchangers in the human colonic apical and basolateral membrane vesicles with kinetically distinct characteristics. To date, however, the molecular nature of these SCFA transporters is not fully defined. Recent studies from the PI's laboratory and others indicated the involvement of monocarboxylate transporter 1 (MCT1) in the SCFA uptake by the human colonic apical membranes as well as the expression of other MCT isoforms in the human colon. The PI hypothesizes that: 1) MCT1 plays a critical role in the SCFA absorption in the human colon, 2) MCT1 regulation involves regulation by kinases, or via alterations in trafficking or targeting to plasma membranes in polarized epithelial cells; and 3) its expression is transcriptionally regulated. The Specific aims are designed to: i) characterize the expression, distribution and function of the apical membrane MCT transporter(s) of the human intestine; ii) to elucidate the structure-function relationship of the human MCT1 and to delineate the sequences essential for protein trafficking and polarized distribution in epithelial cells; and iii) to characterize genomic clones corresponding to the 5' regulatory region for the human MCT1. For distribution, membrane localization and crypt/surface expression of MCT1 or other MCTs, mRNA and protein in the human intestine, RT-PCR, Rnase protection, Western analysis, in situ hybridization and immunohistochemistry in parallel to an analysis of MCT function will be performed. MCT1 structure/function relationship will be elucidated by utilizing truncation and deletion mutants and expression in a human breast cancer epithelial cell line to determine the relationship of various domains to SCFA transport, inhibition, and possible regulation by kinases. For trafficking studies, green fluorescent protein constructs of hMCT1 and expression in intestinal epithelial cells will be followed by confocal microscopy. MCT1 promoter will be cloned and DNA-protein interactions will be studied by mobility shift and foot printing analyses to yield important information on the cis- and trans-acting elements involved in regulation of MCT1 function and expression. An investigation of the molecular mechanisms of the colonic SCFA transporters, their structure-function analysis and their regulation would be critical for a better understanding of the role of SCFA in basic physiology of the colonocyte as well as in modulation of colonic electrolyte absorption, colitis and colonic malignancies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HUMAN INFLAMMATION

PHAGOCYTES,

OXYGEN

METABOLITES

AND

Principal Investigator & Institution: Weiss, Stephen J.; Upjohn Professor of Medicine, Chief; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-JUL-1984; Project End 31-MAR-2003

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Summary: In chronic inflammatory disease states ranging from rheumatoid arthritis to ulcerative colitis, blood monocytes infiltrate affected tissues and differentiate into tissue-destructive populations of macrophages. Unlike neutrophils or eosinophils which predominantly rely on their ability to generate halogenated oxidants and release serine proteinases to mediate tissue damage, the destructive systems mobilized by human macrophages remain undefined. In order to identify and characterize the mechanisms by which macrophages mediate tissue-destructive effects in chronic inflammatory disease states, human monocytes will be cultured in vitro and induced to mature into a macrophage population capable of expressing an extracellular matrix-degrading phenotype hundreds of times greater than that of any other leukocyte population described previously. Based on preliminary data, the macrophage's unique destructive activity is mediated by the exocytosis/secretion of active cysteine proteinases, a class of acid proteases normally categorized as intracellular, lysosomal catabolic enzymes. To date, little is known with regard to the function of these enzymes in human macrophages since many members of this proteinase family have only recently been identified and few molecular or biochemical tools have been developed for their analysis in intact cell systems. Furthermore, the mechanisms by which lysosomal enzymes could be routed to an extracellular compartment in which conditions permissive for cysteine proteinase activity could be generated and maintained remain unknown. Thus, in an attempt to identify a novel role for cysteine proteinases in macrophage effector functions, the following five aims will be addressed. First, to characterize the intracellular and extracellular expression of the cysteine proteinases, cathepsins B, L and S, as well as the cysteine proteinase inhibitor, cystatin C, in monocyte-derived macrophages. Second, to determine the role of the mannose-6phosphate receptor recognition systems in directing cysteine proteinase traffic from the lysosomal to the extracellular compartment. Third, to characterize the role of the macrophage vacuolar-type H+-ATPase and L-cystine transport systems in generating an acidic and reducing extracellular environment permissive for cysteine proteinase activity. Fourth, to assess the role of the cysteine proteinase system in the macrophagemediated degradation of the extracellular matrix via the selective "knockout" of individual cathepsins, the vacuolar-type H+-- ATPase or the L-cystine transport system. Fifth, and finally, to determine the response and function of the macrophage cysteine proteinase system during chemotactic factor-induced tissue invasion. The characterization of the cysteine proteinase system mobilized by human macrophages at inflamed sites should not only provide new insights into the pathogenesis and treatment of chronic inflammatory disease states, but also into the regulation of the tissue-invasive phenotype in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IDENTIFICATION OF THE IBD GENES ON CHROMOSOMES 3P AND 6P Principal Investigator & Institution: Rioux, John D.; Research Scientist; Whitehead Institute for Biomedical Res Biomedical Research Cambridge, Ma 02142 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Crohn's disease (CD) and ulcerative colitis (UC) are idiopathic inflammatory bowel diseases (IBD) that have a combined prevalence of approximately 100-200 per 100,000 in developed countries. Both diseases involve altered expression of proinflammatory and immunoregulatory cytokines within the intestinal mucosa; however, the clinical and pathological profiles for CD and UC are distinct. Epidemiological studies reveal a significant genetic contribution to the pathogenesis of

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IBD. The relative risk to siblings of affected individuals (ns) is estimated at 30-40 fold for CD and 10-20 fold for UC. In this application we propose to identify the genetic variation located in chromosomal regions 3p and 6p that confers genetic susceptibility to IBD. These regions were selected because of repeated evidence of linkage that has been observed in multiple genome-wide scans and strong evidence in a meta-analysis that we recently performed. Moreover, the chromosome 6p region contains the human leukocyte antigen (HLA) cluster of genes for which many associations to IBD have been reported, although the causal variants have yet to be identified. Prior studies in our laboratory provided the first extensive high resolution SNP analysis of the human genome. Specifically we performed SNP discovery by re-sequencing 470 kb in 8 individuals (>3.7 Mb of total sequence) in the cytokine gene cluster of chromosome 5q31 and discovered the underlying haplotype (haplotype = specific combinations of alleles) structure of the human genome. We recently demonstrated that the use of this haplotype structure could provide a powerful approach to performing association studies. The successful application of this approach enabled the identification of the genetic variation in the 5q31 cytokine gene cluster that confers susceptibility to Crohn's disease. In the current proposal we aim to take advantage of the haplotype structure of the genome to narrow down the linked regions on chromosomes 3p and 6p and to identify the causal genetic variation conferring susceptibility to IBD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IFN-BETA CONTROL OF TH CELL DIFFERENTIATION/FUNCTION Principal Investigator & Institution: Van Seventer, Gijsbert A.; Associate Professor; Environmental Health; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: Regulation by IFN-beta of Th Cell Differentiation and Function. An effective T helper (Th) cell immune response is dependent upon the activation and differentiation of resting naive CD4+ T cells into memory/effector Th cells displaying appropriate effector functions. Differentiated Th cells can be characterized as functionally distinct subsets according to their pattern of secreted cytokines, which has led to the now established paradigm of inflammatory Th1-like cells (secreting IL-2, IFN-gamma and LT) and anti-inflammatory Th2-like cells (secreting IL-4, IL-5 and IL-10). Aberrant expression of Th1-like cells has been shown to cause inflammatory autoimmune disease in certain animal models, such as experimental allergic encephalomyelitis (EAE) (multiple sclerosis model), experimental colitis (inflammatory bowel disease model) and collagen-induced arthritis (rheumatoid arthritis model). Recently, interferon-beta (IFN-beta), a type I IFN, has been shown to prevent the development of EAE. Furthermore, in patients with multiple sclerosis (MS) IFN-beta provides clinical improvement and is now standard therapy for the disease. The mode of action of IFNbeta in preventing EAE and in treating MS is unknown. We have recently shown, in a series of in vitro studies, that IFN-beta influences human Th cell subset differentiation by 1) preventing the generation of IFN-gamma-secreting Th1-like cells, through the inhibition of CD40-induced IL-12 secretion by dendritic cells, and 2) by inducing the generation of a novel Th cell subset (non-Th1-\Th2-like) that secretes high levels of the anti-inflammatory cytokine IL-10, but does not secrete IFN-gamma, IL-4 or IL-5. We hypothesize that one of the ways in which IFN-beta downregulates inflammatory autoimmune responses is through its effects on Th cell differentiation, specifically, through its ability to prevent the generation of IFN-gamma secreting Th1 cells and to induce a novel IL-10-secreting regulatory Th cell subset. The studies outlined in this

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research proposal will identify the molecular mechanism(s) by which IFN-beta regulates the secretion of IFN- gamma and IL-10 by human Th cells during their differentiation (Aim #1), and will functionally characterize the human Th cell subset induced by IFNbeta (Aim #2). In addition, murine models will be used to examine the role of both IFNbeta and Th cell subsets induced by IFN-beta in regulating immune responses (Aim #3). The information from these studies will identify mechanism(s) involved in the regulation of Th cell differentiation. The results will provide insight into an often not well appreciated interplay which is integral to the generation of a physiological immune response, that is the interaction between components of the innate immune system (i.e. type 1 IFNs) and the adaptive immune system (i.e. Th cell subsets). Lastly, defining the mechanism(s) by which IFN-beta modulates Th cell differentiation and effector function may not only lead to the development of new, more effective drugs and complementary therapies for the treatment of MS, but could also lead to the use of IFN-beta as treatment of other inflammatory autoimmune diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IKK BETA IN INTESTINAL INFLAMMATION Principal Investigator & Institution: Egan, Laurence J.; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: Inflammatory bowel disease is a major cause of suffering in the developed world. Pro-inflammatory cytokines, chemokines and eicosanoids are present in high concentrations in inflammatory bowel disease. Many of these inflammatory mediators can be positively regulated by nuclear factor kappa B (NF-kappaB) family of transcription factors. However, it is not known if NF-kappaB activation in vivo promotes intestinal inflammation, or plays a role in protective host responses by inhibiting apoptosis in the inflamed intestine. Our central hypothesis is that NF-kappaB activation in cells of the innate immune system regulates intestinal inflammation and host responses to inflammation in vivo. This hypothesis will be tested by studying the key molecule that activates NF-kappaB, inhibitory kappa B kinase beta (IKKbeta). Studies in specific aim 1 will generate and characterize a transgenic mouse line that expresses cre recombinase exclusively in intestinal epithelial cells. Studies in specific aim 2 will determine the role of IKKbeta in the activation of NF-kappa B in cells of the mucosal innate immune system. Two conditional knockout mouse strains will be generated by cre/loxP-mediated recombinant of the IKKbeta locus: a) Mice that express cre recombinase in intestinal epithelial cells will be crossed with mice bearing a loxPflanked IKKbeta locus to produce intestinal epithelial IKKbeta knockout mice; b) Existing mice that express cre recombinase in macrophages and neutrophils will be crossed with mice bearing a loxP-flanked IKKbeta locus to produce macrophage and neutrophil IKKbeta knockout mice. Studies in specific aim 3 will determine the role of NF-kappa B activation in the pathogenesis of intestinal inflammation by analzing the course of colitis induced by feeding dextran sulfatesodium to mice that lack IKKbeta in intestinal epithelial cells or in macrophages and neutrophils. The mentored clinical Scientist Development Award will provide me with essential resources with which to perform this research. I will acquire the theoretical and experimental skills to launch a productive independent investigate career with the assistance of this award and of my institution, the Mayo Foundation for Medical Education and Research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFLAMMATORY BOWEL DISEASE IN TCR-MUTANT MICE Principal Investigator & Institution: Bhan, Atul K.; Associate Pathologist; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-SEP-1994; Project End 31-AUG-2007 Summary: (provided by applicant): The spontaneous chronic colitis in T cell receptor (TCR) alpha mutant (knockout) mice provides an excellent experimental model of inflammatory bowel disease. The colitis shares many features with ulcerative colitis and is mediated by the T helper 2 pathway. Colonies of TCRalpha knockout mice deficient in cytokines and B cells have been developed at the Massachusetts General Hospital. The project will focus on the hypothesis that an unregulated immune response to enteric bacterial antigens at the mucosal site results in chronic colonic inflammation and autoantibody production. Certain enteric bacteria may play a protective role in the development of intestinal inflammation. The role of the appendix in the presentation of enteric bacterial antigens and in providing both pathogenic and regulatory cells in the pathogenesis of chronic colitis will be explored. A major focus of the project will be to examine the regulatory role of B cells in colitis. We have developed a new model of granulomatous colitis in B cell and lL-4 deficient TCRalpha knockout mice. Thus, the development of two distinct colitis models in mice that are of genetically of identical background and exposed to the same environment, provides an opportunity to analyze the mechanisms involved in T helper 2-mediated ulcerative colitis-like and T helper 1mediated Crohn's disease-like colitis. Additional models of T helper 1-mediated colitis in IL-10 KO mice and CD45RB high transfer model will also be studied. Experiments will be designed to develop specific interventions, including B cell based therapies, to prevent and suppress chronic intestinal inflammation and contribute to the development of new therapeutic modalities for human inflammatory bowel disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFLAMMATORY BOWEL DISEASE: NON-INVASIVE DIAGNOSIS Principal Investigator & Institution: Nair, Padmanabhan P.; Nair Consultants, Llc 4520 Hemlock Cone Way Ellicott City, Md 21042 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2003 Summary: (Verbatim from the Applicant's Abstract): Inflammatory Bowel Disease (IBD) remains an intractable chronic disease affecting nearly a quarter million individual in the United States. A persistent inflammatory reaction is an integral component of this disease. Radiologic, endoscopic and pathologic examinations of biopsy specimens are the current accepted approach for its diagnosis. While this is an essential set of procedures for confirming a diagnosis of IBD, it remains an invasive and expensive strategy for screening subjects and for frequent follow-up of established cases. Recent technological advances in the exfoliative biology of the colon have shown that colonic cells and inflammatory cells could be recovered in a viable state from stool samples and examined for markers of colonic disease. It is now possible to apply this noninvasive approach to screen patients suspected of having IBD by demonstrating the presence of inflammatory cells in stools by flow cytometry and by PCR amplification of COX-2, the biomarker for the inflammatory response. This new emerging science of coprocytobiology, involving the isolation of cells from stool and screening these cell populations for markers of colonic pathology (eg. malignancy, IBD) is an exciting development. The objective of this SBIR, Phase II is two-fold. The first one is to conduct a double blind cross sectional clinical trial to establish the relationship between IBD disease severity and the expression of GOX-2 in isolated colonocytes and inflammatory

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cells of lymphoid lineage. The second one is to determine the correlation between indices of clinical findings (GELS, Global Estimates of Lesion Severity) and an Index of Inflammatory Activity (IIA) generated from two sets of outcome measures - ratio of PCR band density COX-2/COX-1 and the ratio COX-2/Cytokeratin l9. The Index of Inflammatory Activity (IIA) may become a non-invasive standard by which physicians can follow IBD patients more frequently for monitoring epithelial restitution of the colonic mucosa during treatment. PROPOSED COMMERCIAL APPLICATION: A standardized kit may become available to clinicians to monitor IBD disease severity by an objective laboratory test. Diagnostic laboratories, research centers, clinical drug trials will be potential users. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INHIBITION OF MICROFLORA-INDUCED COLITIS BY NF-KB Principal Investigator & Institution: Horwitz, Bruce H.; Assistant Professor of Pediatrics; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant): The purpose of this proposal is to define the cellular and molecular mechanisms by which the NF-kappaB subunits p50 and p65 inhibit inflammation within the lower bowel. The inhibitory functions of p50 may be especially relevant to the control of inflammation within the colon, as our laboratory has shown that mice lacking p50 (p50-/-) are sensitive to colitis induced by Helicobacter hepaticus, and this sensitivity is significantly exacerbated in mice that both lack p50 and are heterozygous for p65 (p50-/-p65+/-). These mice are sensitized to the development of colitis by a defect intrinsic to the innate immune system. This defect may reflect an inability to control H. hepaticus-induced inflammatory gene expression within antigen presenting cells (APCs), as H. hepaticus infection induces higher levels of the critical inflammatory cytokines IL-12p40 and IP-10 in p50-/- and p50-/-p65+/- macrophages than in WT macrophages. The goals of this proposal are: 1) To determine the mechanism by which p50 and p65 within cells of the innate immune system contribute to inhibiting the inflammatory response to H. hepaticus. Using a novel mouse strain created in our laboratory (p50-/-p65+/-RAG-2-/-), we will evaluate the possibility that p50/p65 activity is required within the innate immune system to facilitate the inhibitory function of regulatory T cells. 2) To determine the mechanisms by which p50 and p65 inhibit H. hepaticus induced inflammatory gene expression. We will use molecular techniques to compare the function of endogenous IL-12p40 and IP-10 promoters in WT, p50-/-, and p50-/-p65+/- macrophages. 3) To determine whether p50 and p65 prevent an overaggressive immune response that injures the host, or alternatively, whether p50 and p65 prevent an immune deficiency that leads to increased bacterial burden. We will compare bacterial burden in RAG-2-/- and p50-/-p65+/-RAG-2-/- mice, and determine whether introduction of functional innate immune cells into p50-/-p65+/-RAG-2-/mice can prevent H. hepaticus-induced inflammation. Taken together, we believe that these studies will lead to insights regarding the molecular pathogenesis of inflammatory bowel disease that could lead to novel therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERVENTION STRATEGIES OF HEMORRHAGIC COLITIS AND HUS Principal Investigator & Institution: Boedeker, Edgar C.; Professor; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201

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Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: (provided by applicant): The broad aim of this proposal is to develop and utilize new and established animal model of enterohemorrhagic E. coli (EHEC) infection, in rabbits and dogs, to develop therapeutic regimens to prevent and treat EHEC disease. It is well recognized that shiga-toxin- (Stx)-producing strains of E. coli, acquired by ingestion of inadequately cooked meat, or other contaminated foods, cause hemorrhagic colitis, and may induce fatal hemolytic uremic syndrome (HUS). EHEC strains produce potent protein toxins named Shiga-like toxins (Stxs) because of their relatedness to Shiga toxin of Shigella dysenteriae. In addition, most EHEC share the ability to adhere intimately to intestinal epithelial cells by "attaching and effacing" (A/E)(7) mechanisms (Fig.2). Although EHEC attachment mechanisms may directly contribute to diarrheal disease, and may influence toxin delivery, the most severe intestinal and renal manifestations of EHEC infection result from toxin-mediated damage to vascular endothelium, with tissue edema, inflammatory infiltrates, cytokine production and vascular thrombi. At present, only supportive care is available to prevent the development of the severe, and frequently fatal, complications of EHEC infection. Strategies aimed at decreasing the toxin burden and preventing the interaction of Stxs with their endothelial receptors should prevent or ameliorate disease and damage in target organs (gut, CNS and kidney). Interventions developed in animal models can subsequently be applied to the prevention and management of EHEC disease. E. coli strain RDEC-HI9A infection of rabbits serves as the established animal model of EHEC disease for the initial intervention studies (Aims 1-4). RDEC-H19A, produced by the transfer of the toxin-converting phage H19A of an O26:H11 EHEC to the rabbit entero-pathogenic E. coli RDEC-1, is an attaching and effacing rabbit pathogen which produces high levels of Shiga-like toxin I (Stx-I), colonizes cecum and colon, and induces intestinal disease in rabbits with pathologic changes resembling human EHEC disease. Specific aims (1-4) of the proposal are to use animal models of EHEC infection to: 1). Test the ability of new toxin-receptor analogs, administered paretenteraly or enterically to prevent EHEC disease. 2). Further test the ability of passively administered immunoglobulin with anti-toxic activity to prevent EHEC disease. 3). Further examine whether antibiotic therapy has beneficial or harmful effects on the course of disease. 4). Further develop strategies for active immunization against EHEC using the Stx toxins of EHEC. 5). Specific aim 5 is to utilize canine specific A/E strains to produce new STECcapable of infecting dogs, which are susceptible to renal vascular lesions. We will transfer our labeled Stx-1 encoding phage to dog-specific A/E strains of E. coli and test their ability to produce intestinal and renal disease. The clinical studies in dogs will be performed at Kansas State University by Dr. Brad Fenwick who has described the Cutaneous and Renal Glomerular Vasculopathy (CRGV) in greyhound dogs exposed to Stx. 6). Specific Aim 6 is to extend our rabbit and dog models to be able to test similar strategies against EBEC strains expressing Stx-2. We will label and transfer toxin converting phage encoding Stx-2 to rabbit and dog specific A/E strains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTESTINAL ADENOSINE A2B RECEPTOR Principal Investigator & Institution: Sitaraman, Shanthi V.; Pathology and Lab Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (adapted from the application) The overall aim of this project is to better define the characteristics of intestinal epithelial cell-neutrophil interaction as it relates to

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fluid and electrolyte secretion. Many intestinal disorders, particularly the acute flare of inflammatory bowel disease (IBD), are characterized by migration of neutrophils across the intestinal epithelium into the lumen to form 'crypt abscess'. Crypt abscesses are pathognomic of active IBD and infectious colitis and correlate with severity of disease as well as clinical symptoms. We have previously shown that neutrophil migration into the intestinal lumen elicits electrogenic chloride secretion (secretory diarrhea) and the major effector of this chloride secretory response is the neutrophil-derived secretagogue, 5'AMP. Intestinal epithelia express an ectonucleotidase, which converts 5' AMP to adenosine which then interacts with intestinal epithelial adenosine 2b (A2b) receptor to elicit chloride secretion. Thus the A2b receptor plays a central role in orchestrating chloride secretion induced by neutrophils. An understanding of the regulation and signaling mechanism of A2b receptor may therefore lead to designing of novel treatments for this component of IBD. In this proposal, I intend to characterize the biology of intestinal A2b receptor using two intestinal epithelial cell models: T84 cells and Caco-2 bbe cells transfected with the A2b receptor. A2b receptor is the only adenosine receptor in T84 cells while Caco-2 bbe cells lack A2b receptor. First, I will study the polarity of surface expression, distribution, kinetics of turnover, structural requirements for ligand binding, desensitization, and G-protein recognition. Second, I will analyze the existence of ectonucleotidase and A2b receptor in signaling membrane microdomain such as caveolae. These microdomains represent invagination of plasma membrane enriched in glycosphingolipid, which have been shown to contain signaling proteins. Third, I will study the role of adenosine receptor in the modulation and feedback regulation of neutrophil-epithelial interaction including transmigration and chemokine secretion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTESTINAL SECRETION & INFLAMMATION - IMPACT OF AMMONIA Principal Investigator & Institution: Matthews, Jeffrey B.; Christian R. Holmes Professor and Chairm; Surgery; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2001; Project Start 01-SEP-1996; Project End 31-AUG-2005 Summary: Numerous diseases affecting the GI tract, ranging from secretory diarrhea to cystic fibrosis, are characterized by dysregulation of epithelial C1- secretion. This project originally identified that ammonium ion (NH4+, normally present at high concentrations in the colonic lumen) may be a novel endogenous regulator of C1secretion via effects via effects on K+ channels and begins to define the interaction of NH4+ with the basolateral membrane K+ transporters also required for Cl-secretion. Based on work already accomplished, the current application considers how altered K+ channel regulation may influence various intestinal disease states. Preliminary data indicate that the ammonia-derived oxidant monochloramine (NH2Cl) may contribute to the diarrhea of colitis by potentiating Ca2+- dependent K+ channels. Experiments also suggest that docosahexaenoic acid (DHA, a component of fish oil) can augment Ca+2dependent K+ channels, finding of particular interest as DHA begins clinical evaluation as therapy in CF. Preliminary findings suggest that the actin cytoskeleton an functionally alter Ca2+-dependent K+ channels, and conversely, that these K+ channels can modulate cell functions such as epithelial restitution that involve actin remodeling. Three sets of studies are proposed. First, the impact of ammonia on colonic epithelial transport will be further characterized in cultured epithelial ells and in human colonic mucosal preparations, with attention to the interaction of NH4+ with the basolateral Na+-k+-2Cl- co- transporter, Na+_K+ ATPase, and K+ channels. Second, potentiation of

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basolateral Ca+2-dependent K+ channels by cAMP and NH2Cl will be explored using cultured epithelial cells as model systems with the goal of defining a common mechanism for K+ channel potentiation by these seemingly diverse stimuli. The potential for therapeutic modulation of basolateral K + channels will be explored, specifically examining wheth4r docosahexaenoic acid (DHA) can augment Ca2+dependent Cl- secretion in T84 cells and human colon, and, if so, to determine its mechanism of action. Finally, the studies will define the effect of chemical manipulation of F-actin on Ca2+-dependent K+ channel regulation and extend preliminary findings suggesting that K+ channel regulation affects the actin-regulated process of epithelial restitution. These studies highlight the importance of basolateral K+ channels in the regulation of secretion and other epithelial functions and reinforce their potential as targets for new drug design. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTL PEDIATRIC INFLAMMATORY BOWEL DISEASE (IBD) MEETING Principal Investigator & Institution: Fiocchi, Claudio; Professor; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): Funding is requested for a scientific workshop entitled "International Pediatric Inflammatory Bowel Disease (IBD) Meeting". The workshop is under the auspices of Case Western Reserve University and the Crohn's & Colitis Foundation of America, and will be held from September 16 through 18, 2003. The workshop will be attended by approximately 100 participants and will include five scientific sessions, each one presided by leading investigators and including 6 speakers. The conference, the very first ever of its kind, will focus on the issue of the raising incidence of IBD in the pediatric population worldwide, and address the serious lack of studies on the pathogenesis of Crohn's disease and ulcerative colitis in children. The major topics will include the development of the immune system in children and its impact on neonatal and adult immunity, the differential reactivity of T-cells in early and adult life in health and disease, the intestinal microbiota and its relevance to IBD, the impact of environmental factors on IBD pathogenesis and manifestations, and new trends in the treatment to pediatric IBD in face of emerging diagnostic and therapeutic technologies. These are completely novel and unexplored areas of undeniable importance to IBD. The outcome of the workshop is expected to define the reasons for the lack of pathophysiology-based research in pediatric IBD and stimulate investigation in areas so far unexplored by pediatric gastroenterologists and IBD investigators. A major goal of the conference is to foster a close interaction and scientific exchange between scientists outside of the field of IBD with established and new investigators interested in Crohn's disease and ulcerative colitis. An additional goal of the workshop is to expose a substantial number of trainees, post-doctoral fellows and junior faculty members to novel ideas, concepts and methodologies that will become the center of scientific attention in pediatric IBD in the immediate future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INVESTIGATING PATHOGENESIS

ENTAMOEBA

HISTOLYTICA

COLONIC

Principal Investigator & Institution: Singh, Upinder; Professor; Medicine; Stanford University Stanford, Ca 94305

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Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by the applicant): The protozoan parasite Entamoeba histolytica causes an estimated 50 million cases of invasive disease annually. The most common manifestation of amebic infection is colonic disease (dysentery). Several virulence factors have been identified that are important for parasite pathogenesis, however the molecular mechanisms that the parasite utilizes as it establishes invasive disease remain unclear. Transcriptional regulation of amebic genes has been shown in a number of biologically relevant conditions including encystation, phagocytosis, drug resistance, stress and nutrient deprivation. Our hypothesis is that amebic virulence determinants that are important in causing invasive colonic disease will be regulated by the stimuli present in the colonic environment and can be identified by methods that detect message abundance. Our goal is to develop and use E. histolytica DNA micro-arrays to investigate amebic colonic pathogenesis. To identify virulence determinants that are important in causing colonic disease we will identify amebic genes that are regulated due to interaction of the parasite with (i) enteric bacteria, (ii) colonic epithelial cells, and (iii) erythrocytes. These conditions to a large extent mimic the environment encountered by the parasite within the host colon. For each given condition we will identify cohorts of genes whose transcript abundance is increased, decreased, or unchanged. Ultimately we would hope to identify genes, which are coordinately regulated (i.e. induced under all the conditions tested or repressed under all the conditions tested) as these may represent virulence determinants in causing colonic disease. Genes of interest will be characterized and their roles in amebic invasiveness and virulence investigated using molecular and genetic approaches. This approach promises to unveil novel molecular aspects of amebic pathogenicity and provide a number of genetic targets for improved diagnostic and treatment strategies. Additionally, the micro-arrays generated as a part of this grant will have a multitude of uses and will prove useful to a number of scientists in the scientists in the Entamoeba scientific community to study varied aspects of amebic pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INVOLVEMENT OF TNF-ALPHA IN INTESTINAL INFLAMMATION IN A MODEL OF COLITIS Principal Investigator & Institution: Appleyard, Caroline B.; Associate Professor; Ponce School of Medicine G.P.O. Box 7004 Ponce, Pr 00731 Timing: Fiscal Year 2001; Project Start 30-SEP-1986; Project End 31-MAY-2005 Description (provided by applicant): Ailments of the gastrointestinal tract are often very debilitating yet despite decades of research, the basic pathogenic mechanisms involved in inflammatory bowel diseases (IBD) are unknown with no cure for diseases such as Crohn?s and Ulcerative Colitis. Until now the lack of a clinically relevant animal model which mimics the periods of remission and relapse seen in the human condition has limited our understanding of the disease pathogenesis. The recent development of a "reactivated" model of colitis represents a more realistic model for the study of colitisinduced inflammation and ulceration. Previous investigations have shown significantly increased levels of inflammatory mediators in inflammatory bowel disease (IBD). This has led to the suggestion that cytokines, prostaglandins and leukotrienes may play an important role in the pathogenesis of IBD. Recent data suggest that the proinflammatory mediator tumor necrosis factor alpha (TNF-alpha) may be a key player in thc inflammatory process. Three sets of experiments will test this central hypothesis: (1) Absolute levels of TNF-alpha will be measured in a reactivated animal model of colitis and the possible cellular source will be investigated (hypothesis: TNF-alpha levels are

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increased in periods of relapse and inflammation in inflammatory bowel disease). (2) The underlying mechanism of action of TNF-alpha will be characterized by the administration of various inhibitors, drugs or antibodies (hypothesis: involvement of TNF-alpha in this reactivated model of colitis is an essential step in the inflammatory process and resultant ulceration; moreover this is regulated by the nuclear transcription factor kappa beta, NF-kB). (3) The effect of TNF-alpha on ion transport will be investigated using Ussing chambers (hypothesis: TNF-alpha contributes to the pathogenesis of one of the major symptoms of IBD, diarrhea). This research will advance our understanding of the cytokine network and interactions involved in inflammatory bowel disease. It will provide new avenues for potential therapeutic intervention and, ultimately, offer a preferable alternative to the pharmacologic agents and surgical procedures currently employed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METABOLISM AND CARCINOGENICITY OF HETEROCYCLIC AMINES Principal Investigator & Institution: Zenser, Terry V.; Internal Medicine; St. Louis University St. Louis, Mo 63110 Timing: Fiscal Year 2003; Project Start 01-JUL-1998; Project End 31-AUG-2008 Summary: (provided by applicant): Colorectal cancer is one of the leading causes of cancer deaths in the United States. Both cooked red meat intake and chronic inflammation/infection play a role in the etiology of colon cancer. During the cooking process, genotoxic heterocyclic amines (HCAs), i.e., 2-amino-3-methylimidazo[4,5f]quinoline (IQ), are formed which can initiate colon cancer. Colorectal carcinoma incidence in patients with inflammatory bowel disease is 20-fold higher and occurs 20 years earlier than the general population. Findings in patients are paralleled in animal models with persistent severe inflammation in the colonic mucosa thought to cause development of colorectal cancer. Dextran sulfate sodium (DSS)-induced colitis is an animal model for studying both inflammation and colitis-associated neoplasia. Reactive nitrogen oxygen species (RNOS), components of the inflammatory response, contribute to deleterious effects of inflammation. RNOS catalyze nitrosation, oxidation, and nitration reactions. However, the influence of RNOS on HCA carcinogenicity has not been evaluated. Such an evaluation is essential to understanding the strong association between cooked red meat intake and chronic infection/inflammation in colon cancer. Because we recently demonstrated RNOS transformation of IQ to an N-nitroso product N-NO-IQ), which forms DNA adducts and is mutagenic, we hypothesize that RNOS derived from the inflammatory response react with HCAs forming N-nitroso products that initiate colon cancer. Critical to testing this hypothesis is the identification and measurement of N-nitroso products in animals and cells responding to inflammatory stimuli; the demonstration that N-nitroso products are genotoxic and that HCA-induced colon cancer is increased in DSS-treated mice. The following specific aims will test our hypothesis: 1. Investigate HCA transformation by RNOS; 2. Determine reactivity and potential genotoxicity of HCAs and their RNOS-derived N-nitroso products; 3. Evaluate formation and metabolism of N-NO-IQ and its products by in vitro cellular systems, using inflammatory models; 4. Assess formation and metabolism of N-NO-IQ in mice with DSS-induced colitis; 5. Determine effect of DSS-induced colitis inflammation) in IQ carcinogenicity. The long-term goal is to understand the role of RNOS on HCA carcinogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MUCOSAL IMMUNE REGULATION BY BACTERIAL DNA Principal Investigator & Institution: Raz, Eyal; Professor; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: The intestinal tract is exposed to numerous commensal bacteria, and is an important entry portal for clinically relevant bacterial pathogens. Toll-like receptors (TLRs) are a family of receptors that recognize bacterial products and, once activated, can initiate innate immune defenses in the host. TLR9 recognizes bacterial DNA (bDNA) and its synthetic derivatives carrying an unmethylated CpG motif, which is absent from mammalian DNA. Functional TLR9 is expressed by various immune and inflammatory cells (macrophages, B cells), and, as shown in preliminary studies, also in intestinal epithelial cells. Administration of bDNA to mice can be immunostimulatory (e.g., adjuvant functions in immunizations), but can also downregulate inflammatory responses, as we showed in murine colitis models. To explain these different effects ofbDNA, when administered exogenously or after release from pathogenic and commensal intestinal bacteria, this Research Unit will focus on the physiologic functions of the receptor for bDNA, TLR9, in the intestine. Our studies will test the overall hypothesis that TLR9 exerts anti-inflammatory functions in the intestine in vivo. The studies have the following Specific Aims: Aim 1. To define the signaling pathways activated by bDNA in intestinal epithelial cells. We will define the polarity and subcellular localization of TLR9 in polarized human intestinal epithelial cells in vitro and in vivo, and determine the signaling pathways and cellular functions induced by TLR9 activation in these cells. Aim 2. To determine the functions of TLR9 in regulating colonic inflammation. These studies will use TLR9 deficient mice to define the physiologic functions of TLR9 in different murine colitis models, and in mediating the beneficial effects ofprobiotic bacterial preparations in colitis. Aim 3. To define the importance of indoleamine 2,3-dioxygenase (IDO) in mediating the anti-inflammatory functions of bDNA in colitis. Based on preliminary data that inhibition of the tryptophan-catabolizing enzyme, IDO, reverses the anti-inflammatory effects of bDNA, the studies will use IDO deficient mice and pharmacological and histological approaches to begin to address mechanisms by which bDNA and TLR9 modulate intestinal inflammation. Together, these studies will yield new insights into the physiologic functions of bacterial DNA and TLR9 in the intestine, which will form a basis for the design of new therapeutic strategies that exploit the underlying biological principles. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MUCOSAL PROTECTIVE FACTORS IN HUMAN MILK Principal Investigator & Institution: Rao, Radhakrishna; Professor; Physiology and Biophysics; University of Tennessee Health Sci Ctr Health Science Center Memphis, Tn 38163 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2004 Summary: Neonatal necrotizing enterocolitis (NEC), the acute necrosis of the small intestine, is the most common non-respiratory, life-threatening disease among infants admitted to neonatal intensive care units. Although etiologic and epidemiologic characteristics of NEC are poorly understood, two major factors closely associated with NEC are prematurity and enteral feeding. A striking observation made by several groups of scientists is that feeding breast milk reduces the risk of NEC in premature infants. Such a beneficial effect was not observed by feeding infant formula. We recently

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demonstrated that human milk contains protective factors that protect the intestinal epithelial barrier function from oxidative-stress induced disruption. Our preliminary studies indicate that there are at least two protective factors in human milk, one heat stable and the other heat-sensitive. On the basis of preliminary results it is hypothesized that milk-borne factors protect the intestinal mucosal barrier function. Our long-range goal is to determine the mechanism involved in breast milk-mediated protection of the gastrointestinal mucosa, and to determine the role of milk-borne mucosal protective factors in preventing neonatal gastrointestinal diseases, such as NEC. Our next step towards this goal will be to isolate two distinct milk-borne protective factors that prevent hydrogen peroxide-induced barrier disruption, and to characterize their physical and chemical properties to reveal their identity. This goal will be achieved by: 1) isolation of protective factors to homogeneity by liquid chromatography, and 2) characterization of physical and chemical properties of isolated protective factors. These studies will reveal the identity of at least two distinct mucosal protective factors in breast milk, and provide the basis for further characterization of the mechanisms involved in mucosal protection by breast milk, and their role in preventing neonatal gastrointestinal diseases Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MULTICENTERED RANDOMIZED TRIAL OF HIGH-DOSE URSO IN PSC Principal Investigator & Institution: Lindor, Keith D.; Professor and Director; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Primary sclerosing cholangitis (PSC) is a progressive chronic cholestatic liver disease of unknown etiology that is commonly associated with chronic colitis. PSC, a common liver disease among adults, usually leads to advanced liver disease and liver failure, and as such, is an important indication for liver transplantation. Unfortunately, no effective medical therapy currently exists for PSC. The group of investigators has a longstanding track record of clinical trials in chronic cholestatic liver disease, particularly in primary sclerosing cholangitis. Recently we have generated promising results from a pilot study using high doses of ursodeoxycholic acid in the treatment of PSC. Lower doses of ursodeoxycholic acid in patients with PSC led to biochemical improvement but did not affect other clinically important endpoints in a previous study. Our pilot data is supported by data from another group showing in a small, randomized trial that high dose ursodeoxycholic acid led to biochemical, histologic, and cholangiographic improvement compared to placebo at two years. In this submission, we propose a large-scale multi-center placebo-controlled randomized trial with a minimum follow-up of four years for 150 patients with primary sclerosing cholangitis. Primary endpoints of the study will include histologic progression to cirrhosis, development of esophageal or gastric varices, need for liver transplantation, and survival. Secondary endpoints will include measurements of the effects of urosodeoxycholic acid (28-30 mg/kd/d) on liver biochemistries, histologic stage, cholangiographic features, Mayo risk score, and quality of life, using validated questionnaires. This study will be the largest ever conducted in PSC and the follow-up will be the most extensive. This will provide an invaluable resource for studying the natural history of this disease and as part of this study we will also collect serum, cells for extraction of DNA, bile, and tissue from the liver and colon as a resource for future studies. The multi-centered nature of this trial will allow recruitment of patients into this study from a diverse patient population, representative of the gender and racial

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distribution of this disease. Chances of successful completion of this study are enhanced by the large PSC patient population that the participating centers currently manage, recognition of these sites as referral centers for new patients with PSC, as well as a longstanding track record in clinical trials in cholestatic liver disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MYCOBACTERIUM AVIUM SUBSPECIES IN CROHN'S DISEASE Principal Investigator & Institution: Naser, Saleh A.; Molecular Biol & Microbiology; University of Central Florida 4000 Central Florida Blvd Orlando, Fl 32816 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: Crohn's disease (CD) is a debilitating chronic inflammatory bowel disease characterized by patches of inflamed tissue. The underlining cause of inflammation and provocation of the immune response in CD patients has yet to be determined. In theory, the immune system usually reacts against an invading organism such as an insect bite or bacterial infection, or is over-sensitive, as in allergic reactions to grass pollen etc. These reactions cause irritation and pain in the affected area, which subside when the immune system has dealt with the potential threat. Defects in the immune system of CD patients have been reported, both in the ability of the cell to phagocytose and in immune killing after phagocytosis, The cytokine pattern in CD is Th1-like and defect in the ratio of proinflammatory to anti- inflammatory cytokines has been proposed. A specific antigenic stimuli has not been identified, but pathogenic bacteria such as Mycobacterium avium subsp paratuberculosis (MAP) and specific invasive E. coli strains have been proposed. In addition, autoantibodies derived from molecular mimicry from bacterial antigens, or from host origin may also be causative agents of the inflammatory lesions in CD. Defects in the ability of macrophages to present antigen to T-cells and B-cells may also have a role. The mycobacterial theory is based on the significant similarity between CD and Johne's disease, a chronic enteritis in cattle that is caused by MAP. The two diseases share histological and pathological characteristics similar to those in tuberculosis and sarcoidosis. It is believed that MAP may be causing an immune reaction in the gut, resulting in a continuous immune response, which gets better and worse as the number of bacteria increase and decrease. Another possibility is that some parts of MAP like the heat shock proteins similar to parts of the gut lining resulting in triggering an immune response: a process known as autoimmunity. Finally, there may be defects in the immune reaction to MAP or proteins in the gut. In this case, the immune cells fail to deal with the invading organism, which is able to persist in the tissues, causing further inflammation. Many studies have been performed in an attempt to investigate a mycobacterial role in the etiology of CD and its pathogenesis. The outcome has been inconsistent which has added to the controversy. The role of MAP, if any, in the etiology of CD has become increasingly debated in recent years causing a need for clear elucidation. While positive results would change the course of therapy and investigation in CD, a negative result will go a long way toward clearing up the MAP debate. In this study, our team will investigate the overall role of MAP, if any, in CD etiology by addressing the following questions: Is MAP present in CD lesions? Is it culturable? Can MAP be identified using PCR, RT-PCR or fluorescence in situ hybridization (FISH) techniques? Is there any immune reaction activity against MAP in CD patients? Is it cellular, humoral or both? What types of immune cells are present in CD lesions compared to non-inflammatory tissue or tissue from non-IBD and healthy controls? Are there any abnormalities in bacterial phagocytosis by peripheral blood monocytes and neutrophils from CD patients compared to normal cells? Are there factors inhibitory to phagocytosis in CD serum? Are there any abnormalities in antigen

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presentation and lymphocyte transformation to recall antigens from MAP? Are there any inhibitory or augmenting factors present in the serum from CD patients (cellular and serum crossover)? Our approach in this project is to determine if MAP or reactions against MAP are present in full thickness surgical tissue, heparinized blood and sera specimens from patients with CD using well-developed methodology in the fields of microbiology, immunology and molecular microbiology. We will investigate the presence of MAP in tissue specimens directly by using nested PCR, RT-PCR and FISH and indirectly by culture using a newly developed culture media appropriate for isolation of cell wall deficient form of MAP. We will also investigate the humoral immune reaction in CD sera using p20 antigen, a MAP specific protein. Additionally, the type and state of immune cells will be determined in inflamed versus non-inflamed tissue specimens from CD patients. We will also examine how these cells from CD patient blood are able to ingest and kill MAP, and whether this ingestion results in a normal immune response. This is the first study designed to comprehensively examine the overall presence/absence of MAP in CD tissue and the immune response in CD patients. The results will give us a better idea as to whether MAP causes CD, or whether there is an inherent defect in the immune system, which allows bacterial persistence or autoimmunity to occur in the gut. Ultimately, the outcome of this study will go a long way toward clearing up the MAP debate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROENDOCRINE MEDIATION OF E. COLI 0157:H7 INFECTION Principal Investigator & Institution: Lyte, Mark; Professor; Minneapolis Medical Research Fdn, Inc. 600 Hfa Bldg Minneapolis, Mn 55404 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: This application proposes the new theory of directed neuroendocrinebacterial interactions as a mechanism governing the ability of an enteric pathogen to infect a host. This hypothesis is based on the in vitro and in vivo ability of the neuroendocrine hormone norepinephrine (NE) to increase growth and production of virulence-associated factors of the enteric pathogen Escherichia coli O157:H7. High concentration of NE occur in foods such as ground beef which are contaminated by E. coli O157:H7. Equally high concentrations of NE also occur within the gastrointestinal tract due to enteric nervous system activity. The proposed research will therefore examine whether the presence of NE from the time of E. coli O157:H7 contamination of NE-rich foods to infection within the gut may be a factor mediating the development of hemorrhagic colitis. Results from this laboratory have shown that the effect of NE on E. coli O157:H7 contamination of NE-rich foods to infection within the gut may be a factor mediating the development of hemorrhagic colitis. Results from this laboratory have shown that the effect of NE on E. coli O157: H7 is due to the production of an autoinducer of growth. Thus, our Specific Aims are: 1) To determine the ability of a purified diet supplemented with levels of NE found in commonly contaminated foods to "prime" E. coli O157:H7 for the NE-rich environment within the gastrointestinal system; 2) To examine the ability of E. coli O157:H7 isolated from gastrointestinal trat of stressed and non-stressed mice since differences in luminal levels of NE between stressed and control animals would provide greater understanding of the recognized ability of stress to alter susceptibility to colitis; 4) To determine the ability of stress of alter the susceptibility of mice to oral challenge with E. coli O157:H7 exposed in vitro to control of NE supplemented diets; 5) To examine whether blockage of NE release within the gastrointestinal tract can alter susceptibility to challenge with E. coli P157:H7; and 6) To purify the serum-bound form of the NE-induced E. coli O157:H7 autoinducer of

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growth and determine its structure which may provide the basis for the development of agents to specifically interrupt bacterial division as well as identify the gene(s) involved in its production. Collectively, the above aims will seek to establish a direct cause and effect relationship between the NE content within food and the gastrointestinal trat to influence the ability of E. coli O157:H7 to cause infection. The demonstration of direct neuroendocrine-bacterial interaction as a mechanism in the pathogenesis of E. coli O157:H7 infection may yield new treatments for both the prevention and treatment of hemorrhagic colitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NITROXIDE THERAPY FOR INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Hsia, Carleton Jc.; Synzyme Technology, Inc. 1 Technology Dr, E-309 Irvine, Ca 92618 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 31-OCT-2001 Summary: (Adapted from the application): Free radicals play important roles in inflammatory bowel disease (IBD), and the reduction or elimination of the adverse effects of these oxidants could provide novel therapies. Antioxidants have been reported to reduce tissue injury in colitis models, but more potent, stable and bioavailable antioxidant compounds are required. This project will test a new class ofantioxidants based on polynitroxylation technology, or linkage of nitroxides (stable N-oxyl radicals) to biological macromolecules. In a preliminary study, polynitroxyl-starch (PNS) acted synergistically with the free (unbound) nitroxide compound Tempol to reduce oxidants (especially superoxide) and attenuate inflammation in TNBS-induced murine colitis. We hypothesize that TNBS colitis involves significant superoxide-mediated injury, and that PNS and Tempol can attenuate this injury. Specific aims are: (1) Produce PNS and characterize its antioxidant activity. (2) Pharmacokinetically define optimal dose and route of administration. (3) Define efficacy in TNBS-induced mouse colitis. If this is successful, Phase II will define mechanisms of action in animal models of IBD (including the IL-10-/- knockout mouse which spontaneously develops colitis) and other studies required for progression to clinical testing in IBD. PROPOSED COMMERCIAL APPLICATION: Inflammatory bowel disease is a significant health problem. If successful this research will lead to the development of a novel therapeutic agent(s) for the treatment of IBD. This would represent a significant commercial opportunity and provide substantial benefit to patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NOD2: A SUSCEPTIBILITY GENE FOR CROHN'S DISEASE Principal Investigator & Institution: Nunez, Gabriel; Professor; Pathology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 08-APR-2002; Project End 31-MAR-2007 Summary: The idiopathic inflammatory bowel diseases (IBD) which includes Crohn's disease and ulcerative colitis are chronic disorders of the gastrointestinal tract of unknown etiology with a combined prevalence of about 150-200 cases per 100,000 in western countries. Although the etiology of IBD is unknown, a large body of evidence suggest that these diseases are multifactorial and likely caused by an abnormal inflammatory response directed against luminal and/or enteric microflora in a genetically susceptible host. However, the genetic basis for this abnormal inflammatory response to enteric bacteria is unknown. Genome-wide searches for IBD-susceptibility genes have resulted in the identification of several loci harboring potential predisposing

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genes for Crohn's disease. Of these, linkage to the pericentromeric region of chromosome 16 (IBD1 locus) has been replicated by several independent studies to confer susceptibility to disease. We have identified Nod2, a gene that encodes a protein with homology to plant disease resistance gene products, that is located in the peak region of linkage disequilibrium on chromosome 16. We have found that a frameshift mutation and genetic variants of Nod2 are highly associated with susceptibility to Crohn's disease by genetic analysis in multi-case disease families and case-control studies. Nod2 is expressed in monocytes and activates NF- kappaB. Significantly, wildtype Nod2 confers responsiveness to bacterial lipopolysaccharides and this activity is deficient in mutant-Nod2 associated with Crohn's disease. These observations suggest a link between an innate immunity pathway controlled : byNod2 and susceptibility to Crohn's disesase. Our overall hypothesis is that Nod2 recognizes lipopolysaccharidesin the cytosol and activates a NF-kappaB signaling pathway in the host cell that protects the host against entericbacteria. Our preliminary results suggest a model in which deficiency in the Nod2 pathway leads to an abnormal T cell-mediated response to enteric bacteria and tissue destruction. We propose three Specific Aims to explore our hypothesis: (i) Determine the sequence of Nod2 that mediates functional activity and - recognition of bacterial LPS. The analyses will include study of Nod2 variants associated with Crohn's disease and systematic mutagenesis of Nod2; (ii) Determine the structure of LPS recognized by Nod2 and (iii) Characterize mice deficient in Nod2 to determine its role in the response to luminal and pathogenic enteric bacteria. The proposed studies should improve our understanding of the role of Nod2 in innate immunity and provideimportant insight into the link between genetic variation in Nod2 and susceptibility to Crohn's disease. The studies may lead to novel therapeutic approaches for Crohn's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL PARS INHIBITOR FOR THERAPY OF COLITIS Principal Investigator & Institution: Jagtap, Prakash; Corporation 100 Cummings Ctr, Ste 419E Beverly, Ma 01915

Inotek

Pharmaceuticals

Timing: Fiscal Year 2001; Project Start 15-APR-1999; Project End 31-MAY-2003 Summary: (Applicant's Abstract): Current treatment of inflammatory bowel disease (IBD) is of limited efficacy, as there are no entirely non-toxic pharmaceuticals that totally halt or reverse the progression of IBD. To address this need, Inotek has invented a novel anti-colitic agent (PJ-34) that is a nanomolar-potent inhibitor of poly (ADP-ribose) synthetase (PARS). PARS are a nuclear enzyme whose activation by inflammatory oxidant stress results in energetic depletion, NF-kappa B nuclear translocation, granulocyte recruitment, and intestinal mucosal barrier dysfunction. We have shown that PARS deficient mice are virtually protected from autoimmune models of enterocolitis. In the Phase I SBIR, we have obtained proof of principle that the ultrapotent PARS inhibitor PJ-34 reverses established murine colitis, resulting in a dramatic reduction in intestinal tissue injury, inflammatory cell infiltration, mortality, and weight loss. In the Phase II SBIR, we intend to demonstrate that the in vivo toxicological profile of PJ-34 meets FDA standards for progression to clinical studies. Specific Aim #1: Scale-up synthesis of PJ-34 to kilogram batch production level. Preclinical evaluation of PJ-34, including toxicology, metabolism, and pharmacokinetic studies, requires process scale-up to produce kilogram scale GLP-grade material. Specific Aim #2: Determine the biochemical, hematological, and histopathologic toxicology profile of PJ-34. Range-finding toxicity studies will provide a comprehensive behavioral, biochemical, and histopathologic profile. These studies will provide the

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foundation for clinical testing, commercial development, and first market entry of an ultrapotent PARS inhibitor for therapy of IBD. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL USE OF ZEBRAFISH FOR APOPTOSIS ASSAY Principal Investigator & Institution: Parng, Chuenlei; Pharmaceuticals, Inc. 100 Inman St, Ste 300 Cambridge, Ma 02139

Scientist;

Phylonix

Timing: Fiscal Year 2003; Project Start 15-APR-1999; Project End 31-MAR-2005 Summary: (provided by applicant): Inappropriate apoptosis is the cause of many human diseases, including cancer, neuronal degeneration, hearing loss, organ failure, myelodysplastic syndrome, multiple sclerosis, type 1 diabetes mellitus, thyroiditis, and ulcerative colitis. Compounds that affect apoptosis are potential therapeutics. Cell based assays are widely used in drug development, however, many promising candidates fail in subsequent mammalian testing. Zebrafish assays can serve as an intermediate step between cellular evaluation and mammalian testing. Zebrafish has several advantages, including transparent embryos for easy visual analysis, rapid embryonic development and low cost. Furthermore, similar pharmacological responses to those in the mammalian apoptotic machinery are present in zebrafish. Currently the standard whole animal apoptosis assay is TUNEL, a histochemical staining technique which detects apoptotic cells in sectioned tissue. This assay is time-consuming and permits examination at only a single time point. Since many degenerative diseases occur in stages, assay formats that permit continuous examination of changes in the apoptosis pattern and the duration of drug effects are needed. Using zebrafish embryos, this proposal will develop a quantitative microplate assay for high throughput screening of compounds. Complementary visual and flow cytometry based assays will also be developed to provide comprehensive analysis of apoptosis in zebrafish. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ORAL CONDITIONS AND PREGNANCY--NEONATAL OUTCOMES Principal Investigator & Institution: Auten, Richard L.; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2002 Summary: This supplemental application extends the evaluation of oral inflammation and infection, effects on pregnancy to the potential impact on premature newborns and the leading complications of prematurity, lung and brain damage. The general hypothesis is that subclinical infection, possibly originating in periodontal disease, affects the inflammatory and immune responses in women, placing them at higher risk for preterm labor and delivery. Pro-inflammatory cytokines, associated with periodontal disease and intrauterine infection, have been implicated in the initiation of preterm labor. Our proposed studies will assess how these maternal processes affect the inflammatory cascade in the premature low birth eight infant and the risk for inflammatory complication of prematurity. Prenatal infection and inflammation are associated with brain injury in premature newborns, in particular intraventricular hemorrhage and periventricular leukomalacia. Inflammatory cytokines are found in the tracheal secretions of premature newborns who later develop bronchopulmonary dysplasia. Necrotizing enterocolitis is another serious life-threatening complication of prematurity associated with elevations in pro-inflammatory cytokines. Genetic polymorphisms encoding IL-1beta and TNFalpha are associated with increased cytokine

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expression and may predispose to an exaggerated inflammatory response. We will measure pro-inflammatory cytokines in pregnant women and compare them to those in their premature newborns. Cytokines will be correlated with the inflammatory complications of prematurity: bronchopulmonary dysplasia, intraventricular hemorrhage/periventricular leukomalacia, and necrotizing enterocolitis, using logistic regression analysis. Polymorphisms will be identified and correlated with these inflammatory complications with the abundance of cytokine protein and mRNA in tracheal aspirates cells and in blood. We will test whether a panel of mediators identified at risk with high sensitivity and specificity. Our long-term aim is to develop markers that identify newborns at highest risk and provide the basis for future therapy to prevent these complications of prematurity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENESIS OF EXPERIMENTAL BOWEL NECROSIS Principal Investigator & Institution: Hsueh, Wei; Professor; Children's Memorial Hospital (Chicago) Chicago, Il 606143394 Timing: Fiscal Year 2001; Project Start 01-DEC-1983; Project End 31-MAR-2002 Summary: In this study we will use a model of ischemic bowel necrosis, or necrotizing enterocolitis (NEC) in rats and mice, by injecting PAF systemically. That PAF may be an important mediator for NEC is based on our previous findings: 1)PAF induces small bowel necrosis. 2)PAF mediates bowel injury induced by LPS, TNF or hypoxia. 3)PAF is rapidly produced after LPS injection, especially in the ileum. 4) PAF-R expression is very high in the small bowel. 5)Experimental NEC induced by hypoxia and formula feeding is prevented by PAF antagonist. 6) NEC patients have elevated serum PAF, and suppressed acetylhydrolase, the enzyme degrading PAF. We recently found that PAF at low dose (without gross bowel injury) also has profound effects on the small bowel, including inducing villus apoptosis and increasing mucosal permeability. Thus, Aim 1 is to examine the effect of low dose PAF on intestinal apoptosis and mucosal permeability (an early event before NEC occurs); and to study the respective mechanisms (roles of Fas/FasL, PMNs, lymphocytes, TNF, ROS, iNOS (inducible nitric oxide synthase), tyrosine kinase, eiconsanoids, tyrosine kinases, IFN- gamma and gut bacteria/LPS). Aim 2 is to test the hypothesis that intestinal necrosis occurs due to an imbalance between the protective cNOS (constitutive NOS) and the injurious iNOS ans xanthine oxidase (XO). This is based on our finding that PAF suppresses the former and stimulates the latter two. Aim 3 is based on our observations that (a) PAF up- regulates ileal PAF-R expression, an effect mediated via endogenous PAF and TNF, (b) PAF-receptor (PAF-R) localizes mainly in lamina propria (LP) eosinophils, (C) PAF permits LPS entry, which binds to LP eosinophils and (d)LPS/bacterial products are required for the development of NEC. We will examine the role of PAF-R, LP eosinophils and LPS in PAF induced LPS entry (a consequence of mucosal permeability increase), and its effect on the pathogenesis of bowel necrosis, release of mediators (e.g., PAF, LTC4,TNF) and consequent intestinal injury. These 3 closely related aims may lead to the elucidation of the pathophysiological function of PAF in the bowel, and the mechanisms of intestinal defense and injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHOGENESIS OF FEVER IN HUMANS Principal Investigator & Institution: Dinarello, Charles A.; Professor of Medicine; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508

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Timing: Fiscal Year 2003; Project Start 01-DEC-1986; Project End 31-JAN-2008 Summary: (provided by applicant): Anti-cytokine therapy for acute and chronic inflammatory diseases has entered clinical medicine. The main targets for anti-cytokinebased therapies are tumor necrosis factor (TNF) and interleukin-1 (IL-1), pleiotropic, proinflammatory cytokines. The IL-1 receptor antagonist (IL-1Ra) has been approved by the FDA for the treatment of rheumatoid arthritis. Other inhibitors of the IL-1 beta are in Phase II trials for various diseases. IL-18, a member of the IL-1 family and closely related to IL-1 beta, also appears to be a target for therapeutic intervention in disease. Specific inhibitors of ICE reduce the release and hence the biological activity of both IL-1 and IL18. We have demonstrated that IL-18 has broad effects similar to those of IL-1 beta such as inducing the synthesis of other pro-inflammatory cytokines, the family of chemokines, activation of neutrophils, and upregulation of Fas ligand and endothelial adhesion molecules. Therefore, the host likely mounts various strategies to limit the biological activities of IL-18. We isolated and cloned a novel IL-18 inhibitor, the IL-18 binding protein (IL-18BP), which binds and neutralizes IL-18; the IL-18BP is a constitutively expressed and secreted inhibitor of IL-18 activity. Another member of the IL-1 family is the IL-1 homologue 4 (IL-1H4), which is structurally related to IL-18, binds to IL-18 receptor alpha chain, which is the ligand binding chain of the IL-18 receptor complex. However, IL-1H4 exhibits no agonist activities. Although likely to be the "receptor antagonist" for IL-18, recombinant IL-1H4 exhibits no receptor antagonist activities for IL-18. We propose to study the function of IL-1 H4 and assess its role in disease as a naturally occurring inhibitor of IL-18 activity. Preliminary data indicate that IL-1H4 binds to the IL-18BP and that this complex recruits the signaling beta chain of the IL-18 receptor complex, thereby depriving the cell of the beta chain for signal transduction. As such, IL-1H4 appears to function as a "decoy" cytokine. The proposed studies are intended to show that IL-1H4 plays a role in disease via this novel mechanism using animal models of inflammatory disease. Human IL-1H4 appears to reduce the activities of mouse IL-18, therefore, we will generate transgenic mice overexpressing human IL-1H4 and challenge these mice using IL-18-dependent models of disease. These studies may have implications for the use of IL-1H4 to treat IL-18related diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEPTIDE ANTIGENS IN CD45RBHIGH CD4+T CELL COLITIS MODEL Principal Investigator & Institution: Saubermann, Lawrence J.; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Chronic human inflammatory bowel diseases (IBD), such as Crohn?s Disease and Ulcerative Colitis, afflicts approximately two million individuals in this country alone. These disorders are primarily characterized by the presence of activated forms of T lymphocytes in the intestinal mucosal compartment. Through a number of investigations in murine models of IBD, as well as human studies, it is becoming increasingly recognized that IBD is associated with luminal or environmental stimuli in a genetically susceptible host. One of the best-characterized murine models of IBD is the CD45RBhigh CD4+ T cell transfer model. Adoptive transfer of this particular subset of T cells into a severe combined immunodeficient (SCID) congeneic recipient, who lacks functional B or T cells, results in colitis. However, adoptive transfer of the CD45RBlow CD25+ CD4+ T cells inhibits colitis. Recent evidence indicates that both T cell subsets are dependent on MHC class II and are

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activated through a restricted set of T cell receptors, which indicates expansion to a limited set of antigens. The model is also dependent on environmental antigen exposure, as SCID mice raised under germ-free conditions, do not develop colitis following cell transfer. Taken together, this implies that the effector and regulatory CD4plus T cells in this transfer model of colitis are most likely activated by a limited number of peptide antigens presented in a MHC class II dependent fashion, and possibly derived from the luminal environment. Therefore, the primary goal of this project is to elucidate the peptide antigen(s) involved in the CD45RBhigh CD4+ T cell population effector response or the CD45RBlow CD25+ CD4+ inhibitory response. Specifically, we plan to use a methodological approach involving cDNA expression libraries to identify unknown peptide antigens for these subsets of T cells. Preliminary experiments with murine DO11.10 CD4+ T cell hybridoma cells, which recognize a 17 amino-acid peptide epitope of chicken ovalbumin in the context of MHC class II, has indicated the initial parameters of this methodology. The primary goal is to identify expressed peptide(s) from recombinant fusion proteins created from cDNA libraries made from tissue and cecal bacteria extracts. The libraries will be screened for reactive epitopes by proliferation and cytokine production. Next, these important T cells will undergo T cell receptor evaluation. Potentially, by this approach, antigens responsible for CD45RBhigh CD4plus T cell adoptive transfer model of colitis can be elucidated, this may lead to a better understanding of human inflammatory bowel disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POLYAMINES AND EARLY GI MUCOSAL RESTITUTION Principal Investigator & Institution: Johnson, Leonard R.; Professor and Chairman; Physiology and Biophysics; University of Tennessee Health Sci Ctr Health Science Center Memphis, Tn 38163 Timing: Fiscal Year 2001; Project Start 01-SEP-1997; Project End 31-JUL-2002 Summary: The overall goal of this grant application is to understand how polyamines influence the migration of GI mucosal cells during the process of early mucosal restitution. Experiments supported during the past 10 years have shown that: 1) polyamines are essential to the healing of gastric and duodenal mucosal, 2) polyamines are required for the mucosal restitution that depends on cell migration, 3) polyamines are essential to migration in a normal line (IEC-6) of intestinal epithelial cells in a model that mimics mucosal restitution, and 4) polyamines alters some components of the cytoskeleton that are essential for cell migration. The first set of specific aims is designed to define the manner in which polyamines interact with the cytoskeleton. These studies will examine the effect of polyamines on the equilibrium between and distribution of, Fand G-actin, determine whether polyamines alter the amounts of distribution of G-actin binding proteins, determine whether polyamines are involved in the attachment of cells to their substrates, and then whether they alter the amounts and distributions of integrins and attachment proteins. Most of these studies will be carried out using immunocytochemical techniques. Preliminary evidence from the PI's laboratory indicates that the small GTP binding protein Rho regulates cell migration in IEC-6 cells. The second set of specific aims tests this hypothesis by inhibiting Rho function and examining the effects on cell migration and the cytoskeleton. Rho function will be inhibited with toxins A and B from C. difficile, C3 toxin from C. botulinum, and recombinant dominant negative Rho(A) T19N protein. These experiments will establish the role of Rho in the regulation of GI epithelial cell migration. In the third set of specific aims, studies will determine whether and how polyamines affect Rho function. Western blot analysis of preliminary results indicates that polyamine depletion decreases the

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amount of Rho protein. These studies will be pursued along with those involving Rho mRNA and Rho GTPase activity. The experiments outlined will explain the original observations of the PI on mucosal healing in whole animals in terms of cell function and describe, in turn, how it is regulated at the molecular level. These results will provide the first description of the involvement of polyamines in the migration of any cell type, and be the first to indicate how Rho regulates GI mucosal cell migration and how it in turn is dependent on polyamines. These studies have clinical application in peptic ulcer disease, cancer, colitis and all conditions where cell migration is important. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: QUALITY OF LIFE IN PEDIATRIC INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Perrin, James M.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2004 Summary: (provided by applicant): Measurement of the quality of life (QoL) of children and adolescents with inflammatory bowel diseases (IBD) has had little attention, despite the importance of understanding key factors affecting QoL, especially for measuring the effects of clinical trials to improve IBD outcomes. The main purpose of this pilot study is to examine the impact of clinical severity and treatment social factors on the quality of life (QoL) of a diverse population of children and adolescents with inflammatory bowel disease (IBD). Secondary purposes include determining the effects of sociodemographic factors on QoL and exploring the concordance of views of parents and children of QoL. The study aims are to 1) determine the associations of of clinical characteristics (condition type, activity/severity, and treatment) with specific components of general health-related quality of life and IBD-specific QoL; 2) describe the effects of sociodemographic characteristics (SES, age, and gender) on these measures; and 3) compare the views of different observers (parent and child with IBD) of the child's QoL. The study will apply both general and condition-specific QoL measures among a random sample of 250 children and adolescents with IBD, ages 5-18 years, in six clinical sites. We will obtain measures of QoL from both the child and a parent in each case. The study will obtain additional data regarding the subjects' clinical condition (condition type, severity/activity, treatment [including surgery], age of onset) and socioeconomic status (household structure and income). Main analyses will compare general and specific measures of QoL and examine the influence of clinical and sociodemographic variables on QoL, through multivariate regression techniques. We will also examine the differences in child and parent assessments of QoL. The information from this study will provide a stronger base for future studies of treatment and natural history of IBD. It will help to clarify the life domains that are affected by IBD and will inform interventions to improve QoL for children with IBD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RECOMBINANT SHIGA-TOXIN-SPECIFIC HUMAN ANTIBODIES Principal Investigator & Institution: Tzipori, Saul V.; Professor and Head; Biomedical Sciences; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: This proposal is in response to RFA: DK-00-005 "Foodborne Illness, Gastrointestinal and Renal Complications", specifically addressing "Development of interventions and/or clinical strategies to prevent complications of E. coli 0157:H7-

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related illnesses during the initial critical interval between the occurrence of hemorrhagic colitis and the development of HUS". The goal of this proposal is to develop an effective immune-based formulation which can be administered safely to children at risk of developing Shiga-toxin (Stx)-related hemolytic uremic syndrome (HUS). The target populations for this treatment include children in whom the disease can directly or indirectly be attributed to Stx. Currently there is no effective treatment or prevention for HUS. In this proposal we demonstrate that exogenous Stx-specific human monoclonal antibodies (Hu-mAbs) which we have generated under a separate NIH award, protect gnotobiotic piglets against Stx-mediated fatal neurological symptoms when administered 6-12 hours after oral challenge with E. coli 0157:H7. In contrast, piglets treated with placebo develop vascular-mediated fatal neurological symptoms within 2-3 days after the oral challenge. In this application we wish to express several of these anti-Stx Hu-mAbs in an eukaryotic system. This will allow us to produce them in large quantities (Specific Aim 1) and in different forms, such as isotype-variants (Specific Aim 2) and Fab fragments (aim 3) to determine which form would provide the most effective protection in vitro and in vivo (Specific Aim 4). We anticipate the final product will contain a cocktail of Hu-mAbs active against the A and B subunits of Stx1 and Stx2 (Specific Aim 4). Given our Preliminary Data, we are confident that specifically designed and highly concentrated Hu-mAbs will be safe and effective in protecting children at risk of HUS. We believe recombinant Hu-mAbs, either as whole molecules or Fabs, will be equally effective. Recombinant Hu- mAbs will considerably improve the efficiency of production of these reagents and make them available for clinical use. In contrast to other sources, such as polyclonal antibodies or murine/chimeric mAbs, HumAbs have longer half-life, better affinity for targets, higher potency, require a lower dose, are safer, and are clearly the wave of the future. We are confident that at the end of the five-year support period we will have expressed in an eukaryotic system, a fully characterized panel of effective recombinant Stx-specific Hu-mAbs, ready to be produced under FDA guidelines for clinical evaluation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF COLITIS BY CYCLOOXYGENASE-2 Principal Investigator & Institution: Wilson, Keith T.; Associate Professor of Medicine; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-JAN-2003 Summary: (adapted from the application) Our investigations to date indicate that inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, enzymes which produce high output nitric oxide and prostanoids, respectively, are consistently upregulated in gastrointestinal mucosal inflammation. Further, expression of these genes can regulate inflammatory pathways. We have identified important protective effects of iNOS and COX-2 in specific in vivo and in vitro models. We have also found important differences in the effects of NOS and COX-2 on inflammatory events. We have used mice with targeted deletion of either iNOS or COX-2 to assess mucosal responses to a known and common pathogen, Helicobacter pylori. iNOS deletion had no effect on H. pylori infection or the severity of gastritis. In contrast, COX-2 deletion resulted in a marked exacerbation of both acute and chronic histologic gastritis, resulted in frequent duodenal ulcer formation, which was not present in controls, and increased colonization levels of H. pylori. In addition, the tissues from H. pylori-infected COX-2deficient [COX-2(-/-)] mice exhibited an exacerbation of the Th1-predominant, IL-12driven dysfunctional immune response which characterizes H. pylori gastritis. COX-2 deletion was also associated with increased epithelial injury due to apoptosis. We have

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also confirmed these alterations of the immune response and apoptosis in vitro. The importance of understanding the role of COX-2 in different forms of GI mucosal inflammation is highlighted by the recent FDA approval and rapid utilization of multiple COX-2 selective inhibitors for treatment of musculoskeletal diseases. Based on our preliminary data and my long-standing interest in inflammatory bowel disease, in the current proposal we will determine the role of COX-2 in several important mouse models of colitis. We will use hapten models in which the mucosal immune response has been described, as well as two pertinent colonic infections, namely Helicobacter hepaticus and Citrobacter rodentia. These infection models were selected because of our findings in H. pylori gastritis and the recognition that murine IBD models appear to depend on the presence of enteric bacteria. Our specific aims are to compare COX-2(-/-) vs. (+/+) mice and wild-type mice treated with COX-2 inhibitors vs. placebo and determine the regulatory role of COX-2 in: 1. models of Th1 (TNBS) and Th2 (oxazolone) mediated colitis and 2. Colonic inflammation and injury due to H. hepaticus and C. rodentia. In both aims we will assess the effect of COX-2 on A. gross and microscopic injury; B. I1-12, Th1, pro-inflammatory and Th2 cytokine levels; and C. epithelial apoptosis. These studies are designed to establish these models and the role of COX-2 in the associated diseases, and will serve as the basis for future investigations and funding applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF GASTROINTESTINAL EOSINOPHILS Principal Investigator & Institution: Rothenberg, Marc E.; Associate Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Eosinophil accumulation in the gastrointestinal tract occurs in numerous diseases (i.e. food allergy, eosinophilic gastroenteritis, allergic colitis, and gastroesophageal reflex). Some of these disorders are highly prevalent and clinically important. For example, food allergy has been documented in 2-4% of children and can by life threatening. Despite the common finding of eosinophils in tissue specimens from these patients, and increasing evidence that these cells have a pathogenic role in these disorders, there has been only a limited understanding of the biological and pathological significance of eosinophils in the gastrointestinal tract. We have begun to elucidate the mechanisms of eosinophil trafficking into the gastrointestinal tract and have developed a novel model of food allergen-induced gastrointestinal inflammation. This grant application proposes to elucidate the cellular and molecular mechanisms involved in regulating eosinophil trafficking into the gastrointestinal tract. The application is based on the main hypothesis that eosinophils normally reside in the gastrointestinal tract and that their homing into this organ is regulated by locally generated eotaxin, a CC chemokine with eosinophil selective activity, that works cooperatively with interleukin (IL)-5. The regulation of gastrointestinal eosinophils by these two cytokines and T cells will be evaluated in healthy states, following oral allergen challenge in the model of allergen-induced gastrointestinal inflammation, and by transgenic over-expression of these cytokines specifically in the intestine. Four aims will be undertaken: (I) the mechanisms of eosinophil homing into the gastrointestinal tract during health states; (ii) characterization of the early and late phase response in the gastrointestinal tract during allergic inflammation; (iii) the mechanism of eosinophil trafficking into the gastrointestinal tract during allergic inflammation; and (IV) the consequences of transgenic expression of eotaxin and IL-5 in the intestine. The proposed experiments will define the mechanisms that regulate gastrointestinal eosinophils at

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baseline and following acute (allergic) and chronic (transgenic) inflammatory stimuli in the gastrointestinal tract. These basic studies will hopefully provide a better understanding of physiological processes in the gastrointestinal tract and diseases processes such as food allergy which may be related, at least in part, to dysregulation of eosinophil trafficking. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF GUT SUBSTANCE P RECEPTORS Principal Investigator & Institution: Vigna, Steven R.; Associate Professor; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-APR-1996; Project End 31-DEC-2006 Summary: (provided by applicant): Substance P (SP) is a neuropeptide involved in physiological regulation and has also been implicated in the pathway resulting in pain and inflammation. In the previous funding period we showed that the SP neurokinin-1 receptor (NK-1R) desensitizes more rapidly and extensively than may other G proteincoupled receptor and that this is caused by receptor phosphorylation and is correlated with receptor-mediated physiological responses. In addition, we showed that the NK-1R undergoes vigorous agonist-dependent endocytosis and recycling as a primary mechanism of resensitization. We also showed that the NK-1R in the rat intestine mediates Clostridium difficile toxin A-induced inflammation, secretion, and tissue damage. These observations suggest that the NK-1R is highly regulated and plays a major role in intestinal inflammation, but the mechanisms of NK-1R regulation are incompletely understood. The current proposal describes studies designed to reveal additional mechanisms of NK-1R regulation. The proposed specific aims are to 1) test the hypothesis that the N-terminus of SP plays a role in homologous desensitization of the NK-1R even though the C-terminus contains all of the agonist activity of the peptide, 2) test the hypothesis that the cytoplasmic microfilament component of the cytoskeleton in NK-1R-expressing cells plays a role in SP-mediated signaling, and 3) test several hypotheses concerning the mechanisms of SP-stimulation of MAP Kinase activity via the NK-1R. These hypotheses will be tested by multiple approaches including assessment of NK-1R signaling and desensitization after site-directed NK-1R mutagenesis. These studies will lead to insight into the normal mechanisms of SP NK-1R regulation and will suggest possible mechanisms of abnormal NK-1R regulation in intestinal inflammatory diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF CHEMOKINES IN T CELL MEDIATED COLITIS Principal Investigator & Institution: Lillard, James W.; Assistant Professor; Microbiology, Biochemistry & Immunology; Morehouse School of Medicine Atlanta, Ga 30310 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: Inflammatory bowel diseases (IBD) are chronic, relapsing and tissue destructive diseases. T helper type l (Thl) cells secreting TNF-alpha and IFN-gamma have been emphasized in ulcerative colitis, while Th2 cells may be more closely associated with Crohn's disease. However, either Thl or Th2 cells can induce colitis in several mouse models; hence the precise causes of these two forms of IBD are incompletely understood. It has recently been shown that the mechanisms of IBD involve antigen- dependent interactions between CD4+ T cells and antigen-presenting cells (APCs) as well as genetic factors. A major deficiency in understanding the steps

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responsible for IBD, is the lack of comprehension for the role innate and early acting factors play in mucosal immune responses. Chemokines are a family of proteins that are resistant to inactivation by pH or proteolysis as well as affect the chemotaxis and angiogenesis of leukocytes and endothelial cells. Therefore, chemokines no doubt play a pivotal role in the regulation (i.e., initiation, maintenance, and suppression) of mucosal inflammation and tissue destruction. In fact, human interleukin-8 (IL-8), IFN-gamma inducible protein - l0 (IP-l0), CXCR3 (the receptor for IP-10), RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted), and MCP-l/JE (monocyte chemotactic protein-1) have been shown to be unregulated at the sites of mucosal inflammation (IBD). The current proposal stems from our recent findings that RANTES, IP-10, IL- 8, lymphotactin (Lptn), but not MCP-l/JE, can enhance mucosal adaptive immune responses. Since these chemolcines act at several levels, four Specific Aims will be addressed to elucidate the precise role of these chemokines and their corresponding receptors in IBD. The first aim will define the regulatory role of chemokines that are secreted by CD45RBHI CD4+ T cells subsets, which cause experimental IBD after adoptive transfer. The second aim will assess the role of mIL-8Rh (murine IL- 8/GCP2 receptor), CCR5 (a RANTES receptor), CXCR3, and XCRl (Lptn receptor) interactions in the CD45RBHI CD4+ T cell transfer model of murine IBD. The third aim will evaluate the chemokines, cytokines, and corresponding receptors that are expressed by the IBD inducers (CD45RBHI) and IBD suppressors (CDRB45LO) CD4+ T cells subsets. The fourth aim will ascertain the angiogenic or angiostatic factors and cell signaling molecules that are expressed or activated, respectively, by chemokines that regulate IBD. These proposed studies will provide important and novel information regarding the cellular and molecular mechanisms that chemokines use to induce, maintain, and suppress mucosal inflammation and angiogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE ENTEROCOLITIS

OF

EGF

IN

DEVELOPMENT

OF

NECROTIZING

Principal Investigator & Institution: Warner, Barbara B.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Necrotizing Enterocolitis (NEC) is the most common acute gastrointestinal emergency in the neonatal period and is primarily found in preterm infants. As more preterm infants survive, the impact of NEC is more profound. Despite the significant effect of this disease on neonatal morbidity and mortality, the research directed in this area is relatively sparse. The single most important risk factor in the development of NEC is a premature gastrointestinal tract. Epidermal growth factor (EGF) is an established growth factor crucial to the development and maintenance of the gastrointestinal epithelium. Preliminary studies have revealed significantly reduced salivary EGF levels in infants following intestinal resection for NEC. This proposal will expand upon this observation and directly test the novel hypothesis that low salivary EGF levels are linked to the development of NEC. To test this hypothesis two specific aims are proposed. Aim 1 - Determine the ontogeny of EGF expression in neonates. Since prematurity is the single most important risk factor for the development of NEC, this first aim tests the hypothesis that salivary EGF expression is directly related to gestational age. The developmental pattern of salivary EGF will be correlated with serum values and measured across different gestational ages, as well as longitudinally for each individual patient. Aim 2 - Determine the predictive value of salivary EGF in the development of NEC. This aim tests the hypothesis that the pattern of salivary EGF

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is predictive for the development of NEC. To test this hypothesis, the pattern of salivary EGF expression and its relationship to the development of NEC will be modeled, controlling for detailed clinical and demographic data on variables related to the development of NEC and expression of EGF. These experiments will provide essential original information regarding baseline serum and saliva EGF levels and their predictive value in the development of NEC. This information is requisite toward the development of innovative clinical trials using exogenous EGF as a new therapeutic modality in the treatment/prevention of NEC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF LEPTIN IN MURINE MODELES OF IBD Principal Investigator & Institution: Fantuzzi, Giamila; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The goal of this project is to investigate the mechanisms by which leptin deficiency regulates susceptibility to intestinal inflammation in mice. In addition to act as a regulator of food intake and energy expenditure, leptin also modulates the immune and inflammatory response. Preliminary data indicate that leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice are resistant to colitis induced by chronic administration of DSS or TNBS. The current application will attempt to identify the cell populations responsible for the observed effects. In Specific Aim 1, to evaluate the relative role played by neuronal leptin receptors (Ob-R) in regulation of intestinal inflammation. DSS and TNBS will be administered to mice with a selective deficiency of Ob-R in neurons and their response compared with that of WF mice. To analyze in more detail the role of hypothalamic ObR, DSS- and TNBS-induced intestinal inflammation will be studied in mice in which ObR have been specifically deleted in the arcuate and ventromedial nuclei of the hypothalamus by injecting a vector expressing cre recombinase into Ob-Rflox/flox mice. Because the effects of leptin on both bone marrow- and non-bone marrow-derived cells could contribute to modulation of colitis in the models of DSS and TNBS administration, in Specific Aim 2 the relative contribution of Ob-R expression in these two cell populations will be investigated using bone marrow chimeras for Ob-R. WT bone marrow will be transplanted into db/db mice, while WT mice will receive db/db bone marrow and colitis development will be studied. Furthermore, the direct effects of leptin on T lymphocytes. Preliminary data indicate that Ob-R expression on donor T lymphocytes regulates induction of colitis in the model of CD4+ CD45RBhigh cells transfer into SCID mice. The transfer model will be employed in the attempt to dissect the relative role played by Ob-R expression in donor T lymphocytes versus cells in the recipient mouse. To investigate the direct role of Ob-R expression in T lymphocytes in the modulation of colitis induced by DSS or TNBS, mice with a selective deletion of ObR in T lymphocytes will be employed. Finally, in Specific Aim 3 production of leptin by immune cells at the site of intestinal inflammation will be evaluated in murine models and in biopsies of patients with IBD. The possible participation of immune-derived leptin in the local inflammatory network will also be investigated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SAFE FOCUSED DELIVERY OF GENE THERAPEUTICS TO COLON Principal Investigator & Institution: Sano, Takeshi; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215

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Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The long-term goal of this project is to develop a safe, efficient gene transfer technology that can be used for gene therapy of diseases in the colorectal system. The R21 phase of this project will focus on the development of a gene transfer technology that allows safe, efficient, and focused delivery of transgenes to the colorectal system. During this technology development phase, we will use inflammatory bowel disease (IBD), which consists of Crohn's disease and ulcerative colitis, as a first target to assess the efficacy of the gene transfer technology. We have recently developed a novel gene transfer technology, in which viral particles (adenoviral vectors and adeno-associated viral vectors) are delivered to target sites in a microbeadassociated form. These virus-microbead conjugates can infect target cells at efficiencies much greater than the same viral vectors used free in solution. A key feature of this gene transfer technology is that the infection sites by viral vectors are equal to the contact sites between target cells and virus-microbead conjugates. This allows focused delivery of transgenes to target sites with high transduction efficiencies by placing virusmicrobead conjugates at the site of interest. Since each viral particle on the microbeads either mediates infection of a cell or stays on the microbeads, no free viral particles should be present. Thus, uncontrolled transduction of other non-target tissues or organs by viral vectors can be eliminated, and immune responses to viral vectors can be minimized. These and other characteristics suggest that this technology could allow for the efficient, safe delivery of transgenes to the colorectal system. In particular, it could be very useful for the development of effective gene therapy protocols for IBD, since a potentially efficacious gene therapy strategy for IBD is to repress intense inflammation in the colon by local, high-level expression of anti-inflammatory cytokines at inflamed lesions. We will investigate the potential of this gene transfer technology for the safe, focused delivery of the gene for a potent anti-inflammatory cytokine, interleukin-10 (IL10), to inflamed lesions in the colon for the amelioration of established colitis. We hypothesize that this technology will allow for safe, efficient, and focused delivery of the IL-10 gene to inflamed lesions in the colon, resulting in the local expression and secretion of IL-10 in the inflamed lesions for the amelioration of established colitis with minimal detrimental effects on other tissues and organs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SELENIUM-AFFORDED ATHEROSCLEROSIS

PROTECTION

AGAINST

Principal Investigator & Institution: Chu, Fong-Fong; City of Hope National Medical Center Duarte, Ca 91010 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant) The long-term objective is to understand the mechanism for the antioxidant effect of selenium against inflammation. Low Se content is associated with a higher incidence of cardiovascular diseases. The pathogenesis of atherosclerosis is recognized as a chronic inflammatory disease in endothelium, and inflammation in other organs may also increase the risk of atherogenesis. The investigators have recently found that mice deficient in two Se-dependent glutathione peroxidase (GPX) isozymes, GPX-1 and GPX-GI (encoded by Gpxl and Gpx2) develop severe colitis by the time they are weaned. Because GPX isozymes have been implicated to be the anti-atherosclerotic activity of Se, the investigators propose that the GPX-1 and GPX-GI protect against atherosclerotic lesions. In the first aim, the investigators plan to determine if GPX-1 and GPX-GI are the major anti-atherosclerotic activity of Se. They will study if mice deficient in either the Gpxl or the Gpx2 gene, or both genes, in

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C57BW6J background have more severe atherosclerotic lesions than the control mice. If these mice deficient in one or both of GPX isozymes no longer respond to dietary Se modulation, this suggests that the GPX isozyrnes are the major Se-dependent antiatherosclerotic activity. If one or both GPX-1 and GPX-GI have anti-atherosclerotic activity, the investigators will distinguish this activity in the prevention of low density lipoprotein (LDL) oxidation originated from dietary and endogenous sources in the second aim. If Gpx2-knockout mice have a higher level of oxidized LDL in the plasma than control mice after being fed a high fat diet, because the Gpx2 gene is highly expressed in the intestinal epithelium, this suggests that the LDL oxidation may occur from the dietary source. If Gpxl-knockout monocytes or neutrophils can generate more oxidized LDL than control cells, this suggests that GPX-1 can prevent LDL oxidation from endogenous cells. Whether GPX-1 inhibits NF-KB activation, which plays a pivotal role in inflammatory response, will be analyzed in macrophages/monocytes. If neither GPX-1 nor GPX-GI has anti-atherosclerotic activity, or these 2 isozymes are not the major Se-dependent anti-atherosclerotic activity, it suggests other selenoproteins contribute. The investigators will generate GpxS-knockout mice deficient in the plasma GPX isozyme, GPX-P, to study this activity as they have done for Gpx2-knockout mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SHIGA TOXIN EFFECTS ON GENE REGULATION Principal Investigator & Institution: Thorpe, Cheleste M.; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-MAY-2004 Summary: (adapted from applicant's abstract): Shiga toxin-producing E. coli (STEC) have emerged as a major health problem in the developed world and are associated with diseases such as hemorrhagic colitis and hemolytic uremic syndrome. Our understanding of the role of Shiga toxins in the pathogenesis of STEC-associated disease is incomplete. Classical thinking about Shiga toxins' role in disease pathogenesis is that Shiga toxins harm the host by causing toxic effects on sensitive cells by inhibiting protein synthesis of critical proteins needed for cell survival. We have found that Shiga toxins are capable of inducing and superinducing IL-8, in intestinal epithelial cells. Paradoxically, IL-8 is secreted by these cells despite overall blockade of mRNA translation. Our data suggest that this may occur through alterations in host signal transduction. These data support a new model of how Stxs may contribute to disease, namely that Stxs are involved in altering the regulation of one or more host cell processes, resulting in synthesis of proteins by the host that contribute to pathogenesis. The goals of the proposed work are: 1) to characterize how Shiga toxins affect IL-8 gene regulation in intestinal epithelial cells 2) to determine how Shiga toxins are able to increase IL-8 mRNA and protein while inhibiting translation, and 3) to assess the effects of Shiga toxins on related genes in the intestine and the kidney. Shiga toxin-induced alterations in IL-8 gene regulation will be assessed at the level of transcription. The role of Shiga toxin glycohydrolase activity in IL-8 mRNA induction will be assessed. Effects of Shiga toxins on host signal transduction will be assessed. Intracellular trafficking pathway inhibitors will be employed to determine if specific Shiga toxin trafficking pathways are necessary for IL-8 synthesis. Using confocal microscopy, co-localization of IL-8 mRNA and intracellular Shiga toxin will determine if the site of IL-8 mRNA translation is distinct from where Shiga toxin traffics. Finally, the effects of Shiga toxins on gene regulation in epithelial cells will be assessed on a genomic level using cDNA microarray hybridization techniques. Understanding how this toxin may augment a host inflammatory response through affecting host gene regulation may allow us to

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better understand the pathogenesis of a disease for which there is no vaccine and only supportive therapies. Through coursework, seminars, and supervised research, Dr. Thorpe will gain knowledge and expertise in techniques pertinent to the proposed research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SHIGA TOXIN ENCODING PHAGE AND INTESTINAL E.COLI Principal Investigator & Institution: Weiss, Alison A.; Professor; Molecular Genetics, Biochemistry & Microbiology; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 31-JAN-2005 Summary: (provided by applicant): Shiga toxin-producing Escherichia coli, including O157:H7, are emerging pathogens of major importance. Bacterial colonization is associated with intestinal disturbances; however, the severe, potentially fatal symptoms of bloody diarrhea (hemorrhagic colitis) and destruction of the kidney leading to hemolytic uremic syndrome (HUS) are due to a bacterial toxin, Shiga toxin. The genes for Shiga toxin are encoded by a temperate bacteriophage in the late gene operon. Shiga toxin is expressed when the phage lytic cycle is induced, along with the genes necessary for production of viral particles and bacterial lysis. Phage-mediated bacterial lysis is necessary for toxin secretion. The viral particles produced during infection with the pathogenic O157:H7 can infect the nonpathogenic intestinal E. coli. When this occurs, the previously harmless E. coli will produce Shiga toxin and amplify the pathogenic process. Our preliminary data suggest that the Shiga toxin production by intestinal flora can be substantial and that severe, possibly life-threatening disease is more likely to occur in individuals whose intestinal flora can be infected by the Shiga toxin phage. In contrast, individuals with intestinal flora that are resistant to the Shiga toxin phage will be protected from severe disease. Currently, it is difficult to prevent disease by E. coli O157:H7 since the infectious dose is very low, and antibiotic treatment, instead of being beneficial, can enhance progression to fatal disease. We propose to develop methods to convert the intestinal flora to phage-resistance as a therapeutic approach to controlling disease caused by Shiga toxin-producing pathogens. This is especially important since there is no treatment, other than supportive care, once disease has developed. The specific aims of this application are to: 1) Characterize Shiga toxin production by clinical isolates of O157:H7 in the presence of susceptible or resistant human intestinal E. coli; and 2) Develop methods to convert intestinal flora to phage resistance using a mouse model of disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SOCS2 AND INTESTINAL FIBROSIS Principal Investigator & Institution: Fruchtman, Shira; Cellular/Molecular Physiology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 01-DEC-2003; Project End 31-AUG-2004 Summary: (provided by applicant): The long-term objective of this proposal is to identify intrinsic negative modulators of inflammation-induced fibrosis, an incurable complication of Crohn's disease. The key to controlling fibrosis is to define mechanisms which permit normal wound healing but prevent these healing responses from becoming excessive. Considerable evidence indicates that locally expressed insulin-like growth factor-I (IGF-I) is upregulated in myofibroblasts at sites of fibrosis in Crohn's

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disease and in animals models with experimentally induced intestinal inflammation. Preliminary evidence supports the hypothesis that suppressor of cytokine signaling-2 (SOCS2) limits the fibrogenic effects of IGF-I in the inflamed intestine. After acute colitis, mice deficient in both SOCS2 alleles show increased collagen deposition and augmented IGF-I expression compared to wild type (WT) mice suggesting that SOCS2 may suppress inflammation-induced fibrosis mediated by IGF-I. One aim of this study is to determine the mechanism by which SOCS2 limits IGF-I action. These studies will use cultured myofibroblasts which overexpress SOCS2 to define those signaling molecules within the IGF-I pathway that are inhibited by SOCS2. The second aim is to test the hypothesis that mice with mesenchymal cell-specific ablation of SOCS2 show more severe fibrosis than WT littermates after acute mucosal injury induced by sodium dextran sulfate (DSS) or colitis induced by trinitrobenzene sulfonic acid (TNBS). Defining how SOCS2 limits fibrosis may provide new insights into strategies or therapies that limit or prevent fibrosis in Crohn's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STCE, AN E.COLI O157:H7 PROTEASE SPECIFIC FOR C1-INH Principal Investigator & Institution: Welch, Rodney A.; Professor & Chair; Medical Microbiol & Immunology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 16-JAN-2003; Project End 31-DEC-2007 Summary: (Provided by applicant): Enterohemorrhagic Escherichia coli (EHEC), principally serotype O157:H7, cause an estimated 20,000 cases of diarrheal disease in the United States per year. 2-6 percent of the infected individuals, mostly young children progress to a severe renal disease, hemolytic uremic syndrome (HUS). The EHEC pathogenic factors that lead to bloody colitis and HUS are poorly understood, but knowledge of some mechanisms has recently emerged. Intimin-mediated adherence and type III effectors are encoded by a chromosomal locus termed LEE. The phage-encoded Shiga toxins (Stxs) are responsible for significant aspects of EHEC disease. EHEC strains commonly possess large plasmids, the prototype being pO157. We have identified a new pO157 gene, stcE, which encodes an extracellular zinc-metalloendoprotease (ZMP) that specifically cleaves the critical anti-inflammatory regulator C l-esterase inhibitor (C 1-Inh). C 1-Inh is a serine protease inhibitor (serpin) that provides the principal inhibition of the proteolytic cascades involved in classic and mannan-binding ligand complement activation, contact activation and intrinsic coagulation. C l-Inh inhibits diverse proteases: Clr and Cls, MASP-1, MASP-2, kallikrein, FXIIa, FXIa, and plasmin. Deficiencies in Cl-Inh cause profound clinical syndromes. The best known is hereditary angioedema (HAE), a genetic deficiency in Cl-Inh, which is characterized by transient, recurrent attacks of intestinal cramps, vomiting, diarrhea and life-threatening episodes of tracheal swelling. Fluorescenated StcE binds to cultured macrophages, B- and T-cells. Thus, StcE is an example of a growing class of ZMPs such as tetanus, botulinum and anthrax lethal factor toxins. These ZMPs, in contrast to the homologous Pseudomonas and Vibrio ZMPs, have specific, non-extracellular matrix protein targets. We will test the hypothesis that StcE degrades soluble or cell-associated Cl-Inh, and this results in poorly regulated serine protease cascades involving complement activation, contact activation and coagulation. This dysregulation would then contribute to local inflammation, tissue damage and edema. The elucidation of StcE structure and function(s) may result in new targets for chemotherapeutic or immune prevention or treatment of EHEC infections, which now are best managed only by supportive therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SUPPRESSION OF CLOSTRIDIUM DIFFICILE BY COMMENSALS Principal Investigator & Institution: Wilson, Kenneth H.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The human colon harbors an ecosystem with a rich variety of commensal bacteria that suppress populations of pathogenic bacteria such as Clostridium difficile, the cause of antibiotic-associated colitis. C. difficile disease results when antibiotics damage bacteria that suppress this pathogen, allowing toxigenic strains to establish significant populations in the colon. Initial data from the Pl's lab strongly suggest that a specific phylogenetic group of human commensals is important for the suppression of C. difficile. The goal of the work proposed in this application is to pursue further data to either support or refute the hypothesis that Clostridium coccoides and related organisms protect humans from C. difficile disease. The Specific Aims are 1) to observe the correlation between the population size of C. difficile and the size and complexity of the C. coccoides group in patients treated with antibiotics, 2) to compare the population size of C. difficile in germfree mice with that in gnotobiotic mice colonized with these human commensals and 3) to determine how these commensals suppress C. difficile in a continuous-flow culture model of the colonic ecosystem. Work related to Specific Aim 1 will involve a prospective study of patients on antibiotics. Before and after antibiotic treatment, fecal specimens will be obtained for assessment of C. difficile population size (quantitative cultures) and for determination of the composition of fecal biota. Ribosomal DNA in these specimens will be amplified with PCR, then studied by using 1) high throughput sequencing and phylogenetic analysis of obtained sequences, 2) denaturation gradient gel electrophoresis and 3) a novel 16S rDNA photolithography chip. Because there is not an adequate basis for a power calculation in Specific Aim 1, data obtained might not answer the primary question, but would allow a valid power calculation to be performed to support further study. For Specific Aim 2, germfree mice will be monoassociated with C. difficile followed by either 20 C. coccoides-related organisms, 20 C. leptum-related organisms, or no further biota. C. difficile population size will be followed by quantitative cultures. The mechanisms of suppression (Specific Aim 3) will be determined in a Freter continuousflow culture model of the large bowel, with emphasis being placed on competition for metabolic substrates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TARGETING ANGIOGENESIS WITH TOXIN VEGF FUSION PROTEINS Principal Investigator & Institution: Backer, Joseph M.; Chief Executive Officer; Sibtech, Inc. 705 N Moutain Rd Newington, Ct 06111 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-JUL-2003 Summary: (Applicant's Description) The overall goal of this project is to develop a commercially viable bacterial toxin-VEGF (vascular endothelial growth factor) fusion protein for selective targeting of endothelial cells at sites of angiogenesis, primarily in solid tumors and growing metastases. VEGF interacts with the endothelial cell specific KDR/flk-1 receptor that is overexpressed in endothelial cells at the sites of angiogenesis relative to its expression on quiescent endothelium. In Phase I of this project we have constructed, expressed and purified two novel fusion proteins, SLT-VEGF/L and SLTVEGF/S which contain, respectively, The A subunit of Shiga-like toxin I (SLT) and a functionally active fragment of the A subunit. SLT causes hemorrhagic colitis and

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hemolytic uremic syndrome by damaging endothelial cells suggesting that endothelial cells are particularly sensitive to SLT. SLT-VEGF/L and SLT-VEGF/S proteins selectively inhibit growth of endothelial cells overexpressing KDR/flk-1 receptors with IC-50 of 0.15 nM. At low nanomolar concentrations SLT-VEGF/L is cytotoxic for endothelial cells overexpressing KDR/flk-l receptors. However, these proteins do not affect growing endothelial cells with low numbers of KDR/flk-l receptors, quiescent endothelial cells, and growing non-endothelial cells. These results provide a rationale for Phase II in vivo testing of SLT-VEGF fusion proteins as highly selective inhibitors of angiogenesis. We will also test whether SLT-VEGF proteins may synergize with other antitumor drugs by enhancing delivery through damaged tumor endothelium or by creating hypoxic conditions for bioreductive therapeutics. Finally, we will optimize SLTVEGF fusion proteins to achieve high levels of expression, activity, and stability that are necessary for preclinical and clinical trials. PROPOSED COMMERCIAL APPLICATION: A brief summary of the potential commercial applications of the research: VEGF-toxin fusion proteins that inhibit angiogenesis but do not affect normal endothelium or normal cells will be commercial products for therapy of angioaenesis-dependent pathologies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE PATHOGENESIS OF COLITIS IN A NOVEL TH2 MODEL OF IBD Principal Investigator & Institution: Snapper, Scott B.; Assistant Professor of Medicine; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 05-APR-2002; Project End 31-MAR-2005 Summary: (provided by applicant): The overall objective of this project is to gain further understanding of the mucosal immune system and the defects that contribute to the pathogenesis of human inflammatory bowel disease (IBD). The generation of a number of murine models of IBD has facilitated investigation into the basic mechanisms underlying IBD pathogenesis. Despite the fact that most murine models of IBD result from a defect in a single protein known to affect leukocyte function, the specific autoreactive or regulatory cell population responsible for disease pathogenesis remains unknown. The Wiskott-Aldrich syndrome (WAS) is one of several immunodeficiencies that have been associated with autoimmunity, including IBD. We have recently generated a mouse model of IBD that results from the targeted disruption of the Wiskott-Aldrich syndrome protein (WASP). WASP is expressed solely in hematopoietic cells and is a signaling molecule that regulates cell surface receptor signals to the cytoskeleton. Abnormalities in this protein lead to the rare X-linked primary immunodeficiency that carries its name. The majority of WASP KO (WKO) mice also develop colitis. Our preliminary studies suggest that the colitis in WKO mice is unique, and perhaps more similar to human IBD than other murine models of IBD, because WASP-deficiency does not result in the loss of a specific T-cell class (e.g., alpha-beta T cells) or the absence of one specific cytokine (e.g., IL-2, IL-10 The development of each hematopoietic lineage is intact despite the fact that WASP regulates the actin cytoskeleton in all hematopoietic cells. In contrast with most murine models of IBD that have a Th1 bias, we demonstrate that lymphocytes isolated from the colonic lamina propria of WKO mice secrete a Th2 cytokine pattern. In addition, our genetic and adoptive transfer studies have established the requirement for lymphocytes in disease pathogenesis and the specific ability of CD4+ T-cells to transfer disease. Furthermore, WKO mice have a reduction in regulatory T-cells that are known to regulate autoimmunity in mice. Preliminary data also suggests that microbes play an essential

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role in disease pathogenesis. Interestingly, non-lethal irradiation leads to a dramatic increase in the severity of colitis with 100 percent disease penetrance. Our first aim is to define the role of WASP in regulatory and effector T-cell function and the contribution of additional leukocyte populations in IBD initiation and maintenance. Our second goal is to define the requirement of Th2 cytokines and the role of inflammatory and suppressor cytokines in colitis development. Our final goal of this proposal is to evaluate the role of bacteria and barrier function in colitis initiation in WKO mice. Overall, this project seeks to take advantage of the opportunity to study a murine model of colitis with several unique features that also has a human correlate in order to elucidate the role of cytoskeletal regulation of leukocytes in mucosal homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ENTEROCOLITIS

ROLE

OF

PAF

IN

NEONATAL-NECROTIZING

Principal Investigator & Institution: Caplan, Michael S.; Evanston Northwestern Healthcare Res Ins Evanston, Il 60201 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-MAY-2004 Summary: Necrotizing enterocolitis (NEC) is a common gastrointestinal disease of premature infants without clearly defined etiology or treatment. Current theory suggests that many factors including hypoxia, bacterial colonization, feeding, and prematurity contribute to the development of disease, but the final common pathway associating the risk factors with the intestinal pathology remains unclear. Our previous studies have shown that the inflammatory mediator platelet activating factor (PAF) may be involved in the pathogenesis of bowel necrosis. The overall emphasis of this proposal is to investigate the importance of PAF and altered PAF metabolism in this disease, and to delineate specific mechanisms involved in the pathogenesis. We hypothesize that local intestinal PAF metabolism is altered in neonatal NEC, that PAF dysregulation leads to apoptosis of intestinal epithelium, disruption of tight junctional integrity, mucosal permeability, and activation of the secondary inflammatory cascade, and that this modulation is critical for the development of the disease. Therefore the specific aims of this proposal are: l) To elucidate the mechanisms of altered PAF metabolism and biological activity in the developing and injured intestine, and 2) To investigate the mechanisms of PAF-induced mucosal damage, and to delineate the underlying role of PAF-induced mucosal damage in NEC pathogenesis. To accomplish our goals, we have developed a neonatal rat model of NEC that mimics the human condition, and will study the effects of altered PAF metabolism on the development of intestinal nectosis, and on pathophysiologic events preceding the evolution of bowel injury. in addition, to identify the cellular and molecular level regulation of epithelial cell damage, we will use various tissue culture models of the intestinal epithelium. To elucidate specific mechanisms resulting in altered PAF regulation in the intestinal microenvironment we will evaluate if activation of local PAF production, decreased PAF degradation, or altered PAF- receptor expression and function results from typical NEC risk factors (formula feeding and asphyxia) or change during developmental maturation. in addition, we will evaluate the effect of altered PAF regulation on apoptosis and mucosal penneability, and clarify the roles of these factors in the initiation of NEC and the signal transduction mechanisms that lead to these events following PAF receptor activation. Results from these experiments should clarify key mechanisms linking the risk factors of NEC with the pathologic outcome, and may provide new strategies for the prevention of NEC in premature newborns. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TNF RECEPTORS OF COLONIC EPITHELIAL CELLS IN IBD Principal Investigator & Institution: Mizoguchi, Emiko; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Tumor necrosis factor-alpha (TNFalpha) induces multiple physiological effects through distinct signaling cascades associated with TNF receptor-type I (TNFR1) and -type II (TNFR2). TNFalpha plays an important role in the pathogenesis of inflammatory bowel disease (IBD) and neutralization of TNFalpha is effective in the treatment of Crohn's disease (CD). TNFR2 can be expressed by inflammatory cells including lymphocytes and macrophages as well as colonic epithelial cells (CEC) under inflammatory conditions, and the induction of TNFR2 expression on CEC is associated with the development of IBD. TNFR1 which is constitutively expressed on the CEC seems to be involved in the regulation of TNFR2 expression. The experiments in the proposal are designed to test the hypothesis that TNFalpha/TNFRs interactions on CEC play functionally distinct roles from those on immune cells in the development of colitis. We also hypothesize that the TNFRs mediate different responses in T helper type 1 (Th1)- and T helper type 2 (Th2)-dominant chronic colitis. In Aim I, we plan to define the cooperative effect of TNFR1 and TNFR2 on the CEC proliferation in the context of experimental inflammation. In Aim II, we plan to define the role of TNFR2 on CEC and macrophages in the development of Th1-mediated colitis. In Aim III, we plan to define the role of TNFRs on CEC in the pathogenesis of Th2-mediated chronic colitis. These studies will help clarify the functional role of TNF/TNFRs interaction on CEC in the pathogenesis of IBD. This application is for a Mentored Clinical Scientist Development Award to an applicant who has completed training in internal medicine, and has received pre-and post-doctoral training in Immunology and immunopathology. The applicant's long term goals are to establish and direct her own independent basic research program in studies to link epithelial biology in inflammatory bowel disease. Accordingly, these studies are sponsored by Dr. Daniel K. Podolsky from the Division of Gastroenterology and by Dr. Atul K. Bhan from the Immunopathology Unit, both at Massachusetts General Hospital and Harvard Medical School. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TREFOIL FACTOR FAMILY 3 IN NECROTIZING ENTEROCOLITIS Principal Investigator & Institution: Lin, Jing; Pediatrics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 15-SEP-1999; Project End 31-AUG-2004 Summary: Necrotizing enterocolitis (NEC) is a major cause of morbidity and mortality in premature infants; its etiology and pathogenesis remain elusive. NEC primarily affects premature infants suggesting that the immaturity of the mucosal barrier of the developing intestinal tract may be associated with the premature infant's particular susceptibility to mucosal injury. Trefoil factor family 3 (TFF3), a member of the newly defined trefoil factor family, is secreted abundantly at the mucosal surface by goblet cells throughout the small and large intestine in adults. As TFF3 has an important role in the maintenance and repair of the intestinal mucosal barrier, its deficiency in premature infants may play a role in the susceptibility of premature infants to NEC. This research proposal will characterize the developmental expression of TFF3 and examine the effect of prenatal steroids on its expression during rat intestinal development and injury. Specifically, rat intestinal tissues will be examined for TFF3 gene and protein expression

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at various developmental time points. Further, the effects of glucocorticoid on developmental expression of TFF3 will be determined. Using a rat NEC model, changes in TFF3 expression, as well as the effect of glucocorticoids on TFF3 expression and enteral TFF3 administration in prevention of NEC will be investigated. Further, TFF3 expression during human intestinal development will also be determined in two ways, first by examining TFF3 expression in intestinal tissues from early aborted fetuses and infants of different gestational age, and also by enzyme-linked immunoassay, to measure TFF3 in stool and compare TFF3 expression in stools of premature infants who develop NEC and of those without NEC. These studies should provide novel insights into the development of the intestinal mucosal barrier and unique possible strategies for the early diagnosis and prevention of NEC in premature infants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRIMERIC G PROTEINS AND CONTROL OF HOMEOSTASIS Principal Investigator & Institution: Birnbaumer, Mariel; Professor; Anesthesiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 12-SEP-1994; Project End 31-MAR-2002 Summary: (Adapted from applicant's abstract): Our long term goals are to study transmembrane signalling by heterotrimeric G proteins. The structure and most molecular aspects of transmembrane signalling G proteins have been solved, but their respective participation in complex homeostatic processes such as inflammatory reactions, pain perception, behavior and maintenance of normal glycemia remains largely unknown. During the previous and this last granting period we began addressing the roles of G proteins in homeostasis by creating mice lacking specific G proteins (knockout mice). We have now individually knocked out four of the 15 G protein alpha subunit genes: Gi1, Gi2, Gi3 and Go, and we also have a double and Gi1/Gi3 knockout. These G proteins form the group of non-sensory pertussis toxin (PTX)-sensitive G proteins which couples a distinct set of receptors to a common set of effectors. Two of the knockouts (Gi1 and Gi3, and their combination) are so far asymptomatic. Gi2-/- mice develop ulcerative colitis (UC) and adeno-carcinomas, but in a context sensitive manner, i.e., depending on the strain (genomic background). Go-/mice have multiple neurological alterations and term this phenotype 'rotator'. Go-/mice also show unexpected alterations in Ca2+ channel function and, when subjected to a glucose load, respond with a much tighter control of glycemia than controls. For the coming years we propose: a. To complete the disruption of the Gz G protein, which shares with the inactivated G protein alpha subunits a high degree of structural and functional similarity, coupling the same set of receptors to the same set of effectors, but is PTX- insensitive. This will be complemented by the creation by breeding of the compound G protein deficiencies. b. To search for and characterize one or more genes responsible for suppression (or promotion) of the development of UC and adenocarcinomas in Gi2-/- mice. c. To search for the neurotransmitter system(s) in the CNS affected by lack of Go and, if possible, interpret the rotator phenotype in terms of existing theories of central nervous system motor circuits. And d. to characterize insulin secreting properties of Go-/- islets in vivo and in vitro. The identification of one or more modifier genes of UC and/or adenocarcinoma formation may aid in the elucidation of the etiology of human UC and its complications (adenocarcinomas). Investigation of the role of Gz is expected to shed new light on molecular mechanisms involved in thrombus formation. The elucidation of the mechanism(s) altered by lack of Go may aid in the

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understanding of human motor disorders and may shed new light on development and/or treatment of type II diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VASCULAR INFLAMMATION

ENDOTHELIAL

CADHERIN

FUNCTION

IN

Principal Investigator & Institution: Shaw, Sunil K.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 15-MAR-2000; Project End 31-DEC-2002 Summary: Candidate: The applicant has researched mucosal lymphocyte homing and recirculation for the past 8 years. Accomplishments include contributions at both molecular and cell biological levels to interaction of intraepithelial lymphocytes with epithelial cells. Environment: Brigham and Women's hospital, affiliated with Harvard University, is recognized as a leader in medical research, and will provide a supportive and stimulating environment. The mentor's lab at the Vascular Research Division has access to specialized equipment and tissues necessary for this research. Research: Gastritis, ulceration, celiac sprue, Crohn disease and ulcerative colitis, glomerulonephritis, interstitial nephritis and pyelonephritis are all characterized by the activation of inflammatory cells leading to tissue injury. Leukocyte transmigration and accompanying increased vascular permeability are critical steps during the inflammatory response. Thus, integrity of the organ vasculature is necessary for normal system function, and the endothelial barrier must be breached to lead to tissue injury in these diseases. Although much is known about leukocyte-endothelial adhesion and inflammation, less information is available concerning the role played by endothelial cells in regulating permeability and leukocytes and macromolecules. Vascular endothelial cadherin is located at endothelial adherens and junctions and may regulate monolayer permeability to leukocytes and inflammatory factors. The objective of this proposal is to study the role of VE-cadherin in barrier function and cell growth in vascular endothelial cells by disruption via a dominant negative mechanism. A high efficiency if transfection will be achieved using an adenoviral expression system. This approach will allow specific disruption of one component of the adherens junction, and allow subsequent analysis of endothelial specific functions. These techniques will be used to probe the function of adherens junctions in endothelium from various vascular beds and their contribution to inflammation. The proposed studies are anticipated to allow a better understanding of the role of endothelial adherens junctions in normal and disease conditions, and may lead to novel therapeutic approaches and targets for intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and 3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age.

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unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “colitis” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for colitis in the PubMed Central database: •

A major quantitative trait locus on chromosome 3 controls colitis severity in IL-10deficient mice. by Farmer MA, Sundberg JP, Bristol IJ, Churchill GA, Li R, Elson CO, Leiter EH.; 2001 Nov 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61125

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A Novel Urease-Negative Helicobacter Species Associated with Colitis and Typhlitis in IL-10-Deficient Mice. by Fox JG, Gorelick PL, Kullberg MC, Ge Z, Dewhirst FE, Ward JM.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96525

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Absence of All Components of the Flagellar Export and Synthesis Machinery Differentially Alters Virulence of Salmonella enterica Serovar Typhimurium in Models of Typhoid Fever, Survival in Macrophages, Tissue Culture Invasiveness, and Calf Enterocolitis. by Schmitt CK, Ikeda JS, Darnell SC, Watson PR, Bispham J, Wallis TS, Weinstein DL, Metcalf ES, O'Brien AD.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98677

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Application of 16S rRNA gene PCR to study bowel flora of preterm infants with and without necrotizing enterocolitis. by Millar MR, Linton CJ, Cade A, Glancy D, Hall M, Jalal H.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229306

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Chronic Diarrhea, Hemorrhagic Colitis, and Hemolytic-Uremic Syndrome Associated with HEp-2 Adherent Escherichia coli in Adults Infected with Human Immunodeficiency Virus in Bangui, Central African Republic. by Mossoro C, Glaziou P, Yassibanda S, Lan NT, Bekondi C, Minssart P, Bernier C, Le Bouguenec C, Germani Y.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120615

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Collagen-binding integrin [alpha]1[beta]1 regulates intestinal inflammation in experimental colitis. by Krieglstein CF, Cerwinka WH, Sprague AG, Laroux FS, Grisham MB, Koteliansky VE, Senninger N, Granger DN, de Fougerolles AR.; 2002 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151649

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Colonic Bacteria Express an Ulcerative Colitis pANCA-Related Protein Epitope. by Cohavy O, Bruckner D, Gordon LK, Misra R, Wei B, Eggena ME, Targan SR, Braun J.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97313

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Critical Role for Tumor Necrosis Factor Alpha in Controlling the Number of Lumenal Pathogenic Bacteria and Immunopathology in Infectious Colitis. by Goncalves NS, Ghaem-Maghami M, Monteleone G, Frankel G, Dougan G, Lewis DJ, Simmons CP, MacDonald TT.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100039

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The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

Studies

89

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Different Subsets of Enteric Bacteria Induce and Perpetuate Experimental Colitis in Rats and Mice. by Rath HC, Schultz M, Freitag R, Dieleman LA, Li F, Linde HJ, Scholmerich J, Sartor RB.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98156

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Differential Induction of Colitis and Gastritis in HLA-B27 Transgenic Rats Selectively Colonized with Bacteroides vulgatus or Escherichia coli. by Rath HC, Wilson KH, Sartor RB.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96608

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Duodenal Microflora in Very-Low-Birth-Weight Neonates and Relation to Necrotizing Enterocolitis. by Hoy CM, Wood CM, Hawkey PM, Puntis JW.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87634

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Enterocolitis induced by autoimmune targeting of enteric glial cells: A possible mechanism in Crohn's disease? by Cornet A, Savidge TC, Cabarrocas J, Deng WL, Colombel JF, Lassmann H, Desreumaux P, Liblau RS.; 2001 Nov 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60866

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Fecal lactoferrin, interleukin-1beta, and interleukin-8 are elevated in patients with severe Clostridium difficile colitis. by Steiner TS, Flores CA, Pizarro TT, Guerrant RL.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170647

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Genetic Analysis for Virulence Factors in Escherichia coli O104:H21 That Was Implicated in an Outbreak of Hemorrhagic Colitis. by Feng P, Weagant SD, Monday SR.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87673

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GT160-246, a Toxin Binding Polymer for Treatment of Clostridium difficile Colitis. by Kurtz CB, Cannon EP, Brezzani A, Pitruzzello M, Dinardo C, Rinard E, Acheson DW, Fitzpatrick R, Kelly P, Shackett K, Papoulis AT, Goddard PJ, Barker RH Jr, Palace GP, Klinger JD.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90651

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Helicobacter hepaticus Does Not Induce or Potentiate Colitis in Interleukin-10Deficient Mice. by Dieleman LA, Arends A, Tonkonogy SL, Goerres MS, Craft DW, Grenther W, Sellon RK, Balish E, Sartor RB.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101749

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Helicobacter hepaticus Triggers Colitis in Specific-Pathogen-Free Interleukin-10 (IL10)-Deficient Mice through an IL-12- and Gamma Interferon-Dependent Mechanism. by Kullberg MC, Ward JM, Gorelick PL, Caspar P, Hieny S, Cheever A, Jankovic D, Sher A.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108643

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Helicobacter hepaticus-Induced Colitis in Interleukin-10-Deficient Mice: Cytokine Requirements for the Induction and Maintenance of Intestinal Inflammation. by Kullberg MC, Rothfuchs AG, Jankovic D, Caspar P, Wynn TA, Gorelick PL, Cheever AW, Sher A.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98456

90

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Identification of Serpulina species associated with porcine colitis by biochemical analysis and PCR. by Fellstrom C, Pettersson B, Thomson J, Gunnarsson A, Persson M, Johansson KE.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229600

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Immune Responses in Ileostomy Fluid and Serum after Oral Cholera Vaccination of Patients Colectomized because of Ulcerative Colitis. by Kilhamn J, Brevinge H, Svennerholm AM, Jertborn M.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108473

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Increased Circulating Levels of Lipopolysaccharide Binding Protein in Children with Escherichia coli O157:H7 Hemorrhagic Colitis and Hemolytic Uremic Syndrome. by Proulx F, Seidman E.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95773

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Inflammation in the developing human intestine: A possible pathophysiologic contribution to necrotizing enterocolitis. by Nanthakumar NN, Fusunyan RD, Sanderson I, Walker WA.; 2000 May 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18555

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Intestinal Nematode Infection Ameliorates Experimental Colitis in Mice. by Khan WI, Blennerhasset PA, Varghese AK, Chowdhury SK, Omsted P, Deng Y, Collins SM.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130294

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Invasive amoebiasis in two patients with AIDS and cytomegalovirus colitis. by Fatkenheuer G, Arnold G, Steffen HM, Franzen C, Schrappe M, Diehl V, Salzberger B.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229929

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Isolation of Helicobacter cinaedi from the Colon, Liver, and Mesenteric Lymph Node of a Rhesus Monkey with Chronic Colitis and Hepatitis. by Fox JG, Handt L, Sheppard BJ, Xu S, Dewhirst FE, Motzel S, Klein H.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87974

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Laboratory Diagnosis of Clostridium difficile-Associated Diarrhea and Colitis: Usefulness of Premier Cytoclone A +B Enzyme Immunoassay for Combined Detection of Stool Toxins and Toxigenic C. difficile Strains. by Lozniewski A, Rabaud C, Dotto E, Weber M, Mory F.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88068

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Mice Lacking T and B Lymphocytes Develop Transient Colitis and Crypt Hyperplasia yet Suffer Impaired Bacterial Clearance during Citrobacter rodentium Infection. by Vallance BA, Deng W, Knodler LA, Finlay BB.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127821

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Neutral endopeptidase (EC 3.4.24.11 ) terminates colitis by degrading substance P. by Sturiale S, Barbara G, Qiu B, Figini M, Geppetti P, Gerard N, Gerard C, Grady EF, Bunnett NW, Collins SM.; 1999 Sep 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18089

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Novel Intestinal Helicobacter Species Isolated from Cotton-Top Tamarins (Saguinus oedipus) with Chronic Colitis. by Saunders KE, Shen Z, Dewhirst FE, Paster BJ, Dangler CA, Fox JG.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84191

Studies

91

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Outbreak of Necrotizing Enterocolitis Associated with Enterobacter sakazakii in Powdered Milk Formula. by van Acker J, de Smet F, Muyldermans G, Bougatef A, Naessens A, Lauwers S.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87717

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Persistent hepatitis and enterocolitis in germfree mice infected with Helicobacter hepaticus. by Fox JG, Yan L, Shames B, Campbell J, Murphy JC, Li X.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174280

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Pretreatment of Mice with Streptomycin Provides a Salmonella enterica Serovar Typhimurium Colitis Model That Allows Analysis of Both Pathogen and Host. by Barthel M, Hapfelmeier S, Quintanilla-Martinez L, Kremer M, Rohde M, Hogardt M, Pfeffer K, Russmann H, Hardt WD.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153285

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Proliferative Enterocolitis Associated with Dual Infection with Enteropathogenic Escherichia coli and Lawsonia intracellularis in Rabbits. by Schauer DB, McCathey SN, Daft BM, Jha SS, Tatterson LE, Taylor NS, Fox JG.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104903

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Proteinase-activated receptor 2 is an anti-inflammatory signal for colonic lamina propria lymphocytes in a mouse model of colitis. by Fiorucci S, Mencarelli A, Palazzetti B, Distrutti E, Vergnolle N, Hollenberg MD, Wallace JL, Morelli A, Cirino G.; 2001 Nov 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61145

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Pseudomembranous Colitis Caused by a Toxin A[minus sign] B + Strain of Clostridium difficile. by Limaye AP, Turgeon DK, Cookson BT, Fritsche TR.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86532

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Quality-of-Life Research on the Internet Feasibility and Potential Biases in Patients with Ulcerative Colitis. by Soetikno RM, Mrad R, Pao V, Lenert LA.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61260

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Resident Enteric Bacteria Are Necessary for Development of Spontaneous Colitis and Immune System Activation in Interleukin-10-Deficient Mice. by Sellon RK, Tonkonogy S, Schultz M, Dieleman LA, Grenther W, Balish E, Rennick DM, Sartor RB.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108652

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Responses of Human Intestinal Microvascular Endothelial Cells to Shiga Toxins 1 and 2 and Pathogenesis of Hemorrhagic Colitis. by Jacewicz MS, Acheson DW, Binion DG, West GA, Lincicome LL, Fiocchi C, Keusch GT.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96478

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Salmonella Excretion after Cessation of Tosufloxacin Therapy in Acute Nontyphoid Salmonella Enterocolitis. by Ohnishi K, Kimura K.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90566

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SCID/NCr Mice Naturally Infected with Helicobacter hepaticus Develop Progressive Hepatitis, Proliferative Typhlitis, and Colitis. by Li X, Fox JG, Whary MT, Yan L, Shames B, Zhao Z.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108686

92

Colitis

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Tapeworm Infection Reduces Epithelial Ion Transport Abnormalities in Murine Dextran Sulfate Sodium-Induced Colitis. by Reardon C, Sanchez A, Hogaboam CM, McKay DM.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98514

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The inflammatory infiltrate in the acute stage of the dextran sulphate sodium induced colitis: B cell response differs depending on the percentage of DSS used to induce it. by Stevceva L, Pavli P, Husband AJ, Doe WF.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=57007

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THE MANAGEMENT OF COLITIS. by [No authors listed]; 1935 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=234150

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The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut. by Kabashima K, Saji T, Murata T, Nagamachi M, Matsuoka T, Segi E, Tsuboi K, Sugimoto Y, Kobayashi T, Miyachi Y, Ichikawa A, Narumiya S.; 2002 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150928

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Toll-like receptor-dependent production of IL-12p40 causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice. by Kobayashi M, Kweon MN, Kuwata H, Schreiber RD, Kiyono H, Takeda K, Akira S.; 2003 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154445

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with colitis, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “colitis” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for colitis (hyperlinks lead to article summaries): •

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A case of Evans' syndrome in a patient with ulcerative colitis. Author(s): Ucci G, Ferrando P, Valentini D, Zavallone L. Source: Dig Liver Dis. 2003 June; 35(6): 439-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868682&dopt=Abstract

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

Studies

93

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A comparison of the clinical presentation and outcome of focal intestinal perforation and necrotizing enterocolitis in very-low-birth-weight neonates. Author(s): Okuyama H, Kubota A, Oue T, Kuroda S, Ikegami R, Kamiyama M. Source: Pediatric Surgery International. 2002 December; 18(8): 704-6. Epub 2002 December 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598969&dopt=Abstract

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A different therapeutic approach in patients with severe ulcerative colitis: hyperbaric oxygen treatment. Author(s): Gurbuz AK, Elbuken E, Yazgan Y, Yildiz S. Source: Southern Medical Journal. 2003 June; 96(6): 632-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12938799&dopt=Abstract

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A pilot trial of Saccharomyces boulardii in ulcerative colitis. Author(s): Guslandi M, Giollo P, Testoni PA. Source: European Journal of Gastroenterology & Hepatology. 2003 June; 15(6): 697-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840682&dopt=Abstract

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A specific genetic alteration on chromosome 6 in ulcerative colitis-associated colorectal cancers. Author(s): Ezaki T, Watanabe M, Inoue N, Kanai T, Ogata H, Iwao Y, Ishii H, Hibi T. Source: Cancer Research. 2003 July 1; 63(13): 3747-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839969&dopt=Abstract

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A study of the relationships between self-evaluation of physical condition and perception of difficulties of life in ulcerative colitis patients. Author(s): Tanaka M, Miyawaki I, Kazuma K. Source: Gastroenterology Nursing : the Official Journal of the Society of Gastroenterology Nurses and Associates. 2003 May-June; 26(3): 115-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811322&dopt=Abstract

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Abnormal mucosal extracellular matrix deposition is associated with increased TGFbeta receptor-expressing mesenchymal cells in a mouse model of colitis. Author(s): Whiting CV, Tarlton JF, Bailey M, Morgan CL, Bland PW. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 2003 September; 51(9): 1177-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923243&dopt=Abstract

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Abnormal p53 immunohistochemistry is associated with an increased colorectal cancer-related mortality in patients with ulcerative colitis. Author(s): Lashner BA, Bauer WM, Rybicki LA, Goldblum JR. Source: The American Journal of Gastroenterology. 2003 June; 98(6): 1423-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818291&dopt=Abstract

94

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Acute CMV-colitis in a patient with a history of ulcerative colitis. Author(s): Streetz KL, Buhr T, Wedemeyer H, Bleck J, Schedel I, Manns MP, Goke MN. Source: Scandinavian Journal of Gastroenterology. 2003 January; 38(1): 119-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608474&dopt=Abstract

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Acute pancreatitis after long-term therapy with mesalazine, and hyperamylasaemia associated with azathioprine in a patient with ulcerative colitis. Author(s): Toubanakis C, Batziou E, Sipsas N, Galanopoulos G, Tzivras M, Archimandritis A. Source: European Journal of Gastroenterology & Hepatology. 2003 August; 15(8): 933-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867808&dopt=Abstract

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Adenocarcinoma in the anal transitional zone after ileal pouch for ulcerative colitis: report of a case. Author(s): Bell SW, Parry B, Neill M. Source: Diseases of the Colon and Rectum. 2003 August; 46(8): 1134-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907913&dopt=Abstract

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Altered expression of epimorphin in ulcerative colitis. Author(s): Shirasaka T, Iizuka M, Yukawa M, Hirai Y, Horie Y, Itou H, Kon-No S, Fukushima T, Watanabe S. Source: Journal of Gastroenterology and Hepatology. 2003 May; 18(5): 570-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702050&dopt=Abstract

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Amebic colitis in an asymptomatic patient. Author(s): Weinrach DM, Wang KL. Source: Archives of Pathology & Laboratory Medicine. 2003 June; 127(6): 762. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741911&dopt=Abstract

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Apoptosis regulation differs between ulcerative colitis-associated and sporadic colonic tumors. Association with survivin and bcl-2. Author(s): Mikami T, Yoshida T, Akino F, Motoori T, Yajima M, Okayasu I. Source: American Journal of Clinical Pathology. 2003 May; 119(5): 723-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760292&dopt=Abstract

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Appendicectomy and ulcerative colitis. Author(s): ter Borg PC, van Buuren HR. Source: Gut. 2003 May; 52(5): 768; Author Reply 768-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692069&dopt=Abstract

Studies

95

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Association of common variable immunodeficiency with atypical collagenous colitis. Author(s): Byrne MF, Royston D, Patchett SE. Source: European Journal of Gastroenterology & Hepatology. 2003 September; 15(9): 1051-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923382&dopt=Abstract

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Atrophy and neoplastic transformation of the ileal pouch mucosa in patients with ulcerative colitis and primary sclerosing cholangitis: a case control study. Author(s): Stahlberg D, Veress B, Tribukait B, Broome U. Source: Diseases of the Colon and Rectum. 2003 June; 46(6): 770-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794579&dopt=Abstract

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Attenuated mild colonic inflammation and improved survival from severe DSScolitis of transgenic Cu/Zn-SOD mice. Author(s): Kruidenier L, van Meeteren ME, Kuiper I, Jaarsma D, Lamers CB, Zijlstra FJ, Verspaget HW. Source: Free Radical Biology & Medicine. 2003 March 15; 34(6): 753-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633752&dopt=Abstract

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Autoimmune enteropathy and colitis in an adult patient. Author(s): Carroccio A, Volta U, Di Prima L, Petrolini N, Florena AM, Averna MR, Montalto G, Notarbartolo A. Source: Digestive Diseases and Sciences. 2003 August; 48(8): 1600-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924654&dopt=Abstract

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Azathioprine versus sulfasalazine in maintenance of remission in severe ulcerative colitis. Author(s): Sood A, Midha V, Sood N, Avasthi G. Source: Indian J Gastroenterol. 2003 May-June; 22(3): 79-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839376&dopt=Abstract

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Bacterial hemorrhagic enterocolitis. Author(s): Ina K, Kusugami K, Ohta M. Source: Journal of Gastroenterology. 2003; 38(2): 111-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640523&dopt=Abstract

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Balsalazide is superior to mesalamine in the time to improvement of signs and symptoms of acute mild-to-moderate ulcerative colitis. Author(s): Pruitt R, Hanson J, Safdi M, Wruble L, Hardi R, Johanson J, Koval G, Riff D, Winston B, Cross A, Doty P, Johnson LK. Source: The American Journal of Gastroenterology. 2002 December; 97(12): 3078-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492193&dopt=Abstract

96

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Balsalazide: a review of its therapeutic use in mild-to-moderate ulcerative colitis. Author(s): Muijsers RB, Goa KL. Source: Drugs. 2002; 62(11): 1689-705. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109930&dopt=Abstract

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Basiliximab (anti-CD25) in combination with steroids may be an effective new treatment for steroid-resistant ulcerative colitis. Author(s): Creed TJ, Norman MR, Probert CS, Harvey RF, Shaw IS, Smithson J, Anderson J, Moorghen M, Gupta J, Shepherd NA, Dayan CM, Hearing SD. Source: Alimentary Pharmacology & Therapeutics. 2003 July 1; 18(1): 65-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848627&dopt=Abstract

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Behcet's ileocolitis: successful treatment with tumor necrosis factor-alpha antibody (infliximab) therapy: report of a case. Author(s): Kram MT, May LD, Goodman S, Molinas S. Source: Diseases of the Colon and Rectum. 2003 January; 46(1): 118-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544532&dopt=Abstract

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Bile composition in inflammatory bowel disease: ileal disease and colectomy, but not colitis, induce lithogenic bile. Author(s): Pereira SP, Bain IM, Kumar D, Dowling RH. Source: Alimentary Pharmacology & Therapeutics. 2003 April 1; 17(7): 923-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656695&dopt=Abstract

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Bloody diarrhea, fever, and pancytopenia in a patient with active ulcerative colitis. Author(s): Jani AL, Hamilos D. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 April; 90(4): 383-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722958&dopt=Abstract

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Bowel wall “thumbprinting” in pseudomembranous colitis. Author(s): Liberman M, Labos C, Wiseman J. Source: The Medical Journal of Australia. 2003 July 21; 179(2): 107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921104&dopt=Abstract

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Budesonide treatment for collagenous colitis: a randomized, double-blind, placebocontrolled, multicenter trial. Author(s): Miehlke S, Heymer P, Bethke B, Bastlein E, Meier E, Bartram HP, Wilhelms G, Lehn N, Dorta G, DeLarive J, Tromm A, Bayerdorffer E, Stolte M. Source: Gastroenterology. 2002 October; 123(4): 978-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12360457&dopt=Abstract

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Budesonide treatment of collagenous colitis: a randomised, double blind, placebo controlled trial with morphometric analysis. Author(s): Bonderup OK, Hansen JB, Birket-Smith L, Vestergaard V, Teglbjaerg PS, Fallingborg J. Source: Gut. 2003 February; 52(2): 248-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524408&dopt=Abstract

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Butyrate inhibits NF-kappaB activation in lamina propria macrophages of patients with ulcerative colitis. Author(s): Luhrs H, Gerke T, Muller JG, Melcher R, Schauber J, Boxberge F, Scheppach W, Menzel T. Source: Scandinavian Journal of Gastroenterology. 2002 April; 37(4): 458-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11989838&dopt=Abstract

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Cardiac sources of embolism should be routinely screened in ischemic colitis. Author(s): Hourmand-Ollivier I, Bouin M, Saloux E, Morello R, Rousselot P, Piquet MA, Dao T, Verwaerde JC. Source: The American Journal of Gastroenterology. 2003 July; 98(7): 1573-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873580&dopt=Abstract

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Case 11-2003: ulcerative colitis and primary sclerosing cholangitis in a 14-year-old boy. Author(s): Mukherjee S. Source: The New England Journal of Medicine. 2003 October 9; 349(15): 1482. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14535266&dopt=Abstract

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Case 11-2003: ulcerative colitis and primary sclerosing cholangitis in a 14-year-old boy. Author(s): Drewe E, Zaitoun AM, Walker DA. Source: The New England Journal of Medicine. 2003 October 9; 349(15): 1482. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14534348&dopt=Abstract

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Characterization and clinical behavior of Crohn's disease initially presenting predominantly as colitis. Author(s): Morpurgo E, Petras R, Kimberling J, Ziegler C, Galandiuk S. Source: Diseases of the Colon and Rectum. 2003 July; 46(7): 918-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847366&dopt=Abstract

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Chromoscopy might improve diagnostic accuracy in cancer surveillance for ulcerative colitis. Author(s): Matsumoto T, Nakamura S, Jo Y, Yao T, Iida M. Source: The American Journal of Gastroenterology. 2003 August; 98(8): 1827-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907339&dopt=Abstract

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Clinical features and pattern of indeterminate colitis: Crohn's disease with ulcerative colitis-like clinical presentation. Author(s): Matsui T, Yao T, Sakurai T, Yao K, Hirai F, Matake H, Tsuda S, Wada Y, Iwashita A, Kamachi S. Source: Journal of Gastroenterology. 2003; 38(7): 647-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898357&dopt=Abstract

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Clostridium difficile colitis causing toxic megacolon, severe sepsis and multiple organ dysfunction syndrome. Author(s): Dobson G, Hickey C, Trinder J. Source: Intensive Care Medicine. 2003 June; 29(6): 1030. Epub 2003 May 07. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734650&dopt=Abstract

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Clostridium difficile colitis following an open fracture: complications occur, even with straightforward trauma and straightforward decisions. Author(s): Harrahill M. Source: Journal of Emergency Nursing: Jen : Official Publication of the Emergency Department Nurses Association. 2003 June; 29(3): 294-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776090&dopt=Abstract

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Collagenous colitis associated with Clostridium difficile: a cause effect? Author(s): Erim T, Alazmi WM, O'Loughlin CJ, Barkin JS. Source: Digestive Diseases and Sciences. 2003 July; 48(7): 1374-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870798&dopt=Abstract

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Collagenous colitis: constipation or diarrhoea? Author(s): Barta Z, Toth L, Szabo GG, Szegedi G. Source: Gut. 2003 August; 52(8): 1230. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865295&dopt=Abstract

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Colonic perforation due to necrotizing amoebic colitis. Author(s): Hasan M, Islam MA, Siddiqua SS, Shuvra MR. Source: Mymensingh Med J. 2003 January; 12(1): 61-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715648&dopt=Abstract

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Colonic ulcers accompanying collagenous colitis: implication of nonsteroidal antiinflammatory drugs. Author(s): Kakar S, Pardi DS, Burgart LJ. Source: The American Journal of Gastroenterology. 2003 August; 98(8): 1834-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907340&dopt=Abstract

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Concomitant colitis associated with primary sclerosing cholangitis. Author(s): Uchida N, Ezaki T, Fukuma H, Tsutsui K, Kobara H, Matsuoka M, Masaki T, Watanabe S, Yoshida M, Maeta T, Koi F, Nakatsu T, Kuriyama S. Source: Journal of Gastroenterology. 2003; 38(5): 482-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768392&dopt=Abstract

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Correlation between circulating soluble ICAM-1 and prednisolone-induced amelioration of ulcerative colitis. Author(s): Vainer B, Nielsen OH. Source: Scandinavian Journal of Gastroenterology. 2003 March; 38(3): 283-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737443&dopt=Abstract

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Cost-effectiveness of colorectal cancer surveillance in ulcerative colitis. Author(s): Inadomi JM. Source: Scandinavian Journal of Gastroenterology. Supplement. 2003; (237): 17-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797675&dopt=Abstract

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Current controversies in the understanding of necrotizing enterocolitis. Part 1. Author(s): Noerr B. Source: Advances in Neonatal Care : Official Journal of the National Association of Neonatal Nurses. 2003 June; 3(3): 107-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891835&dopt=Abstract

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Cyclin D1 and p21 in ulcerative colitis-related inflammation and epithelial neoplasia: a study of aberrant expression and underlying mechanisms. Author(s): Wong NA, Mayer NJ, Anderson CE, McKenzie HC, Morris RG, Diebold J, Mayr D, Brock IW, Royds JA, Gilmour HM, Harrison DJ. Source: Human Pathology. 2003 June; 34(6): 580-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12827612&dopt=Abstract

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Cytology and image cytometry after colonic lavage: a complementary diagnostic tool in patients with ulcerative colitis. Author(s): Keller R, Brandt B, Terpe HJ, Winde G, Foerster EC, Domschke W. Source: Dig Liver Dis. 2003 January; 35(1): 24-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725604&dopt=Abstract

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Cytomegalovirus colitis and haemolytic anaemia in a glucose-6-phosphate dehydrogenase-deficient immunocompetent patient. Author(s): Farah R, Sbeit W, Nassar F, Cohen H, Reshef R. Source: European Journal of Gastroenterology & Hepatology. 2003 September; 15(9): 1029-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923377&dopt=Abstract

100 Colitis

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Cytomegalovirus colitis following immunosuppressive therapy for lupus peritonitis and lupus nephritis. Author(s): Ohashi N, Isozaki T, Shirakawa K, Ikegaya N, Yamamoto T, Hishida A. Source: Intern Med. 2003 April; 42(4): 362-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729328&dopt=Abstract

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Decompressive colonoscopy with intracolonic vancomycin administration for the treatment of severe pseudomembranous colitis. Author(s): Cirocco WC. Source: Surgical Endoscopy. 2003 June; 17(6): 1001. Epub 2003 March 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806525&dopt=Abstract

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Defining relapse of ulcerative colitis using a symptom-based activity index. Author(s): Jowett SL, Seal CJ, Phillips E, Gregory W, Barton JR, Welfare MR. Source: Scandinavian Journal of Gastroenterology. 2003 February; 38(2): 164-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678333&dopt=Abstract

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Delayed pressure urticaria in a patient with ulcerative colitis. Author(s): Hassiko H, Le Guilchard F, Nembo J, Lespessailles E, Martin L, Benhamou CL. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 October; 69(5): 519-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477241&dopt=Abstract

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Depletion and decreased function of antigen-presenting dendritic cells caused by lymphocytapheresis in ulcerative colitis. Author(s): Ikeda Y, Akbar SM, Matsui H, Murakami H, Onji M. Source: Diseases of the Colon and Rectum. 2003 April; 46(4): 521-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682548&dopt=Abstract

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Detection of measles virus in children with ileo-colonic lymphoid nodular hyperplasia, enterocolitis and developmental disorder. Author(s): Martin CM, Uhlmann V, Killalea A, Sheils O, O'Leary JJ. Source: Molecular Psychiatry. 2002; 7 Suppl 2: S47-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142949&dopt=Abstract

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Development of ulcerative colitis despite long-term immunosuppression with cyclosporin and azathioprine in an Australian Aborigine. Author(s): Teo M, Rodgers NG, Cummins AG. Source: Journal of Gastroenterology and Hepatology. 2002 October; 17(10): 1130-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12201879&dopt=Abstract

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Dexamethasone pulse steroids in ulcerative colitis--is it time for a change? Author(s): Patel SM, Falchuk K. Source: Inflammatory Bowel Diseases. 2003 May; 9(3): 213. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797351&dopt=Abstract

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Different distribution of mast cells and macrophages in colonic mucosa of patients with collagenous colitis and inflammatory bowel disease. Author(s): Nishida Y, Murase K, Isomoto H, Furusu H, Mizuta Y, Riddell RH, Kohno S. Source: Hepatogastroenterology. 2002 May-June; 49(45): 678-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12063968&dopt=Abstract

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Differential expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in ulcerative colitis and Crohn's disease. Author(s): Arihiro S, Ohtani H, Suzuki M, Murata M, Ejima C, Oki M, Kinouchi Y, Fukushima K, Sasaki I, Nakamura S, Matsumoto T, Torii A, Toda G, Nagura H. Source: Pathology International. 2002 May-June; 52(5-6): 367-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100519&dopt=Abstract

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Differentiation between ulcerative colitis and Crohn's disease by a quantitative immunohistochemical evaluation of T lymphocytes, neutrophils, histiocytes and mast cells. Author(s): Sasaki Y, Tanaka M, Kudo H. Source: Pathology International. 2002 April; 52(4): 277-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031083&dopt=Abstract

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Digitate dermatosis associated with ulcerative colitis? Author(s): Sawamura D, Umeki K. Source: Clinical and Experimental Dermatology. 2002 November; 27(8): 716-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472556&dopt=Abstract

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Distal ulcerative colitis refractory to rectal mesalamine: role of transdermal nicotine versus oral mesalamine. Author(s): Guslandi M, Frego R, Viale E, Testoni PA. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2002 May; 16(5): 293-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12045777&dopt=Abstract

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Distinct gene expression of osteopontin in patients with ulcerative colitis. Author(s): Masuda H, Takahashi Y, Asai S, Takayama T. Source: The Journal of Surgical Research. 2003 May 1; 111(1): 85-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842452&dopt=Abstract

102 Colitis

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Diverse p53 alterations in ulcerative colitis-associated low-grade dysplasia: fulllength gene sequencing in microdissected single crypts. Author(s): Yoshida T, Mikami T, Mitomi H, Okayasu I. Source: The Journal of Pathology. 2003 February; 199(2): 166-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12533829&dopt=Abstract

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Diversion colitis with a mucosal tear on endoscopic insufflation. Author(s): Komuro Y, Watanabe T, Hata K, Nagawa H. Source: Gut. 2003 September; 52(9): 1388-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912883&dopt=Abstract

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DNA fingerprinting abnormalities can distinguish ulcerative colitis patients with dysplasia and cancer from those who are dysplasia/cancer-free. Author(s): Chen R, Rabinovitch PS, Crispin DA, Emond MJ, Koprowicz KM, Bronner MP, Brentnall TA. Source: American Journal of Pathology. 2003 February; 162(2): 665-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547724&dopt=Abstract

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Does length really matter?. Oral and topical 5-aminosalicylic acid therapy for ulcerative colitis. Author(s): Lashner BA. Source: Dig Liver Dis. 2002 November; 34(11): 766-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546510&dopt=Abstract

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Does patient knowledge affect the colorectal cancer risk in ulcerative colitis? Author(s): Eaden JA, Abrams K, Mayberry JF. Source: Postgraduate Medical Journal. 2002 October; 78(924): 615-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415086&dopt=Abstract

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Donor human milk versus formula for preventing necrotising enterocolitis in preterm infants: systematic review. Author(s): McGuire W, Anthony MY. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2003 January; 88(1): F11-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496220&dopt=Abstract

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Double stapled ileal pouch anal anastomosis (DS-IPAA) for mucosal ulcerative colitis (MUC): is there a correlation between the tissue type in the circular stapler donuts and in follow-up biopsy? Author(s): Saigusa N, Choi HJ, Wexner SD, Woodhouse SL, Singh JJ, Weiss EG, Nogueras JJ, Belin B. Source: Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland. 2003 March; 5(2): 153-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780905&dopt=Abstract

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Early gallbladder carcinoma associated with primary sclerosing cholangitis and ulcerative colitis. Author(s): Yamamoto T, Uki K, Takeuchi K, Nagashima N, Honjo H, Sakurai N, Okuda C, Watanabe G, Mori M, Kuyama Y. Source: Journal of Gastroenterology. 2003; 38(7): 704-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898366&dopt=Abstract

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Effect of oral tacrolimus (FK 506) on steroid-refractory moderate/severe ulcerative colitis. Author(s): Hogenauer C, Wenzl HH, Hinterleitner TA, Petritsch W. Source: Alimentary Pharmacology & Therapeutics. 2003 August 15; 18(4): 415-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12940927&dopt=Abstract

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Effect of smoking and transdermal nicotine on colonic nicotinic acetylcholine receptors in ulcerative colitis. Author(s): Richardson CE, Morgan JM, Jasani B, Green JT, Rhodes J, Williams GT, Lindstrom J, Wonnacott S, Peel S, Thomas GA. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 January; 96(1): 5765. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509650&dopt=Abstract

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Effects of appendicectomy on the course of ulcerative colitis. Author(s): Cosnes J, Carbonnel F, Beaugerie L, Blain A, Reijasse D, Gendre JP. Source: Gut. 2002 December; 51(6): 803-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427780&dopt=Abstract

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Efficacy of cyclosporin with corticotropin for refractory ulcerative colitis. Author(s): Okamura S, Aoki H, Ohashi S, Urano F, Shimodaira M, Kanamori S, Ishikawa H, Segawa K. Source: Hepatogastroenterology. 2003 January-February; 50(49): 91-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629999&dopt=Abstract

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Efficacy of etanercept for treatment of Crohn's related spondyloarthritis but not colitis. Author(s): Marzo-Ortega H, McGonagle D, O'Connor P, Emery P. Source: Annals of the Rheumatic Diseases. 2003 January; 62(1): 74-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480676&dopt=Abstract

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Elevated serum values of procollagen III peptide (PIIIP) in patients with ulcerative colitis who will develop pseudopolyps. Author(s): Babic Z, Jagic V, Petrovic Z, Bilic A, Dinko K, Kubat G, Troskot R, Vukelic M. Source: World Journal of Gastroenterology : Wjg. 2003 March; 9(3): 619-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632532&dopt=Abstract

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Elimination of mucosectomy during restorative proctocolectomy in patients with ulcerative colitis may provide better results in low-volume centers. Author(s): Kayaalp C, Nessar G, Akoglu M, Atalay F. Source: American Journal of Surgery. 2003 March; 185(3): 268-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620569&dopt=Abstract

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Enterocolitis as initial presentation of acute myelogenous leukemia exacerbated by induction chemotherapy with idarubicin-cytosine arabinoside. Author(s): Wood RA. Source: Mayo Clinic Proceedings. 2002 October; 77(10): 1133. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374257&dopt=Abstract

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Eosinophilic colitis accompanied by Tolosa-Hunt syndrome: report of a case. Author(s): Kosugi S, Date K, Minagawa M, Ishikawa H, Hatakeyama K, Endo K, Kimura Y. Source: Journal of Gastroenterology. 2003; 38(6): 613-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858845&dopt=Abstract

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Eosinophilic colitis in a patient with acute myeloid leukemia after allogeneic bone marrow transplantation. Author(s): Ashida T, Shimada T, Kawanishi K, Miyatake J, Kanamaru A. Source: International Journal of Hematology. 2003 July; 78(1): 76-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894856&dopt=Abstract

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Epidemiology of neonatal necrotising enterocolitis: a population-based study. Author(s): Llanos AR, Moss ME, Pinzon MC, Dye T, Sinkin RA, Kendig JW. Source: Paediatric and Perinatal Epidemiology. 2002 October; 16(4): 342-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445151&dopt=Abstract

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Epidermal growth factor enemas with oral mesalamine for mild-to-moderate leftsided ulcerative colitis or proctitis. Author(s): Sinha A, Nightingale J, West KP, Berlanga-Acosta J, Playford RJ. Source: The New England Journal of Medicine. 2003 July 24; 349(4): 350-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878742&dopt=Abstract

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Epidermal growth factor for ulcerative colitis. Author(s): Farrell RJ. Source: The New England Journal of Medicine. 2003 July 24; 349(4): 395-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878748&dopt=Abstract

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Erosive enterocolitis in mycophenolate mofetil-treated renal-transplant recipients with persistent afebrile diarrhea. Author(s): Maes BD, Dalle I, Geboes K, Oellerich M, Armstrong VW, Evenepoel P, Geypens B, Kuypers D, Shipkova M, Geboes K, Vanrenterghem YF. Source: Transplantation. 2003 March 15; 75(5): 665-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640307&dopt=Abstract

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Evolving medical therapies for ulcerative colitis. Author(s): Cohen RD. Source: Current Gastroenterology Reports. 2002 December; 4(6): 497-505. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441040&dopt=Abstract

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Exacerbation of Crohn's colitis with severe colonic hemorrhage in a patient on rofecoxib. Author(s): Gornet JM, Hassani Z, Modiglian R, Lemann M. Source: The American Journal of Gastroenterology. 2002 December; 97(12): 3209-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492220&dopt=Abstract

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Exacerbation of ulcerative colitis by cytomegalovirus infection in an immunocompetent Indian patient. Author(s): Malhi NS, Bhasin DK, Gupta NM, Vaiphei K, Singh K. Source: Trop Gastroenterol. 2002 April-June; 23(2): 88-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632977&dopt=Abstract

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Expression of protease-activated receptor 2 in ulcerative colitis. Author(s): Kim JA, Choi SC, Yun KJ, Kim DK, Han MK, Seo GS, Yeom JJ, Kim TH, Nah YH, Lee YM. Source: Inflammatory Bowel Diseases. 2003 July; 9(4): 224-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902845&dopt=Abstract

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Extracorporeal monocyte granulocytapheresis was effective for a patient of erythema nodosum concomitant with ulcerative colitis. Author(s): Fukunaga K, Sawada K, Fukuda Y, Matoba Y, Natsuaki M, Ohnishi K, Fukui S, Satomi M, Shimoyama T. Source: Therap Apher Dial. 2003 February; 7(1): 122-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921128&dopt=Abstract

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Faecal calprotectin concentrations and diagnosis of necrotising enterocolitis. Author(s): Carroll D, Corfield A, Spicer R, Cairns P. Source: Lancet. 2003 January 25; 361(9354): 310-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559868&dopt=Abstract

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Familial occurrence of microscopic colitis: an opportunity to study the relationship between microscopic colitis and coeliac disease? Author(s): Kong SC, Keogh S, Carter MJ, Lobo AJ, Sanders DS. Source: Scandinavian Journal of Gastroenterology. 2002 November; 37(11): 1344-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465738&dopt=Abstract

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Fatal Bacillus cereus sepsis following resolving neutropenic enterocolitis during the treatment of acute leukemia. Author(s): Ginsburg AS, Salazar LG, True LD, Disis ML. Source: American Journal of Hematology. 2003 March; 72(3): 204-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605393&dopt=Abstract

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Fatal pseudomembranous colitis in a continent urinary neobladder. Author(s): Mathai MG, Shanthaveerapa HN, Byrd RP Jr, Roy TM. Source: J Ky Med Assoc. 2002 June; 100(6): 234-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12101580&dopt=Abstract

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Female reproductive health after ileal pouch anal anastomosis for ulcerative colitis. Author(s): Wax JR, Pinette MG, Cartin A, Blackstone J. Source: Obstetrical & Gynecological Survey. 2003 April; 58(4): 270-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665707&dopt=Abstract

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Finding mucosal tears in collagenous colitis during colonoscopic insufflation. Author(s): Yarze JC. Source: Gut. 2003 April; 52(4): 613-4; Author Reply 614. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631685&dopt=Abstract

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First reported case of colitis cystica profunda in association with Crohn's disease. Author(s): Madan A, Minocha A. Source: The American Journal of Gastroenterology. 2002 September; 97(9): 2472-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358281&dopt=Abstract

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First two patients with ulcerative colitis who developed classical thrombotic thrombocytopenic purpura successfully treated with medical therapy and plasma exchange. Author(s): Baron BW, Jeon HR, Glunz C, Peterson A, Cohen R, Hanauer S, Rubin D, Hart J, Baron JM. Source: Journal of Clinical Apheresis. 2002; 17(4): 204-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12494414&dopt=Abstract

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Fluorescence endoscopy for the detection of low and high grade dysplasia in ulcerative colitis using systemic or local 5-aminolaevulinic acid sensitisation. Author(s): Messmann H, Endlicher E, Freunek G, Rummele P, Scholmerich J, Knuchel R. Source: Gut. 2003 July; 52(7): 1003-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801958&dopt=Abstract

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Focally enhanced gastritis in children with Crohn's disease and ulcerative colitis. Author(s): Sharif F, McDermott M, Dillon M, Drumm B, Rowland M, Imrie C, Kelleher S, Harty S, Bourke B. Source: The American Journal of Gastroenterology. 2002 June; 97(6): 1415-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094859&dopt=Abstract

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Food protein-induced enterocolitis syndrome caused by solid food proteins. Author(s): Nowak-Wegrzyn A, Sampson HA, Wood RA, Sicherer SH. Source: Pediatrics. 2003 April; 111(4 Pt 1): 829-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671120&dopt=Abstract

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Fracture risk in patients with celiac Disease, Crohn's disease, and ulcerative colitis: a nationwide follow-up study of 16,416 patients in Denmark. Author(s): Vestergaard P, Mosekilde L. Source: American Journal of Epidemiology. 2002 July 1; 156(1): 1-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076883&dopt=Abstract

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Frequency of and risk factors for necrotizing enterocolitis in infants born before 33 weeks of gestation. Author(s): Hallstrom M, Koivisto AM, Janas M, Tammela O. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003; 92(1): 111-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650310&dopt=Abstract

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From uninformed patient to CWOCN: My life with ulcerative colitis and the ileoanal reservoir. Author(s): Follett SB. Source: Journal of Wound, Ostomy, and Continence Nursing : Official Publication of the Wound, Ostomy and Continence Nurses Society / Wocn. 2003 January; 30(1): 4-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529587&dopt=Abstract

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Fulminant amoebic colitis with perforation successfully treated by staged surgery: a case report. Author(s): Ishida H, Inokuma S, Murata N, Hashimoto D, Satoh K, Ohta S. Source: Journal of Gastroenterology. 2003; 38(1): 92-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560929&dopt=Abstract

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Fulminant Clostridium difficile colitis without diarrhea: lack of emphasis in diagnostic guidelines. Author(s): Zahariadis G, Connon JJ, Fong IW. Source: The American Journal of Gastroenterology. 2002 November; 97(11): 2929-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425579&dopt=Abstract

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Fulminant ischaemic colitis with atypical clinical features complicating sickle cell disease. Author(s): Karim A, Ahmed S, Rossoff LJ, Siddiqui R, Fuchs A, Multz AS. Source: Postgraduate Medical Journal. 2002 June; 78(920): 370-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151697&dopt=Abstract

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Functional outcome and patient satisfaction after ileal pouch anal anastomosis for ulcerative colitis in a developing country. Author(s): Rao YG, Saxena R, Sahni P, Pande GK, Chattopadhyay TK. Source: Trop Gastroenterol. 2002 April-June; 23(2): 66-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632971&dopt=Abstract

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Further report of familial occurrence of collagenous colitis. Author(s): Thomson A, Kaye G. Source: Scandinavian Journal of Gastroenterology. 2002 September; 37(9): 1116. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374242&dopt=Abstract

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Fusobacterium varium localized in the colonic mucosa of patients with ulcerative colitis stimulates species-specific antibody. Author(s): Ohkusa T, Sato N, Ogihara T, Morita K, Ogawa M, Okayasu I. Source: Journal of Gastroenterology and Hepatology. 2002 August; 17(8): 849-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164960&dopt=Abstract

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Gasless laparoscopic surgery for ulcerative colitis and familial adenomatous polyposis:initial experience of 7 cases. Author(s): Ishida H, Hashimoto D, Inokuma S, Nakada H, Ohsawa T, Hoshino T. Source: Surgical Endoscopy. 2003 June; 17(6): 899-902. Epub 2003 March 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618933&dopt=Abstract

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Gastrointestinal disorders and the critically ill. Clostridium difficile infection and pseudomembranous colitis. Author(s): Wilcox MH. Source: Best Practice & Research. Clinical Gastroenterology. 2003 June; 17(3): 475-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763508&dopt=Abstract

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Gastrointestinal stromal tumor (GIST) and ulcerative colitis. Author(s): Grieco A, Cavallaro A, Potenza AE, Mule A, Tarquini E, Miele L, Gasbarrini G. Source: J Exp Clin Cancer Res. 2002 December; 21(4): 617-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636111&dopt=Abstract

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Genetic variants of the interleukin-18 promoter region (-607) influence the course of necrotising enterocolitis in very low birth weight neonates. Author(s): Heninger E, Treszl A, Kocsis I, Derfalvi B, Tulassay T, Vasarhelyi B. Source: European Journal of Pediatrics. 2002 July; 161(7): 410-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174825&dopt=Abstract

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GI distension in severe ulcerative colitis. Author(s): Latella G, Vernia P, Viscido A, Frieri G, Cadau G, Cocco A, Cossu A, Tomei E, Caprilli R. Source: The American Journal of Gastroenterology. 2002 May; 97(5): 1169-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014723&dopt=Abstract

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Giant inflammatory polyposis of the descending colon associated with a Crohn's disease-like colitis. Author(s): Kosugi I, Tada T, Tsutsui Y, Sato Y, Mitsui T, Itazu I. Source: Pathology International. 2002 April; 52(4): 318-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031089&dopt=Abstract

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Glucagon-like peptide-2 and common therapeutics in a murine model of ulcerative colitis. Author(s): L'Heureux MC, Brubaker PL. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 July; 306(1): 347-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12815012&dopt=Abstract

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Glutamine distribution in patients with ulcerative colitis and in patients with familial adenomatous polyposis coli before and after restorative proctocolectomy. Author(s): Heuschen UA, Allemeyer EH, Hinz U, Langer K, Heuschen G, DeckerBaumann C, Herfarth C, Stern J. Source: International Journal of Colorectal Disease. 2002 July; 17(4): 245-52. Epub 2001 December 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12073073&dopt=Abstract

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Graft-versus-host disease-type colitis: an unusual association of malignant thymoma. Author(s): Sader C, Sharma S, Edwards MG. Source: The Annals of Thoracic Surgery. 2002 June; 73(6): 1947-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12078795&dopt=Abstract

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Graft-versus-host-like colitis and malignant thymoma. Author(s): Lowry PW, Myers JD, Geller A, Bostwick DG, Clain JE. Source: Digestive Diseases and Sciences. 2002 September; 47(9): 1998-2001. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353844&dopt=Abstract

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Granulocyte adsorptive apheresis for pediatric patients with ulcerative colitis. Author(s): Tomomasa T, Kobayashi A, Kaneko H, Mika S, Maisawa S, Chino Y, Syou H, Yoden A, Fujino J, Tanikawa M, Yamashita T, Kimura S, Kanoh M, Sawada K, Morikawa A. Source: Digestive Diseases and Sciences. 2003 April; 48(4): 750-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741466&dopt=Abstract

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Granulocyte and monocyte adsorption apheresis in a patient with antiglomerular basement membrane glomerulonephritis and active ulcerative colitis. Author(s): Nakamura T, Suzuki Y, Koide H. Source: The American Journal of the Medical Sciences. 2003 May; 325(5): 296-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792251&dopt=Abstract

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Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis. Author(s): Mahadeva U, Martin JP, Patel NK, Price AB. Source: Histopathology. 2002 July; 41(1): 50-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12121237&dopt=Abstract

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Guided self-management and patient-directed follow-up of ulcerative colitis: a randomised trial. Author(s): Kurbegow AC, Ferry GD. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 April; 34(4): 428-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981954&dopt=Abstract

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Gut hormones in preterm infants with necrotizing enterocolitis during starvation and reintroduction of enteral nutrition. Author(s): Sharman-Koendjbiharie M, Hopman WP, Piena-Spoel M, Albers MJ, Jansen JB, Tibboel D. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 November; 35(5): 6749. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454585&dopt=Abstract

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Health related quality of life in Crohn's proctocolitis does not differ from a general population when in remission. Author(s): Andersson P, Olaison G, Bendtsen P, Myrelid P, Sjodahl R. Source: Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland. 2003 January; 5(1): 56-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780929&dopt=Abstract

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Hemorrhagic colitis caused by amyloid. Author(s): Kram MT, Olsen DA, May LD, Goodman S. Source: Gastrointestinal Endoscopy. 2002 October; 56(4): 564-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297776&dopt=Abstract

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Hepatitis C, collagenous colitis, and dermatomyositis occurring in the same patient. Author(s): Germany RE, Cohen SM. Source: The American Journal of Gastroenterology. 2002 July; 97(7): 1848-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135055&dopt=Abstract

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Hepatocyte growth factor facilitates colonic mucosal repair in experimental ulcerative colitis in rats. Author(s): Tahara Y, Ido A, Yamamoto S, Miyata Y, Uto H, Hori T, Hayashi K, Tsubouchi H. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 October; 307(1): 146-51. Epub 2003 September 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954797&dopt=Abstract

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Herpes simplex virus colitis in a neonate. Author(s): Daley AJ, Craven P, Holland AJ, Jones CA, Badawi N, Isaacs D. Source: The Pediatric Infectious Disease Journal. 2002 September; 21(9): 887-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12380594&dopt=Abstract

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High normal serum levels of C3 and C1 inhibitor, two acute-phase proteins belonging to the complement system, occur more frequently in patients with Crohn's disease than ulcerative colitis. Author(s): Bene L, Fust G, Fekete B, Kovacs A, Horvath L, Prohaszka Z, Miklos K, Palos G, Daha M, Farkas H, Varga L. Source: Digestive Diseases and Sciences. 2003 June; 48(6): 1186-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822883&dopt=Abstract

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High resolution analysis of chromosome 18 alterations in ulcerative colitis-related colorectal cancer. Author(s): Terdiman JP, Aust DE, Chang CG, Willenbucher RF, Baretton GB, Waldman FM. Source: Cancer Genetics and Cytogenetics. 2002 July 15; 136(2): 129-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12237237&dopt=Abstract

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Histamine content and histamine secretion of the colonic mucosa in patients with collagenous colitis. Author(s): Schwab D, Hahn EG, Raithel M. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 2002 April; 51 Suppl 1: S33-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12013399&dopt=Abstract

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Histological and immunological features of appendix in patients with ulcerative colitis. Author(s): Jo Y, Matsumoto T, Yada S, Nakamura S, Yao T, Hotokezaka M, Mibu R, Iida M. Source: Digestive Diseases and Sciences. 2003 January; 48(1): 99-108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645797&dopt=Abstract

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Histopathological features of the terminal ileum in lymphocytic and collagenous colitis: a study of 32 cases and review of literature. Author(s): Padmanabhan V, Callas PW, Li SC, Trainer TD. Source: Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 2003 February; 16(2): 115-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591963&dopt=Abstract

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Histopathology of ulcerative colitis in initial rectal biopsy in children. Author(s): Washington K, Greenson JK, Montgomery E, Shyr Y, Crissinger KD, Polk DB, Barnard J, Lauwers GY. Source: The American Journal of Surgical Pathology. 2002 November; 26(11): 1441-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409720&dopt=Abstract

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HLA-DRB1*1502 confers susceptibility to ulcerative colitis, but is negatively associated with its intractability: a Korean study. Author(s): Myung SJ, Yang SK, Jung HY, Chang HS, Park B, Hong WS, Kim JH, Min I. Source: International Journal of Colorectal Disease. 2002 July; 17(4): 233-7. Epub 2001 December 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12073071&dopt=Abstract

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Hodgkin s disease with nephrotic syndrome as a complication of ulcerative colitis: case report. Author(s): Basic-Jukic N, Radman I, Roncevic T, Jakic-Razumovic J. Source: Croatian Medical Journal. 2002 October; 43(5): 573-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12402399&dopt=Abstract

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How could pathologists improve the initial diagnosis of colitis? Evidence from an international workshop. Author(s): Bentley E, Jenkins D, Campbell F, Warren B. Source: Journal of Clinical Pathology. 2002 December; 55(12): 955-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12461067&dopt=Abstract

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Hypertrophic osteoarthropathy in untreated ulcerative colitis. Author(s): Crone J, Huber WD, Resch R, Ponhold W, Granditsch G. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 August; 35(2): 213-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12187300&dopt=Abstract

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IBD5 is a general risk factor for inflammatory bowel disease: replication of association with Crohn disease and identification of a novel association with ulcerative colitis. Author(s): Giallourakis C, Stoll M, Miller K, Hampe J, Lander ES, Daly MJ, Schreiber S, Rioux JD. Source: American Journal of Human Genetics. 2003 July; 73(1): 205-11. Epub 2003 May 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776251&dopt=Abstract

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Image of the month. Cytomegalovirus (CMV) colitis. Author(s): Napierkowski JJ, Sachar DS, Cumings M, Kaplan K, Wong RK. Source: Gastroenterology. 2003 July; 125(1): 8, 281. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851865&dopt=Abstract

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Images in clinical medicine. Chronic ulcerative colitis with megacolon. Author(s): Kaiser AM, Beart RW. Source: The New England Journal of Medicine. 2003 July 24; 349(4): 358. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878743&dopt=Abstract

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Impaired expression of peroxisome proliferator-activated receptor gamma in ulcerative colitis. Author(s): Dubuquoy L, Jansson EA, Deeb S, Rakotobe S, Karoui M, Colombel JF, Auwerx J, Pettersson S, Desreumaux P. Source: Gastroenterology. 2003 May; 124(5): 1265-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730867&dopt=Abstract

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In search of a better treatment for ulcerative colitis. Author(s): Sharma MP, Makharia G. Source: Indian J Gastroenterol. 2003 May-June; 22(3): 77-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839375&dopt=Abstract

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Incomplete remission with short-term prednisolone treatment in collagenous colitis: a randomized study. Author(s): Munck LK, Kjeldsen J, Philipsen E, Fischer Hansen B. Source: Scandinavian Journal of Gastroenterology. 2003 June; 38(6): 606-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825868&dopt=Abstract

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Increasing fecal butyrate in ulcerative colitis patients by diet: controlled pilot study. Author(s): Hallert C, Bjorck I, Nyman M, Pousette A, Granno C, Svensson H. Source: Inflammatory Bowel Diseases. 2003 March; 9(2): 116-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769445&dopt=Abstract

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Inducible and constitutive beta-defensins are differentially expressed in Crohn's disease and ulcerative colitis. Author(s): Wehkamp J, Harder J, Weichenthal M, Mueller O, Herrlinger KR, Fellermann K, Schroeder JM, Stange EF. Source: Inflammatory Bowel Diseases. 2003 July; 9(4): 215-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902844&dopt=Abstract

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Infliximab for refractory ulcerative colitis or indeterminate colitis: an open-label multicentre study. Author(s): Gornet JM, Couve S, Hassani Z, Delchier JC, Marteau P, Cosnes J, Bouhnik Y, Dupas JL, Modigliani R, Taillard F, Lemann M. Source: Alimentary Pharmacology & Therapeutics. 2003 July 15; 18(2): 175-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869077&dopt=Abstract

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Infliximab for ulcerative colitis. Author(s): Actis GC. Source: The American Journal of Gastroenterology. 2003 March; 98(3): 709. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650824&dopt=Abstract

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Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial. Author(s): Probert CS, Hearing SD, Schreiber S, Kuhbacher T, Ghosh S, Arnott ID, Forbes A. Source: Gut. 2003 July; 52(7): 998-1002. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801957&dopt=Abstract

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Infliximab in refractory pouchitis complicated by fistulae following ileo-anal pouch for ulcerative colitis. Author(s): Viscido A, Habib FI, Kohn A, Papi C, Marcheggiano A, Pimpo MT, Vernia P, Cadau G, Caprilli R. Source: Alimentary Pharmacology & Therapeutics. 2003 May 15; 17(10): 1263-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755839&dopt=Abstract

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Infliximab in ulcerative colitis: is there a placebo (effect) in the house? Author(s): Cohen RD. Source: Gastroenterology. 2003 June; 124(7): 1990-1; Discussion 1991. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806639&dopt=Abstract

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Infliximab salvage therapy after cyclosporine in an acute flare of chronic ulcerative colitis. Author(s): Lam EC, Bailey RJ. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 March; 17(3): 198-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12677271&dopt=Abstract

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Interferon beta-1a in ulcerative colitis: a placebo controlled, randomised, dose escalating study. Author(s): Nikolaus S, Rutgeerts P, Fedorak R, Steinhart AH, Wild GE, Theuer D, Mohrle J, Schreiber S. Source: Gut. 2003 September; 52(9): 1286-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912859&dopt=Abstract

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Interventions for treating collagenous colitis. Author(s): Chande N, McDonald JW, MacDonald JK. Source: Cochrane Database Syst Rev. 2003; (3): Cd003575. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917974&dopt=Abstract

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Intestinal bacteria and ulcerative colitis. Author(s): Cummings JH, Macfarlane GT, Macfarlane S. Source: Curr Issues Intest Microbiol. 2003 March; 4(1): 9-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691258&dopt=Abstract

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Is colonoscopy alone sufficient to screen for ulcerative colitis-associated colorectal carcinoma? Author(s): Bruewer M, Krieglstein CF, Utech M, Bode M, Rijcken E, Anthoni C, Laukoetter MG, Schuermann G, Senninger N. Source: World Journal of Surgery. 2003 May; 27(5): 611-5. Epub 2003 April 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715233&dopt=Abstract

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Ischemic colitis in a young adult during sickle cell crisis: case report and review. Author(s): Green BT, Branch MS. Source: Gastrointestinal Endoscopy. 2003 April; 57(4): 605-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665783&dopt=Abstract

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Isolation of peptides useful for differential diagnosis of Crohn's disease and ulcerative colitis. Author(s): Saito H, Fukuda Y, Katsuragi K, Tanaka M, Satomi M, Shimoyama T, Saito T, Tachikawa T. Source: Gut. 2003 April; 52(4): 535-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631665&dopt=Abstract

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Lansoprazole-associated microscopic colitis: a case series. Author(s): Thomson RD, Lestina LS, Bensen SP, Toor A, Maheshwari Y, Ratcliffe NR. Source: The American Journal of Gastroenterology. 2002 November; 97(11): 2908-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425567&dopt=Abstract

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Laparoscopic restorative proctocolectomy for patients with ulcerative colitis. Author(s): Hasegawa H, Watanabe M, Baba H, Nishibori H, Kitajima M. Source: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A. 2002 December; 12(6): 403-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590719&dopt=Abstract

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Laparotomy in very small premature infants with necrotizing enterocolitis or focal intestinal perforation: postoperative outcome. Author(s): Camberos A, Patel K, Applebaum H. Source: Journal of Pediatric Surgery. 2002 December; 37(12): 1692-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12483632&dopt=Abstract

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Large-bowel obstruction secondary to localized rectal giant pseudopolyposis complicating ulcerative colitis: first reported case. Author(s): Hurlstone DP. Source: Endoscopy. 2002 December; 34(12): 1025. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12471554&dopt=Abstract

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Leucocytoclastic vasculitis as onset symptom of ulcerative colitis. Author(s): Iannone F, Scioscia C, Musio A, Piscitelli D, Lapadula G. Source: Annals of the Rheumatic Diseases. 2003 August; 62(8): 785-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860742&dopt=Abstract

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Liaison between rheumatoid arthritis and ulcerative colitis. Author(s): Aydin Y, Ozcakar L, Yildiz M, Akinci A. Source: Rheumatology International. 2003 January; 23(1): 47-8. Epub 2002 December 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548442&dopt=Abstract

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Linear IgA bullous dermatosis: an association with ulcerative colitis versus renal cell carcinoma. Author(s): Keller AS, Bouldin MB, Drage LA, Hauser SC, Davis MD. Source: Digestive Diseases and Sciences. 2003 April; 48(4): 783-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741472&dopt=Abstract

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Liver abscess and diarrhea as initial manifestations of ulcerative colitis: case report and review of the literature. Author(s): Song J, Swekla M, Colorado P, Reddy R, Hoffmann S, Fine S. Source: Digestive Diseases and Sciences. 2003 February; 48(2): 417-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643625&dopt=Abstract

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Local delivery of adenoviral vectors encoding murine interleukin 10 induces colonic interleukin 10 production and is therapeutic for murine colitis. Author(s): Lindsay JO, Ciesielski CJ, Scheinin T, Brennan FM, Hodgson HJ. Source: Gut. 2003 July; 52(7): 981-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801955&dopt=Abstract

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Local delivery of adenoviral vectors encoding murine interleukin 10 induces colonic interleukin 10 production and is therapeutic for murine colitis. Author(s): Lindsay JO, Ciesielski CJ, Scheinin T, Brennan FM, Hodgson HJ. Source: Gut. 2003 March; 52(3): 363-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584217&dopt=Abstract

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Long-term aminosalicylate therapy is under-used in patients with ulcerative colitis: a cross-sectional survey. Author(s): Rubin G, Hungin AP, Chinn D, Dwarakanath AD, Green L, Bates J. Source: Alimentary Pharmacology & Therapeutics. 2002 November; 16(11): 1889-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390097&dopt=Abstract

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Long-term failure after restorative proctocolectomy for ulcerative colitis. Author(s): Tulchinsky H, Hawley PR, Nicholls J. Source: Annals of Surgery. 2003 August; 238(2): 229-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894016&dopt=Abstract

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Long-term follow-up of patients with necrotizing enterocolitis. Author(s): Stanford A, Upperman JS, Boyle P, Schall L, Ojimba JI, Ford HR. Source: Journal of Pediatric Surgery. 2002 July; 37(7): 1048-1050; Discussion 1048-1050. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12077769&dopt=Abstract

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Long-term functional results after ileal pouch anal restorative proctocolectomy for ulcerative colitis: a prospective observational study. Author(s): Michelassi F, Lee J, Rubin M, Fichera A, Kasza K, Karrison T, Hurst RD. Source: Annals of Surgery. 2003 September; 238(3): 433-41; Discussion 442-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501509&dopt=Abstract

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Long-term results of low-dose intravenous ciclosporin for acute severe ulcerative colitis. Author(s): Rayner CK, McCormack G, Emmanuel AV, Kamm MA. Source: Alimentary Pharmacology & Therapeutics. 2003 August 1; 18(3): 303-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12895214&dopt=Abstract

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Low plasma protein Z levels in patients with ischemic colitis. Author(s): Koutroubakis IE, Theodoropoulou A, Sfiridaki A, Kouroumalis EA. Source: Digestive Diseases and Sciences. 2003 September; 48(9): 1673-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14560981&dopt=Abstract

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Lower gastrointestinal bleeding and ischemic colitis. Author(s): Newman JR, Cooper MA. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2002 September; 16(9): 597-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362211&dopt=Abstract

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Luminal nitric oxide and epithelial expression of inducible and endothelial nitric oxide synthase in collagenous and lymphocytic colitis. Author(s): Olesen M, Middelveld R, Bohr J, Tysk C, Lundberg JO, Eriksson S, Alving K, Jarnerot G. Source: Scandinavian Journal of Gastroenterology. 2003 January; 38(1): 66-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608467&dopt=Abstract

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Lymphocytic and collagenous colitis: the emerging entity of microscopic colitis. An update on pathophysiology, diagnosis and management. Author(s): Abdo AA, Urbanski SJ, Beck PL. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 July; 17(7): 425-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915915&dopt=Abstract

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Lymphocytic colitis: clinical features, treatment, and outcomes. Author(s): Pardi DS, Ramnath VR, Loftus EV Jr, Tremaine WJ, Sandborn WJ. Source: The American Journal of Gastroenterology. 2002 November; 97(11): 2829-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425555&dopt=Abstract

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Management of acute severe colitis. Author(s): Dunckley P, Jewell D. Source: Best Practice & Research. Clinical Gastroenterology. 2003 February; 17(1): 89103. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617885&dopt=Abstract

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Management of ovarian cysts in women undergoing restorative proctocolectomy for ulcerative colitis. Author(s): Thakur A, Yang I, Lin A, Buchmiller-Crair T, Fonkalsrud EW. Source: The American Surgeon. 2003 April; 69(4): 339-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716094&dopt=Abstract

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Mannan-binding lectin in children with Escherichia coli O157:H7 haemmorrhagic colitis and haemolytic uraemic syndrome. Author(s): Proulx F, Wagner E, Toledano B, Decaluwe H, Seidman EG, Rivard GE. Source: Clinical and Experimental Immunology. 2003 September; 133(3): 360-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930361&dopt=Abstract

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Mast cells and inflammatory mediators in chronic ulcerative colitis. Author(s): Stoyanova II, Gulubova MV. Source: Acta Histochemica. 2002; 104(2): 185-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086339&dopt=Abstract

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Mechanism of diarrhea in collagenous colitis. Author(s): Rubio CA, Befrits R, Jaramillo E, Fisher H, Lindblom A. Source: Gastroenterology. 2003 June; 124(7): 2000. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12812193&dopt=Abstract

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Mediastinal widening in a patient of ulcerative colitis. Author(s): Mohapatra PR, Das SK, Deb A, Saini V. Source: Indian J Chest Dis Allied Sci. 2003 April-June; 45(2): 131-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715937&dopt=Abstract

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Medication nonadherence and the outcomes of patients with quiescent ulcerative colitis. Author(s): Kane S, Huo D, Aikens J, Hanauer S. Source: The American Journal of Medicine. 2003 January; 114(1): 39-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543288&dopt=Abstract

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Melatonin for ulcerative colitis? Author(s): Mann S. Source: The American Journal of Gastroenterology. 2003 January; 98(1): 232-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526981&dopt=Abstract

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Mesalazine-associated benign intracranial hypertension in a patient with ulcerative colitis. Author(s): Rosa N, Giamundo A, Jura A, Iaccarino G, Romano A. Source: American Journal of Ophthalmology. 2003 July; 136(1): 212-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834704&dopt=Abstract

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Mesenteric phlebosclerosis: a new disease entity causing ischemic colitis. Author(s): Iwashita A, Yao T, Schlemper RJ, Kuwano Y, Yao T, Iida M, Matsumoto T, Kikuchi M. Source: Diseases of the Colon and Rectum. 2003 February; 46(2): 209-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576895&dopt=Abstract

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Methotrexate in ulcerative colitis. Author(s): Siveke JT, Folwaczny C. Source: Alimentary Pharmacology & Therapeutics. 2003 February; 17(3): 479-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562464&dopt=Abstract

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Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis. Author(s): Kiesslich R, Fritsch J, Holtmann M, Koehler HH, Stolte M, Kanzler S, Nafe B, Jung M, Galle PR, Neurath MF. Source: Gastroenterology. 2003 April; 124(4): 880-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671882&dopt=Abstract

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Microscopic colitis. Author(s): Pardi DS. Source: Mayo Clinic Proceedings. 2003 May; 78(5): 614-6; Quiz 616-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744549&dopt=Abstract

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Microscopic colitis: a clinical and pathological review. Author(s): Fraser AG, Warren BF, Chandrapala R, Jewell DP. Source: Scandinavian Journal of Gastroenterology. 2002 November; 37(11): 1241-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465719&dopt=Abstract

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MMR and autistic enterocolitis: consistent epidemiological failure to find an association. Author(s): Fombonne E, Cook EH. Source: Molecular Psychiatry. 2003 February; 8(2): 133-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610643&dopt=Abstract

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Motion - colonoscopic surveillance is more cost effective than colectomy in patients with ulcerative colitis: arguments against the motion. Author(s): Ekbom A. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 February; 17(2): 122-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605251&dopt=Abstract

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Motion - colonoscopic surveillance is more cost effective than colectomy in patients with ulcerative colitis: Arguments for the motion. Author(s): Lashner BA. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 February; 17(2): 119-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605250&dopt=Abstract

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MUC-2 mucin production in Hirschsprung's disease: possible association with enterocolitis development. Author(s): Mattar AF, Coran AG, Teitelbaum DH. Source: Journal of Pediatric Surgery. 2003 March; 38(3): 417-21; Discussion 417-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632359&dopt=Abstract

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Mucosal secretion and expression of basic fibroblast growth factor in patients with collagenous colitis. Author(s): Taha Y, Raab Y, Larsson A, Carlson M, Loof L, Gerdin B, Thorn M. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 2011-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499780&dopt=Abstract

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Multicenter randomized controlled trial for the treatment of ulcerative colitis with a leukocytapheresis column. Author(s): Sawada K, Muto T, Shimoyama T, Satomi M, Sawada T, Nagawa H, Hiwatashi N, Asakura H, Hibi T. Source: Current Pharmaceutical Design. 2003; 9(4): 307-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570823&dopt=Abstract

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Na+/H+ exchanger blockade inhibits enterocyte inflammatory response and protects against colitis. Author(s): Nemeth ZH, Deitch EA, Szabo C, Mabley JG, Pacher P, Fekete Z, Hauser CJ, Hasko G. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2002 July; 283(1): G122-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065299&dopt=Abstract

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N-acetyltransferase 1 and 2 genotypes do not predict response or toxicity to treatment with mesalamine and sulfasalazine in patients with ulcerative colitis. Author(s): Ricart E, Taylor WR, Loftus EV, O'Kane D, Weinshilboum RM, Tremaine WJ, Harmsen WS, Zinsmeister AR, Sandborn WJ. Source: The American Journal of Gastroenterology. 2002 July; 97(7): 1763-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135032&dopt=Abstract

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Necrotizing amebic colitis in a child. Author(s): Roy Choudhury S, Sen AK. Source: Pediatric Surgery International. 2002 September; 18(5-6): 498-500. Epub 2002 May 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415391&dopt=Abstract

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Necrotizing enterocolitis complicated with perforation in extremely low birth-weight premature infants. Author(s): Wu CH, Tsao PN, Chou HC, Tang JR, Chan WK, Tsou KI. Source: Acta Paediatr Taiwan. 2002 May-June; 43(3): 127-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12148961&dopt=Abstract

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Necrotizing enterocolitis in full-term infants. Author(s): Ostlie DJ, Spilde TL, St Peter SD, Sexton N, Miller KA, Sharp RJ, Gittes GK, Snyder CL. Source: Journal of Pediatric Surgery. 2003 July; 38(7): 1039-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861534&dopt=Abstract

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Necrotizing enterocolitis, pathogenesis and the protector effect of prenatal corticosteroids. Author(s): Precioso AR, Proenca RS. Source: Revista Do Hospital Das Clinicas. 2002 September-October; 57(5): 243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12436182&dopt=Abstract

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Necrotizing enterocolitis: prevention is the ultimate goal. Author(s): Falcao MC. Source: Revista Do Hospital Das Clinicas. 2002 September-October; 57(5): 199-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12436174&dopt=Abstract

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Neonatal necrotizing enterocolitis with intestinal perforation in extremely premature infants receiving early indomethacin treatment for patent ductus arteriosus. Author(s): Fujii AM, Brown E, Mirochnick M, O'Brien S, Kaufman G. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2002 October-November; 22(7): 535-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368968&dopt=Abstract

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Neonatal necrotizing enterocolitis: a focus on. Author(s): Pellegrini M, Lagrasta N, Garcia Garcia C, Campos Serna J, Zicari E, Marzocca G. Source: Eur Rev Med Pharmacol Sci. 2002 January-February; 6(1): 19-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608653&dopt=Abstract

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Neonatal necrotizing enterocolitis: an overview. Author(s): Kafetzis DA, Skevaki C, Costalos C. Source: Current Opinion in Infectious Diseases. 2003 August; 16(4): 349-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861088&dopt=Abstract

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Neonatal necrotizing enterocolitis: clinical considerations and pathogenetic concepts. Author(s): Hsueh W, Caplan MS, Qu XW, Tan XD, De Plaen IG, Gonzalez-Crussi F. Source: Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2003 January-February; 6(1): 6-23. Epub 2002 November 11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424605&dopt=Abstract

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Neutropenic colitis after treatment of acute myelogenous leukemia with idarubicin and cytosine arabinoside. Author(s): Hogan WJ, Letendre L, Litzow MR, Tefferi A, Hoagland HC, Pruthi RK, Kaufmann SH. Source: Mayo Clinic Proceedings. 2002 August; 77(8): 760-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173711&dopt=Abstract

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Neutropenic enterocolitis (typhlitis) after pediatric bone marrow transplant. Author(s): Otaibi AA, Barker C, Anderson R, Sigalet DL. Source: Journal of Pediatric Surgery. 2002 May; 37(5): 770-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11987097&dopt=Abstract

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Neutropenic enterocolitis in a woman treated with 5-fluorouracil and leucovorin for colon carcinoma. Author(s): Hayes D Jr, Leonardo JM. Source: N C Med J. 2002 May-June; 63(3): 132-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181847&dopt=Abstract

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Neutropenic enterocolitis. Author(s): Bavaro MF. Source: Current Gastroenterology Reports. 2002 August; 4(4): 297-301. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149175&dopt=Abstract

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Neutrophilic pustulosis and ulcerative colitis. Author(s): Vazquez J, Almagro M, del Pozo J, Fonseca E. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 January; 17(1): 77-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602978&dopt=Abstract

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Nitric oxide damage to colonocytes in colitis-by-association: remote transfer of nitric oxide to the colon. Author(s): Roediger WE. Source: Digestion. 2002; 65(4): 191-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239458&dopt=Abstract

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Non-steroidal anti-inflammatory drugs, aspirin and newly diagnosed colitis: a casecontrol study. Author(s): Gleeson MH, Davis AJ. Source: Alimentary Pharmacology & Therapeutics. 2003 March 15; 17(6): 817-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641504&dopt=Abstract

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Novel therapies in the treatment of ulcerative colitis. Author(s): Tuvlin JA, Kane SV. Source: Expert Opinion on Investigational Drugs. 2003 March; 12(3): 483-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605569&dopt=Abstract

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Nursing care of the child with neutropenic enterocolitis. Author(s): King N. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 2002 November-December; 19(6): 198-204. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444572&dopt=Abstract

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Octreotide in patients with active ulcerative colitis treated with high dose corticosteroids (OPUS 1). Author(s): van Bergeijk JD, Wilson JH, Nielsen OH, von Tirpitz C, Karvonen AL, Lygren I, Radler A, Waldum HL, Mulder CJ, Friis S, Tefera S, Hoogkamer JF; OPUS 1 study group. Source: European Journal of Gastroenterology & Hepatology. 2002 March; 14(3): 243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953688&dopt=Abstract

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Oligofructose and experimental model of neonatal necrotising enterocolitis. Author(s): Butel MJ, Waligora-Dupriet AJ, Szylit O. Source: The British Journal of Nutrition. 2002 May; 87 Suppl 2: S213-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088521&dopt=Abstract

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Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis. Author(s): Sutherland L, MacDonald JK. Source: Cochrane Database Syst Rev. 2003; (3): Cd000543. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917894&dopt=Abstract

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Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Author(s): Sutherland L, Roth D, Beck P, May G, Makiyama K. Source: Cochrane Database Syst Rev. 2002; (4): Cd000544. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519547&dopt=Abstract

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Oral administration of ketotifen in a patient with eosinophilic colitis and severe osteoporosis. Author(s): Katsinelos P, Pilpilidis I, Xiarchos P, Christodoulou K, Papagiannis A, Tsolkas P, Capelidis P, Vasiliadis I. Source: The American Journal of Gastroenterology. 2002 April; 97(4): 1072-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003402&dopt=Abstract

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Oral and topical 5-aminosalicylic acid (mesalazine) in inducing and maintaining remission in mild-moderate relapse of ulcerative colitis: one-year randomised multicentre trial. Author(s): Paoluzi P, D'Albasio G, Pera A, Bianchi Porro G, Paoluzi OA, Pica R, Cottone M, Miglioli M, Prantera C, Sturniolo G, Ardizzone S. Source: Dig Liver Dis. 2002 November; 34(11): 787-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546514&dopt=Abstract

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Oral beclometasone dipropionate in the treatment of active ulcerative colitis: a double-blind placebo-controlled study. Author(s): Rizzello F, Gionchetti P, D'Arienzo A, Manguso F, Di Matteo G, Annese V, Valpiani D, Casetti T, Adamo S, Prada A, Castiglione GN, Varoli G, Campieri M. Source: Alimentary Pharmacology & Therapeutics. 2002 June; 16(6): 1109-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030952&dopt=Abstract

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Oral beclometasone dipropionate in the treatment of extensive and left-sided active ulcerative colitis: a multicentre randomised study. Author(s): Campieri M, Adamo S, Valpiani D, D'Arienzo A, D'Albasio G, Pitzalis M, Cesari P, Casetti T, Castiglione GN, Rizzello F, Manguso F, Varoli G, Gionchetti P. Source: Alimentary Pharmacology & Therapeutics. 2003 June 15; 17(12): 1471-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823149&dopt=Abstract

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Oral cyclosporine in patients with active severe ulcerative colitis not responding to steroids. Author(s): Sood A, Midha V, Sood N. Source: Indian J Gastroenterol. 2002 July-August; 21(4): 155-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385545&dopt=Abstract

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Oral prednisolone metasulphobenzoate in the treatment of active ulcerative colitis. Author(s): Cameron EA, Binnie JA, Balan K, Skerratt SA, Swift A, Solanki C, Middleton SJ. Source: Scandinavian Journal of Gastroenterology. 2003 May; 38(5): 535-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795466&dopt=Abstract

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Outcome of patients undergoing ileal pouch-anal anastomosis for left-sided chronic ulcerative colitis. Author(s): Hassan I, Horgan AF, Nivatvongs S, Harrington J, Larson DR. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2003 May-June; 7(4): 567-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763418&dopt=Abstract

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Outpatient treatment of moderately severe active ulcerative colitis with pulsed steroid therapy and conventional steroid therapy. Author(s): Oshitani N, Kamata N, Ooiso R, Kawashima D, Inagawa M, Sogawa M, Iimuro M, Jinno Y, Watanabe K, Higuchi K, Matsumoto T, Arakawa T. Source: Digestive Diseases and Sciences. 2003 May; 48(5): 1002-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772803&dopt=Abstract

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Over-expression of interleukin 10 in mucosal T cells of patients with active ulcerative colitis. Author(s): Melgar S, Yeung MM, Bas A, Forsberg G, Suhr O, Oberg A, Hammarstrom S, Danielsson A, Hammarstrom ML. Source: Clinical and Experimental Immunology. 2003 October; 134(1): 127-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974765&dopt=Abstract

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Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL13-producing NK-T cells. Author(s): Heller F, Fuss IJ, Nieuwenhuis EE, Blumberg RS, Strober W. Source: Immunity. 2002 November; 17(5): 629-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433369&dopt=Abstract

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Oxidative stress and ulcerative colitis-associated carcinogenesis: studies in humans and animal models. Author(s): Seril DN, Liao J, Yang GY, Yang CS. Source: Carcinogenesis. 2003 March; 24(3): 353-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663492&dopt=Abstract

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Pancreatitis and E. coli O157:H7 colitis without hemolytic uremic syndrome. Author(s): Sass DA, Chopra KB, Regueiro MD. Source: Digestive Diseases and Sciences. 2003 February; 48(2): 415-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643624&dopt=Abstract

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Pathological subgroups may predict complications but not late failure after ileal pouch-anal anastomosis for indeterminate colitis. Author(s): Gramlich T, Delaney CP, Lynch AC, Remzi FH, Fazio VW. Source: Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland. 2003 July; 5(4): 315-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814408&dopt=Abstract

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Peri-operative blood lactate concentrations in pre-term babies with necrotising enterocolitis. Author(s): Abubacker M, Yoxall CW, Lamont G. Source: European Journal of Pediatric Surgery : Official Journal of Austrian Association of Pediatric Surgery. [et Al] = Zeitschrift Fur Kinderchirurgie. 2003 February; 13(1): 35-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664413&dopt=Abstract

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Pneumatosis coli, a benign form of necrotising enterocolitis. Author(s): Travadi JN, Patole SK, Gardiner K. Source: Indian Pediatrics. 2003 April; 40(4): 349-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736409&dopt=Abstract

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Polymorphisms of the IL-1beta and IL-1beta-inducible genes in ulcerative colitis. Author(s): Nohara H, Saito Y, Higaki S, Okayama N, Hamanaka Y, Okita K, Hinoda Y. Source: Journal of Gastroenterology. 2002 November; 37 Suppl 14: 107-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572877&dopt=Abstract

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Poorly controlled ulcerative colitis treated by colectomy during remission induced by extracorporeal leukocyte removal therapy. Author(s): Fukunaga K, Fukuda Y, Sawada K, Hori K, Matoba Y, Sagayama K, Ohnishi K, Fukui S, Shimoyama T. Source: Journal of Gastroenterology. 2003; 38(7): 684-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898362&dopt=Abstract

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Possible involvement of neutrophil elastase in impaired mucosal repair in patients with ulcerative colitis. Author(s): Kuno Y, Ina K, Nishiwaki T, Tsuzuki T, Shimada M, Imada A, Nishio Y, Nobata K, Suzuki T, Ando T, Hibi K, Nakao A, Yokoyama T, Yokoyama Y, Kusugami K. Source: Journal of Gastroenterology. 2002 November; 37 Suppl 14: 22-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572862&dopt=Abstract

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Pregnancy delivery and pouch function after ileal pouch-anal anastomosis for ulcerative colitis. Author(s): Ramalingam T, Box B, Mortensen NM. Source: Diseases of the Colon and Rectum. 2003 September; 46(9): 1292. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972978&dopt=Abstract

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Preoperative enterocolitis is associated with poorer long-term bowel function after Soave-Boley endorectal pull-through for Hirschsprung's disease. Author(s): Murthi GV, Raine PA. Source: Journal of Pediatric Surgery. 2003 January; 38(1): 69-72; Discussion 69-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592622&dopt=Abstract

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Prevalence of microscopic colitis in patients with symptoms suggesting irritable bowel syndrome. Author(s): Tuncer C, Cindoruk M, Dursun A, Karakan T. Source: Acta Gastroenterol Belg. 2003 April-June; 66(2): 133-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891921&dopt=Abstract

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Prevention of gut inflammation by Bifidobacterium in dextran sulfate-treated gnotobiotic mice associated with Bacteroides strains isolated from ulcerative colitis patients. Author(s): Setoyama H, Imaoka A, Ishikawa H, Umesaki Y. Source: Microbes and Infection / Institut Pasteur. 2003 February; 5(2): 115-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650769&dopt=Abstract

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Primary biliary cirrhosis and ulcerative colitis: a case report and review of literature. Author(s): Xiao WB, Liu YL. Source: World Journal of Gastroenterology : Wjg. 2003 April; 9(4): 878-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679954&dopt=Abstract

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Prolonging small feeding volumes early in life decreases the incidence of necrotizing enterocolitis in very low birth weight infants. Author(s): Berseth CL, Bisquera JA, Paje VU. Source: Pediatrics. 2003 March; 111(3): 529-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612232&dopt=Abstract

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Pseudomembranous collagenous colitis. Author(s): Yuan S, Reyes V, Bronner MP. Source: The American Journal of Surgical Pathology. 2003 October; 27(10): 1375-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14508399&dopt=Abstract

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Pseudoneoplastic appearance of cytomegalovirus-associated colitis in nonimmunocompromised patients: report of 2 cases. Author(s): Maiorana A, Torricelli P, Giusti F, Bellini N. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 September 1; 37(5): E68-71. Epub 2003 August 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12942421&dopt=Abstract

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Pump implantation for intrathecal baclofen infusion after laparotomy for necrotizing enterocolitis. Author(s): Piatt JH Jr. Source: Pediatric Neurosurgery. 2003 September; 39(3): 166-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876397&dopt=Abstract

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Quality of life before and after proctocolectomy and IPAA in patients with ulcerative proctocolitis--a prospective study. Author(s): Berndtsson I, Oresland T. Source: Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland. 2003 March; 5(2): 173-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780909&dopt=Abstract

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Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis. Author(s): Van Assche G, D'Haens G, Noman M, Vermeire S, Hiele M, Asnong K, Arts J, D'Hoore A, Penninckx F, Rutgeerts P. Source: Gastroenterology. 2003 October; 125(4): 1025-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14517785&dopt=Abstract

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RDP58, a novel immunomodulatory peptide with anti-inflammatory effects. A pharmacological study in trinitrobenzene sulphonic acid colitis and Crohn disease. Author(s): Bourreille A, Doubremelle M, de la Bletiere DR, Segain JP, Toquet C, Buelow R, Galmiche JP. Source: Scandinavian Journal of Gastroenterology. 2003 May; 38(5): 526-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795464&dopt=Abstract

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Re: Mann--melatonin for ulcerative colitis? Author(s): Jan JE, Freeman RD. Source: The American Journal of Gastroenterology. 2003 June; 98(6): 1446. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818299&dopt=Abstract

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Recurrent colitis with different causes. Author(s): Sugiyama Y, Ohni M, Sudoh N, Mizukawa S, Akishita M, Toba K. Source: Journal of the American Geriatrics Society. 2003 May; 51(5): 723-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752856&dopt=Abstract

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Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis: a randomized, double-blind, placebo-controlled, dose-escalation trial. Author(s): Sandborn WJ, Sands BE, Wolf DC, Valentine JF, Safdi M, Katz S, Isaacs KL, Wruble LD, Katz J, Present DH, Loftus EV Jr, Graeme-Cook F, Odenheimer DJ, Hanauer SB. Source: Alimentary Pharmacology & Therapeutics. 2003 June 1; 17(11): 1355-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786629&dopt=Abstract

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Restorative proctocolectomy with ileal pouch-anal anastomosis in very young patients with refractory ulcerative colitis. Author(s): Robb BW, Gang GI, Hershko DD, Stoops MM, Seeskin CS, Warner BW. Source: Journal of Pediatric Surgery. 2003 June; 38(6): 863-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778382&dopt=Abstract

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Retropharyngeal and splenic aseptic abscesses treated with prednisone and cyclophosphamide in a patient with ulcerative colitis. Author(s): Andre M, Piette JC, Frances C, Wechsler B, Delevaux I, Aumaitre O. Source: Digestive Diseases and Sciences. 2003 June; 48(6): 1193-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822884&dopt=Abstract

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Review article: colitis-associated cancer -- time for new strategies. Author(s): Shanahan F. Source: Alimentary Pharmacology & Therapeutics. 2003 September; 18 Suppl 2: 6-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950414&dopt=Abstract

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Review article: medical treatment of severe ulcerative colitis. Author(s): Rizzello F, Gionchetti P, Venturi A, Campieri M. Source: Alimentary Pharmacology & Therapeutics. 2003 June; 17 Suppl 2: 7-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786606&dopt=Abstract

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Risk of congenital abnormalities in children born to women with ulcerative colitis: a population-based, case-control study. Author(s): Norgard B, Puho E, Pedersen L, Czeizel AE, Sorensen HT. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 2006-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499779&dopt=Abstract

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Secreted effector proteins of Salmonella enterica serotype typhimurium elicit hostspecific chemokine profiles in animal models of typhoid fever and enterocolitis. Author(s): Zhang S, Adams LG, Nunes J, Khare S, Tsolis RM, Baumler AJ. Source: Infection and Immunity. 2003 August; 71(8): 4795-803. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874363&dopt=Abstract

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Septicaemia and liver abscesses secondary to non-O1/non-O139 Vibrio cholerae colitis. Author(s): Farmachidi JP, Sobesky R, Boussougant Y, Quilici ML, Coffin B. Source: European Journal of Gastroenterology & Hepatology. 2003 June; 15(6): 699-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840683&dopt=Abstract

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Signet-ring cells associated with pseudomembranous colitis. Author(s): Abdulkader I, Cameselle-Teijeiro J, Forteza J. Source: Virchows Archiv : an International Journal of Pathology. 2003 April; 442(4): 4124. Epub 2003 April 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684766&dopt=Abstract

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Simultaneous assays for Clostridium difficile and faecal lactoferrin in ulcerative colitis. Author(s): Vaishnavi C, Kochhar R, Bhasin D, Thennarasu K, Singh K. Source: Trop Gastroenterol. 2003 January-March; 24(1): 13-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974208&dopt=Abstract

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Spontaneous intestinal perforation and Candida peritonitis presenting as extensive necrotizing enterocolitis. Author(s): Robertson NJ, Kuna J, Cox PM, Lakhoo K. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003; 92(2): 258-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710658&dopt=Abstract

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Sporadic adenomas in chronic ulcerative colitis. Author(s): Fogt F. Source: Zeitschrift Fur Gastroenterologie. 2003 April; 41(4): 343-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695941&dopt=Abstract

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Subtotal colectomy for severe acute colitis: a 20-year experience of a tertiary care center with an aggressive and early surgical policy. Author(s): Alves A, Panis Y, Bouhnik Y, Maylin V, Lavergne-Slove A, Valleur P. Source: Journal of the American College of Surgeons. 2003 September; 197(3): 379-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12946792&dopt=Abstract

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Successful treatment of acute haemorrhagic cytomegalovirus colitis with ganciclovir in an individual without overt immunocompromise. Author(s): Patel SM, Cohen P, Pickering MC, Gazzard BG, Andreyev J. Source: European Journal of Gastroenterology & Hepatology. 2003 September; 15(9): 1055-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923383&dopt=Abstract

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Successful treatment of steroid resistant ulcerative colitis associated with severe autoimmune hemolytic anemia with oral microemulsion cyclosporin--a brief case report. Author(s): Molnar T, Szepes Z, Nagy F, Lonovics J. Source: The American Journal of Gastroenterology. 2003 May; 98(5): 1207-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809856&dopt=Abstract

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Suspicion of microscopic colitis raised by sonographic examination. Author(s): Hollerweger A, Macheiner P, Brunner W. Source: Journal of Clinical Ultrasound : Jcu. 2003 May; 31(4): 207-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692829&dopt=Abstract

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Ten year follow up of ulcerative colitis patients with and without low grade dysplasia. Author(s): Lim CH, Dixon MF, Vail A, Forman D, Lynch DA, Axon AT. Source: Gut. 2003 August; 52(8): 1127-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865270&dopt=Abstract

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TGF-beta1 production in inflammatory bowel disease: differing production patterns in Crohn's disease and ulcerative colitis. Author(s): Del Zotto B, Mumolo G, Pronio AM, Montesani C, Tersigni R, Boirivant M. Source: Clinical and Experimental Immunology. 2003 October; 134(1): 120-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974764&dopt=Abstract

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The clinical significance of focal active colitis in pediatric patients. Author(s): Xin W, Brown PI, Greenson JK. Source: The American Journal of Surgical Pathology. 2003 August; 27(8): 1134-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883246&dopt=Abstract

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The colon single-stripe sign and its relationship to ischemic colitis. Author(s): Zuckerman GR, Prakash C, Merriman RB, Sawhney MS, DeSchryverKecskemeti K, Clouse RE. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 2018-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499781&dopt=Abstract

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The influence of demographic and disease-related factors on health-related quality of life in patients with ulcerative colitis. Author(s): Hjortswang H, Jarnerot G, Curman B, Sandberg-Gertzen H, Tysk C, Blomberg B, Almer S, Strom M. Source: European Journal of Gastroenterology & Hepatology. 2003 September; 15(9): 1011-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923375&dopt=Abstract

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The use of a mini-laparotomy in total abdominal colectomy for mucosal ulcerative colitis. Author(s): Nakagoe T, Sawai T, Tsuji T, Jibiki MA, Nanashima A, Yamaguchi H, Yasutake T, Ayabe H. Source: Hepatogastroenterology. 2003 May-June; 50(51): 704-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828065&dopt=Abstract

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The value of serologic markers in indeterminate colitis: a prospective follow-up study. Author(s): Castillo S, Ramaiah B, Blum S, Remy P. Source: Gastroenterology. 2003 September; 125(3): 999; Author Reply 999-1000. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974272&dopt=Abstract

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Transient ischaemic colitis following an aeroplane flight. Author(s): Koutroubakis IE, Theodoropoulou A, Kouroumalis EA. Source: Gut. 2003 July; 52(7): 1072-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801974&dopt=Abstract

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Treatment of ulcerative colitis using fecal bacteriotherapy. Author(s): Borody TJ, Warren EF, Leis S, Surace R, Ashman O. Source: Journal of Clinical Gastroenterology. 2003 July; 37(1): 42-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811208&dopt=Abstract

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Tumor necrosis factor alpha is a key mediator of gut inflammation seen in amebic colitis in human intestine in the SCID mouse-human intestinal xenograft model of disease. Author(s): Zhang Z, Mahajan S, Zhang X, Stanley SL Jr. Source: Infection and Immunity. 2003 September; 71(9): 5355-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933883&dopt=Abstract

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Ulcerative colitis associated with aplastic anemia. Author(s): Kishikawa H, Nishida J, Nakano M, Hirano E, Morishita T, Ishii H. Source: Digestive Diseases and Sciences. 2003 July; 48(7): 1376-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870799&dopt=Abstract

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Ulcerative colitis associated with Takayasu arteritis. Author(s): Bansal R, Aggarwal P, Handa R, Biswas A, Bandhu S, Wali JP. Source: International Journal of Cardiology. 2003 March; 88(1): 91-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659990&dopt=Abstract

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Ulcerative colitis in a patient with Wiskott-Aldrich syndrome. Author(s): Folwaczny C, Ruelfs C, Walther J, Konig A, Emmerich B. Source: Endoscopy. 2002 October; 34(10): 840-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12244510&dopt=Abstract

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Ulcerative colitis in children: medical management. Author(s): Gremse DA, Crissinger KD. Source: Paediatric Drugs. 2002; 4(12): 807-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431133&dopt=Abstract

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Ulcerative colitis in monozygotic twin sisters. Author(s): Iwaizumi M, Yamada M, Kitagawa M, Takehira Y, Hanajima K, Murohisa G, Kawamura M, Iwaoka Y, Wada T, Morita S, Kawata K. Source: Intern Med. 2002 August; 41(8): 629-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12211531&dopt=Abstract

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Ulcerative colitis, primary sclerosing cholangitis and coeliac disease: two cases and review of the literature. Author(s): Wurm P, Dixon AD, Rathbone BJ. Source: European Journal of Gastroenterology & Hepatology. 2003 July; 15(7): 815-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811313&dopt=Abstract

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Ulcerative colitis, seronegative spondyloarthropathies and allergic diseases: the search for a link. Author(s): D'Arienzo A, Manguso F, Scarpa R, Astarita C, D'Armiento FP, Bennato R, Gargano D, Sanges M, Mazzacca G. Source: Scandinavian Journal of Gastroenterology. 2002 October; 37(10): 1156-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12408520&dopt=Abstract

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Ultrasonographic findings of amebic colitis. Author(s): Tsujimoto T, Kuriyama S, Yoshiji H, Fujimoto M, Kojima H, Yoshikawa M, Fukui H. Source: Journal of Gastroenterology. 2003; 38(1): 82-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560927&dopt=Abstract

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Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis. Author(s): Pardi DS, Loftus EV Jr, Kremers WK, Keach J, Lindor KD. Source: Gastroenterology. 2003 April; 124(4): 889-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671884&dopt=Abstract

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Use of the 'nutriceutical', bovine colostrum, for the treatment of distal colitis: results from an initial study. Author(s): Khan Z, Macdonald C, Wicks AC, Holt MP, Floyd D, Ghosh S, Wright NA, Playford RJ. Source: Alimentary Pharmacology & Therapeutics. 2002 November; 16(11): 1917-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390100&dopt=Abstract

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Validity of simple mucosal biopsy criteria combined with endoscopy predicting patients with ulcerative colitis ultimately requiring surgery: a multicenter study. Author(s): Tanaka M, Kusumi T, Oshitani N, Nishigami T, Iwao Y, Hatada Y, Sugita A, Yao T, Takano M, Iizuka B, Mukai M, Maeda K, Fukuda S, Morita T, Hara M, Saito H, Kudo H. Source: Scandinavian Journal of Gastroenterology. 2003 June; 38(6): 594-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825866&dopt=Abstract

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Verocytotoxin-producing Escherichia coli EH 0157:H7 colitis. Author(s): Morandi E, Grassi C, Cellerino P, Massara PP, Corsi F, Trabucchi E. Source: Journal of Clinical Gastroenterology. 2003 January; 36(1): 44-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488708&dopt=Abstract

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Vinorelbine and ischaemic colitis. Author(s): Olithselvan A, Gorard DA. Source: Clin Oncol (R Coll Radiol). 2003 May; 15(3): 166-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801059&dopt=Abstract

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Vulvar lichen planus associated with ulcerative colitis. A case report. Author(s): Giomi B, Pestelli E, Massi D, Caproni M, Fabbri P. Source: J Reprod Med. 2003 March; 48(3): 209-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698783&dopt=Abstract

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What is diverticular colitis? Author(s): Ludeman L, Shepherd NA. Source: Pathology. 2002 December; 34(6): 568-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555996&dopt=Abstract

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Wheat grass juice in the treatment of active distal ulcerative colitis: a randomized double-blind placebo-controlled trial. Author(s): Ben-Arye E, Goldin E, Wengrower D, Stamper A, Kohn R, Berry E. Source: Scandinavian Journal of Gastroenterology. 2002 April; 37(4): 444-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11989836&dopt=Abstract

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When should prophylactic colectomy be considered in patients with ulcerative colitis? Author(s): Lashner BA. Source: Cleve Clin J Med. 2003 March; 70(3): 221-2. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678211&dopt=Abstract

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CHAPTER 2. NUTRITION AND COLITIS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and colitis.

Finding Nutrition Studies on Colitis The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “colitis” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following is a typical result when searching for recently indexed consumer information on colitis: •

23 cases of chronic nonspecific ulcerative colitis treated by acupuncture and moxibustion. Author(s): Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine. Source: Zhang, X J-Tradit-Chin-Med. 1998 September; 18(3): 188-91 0254-6272

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Allergic colitis: a mimic of Hirschsprung disease. Author(s): Department of Radiology, Children's Radiological Institute, Columbus Children's Hospital, 700 Children's Drive, Columbus OH 43205-2696, USA. Source: Bloom, D A Buonomo, C Fishman, S J Furuta, G Nurko, S Pediatr-Radiol. 1999 January; 29(1): 37-41 0301-0449

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alpha-Phenyl-N-tert-butylnitrone provides protection from dextran sulfate sodiuminduced colitis in mice. Author(s): First Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan. [email protected] Source: Naito, Yuji Takagi, Tomohisa Ishikawa, Takeshi Handa, Osamu Matsumoto, Naoyuki Yagi, Nobuaki Matsuyama, Kiichi Yoshida, Norimasa Yoshikawa, Toshikazu Kotake, Yashige Antioxid-Redox-Signal. 2002 February; 4(1): 195-206 1523-0864

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An analysis of 10218 ulcerative colitis cases in China. Author(s): Department of Gastroenterology, Chinese PLA General Hospital of Jinan Command,25 Shifanlu,Jinan 250031,Shandong Province,China. [email protected] Source: Jiang, Xue Liang Cui, Hui Fei World-J-Gastroenterol. 2002 February; 8(1): 158-61 1007-9327

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Anti-inflammatory activity of phycocyanin extract in acetic acid-induced colitis in rats. Author(s): Pharmacology Department, National Center for Scientific Research, PO Box 6990, Havan, Cuba. Source: Gonzalez, R Rodriguez, S Romay, C Ancheta, O Gonzalez, A Armesto, J Remirez, D Merino, N Pharmacol-Res. 1999 January; 39(1): 55-9 1043-6618

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Anti-inflammatory effects of 5-aminosalicylic acid conjugates with chenodeoxycholic acid and ursodeoxycholic acid on carrageenan-induced colitis in guinea-pigs. Author(s): Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan. Source: Goto, M Okamoto, Y Yamamoto, M Aki, H J-Pharm-Pharmacol. 2001 December; 53(12): 1711-20 0022-3573

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Carrageenan colitis in the guinea pig: pathological changes and the importance of ascorbic acid deficiency in disease induction. Source: Langman, J.M. Rowland, R. Vernon Roberts, B. Aust-J-Exp-Biol-Med-Sci. Adelaide : University of Adelaide. October 1985. volume 63 (pt.5) page 545-553. ill. 0004945X

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Catgut point-embedding therapy in treatment of 76 cases of ulcerative colitis. Author(s): Xuchang Municipal Hospital of Traditional Chinese Medicine, Henan Province 461000. Source: Xiao, G Zhou, G J-Tradit-Chin-Med. 2001 June; 21(2): 116-7 0254-6272

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CD4 T cells monospecific to ovalbumin produced by Escherichia coli can induce colitis upon transfer to BALB/c and SCID mice. Author(s): Divisions of Clinical Bio-regulatory Science, and Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogo-in, Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan. Source: Yoshida, M Watanabe, T Usui, T Matsunaga, Y Shirai, Y Yamori, M Itoh, T Habu, S Chiba, T Kita, T Wakatsuki, Y Int-Immunol. 2001 December; 13(12): 1561-70 0953-8178

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Cerebral venous thrombosis in ulcerative colitis. Author(s): Department of Neurology, Neurosciences Center, All India Institute of Medical Sciences, New Delhi, 110029, India. Source: Srivastava, A K Khanna, N Sardana, V Gaekwad, S Prasad, K Behari, M NeurolIndia. 2002 June; 50(2): 215-7 0028-3886

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Colonic histopathology in untreated celiac sprue or refractory sprue: is it lymphocytic colitis or colonic lymphocytosis? Author(s): Department of Pathology, Baylor University Medical Center, Dallas, TX 75246, USA. Source: Fine, K D Lee, E L Meyer, R L Hum-Pathol. 1998 December; 29(12): 1433-40 00468177

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Comparative study of D-002 versus sulfasalazine on acetic acid-induced colitis in rats. Author(s): Department of Pharmacology, National Center for Scientific Research, Havana, Cuba. [email protected] Source: Noa, M Carbajal, D Molina, V Valdes, S Mas, R Drugs-Exp-Clin-Res. 2000; 26(1): 13-7 0378-6501

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Compensatory response of colon tissue to dextran sulfate sodium-induced colitis. Author(s): Department of Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan. Source: Nakano, S Ohara, S Kubota, T Saigenji, K Hotta, K J-Gastroenterol. 1999 April; 34(2): 207-14 0944-1174

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CpG motifs of bacterial DNA exacerbate colitis of dextran sulfate sodium-treated mice. Author(s): Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. Source: Obermeier, Florian Dunger, Nadja Deml, Ludwig Herfarth, Hans Scholmerich, Jurgen Falk, Werner Eur-J-Immunol. 2002 July; 32(7): 2084-92 0014-2980

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Development of colonic neoplasms and expressions of p53 and p21 proteins in experimental colitis of mice induced by dextran sulfate sodium. Author(s): Dept. of General Surgery, Fukuoka Dental College Hospital, Japan. Source: Takesue, F Korenaga, D Yao, T Kabashima, A Sugimachi, K J-Exp-Clin-CancerRes. 2001 September; 20(3): 413-8 0392-9078

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Dextran sulphate sodium-induced colitis is ameliorated in interleukin 4 deficient mice. Author(s): Division of Molecular Medicine, John Curtin School of Medical Research, ANU, Canberra, ACT, 2601, Australia. [email protected] Source: Stevceva, L Pavli, P Husband, A Ramsay, A Doe, W F Genes-Immun. 2001 October; 2(6): 309-16 1466-4879

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Diversion colitis--new light through old windows. Author(s): Department of Gastroenterology, John Radcliffe Hospital, Oxford, UK. [email protected] Source: Edwards, C M George, B Warren, B Histopathology. 1999 January; 34(1): 1-5 0309-0167

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Effect of BP 2.94, a histamine H3-receptor agonist prodrug, on different models of colitis. Author(s): Institute of Pharmacology, University of Parma, Italy. [email protected] Source: Coruzzi, G Poli, E Pozzoli, C Nosalova, V Grandi, D Lazzaretti, M Schunack, W Inflamm-Res. 2002 April; 51 Suppl 1: S31-2 1023-3830

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Effect of D-002 on acetic acid-induced colitis in rats at single and repeated doses. Author(s): Department of Pharmacology, Laboratory of Histology, Center of Natural Products, National Center for Scientific Research, 25 Ave and 158 Street, Playa, Havana, Cuba. Source: Noa, M Mas, R Carbajal, D Valdes, S Pharmacol-Res. 2000 April; 41(4): 391-5 1043-6618

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Effect of nepadutant, a neurokinin 2 tachykinin receptor antagonist, on immediateearly gene expression after trinitrobenzenesulfonic acid-induced colitis in the rat. Author(s): Department of Medicine-Laboratory of Epithelial Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. [email protected] Source: Birder, L A Kiss, S de Groat, W C Lecci, A Maggi, C A J-Pharmacol-Exp-Ther. 2003 January; 304(1): 272-6 0022-3565

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Effect of pleuran (beta-glucan from Pleurotus ostreatus) in diet or drinking fluid on colitis in rats. Author(s): Institute of Preventive and Clinical Medicine, Limbova 14, SK-83337 Bratislava, Slovak Republic. Source: Bobek, P Nosalova, V Cerna, S Nahrung. 2001 October; 45(5): 360-3 0027-769X

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Effect of zinc supplementation on trace elements and intestinal metallothionein concentrations in experimental colitis in the rat. Author(s): Department of Surgical and Gastroenterological Sciences, University of Padua, Italy. Source: Di Leo, V D'Inca, R Barollo, M Tropea, A Fries, W Mazzon, E Irato, P Cecchetto, A Sturniolo, G C Dig-Liver-Dis. 2001 March; 33(2): 135-9

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Effective maintenance leukocytapheresis for patients with steroid dependent or resistant ulcerative colitis. Author(s): Department of Medicine, Division of Gastroenterology, Social Insurance Chuo General Hospital, Hyakunincho, Tokyo, Japan. Source: Kondo, K Shinoda, T Yoshimoto, H Takazoe, M Hamada, T Ther-Apher. 2001 December; 5(6): 462-5 1091-6660

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Effects of gum resin of Boswellia serrata in patients with chronic colitis. Author(s): Department of Medicine, Medical College Jammu, J&K, India. Source: Gupta, I Parihar, A Malhotra, P Gupta, S Ludtke, R Safayhi, H Ammon, H P Planta-Med. 2001 July; 67(5): 391-5 0032-0943

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Effects of pleuran (beta-glucan isolated from Pleurotus ostreatus) on experimental colitis in rats. Author(s): Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava. [email protected]

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Source: Nosal'ova, V Bobek, P Cerna, S Galbavy, S Stvrtina, S Physiol-Res. 2001; 50(6): 575-81 0862-8408 •

Effects of silymarin on the acute stage of the trinitrobenzenesulphonic acid model of rat colitis. Source: Cruz, T. Galvez, J. Crespo, E. Ocete, M.A. Zarzuelo, A. Planta-med. Stuttgart : Georg Thieme Verlag,. February 2001. volume 67 (1) page94-96. 0032-0943

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Evaluation of the anti-inflammatory effect of baicalein on dextran sulfate sodiuminduced colitis in mice. Source: Hong, T. Jin, G.B. Cho, S. Cyong, J.C. Planta-med. Stuttgart : Georg Thieme Verlag,. March 2002. volume 68 (3) page 268-271. 0032-0943

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Foods with low numbers of microorganisms may not be the safest foods or, why did human listeriosis and hemorrhagic colitis become foodborne diseases. Source: Jay, J.M. Dairy-food-environ-sanit. Des Moines, IA : International Association of Milk, Food and Environmental Sanitarians, Inc. November 1995. volume 15 (11) page 674-677. 1043-3546

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Fulminant colitis: the case for operative treatment. Author(s): Department of Colorectal Surgery, The Cleveland Clinic Foundation, A111, 9500 Euclid Avenue, Cleveland, OH 44195, U.S.A. Source: Strong, Scott A Inflamm-Bowel-Dis. 2002 March; 8(2): 135-7; discussion 138-9 1078-0998

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Gangrenous ischaemic colitis following non-steroidal anti-inflammatory drug overdose. Author(s): Department of Surgery, Western Hospital, Footscray,Victoria, Australia. Source: Appu, S Thompson, G ANZ-J-Surg. 2001 November; 71(11): 694-5 1445-1433

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Glycoaminoglycan (GAG) deficiency in protective barrier as an underlying, primary cause of ulcerative colitis, Crohn's disease interstitial cystitis and possibly Reiter's syndrome. Source: Russell, A L Med-Hypotheses. 1999 April; 52(4): 297-301 0306-9877

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Histiocytic ulcerative colitis in three non-boxer dogs. Author(s): Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing 48824, USA. Source: Stokes, J E Kruger, J M Mullaney, T Holan, K Schall, W J-Am-Anim-Hosp-Assoc. 2001 Sep-October; 37(5): 461-5 0587-2871

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Hodgkin s disease with nephrotic syndrome as a complication of ulcerative colitis: case report. Author(s): Division of Hematology, Department of Medicine, Zagreb University Hospital Center, Kispaticeva 12, Croatia. [email protected] Source: Basic Jukic, N Radman, I Roncevic, T Jakic Razumovic, J Croat-Med-J. 2002 October; 43(5): 573-5 0353-9504

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Immunomodulation of experimental colitis via caloric restriction: role of Nk1.1+ T cells. Author(s): Liver Unit, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel. [email protected] Source: Shibolet, O Alper, R Avraham, Y Berry, E M Ilan, Y Clin-Immunol. 2002 October; 105(1): 48-56 1521-6616

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Infliximab in the treatment of severe, steroid-refractory ulcerative colitis: a pilot study. Author(s): Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston 02114, USA. Source: Sands, B E Tremaine, W J Sandborn, W J Rutgeerts, P J Hanauer, S B Mayer, L Targan, S R Podolsky, D K Inflamm-Bowel-Dis. 2001 May; 7(2): 83-8 1078-0998

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Interventions for treating collagenous colitis. Author(s): c/o 5-OF 12 LHSC-UC, 339 Windermere Road, London, Ontario, Canada, N6A 5A5. [email protected] Source: Chande, N McDonald, J W MacDonald, J K Cochrane-Database-Syst-Revolume 2002; (4): CD003575 1469-493X

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Lactobacillus plantarum 299V in the treatment and prevention of spontaneous colitis in interleukin-10-deficient mice. Author(s): Center for GI Biology and Disease, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599-7038, U.S.A. Source: Schultz, Michael Veltkamp, Claudia Dieleman, Levinus A Grenther, Wetonia B Wyrick, Pricilla B Tonkonogy, Susan L Sartor, R Balfour Inflamm-Bowel-Dis. 2002 March; 8(2): 71-80 1078-0998

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Lymphocytic colitis, induced by ticlopidine. Author(s): DRK-Krankenhaus Neuwied. Germany. Source: Feurle, G E Bartz, K O Schmitt Graff, A Z-Gastroenterol. 1999 November; 37(11): 1105-8 0044-2771

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Medium-chain triglyceride-rich enteral nutrition is more effective than low-fat enteral nutrition in rat colitis, but is equal in enteritis. Author(s): Second Department of Internal Medicine, Shiga University of Medical Science, Seta, Otsu, Japan. Source: Tsujikawa, T Ohta, N Nakamura, T Yasuoka, T Satoh, J Fukunaga, T Itohi, A Uda, K Ihara, T Andoh, A Sasaki, M Fujiyama, Y Bamba, T J-Gastroenterol. 2001 October; 36(10): 673-80 0944-1174

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Mistaken diagnosis of eosinophilic colitis. Author(s): Chair of Gastroenterology, IRCCS, Ospedale Maggiore, Milan, Italy. Source: Corsetti, M Basilisco, G Pometta, R Allocca, M Conte, D Ital-J-GastroenterolHepatol. 1999 October; 31(7): 607-9 1125-8055

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Mucosal dysplasia of the colon in patients with chronic ulcerative colitis. Source: Lashner, B.A. Pennington-Cent-Nutr-Ser. Baton Rouge : Louisiana State University Press. 1993. volume 3 page 209-219.

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Neutropenic colitis as a complication of high-dose chemotherapy for refractory testicular cancer. Author(s): Department of Urology, University of Tsukuba, Ibaraki, Japan. Source: Kawai, K Imada, S Iida, K Tsukamoto, S Miyanaga, N Akaza, H Jpn-J-ClinOncol. 1998 September; 28(9): 571-3 0368-2811

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Observation of the efficacy of acupuncture and moxibustion in 62 cases of chronic colitis. Author(s): Liuzhou Hospital of Traditional Chinese Medicine. Source: Yang, C Yan, H J-Tradit-Chin-Med. 1999 June; 19(2): 111-4 0254-6272

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Participation of mast cells in colitis inflammation induced by dextran sulfate sodium. Author(s): Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Okayama, Japan.

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Source: Iba, Y Sugimoto, Y Kamei, C Methods-Find-Exp-Clin-Pharmacol. 2002 JanFebruary; 24(1): 15-8 0379-0355 •

Peroxisome proliferator-activated receptor gamma agonist ligands stimulate a Th2 cytokine response and prevent acute colitis. Author(s): [email protected] Source: Saubermann, L J Nakajima, A Wada, K Zhao, S Terauchi, Y Kadowaki, T Aburatani, H Matsuhashi, N Nagai, R Blumberg, R S Inflamm-Bowel-Dis. 2002 September; 8(5): 330-9 1078-0998

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Plasmacytic lymphocytic colitis in the dog. Source: Leib, M.S. Hiler, L.A. Roth, L. Thatcher, C. Monroe, W.E. Shell, L.G. Semin-VetMed-Surg-Small-Anim. Philadelphia, Pa. : W.B. Saunders Co. August 1989. volume 4 (3) page 241-246. 0882-0511

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Prebiotic treatment of experimental colitis with germinated barley foodstuff: A comparison with probiotic or antibiotic treatment. Author(s): Pharmaceutical Division, Kirin Brewery Co. Ltd., Shibuya-ku, Tokyo 1508011, Japan. Source: Fukuda, Masanobu Kanauchi, Osamu Araki, Yoshio Andoh, Akira Mitsuyama, Keiichi Takagi, Kohsuke Toyonaga, Atsushi Sata, Michio Fujiyama, Yoshihide Fukuoka, Masamichi Matsumoto, Yoshiaki Bamba, Tadao Int-J-Mol-Med. 2002 January; 9(1): 65-70 1107-3756

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Preventive effect of TAK-751S on complications of hemorrhagic colitis (results of clinical study of TAK-751S). Author(s): Kiyose Children's Hospital. Source: Ito, Hiroshi Takeda, Tae Honda, Masataka Igarashi, Takashi Joh, Kosuke Hashizume, Takao Yamaoka, Kanji Jpn-J-Antibiot. 2002 April; 55(2): 203-27 0368-2781

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Preventive efficacy of butyrate enemas and oral administration of Clostridium butyricum M588 in dextran sodium sulfate-induced colitis in rats. Author(s): Second Department of Internal Medicine, Shiga University of Medical Science, Seta, Otsu, Japan. Source: Okamoto, T Sasaki, M Tsujikawa, T Fujiyama, Y Bamba, T Kusunoki, M JGastroenterol. 2000; 35(5): 341-6 0944-1174

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Pseudomembranous colitis. Source: Aboud, W Marshall, R Berkelhammer, C Gastrointest-Endosc. 2000 August; 52(2): 234 0016-5107

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Role of bile acids in lymphocytic colitis. Author(s): Department of Internal Medicine, Division of Gastroenterology, Sahlgrenska University Hospital, SE-413 45 Goteborg, Sweden. [email protected] Source: Ung, K A Kilander, A Willen, R Abrahamsson, H Hepatogastroenterology. 2002 Mar-April; 49(44): 432-7 0172-6390

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Roles of mucosal bacteria and succinic acid in colitis caused by dextran sulfate sodium in mice. Author(s): First Department of Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University, Japan. Source: Ariake, K Ohkusa, T Sakurazawa, T Kumagai, J Eishi, Y Hoshi, S Yajima, T JMed-Dent-Sci. 2000 December; 47(4): 233-41 1342-8810

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Small intestinal absorption and tolerance of enteral nutrition in acute colitis. Source: Rao, S.S.C. Holdsworth, C.D. Forrest, A.R.W. Brit-Med-J. London : British Medical Association. Sept 19, 1987. volume 295 (6600) page 698. charts. 0267-0623

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Suppressive effects of a new anti-inflammatory agent, IS-741, on dextran sulfate sodium-induced experimental colitis in rats. Author(s): Department of Internal Medicine, Shiga University of Medical Science, SetaTsukinowa, Otsu, Japan. Source: Makino, Jin Andoh, Akira Hata, Kazunori Yotsuya, Shuichi Shikama, Hiroshi Araki, Yoshio Fujiyama, Yoshihide Bamba, Tadao Int-J-Mol-Med. 2002 April; 9(4): 391-6 1107-3756

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The natural plant product tryptanthrin ameliorates dextran sodium sulfate-induced colitis in mice. Author(s): Fujisaki Institute, Hayashibara Biochemical Laboratories Inc, Okayama, Japan. [email protected] Source: Micallef, M J Iwaki, K Ishihara, T Ushio, S Aga, M Kunikata, T Koya Miyata, S Kimoto, T Ikeda, M Kurimoto, M Int-Immunopharmacol. 2002 March; 2(4): 565-78 15675769

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Thumbprinting due to ischemic colitis in a patient on oral anticoagulation. Author(s): Department of Radiology, Clinique St. Elisabeth, Bruxelles. Source: Crombe, D Pringot, J Van Isveldt, J Van Campenhoudt, M JBR-BTR. 2002 AugSeptember; 85(4): 220 0302-7430

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Treating colitis. Source: Twedt, D.C. Proc-North-Am-Vet-Conf. [Gainesville, Fla.] : Eastern States Veterinary Association, 1992-. 1998. volume 12 page 318.

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Treatment of ulcerative colitis by feeding with germinated barley foodstuff: first report of a multicenter open control trial. Author(s): Nutrient Food and Feed Division, Kirin Brewery, 10-1-2 Shinkawa, Chuo-ku, Tokyo 104-8288, Japan. Source: Kanauchi, O Suga, T Tochihara, M Hibi, T Naganuma, M Homma, T Asakura, H Nakano, H Takahama, K Fujiyama, Y Andoh, A Shimoyama, T Hida, N Haruma, K Koga, H Mitsuyama, K Sata, M Fukuda, M Kojima, A Bamba, T J-Gastroenterol. 2002 November; 37 Suppl 14: 67-72 0944-1174

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Ulcerative colitis in Thailand: a clinical study and long term follow-up. Author(s): Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Source: Pongprasobchai, S Manatsathit, S Leelakusolvong, S Sattawatthamrong, Y Boonyapisit, S J-Med-Assoc-Thai. 2001 September; 84(9): 1281-8 0125-2208

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Update on medical management of inflammatory bowel disease: ulcerative colitis. Author(s): Section of Gastroenterology and Nutrition, University of Chicago, Pritzker School of Medicine, Chicago, IL, USA. Source: Hanauer, S B Rev-Gastroenterol-Disord. 2001; 1(4): 169-76 1533-001X

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Validation of a pharmacokinetic model of colon-specific drug delivery and the therapeutic effects of chitosan capsules containing 5-aminosalicylic acid on 2,4,6trinitrobenzenesulphonic acid-induced colitis in rats. Author(s): Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan. Source: Tozaki, H Fujita, T Odoriba, T Terabe, A Okabe, S Muranishi, S Yamamoto, A JPharm-Pharmacol. 1999 October; 51(10): 1107-12 0022-3573

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Variable response to probiotics in two models of experimental colitis in rats. Author(s): Department of Medicine, Hadassah University Hospital, Mount Scopus, Jerusalem. [email protected]

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Source: Shibolet, O Karmeli, F Eliakim, R Swennen, E Brigidi, P Gionchetti, P Campieri, M Morgenstern, S Rachmilewitz, D Inflamm-Bowel-Dis. 2002 November; 8(6): 399-406 1078-0998 The following information is typical of that found when using the “Full IBIDS Database” to search for “colitis” (or a synonym): •

23 cases of chronic nonspecific ulcerative colitis treated by acupuncture and moxibustion. Author(s): Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine. Source: Zhang, X J-Tradit-Chin-Med. 1998 September; 18(3): 188-91 0254-6272

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Allergic colitis: a mimic of Hirschsprung disease. Author(s): Department of Radiology, Children's Radiological Institute, Columbus Children's Hospital, 700 Children's Drive, Columbus OH 43205-2696, USA. Source: Bloom, D A Buonomo, C Fishman, S J Furuta, G Nurko, S Pediatr-Radiol. 1999 January; 29(1): 37-41 0301-0449

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alpha-Phenyl-N-tert-butylnitrone provides protection from dextran sulfate sodiuminduced colitis in mice. Author(s): First Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan. [email protected] Source: Naito, Yuji Takagi, Tomohisa Ishikawa, Takeshi Handa, Osamu Matsumoto, Naoyuki Yagi, Nobuaki Matsuyama, Kiichi Yoshida, Norimasa Yoshikawa, Toshikazu Kotake, Yashige Antioxid-Redox-Signal. 2002 February; 4(1): 195-206 1523-0864

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An analysis of 10218 ulcerative colitis cases in China. Author(s): Department of Gastroenterology, Chinese PLA General Hospital of Jinan Command,25 Shifanlu,Jinan 250031,Shandong Province,China. [email protected] Source: Jiang, Xue Liang Cui, Hui Fei World-J-Gastroenterol. 2002 February; 8(1): 158-61 1007-9327

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Anti-inflammatory activity of phycocyanin extract in acetic acid-induced colitis in rats. Author(s): Pharmacology Department, National Center for Scientific Research, PO Box 6990, Havan, Cuba. Source: Gonzalez, R Rodriguez, S Romay, C Ancheta, O Gonzalez, A Armesto, J Remirez, D Merino, N Pharmacol-Res. 1999 January; 39(1): 55-9 1043-6618

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Anti-inflammatory effects of 5-aminosalicylic acid conjugates with chenodeoxycholic acid and ursodeoxycholic acid on carrageenan-induced colitis in guinea-pigs. Author(s): Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan. Source: Goto, M Okamoto, Y Yamamoto, M Aki, H J-Pharm-Pharmacol. 2001 December; 53(12): 1711-20 0022-3573

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Carrageenan colitis in the guinea pig: pathological changes and the importance of ascorbic acid deficiency in disease induction. Source: Langman, J.M. Rowland, R. Vernon Roberts, B. Aust-J-Exp-Biol-Med-Sci. Adelaide : University of Adelaide. October 1985. volume 63 (pt.5) page 545-553. ill. 0004945X

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Catgut point-embedding therapy in treatment of 76 cases of ulcerative colitis. Author(s): Xuchang Municipal Hospital of Traditional Chinese Medicine, Henan Province 461000. Source: Xiao, G Zhou, G J-Tradit-Chin-Med. 2001 June; 21(2): 116-7 0254-6272

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CD4 T cells monospecific to ovalbumin produced by Escherichia coli can induce colitis upon transfer to BALB/c and SCID mice. Author(s): Divisions of Clinical Bio-regulatory Science, and Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogo-in, Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan. Source: Yoshida, M Watanabe, T Usui, T Matsunaga, Y Shirai, Y Yamori, M Itoh, T Habu, S Chiba, T Kita, T Wakatsuki, Y Int-Immunol. 2001 December; 13(12): 1561-70 0953-8178

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Cerebral venous thrombosis in ulcerative colitis. Author(s): Department of Neurology, Neurosciences Center, All India Institute of Medical Sciences, New Delhi, 110029, India. Source: Srivastava, A K Khanna, N Sardana, V Gaekwad, S Prasad, K Behari, M NeurolIndia. 2002 June; 50(2): 215-7 0028-3886

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Colonic histopathology in untreated celiac sprue or refractory sprue: is it lymphocytic colitis or colonic lymphocytosis? Author(s): Department of Pathology, Baylor University Medical Center, Dallas, TX 75246, USA. Source: Fine, K D Lee, E L Meyer, R L Hum-Pathol. 1998 December; 29(12): 1433-40 00468177

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Comparative study of D-002 versus sulfasalazine on acetic acid-induced colitis in rats. Author(s): Department of Pharmacology, National Center for Scientific Research, Havana, Cuba. [email protected] Source: Noa, M Carbajal, D Molina, V Valdes, S Mas, R Drugs-Exp-Clin-Res. 2000; 26(1): 13-7 0378-6501

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Compensatory response of colon tissue to dextran sulfate sodium-induced colitis. Author(s): Department of Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan. Source: Nakano, S Ohara, S Kubota, T Saigenji, K Hotta, K J-Gastroenterol. 1999 April; 34(2): 207-14 0944-1174

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CpG motifs of bacterial DNA exacerbate colitis of dextran sulfate sodium-treated mice. Author(s): Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. Source: Obermeier, Florian Dunger, Nadja Deml, Ludwig Herfarth, Hans Scholmerich, Jurgen Falk, Werner Eur-J-Immunol. 2002 July; 32(7): 2084-92 0014-2980

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Development of colonic neoplasms and expressions of p53 and p21 proteins in experimental colitis of mice induced by dextran sulfate sodium. Author(s): Dept. of General Surgery, Fukuoka Dental College Hospital, Japan. Source: Takesue, F Korenaga, D Yao, T Kabashima, A Sugimachi, K J-Exp-Clin-CancerRes. 2001 September; 20(3): 413-8 0392-9078

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Dextran sulphate sodium-induced colitis is ameliorated in interleukin 4 deficient mice. Author(s): Division of Molecular Medicine, John Curtin School of Medical Research, ANU, Canberra, ACT, 2601, Australia. [email protected]

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Source: Stevceva, L Pavli, P Husband, A Ramsay, A Doe, W F Genes-Immun. 2001 October; 2(6): 309-16 1466-4879 •

Diversion colitis--new light through old windows. Author(s): Department of Gastroenterology, John Radcliffe Hospital, Oxford, UK. [email protected] Source: Edwards, C M George, B Warren, B Histopathology. 1999 January; 34(1): 1-5 0309-0167

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Effect of BP 2.94, a histamine H3-receptor agonist prodrug, on different models of colitis. Author(s): Institute of Pharmacology, University of Parma, Italy. [email protected] Source: Coruzzi, G Poli, E Pozzoli, C Nosalova, V Grandi, D Lazzaretti, M Schunack, W Inflamm-Res. 2002 April; 51 Suppl 1: S31-2 1023-3830

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Effect of D-002 on acetic acid-induced colitis in rats at single and repeated doses. Author(s): Department of Pharmacology, Laboratory of Histology, Center of Natural Products, National Center for Scientific Research, 25 Ave and 158 Street, Playa, Havana, Cuba. Source: Noa, M Mas, R Carbajal, D Valdes, S Pharmacol-Res. 2000 April; 41(4): 391-5 1043-6618

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Effect of nepadutant, a neurokinin 2 tachykinin receptor antagonist, on immediateearly gene expression after trinitrobenzenesulfonic acid-induced colitis in the rat. Author(s): Department of Medicine-Laboratory of Epithelial Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. [email protected] Source: Birder, L A Kiss, S de Groat, W C Lecci, A Maggi, C A J-Pharmacol-Exp-Ther. 2003 January; 304(1): 272-6 0022-3565

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Effect of pleuran (beta-glucan from Pleurotus ostreatus) in diet or drinking fluid on colitis in rats. Author(s): Institute of Preventive and Clinical Medicine, Limbova 14, SK-83337 Bratislava, Slovak Republic. Source: Bobek, P Nosalova, V Cerna, S Nahrung. 2001 October; 45(5): 360-3 0027-769X

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Effect of zinc supplementation on trace elements and intestinal metallothionein concentrations in experimental colitis in the rat. Author(s): Department of Surgical and Gastroenterological Sciences, University of Padua, Italy. Source: Di Leo, V D'Inca, R Barollo, M Tropea, A Fries, W Mazzon, E Irato, P Cecchetto, A Sturniolo, G C Dig-Liver-Dis. 2001 March; 33(2): 135-9

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Effective maintenance leukocytapheresis for patients with steroid dependent or resistant ulcerative colitis. Author(s): Department of Medicine, Division of Gastroenterology, Social Insurance Chuo General Hospital, Hyakunincho, Tokyo, Japan. Source: Kondo, K Shinoda, T Yoshimoto, H Takazoe, M Hamada, T Ther-Apher. 2001 December; 5(6): 462-5 1091-6660

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Effects of gum resin of Boswellia serrata in patients with chronic colitis. Author(s): Department of Medicine, Medical College Jammu, J&K, India. Source: Gupta, I Parihar, A Malhotra, P Gupta, S Ludtke, R Safayhi, H Ammon, H P Planta-Med. 2001 July; 67(5): 391-5 0032-0943

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Effects of pleuran (beta-glucan isolated from Pleurotus ostreatus) on experimental colitis in rats. Author(s): Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava. [email protected] Source: Nosal'ova, V Bobek, P Cerna, S Galbavy, S Stvrtina, S Physiol-Res. 2001; 50(6): 575-81 0862-8408

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Effects of silymarin on the acute stage of the trinitrobenzenesulphonic acid model of rat colitis. Source: Cruz, T. Galvez, J. Crespo, E. Ocete, M.A. Zarzuelo, A. Planta-med. Stuttgart : Georg Thieme Verlag,. February 2001. volume 67 (1) page94-96. 0032-0943

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Evaluation of the anti-inflammatory effect of baicalein on dextran sulfate sodiuminduced colitis in mice. Source: Hong, T. Jin, G.B. Cho, S. Cyong, J.C. Planta-med. Stuttgart : Georg Thieme Verlag,. March 2002. volume 68 (3) page 268-271. 0032-0943

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Foods with low numbers of microorganisms may not be the safest foods or, why did human listeriosis and hemorrhagic colitis become foodborne diseases. Source: Jay, J.M. Dairy-food-environ-sanit. Des Moines, IA : International Association of Milk, Food and Environmental Sanitarians, Inc. November 1995. volume 15 (11) page 674-677. 1043-3546

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Fulminant colitis: the case for operative treatment. Author(s): Department of Colorectal Surgery, The Cleveland Clinic Foundation, A111, 9500 Euclid Avenue, Cleveland, OH 44195, U.S.A. Source: Strong, Scott A Inflamm-Bowel-Dis. 2002 March; 8(2): 135-7; discussion 138-9 1078-0998

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Gangrenous ischaemic colitis following non-steroidal anti-inflammatory drug overdose. Author(s): Department of Surgery, Western Hospital, Footscray,Victoria, Australia. Source: Appu, S Thompson, G ANZ-J-Surg. 2001 November; 71(11): 694-5 1445-1433

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Glycoaminoglycan (GAG) deficiency in protective barrier as an underlying, primary cause of ulcerative colitis, Crohn's disease interstitial cystitis and possibly Reiter's syndrome. Source: Russell, A L Med-Hypotheses. 1999 April; 52(4): 297-301 0306-9877

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Histiocytic ulcerative colitis in three non-boxer dogs. Author(s): Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing 48824, USA. Source: Stokes, J E Kruger, J M Mullaney, T Holan, K Schall, W J-Am-Anim-Hosp-Assoc. 2001 Sep-October; 37(5): 461-5 0587-2871

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Hodgkin s disease with nephrotic syndrome as a complication of ulcerative colitis: case report. Author(s): Division of Hematology, Department of Medicine, Zagreb University Hospital Center, Kispaticeva 12, Croatia. [email protected] Source: Basic Jukic, N Radman, I Roncevic, T Jakic Razumovic, J Croat-Med-J. 2002 October; 43(5): 573-5 0353-9504

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Immunomodulation of experimental colitis via caloric restriction: role of Nk1.1+ T cells. Author(s): Liver Unit, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel. [email protected]

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Source: Shibolet, O Alper, R Avraham, Y Berry, E M Ilan, Y Clin-Immunol. 2002 October; 105(1): 48-56 1521-6616 •

Infliximab in the treatment of severe, steroid-refractory ulcerative colitis: a pilot study. Author(s): Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston 02114, USA. Source: Sands, B E Tremaine, W J Sandborn, W J Rutgeerts, P J Hanauer, S B Mayer, L Targan, S R Podolsky, D K Inflamm-Bowel-Dis. 2001 May; 7(2): 83-8 1078-0998

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Interventions for treating collagenous colitis. Author(s): c/o 5-OF 12 LHSC-UC, 339 Windermere Road, London, Ontario, Canada, N6A 5A5. [email protected] Source: Chande, N McDonald, J W MacDonald, J K Cochrane-Database-Syst-Revolume 2002; (4): CD003575 1469-493X

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Lactobacillus plantarum 299V in the treatment and prevention of spontaneous colitis in interleukin-10-deficient mice. Author(s): Center for GI Biology and Disease, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599-7038, U.S.A. Source: Schultz, Michael Veltkamp, Claudia Dieleman, Levinus A Grenther, Wetonia B Wyrick, Pricilla B Tonkonogy, Susan L Sartor, R Balfour Inflamm-Bowel-Dis. 2002 March; 8(2): 71-80 1078-0998

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Lymphocytic colitis, induced by ticlopidine. Author(s): DRK-Krankenhaus Neuwied. Germany. Source: Feurle, G E Bartz, K O Schmitt Graff, A Z-Gastroenterol. 1999 November; 37(11): 1105-8 0044-2771

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Medium-chain triglyceride-rich enteral nutrition is more effective than low-fat enteral nutrition in rat colitis, but is equal in enteritis. Author(s): Second Department of Internal Medicine, Shiga University of Medical Science, Seta, Otsu, Japan. Source: Tsujikawa, T Ohta, N Nakamura, T Yasuoka, T Satoh, J Fukunaga, T Itohi, A Uda, K Ihara, T Andoh, A Sasaki, M Fujiyama, Y Bamba, T J-Gastroenterol. 2001 October; 36(10): 673-80 0944-1174

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Mistaken diagnosis of eosinophilic colitis. Author(s): Chair of Gastroenterology, IRCCS, Ospedale Maggiore, Milan, Italy. Source: Corsetti, M Basilisco, G Pometta, R Allocca, M Conte, D Ital-J-GastroenterolHepatol. 1999 October; 31(7): 607-9 1125-8055

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Mucosal dysplasia of the colon in patients with chronic ulcerative colitis. Source: Lashner, B.A. Pennington-Cent-Nutr-Ser. Baton Rouge : Louisiana State University Press. 1993. volume 3 page 209-219.

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Neutropenic colitis as a complication of high-dose chemotherapy for refractory testicular cancer. Author(s): Department of Urology, University of Tsukuba, Ibaraki, Japan. Source: Kawai, K Imada, S Iida, K Tsukamoto, S Miyanaga, N Akaza, H Jpn-J-ClinOncol. 1998 September; 28(9): 571-3 0368-2811

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Observation of the efficacy of acupuncture and moxibustion in 62 cases of chronic colitis. Author(s): Liuzhou Hospital of Traditional Chinese Medicine. Source: Yang, C Yan, H J-Tradit-Chin-Med. 1999 June; 19(2): 111-4 0254-6272

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Participation of mast cells in colitis inflammation induced by dextran sulfate sodium. Author(s): Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Okayama, Japan. Source: Iba, Y Sugimoto, Y Kamei, C Methods-Find-Exp-Clin-Pharmacol. 2002 JanFebruary; 24(1): 15-8 0379-0355

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Peroxisome proliferator-activated receptor gamma agonist ligands stimulate a Th2 cytokine response and prevent acute colitis. Author(s): [email protected] Source: Saubermann, L J Nakajima, A Wada, K Zhao, S Terauchi, Y Kadowaki, T Aburatani, H Matsuhashi, N Nagai, R Blumberg, R S Inflamm-Bowel-Dis. 2002 September; 8(5): 330-9 1078-0998

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Plasmacytic lymphocytic colitis in the dog. Source: Leib, M.S. Hiler, L.A. Roth, L. Thatcher, C. Monroe, W.E. Shell, L.G. Semin-VetMed-Surg-Small-Anim. Philadelphia, Pa. : W.B. Saunders Co. August 1989. volume 4 (3) page 241-246. 0882-0511

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Prebiotic treatment of experimental colitis with germinated barley foodstuff: A comparison with probiotic or antibiotic treatment. Author(s): Pharmaceutical Division, Kirin Brewery Co. Ltd., Shibuya-ku, Tokyo 1508011, Japan. Source: Fukuda, Masanobu Kanauchi, Osamu Araki, Yoshio Andoh, Akira Mitsuyama, Keiichi Takagi, Kohsuke Toyonaga, Atsushi Sata, Michio Fujiyama, Yoshihide Fukuoka, Masamichi Matsumoto, Yoshiaki Bamba, Tadao Int-J-Mol-Med. 2002 January; 9(1): 65-70 1107-3756

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Preventive effect of TAK-751S on complications of hemorrhagic colitis (results of clinical study of TAK-751S). Author(s): Kiyose Children's Hospital. Source: Ito, Hiroshi Takeda, Tae Honda, Masataka Igarashi, Takashi Joh, Kosuke Hashizume, Takao Yamaoka, Kanji Jpn-J-Antibiot. 2002 April; 55(2): 203-27 0368-2781

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Preventive efficacy of butyrate enemas and oral administration of Clostridium butyricum M588 in dextran sodium sulfate-induced colitis in rats. Author(s): Second Department of Internal Medicine, Shiga University of Medical Science, Seta, Otsu, Japan. Source: Okamoto, T Sasaki, M Tsujikawa, T Fujiyama, Y Bamba, T Kusunoki, M JGastroenterol. 2000; 35(5): 341-6 0944-1174

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Pseudomembranous colitis. Source: Aboud, W Marshall, R Berkelhammer, C Gastrointest-Endosc. 2000 August; 52(2): 234 0016-5107

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Role of bile acids in lymphocytic colitis. Author(s): Department of Internal Medicine, Division of Gastroenterology, Sahlgrenska University Hospital, SE-413 45 Goteborg, Sweden. [email protected] Source: Ung, K A Kilander, A Willen, R Abrahamsson, H Hepatogastroenterology. 2002 Mar-April; 49(44): 432-7 0172-6390

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Roles of mucosal bacteria and succinic acid in colitis caused by dextran sulfate sodium in mice. Author(s): First Department of Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University, Japan. Source: Ariake, K Ohkusa, T Sakurazawa, T Kumagai, J Eishi, Y Hoshi, S Yajima, T JMed-Dent-Sci. 2000 December; 47(4): 233-41 1342-8810

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Small intestinal absorption and tolerance of enteral nutrition in acute colitis. Source: Rao, S.S.C. Holdsworth, C.D. Forrest, A.R.W. Brit-Med-J. London : British Medical Association. Sept 19, 1987. volume 295 (6600) page 698. charts. 0267-0623

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Suppressive effects of a new anti-inflammatory agent, IS-741, on dextran sulfate sodium-induced experimental colitis in rats. Author(s): Department of Internal Medicine, Shiga University of Medical Science, SetaTsukinowa, Otsu, Japan. Source: Makino, Jin Andoh, Akira Hata, Kazunori Yotsuya, Shuichi Shikama, Hiroshi Araki, Yoshio Fujiyama, Yoshihide Bamba, Tadao Int-J-Mol-Med. 2002 April; 9(4): 391-6 1107-3756

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The natural plant product tryptanthrin ameliorates dextran sodium sulfate-induced colitis in mice. Author(s): Fujisaki Institute, Hayashibara Biochemical Laboratories Inc, Okayama, Japan. [email protected] Source: Micallef, M J Iwaki, K Ishihara, T Ushio, S Aga, M Kunikata, T Koya Miyata, S Kimoto, T Ikeda, M Kurimoto, M Int-Immunopharmacol. 2002 March; 2(4): 565-78 15675769

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Thumbprinting due to ischemic colitis in a patient on oral anticoagulation. Author(s): Department of Radiology, Clinique St. Elisabeth, Bruxelles. Source: Crombe, D Pringot, J Van Isveldt, J Van Campenhoudt, M JBR-BTR. 2002 AugSeptember; 85(4): 220 0302-7430

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Treating colitis. Source: Twedt, D.C. Proc-North-Am-Vet-Conf. [Gainesville, Fla.] : Eastern States Veterinary Association, 1992-. 1998. volume 12 page 318.

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Treatment of ulcerative colitis by feeding with germinated barley foodstuff: first report of a multicenter open control trial. Author(s): Nutrient Food and Feed Division, Kirin Brewery, 10-1-2 Shinkawa, Chuo-ku, Tokyo 104-8288, Japan. Source: Kanauchi, O Suga, T Tochihara, M Hibi, T Naganuma, M Homma, T Asakura, H Nakano, H Takahama, K Fujiyama, Y Andoh, A Shimoyama, T Hida, N Haruma, K Koga, H Mitsuyama, K Sata, M Fukuda, M Kojima, A Bamba, T J-Gastroenterol. 2002 November; 37 Suppl 14: 67-72 0944-1174

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Ulcerative colitis in Thailand: a clinical study and long term follow-up. Author(s): Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Source: Pongprasobchai, S Manatsathit, S Leelakusolvong, S Sattawatthamrong, Y Boonyapisit, S J-Med-Assoc-Thai. 2001 September; 84(9): 1281-8 0125-2208

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Update on medical management of inflammatory bowel disease: ulcerative colitis. Author(s): Section of Gastroenterology and Nutrition, University of Chicago, Pritzker School of Medicine, Chicago, IL, USA. Source: Hanauer, S B Rev-Gastroenterol-Disord. 2001; 1(4): 169-76 1533-001X

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Validation of a pharmacokinetic model of colon-specific drug delivery and the therapeutic effects of chitosan capsules containing 5-aminosalicylic acid on 2,4,6trinitrobenzenesulphonic acid-induced colitis in rats. Author(s): Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan. Source: Tozaki, H Fujita, T Odoriba, T Terabe, A Okabe, S Muranishi, S Yamamoto, A JPharm-Pharmacol. 1999 October; 51(10): 1107-12 0022-3573

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Variable response to probiotics in two models of experimental colitis in rats. Author(s): Department of Medicine, Hadassah University Hospital, Mount Scopus, Jerusalem. [email protected] Source: Shibolet, O Karmeli, F Eliakim, R Swennen, E Brigidi, P Gionchetti, P Campieri, M Morgenstern, S Rachmilewitz, D Inflamm-Bowel-Dis. 2002 November; 8(6): 399-406 1078-0998

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMD®Health: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to colitis; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Folic Acid Source: Healthnotes, Inc.; www.healthnotes.com Folic Acid Alternative names: Vitamin B9 (Folic Acid) Source: Integrative Medicine Communications; www.drkoop.com Vitamin a Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B9 (folic Acid) Alternative names: Folate Source: Integrative Medicine Communications; www.drkoop.com Vitamin K Source: Prima Communications, Inc.www.personalhealthzone.com

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Minerals Folate Alternative names: Vitamin B9 (Folic Acid) Source: Integrative Medicine Communications; www.drkoop.com Iron Source: Healthnotes, Inc.; www.healthnotes.com Sulfur Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com

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Food and Diet Omega-3 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com

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Saturated Fats Source: Healthnotes, Inc.; www.healthnotes.com Trans-Fats Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND COLITIS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to colitis. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to colitis and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “colitis” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to colitis: •

(51)CrEDTA colonic permeability and therapy response in patients with ulcerative colitis. Author(s): Arslan G, Atasever T, Cindoruk M, Yildirim IS. Source: Nuclear Medicine Communications. 2001 September; 22(9): 997-1001. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11505209&dopt=Abstract

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23 cases of chronic nonspecific ulcerative colitis treated by acupuncture and moxibustion. Author(s): Zhang X. Source: J Tradit Chin Med. 1998 September; 18(3): 188-91. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10453610&dopt=Abstract

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A 66-year-old woman with ulcerative colitis. Author(s): Peppercorn MA.

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Source: Jama : the Journal of the American Medical Association. 1998 March 25; 279(12): 949-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9544770&dopt=Abstract •

A different therapeutic approach in patients with severe ulcerative colitis: hyperbaric oxygen treatment. Author(s): Gurbuz AK, Elbuken E, Yazgan Y, Yildiz S. Source: Southern Medical Journal. 2003 June; 96(6): 632-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12938799&dopt=Abstract

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A double-blind, randomized, placebo-controlled trial of essential fatty acid supplementation in the maintenance of remission of ulcerative colitis. Author(s): Middleton SJ, Naylor S, Woolner J, Hunter JO. Source: Alimentary Pharmacology & Therapeutics. 2002 June; 16(6): 1131-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030955&dopt=Abstract

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A new prebiotic from germinated barley for nutraceutical treatment of ulcerative colitis. Author(s): Bamba T, Kanauchi O, Andoh A, Fujiyama Y. Source: Journal of Gastroenterology and Hepatology. 2002 August; 17(8): 818-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164955&dopt=Abstract

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A pilot trial of Saccharomyces boulardii in ulcerative colitis. Author(s): Guslandi M, Giollo P, Testoni PA. Source: European Journal of Gastroenterology & Hepatology. 2003 June; 15(6): 697-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840682&dopt=Abstract

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A randomized controlled study of evening primrose oil and fish oil in ulcerative colitis. Author(s): Greenfield SM, Green AT, Teare JP, Jenkins AP, Punchard NA, Ainley CC, Thompson RP. Source: Alimentary Pharmacology & Therapeutics. 1993 April; 7(2): 159-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8485269&dopt=Abstract

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A review of recent clinical trials of the nutritional supplement Chlorella pyrenoidosa in the treatment of fibromyalgia, hypertension, and ulcerative colitis. Author(s): Merchant RE, Andre CA. Source: Alternative Therapies in Health and Medicine. 2001 May-June; 7(3): 79-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11347287&dopt=Abstract

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Abnormal colonic accumulation of fluorine-18-FDG in pseudomembranous colitis. Author(s): Hannah A, Scott AM, Akhurst T, Berlangieri S, Bishop J, McKay WJ. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1996 October; 37(10): 1683-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8862310&dopt=Abstract

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Acetic acid-induced colitis in normal and essential fatty acid deficient rats. Author(s): Mascolo N, Izzo AA, Autore G, Maiello FM, Di Carlo G, Capasso F. Source: The Journal of Pharmacology and Experimental Therapeutics. 1995 January; 272(1): 469-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7815363&dopt=Abstract

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Allergic colitis in infancy: clinical and pathologic aspects. Author(s): Machida HM, Catto Smith AG, Gall DG, Trevenen C, Scott RB. Source: Journal of Pediatric Gastroenterology and Nutrition. 1994 July; 19(1): 22-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7965472&dopt=Abstract

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Altered expression of the Na+/H+ exchanger isoform-3 in experimental colitis: effect of garlic. Author(s): Khan I, Ali M. Source: Molecular and Cellular Biochemistry. 1999 October; 200(1-2): 77-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10569186&dopt=Abstract

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Amelioration of murine colitis by feeding a solution of lysed Escherichia coli. Author(s): Konrad A, Mahler M, Flogerzi B, Kalousek MB, Lange J, Varga L, Seibold F. Source: Scandinavian Journal of Gastroenterology. 2003 February; 38(2): 172-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678334&dopt=Abstract

•

An analysis of 10218 ulcerative colitis cases in China. Author(s): Jiang XL, Cui HF. Source: World Journal of Gastroenterology : Wjg. 2002 February; 8(1): 158-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833094&dopt=Abstract

•

An animal model of necrotizing enterocolitis induced by infant formula and ischemia in developing piglets. Author(s): Crissinger KD, Burney DL, Velasquez OR, Gonzalez E. Source: Gastroenterology. 1994 May; 106(5): 1215-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8174883&dopt=Abstract

•

An open trial of Cedemin, a Gingko biloba extract with PAF-antagonistic effects for ulcerative colitis. Author(s): Sandberg-Gertzen H.

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Source: The American Journal of Gastroenterology. 1993 April; 88(4): 615-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8470656&dopt=Abstract •

Anti-inflammatory activity of diosmin and hesperidin in rat colitis induced by TNBS. Author(s): Crespo ME, Galvez J, Cruz T, Ocete MA, Zarzuelo A. Source: Planta Medica. 1999 October; 65(7): 651-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10575379&dopt=Abstract

•

Antiinflammatory effects of Cordia myxa fruit on experimentally induced colitis in rats. Author(s): Al-Awadi FM, Srikumar TS, Anim JT, Khan I. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2001 May; 17(5): 391-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377132&dopt=Abstract

•

Arginine supplementation and the prevention of necrotizing enterocolitis in very low birth weight infants. Author(s): Neu J. Source: The Journal of Pediatrics. 2002 April; 140(4): 389-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006949&dopt=Abstract

•

Arginine supplementation prevents necrotizing enterocolitis in the premature infant. Author(s): Amin HJ, Zamora SA, McMillan DD, Fick GH, Butzner JD, Parsons HG, Scott RB. Source: The Journal of Pediatrics. 2002 April; 140(4): 425-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006956&dopt=Abstract

•

Attenuation of epithelial injury in acute experimental colitis by immunomodulators. Author(s): Higa A, McKnight GW, Wallace JL. Source: European Journal of Pharmacology. 1993 August 3; 239(1-3): 171-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7693488&dopt=Abstract

•

Bacteria as the cause of ulcerative colitis. Author(s): Campieri M, Gionchetti P. Source: Gut. 2001 January; 48(1): 132-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11115835&dopt=Abstract

•

Betel nut and smoking. Are they both protective in ulcerative colitis? A pilot study. Author(s): Lee CN, Jayanthi V, McDonald B, Probert CS, Mayberry JF. Source: Arquivos De Gastroenterologia. 1996 January-March; 33(1): 3-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8762679&dopt=Abstract


•

Biological therapies for ulcerative colitis. Author(s): Sands BE. Source: Acta Gastroenterol Belg. 2001 April-June; 64(2): 205-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11475137&dopt=Abstract

•

Bowman-Birk inhibitor concentrate reduces colon inflammation in mice with dextran sulfate sodium-induced ulcerative colitis. Author(s): Ware JH, Wan XS, Newberne P, Kennedy AR. Source: Digestive Diseases and Sciences. 1999 May; 44(5): 986-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10235608&dopt=Abstract

•

Catgut point-embedding therapy in treatment of 76 cases of ulcerative colitis. Author(s): Xiao G, Zhou G. Source: J Tradit Chin Med. 2001 June; 21(2): 116-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11498899&dopt=Abstract

•

CD26-/DPP IV-positive lymphocytes in murine acute experimental colitis. Author(s): Fatima S, Ruter J, Niess JH, Klapp BF, Arck PC, Hildebrandt M. Source: Advances in Experimental Medicine and Biology. 2003; 524: 345-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675257&dopt=Abstract

•

CD4/CD8 double-positive adult T cell leukemia with preceding cytomegaloviral gastroenterocolitis. Author(s): Ohata J, Matsuoka M, Yamashita T, Tojo A, Tani K, Asano S. Source: International Journal of Hematology. 1999 February; 69(2): 92-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10071457&dopt=Abstract

•

Chronisch-entzundliche Darmerkrankungen (Colitis ulcerosa; Enteritis regionalis Crohn): Atiologie und Therapieergebnisse unter Anwendung der bioenergetischen Funktionsdiagnostik und der Magnetfrequenzakupunktur. Author(s): Erpenbach K, Molitor H. Source: Forschende Komplementarmedizin. 1998 August; 5(4): 178-182. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9761998&dopt=Abstract

•

Clinical study on 118 cases of ulcerative colitis treated by integration of traditional Chinese and Western medicine. Author(s): Chen Q, Zhang H. Source: J Tradit Chin Med. 1999 September; 19(3): 163-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10921142&dopt=Abstract

•

Colitis and docetaxel-based chemotherapy. Author(s): Kreis W, Petrylak D, Savarese D, Budman D.

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Source: Lancet. 2000 June 17; 355(9221): 2164. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10902651&dopt=Abstract •

Colitis associated with docetaxel-based chemotherapy in patients with metastatic breast cancer. Author(s): Ibrahim NK, Sahin AA, Dubrow RA, Lynch PM, Boehnke-Michaud L, Valero V, Buzdar AU, Hortobagyi GN. Source: Lancet. 2000 January 22; 355(9200): 281-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10675076&dopt=Abstract

•

Colitis associated with docetaxel-based chemotherapy. Author(s): Sezer O, Eucker J, Possinger K. Source: Lancet. 2000 May 20; 355(9217): 1823-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10832856&dopt=Abstract

•

Colitis cystica profunda: imaging diagnosis and conservative treatment: report of two cases. Author(s): Valenzuela M, Martin-Ruiz JL, Alvarez-Cienfuegos E, Caballero AM, Gallego F, Carmona I, Rodriguez-Tellez M. Source: Diseases of the Colon and Rectum. 1996 May; 39(5): 587-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8620815&dopt=Abstract

•

Colitis ulcerosa complicated by malignant lymphoma: case report and analysis of published works. Author(s): Lenzen R, Borchard F, Lubke H, Strohmeyer G. Source: Gut. 1995 February; 36(2): 306-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7883235&dopt=Abstract

•

Colitis-related rat colon carcinogenesis induced by 1-hydroxy-anthraquinone and methylazoxymethanol acetate (Review). Author(s): Tanaka T, Kohno H, Murakami M, Shimada R, Kagami S. Source: Oncol Rep. 2000 May-June; 7(3): 501-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10767359&dopt=Abstract

•

Collagenous colitis: report of nine cases and review of the literature. Author(s): Gubbins GP, Dekovich AA, Ma CK, Batra SK. Source: Southern Medical Journal. 1991 January; 84(1): 33-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1986425&dopt=Abstract

•

Comparison of omega-3 fatty acids and sulfasalazine in ulcerative colitis. Author(s): Dichi I, Frenhane P, Dichi JB, Correa CR, Angeleli AY, Bicudo MH, Rodrigues MA, Victoria CR, Burini RC.


Source: Nutrition (Burbank, Los Angeles County, Calif.). 2000 February; 16(2): 87-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10696629&dopt=Abstract •

Cytomegalovirus colitis after administration of docetaxel-5-fluorouracil-cisplatin chemotherapy for locally advanced hypopharyngeal cancer. Author(s): Van den Brande J, Schrijvers D, Colpaert C, Vermorken JB. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 1999 November; 10(11): 1369-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10631467&dopt=Abstract

•

Dietary fiber fraction of germinated barley foodstuff attenuated mucosal damage and diarrhea, and accelerated the repair of the colonic mucosa in an experimental colitis. Author(s): Kanauchi O, Iwanaga T, Andoh A, Araki Y, Nakamura T, Mitsuyama K, Suzuki A, Hibi T, Bamba T. Source: Journal of Gastroenterology and Hepatology. 2001 February; 16(2): 160-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11207896&dopt=Abstract

•

Dietary fish oil reduces progression of chronic inflammatory lesions in a rat model of granulomatous colitis. Author(s): Vilaseca J, Salas A, Guarner F, Rodriguez R, Martinez M, Malagelada JR. Source: Gut. 1990 May; 31(5): 539-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2161781&dopt=Abstract

•

Dietary iron supplementation enhances DSS-induced colitis and associated colorectal carcinoma development in mice. Author(s): Seril DN, Liao J, Ho KL, Warsi A, Yang CS, Yang GY. Source: Digestive Diseases and Sciences. 2002 June; 47(6): 1266-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064801&dopt=Abstract

•

Dietary monounsaturated n-3 and n-6 long-chain polyunsaturated fatty acids affect cellular antioxidant defense system in rats with experimental ulcerative colitis induced by trinitrobenzene sulfonic acid. Author(s): Nieto N, Fernandez MI, Torres MI, Rios A, Suarez MD, Gil A. Source: Digestive Diseases and Sciences. 1998 December; 43(12): 2676-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9881500&dopt=Abstract

•

Dietary polyunsaturated fatty acids improve histological and biochemical alterations in rats with experimental ulcerative colitis. Author(s): Nieto N, Torres MI, Rios A, Gil A. Source: The Journal of Nutrition. 2002 January; 132(1): 11-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11773501&dopt=Abstract

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Dietary supplementation of catechins and alpha-tocopherol accelerates the healing of trinitrobenzene sulfonic acid-induced ulcerative colitis in rats. Author(s): Sato K, Kanazawa A, Ota N, Nakamura T, Fujimoto K. Source: J Nutr Sci Vitaminol (Tokyo). 1998 December; 44(6): 769-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10197308&dopt=Abstract

•

Dietary supplementation with fish oil in ulcerative colitis. Author(s): Stenson WF, Cort D, Rodgers J, Burakoff R, DeSchryver-Kecskemeti K, Gramlich TL, Beeken W. Source: Annals of Internal Medicine. 1992 April 15; 116(8): 609-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1312317&dopt=Abstract

•

Disruption of intestinal barrier function associated with experimental colitis: possible role of mast cells. Author(s): Stein J, Ries J, Barrett KE. Source: The American Journal of Physiology. 1998 January; 274(1 Pt 1): G203-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9458791&dopt=Abstract

•

Distal proctocolitis and n-3 polyunsaturated fatty acids (n-3 PUFAs): the mucosal effect in situ. Author(s): Almallah YZ, Ewen SW, El-Tahir A, Mowat NA, Brunt PW, Sinclair TS, Heys SD, Eremin O. Source: Journal of Clinical Immunology. 2000 January; 20(1): 68-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10798610&dopt=Abstract

•

Distal procto-colitis and n-3 polyunsaturated fatty acids: the mechanism(s) of natural cytotoxicity inhibition. Author(s): Almallah YZ, El-Tahir A, Heys SD, Richardson S, Eremin O. Source: European Journal of Clinical Investigation. 2000 January; 30(1): 58-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10620003&dopt=Abstract

•

Distal procto-colitis, natural cytotoxicity, and essential fatty acids. Author(s): Almallah YZ, Richardson S, O'Hanrahan T, Mowat NA, Brunt PW, Sinclair TS, Ewen S, Heys SD, Eremin O. Source: The American Journal of Gastroenterology. 1998 May; 93(5): 804-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9625132&dopt=Abstract

•

Diverticular colitis: diagnosis and management. Author(s): Rampton DS. Source: Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland. 2001 May; 3(3): 149-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12790980&dopt=Abstract


•

Diverticular disease-associated chronic colitis. Author(s): Makapugay LM, Dean PJ. Source: The American Journal of Surgical Pathology. 1996 January; 20(1): 94-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8540614&dopt=Abstract

•

Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis. Author(s): Kruis W, Schutz E, Fric P, Fixa B, Judmaier G, Stolte M. Source: Alimentary Pharmacology & Therapeutics. 1997 October; 11(5): 853-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9354192&dopt=Abstract

•

Downregulation of electroacupuncture at ST36 on TNF-alpha in rats with ulcerative colitis. Author(s): Tian L, Huang YX, Tian M, Gao W, Chang Q. Source: World Journal of Gastroenterology : Wjg. 2003 May; 9(5): 1028-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717850&dopt=Abstract

•

Drug induced lymphocytic colitis. Author(s): Beaugerie L, Luboinski J, Brousse N, Cosnes J, Chatelet FP, Gendre JP, Le Quintrec Y. Source: Gut. 1994 March; 35(3): 426-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8150360&dopt=Abstract

•

Effect of dietary n-3 fatty acids on hypoxia-induced necrotizing enterocolitis in young mice. n-3 fatty acids alter platelet-activating factor and leukotriene B4 production in the intestine. Author(s): Akisu M, Baka M, Coker I, Kultursay N, Huseyinov A. Source: Biology of the Neonate. 1998; 74(1): 31-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9657667&dopt=Abstract

•

Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. Author(s): Gomez G. Source: Gastroenterology. 1991 June; 100(6): 1789-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1859539&dopt=Abstract

•

Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. A case-control study. Author(s): Lashner BA, Heidenreich PA, Su GL, Kane SV, Hanauer SB. Source: Gastroenterology. 1989 August; 97(2): 255-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2568304&dopt=Abstract

164 Colitis

•

Effect of ingestion of eicosapentaenoic acid ethyl ester on carrageenan-induced colitis in guinea pigs. Author(s): Kitsukawa Y, Saito H, Suzuki Y, Kasanuki J, Tamura Y, Yoshida S. Source: Gastroenterology. 1992 June; 102(6): 1859-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1316857&dopt=Abstract

•

Effect of iron supplementation on oxidative stress and intestinal inflammation in rats with acute colitis. Author(s): Aghdassi E, Carrier J, Cullen J, Tischler M, Allard JP. Source: Digestive Diseases and Sciences. 2001 May; 46(5): 1088-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11341654&dopt=Abstract

•

Effect of oral iron supplementation on oxidative stress and colonic inflammation in rats with induced colitis. Author(s): Carrier J, Aghdassi E, Platt I, Cullen J, Allard JP. Source: Alimentary Pharmacology & Therapeutics. 2001 December; 15(12): 1989-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11736731&dopt=Abstract

•

Effect of polyunsaturated fatty acid (PUFA) supplementation on intestinal inflammation and necrotizing enterocolitis (NEC) in a neonatal rat model. Author(s): Caplan MS, Russell T, Xiao Y, Amer M, Kaup S, Jilling T. Source: Pediatric Research. 2001 May; 49(5): 647-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328947&dopt=Abstract

•

Effect of zinc supplementation on intestinal permeability in experimental colitis. Author(s): Sturniolo GC, Fries W, Mazzon E, Di Leo V, Barollo M, D'inca R. Source: The Journal of Laboratory and Clinical Medicine. 2002 May; 139(5): 311-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032492&dopt=Abstract

•

Effect of zinc supplementation on trace elements and intestinal metallothionein concentrations in experimental colitis in the rat. Author(s): Di Leo V, D'Inca R, Barollo M, Tropea A, Fries W, Mazzon E, Irato P, Cecchetto A, Sturniolo GC. Source: Dig Liver Dis. 2001 March; 33(2): 135-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11346141&dopt=Abstract

•

Effects of Boswellia serrata gum resin in patients with ulcerative colitis. Author(s): Gupta I, Parihar A, Malhotra P, Singh GB, Ludtke R, Safayhi H, Ammon HP. Source: European Journal of Medical Research. 1997 January; 2(1): 37-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9049593&dopt=Abstract

•

Effects of gum resin of Boswellia serrata in patients with chronic colitis. Author(s): Gupta I, Parihar A, Malhotra P, Gupta S, Ludtke R, Safayhi H, Ammon HP.


Source: Planta Medica. 2001 July; 67(5): 391-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11488449&dopt=Abstract •

Effects of n-3 polyunsaturated fatty acids and vitamin E on colonic mucosal leukotriene generation, lipid peroxidation, and microcirculation in rats with experimental colitis. Author(s): Shimizu T, Igarashi J, Ohtuka Y, Oguchi S, Kaneko K, Yamashiro Y. Source: Digestion. 2001; 63(1): 49-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11173900&dopt=Abstract

•

Effects of nitric oxide synthase inhibition or sulfasalazine on the spontaneous colitis observed in HLA-B27 transgenic rats. Author(s): Aiko S, Fuseler J, Grisham MB. Source: The Journal of Pharmacology and Experimental Therapeutics. 1998 February; 284(2): 722-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9454820&dopt=Abstract

•

Effects of silymarin on the acute stage of the trinitrobenzenesulphonic acid model of rat colitis. Author(s): Cruz T, Galvez J, Crespo E, Ocete MA, Zarzuelo A. Source: Planta Medica. 2001 February; 67(1): 94-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11270735&dopt=Abstract

•

Effects of smoking on the urine excretion of oral 51Cr EDTA in ulcerative colitis. Author(s): Benoni C, Prytz H. Source: Gut. 1998 May; 42(5): 656-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9659159&dopt=Abstract

•

Efficacy of use of colonoscopy in dextran sulfate sodium induced ulcerative colitis in rats: the evaluation of the effects of antioxidant by colonoscopy. Author(s): Ahn BO, Ko KH, Oh TY, Cho H, Kim WB, Lee KJ, Cho SW, Hahm KB. Source: International Journal of Colorectal Disease. 2001 June; 16(3): 174-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11459291&dopt=Abstract

•

Evaluation of antigenicity of germinated barley foodstuff for the treatment of ulcerative colitis in a chronic murine colitis model. Author(s): Kanauchi O, Serizawa I, Matsumura T, Fukuda Y, Satomi M. Source: International Journal of Molecular Medicine. 2001 February; 7(2): 143-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11172616&dopt=Abstract

•

Evaluation of the anti-inflammatory effect of baicalein on dextran sulfate sodiuminduced colitis in mice. Author(s): Hong T, Jin GB, Cho S, Cyong JC.

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Source: Planta Medica. 2002 March; 68(3): 268-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11914968&dopt=Abstract •

Exudative and absorptive permeability in different phases of an experimental colitis condition. Author(s): McHugh KJ, Svensjo E, Persson CG. Source: Scandinavian Journal of Gastroenterology. 1996 September; 31(9): 900-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8888438&dopt=Abstract

•

Fatal neutropenic colitis complicating successful chemotherapy for small cell lung cancer: a case report. Author(s): Stein M, Zalik M, Drumea K, Lachter J, Militianu D, Haim N. Source: Isr J Med Sci. 1995 February-March; 31(2-3): 194-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7744595&dopt=Abstract

•

Fish oil fatty acid supplementation in active ulcerative colitis: a double-blind, placebo-controlled, crossover study. Author(s): Aslan A, Triadafilopoulos G. Source: The American Journal of Gastroenterology. 1992 April; 87(4): 432-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1553930&dopt=Abstract

•

Fish oil supplementation and ulcerative colitis. Author(s): Gorson DM. Source: Annals of Internal Medicine. 1992 September 15; 117(6): 535; Author Reply 536. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1503361&dopt=Abstract

•

Fish oil-enriched diet is mucosal protective against acetic acid-induced colitis in rats. Author(s): Empey LR, Jewell LD, Garg ML, Thomson AB, Clandinin MT, Fedorak RN. Source: Canadian Journal of Physiology and Pharmacology. 1991 April; 69(4): 480-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1647851&dopt=Abstract

•

Folate supplementation in ulcerative colitis. Author(s): Ransohoff DF. Source: Gastroenterology. 1990 February; 98(2): 544. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2295414&dopt=Abstract

•

Folic acid supplementation and cell kinetics of rectal mucosa in patients with ulcerative colitis. Author(s): Biasco G, Zannoni U, Paganelli GM, Santucci R, Gionchetti P, Rivolta G, Miniero R, Pironi L, Calabrese C, Di Febo G, Miglioli M.


Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1997 June; 6(6): 469-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9184782&dopt=Abstract •

Food protein-induced enterocolitis syndrome: clinical perspectives. Author(s): Sicherer SH. Source: Journal of Pediatric Gastroenterology and Nutrition. 2000; 30 Suppl: S45-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10634298&dopt=Abstract

•

Germinated barley foodstuff, a prebiotic product, ameliorates inflammation of colitis through modulation of the enteric environment. Author(s): Kanauchi O, Serizawa I, Araki Y, Suzuki A, Andoh A, Fujiyama Y, Mitsuyama K, Takaki K, Toyonaga A, Sata M, Bamba T. Source: Journal of Gastroenterology. 2003; 38(2): 134-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640526&dopt=Abstract

•

Growth failure occurs through a decrease in insulin-like growth factor 1 which is independent of undernutrition in a rat model of colitis. Author(s): Ballinger AB, Azooz O, El-Haj T, Poole S, Farthing MJ. Source: Gut. 2000 May; 46(5): 694-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10764714&dopt=Abstract

•

Haemorrhagic colitis induced by Citrullus colocynthis. Author(s): Al Faraj S. Source: Annals of Tropical Medicine and Parasitology. 1995 December; 89(6): 695-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8745947&dopt=Abstract

•

Hemodynamic and permeability characteristics of acute experimental necrotizing enterocolitis. Author(s): Miller MJ, Adams J, Gu XA, Zhang XJ, Clark DA. Source: Digestive Diseases and Sciences. 1990 October; 35(10): 1257-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1698596&dopt=Abstract

•

Hemorrhagic colitis and pseudomelanosis coli in ipecac ingestion by proxy. Author(s): Johnson JE, Carpenter BL, Benton J, Cross R, Eaton LA Jr, Rhoads JM. Source: Journal of Pediatric Gastroenterology and Nutrition. 1991 May; 12(4): 501-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1678009&dopt=Abstract

168 Colitis

•

Hodgkin s disease with nephrotic syndrome as a complication of ulcerative colitis: case report. Author(s): Basic-Jukic N, Radman I, Roncevic T, Jakic-Razumovic J. Source: Croatian Medical Journal. 2002 October; 43(5): 573-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12402399&dopt=Abstract

•

Hyperbaric oxygen improves healing in experimental rat colitis. Author(s): Akin ML, Gulluoglu BM, Uluutku H, Erenoglu C, Elbuken E, Yildirim S, Celenk T. Source: Undersea & Hyperbaric Medicine : Journal of the Undersea and Hyperbaric Medical Society, Inc. 2002 Winter; 29(4): 279-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797669&dopt=Abstract

•

Hyperbaric oxygen therapy for severe ulcerative colitis. Author(s): Buchman AL, Fife C, Torres C, Smith L, Aristizibal J. Source: Journal of Clinical Gastroenterology. 2001 October; 33(4): 337-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588553&dopt=Abstract

•

Hyperbaric oxygen therapy in a case of post-total body irradiation colitis. Author(s): Favre C, Ventura A, Nardi M, Massimetti M, Papineschi F, Macchia P. Source: Bone Marrow Transplantation. 1998 March; 21(5): 519-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9535045&dopt=Abstract

•

Hyperbaric oxygen: a novel modality to ameliorate experimental colitis. Author(s): Rachmilewitz D, Karmeli F, Okon E, Rubenstein I, Better OS. Source: Gut. 1998 October; 43(4): 512-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9824579&dopt=Abstract

•

Hypnosis and the treatment of ulcerative colitis and Crohn's disease. Author(s): Schafer DW. Source: Am J Clin Hypn. 1997 October; 40(2): 111-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9385722&dopt=Abstract

•

Impact of parenteral n-3 fatty acids on experimental acute colitis. Author(s): Campos FG, Waitzberg DL, Habr-Gama A, Logullo AF, Noronha IL, Jancar S, Torrinhas RS, Furst P. Source: The British Journal of Nutrition. 2002 January; 87 Suppl 1: S83-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898774&dopt=Abstract

•

Impact on the composition of the faecal flora by a new probiotic preparation: preliminary data on maintenance treatment of patients with ulcerative colitis. Author(s): Venturi A, Gionchetti P, Rizzello F, Johansson R, Zucconi E, Brigidi P, Matteuzzi D, Campieri M.


Source: Alimentary Pharmacology & Therapeutics. 1999 August; 13(8): 1103-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468688&dopt=Abstract •

In vivo butyrate metabolism and colonic permeability in extensive ulcerative colitis. Author(s): Den Hond E, Hiele M, Evenepoel P, Peeters M, Ghoos Y, Rutgeerts P. Source: Gastroenterology. 1998 September; 115(3): 584-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9721155&dopt=Abstract

•

Increasing fecal butyrate in ulcerative colitis patients by diet: controlled pilot study. Author(s): Hallert C, Bjorck I, Nyman M, Pousette A, Granno C, Svensson H. Source: Inflammatory Bowel Diseases. 2003 March; 9(2): 116-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769445&dopt=Abstract

•

Inflammatory bowel disease Part 1: ulcerative colitis--pathophysiology and conventional and alternative treatment options. Author(s): Head KA, Jurenka JS. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2003 August; 8(3): 247-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12946238&dopt=Abstract

•

Influence of intravenous n-3 lipid supplementation on fatty acid profiles and lipid mediator generation in a patient with severe ulcerative colitis. Author(s): Grimminger F, Fuhrer D, Papavassilis C, Schlotzer E, Mayer K, Heuer KU, Kiss L, Walmrath D, Piberhofer S, Lubbecke F, et al. Source: European Journal of Clinical Investigation. 1993 November; 23(11): 706-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8307090&dopt=Abstract

•

Intestinal anti-inflammatory activity of morin on chronic experimental colitis in the rat. Author(s): Galvez J, Coelho G, Crespo ME, Cruz T, Rodriguez-Cabezas ME, Concha A, Gonzalez M, Zarzuelo A. Source: Alimentary Pharmacology & Therapeutics. 2001 December; 15(12): 2027-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11736735&dopt=Abstract

•

Intestinal bacteria and ulcerative colitis. Author(s): Cummings JH, Macfarlane GT, Macfarlane S. Source: Curr Issues Intest Microbiol. 2003 March; 4(1): 9-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691258&dopt=Abstract

•

Intestinal permeability to 51Cr-ethylenediaminetetraacetate in patients with ulcerative colitis. Author(s): Zuckerman MJ, Watts MT.

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Source: The American Journal of Gastroenterology. 1993 November; 88(11): 1978-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8237961&dopt=Abstract •

Irinotecan (CPT-11) induced colitis: report of a case and review of Food and Drug Administration MEDWATCH reporting. Author(s): Sears S, McNally P, Bachinski MS, Avery R. Source: Gastrointestinal Endoscopy. 1999 December; 50(6): 841-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10570349&dopt=Abstract

•

Iron supplementation increases disease activity and vitamin E ameliorates the effect in rats with dextran sulfate sodium-induced colitis. Author(s): Carrier J, Aghdassi E, Cullen J, Allard JP. Source: The Journal of Nutrition. 2002 October; 132(10): 3146-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368409&dopt=Abstract

•

Iron supplementation may aggravate inflammatory status of colitis in a rat model. Author(s): Reifen R, Matas Z, Zeidel L, Berkovitch Z, Bujanover Y. Source: Digestive Diseases and Sciences. 2000 February; 45(2): 394-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10711457&dopt=Abstract

•

Is administration of n-3 fatty acids by mucosal enema protective against trinitrobenzene-induced colitis in rats? Author(s): Yuceyar H, Ozutemiz O, Huseyinov A, Saruc M, Alkanat M, Bor S, Coker I, Batur Y. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 1999 December; 61(6): 339-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10718105&dopt=Abstract

•

Ischemic colitis and herbal treatment. Author(s): Jones GW. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2002 November-December; 15(6): 511. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12463304&dopt=Abstract

•

Ischemic colitis associated with herbal product use in a young woman. Author(s): Ryan CK, Reamy B, Rochester JA. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2002 July-August; 15(4): 309-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150465&dopt=Abstract

•

Ischemic colitis associated with paclitaxel and carboplatin chemotherapy. Author(s): Tashiro M, Yoshikawa I, Kume K, Otsuki M.


Source: The American Journal of Gastroenterology. 2003 January; 98(1): 231-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526980&dopt=Abstract •

Ischemic colitis associated with paclitaxel. Author(s): Daniele B, Rossi GB, Losito S, Gridelli C, de Bellis M. Source: Journal of Clinical Gastroenterology. 2001 August; 33(2): 159-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11468447&dopt=Abstract

•

Ispaghula husk may relieve gastrointestinal symptoms in ulcerative colitis in remission. Author(s): Hallert C, Kaldma M, Petersson BG. Source: Scandinavian Journal of Gastroenterology. 1991 July; 26(7): 747-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1654592&dopt=Abstract

•

Kui jie qing in the treatment of chronic non-specific ulcerative colitis. Author(s): Wang B, Ren S, Feng W, Zhong Z, Qin C. Source: J Tradit Chin Med. 1997 March; 17(1): 10-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10437236&dopt=Abstract

•

Lactobacillus GG prevents recurrence of colitis in HLA-B27 transgenic rats after antibiotic treatment. Author(s): Dieleman LA, Goerres MS, Arends A, Sprengers D, Torrice C, Hoentjen F, Grenther WB, Sartor RB. Source: Gut. 2003 March; 52(3): 370-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584218&dopt=Abstract

•

Lactobacillus plantarum 299V in the treatment and prevention of spontaneous colitis in interleukin-10-deficient mice. Author(s): Schultz M, Veltkamp C, Dieleman LA, Grenther WB, Wyrick PB, Tonkonogy SL, Sartor RB. Source: Inflammatory Bowel Diseases. 2002 March; 8(2): 71-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11854603&dopt=Abstract

•

Lactobacillus species prevents colitis in interleukin 10 gene-deficient mice. Author(s): Madsen KL, Doyle JS, Jewell LD, Tavernini MM, Fedorak RN. Source: Gastroenterology. 1999 May; 116(5): 1107-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10220502&dopt=Abstract

•

Long-term double-blind study on the influence of dietary fibres on faecal bile acid excretion in juvenile ulcerative colitis. Author(s): Ejderhamn J, Hedenborg G, Strandvik B.

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Source: Scandinavian Journal of Clinical and Laboratory Investigation. 1992 November; 52(7): 697-706. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1360699&dopt=Abstract •

Lycopene supplementation attenuates the inflammatory status of colitis in a rat model. Author(s): Reifen R, Nur T, Matas Z, Halpern Z. Source: Int J Vitam Nutr Res. 2001 November; 71(6): 347-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11840838&dopt=Abstract

•

Mechanisms of increased intestinal [51Cr]EDTA absorption during experimental colitis in the rat. Author(s): Pantzar N, Ekstrom GM, Wang Q, Westrom BR. Source: Digestive Diseases and Sciences. 1994 November; 39(11): 2327-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7956599&dopt=Abstract

•

Microsatellite instability in non-neoplastic mucosa of patients with ulcerative colitis: effect of folate supplementation. Author(s): Cravo ML, Albuquerque CM, Salazar de Sousa L, Gloria LM, Chaves P, Dias Pereira A, Nobre Leitao C, Quina MG, Costa Mira F. Source: The American Journal of Gastroenterology. 1998 November; 93(11): 2060-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9820373&dopt=Abstract

•

Morphologic and morphometric analyses of acetic acid-induced colitis in rats after treatment with enemas from Myracrodruon urundeuva Fr. All. (Aroeira do Sertao). Author(s): Rodrigues LV, Ferreira FV, Regadas FS, Matos D, Viana GS. Source: Phytotherapy Research : Ptr. 2002 May; 16(3): 267-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164275&dopt=Abstract

•

Morphological study on colonic pathology in ulcerative colitis treated by moxibustion. Author(s): Wu HG, Zhou LB, Shi DR, Liu SM, Liu HR, Zhang BM, Chen HP, Zhang LS. Source: World Journal of Gastroenterology : Wjg. 2000 December; 6(6): 861-865. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11819709&dopt=Abstract

•

Mucosal inflammatory cytokine production by intestinal biopsies in patients with ulcerative colitis and Crohn's disease. Author(s): Reimund JM, Wittersheim C, Dumont S, Muller CD, Baumann R, Poindron P, Duclos B. Source: Journal of Clinical Immunology. 1996 May; 16(3): 144-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8734357&dopt=Abstract


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Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis. Author(s): Yamazaki M, Yajima T, Tanabe M, Fukui K, Okada E, Okamoto R, Oshima S, Nakamura T, Kanai T, Uehira M, Takeuchi T, Ishikawa H, Hibi T, Watanabe M. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 August 1; 171(3): 1556-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874249&dopt=Abstract

•

n-3 fatty acids only delay early relapse of ulcerative colitis in remission. Author(s): Loeschke K, Ueberschaer B, Pietsch A, Gruber E, Ewe K, Wiebecke B, Heldwein W, Lorenz R. Source: Digestive Diseases and Sciences. 1996 October; 41(10): 2087-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8888725&dopt=Abstract

•

Necrotizing enterocolitis--an unconquered disease. Author(s): Singh J, Sinha S. Source: Indian Pediatrics. 2002 March; 39(3): 229-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910131&dopt=Abstract

•

Neonatal necrotizing enterocolitis: possible role of probiotic supplementation. Author(s): Caplan MS, Jilling T. Source: Journal of Pediatric Gastroenterology and Nutrition. 2000; 30 Suppl 2: S18-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10749397&dopt=Abstract

•

Neutropenic colitis as a complication of high-dose chemotherapy for refractory testicular cancer. Author(s): Kawai K, Imada S, Iida K, Tsukamoto S, Miyanaga N, Akaza H. Source: Japanese Journal of Clinical Oncology. 1998 September; 28(9): 571-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9793033&dopt=Abstract

•

Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Author(s): Rembacken BJ, Snelling AM, Hawkey PM, Chalmers DM, Axon AT. Source: Lancet. 1999 August 21; 354(9179): 635-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10466665&dopt=Abstract

•

Novel therapies in the treatment of ulcerative colitis. Author(s): Tuvlin JA, Kane SV. Source: Expert Opinion on Investigational Drugs. 2003 March; 12(3): 483-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605569&dopt=Abstract

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Nutritional regulation of porcine bacterial-induced colitis by conjugated linoleic acid. Author(s): Hontecillas R, Wannemeulher MJ, Zimmerman DR, Hutto DL, Wilson JH, Ahn DU, Bassaganya-Riera J. Source: The Journal of Nutrition. 2002 July; 132(7): 2019-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097686&dopt=Abstract

•

Nutritional therapies for ulcerative colitis: literature review, chart review study, and future research. Author(s): Edman JS, Williams WH, Atkins RC. Source: Alternative Therapies in Health and Medicine. 2000 January; 6(1): 55-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10631823&dopt=Abstract

•

Observation of the efficacy of acupuncture and moxibustion in 62 cases of chronic colitis. Author(s): Yang C, Yan H. Source: J Tradit Chin Med. 1999 June; 19(2): 111-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10681867&dopt=Abstract

•

Obstructed defecation after undiverted ileoanal pouch reconstruction for ulcerative colitis: pharmacologic approach. Report of a case. Author(s): Abbasakoor F, Evans A, Stephenson BM. Source: Diseases of the Colon and Rectum. 2000 November; 43(11): 1599-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11089600&dopt=Abstract

•

Pectin-supplemented enteral diet reduces the severity of methotrexate induced enterocolitis in rats. Author(s): Mao Y, Kasravi B, Nobaek S, Wang LQ, Adawi D, Roos G, Stenram U, Molin G, Bengmark S, Jeppsson B. Source: Scandinavian Journal of Gastroenterology. 1996 June; 31(6): 558-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8789894&dopt=Abstract

•

Plasma exudation, hyperaemia, and epithelial permeability in rats with oxazoloneinduced colitis: modulatory effects of budesonide. Author(s): Ekstrom GM, Andersson SE. Source: Scandinavian Journal of Gastroenterology. 2000 February; 35(2): 190-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10720119&dopt=Abstract

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Prebiotic treatment of experimental colitis with germinated barley foodstuff: a comparison with probiotic or antibiotic treatment. Author(s): Fukuda M, Kanauchi O, Araki Y, Andoh A, Mitsuyama K, Takagi K, Toyonaga A, Sata M, Fujiyama Y, Fukuoka M, Matsumoto Y, Bamba T.


Source: International Journal of Molecular Medicine. 2002 January; 9(1): 65-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744999&dopt=Abstract •

Prevention and reversal of experimental colitis by a monoclonal antibody which inhibits leukocyte adherence. Author(s): Wallace JL, Higa A, McKnight GW, MacIntyre DE. Source: Inflammation. 1992 August; 16(4): 343-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1326482&dopt=Abstract

•

Prevention of further recurrences of Clostridium difficile colitis with Saccharomyces boulardii. Author(s): Kimmey MB, Elmer GW, Surawicz CM, McFarland LV. Source: Digestive Diseases and Sciences. 1990 July; 35(7): 897-901. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2364845&dopt=Abstract

•

Proactive sensitizing effects of acute stress on acoustic startle responses and experimentally induced colitis in rats: relationship to corticosterone. Author(s): Milde AM, Sundberg H, Roseth AG, Murison R. Source: Stress (Amsterdam, Netherlands). 2003 March; 6(1): 49-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637207&dopt=Abstract

•

Probiotic therapy fails to improve gut permeability in a hapten model of colitis. Author(s): Kennedy RJ, Hoper M, Deodhar K, Kirk SJ, Gardiner KR. Source: Scandinavian Journal of Gastroenterology. 2000 December; 35(12): 1266-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11199365&dopt=Abstract

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Probiotic therapy with E. coli for ulcerative colitis: take the good with the bad. Author(s): Faubion WA, Sandborn WJ. Source: Gastroenterology. 2000 March; 118(3): 630-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10702217&dopt=Abstract

•

Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study. Author(s): Dani C, Biadaioli R, Bertini G, Martelli E, Rubaltelli FF. Source: Biology of the Neonate. 2002 August; 82(2): 103-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169832&dopt=Abstract

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Prophylactic effect of dietary glutamine supplementation on interleukin 8 and tumour necrosis factor alpha production in trinitrobenzene sulphonic acid induced colitis. Author(s): Ameho CK, Adjei AA, Harrison EK, Takeshita K, Morioka T, Arakaki Y, Ito E, Suzuki I, Kulkarni AD, Kawajiri A, Yamamoto S.

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Source: Gut. 1997 October; 41(4): 487-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9391247&dopt=Abstract •

Protective effect of boldine in experimental colitis. Author(s): Gotteland M, Jimenez I, Brunser O, Guzman L, Romero S, Cassels BK, Speisky H. Source: Planta Medica. 1997 August; 63(4): 311-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9270374&dopt=Abstract

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Protective effect of dietary supplementation with L-arginine and L-carnitine on hypoxia/reoxygenation-induced necrotizing enterocolitis in young mice. Author(s): Akisu M, Ozmen D, Baka M, Habif S, Yalaz M, Arslanoglu S, Kultursay N, Bayindir O. Source: Biology of the Neonate. 2002; 81(4): 260-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12011570&dopt=Abstract

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Protective effects of Polygalae root in experimental TNBS-induced colitis in mice. Author(s): Hong T, Jin GB, Yoshino G, Miura M, Maeda Y, Cho S, Cyong JC. Source: Journal of Ethnopharmacology. 2002 March; 79(3): 341-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11849839&dopt=Abstract

•

Pseudomembranous colitis in a patient treated with paclitaxel for carcinoma of the breast: a case report. Author(s): Ang P, Cheong WK, Khoo KS. Source: Ann Acad Med Singapore. 2000 January; 29(1): 132-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10748982&dopt=Abstract

•

Pseudomembranous colitis. Author(s): Aboud W, Marshall R, Berkelhammer C. Source: Gastrointestinal Endoscopy. 2000 August; 52(2): 234. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10922098&dopt=Abstract

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Pyoderma gangrenosum induced by acupuncture in a patient with ulcerative colitis. Author(s): Castro-Duran J, Martin-Armada M, Jimenez-Alonso J. Source: Archives of Internal Medicine. 2000 August 14-28; 160(15): 2394. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10927741&dopt=Abstract

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Randomized clinical trial of Plantago ovata seeds (dietary fiber) as compared with mesalamine in maintaining remission in ulcerative colitis. Spanish Group for the Study of Crohn's Disease and Ulcerative Colitis (GETECCU). Author(s): Fernandez-Banares F, Hinojosa J, Sanchez-Lombrana JL, Navarro E, Martinez-Salmeron JF, Garcia-Puges A, Gonzalez-Huix F, Riera J, Gonzalez-Lara V, Dominguez-Abascal F, Gine JJ, Moles J, Gomollon F, Gassull MA.


Source: The American Journal of Gastroenterology. 1999 February; 94(2): 427-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10022641&dopt=Abstract •

Randomized controlled trial of the effect of bifidobacteria-fermented milk on ulcerative colitis. Author(s): Ishikawa H, Akedo I, Umesaki Y, Tanaka R, Imaoka A, Otani T. Source: Journal of the American College of Nutrition. 2003 February; 22(1): 56-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569115&dopt=Abstract

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Recurrent Clostridium difficile-associated diarrhea and colitis treated with Saccharomyces cerevisiae (Baker's yeast) in combination with antibiotic therapy: a case report. Author(s): Kovacs DJ, Berk T. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2000 March-April; 13(2): 138-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10764197&dopt=Abstract

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Reduced incidence of necrotizing enterocolitis associated with enteral administration of Lactobacillus acidophilus and Bifidobacterium infantis to neonates in an intensive care unit. Author(s): Hoyos AB. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 1999 Summer; 3(4): 197-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10575148&dopt=Abstract

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Response to article by Buchman et al. Use of hyperbaric oxygenation in the treatment of ulcerative colitis. Author(s): Connor DJ, Bennett M. Source: Journal of Clinical Gastroenterology. 2002 July; 35(1): 98; Author Reply 98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12080236&dopt=Abstract

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Review article: colitis-associated cancer -- time for new strategies. Author(s): Shanahan F. Source: Alimentary Pharmacology & Therapeutics. 2003 September; 18 Suppl 2: 6-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950414&dopt=Abstract

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Role of inducible nitric oxide synthase in trinitrobenzene sulphonic acid induced colitis in mice. Author(s): McCafferty DM, Miampamba M, Sihota E, Sharkey KA, Kubes P. Source: Gut. 1999 December; 45(6): 864-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10562585&dopt=Abstract

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Rutoside as mucosal protective in acetic acid-induced rat colitis. Author(s): Galvez J, Cruz T, Crespo E, Ocete MA, Lorente MD, Sanchez de Medina F, Zarzuelo A. Source: Planta Medica. 1997 October; 63(5): 409-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9342943&dopt=Abstract

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Saccharomyces boulardii for the treatment of Clostridium difficile-associated colitis. Author(s): Eddy JT, Stamatakis MK, Makela EH. Source: The Annals of Pharmacotherapy. 1997 July-August; 31(7-8): 919-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9220059&dopt=Abstract

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Saccharomyces boulardii: a possible addition to the standard treatment and prophylaxis of enterocolitis in Hirschsprung's disease ? Author(s): Herek O. Source: Pediatric Surgery International. 2002 September; 18(5-6): 567. Epub 2002 September 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415416&dopt=Abstract

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Serum bile acids in relation to disease activity and intake of dietary fibers in juvenile ulcerative colitis. Author(s): Ejderhamn J, Strandvik B. Source: Digestion. 1991; 50(3-4): 162-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1667392&dopt=Abstract

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Shark fin enriched diet prevents mucosal lipid abnormalities in experimental acute colitis. Author(s): Marotta F, Chui DH, Safran P, Rezakovic I, Zhong GG, Ideo G. Source: Digestion. 1995; 56(1): 46-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7895932&dopt=Abstract

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Should folic acid supplementation be used to reduce the risk of cancer in ulcerative colitis? Author(s): Williams CN. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 1999 November; 13(9): 715-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10633822&dopt=Abstract

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Study of the mechanisms of acupuncture and moxibustion treatment for ulcerative colitis rats in view of the gene expression of cytokines. Author(s): Wu HG, Zhou LB, Pan YY, Huang C, Chen HP, Shi Z, Hua XG. Source: World Journal of Gastroenterology : Wjg. 1999 December; 5(6): 515-517. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11819501&dopt=Abstract


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Successful conservative treatment of neutropenic enterocolitis complicating taxanebased chemotherapy: a report of five cases. Author(s): Kouroussis C, Samonis G, Androulakis N, Souglakos J, Voloudaki A, Dimopoulos MA, Kotsakis T, Kakolyris S, Kalbakis K, Georgoulias V. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2000 June; 23(3): 309-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10857900&dopt=Abstract

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Suppression of dextran sodium sulfate-induced colitis in mice by zerumbone, a subtropical ginger sesquiterpene, and nimesulide: separately and in combination. Author(s): Murakami A, Hayashi R, Takana T, Kwon KH, Ohigashi H, Safitri R. Source: Biochemical Pharmacology. 2003 October 1; 66(7): 1253-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14505804&dopt=Abstract

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Surgical Therapy for Colitis Cystica Profunda and Solitary Rectal Ulcer Syndrome. Author(s): Beck DE. Source: Current Treatment Options in Gastroenterology. 2002 June; 5(3): 231-237. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003718&dopt=Abstract

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TCM differential treatment of 57 cases of chronic gastritis complicated by ulcerative colitis. Author(s): Meng M. Source: J Tradit Chin Med. 1999 March; 19(1): 10-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10453577&dopt=Abstract

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The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis. Author(s): Lashner BA, Provencher KS, Seidner DL, Knesebeck A, Brzezinski A. Source: Gastroenterology. 1997 January; 112(1): 29-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8978339&dopt=Abstract

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The effect of Oren-gedoku-to on experimental colitis in rats. Author(s): Zhou H, Mineshita S. Source: The Journal of Pharmacy and Pharmacology. 1999 September; 51(9): 1065-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10528991&dopt=Abstract

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The natural plant product tryptanthrin ameliorates dextran sodium sulfate-induced colitis in mice. Author(s): Micallef MJ, Iwaki K, Ishihara T, Ushio S, Aga M, Kunikata T, Koya-Miyata S, Kimoto T, Ikeda M, Kurimoto M. Source: International Immunopharmacology. 2002 March; 2(4): 565-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11962735&dopt=Abstract

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The role of marine fish oils in the treatment of ulcerative colitis. Author(s): Ross E. Source: Nutrition Reviews. 1993 February; 51(2): 47-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8455803&dopt=Abstract

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The role of polyunsaturated fatty acid supplementation in intestinal inflammation and neonatal necrotizing enterocolitis. Author(s): Caplan MS, Jilling T. Source: Lipids. 2001 September; 36(9): 1053-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11724457&dopt=Abstract

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The X-ray contrast medium iodixanol detects increased colonic permeability equally well as 51Cr-labeled ethylenediaminetetraacetic acid in experimental colitis of rats. Author(s): Andersen R, Hosaka J, Halstensen TS, Stordahl A, Tverdal A, Aabakken L, Laerum F. Source: Scandinavian Journal of Gastroenterology. 1996 February; 31(2): 140-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8658036&dopt=Abstract

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Therapeutic efficacy of hyperbaric oxygenation in ulcerative colitis refractory to medical treatment. Author(s): Demirturk L, Ozel M, Yazgan Y, Buchman AL. Source: Journal of Clinical Gastroenterology. 2002 September; 35(3): 286-7; Author Reply 287-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192213&dopt=Abstract

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Therapeutic potential of fish oil in the treatment of ulcerative colitis. Author(s): McCall TB, O'Leary D, Bloomfield J, O'Morain CA. Source: Alimentary Pharmacology & Therapeutics. 1989 October; 3(5): 415-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2562385&dopt=Abstract

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To make a difference: the founding of the Crohn's and Colitis Foundation of America. Author(s): Rosenthal S. Source: The Mount Sinai Journal of Medicine, New York. 2001 March; 68(2): 113-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11268151&dopt=Abstract

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Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Author(s): Steidler L, Hans W, Schotte L, Neirynck S, Obermeier F, Falk W, Fiers W, Remaut E. Source: Science. 2000 August 25; 289(5483): 1352-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10958782&dopt=Abstract


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Treatment of recurrent Clostridium difficile colitis with vancomycin and Saccharomyces boulardii. Author(s): Surawicz CM, McFarland LV, Elmer G, Chinn J. Source: The American Journal of Gastroenterology. 1989 October; 84(10): 1285-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2679049&dopt=Abstract

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Treatment of ulcerative colitis using fecal bacteriotherapy. Author(s): Borody TJ, Warren EF, Leis S, Surace R, Ashman O. Source: Journal of Clinical Gastroenterology. 2003 July; 37(1): 42-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811208&dopt=Abstract

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Treatment of ulcerative colitis with acupuncture. Author(s): Chen Z. Source: J Tradit Chin Med. 1995 September; 15(3): 231-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8569266&dopt=Abstract

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Treatment of ulcerative colitis with fish oil n--3-omega-fatty acid: an open trial. Author(s): Salomon P, Kornbluth AA, Janowitz HD. Source: Journal of Clinical Gastroenterology. 1990 April; 12(2): 157-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2109004&dopt=Abstract

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Treatment of ulcerative colitis with fish oil supplementation: a prospective 12 month randomised controlled trial. Author(s): Hawthorne AB, Daneshmend TK, Hawkey CJ, Belluzzi A, Everitt SJ, Holmes GK, Malkinson C, Shaheen MZ, Willars JE. Source: Gut. 1992 July; 33(7): 922-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1353742&dopt=Abstract

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Treatment of ulcerative colitis with germinated barley foodstuff feeding: a pilot study. Author(s): Mitsuyama K, Saiki T, Kanauchi O, Iwanaga T, Tomiyasu N, Nishiyama T, Tateishi H, Shirachi A, Ide M, Suzuki A, Noguchi K, Ikeda H, Toyonaga A, Sata M. Source: Alimentary Pharmacology & Therapeutics. 1998 December; 12(12): 1225-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9882030&dopt=Abstract

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Typhlitis (neutropenic enterocolitis) after a single dose of vinorelbine. Author(s): Ferrazzi E, Toso S, Zanotti M, Giuliano G. Source: Cancer Chemotherapy and Pharmacology. 2001 March; 47(3): 277-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11320673&dopt=Abstract

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Ulcerative colitis in the Kinneret sub district, Israel 1965-1994: incidence and prevalence in different subgroups. Author(s): Shapira M, Tamir A.

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Source: Journal of Clinical Gastroenterology. 1998 September; 27(2): 134-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9754774&dopt=Abstract •

Ulmus macrocarpa hance for the treatment of ulcerative colitis--a report of 36 cases. Author(s): Ye G, Cao Q, Chen X, Li S, Jia B. Source: J Tradit Chin Med. 1990 June; 10(2): 97-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2392003&dopt=Abstract

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Update on medical management of inflammatory bowel disease: ulcerative colitis. Author(s): Hanauer SB. Source: Reviews in Gastroenterological Disorders. 2001; 1(4): 169-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120183&dopt=Abstract

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Use of bromelain for mild ulcerative colitis. Author(s): Kane S, Goldberg MJ. Source: Annals of Internal Medicine. 2000 April 18; 132(8): 680. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10766699&dopt=Abstract

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Use of the 'nutriceutical', bovine colostrum, for the treatment of distal colitis: results from an initial study. Author(s): Khan Z, Macdonald C, Wicks AC, Holt MP, Floyd D, Ghosh S, Wright NA, Playford RJ. Source: Alimentary Pharmacology & Therapeutics. 2002 November; 16(11): 1917-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390100&dopt=Abstract

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Variable response to probiotics in two models of experimental colitis in rats. Author(s): Shibolet O, Karmeli F, Eliakim R, Swennen E, Brigidi P, Gionchetti P, Campieri M, Morgenstern S, Rachmilewitz D. Source: Inflammatory Bowel Diseases. 2002 November; 8(6): 399-406. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454615&dopt=Abstract

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Vinorelbine and ischaemic colitis. Author(s): Olithselvan A, Gorard DA. Source: Clin Oncol (R Coll Radiol). 2003 May; 15(3): 166-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801059&dopt=Abstract

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Wheat grass juice in the treatment of active distal ulcerative colitis: a randomized double-blind placebo-controlled trial. Author(s): Ben-Arye E, Goldin E, Wengrower D, Stamper A, Kohn R, Berry E. Source: Scandinavian Journal of Gastroenterology. 2002 April; 37(4): 444-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11989836&dopt=Abstract


Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMD®Health: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to colitis; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Abdominal Wall Inflammation Source: Integrative Medicine Communications; www.drkoop.com Colon Cancer Source: Healthnotes, Inc.; www.healthnotes.com Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Crohn's Disease Source: Healthnotes, Inc.; www.healthnotes.com Erythema Source: Integrative Medicine Communications; www.drkoop.com Food Poisoning Source: Integrative Medicine Communications; www.drkoop.com

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High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com High Homocysteine Source: Healthnotes, Inc.; www.healthnotes.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com Inflammatory Bowel Disease Source: Healthnotes, Inc.; www.healthnotes.com Inflammatory Bowel Disease Source: Integrative Medicine Communications; www.drkoop.com Irritable Bowel Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Malabsorption Source: Healthnotes, Inc.; www.healthnotes.com Peptic Ulcer Source: Integrative Medicine Communications; www.drkoop.com Peritonitis Source: Integrative Medicine Communications; www.drkoop.com Proctitis Source: Integrative Medicine Communications; www.drkoop.com Rectal Inflammation Source: Integrative Medicine Communications; www.drkoop.com Rubella Source: Integrative Medicine Communications; www.drkoop.com Ulcerative Colitis Source: Healthnotes, Inc.; www.healthnotes.com Ulcerative Colitis Source: Integrative Medicine Communications; www.drkoop.com •

Alternative Therapy Colon Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,682,00.html Homeopathy Source: Integrative Medicine Communications; www.drkoop.com


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Chinese Medicine Beidougen Alternative names: Asiatic Moonseed Rhizome; Rhizoma Menispermi Source: Chinese Materia Medica Dijincao Alternative names: Creeping Euphorbia; Herba Euphorbiae Humifusae Source: Chinese Materia Medica Kumu Alternative names: Indian Quassiawood; Ramulus et Folium Picrasmae Source: Chinese Materia Medica

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Herbs and Supplements Acidophilus and Other Probiotics Source: Prima Communications, Inc.www.personalhealthzone.com Aloe Alternative names: Aloe vera, Aloe barbadensis Source: Healthnotes, Inc.; www.healthnotes.com Aloe Alternative names: Aloe vera, Aloe barbadensis, Aloe ferox , Aloe Vera Source: Integrative Medicine Communications; www.drkoop.com Aloe Vera Source: Integrative Medicine Communications; www.drkoop.com Aloe Vera Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10001,00.html Aminoglycoside Antibiotics Source: Healthnotes, Inc.; www.healthnotes.com Amoxicillin Source: Healthnotes, Inc.; www.healthnotes.com Ampicillin Source: Healthnotes, Inc.; www.healthnotes.com Antibiotics Source: Healthnotes, Inc.; www.healthnotes.com Azithromycin Source: Healthnotes, Inc.; www.healthnotes.com Blue-green Algae Source: Integrative Medicine Communications; www.drkoop.com

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Boswellia Alternative names: Frankincense; Boswellia serrata Roxb. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Boswellia Alternative names: Boswellia serrata Source: Healthnotes, Inc.; www.healthnotes.com Boswellia Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,759,00.html Calendula Alternative names: Calendula officinalis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Calendula Alternative names: Calendula officinalis Source: Healthnotes, Inc.; www.healthnotes.com Caprylic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10111,00.html Cascara Sagrada Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10013,00.html Cephalosporins Source: Healthnotes, Inc.; www.healthnotes.com Chamomile Alternative names: Matricaria recutita Source: Healthnotes, Inc.; www.healthnotes.com Chlorhexidine Source: Healthnotes, Inc.; www.healthnotes.com Ciprofloxacin Source: Healthnotes, Inc.; www.healthnotes.com Clarithromycin Source: Healthnotes, Inc.; www.healthnotes.com Clindamycin Oral Source: Healthnotes, Inc.; www.healthnotes.com Clindamycin Topical Source: Healthnotes, Inc.; www.healthnotes.com


Collinsonia Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Comfrey Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Corticosteroids Source: Healthnotes, Inc.; www.healthnotes.com Culver's Root Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Dapsone Source: Healthnotes, Inc.; www.healthnotes.com Dehydroepiandrosterone (dhea) Source: Integrative Medicine Communications; www.drkoop.com Dhea Source: Integrative Medicine Communications; www.drkoop.com Dicloxacillin Source: Healthnotes, Inc.; www.healthnotes.com Digestive Enzymes Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10051,00.html Dioscorea Villosa Source: Integrative Medicine Communications; www.drkoop.com Doxycycline Source: Healthnotes, Inc.; www.healthnotes.com Eicosapentaenoic Acid (epa) Source: Integrative Medicine Communications; www.drkoop.com Epa Source: Integrative Medicine Communications; www.drkoop.com Erythromycin Source: Healthnotes, Inc.; www.healthnotes.com Evening Primrose Alternative names: Oenothera biennis, Sun Drop Source: Integrative Medicine Communications; www.drkoop.com

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Foeniculum Alternative names: Fennel; Foeniculum vulgare Mill Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Gentamicin Source: Healthnotes, Inc.; www.healthnotes.com Ginger Alternative names: Zingiber officinale Source: Integrative Medicine Communications; www.drkoop.com Glutamine Source: Prima Communications, Inc.www.personalhealthzone.com Glutamine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10030,00.html Golden Seal Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Green-lipped Mussel Source: Healthnotes, Inc.; www.healthnotes.com Herbal Digestive Formula Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10104,00.html Hops Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Ispaghula Source: Integrative Medicine Communications; www.drkoop.com L. Acidophilus Alternative names: Lactobacillus Acidophilus Source: Integrative Medicine Communications; www.drkoop.com Lactobacillus Acidophilus Alternative names: L. Acidophilus Source: Integrative Medicine Communications; www.drkoop.com Levofloxacin Source: Healthnotes, Inc.; www.healthnotes.com Licorice Alternative names: Glycyrrhiza glabra, Glycyrrhiza uralensis Source: Healthnotes, Inc.; www.healthnotes.com


Licorice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,801,00.html Loracarbef Source: Healthnotes, Inc.; www.healthnotes.com Macrolides Source: Healthnotes, Inc.; www.healthnotes.com Marshmallow Alternative names: Althea officinalis Source: Healthnotes, Inc.; www.healthnotes.com Marshmallow Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Mesalamine Source: Healthnotes, Inc.; www.healthnotes.com Methotrexate Source: Healthnotes, Inc.; www.healthnotes.com Metronidazole Source: Healthnotes, Inc.; www.healthnotes.com Minocycline Source: Healthnotes, Inc.; www.healthnotes.com Myrrh Alternative names: Commiphora molmol Source: Healthnotes, Inc.; www.healthnotes.com Neomycin Source: Healthnotes, Inc.; www.healthnotes.com Nitrofurantoin Source: Healthnotes, Inc.; www.healthnotes.com Oenothera Biennis Source: Integrative Medicine Communications; www.drkoop.com Ofloxacin Source: Healthnotes, Inc.; www.healthnotes.com Oral Corticosteroids Source: Healthnotes, Inc.; www.healthnotes.com Penicillin V Source: Healthnotes, Inc.; www.healthnotes.com

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Penicillins Source: Healthnotes, Inc.; www.healthnotes.com Plantago Isphagula Source: Integrative Medicine Communications; www.drkoop.com Plantago Psyllium Alternative names: Psyllium, Ispaghula; Plantago psyllium/ovata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Potentilla Alternative names: Cinquefoil, Silverweed; Potentilla sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Prickly Ash Alternative names: Zanthoxylum clava-herculis, Zanthoxylum americanum Source: Healthnotes, Inc.; www.healthnotes.com Probiotics Source: Healthnotes, Inc.; www.healthnotes.com Psyllium Alternative names: Plantago ovata, Plantago ispaghula Source: Healthnotes, Inc.; www.healthnotes.com Psyllium Alternative names: Ispaghula,Plantago isphagula Source: Integrative Medicine Communications; www.drkoop.com Quinolones Source: Healthnotes, Inc.; www.healthnotes.com Royal Jelly Source: Healthnotes, Inc.; www.healthnotes.com Sambucus Alternative names: Black Elderberry; Sambucus nigra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Senna Alternative names: Cassia senna, Cassia angustifolia Source: Healthnotes, Inc.; www.healthnotes.com Slippery Elm Source: Prima Communications, Inc.www.personalhealthzone.com Slippery Elm Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10056,00.html


Spirulina Alternative names: Blue-green Algae Source: Integrative Medicine Communications; www.drkoop.com St. John’s Wort Alternative names: Hypericum perforatum Source: Healthnotes, Inc.; www.healthnotes.com Sulfamethoxazole Source: Healthnotes, Inc.; www.healthnotes.com Sulfasalazine Source: Healthnotes, Inc.; www.healthnotes.com Sulfonamides Source: Healthnotes, Inc.; www.healthnotes.com Sun Drop Source: Integrative Medicine Communications; www.drkoop.com Taraxacum Alternative names: Dandelion; Taraxacum officinale (Dhudhal) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tetracycline Source: Healthnotes, Inc.; www.healthnotes.com Tetracyclines Source: Healthnotes, Inc.; www.healthnotes.com Tobramycin Source: Healthnotes, Inc.; www.healthnotes.com Trimethoprim Source: Healthnotes, Inc.; www.healthnotes.com Trimethoprim/sulfamethoxazole Source: Healthnotes, Inc.; www.healthnotes.com Wild Yam Alternative names: Dioscorea villosa Source: Integrative Medicine Communications; www.drkoop.com Yarrow Alternative names: Achillea millefolium Source: Healthnotes, Inc.; www.healthnotes.com Zingiber Officinale Source: Integrative Medicine Communications; www.drkoop.com

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General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON COLITIS Overview In this chapter, we will give you a bibliography on recent dissertations relating to colitis. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “colitis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on colitis, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Colitis ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to colitis. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Characterization of Genomic Instability in Neoplastic Progression of Ulcerative Colitis by Chen, Ru; Phd from University of Washington, 2002, 162 pages http://wwwlib.umi.com/dissertations/fullcit/3062927

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Development of a Model for Experimental Colitis in the Rat and Cat Using Acetic Acid by Macpherson, Brian Roger; Phd from Memorial University of Newfoundland (canada), 1978 http://wwwlib.umi.com/dissertations/fullcit/NK36906

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Expression of Glutathione-s-transferase A4-4 in Human Colon Tissues with Colitis and in Cultured Human Enterocytes (caco-2) by Ortegon Forero, Hernan; Msc from University of Guelph (canada), 2002, 106 pages http://wwwlib.umi.com/dissertations/fullcit/MQ71209

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•

The Role of Inflammatory Mediator Cells in the Pathogenesis of Colitis in Experimental Animal Models by Flanigan, Anne; Phd from Mcp Hahnemann University, 2002, 87 pages http://wwwlib.umi.com/dissertations/fullcit/3043448

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Ulcerative Colitis-associated Colorectal Carcinogenesis: the Role of Iron Supplementation and Mechanisms Involved by Seril, Darren Neil; Phd from Rutgers the State U. of N.j. - New Brunswick and U.m.d.n.j., 2002, 173 pages http://wwwlib.umi.com/dissertations/fullcit/3066775

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. CLINICAL TRIALS AND COLITIS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning colitis.

Recent Trials on Colitis The following is a list of recent trials dedicated to colitis.8 Further information on a trial is available at the Web site indicated. •

A Randomized Trial of Rosiglitazone for Ulcerative Colitis Condition(s): Ulcerative Colitis; Inflammatory Bowel Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); GlaxoSmithKline Purpose - Excerpt: This is a multicenter, randomized, double-blind, placebo-controlled study evaluating rosiglitazone: 4 mg tablets or placebo tablets administered orally twice daily for 12 weeks. The purpose of the study is to evaluate the efficacy and safety of rosiglitazone in the treatment of mild to moderately active ulcerative colitis. Disease activity will be measured using a standard disease activity index. Calculation of the index requires patients to undergo flexible sigmoidoscopy at the start of the study and at week 12. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065065

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Clotrimazole Enemas for Pouchitis in Children and Adults Condition(s): Ulcerative Colitis; Pouchitis; Ileitis; Inflammatory Bowel Disease

8

These are listed at www.ClinicalTrials.gov.

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Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development Purpose - Excerpt: Colectomy with creation of an ileal pouch (IPAA) is now the treatment of choice for patients with ulcerative colitis that is resistant to existing medical therapies. The development of inflammation in these ileal reservoirs, a clinical entity referred to as pouchitis, is the most common long-term complication of this procedure and can affect 50-60% of adults and children. We have previously demonstrated that clotrimazole (delivered as a rectal suppository) is generally safe, effective, and displays poor systemic absorption when used in pediatric and adults with active pouchitis. We saw clinical benefit in patients with pouch disease that had previously failed to respond to standard antibiotic, steroid, or immunosuppressive therapies. The clinical trial outlined here will define the effectiveness and safety of topical clotrimazole therapy (delivered as a rectal enema) in pediatric (aged greater than two years) and adult patients with pouchitis. Subjects in this study will be randomly assigned to receive either placebo (no active drug, 4 subjects) or one of two clotrimazole therapy groups: 2500 mg/day (8 subjects) or 4000mg/day (8 subjects). No washout period is required, and subjects will be allowed to continue their existing antiinflammatory medications during their participation in the study. Clotrimazole will be delivered nightly in the form of an enema. Subjects will undergo flexible sigmoidoscopy (pouchoscopy) prior to and again after completing one month of study therapy, and pouch disease activity will be graded at after each procedure using the Pouchitis Disease Activity Index (PDAI). Clinical improvement will be defined as a drop in PDAI score. If the drop in PDAI scores between placebo and either active clotrimazole treatment group is not significant, and no subject experiences what are determined to be study-related adverse effects, a second cohort of subjects will be recruited and studied after receiving one month of either placebo (4 subjects), 6000 mg/day clotrimazole (8 subjects), or 7500mg/day clotrimazole (8 subjects). Subjects will be assessed for adverse effects at the midpoint of the study. Clotrimazole blood levels will be measured during the first and last day of study participation. In addition, adults will complete a health related quality of life assessment at baseline and after completing study drug therapy. All subjects will be eligible for one month of open-label study drug therapy after completing one month of study drug therapy. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061282 •

FACTS I: A Study to Test the Safety and Effectiveness of a New Medication on the Treatment of Active Ulcerative Colitis Condition(s): Ulcerative Colitis Study Status: This study is currently recruiting patients. Sponsor(s): Otsuka Maryland Research Institute Purpose - Excerpt: The purpose of this study is to evaluate the safety and efficacy of the drug OPC-6535 compared to a placebo in patients with active Ulcerative Colitis. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/show/NCT00064441 •

FACTS II: A Study to Test the Safety and Effectiveness of a New Medication on the Treatment of Active Ulcerative Colitis Condition(s): Ulcerative Colitis Study Status: This study is currently recruiting patients. Sponsor(s): Otsuka Maryland Research Institute Purpose - Excerpt: The purpose of this study is to evaluate the safety and efficacy of the drug OPC-6535 compared to a placebo in patients with active Ulcerative Colitis. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00064454

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Humanized anti-IL-2 receptor monoclonal antibody in moderate-to-severe ulcerative colitis Condition(s): Ulcerative Colitis; Gastrointestinal Disease; Inflammatory Bowel Disease Study Status: This study is currently recruiting patients. Sponsor(s): Protein Design Labs Purpose - Excerpt: The purpose of The PROSPECT Study is to evaluate an investigational medication for the treatment of moderate to severe ulcerative colitis. This study is being conducted at up to 38 clinical research centers in the US, Canada, and Belgium, and is open to male and female patients 12 years and older. Participants in the study will have a number of visits to a research center over a five-month period. All study related care and medication is provided to qualified participants at no cost: this includes all visits, examinations, and laboratory work. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00073047

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Immune Regulation in Ulcerative Colitis or Crohn's Disease Condition(s): Crohn's Disease; Inflammatory Bowel Disease; Ulcerative Colitis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will investigate in patients with Crohn's disease and ulcerative colitis how the body's immune system controls inflammation in the gastrointestinal tract (stomach and intestines)-specifically, how lymphocytes (a type of white blood cell) function in inflammatory responses. This protocol does not involve any experimental treatments. Patients between the ages of 8 and 75 years of age with Crohn's disease or ulcerative colitis or symptoms of inflammatory bowel disease may be eligible for this study. Screening tests may include the following: medical history and physical examination, routine blood tests, examination of stool specimens, X-rays such as barium enema or upper GI series, proctosigmoidoscopy, colonoscopy,

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gastroduodenoscopy, and small bowel biopsy. Participants will receive medical treatment according to the best generally accepted measures for treating Crohn's disease or ulcerative colitis. This may include anti-inflammatory drugs, immunosuppressive drugs, and antibiotics to treat infections. A surgical consultation may be recommended for patients whose disease does not respond to medical treatment. If surgery to remove intestinal tissue is recommended, a qualified gastrointestinal surgeon will perform the procedure. In addition, participants may undergo the following procedures: - Blood drawing - No more than 450 milliliters (30 tablespoons, or 15 ounces) of blood will be taken from adults over a 6-week period. A maximum of 7 ml (1/2 tablespoon) of blood per kilogram (2.2. pounds) of body weight will be obtained from children within the same time period, with no more than 3 ml/kg taken at any one time. - Leukapheresis This procedure is done to collect large quantities of white blood cells. Whole blood is collected through a needle in an arm vein, similar to donating blood. The blood is circulated through a machine that separates it into its components, and the white cells are removed. The rest of the blood is returned to the body, either through the same needle or through another needle in the other arm. - Intestinal biopsies - Intestinal tissue will be obtained during colonoscopy with intestinal biopsy in patients who require this procedure as part of their standard medical care. Patients are given a sedative to reduce anxiety, but are conscious during the procedure. A flexible tube is inserted into the rectum and large intestine, allowing the physician to see the intestinal mucosa. At various places, small pieces of tissue are plucked out. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001184 •

Interferon-beta Treatment of Ulcerative Colitis Condition(s): Ulcerative Colitis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will evaluate the safety and effectiveness of the drug interferon-beta in treating ulcerative colitis and examine the drug's effect on the immune system. People with ulcerative colitis have increased amounts of inflammatory chemicals (cytokines) made by immune cells in the lining of the colon. Studies have shown that interferon-beta may block the activity of these cytokines. Interferon-beta is currently FDA-approved to treat multiple sclerosis, a disease involving inflammation of the brain and spinal cord. Patients 18 years of age and older who have had ulcerative colitis for at least 4 months may be eligible for this study. Candidates will be screened with a review of their medical records, a medical history and physical examination, electrocardiogram (EKG), blood, urine, and stool tests, and a pregnancy test for women of childbearing potential. A colonoscopy will also be done to determine disease activity and extent. This test uses a lighted tube to examine the amount of inflammation in the colon and take tissue samples (biopsies) for testing. Before the test, the patient is given a medicine to allay anxiety and the discomfort of inserting the endoscope into the rectum. This flexible tube allows the doctor to see the intestinal mucosa and project an image of the inner lining of the intestine onto a TV monitor. At various places in the intestine, small pieces of tissue are plucked out by a special device at the tip of the endoscope. The procedure generally lasts 30 minutes to 1 hour. Participants will come to the NIH Clinical Center once a week for 4 weeks to receive an injection of interferon-beta, fill out questionnaires, and have a symptoms check, physical examination, and blood tests.

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Patients whose colitis has not worsened at the end of the 4 weeks and who have not had significant drug side effects will continue to receive weekly injections for an additional 8 weeks. Some patients may receive some of the last eight injections outside of NIH, but all patients will visit the Clinical Center visits every 3 to 4 weeks for a physical exam, symptoms check and blood tests. After the 12 injections are completed, patients will have another colonoscopy to evaluate the response to treatment and will return to the Clinical Center every 6 weeks for a total of four visits, for a physical examination, symptoms check and blood tests. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048347 •

ISIS 2302-CS22, A 6-Week, Active-Controlled Clinical Study to Evaluate the Effectiveness of Alicaforsen (ISIS 2302) in Patients with Mild to Moderate Active Ulcerative Colitis Condition(s): Ulcerative Colitis Study Status: This study is currently recruiting patients. Sponsor(s): Isis Pharmaceuticals Purpose - Excerpt: This is a multi-center trial to test the safety, efficacy and tolerability of alicaforsen (ISIS 2302), a new type of drug called an antisense drug, in patients with mild to moderate active Ulcerative Colitis (UC). Alicaforsen is designed to reduce the production of a specific protein, called ICAM-1, a substance that plays a significant role in the increase of inflammation and is likely to be involved in inflammatory bowel diseases such as ulcerative colitis. The ISIS 2302-CS22 study will examine the effects of one of two dosages of alicaforsen delivered by enema over a six-week period as compared to an active control, mesalamine enema (The probability of receiving the alicaforsen formulation is 2:1). The primary objective of this study is to evaluate the percentage reduction in DAI at Week 6. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063414

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ISIS 2302-CS27, A 6-Week, Placebo-Controlled Clinical Study to Evaluate the Effectiveness of Alicaforsen (ISIS 2302) in Patients with Mild to Moderate Active Ulcerative Colitis. Condition(s): Ulcerative Colitis Study Status: This study is currently recruiting patients. Sponsor(s): Isis Pharmaceuticals Purpose - Excerpt: This is a multi-center trial in the US and Europe to test the safety, efficacy and tolerability of alicaforsen (ISIS 2302), a new type of drug called an antisense drug, in patients with mild to moderate active Ulcerative Colitis (UC). Alicaforsen is designed to reduce the production of a specific protein, called ICAM-1, a substance that plays a significant role in the increase of inflammation and is likely to be involved in

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inflammatory bowel diseases such as ulcerative colitis. The ISIS 2302-CS27 study will compare four dosing regimens and determine the minimum effective dose of alicaforsen enema in UC patients over six weeks as compared to a placebo enema. (The probability of receiving active formulation is 4:1). The primary objective of this study is to evaluate the percentage reduction in DAI at Week 6. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063830 •

Left-Sided Ulcerative Colitis Study Condition(s): Ulcerative Colitis Study Status: This study is currently recruiting patients. Sponsor(s): Wyeth-Ayerst Research Purpose - Excerpt: To explore the safety of orally delivered rhIL-11 in patients with mild to moderate left-sided ulcerative colitis. To explore the effects of orally administered rhIL-11 on pharmacogenomics in blood samples and in colonic biopsy tissue samples. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00038922

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Quality of Life in Pediatric Inflammatory Bowel Disease Condition(s): Crohn's Disease; Ulcerative Colitis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Measurement of the quality of life (QoL) of children and adolescents with inflammatory bowel diseases (IBD) has had little attention, despite the importance of understanding key factors affecting QoL, especially for measuring the effects of clinical trials to improve IBD outcomes. The main purpose of this pilot study is to examine the impact of clinical severity and treatment social factors on the quality of life (QoL) of a diverse population of children and adolescents with inflammatory bowel disease (IBD). Secondary purposes include determining the effects of sociodemographic factors on QoL and exploring the concordance of views of parents and children of QoL. The study aims are to 1) determine the associations of of clinical characteristics (condition type, activity/severity, and treatment) with specific components of general health-related quality of life and IBD-specific QoL; 2) describe the effects of sociodemographic characteristics (SES, age, and gender) on these measures; and 3) compare the views of different observers (parent and child with IBD) of the child's QoL. The study will apply both general and condition-specific QoL measures among a random sample of 250 children and adolescents with IBD, ages 5-18 years, in six clinical sites. We will obtain measures of QoL from both the child and a parent in each case. The study will obtain additional data regarding the subjects' clinical condition (condition type, severity/activity, treatment [including surgery], age of onset) and socioeconomic status (household structure and income). Main analyses will compare general and

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specific measures of QoL and examine the influence of clinical and sociodemographic variables on QoL, through multivariate regression techniques. We will also examine the differences in child and parent assessments of QoL. The information from this study will provide a stronger base for future studies of treatment and natural history of IBD. It will help to clarify the life domains that are affected by IBD and will inform interventions to improve QoL for children with IBD. Study Type: Observational Contact(s): James M Perrin, MD [email protected]; Aziz Chughtai, MPH Web Site: http://clinicaltrials.gov/ct/show/NCT00061737 •

Research Study in Patients With Severe Ulcerative Colitis Condition(s): Ulcerative Colitis Study Status: This study is currently recruiting patients. Sponsor(s): Protein Design Labs Purpose - Excerpt: The purpose of the study is to evaluate an intravenous (by injection) investigational medication to treat severe ulcerative colitis refractory to steroid therapy. The research is being conducted at up to 8 clinical research sites in the US and is open to both men and women ages 18 to 70 years old. Participants in the study will have a number of visits to a research site. All study-related care and medication is provided to qualified participants at no cost: this includes all visits, examinations and laboratory work. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00032305

•

Role of EGF in Development of Necrotizing Enterocolitis Condition(s): Necrotizing Enterocolitis; Premature Birth Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Necrotizing enterocolits (NEC) is a serious gastrointestinal disorder that primarly affects preterm infants. About 10% of babies less than 32 weeks gestation at birth will develop it. Overall, 30% of babies who develop NEC will die from it, with many others developing long term gastrointestinal problems. The most important factor in its development is a premature intestinal tract. Epidermal growth factor (EGF) is an important growth factor in the development and maintenance of the gastrointestinal tract. This study will look for a relationship between EGF levels in premature babies and the development of NEC. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00059449

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Safety and efficacy of two diffrent doses of Asacol in the treatment of moderately active ulcerative colitis Condition(s): Ulcerative Colitis Study Status: This study is currently recruiting patients. Sponsor(s): Procter & Gamble Pharmaceuticals Purpose - Excerpt: This study is a prospective clinical study to evalute the safety and efficacy of two different doses of Asacol for the treatment of moderatively active ulcerative colitis. In addition, a new tablet formulation will be evaluated at one of the two doses. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00073021

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Study of Infliximab for the treatment of patients with active Ulcerative Colitis. Condition(s): Ulcerative Colitis Study Status: This study is currently recruiting patients. Sponsor(s): Centocor Purpose - Excerpt: A research study to evaluate the safety and effectiveness of an investigational drug is currently being conducted in adults with moderate to severe ulcerative colitis. The aim of the international study is to evaluate the efficacy and safety of Infliximab in patients with active ulcerative colitis. The study is being conducted in the US, Canada, Denmark, Spain, UK, Belgium and Germany. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00036439

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A Humanized Anti-Interferon-? Monoclonal Antibody (HuZAF)for Moderate to Severe Crohn's Disease Condition(s): Crohn's Disease; Colitis; Intestinal Disease; Gastrointestinal Disease; Digestive System Disease Study Status: This study is no longer recruiting patients. Sponsor(s): Protein Design Labs Purpose - Excerpt: The purpose of the HARMONY study is to assess the safety and efficacy of an investigational drug called HuZAF, in patients with moderate to severe Crohn's disease (CD). HuZAF is a humanized anti-Interferon-gamma (anti-IFN-?) monoclonal antibody, which binds and blocks IFN-?, a protein in the immune system that is involved in inflammation. Antibodies are proteins normally produced by our immune system to help fight off foreign substances. Scientists have been able to make therapeutic humanized monoclonal antibodies, similar to the antibodies in our bodies, to target diseases. Phase(s): Phase II

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00072943 •

A Randomized Comparative Pharmacokinetic Study of Oral Ganciclovir After Treatment With Intravenous Ganciclovir for Cytomegalovirus Gastrointestinal Disease in AIDS Patients Condition(s): Colitis; HIV Infections Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Hoffmann-La Roche Purpose - Excerpt: To determine the oral bioavailability of three dose levels of oral ganciclovir given with and without glutamic acid hydrochloride in patients with cytomegalovirus (CMV) GI disease, and to compare the bioavailability of these regimens to that of standard intravenous (IV) ganciclovir. Long-term ganciclovir maintenance therapy has been recommended for CMV colitis or esophagitis following induction treatment. Oral ganciclovir is a likely candidate for maintenance because of its possible therapeutic value and ease of administration, but an optimum dose has not been determined. Since oral ganciclovir has a low bioavailability and is more soluble in an acid pH environment, the addition of glutamic acid hydrochloride may enhance gastrointestinal absorption of this drug. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000768

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A Study of Ganciclovir in the Treatment of Cytomegalovirus of the Large Intestine in Patients with AIDS Condition(s): Colitis; HIV Infections Study Status: This study is completed. Sponsor(s): Hoffmann-La Roche Purpose - Excerpt: To attempt to demonstrate the efficacy of ganciclovir (DHPG) treatment of cytomegalovirus (CMV) colitis in AIDS patients by evaluating both clinical and virologic parameters. To determine acceptability and the safety profile of a 2-week course of intravenous (IV) DHPG therapy. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002273

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A Study of GT160-246 Versus Vancomycin in Patients with Clostridium difficileAssociated Diarrhea Condition(s): Clostridium difficile-Associated Diarrhea; Clostridium Enterocolitis; Clostridium Difficile Diarrhea; Antibiotic-Associated Colitis; Antibiotic-Associated Diarrhea

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Study Status: This study is completed. Sponsor(s): Genzyme Drug Discovery and Development Purpose - Excerpt: Approximately 300 patients will be entered into this study taking place throughout the United States, Canada and the United Kingdom. This study aims to determine if an investigational drug is safe and effective for treating the symptoms of C. difficile-associated diarrhea and lowering the risk of repeat episodes of diarrhea. The investigational drug will be evaluated in comparison to current standard antibiotic treatment, so all patients will receive active medication. All study-related care is provided including doctor visits, physical exams, laboratory tests and study medication. Total length of participation is approximately 10 weeks. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034294 •

Phase II Placebo-Controlled Study of 4-Aminosalicylic Acid for Ulcerative Colitis Condition(s): Ulcerative Colitis Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); University of Vermont Purpose - Excerpt: Objectives: I. Assess the safety and efficacy of 4-aminosalicylic acid in patients with mildly to moderately severe ulcerative colitis. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004810

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Safety and Efficacy of OP2000 (deligoparin) in the Treatment of Active Ulcerative Colitis Condition(s): Ulcerative Colitis Study Status: This study is completed. Sponsor(s): Incara Pharmaceuticals Purpose - Excerpt: This study will evaluate the effectiveness and safety of the experimental compound OP2000 (deligoparin) in patients with active ulcerative colitis. Patients eligible for this study will have received (and will continue to receive) stable doses of aminosalicylates (oral, enema and/or suppository), if tolerated. OP2000 is an ultra low molecular weight heparin with anticoagulant (blood thinning) and antiinflammatory actions that may be of benefit for the treatment of ulcerative colitis. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033943

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Study of the Relationship Between Feeding and Late Onset Sepsis and/or Necrotizing Enterocolitis in Low Birth Weight Infants Condition(s): Necrotizing Enterocolitis; Sepsis Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Baylor College of Medicine Purpose - Excerpt: Objectives: I. Compare the incidence of late onset sepsis and/or necrotizing enterocolitis and duration of hospitalization in low birth weight infants fed with fortified mother's milk supplemented with either fortified pasteurized donor human milk or preterm formula, and with fortified mother's milk versus preterm formula. II. Determine the relationship between functional antibody titers in serial milk samples and the incidence of pathogen specific late onset sepsis (e.g., Staphylococcus epidermidis, Staphylococcus aureus) in these patients. III. Determine the long term sequelae (growth, body composition, health, and neurodevelopment) of human milk versus formula feeding in these patients. IV. Determine the relationship between stress and milk production in the mothers of these patients. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005888

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “colitis” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 6. PATENTS ON COLITIS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “colitis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on colitis, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Colitis By performing a patent search focusing on colitis, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We

9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on colitis: •

Chemical compounds having ion channel blocking activity for the treatment of immune dysfunction Inventor(s):.O slashed.dum; Niels (K.o slashed.benhavn, DK), Christophersen; Palle (Ballerup, DK), J.o slashed.rgensen; Tino D. (Solr.o slashed.d Strand, DK), Jensen; Bo S. (K.o slashed.benhavn S, DK), Olsen; S.o slashed.ren-Peter (Klampenborg, DK), Str.o slashed.b.ae butted.k; Dorte (Farum, DK) Assignee(s): NeuroSearch A/S (Ballerup, DK) Patent Number: 6,545,028 Date filed: April 14, 2000 Abstract: This invention relates to treatment or alleviation of a disease, condition or disorder selected from inflammatory bowel disease, Chron's disease, colitis ulcerosa, Coeliac disease, dermatitis herpetiformis, dermatomyositis, enteritis allergia, erytherma nodosum leprosum, ileitis regionalis, psoriasis, purpura, scleritis or scleroderma by administering to a living body certain imidazole, triazole, or 1,4-dihydropyridine derivatives. Excerpt(s): The present invention relates to chemical compounds having inhibitory activity on an intermediate conductance Ca.sup.2+ activated potassium channel (IK.sub.Ca), and the use of such compounds for the treatment or alleviation of diseases or conditions relating to immune dysfunction. Moreover, the invention relates to a method of screening a chemical compound for inhibitory activity on an intermediate conductance Ca.sup.2+ activated potassium channel (IK.sub.Ca). Ion channels are transmembrane proteins, which catalyse the transport of inorganic ions across cell membranes. The ion channels participate in processes as diverse as the generation and timing of action potentials, synaptic transmissions, secretion of hormones, contraction of muscles, etc. Web site: http://www.delphion.com/details?pn=US06545028__

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Diagnosis, prevention and treatment of ulcerative colitis, and clinical subtypes thereof, using microbial UC panca antigens Inventor(s): Braun; Jonathan (Tarzana, CA), Cohavy; Offer (Los Angeles, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,537,768 Date filed: October 12, 1999 Abstract: The present invention relates to microbial UC pANCA antigens. The invention provides methods of diagnosing ulcerative colitis (UC) and methods of inducing tolerance in a pANCA-positive patient with UC using a histone H1-like antigen. The invention further provides methods of diagnosing UC and methods of inducing tolerance in a pANCA-positive patient with UC using a porin antigen. Methods of diagnosing UC and methods of inducing tolerance in a pANCA-positive patient with UC using a Bacteroides antigen also are provided.

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Excerpt(s): The invention relates generally to the fields of immunology and inflammatory bowel disease and more specifically to the diagnosis and treatment of a clinical subtype of ulcerative colitis. Inflammatory bowel disease (IBD) is the collective term used to describe two gastrointestinal disorders of unknown etiology: Crohn's disease (CD) and ulcerative colitis (UC). The course and prognosis of ulcerative colitis, which occurs world-wide and is reported to afflict as many as two million people, varies widely. Onset of ulcerative colitis is predominantly in young adulthood with diarrhea, abdominal pain, and fever the three most common presenting symptoms. The diarrhea may range from mild to severe and often is accompanied by bleeding. Anemia and weight loss are additional common signs of UC. Ten percent to fifteen percent of all patients with inflammatory bowel diseases such as UC will require surgery over a ten year period. In addition, patients with UC are at increased risk for the development of intestinal cancer. Reports of an increasing occurrence of psychological problems, including anxiety and depression, are perhaps not surprising symptoms of what is often a debilitating disease that strikes people in the prime of life. Unfortunately, the available therapies for ulcerative colitis are few, and both diagnosis and treatment have been hampered by a lack of knowledge regarding the etiology of the disease. What is clear, however, is that the pathogenesis of ulcerative colitis involves immune-mediated damage to the intestinal mucosa. Autoantibodies, specifically antibodies against cytoplasmic components of neutrophils (pANCA), have been reported in 68-80% of patients with ulcerative colitis, further supporting a role for immune dysregulation in this disease. However, the antigens recognized by these pANCA autoantibodies, which would be useful in diagnosing and treating UC patients have, to date, escaped identification. Web site: http://www.delphion.com/details?pn=US06537768__ •

Enzyme and DNA sequence encoding krill-derived multifunctional protein Inventor(s): Kay; John (Cardiff, GB), Kille; Peter (Cardiff, GB) Assignee(s): Phairson Medical, Inc. (London, GB) Patent Number: 6,524,814 Date filed: October 26, 1999 Abstract: The present invention provides nucleic acid and corresponding amino acid sequences of a multifunctional protein that has been found to be useful in numerous medical and cosmetic contexts. A protein having "multifunctional activity," is defined herein as including at least one of a chymotrypsin, trypsin, collagenase, elastase or exo peptidase activity or asialo GM.sub.1 ceramide binding activity. These proteins are useful for multiple purposes, including treating viral infections such as herpes outbreaks, fungal, bacterial or parasitic infections, including the primary and secondary infections of leprosy, colitis, ulcers, hemorrhoids, corneal scarring, dental plaque, acne, cystic fibrosis, blood clots, wounds, immune disorders including autoimmune disease and cancer. Excerpt(s): The present invention relates to purified nucleic acids encoding a krillderived enzymes such as proteinases, which can be a multifunctional protein, and to purified polypeptides. A protein having "multifunctional activity," is defined herein as including at least one of a chymotrypsin, trypsin, collagenase, elastase or exo peptidase activity, or asialo GM.sub.1 ceramide binding activity. Multifunctional proteins are useful for multiple purposes, including treating viral infections such as herpes outbreaks, fungal, bacterial or parasitic infections, including the primary and secondary

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infections of leprosy, colitis, ulcers, hemorrhoids, corneal scarring, dental plaque, acne, cystic fibrosis, blood clots, wounds, immune disorders including autoimmune disease, such as lupus erythematosus and multiple sclerosis, and cancer. Purified polypeptides having proteinase or multifunctional activity and purified nucleic acids encoding such polypeptides are desirable to provide pharmaceutically useful products. Other uses for proteinases are well recognized in the art and include digesting proteinaceous material for a variety of purposes including cleaning and creating improved feeds for animals or bacteriology. Until now, sequences encoding krill-derived proteinases similar to those set forth in the Sequence Listing have not been identified. The amino acid sequence included in SEQ ID NOS:4, 5, 6, 10, 20 22 or 24 or other isoforms thereof or chimeric polypeptides thereof are examples of such enzymes. In particular, in many cases the invention is specified in terms of a reference protein sequence which is AA64-300 of SEQ ID NO:4 or a sequence differing therefrom by at least one of the residue differences found in SEQ ID NOS:5, 20, 22, or 24. In an embodiment of the invention, the reference reference sequence further has the differences relative to SEQ ID NO: 4 that are found in SEQ ID NO:8. These differences are illustrated in FIGS. 5 and 6. Web site: http://www.delphion.com/details?pn=US06524814__ •

Intestinal function using leptin Inventor(s): O'Connor; Darlise (Newark, DE), Schwartz; Marshall (Bryn Mawr, PA) Assignee(s): The Nemours Foundation (Wilmington, DE) Patent Number: 6,630,444 Date filed: October 23, 2000 Abstract: A method for treating a patient that has inadequate intestinal function is described. Administering leptin to a subject increases the intestinal function beyond that for a normal intestine and beyond that of a normal adaptive response. Further, administering leptin to a subject results in an increase in amino acid absorption, sugar absorption, mucosal mass, transport mechanisms for amino acids, or transport mechanisms for sugars. The method may be used for treating subjects have conditions such as short bowel syndrome, inflammation of the bowel, necrotizing enterocolitis, intestinal atresia, midgut volvulus, severe acute gastroenteritis, chronic gastroenteritis, cholera, chronic infections of the bowel, immunologic disorders affecting the small intestine, and inflammatory bowel disease such as, chronic ulcerative colitis and Crohn's Disease. Excerpt(s): The present invention relates broadly to enhancing the functions of the small intestine and the treatment of inflammatory bowel diseases in a patient by the administration of leptin. Short bowel syndrome ("SBS") is a devastating clinical disorder resulting from massive small bowel resection. SBS affects many infants and children and threatens normal growth and development. The remnant intestine naturally adapts to resection, however, this adaptation process is often inadequate to meet the patients fluid and nutritional goals. There is no effective treatment and current management includes total parenteral nutrition ("TPN"), which itself is a source of significant morbidity and mortality. Accordingly, there is a need for an alternative method of management for short bowel syndrome. Other disorders of the small intestine can render the bowel nonfunctional for a prolonged period of time such as severe infection and inflammatory bowel disease. It is an object of the present invention to provide an alternative method for management for short bowel syndrome and other disorders of the intestine.

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Web site: http://www.delphion.com/details?pn=US06630444__ •

Isoxazole derivatives to be used as phosphodiesterase VII inhibitors Inventor(s): Eggenweiler; Hans-Michael (Weiterstadt, DE), Gassen; Michael (Griesheim, DE), Jonas; Rochus (Darmstadt, DE), Welge; Thomas (Alsbach, DE), Wolf; Michael (Darmstadt, DE) Assignee(s): Merck Patentgesellschaft (Darmstadt, DE) Patent Number: 6,531,498 Date filed: May 3, 2002 Abstract: The invention relates to compounds of formula I and to their physiologically acceptable salts and solvates which act as phosphodiesterse VII inhibitors and are thus useful for the treatment of allergic disorders, asthma, chronic bronchitis, atopic dermatitis, psoriasis and other skin disorders, inflammatory disorders, autoimmune diseases, rheumatoid arthritis, multiple sclerosis, Crohn's disease, diabetes mellitus or ulcerative colitis, osteoporosis, transplant rejection reactions, cachexia, tumor growth, tumor metastases, sepsis, memory disturbances, atherosclerosis and AIDS. Excerpt(s): and their physiologically acceptable salts and/or solvates as phosphodiesterase VII inhibitors. The invention further relates to the use of the compounds of the formula I for producing a pharmaceutical for controlling allergic disorders, asthma, chronic bronchitis, atopic dermatitis, psoriasis and other skin disorders, inflammatory disorders, autoimmune diseases such as, for example, rheumatoid arthritis, multiple sclerosis, Crohn's disease, diabetes mellitus or ulcerative colitis, osteoporosis, transplant rejection reactions, cachexia, tumour growth or tumour metastases, sepsis, memory disturbances, atherosclerosis and AIDS. Compounds of the formula I are described by Bionet. Web site: http://www.delphion.com/details?pn=US06531498__

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LTA4 hydrolase inhibitor pharmaceutical compositions and methods of use Inventor(s): Chandrakumar; Nizal Samuel (Vernon Hills, IL), Chen; Barbara Baosheng (Glenview, IL), Clare; Michael (Skokie, IL), Desai; Bipinchandra Nanubhai (Vernon Hills, IL), Djuric; Stevan Wakefield (Malvern, PA), Docter; Stephen Hermann (Mt. Prospect, IL), Gasiecki; Alan Frank (Vernon Hills, IL), Haack; Richard Arthur (Chicago, IL), Liang; Chi-Dean (Glenview, IL), Miyashiro; Julie Marion (Chicago, IL), Penning; Thomas Dale (Elmhurst, IL), Russell; Mark Andrew (Gurnee, IL), Yu; Stella Siu-tzyy (Morton Grove, IL) Assignee(s): G.D. Searle & Co. (Chicago, IL) Patent Number: 6,506,876 Date filed: October 11, 1994 Abstract: The present invention provides compounds of the formula Ar.sup.1 --Q-Ar.sup.2 --Y--R--Z and pharmaceutically acceptable salts thereof wherein Ar.sup.1 and Ar.sup.2 are optionally substituted aryl moieties, Z is an optionally substituted nitrogencontaining moiety which may be an acyclic, cyclic or bicyclic amine or an optionally substituted monocyclic or bicyclic nitrogen-containing heteroaromatic moiety; Q is a linking group capable of linking two aryl groups; R is an alkylene moiety; Y is a linking

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moiety capable of linking an aryl group to an alkylene moiety and wherein Z is bonded to R through a nitrogen atom. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of inflammatory diseases which are mediated by LTB.sub.4 production, such as psoriasis, ulcerative colitis, IBD and asthma. Excerpt(s): This invention relates generally to anti-inflammatory compounds and pharmaceutical compositions, and more particularly to anti-inflammatory compounds and compositions which are capable of inhibiting leukotriene A.sub.4 hydrolase. B. Samuelsson, et al., J. Biol Chem., 264, 19469-19472 (1989) have shown that LTB.sub.4 biosynthesis from arachidonic acid involves the action of 2 enzymes, 5-lipoxygenase [5LO] and LTA.sub.4 hydrolase. 5-LO transforms arachidonic acid to 5-HPETE and subsequent formation of LTA.sub.4, which is an unstable allylic epoxide intermediate which is enzymatically hydrolyzed by LTA.sub.4 hydrolase to form the dihydroxy acid LTB.sub.4. wherein X is --CH-- or --N--, and r is 1 or 2, further provided that wherein R.sup.1, R.sup.2 or both R.sup.1 and R.sup.2 are --(CH.sub.2).sub.a COR.sup.15, then a is not O. Web site: http://www.delphion.com/details?pn=US06506876__ •

Method for inhibiting inflammatory disease Inventor(s): Hiebert; Charles (Sunnyvale, CA), Laderoute; Keith R. (Palo Alto, CA), Tuse; Daniel (Menlo Park, CA), Waleh; Nahid (Palo Alto, CA) Assignee(s): Large Scale Biology Corp. (Vacaville, CA), SRI International (Menlo Park, CA) Patent Number: 6,433,012 Date filed: September 6, 2000 Abstract: The present invention relates to methods for effectively inhibiting inflammatory diseases, such as Crohn's disease and ulcerative colitis. In other aspects, this invention relates to methods of reducing or inhibiting granulomas. Excerpt(s): The present invention relates to methods for effectively inhibiting unwanted angiogenesis. More particularly, this invention relates to methods of treating diseases associated with unwanted angiogenesis and to delivering anti-angiogenic activity to mammals having such diseases. Angiogenesis is the development of new blood vessels from existing microvessels. The process of generating new blood vessels plays an important role in embryonic development, in the inflammatory response, in the development of metastases (tumor induced angiogenesis or TIA), in diabetic retinopathy, in the formation of the arthritic panus and in psoriasis. Under normal physiological conditions, humans or animals only undergo angiogenesis in very specific, restricted situations. For example, angiogenesis is normally observed in wound healing, in fetal and embryonal development and in the formation of the corpus luteum, endometrium and placenta. The control of angiogenesis is a highly regulated system involving angiogenic stimulators and inhibitors. The control of angiogenesis has been found to be altered in certain disease states and, in many cases, the pathological damage associated with the disease is related to the uncontrolled angiogenesis. In tumor angiogenesis, for example, capillary sprouts are formed, their formation being induced by a group of tumor cells. However, compared with blood vessels produced in normal angiogenic microenvironments, tumor microvessels are morphologically and functionally unique. Their vascular networks typically show disorganized or aberrant architecture, luminal sizes vary and blood flow can fluctuate chaotically. There are two

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principal types of tumor angiogenesis in terms of the events that follow implantation of metastatic seedlings on surfaces and in organs. The first or primary angiogenesis is the initial vascularization of the mass of multiplying tumor cells and is regarded as an essential prerequisite for the survival and further growth of a metastatic deposit. The second is a continuing or secondary angiogenesis and is the phenomenon, which occurs in waves at the periphery of a growing tumor mass. This second angiogenesis is essential for the accretion of new microcirculatory territories into the service of the expanding and infiltrating tumor. Web site: http://www.delphion.com/details?pn=US06433012__ •

Method for the treatment of inflammatory bowel diseases Inventor(s): Ulmius; Jan (Lund, SE) Assignee(s): Aktiebolaget Draco (Sodertalje, SE) Patent Number: 6,423,340 Date filed: September 23, 1998 Abstract: Described herein are methods comprising the oral administration of budesonide for the treatment of ulcerative colitis and Crohn's colitis in its active phase. The methods can also be applied as relapse preventing therapy for Crohn's colitis in its chronic phase and Crohn's disease in the small intestine. Excerpt(s): The present invention relates to oral pharmaceutical compositions for use in the treatment of inflammatory bowel diseases and the use of certain glucocorticosteroids in the preparation of pharmaceutical compositions for the treatment by the oral route of certain inflammatory bowel diseases. Inflammatory bowel disease is the term generally applied to two diseases, namely ulcerative colitis and Crohn's disease. Ulcerative colitis is a chronic inflammatory disease of unknown aetiology afflicting only the large bowel and, except when very severe, limited to the bowel mucosa. The course of the disease may be continuous or relapsing, mild or severe. It is curable by total colectomy which may be needed for acute severe disease or chronic unremitting disease. Most patient with ulcerative colitis are managed medically rather than surgically. Web site: http://www.delphion.com/details?pn=US06423340__

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Method for treating inflammation using soluble receptors to interleukin-20 Inventor(s): Blumberg; Hal (Seattle, WA), Chandrasekher; Yasmin A. (Mercer Island, WA), Foster; Donald C. (Lake Forest Park, WA), Kelly; James D. (Mercer Island, WA), Thompson; Penny (Snohomish, WA), Xu; Wenfeng (Mukilteo, WA) Assignee(s): ZymoGenetics, Inc. (Seattle, WA) Patent Number: 6,610,286 Date filed: December 22, 2000 Abstract: A method for treating IL-20 induced inflammation. An antagonist to IL-20 is administered to treat inflammation and associated diseases. The antagonist can be an antibody that binds to IL-20 or its receptor or a soluble receptor that binds to IL-20. Examples of such diseases are adult respiratory disease, psoriasis, eczema, contact dermatitis, atopic dermatitis, septic shock, multiple organ failure, inflammatory lung

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injury, bacterial pneumonia, inflammatory bowel disease, rheumatoid arthritis, asthma, ulcerative colitis and Crohn's disease. Excerpt(s): The teachings of all of the references cited herein are incorporated in their entirety herein by reference. Inflammation normally is a localized, protective response to trauma or microbial invasion that destroys, dilutes, or walls-off the injurious agent and the injured tissue. It is characterized in the acute form by the classic signs of pain, heat, redness, swelling, and loss of function. Microscopically, it involves a complex series of events, including dilation of arterioles, capillaries, and venules, with increased permeability and blood flow, exudation of fluids, including plasma proteins, and leukocyte migration into the area of inflammation. Diseases characterized by inflammation are significant causes of morbidity and mortality in humans. Commonly, inflammation occurs as a defensive response to invasion of the host by foreign, particularly microbial, material. Responses to mechanical trauma, toxins, and neoplasia also may results in inflammatory reactions. The accumulation and subsequent activation of leukocytes are central events in the pathogenesis of most forms of inflammation. Deficiencies of inflammation compromise the host. Excessive inflammation caused by abnormal recognition of host tissue as foreign or prolongation of the inflammatory process may lead to inflammatory diseases as diverse as diabetes, arteriosclerosis, cataracts, reperfusion injury, and cancer, to post-infectious syndromes such as in infectious meningitis, rheumatic fever, and to rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis. The centrality of the inflammatory response in these varied disease processes makes its regulation a major element in the prevention control or cure of human disease. Web site: http://www.delphion.com/details?pn=US06610286__ •

Method of treating inflammatory bowel disease using a topical formulation of IL-11 Inventor(s): Bedrosian; Camille L. (Belmont Hills, MA), Keith, Jr.; James C. (Andover, MA), Schendel; Paul F. (Wayland, MA), Schwerschlag; Ullrich S. (Beverly Farms, MA), Warne; Nicholas W. (Andover, MA) Assignee(s): Wyeth (Madison, NJ) Patent Number: 6,540,993 Date filed: September 15, 2000 Abstract: Provided by the present invention are topical formulations of Interleukin-11 and methods for treating a variety of disorders, including inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis, indeterminate colitis, and infectious colitis), mucositis (e.g., oral mucositis, gastrointestinal mucositis, nasal mucositis, and proctitis), necrotizing enterocolitis, inflammatory skin disorders (e.g., psoriasis, atopic dermatitis, and contact hypersensitivity), aphthous ulcers, pharyngitis, esophagitis, peptic ulcers, gingivitis, periodontitis, and ocular diseases (e.g., conjunctivitis, retinitis, and uveitis). Excerpt(s): The present invention relates generally to novel compositions and methods for topical delivery of interleukin-11 (IL-11). In preferred embodiments, patients are treated employing topical delivery of recombinant human IL-11 for inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis, indeterminate colitis, and infectious colitis), mucositis (e.g., oral mucositis, gastrointestinal mucositis, nasal mucositis, and proctitis), necrotizing enterocolitis, inflammatory skin disorders (e.g., psoriasis, atopic dermatitis, and contact hypersensitivity), aphthous ulcers, pharyngitis, esophagitis, peptic ulcers, gingivitis, periodontitis, and ocular diseases (e.g., conjunctivitis, retinitis,

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and uveitis). Inflammatory responses include a broad range of host reaction to a variety of insults, such as injury, infection, or rejection. It is the overproduction of mediators that is believed to be associated with a broad range of disorders, including AIDS, arthritis (rheumatoid arthritis, osteoarthritis, spondyloarthropathies), antibiotic-induced diarrheal diseases, multiple sclerosis, osteoporosis, gingivitis, peptic ulcer disease, esophagitis, diabetes, retinitis, uveitis, reperfusion injury after myocardial infarction, cerebral vascular accident, aphthous ulcers (oral), atherosclerosis, tumor metastases, asthma, preeclampsia, pancreatitis, psoriasis, infertility and allergic disorders such as rhinitis, conjunctivitis, and urticaria. Some of these disorders and their symptoms are briefly summarized below. According to the methods of the present invention, IL-11 is administered topically to modulate the host's over reaction at the site of insult, thereby treating the following disorders. Web site: http://www.delphion.com/details?pn=US06540993__ •

Method of treating inflammatory conditions with progesterone analogs Inventor(s): Schreiber; Alan D. (Philadelphia, PA) Assignee(s): University of Pennsylvania (Philadelphia, PA) Patent Number: 6,610,674 Date filed: September 8, 2000 Abstract: The present invention provides methods for treating inflammatory conditions, including but not limited to, inflammatory bowel disease (ulcerative colitis, Crohn's disease, and proctitis), other noninfectious, inflammatory conditions of the GI tract (microscopic colitis, allergic eosinophilic gastroenteritis, food allergies, pill induced esophagitis, celiac disease, recurrent polyps, and hemorrhoids), and psoriasis, using progesterone or progesterone analogs such as medroxyprogesterone acetate. Excerpt(s): This invention provides methods for treating inflammatory conditions, including but not limited to, inflammatory bowel disease (ulcerative colitis, Crohn's disease, and proctitis), other noninfectious, inflammatory conditions of the GI tract (microscopic colitis, allergic eosinophilic gastroenteritis, food allergies, pill induced esophagitis, celiac disease, recurrent polyps, and hemorrhoids), and psoriasis using progesterone and progesterone analogs. Proctitis, inflammation of the rectum, is invariably present in UC and is sometimes present in CD. It may also occur independently from these diseases. Proctitis is another manifestation of IBD with pathology similar to UC. A patient presenting with proctitis may later develop fullblown UC or CD. Physicians and medical researchers have not been successful in identifying a cause for these diseases, although several theories have been postulated. The diseases may be caused by a pathogen or other antigen that initiates the inflammatory response in the bowel, accompanied by a defect in the ability to downregulate the immune response. Once initiated, many of the pathophysiological events in IBD are related to amplification of the inflammatory process. In response to antigens, cytokines and other inflammatory mediators are released. Some cytokines promote T cell activity. The inflammatory cascade continues with IL-2, helper T cells, B-cell proliferation, and antibody synthesis. Stimulated neutrophils and macrophages accumulate and further damage the tissue by releasing reactive oxygen species and other biologically active products. Additional acute inflammatory cells respond to the tissue damage, whether or not the primary initiating stimulus has ceased. Web site: http://www.delphion.com/details?pn=US06610674__

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Method of treating ulcerative colitis or crohn's disease by administering an antibody to.alpha.E.beta.7 integrin Inventor(s): Brenner; Michael B. (Sherborn, MA), Parker; Christina M. (Arlington, MA) Assignee(s): The Brigham and Women's Hospital, Inc. (Boston, MA) Patent Number: 6,455,042 Date filed: April 16, 1999 Abstract: The present invention relates to a method for treating an autoimmune disease, such ulcerative coliteis or crohns disease characterized by lymphocyte accumulation at epithelial sites. The method involves administering to a subject an effective amount of an antibody that selectively binds to an.alpha.sup.E.beta.sub.7 integrin or an.alpha.sup.E subunit thereof. Excerpt(s): This invention relates to a novel integrin alpha chain; functionally-equivalent peptide fragments and analogs thereof; oligonucleotides encoding the peptide fragments and analogs; vectors containing and cell lines expressing the novel peptides; and methods for using the peptide fragments, analogs and oligonucleotides. The integrin mediated adhesive interactions of cells with other cells and between cells and the extracellular matrix are believed to play critical roles in a wide variety of processes including, for example, modulation of the immune system, regulation of developmental processes and tumor progression and metastasis. These molecules also transduce information from the extracellular to the intracellular environment through poorly understood signalling mechanisms. The integrins represent one of the best characterized superfamilies of adhesion receptors. Integrins are glycoprotein heterodimers which contain a non-covalently associated.alpha. and.beta. subunit. Integrin subunits are transmembrane proteins which contain an extracellular domain for interacting with an extracellular matrix or cellular component, a transmembrane domain spanning the cell membrane and a cytoplasmic domain for interacting with one or more cytoskeletal components. There are fourteen known.alpha. subunits and eight known.beta. subunits which can pair to form at least twenty different integrin molecules. Several distinct integrin.alpha. chains are capable of pairing with one type of.beta. chain to form a.beta. chain subfamily. Thus, for example, the.beta.sub.1 subfamily includes seven members (also known as the VLA proteins:.alpha.sup.1.beta.sub.1 -.alpha.sup.7.beta.sub.1); the.beta.sub.2 subfamily includes three members (the leukocyte cell adhesion molecules or LeuCAMs:.alpha.sup.L.beta.sub.2 or LFA-1,.alpha.sup.M.beta.sub.2 or Mac-1 and.alpha.sup.x.beta.sub.2 or p150,95) and the.beta.sub.3 subfamily includes two members (a.sup.v.beta.sub.3,.alpha.sup.IIb.beta.sub.3). In some instances, an.alpha. chain may pair with more than one.beta. chain, e.g.,.alpha.sup.4 can pair with.beta.sub.1 or.beta.sub.7. Web site: http://www.delphion.com/details?pn=US06455042__

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Methods and materials for treating and preventing inflammation of mucosal tissue Inventor(s): Ponikau; Jens (Rochester, MN) Assignee(s): Mayo Foundation for Medical Education and Research (Rochester, MN) Patent Number: 6,555,566 Date filed: May 25, 2001

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Abstract: The invention involves methods and materials for treating and preventing non-invasive fungus-induced mucositis. Specifically, the invention involves administrating an antifungal agent such that it contact mucus in an amount, at a frequency, and for a duration effective to prevent, reduce, or eliminate non-invasive fungus-induced rhinosinusitis. This invention also provides methods and materials for diagnosing non-invasive fungus-induced rhinosinusitis and culturing non-invasive fungus from a mammalian mucus sample as well as specific antifungal formulations and medical devices for treating and preventing non-invasive fungus-induced rhinosinusitis. In addition, the invention provides methods and materials for treating and preventing other non-invasive fungus-induced mucositis conditions such as chronic otitis media, chronic colitis, and Crohn's disease. Further, the invention involves methods and materials for treating and preventing chronic asthma symptoms. Excerpt(s): The invention relates to methods and materials involved in the treatment and prevention of non-invasive fungus-induced inflammation of mucosal tissue as well as asthma symptoms. Mucositis, the inflammation of mucosal tissue, is a serious medical problem that affects millions of people worldwide. For example, conservative estimates indicate that between 20 to 40 million Americans suffer from chronic rhinosinusitis, an inflammation of the nasal cavity and/or paranasal sinuses. For the most part, the cause of chronic rhinosinusitis is unknown. In a small percentage of patients, however, non-invasive fungal organisms living within mucus seem to be involved. Patients having this condition, now known as allergic fungal sinusitis (AFS), were first described in the early 1980's (Miller J W et al., Prod. Scot. Thor. Soc. 36:710 (1981) and Katzenstein A L A et al., J. Allergy Clin. Immunol. 72:89-93 (1983)). Specifically, about three to eight percent of chronic rhinosinusitis cases requiring surgery because of nasal obstruction caused by polyp formation have been classified as AFS. Briefly, AFS is diagnosed by the presence of inspissated mucus in the nasalparanasal cavities. Typically, this mucus contains clumps or sheets of necrotic eosinophils, Charcot-Leyden crystals, and non-invasive fungal hyphae. In addition, patients with AFS typically have a history of nasal-paranasal polyposis and may have undergone multiple surgeries. Inflammation can affect all nasal-paranasal cavities, but also can be asymmetric involving only one side. Computed topography (CT) scans of patients with AFS have a characteristic appearance and often reveal bone erosion in adjacent structures. Indeed, destruction of bones adjacent to the sinuses and nasal areas ranging from 19 percent to 80 percent has been reported. Web site: http://www.delphion.com/details?pn=US06555566__ •

Methods for treating disorders in which docosahexaenoic acid (DHA) levels are affected Inventor(s): Alvarez; Juan G. (Boston, MA), Freedman; Steven (Brighton, MA) Assignee(s): Beth Israel Deaconess Medical Center, Inc. (Boston, MA) Patent Number: 6,552,081 Date filed: November 3, 2000 Abstract: A method of treating disorders in which DHA levels are affected is described. The method includes administering to a subject suffering from the disorder a therapeutically affective amount of DHA. This method is particularly useful in treating subjects suffering from a disorder characterized by a defect in the CF gene, e.g., cystic fibrosis, or a chronic inflammatory disorder, e.g., ulcerative colitis, Crohn's disease, chronic pancreatitis, asthma, rheumatoid arthritis or chronic gastritis. A method of

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ameliorating affects of cystic fibrosis in a newborn and a method of increasing surfactant levels in a fetus are also described. Excerpt(s): Cystic Fibrosis (CF) is the most prevalent autosomal recessive disorder in the Caucasian population (Gorelick (1991) Gastroenterology 103:681-693). Approximately 1 in 2000 live births are afflicted with CF and 5% of Caucasians in the United States are carriers of the abnormal CF gene. CF individuals rarely survive past their mid-thirties, and most mortalities are a result of recurrent pulmonary infection and, ultimately, pulmonary failure. Two other major clinical manifestations of CF are pancreatic dysfunction and male infertility. By 1989, the CF gene had been cloned and was found to code for a chloride channel. Activation of the channel in the normal pancreas activates the chloride/bicarbonate exchanger, resulting in a net secretion of bicarbonate into the lumenal space and alkalinization of the pancreatic juice. Mutations in the chloride channel like those found in CF result in a reduced chloride conductance and a reduced ability of ductal cells to secrete bicarbonate into the lumenal space. This results in the formation of inspissated plugs within the ducts leading to obstruction of the pancreatic ducts. In recent years, the focus in CF research has shifted towards the coupling of defective chloride channel function and membrane recycling. Recent research has demonstrated that membrane internalization at the apical plasma membrane of the pancreatic acinar cell is dependent on pH of the acinar lumen (Freedman et al., Eur. J. Cell Biol. (1998) 75:153-63), Freedman et al., (1994) Am. J. Physiol. 267:G40-G51, and Freedman et al., (1994) Eur. J. Cell Biol. 65:354-365). Since pH of the acinar lumen is reflective of ductal bicarbonate secretion from the proximal duct cells, a phenomenon regulated via the chloride channel, a coupling may exist between duct and acinar cell function, (Freedman et at., (1994) Am. J. Physiol. 267:G40-G51, and Freedman et al, (1994) Eur. J. Cell Biol. 65:354-365). Research has also confirmed the hypothesis that lack of alkalinization of the acinar lumen leads to inhibition of apical membrane internalization and defective apical endocytosis in pancreatic acinar cells from CF mice. This block in the recycling of membranes following exocytosis leads to eventual deficiency in membranes for reformation of secretory granules. Thus, pancreatic insufficiency appears to be a result of defects in membrane recycling with obstruction of the ducts occurring as a secondary event. Web site: http://www.delphion.com/details?pn=US06552081__ •

Methods of treating colitis using STAT-4 anti-sense oligonucleotides Inventor(s): Fuss; Ivan (Bethesda, MD), Kitani; Atsushi (Rockville, MD), Neurath; Markus (Mainz, DE), Strober; Warren (Bethesda, MD) Assignee(s): The United States of America as represented by the Department of Health and (Washington, DC) Patent Number: 6,479,465 Date filed: March 19, 2001 Abstract: The present invention provides a method of treating or preventing the inflammatory response of an inflammatory bowel disease in a subject, comprising administering to the subject an amount of a STAT-4 antisense oligonucleotide effective in treating or preventing the inflammatory response of the inflammatory bowel disease. Excerpt(s): The present invention relates to a method of preventing or treating the inflammatory response of an inflammatory bowel disease by administering anti-sense oligonucleotides of the signal transducer and activator of transcription-4 (STAT-4).

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There is growing evidence that Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of human inflammatory bowel disease (IBD) are due to dysregulated intestinal immune responses to one or more luminal antigens in the normal intestinal microflora (1-4). These responses are characterized by abnormalities of both CD4+ and CD8+ T cells which manifest both as disordered T cell activation and regulatory function and as cytokine production disturbances that lead to inflammation (2, 5-9). Over the last several years, various murine models of chronic intestinal inflammation resembling IBD have been established which have provided important new insights into the pathogenesis of both CD and UC (10). Thus, in studies of several of the models most closely resembling CD it has been shown that production of large amounts of Th1-type cytokines, e.g., interferon-.gamma. (IFN-.gamma.) and tumor necrosis factor-.alpha. (TNF-.alpha.), by CD4+ T cells is a major and essential feature of the inflammation (6-7, 11). In addition, it has been demonstrated that this disease-causing Th1 cytokine response can be counteracted by induction of a suppressor response involving the generation of T cells producing Th2-type cytokines (IL-4, IL-10) and/or suppressive cytokines, such as TGF-.beta. (12-16). Finally, it has been shown that the Th1 cytokine production in these models is triggered by increased production of IL-12, a cytokine that plays a major role in driving T cell differentiation (17). In the latter regard, increased IL12 production can be detected in the inflamed intestinal tissues of mice with experimental inflammation and, more importantly, systemic administration of anti-IL-12 to such mice leads to abrogation of the inflammation (7, 11). The relevance of these findings to CD is inherent in studies showing that this disease is also associated with an excessive Th1 T cell response characterized by increased IFN-.gamma. production by lamina propria (LP) T cells (9). In addition, a recent report indicates that CD LP cells produce small, but measurable increases, in IL-12 in response to LPS (18). Web site: http://www.delphion.com/details?pn=US06479465__ •

Monocyclic-7H-pyrrolo[2,3-d]pyrimidine compounds, compositions, and methods of use Inventor(s): Blumenkopf; Todd A. (Old Lyme, CT), Brown; Matthew F. (Pawcatuck, CT), Changelian; Paul S. (E. Greenwich, CT), Flanagan; Mark E. (Gales Ferry, CT) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 6,635,762 Date filed: June 17, 1999 Abstract: Novel pyrrolo[2,3-d]pyrimidine compounds useful as inhibitors of the enzyme protein tyrosine kinases such as Janus Kinase 3 as well as immunosuppressive agents for organ transplants, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia and other autoimmune diseases are described. Excerpt(s): The present invention relates to pyrrolo[2,3-d]pyrimidine compounds which are inhibitors of protein tyrosine kinases, such as the enzyme Janus Kinase 3 (hereinafter also referred to as JAK3) and as such are useful therapy as immunosuppressive agents for organ transplants, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia and other indications where immunosuppression would be desirable. This invention also relates to a method of using such compounds in the treatment of the

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above indications in mammals, especially humans, and the pharmaceutical compositions useful therefor. with the proviso that the groups of formulas IV, V, VI or XIII do not contain two or more oxygens, sulfurs or combinations thereof in adjacent positions. Web site: http://www.delphion.com/details?pn=US06635762__ •

Nutritional product for a person having ulcerative colitis Inventor(s): Demichele; Stephen Joseph (Dublin, OH), Fuller; Martha Kay (Westerville, OH), Garleb; Keith Allen (Powell, OH), McEwen; John William (Gahanna, OH) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 6,468,987 Date filed: September 14, 1999 Abstract: An enteral nutritional product for a person having ulcerative colitis contains in combination (a) an oil blend which contains eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), and (b) a source of indigestible carbohydrate which is metabolized to short chain fatty acids by microorganisms present in the human colon. Preferably the nutritional product also contains one or more nutrients which act as antioxidants. Excerpt(s): The present invention relates to a nutritional product for a person having ulcerative colitis. The term "Inflammatory Bowel Disease" is a designation commonly used for two related, but distinct, chronic inflammatory conditions affecting the gastrointestinal tract, namely Crohn's disease and ulcerative colitis. Crohn's disease may involve any segment of the gastrointestinal tract, although characteristically the region of greatest involvement is the distal one quarter of the small intestine and the proximal colon. In ulcerative colitis the inflammation is, by definition, limited to the mucosa of the large bowel. However, the present invention is concerned only with nutritional support for a person having ulcerative colitis. The primary cause of ulcerative colitis is not currently known. At the present time, there is no medical cure for ulcerative colitis and this chronic condition may lead to total proctocolectomy. Current medical treatment is directed toward decreasing the number, frequency and severity of acute exacerbations of inflammatory bowel disease and preventing secondary complications, but at best, the results are disappointing. Long term use of corticosteroids to downregulate the inflammatory response is a common approach to the control of intestinal inflammation. Steroids are considered to exert their antiinflammatory effects through inhibition of the release of free arachidonic acid from membrane phospholipids; Historically the long term use of immunosuppressive agents (steroids) is associated with chronic side effects such as those presented in Table 1. Web site: http://www.delphion.com/details?pn=US06468987__

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PARP inhibitors, pharmaceutical compositions comprising same, and methods of using same Inventor(s): Jackson; Paul F. (Bel Air, MD), Li; Jia-He (Cockeysville, MD), Maclin; Keith M. (Baltimore, MD), Zhang; Jie (Ellicott City, MD) Assignee(s): Guilford Pharmaceuticals Inc. (Baltimore, MD) Patent Number: 6,635,642 Date filed: September 1, 1998 Abstract: The present invention relates to PARP inhibitors, pharmaceutical compositions comprising the same, and methods of using the same to treat tissue damage resulting from cell damage or death due to necrosis or apoptosis, effect neuronal activities not mediated by NMDA toxicity; to treat neural tissue damage resulting from ischemia and reperfusion injury, neurological disorders and neurodegenerative diseases; to prevent or treat vascular stroke; to treat or prevent cardiovascular disorders; to treat other conditions and/or disorders such as age-related macular degeneration, AIDS and other immune senescence diseases, arthritis, atherosclerosis, cachexia, cancer, degenerative diseases of skeletal muscle involving replicative senescence, diabetes, head trauma, immune senescence, inflammatory bowel disorders (such as colitis and Crohn's disease), muscular dystrophy, osteoarthritis, osteoporosis, chronic and/or acute pain (such as neuropathic pain), renal failure, retinal ischemia, septic shock (such as endotoxic shock), organ damage due to transplantation, and skin aging; to extend the lifespan and proliferative capacity of cells; to alter gene expression of senescent cells; or to radiosensitize hypoxic tumor cells. Excerpt(s): The present invention relates to inhibitors of the nucleic enzyme poly(adenosine 5'-diphospho-ribose) polymerase ["poly(ADP-ribose) polymerase" or "PARP", which is also sometimes called "PARS" for poly(ADP-ribose) synthetase]. More particularly, the invention relates to the use of PARP inhibitors to prevent and/or treat tissue damage resulting from cell damage or death due to necrosis or apoptosis; neural tissue damage resulting from ischemia and reperfusion injury; neurological disorders and neurodegenerative diseases; to prevent or treat vascular stroke; to treat or prevent cardiovascular disorders; to treat other conditions and/or disorders such as age-related macular degeneration, AIDS and other immune senescence diseases, arthritis, atherosclerosis, cachexia, cancer, degenerative diseases of skeletal muscle involving replicative senescence, diabetes, head trauma, immune senescence, inflammatory bowel disorders (such as colitis and Crohn's disease), muscular dystrophy, osteoarthritis, osteoporosis, chronic and acute pain (such as neuropathic pain), renal failure, retinal ischemia, septic shock (such as endotoxic shock), and skin aging; to extend the lifespan and proliferative capacity of cells; to alter gene expression of senescent cells; or to radiosensitize hypoxic tumor cells. Poly(ADP-ribose) polymerase ("PARP") is an enzyme located in the nuclei of cells of various organs, including muscle, heart and brain cells. PARP plays a physiological role in the repair of strand breaks in DNA. Once activated by damaged DNA fragments, PARP catalyzes the attachment of up to 100 ADP-ribose units to a variety of nuclear proteins, including histones and PARP itself. While the exact range of functions of PARP has not been fully established, this enzyme is thought to play a role in enhancing DNA repair. During major cellular stresses, however, the extensive activation of PARP can rapidly lead to cell damage or death through depletion of energy stores. Four molecules of ATP are consumed for every molecule of NAD (the source of ADP-ribose) regenerated. Thus, NAD, the substrate of PARP, is depleted by massive PARP activation and, in the efforts to re-synthesize NAD, ATP may also be depleted.

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Pharmaceutical preparations for the targeted treatment of crohn's disease and ulcerative colitis Inventor(s): Posanski; Ulrich (Freiburg, DE) Assignee(s): Novartis AG (CH) Patent Number: 6,503,883 Date filed: November 28, 2000 Abstract: The invention relates to a pharmaceutical preparation, which contains an immunosuppressive active agent in dissolved form in a starch capsule, or hard or soft gelatin capsule which has been coated with one or several polymer films. The invention further relates to a process for the production of the pharmaceutical preparation. Excerpt(s): The invention relates to a pharmaceutical preparation for the enteral treatment of Crohn's disease and ulcerative colitis, which contains an immunosuppressive active agent, which is administered in the form of a special galenic formulation for targeted local activity in the intestinal area, its use and a process for the production thereof. The therapies known today for the treatment of Crohn's disease and ulcerative colitis are not very effective. At the end of drug treatment, the patient usually faces surgical intervention. There are numerous preparations for extending and improving the therapeutical possibilities, but until now no preparation has been able to meet the medicinal requirements to a maximum degree. One possibility of local, enteral therapy of inflammatory intestinal affections was opened up with the development and usage of special mesalazine-containing (5-aminosalicylic acid) preparations, which release the active agent in the distal part of the small intestine and in the large intestine. The preparations concerned are solid forms of administration, which contain the active agent in crystalline form despite its poor solubility. Web site: http://www.delphion.com/details?pn=US06503883__

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Preparation capable of releasing drug at target site in intestine Inventor(s): Ishibashi; Takashi (Sakai, JP), Kubo; Hiroaki (Kobe, JP), Mizobe; Masakazu (Takatsuki, JP), Yoshino; Hiroyuki (Suita, JP) Assignee(s): Tanabe Seiyaku Co., Ltd. (Osaka, JP) Patent Number: 6,638,534 Date filed: January 29, 2001 Abstract: A preparation capable of releasing a medicinal substance at a targeted site in the intestine, wherein the preparation dose not releases medicinal substance in endogastri at all, but can quickly release a medicinal substance when it reaches the desired site in the intestine after a certain period of time from discharge of the preparation from the stomach, and wherein a core material containing a medicinal substance is coated with a mixed film of a hydrophobic organic compound--an enteric polymer. The preparation is useful for a local therapy of inflammatory disease in the intestine such as ulcerative colitis or Crohn's disease, or an oral administrative therapy with a medicinal substance of a peptide which is apt to be decomposed chemically or enzymatically in any site except for a specific site in the intestine such as the large

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intestine, or with a medicinal substance whose absorption site in the intestine is limited, or the like, because a medicinal substance can be delivered selectively to a specific site in the intestine. Excerpt(s): The present invention relates to a preparation capable of releasing a medicinal substance at a targeted site in the intestine, which can selectively deliver a medicinal substance to the large intestine and the like, and a method for preparation thereof. Selective delivery of a medicinal substance to a specific site in the intestine has been desired in pharmacotherapy, for example, a local therapy for inflammatory disease in the gastrointestinal tract such as ulcerative colitis or Crohn's disease, an oral administrative therapy with a medicinal substance of a peptide which is apt to be decomposed chemically or enzymatically in any site except for a specific site in the intestine such as the large intestine, or with a medicinal substance whose absorption site in intestine is limited, or the like. In order to efficiently realize the selective delivery of a medicinal substance in the intestine, it is necessary to design a preparation considering the physical and physiological environment in the human gastrointestinal tract and the traveling time of the preparation through the gastrointestinal tract. With respect to the physical and physiological environment in the gastrointestinal tract, it is recognized that the value of pH in the stomach is usually 1.8 to 4.5 and the value of pH in the intestine is 6.5 to 7.5 in a healthy human. According to the results of the widespread research of Davis et al., in a human, the residence time of a preparation in the stomach is 0.5 to 10 hours and further not only the inter-individual variation thereof is large, but also the residence time is considerably influenced, for example, by a condition of feeding, a size of the preparation to be administered and the like, while the traveling time of a preparation through the small intestine is generally recognized to be 3.+-.1 hours and the variation is relatively small (Journal of Controlled Release, 2, 27-38 (1985)). Web site: http://www.delphion.com/details?pn=US06638534__ •

Preventives/remedies for inflammatory intestinal disease Inventor(s): Nagata; Shigekazu (Minoo, JP), Suda; Takashi (Kanazawa, JP), Yatomi; Takehiro (Tokyo, JP) Assignee(s): Mochida Pharmaceutical Co., Ltd. (Tokyo, JP), Osaka Bioscience Institute (Osaka, JP) Patent Number: 6,562,342 Date filed: August 2, 2000 Abstract: Preventives/remedies for at least one disease selected from the group consisting of inflammatory intestinal disease, ischemic colitis and idiopathic inflammatory intestinal disease induced by infection, chemicals and radiation which contain as the active ingredient an anti-Fas ligand antibody; and preventives and remedies with the use of the same. Excerpt(s): This invention relates to preventives and remedies for inflammatory intestinal disease which contain an anti-Fas ligand antibody as their effective component. Fas is a cell surface antigen which transmits apoptosis signal to the cell, and Fas is recognized by Fas antibody (Yonehara, S. et al., J. Exp. Med., vol. 169, 1747-1756, 1989) which is a monoclonal antibody produced by immunizing a mouse with human fibroblast. Fas gene was recently cloned by Itoh, N. et al., and it was then found out that Fas is a cell membrane protein of about 45 kD, and from the amino acid sequence, it was revealed that Fas is a member of TNF receptor family (Cell, vol. 66, pages 233-243, 1991).

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Mouse Fas gene was also cloned (Watanabe-Fukunaga, et al., J. Immunol., vol. 148, pages 1274-1279, 1992), and the expression of Fas mRNA in thymus, liver, lung, heart, ovary was confirmed. Human Fas ligand is a polypeptide which has been reported by Nagata et al. to be a biological molecule which induces apoptosis of Fas-expressing cells (Takahashi, T. et al., International Immunology, vol. 6, pages 1567-1574, 1994). Human Fas ligand is a glycosilated Type II membrane protein of TNF family with a molecular weight of about 40 kD. As in the case of TNF, human Fas ligand in the human body is estimated to be in the form of a trimer (Tanaka, M. et al., EMBO Journal, vol. 14, pages 1129-1135, 1995). The extracellular domain of the human Fas ligand is highly homologous with the extracellular domain of rat Fas ligand (Suda, T. et al., Cell, vol. 75, pages 1169-1178, 1993) and mouse Fas ligand (Takahashi, T. et al., Cell, vol. 76, pages 969-976, 1994). The human Fas ligand recognizes not only the human Fas but also the mouse Fas to induce the apoptosis, and vice versa, the rat Fas ligand and the mouse Fas ligand also recognize the human Fas to induce the apoptosis. Shirakawa, K. et al. has produced an anti-Fas ligand antibody, and disclosed an assay method for measuring Fas ligand in human body fluids using the thus produced antibody (International Patent Application Publication No. WO 97/02290). Web site: http://www.delphion.com/details?pn=US06562342__ •

Substituted nipecotyl derivatives as inhibitors of cell adhesion Inventor(s): de Laszlo; Stephen E. (Rumson, NJ), Gutteridge; Clare E. (Westfield, NJ), Hagmann; William K. (Westfield, NJ), Kamenecka; Theodore M. (North Brunswick, NJ) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,403,584 Date filed: June 15, 2001 Abstract: Compounds of Formula I are antagonists of VLA-4 and/or.alpha.sub.4.beta.sub.7, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of AIDS-related dementia, allergic conjunctivitis, allergic rhinitis, Alzheimer's disease, asthma, atherosclerosis, autologous bone marrow transplantation, certain types of toxic and immune-based nephritis, contact dermal hypersensitivity, inflammatory bowel disease including ulcerative colitis and Crohn's disease, inflammatory lung diseases, inflammatory sequelae of viral infections, meningitis, multiple sclerosis, multiple myeloma, myocarditis, organ transplantation, psoriasis, pulmonary fibrosis, restenosis, retinitis, rheumatoid arthritis, septic arthritis, stroke, tumor metastasis, uveititis, and type I diabetes. Excerpt(s): The compounds of the present invention are antagonists of the VLA-4 integrin ("very late antigen-4"; CD49d/CD29; or.alpha.sub.4.beta.sub.1), the.alpha.4.beta.7 integrin (LPAM-1 and.alpha.sub.4.beta.sub.p), and/or the.alpha.9.beta.1 integrin, thereby blocking the binding of VLA-4 to its various ligands, such as VCAM-1 and regions of fibronectin,.alpha.4.beta.7 to its various ligands, such as MadCAM-1, VCAM-1 and fibronectin, and/or.alpha.9.beta.1 to its various ligands, such as tenascin, osteopontin and VCAM-1. Thus, these antagonists are useful in inhibiting cell adhesion processes including cell activation, migration, proliferation and differentiation. These antagonists are useful in the treatment, prevention and suppression of diseases mediated by VLA-4-,.alpha.4.beta.7 -, and/or.alpha.9.beta.1 binding and cell adhesion and activation, such as AIDS-related dementia, allergic

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conjunctivitis, allergic rhinitis, Alzheimer's disease, aortic stenosis, asthma, atherosclerosis, autologous bone marrow transplantation, certain types of toxic and immune-based nephritis, contact dermal hypersensitivity, inflammatory bowel disease including ulcerative colitis and Crohn's disease, inflammatory lung diseases, inflammatory sequelae of viral infections, meningitis, multiple sclerosis, myocarditis, organ transplantation, psoriasis, restenosis, retinitis, rheumatoid arthritis, septic arthritis, stroke, tumor metastasis, type I diabetes, and vascular occlusion following angioplasty. The present invention relates to susbstituted cyclic amine derivatives which are useful for the inhibition and prevention of leukocyte adhesion and leukocyte adhesion-mediated pathologies. This invention also relates to compositions containing such compounds and methods of treatment using such compounds. Many physiological processes require that cells come into close contact with other cells and/or extracellular matrix. Such adhesion events may be required for cell activation, migration, proliferation and differentiation. Cell-cell and cell-matrix interactions are mediated through several families of cell adhesion molecules (CAMs) including the selectins, integrins, cadherins and immunoglobulins. CAMs play an essential role in both normal and pathophysiological processes. Therefore, the targetting of specific and relevant CAMs in certain disease conditions without interfering with normal cellular functions is essential for an effective and safe therapeutic agent that inhibits cell-cell and cell-matrix interactions. Web site: http://www.delphion.com/details?pn=US06403584__ •

Substituted quinoxaline derivatives as interleukin-8 receptor antagonists Inventor(s): Carson; Kenneth G. (Needham, MA), Connor; David Thomas (Ann Arbor, MI), Li; Jie Jack (Ann Arbor, MI), Low; Joseph Edwin (Brighton, MI), Luly; Jay R. (Wellesley, MA), Miller; Steven Robert (Ann Arbor, MI), Roth; Bruce David (Plymouth, MI), Trivedi; Bharat Kalidas (Farmington Hills, MI) Assignee(s): Millennium Pharmaceuticals, Inc. (Cambridge, MA) Patent Number: 6,548,499 Date filed: October 20, 2000 Abstract: Quinoxaline compounds are described as well as methods for the preparation and pharmaceutical compositions of same, which are useful as interleukin-8 (IL-8) receptor antagonists and can be used in the treatment of a chemokine-mediated disease wherein the chemokine binds to an IL-8a (CXCR1) or b (CXCR2) receptor such as a chemokine-mediated disease selected from psoriasis, or atopic distress syndrome, arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, gastric ulcer, septic shock, endotoxic shock, gram-negative sepsis, toxic shock syndrome, stroke, cardiac and renal reperfusion injury, glomerulo-nephritis, or thrombosis, Alzheimer's disease, graft versus host reaction, allograft rejections, or allergic diseases. Excerpt(s): The present invention relates to novel quinoxaline compounds useful as pharmaceutical agents, to methods for their production, to pharmaceutical compositions which include these compounds and a pharmaceutical carrier, and to pharmaceutical methods of treatment. The compounds of the present invention are Interleukin-8 (IL-8) receptor antagonists. More particularly, the compounds of the present invention are useful in the treatment of a chemokine-mediated disease wherein the chemokine binds to an IL-8a (CXCR1) or b (CXCR2) receptor such as, for example, a chemokine-mediated disease selected from psoriasis, or atopic dermatitis, tumor growth and angiogenesis, asthma, chronic obstructive pulmonary disease, adult respiratory distress syndrome,

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arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, gastric ulcer, septic shock, endotoxic shock, gram-negative sepsis, toxic shock syndrome, stroke, cardiac and renal reperfusion injury, glomerulo-nephritis, or thrombosis, Alzheimer's disease, graft versus host reaction, allograft rejections, or allergic diseases. We have identified a series of quinoxalines that are IL-8 receptor antagonists and which can additionally be used in psoriasis, or atopic dermatitis, disease associated with pathological angiogenesis (i.e. cancer), asthma, chronic obstructive pulmonary disease, adult respiratory distress syndrome, arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, gastric ulcer, septic shock, endotoxic shock, gram-negative sepsis, toxic shock syndrome, stroke, cardiac and renal reperfusion injury, glomerulonephritis, or thrombosis, Alzheimer's disease, graft versus host reaction, allograft rejections, or allergic diseases. or a pharmaceutically acceptable salt thereof. Web site: http://www.delphion.com/details?pn=US06548499__ •

Synergistic compositions containing aromatic compounds and terpenoids present in alpinia galanga Inventor(s): Jensen; Nina Worm (Koge, DK), Petersen; Morten Just (Verlose, DK), Weidner; Morten Sloth (Virum, DK) Assignee(s): Eurovita A/S (Karlslunde, DK) Patent Number: 6,566,405 Date filed: August 6, 1999 Abstract: Novel compositions of matter containing aromatic compounds and terpenoids which are present in and may preferably be derived from the plant Alpinia galanga (Zingiberaceae) show synergistic effects with respect to immunomodulation, and they significantly suppress hypersensitivity reactions. Thus they are used for preparing medicaments for these purposes and, more specifically, for the treatment or prevention of IgE mediated allergic reactions and conditions, such as asthma, allergic rhinitis, a topic eczema or anaphylaxis, and autoimmune disorders, such as Crohn's disease, ulcerative colitis, rheumatoid arthritis or psoriasis, as well as for the alleviation of pain. They can for example be formulated into pharmaceuticals, cosmetics or dietary supplements. A method of preparing such compositions from Alpinia galanga is also described. Excerpt(s): The present invention relates to novel compositions of matter containing aromatic compounds and terpenoids which are present in and may preferably be derived from the plant Alpinia galanga (Zingiberaceae), and more specifically to novel pharmaceuticals, cosmetics or dietary supplements containing such compositions. Furthermore the invention relates to the use of the compositions for preparing medicaments for the treatment or prevention of hypersensitivity reactions and diseases associated with hypersensitivity reactions. The invention also relates to a method of preparing such compositions from Alpinia galanga. Alpinia galanga (L.), family Zingiberaceae, commonly known as Greater Galangal or Java Galangal, is cultivated and grows wild in Asia. The herb is rhizomatic, 1.8-2.1 m in height with oblong glabrous leaves and greenish white flowers. The fruits are orange-red capsules. The plant is also known under the name Languas galanga, especially in Thailand, and here it is locally called Katuk karohinee. In relation to the present invention the term "Alpinia galanga" refers to any variety of Alpinia galanga or Languas galanga found anywhere in the world.

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Therapeutic agent for treating ulcerative colitis Inventor(s): Aono; Shunji (Toyonaka, JP), Hattori; Ken-ichi (Kagawa, JP), Kawada; Mitsuhiro (Kagawa, JP) Assignee(s): Teikoku Seiyaku Co., Ltd. (Kagawa, JP) Patent Number: 6,586,022 Date filed: August 9, 2001 Abstract: An ulcerative colitis treating therapeutic agent which is very effective in repairing damaged tissues of ulcerative colitis and yet has no need of fear of side effects as those of steroids is provided. It is an therapeutic agent for treating ulcerative colitis which has peony root, especially, dry powders of peony root, or a Chinese medicine formulation containing peony root as an active ingredient. It is also an therapeutic agent for treating ulcerative colitis which has, as an active ingredient, an infused dry extract of peony root, an infused dry extract of a Chinese medicine formulation containing peony root, or especially an infused dry extract of Jia-Wei-Xiao-Yao-San, Dang-Gui-Shao-YaoSan, Shao-Yao-Gan-Cao-Tang, or Gui-Zhi-Fu-Ling-Wan. Excerpt(s): The present invention relates to a therapeutic agent for treating ulcerative colitis, which contains peony root. More particularly, the invention relates to a therapeutic agent for treating ulcerative colitis, having peony root or a Chinese medicine formulation containing peony root, which is very effective in repairing damaged tissues of ulcerative colitis and yet has no fear of side effects as those of steroids. Ulcerative colitis is a diffuse nonspecific inflammatory disease that only causes inflammation mainly in large intestines, that is, the regions from the rectum to the intestinum cecum and is characterized by continuous lesion. The disease is characterized in that the region of inflammation is localized in mucosa and submucosa, remission and exacerbation are repeated, and it cannot be completely cured. From the characteristics, it is said that patients can be relatively easily diagnosed as ulcerative colitis. With respect to the cause of ulcerative colitis, although there are various theories such as a theory that it is caused by food and life style and a theory that the cause is autoimmunity, the cause has not been convinced yet and the true cause is still unknown. Meanwhile, the enlargement process of inflammation of ulcerative colitis has been uncovered to a considerable extent and its knowledge has been disclosed in literatures, academic meetings, and the like. Ulcerative colitis cannot be treated by etiotropic therapy as a matter of fact and is treated by conservative therapy under the present conditions. Web site: http://www.delphion.com/details?pn=US06586022__

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Treatment of C. difficile toxin B associated conditions Inventor(s): Armstrong; Glen D. (Edmonton, CA), Heerze; Louis D. (Edmonton, CA) Assignee(s): SYNSORB Biotech, Inc. (Calgary, CA) Patent Number: 6,465,435 Date filed: June 13, 2000

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Abstract: This invention relates to prevention and/or treatment of antibiotic associated diarrhea, including Clostridium difficile associated diarrhea (CDAD), pseudomembranous colitis (PMC) and other conditions associated with C. difficile infection, using oligosaccharide compositions which bind C. difficile toxin B. More specifically, the invention concerns neutralization of C. difficile toxin B associated with such conditions. Excerpt(s): This invention relates to treatment of antibiotic associated diarrhea, including Clostridium difficile associated diarrhea (CDAD) and pseudomembranous colitis (PMC) and other conditions associated with C. difficile infection. More specifically, the invention concerns neutralization of C. difficile toxin B. a cytotoxin associated with CDAD, PMC and other conditions caused by C. difficile. The following references are cited in the application as numbers in brackets ({ }) at the relevant portion of the application. 1. Bartlett, J. G., et al., "Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia", N. Engl. J. Med., 298:531-534 (1978). Web site: http://www.delphion.com/details?pn=US06465435__

Patent Applications on Colitis As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to colitis: •

1,3,4-Oxadiazolin-2-one derivatives and drugs containing these derivatives as the active ingredient Inventor(s): Ohmoto, Kazuyuki; (Mishima-gun, JP), Okuma, Motohiro; (Mishima-gun, JP), Sekioka, Tomohiko; (Mishima-gun, JP) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037; US Patent Application Number: 20030087831 Date filed: May 31, 2002 Abstract: 1The compounds of formula (I) have an elastase inhibitory activity, therefor, they are useful for the treatment and/or prevention of a disease induced by an abnormal enhancement of degradation of elastin, collagen fiber and/or proteoglycans by elastase, for example, pulmonary emphysema, rheumatoid arthritis, arteriosclerosis, adult respiratory distress syndrome, myocardial infarction, ulcerative colitis and gingivitis. Excerpt(s): (3) a pharmaceutical composition comprising them as active ingredient. Recently, researches and developments concerning elastase inhibitors are becoming active. was disclosed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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This has been a common practice outside the United States prior to December 2000.

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5-Arylsulfonyl-imidazo[1',2':1,6]pyrido[2,3-b]pyrazine-6-amines compounds

and

related

Inventor(s): Kleinman, Edward F.; (Pawcatuck, CT) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030203911 Date filed: April 28, 2003 Abstract: A compound of the formula 1wherein a, X, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined above, useful in the treatment of respiratory, allergic, rheumatoid, body weight regulation, inflammatory and central nervous system disorders such as asthma, chronic obstructive pulmonary disease, adult respiratory diseases syndrome, shock, fibrosis, pulmonary hypersensitivity, allergic rhinitis, atopic dermatitis, psoriasis, weight control, rheumatoid arthritis, cachexia, crohn's disease, ulcerative colitis, arthritic conditions and other inflammatory diseases, depression, multi-infarct dementia and AIDS. Excerpt(s): This non-provisional patent application is based upon and claims priority from U.S. patent application Ser. No. 09/918,099, filed Jul. 30, 2001, which claims priority from United States non-provisional application Ser. No. 09/489,689, filed Jan. 24, 2000, which claims priority from U.S. provisional patent application No. 60/117,875, filed Jan. 29, 1999. This invention relates to 5-arylsulfonyl-imidazo[1',2':1,6]pyrido[2- ,3b]pyrazine-6-amines and related compounds. The compounds are selective inhibitors of phosphodiesterase type 4 (PDE4) and the production of tumor necrosins factor (TNF), and as such are useful in the treatment of respiratory, allergic, rheumatoid, body weight regulation, inflammatory and central nervous system disorders such as asthma, chronic obstructive pulmonary disease, adult respiratory diseases syndrome, shock, fibrosis, pulmonary hypersensitivity, allergic rhinitis, atopic dermatitis, psoriasis, weight control, rheumatoid arthritis, cachexia, Crohn's disease, ulcerative colitis, arthritic conditions and other inflammatory diseases, depression, multi-infarct dementia, and AIDS. This invention also relates to a method of using such compounds in the treatment of the foregoing diseases in mammals, especially humans, and to pharmaceutical compositions containing such compounds. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Allenic aryl sulfonamide hydroxamic acids as matrix metalloproteinase and tace inhibitors Inventor(s): Delos Santos, Efren Guillermo; (Nanuet, NY), Sandanayaka, Vincent Premaratna; (Northboro, MA) Correspondence: Daniel B. Moran; Five Giralda Farms; Madison; NJ; 07940; US Patent Application Number: 20030130238 Date filed: November 1, 2002 Abstract: Compounds of the formula 1are useful in treating disease conditions mediated by TNF-.alpha., such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease, degenerative cartilage loss, graft rejection, cachexia, inflammation, fever, insulin resistance, septic shock, congestive heart failure,

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inflammatory disease of the central nervous system, inflammatory bowel disease and HIV. Excerpt(s): This invention relates to allenic aryl sulfonamide hydroxamic acids which act as inhibitors of TNF-.alpha. converting enzyme (TACE) and matrix metalloproteinase (MMP). The compounds of the present invention are useful in disease conditions mediated by MMP and TACE, such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease, degenerative cartilage loss, graft rejection, cachexia, inflammation, fever, insulin resistance, septic shock, congestive heart failure, inflammatory disease of the central nervous system, inflammatory bowel disease and HIV. TNF-.alpha. converting enzyme (TACE) catalyzes the formation of TNF.alpha. from membrane bound TNF-.alpha. precursor protein. TNF-.alpha. is a proinflammatory cytokine that is believed to have a role in rheumatoid arthritis [Shire, M. G.; Muller, G. W. Exp. Opin. Ther. Patents 1998, 8(5), 531; Grossman, J. M.; Brahn, E. J. Women's Health 1997, 6(6), 627; Isomaki, P.; Punnonen, J. Ann. Med. 1997, 29, 499; Camussi, G.; Lupia, E. Drugs, 1998, 55(5), 613.] septic shock [Mathison, et. al. J. Clin. Invest. 1988, 81, 1925; Miethke, et. al. J. Exp. Med. 1992, 175, 91.], graft rejection [Piguet, P. F.; Grau, G. E.; et. al. J. Exp. Med. 1987, 166, 1280.], cachexia [Beutler, B.; Cerami, A. Ann. Rev. Biochem. 1988, 57, 505.], anorexia, inflammation [Ksontini, R,; MacKay, S. L. D.; Moldawer, L. L. Arch. Surg. 1998, 133, 558.], congestive heart failure [Packer, M. Circulation, 1995, 92(6), 1379; Ferrari, R.; Bachetti, T.; et. al. Circulation, 1995, 92(6), 1479.], post-ischaemic reperfusion injury, inflammatory disease of the central nervous system, inflammatory bowel disease, insulin resistance [Hotamisligil, G. S.; Shargill, N. S.; Spiegelman, B. M.; et. al. Science, 1993, 259, 87.] and HIV infection [Peterson, P. K.; Gekker, G.; et. al. J. Clin. Invest. 1992, 89, 574; Pallares-Trujillo, J.; Lopez-Soriano, F. J. Argiles, J. M. Med. Res. Reviews, 1995, 15(6), 533.]], in addition to its well-documented antitumor properties [Old, L. Science, 1985, 230, 630.]. For example, research with antiTNF-.alpha. antibodies and transgenic animals has demonstrated that blocking the formation of TNF-.alpha. inhibits the progression of arthritis [Rankin, E. C.; Choy, E. H.; Kassimos, D.; Kingsley, G. H.; Sopwith, A. M.; Isenberg, D. A.; Panayi, G. S. Br. J. Rheumatol. 1995, 34, 334; Pharmaprojects, 1996, Therapeutic Updates 17 (Oct.), au197M2Z.]. This observation has recently been extended to humans as well as described in "TNF-.alpha. in Human Diseases", Current Pharmaceutical Design, 1996, 2, 662. Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. Of these classes, the gelatinases have been shown to be the MMPs most intimately involved with the growth and spread of tumors. It is known that the level of expression of gelatinase is elevated in malignancies, and that gelatinase can degrade the basement membrane which leads to tumor metastasis. Angiogenesis, required for the growth of solid tumors, has also recently been shown to have a gelatinase component to its pathology. Furthermore, there is evidence to suggest that gelatinase is involved in plaque rupture associated with atherosclerosis. Other conditions mediated by MMPs are restenosis, MMP-mediated osteopenias, inflammatory diseases of the central nervous system, skin aging, tumor growth, osteoarthritis, rheumatoid arthritis, septic arthritis, corneal ulceration, abnormal wound healing, bone disease, proteinuria, aneurysmal aortic disease, degenerative cartilage loss following traumatic joint injury, demyelinating diseases of the nervous system, cirrhosis of the liver, glomerular disease of the kidney, premature rupture of fetal membranes, inflammatory bowel disease, periodontal disease, age related macular degeneration, diabetic retinopathy, proliferative vitreoretinopathy, retinopathy of prematurity, ocular inflammation, keratoconus, Sjogren's syndrome, myopia, ocular tumors, ocular

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angiogenesis/neo-vascularization and corneal graft rejection. For recent reviews, see: (1) Recent Advances in Matrix Metalloproteinase Inhibitor Research, R. P. Beckett, A. H. Davidson, A. H. Drummond, P. Huxley and M. Whittaker, Research Focus, Vol. 1,16-26, (1996), (2) Curr. Opin. Ther. Patents (1994) 4(1): 7-16, (3) Curr. Medicinal Chem. (1995) 2: 743-762, (4) Exp. Opin. Ther. Patents (1995) 5(2): 1087-110, (5) Exp. Opin. Ther. Patents (1995) 5(12): 1287-1196: (6) Exp. Opin. Ther. Patents (1998) 8(3): 281-259. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

AlphaAED and betaAED regulation of nuclear transcription, gene regulation, and/or gene expression Inventor(s): Loria, Roger M.; (Richmond, VA) Correspondence: Holliseden Pharmaceuticals, INC.; Suite 400; 4435 Eastgate Mall; San Diego; CA; 92121; US Patent Application Number: 20030181434 Date filed: March 21, 2003 Abstract: The present invention provides a means to regulate nuclear transcription and/or gene expression. The present invention also provides a means to regulate the levels of PPAR-.gamma., COX-2 and/or NF.kappa.B in a patient. The method of the present invention involves administering.alpha.AED (or an analogue thereof) or.beta.AED (or an analogue thereof) or both to a patient in need of regulation of nuclear transcription and/or gene expression and/or levels of PPAR-.gamma., COX-2, and/or NF.kappa.B. The methods of the present invention can be used to control adipogenesis (i.e. to treat obesity), angiogenesis, atherosclerosis, mesenteric fat hypertrophy, inflammatory bowel disease, colitis, Alzheimer's disease, and inflammatory glial responses in the brain. The methods of the present invention can also be used for treating diabetes, for regulating the immune response, and for regulating inflammation in a patient. Excerpt(s): This application claims priority from U.S. Provisional Application No. 06/365,817, filed Mar. 21, 2002 (pending), which is hereby incorporated herein by reference in its entirety. The present invention relates to methods of regulating nuclear transcription and inflammation using.alpha.AED and.beta.AED. Peroxisome Proliferator Activated Receptors (PPARs) are a Subclass of nuclear hormone transcription factors that have tissue-specific distribution and regulate gene expression. Three major subtypes of PPARs have been described:.alpha.,.gamma., and.delta. The PPARs were originally thought to be exclusively linked to the control of lipid metabolism and homeostasis. However, studies have revealed that PPAR activation can influence a wide range of biologic activities including cellular proliferation, differentiation and apoptosis. This receptor family is implicated in a wide range of human conditions including, but not limited to, obesity, diabetes, atherosclerosis, inflammation, cancer, and aging (Isemann and Green, Nature 347:645-650 (1990); Collingwood et al, J. Mol. Endocrinol. 23:255-275 (1999); McKenna et al, Endocr. Rev. 20:321-344 (1999); Schoonjans et al, Curr. Opin. Lipidol. 8:159-166 (1997); and Greene et al, Prostaglandins & Other Lipid Mediators 62:45-73 (2000)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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ANTISENSE OLIGONUCLEOTIDES TARGETED TO IL-15 Inventor(s): HAMANAKA, SHOJI; (YOKOSUKA, JP), KUBO, HIROYUKI; (CARLSBAD, CA), NOZAWA, IWAO; (CARLSBAD, CA), VEERAPANANE PH.D, DANGE; (SAN DIEGO, CA) Correspondence: Fish & Richardson, PC; 4350 LA Jolla Village Drive; Suite 500; San Diego; CA; 92122; US Patent Application Number: 20030013668 Date filed: July 7, 1999 Abstract: The invention features antisense oligonucleotide molecules that specifically bind polynucleotides encoding IL-15. The present invention provides antisense oligonucleotides capable of inhibiting IL-15 expression, and methods of use thereof to reduce activity of IL-15 in tissues in order to treat diseases such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, chronic liver disease, ulcerative colitis and cell proliferative disorders. Excerpt(s): This application claims priority from U.S. Provisional Application Ser. No. 60/091,873 filed Jul. 7, 1998, the disclosure of which is incorporated herein by reference. This invention relates generally to the field of therapeutic compositions and more specifically to antisense oligonucleotides that bind to interleukin-15 (IL-15 ) polynucleotides and methods of treatment for diseases associated with IL-15. There are a number of diseases known in humans that affect various tissues, including the joints, and particularly the synovium. These include synovial sarcomas, osteoarthritis, bacterial and fungal infections, and inflammatory, autoimmune, and hemorrhagic diseases. Combined, they are a cause of great pain and suffering in the population, with little effective therapy apart from symptomatic treatment with analgesics and antiinflammatory drugs (reviewed by Gardner, 1994 J. Anat. 184:465-76). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Apparatus and method for debilitating or killing microorganisms within the body Inventor(s): Ganz, Robert A.; (Minnetonka, MN), Melgaard, Hans L.; (North Oaks, MN) Correspondence: James V. Harmon; Pillsbury Center, Suite 2000; 220 South Sixth Street; Minneapolis; MN; 55402; US Patent Application Number: 20030191459 Date filed: April 9, 2002 Abstract: A surgical apparatus has a body portion that includes a shaft terminating in a distal head or tip and a means for directing light radiation from the apparatus onto the lining of a body cavity for treating an ailment in a body cavity of a patient as for example a gastrointestinal ailment of a patient such as gastritis, gastric ulcer, duodenal ulcer, gastric cancer, gastric lymphoma, ulcerative colitis, or Crohn's disease as well as for treating diseases of the circulatory system, urogenital systems and other body cavities. The method of use of the apparatus comprises inserting the shaft of the apparatus into a body cavity, e.g., stomach or colon, of the patient to place the distal tip of the shaft in the desired position. The body cavity of the patient is then irradiated with light radiation so as to kill or debilitate microorganisms lining the body cavity without serious destruction of the body tissue of the patient to thereby improve or alleviate one or more of the symptoms of the ailment. A probiotic comprising innocuous bacteria can

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be administered to the patient to reestablish the growth of normal microbial flora when used in the gastrointestinal tract. Excerpt(s): This invention relates to an apparatus and method for the destruction of micro-organisms on or within a body cavity of a patient through the use of radiation. Infections involving the human gastrointestinal tract are extremely common, involving many millions of people on an annual basis. These infections include bacteria, viruses, and fungi, and are responsible for significant illness, morbidity and, in many cases, death. While the invention has utility in destroying microorganisms in various parts of the body, e.g., the stomach, bowel, lungs, peritoneal cavity, urinary tract, etc., it is particularly useful in the treatment of gastrointestinal infections. It has recently been shown that the most common gastrointestinal infection in the world is due to Helicobacter pylori, a bacterial pathogen that infects the stomach and duodenum. In the United States, for example, Helicobacter pylori is found in approximately 20% of the adult population. It is a chronic gut infection and, once acquired, is notoriously difficult to cure. Most infectious bacteria can be readily destroyed by the human immune system; however, Helicobacter pylori lives in the lumen of the stomach and on the surfaces of the stomach and duodenal cells, making it relatively resistant to a host immune response, even if vigorous. Its position has, however, been taken advantage of in the treatment method and apparatus employed in the present invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Benzoic acid derivatives, processes for producing the same and drugs containing the same as the active ingredient Inventor(s): Kobayashi, Kaoru; (Osaka, JP), Maruyama, Takayuki; (Osaka, JP), Tani, Kousuke; (Osaka, JP) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037; US Patent Application Number: 20030114435 Date filed: August 16, 2002 Abstract: An agent comprising the benzoic acid of formula (I) 1, wherein A, B, R.sup.6, R.sup.7 are carbocyclic ring, heterocyclic ring, etc.; R.sup.1 is hydroxy etc.; R.sup.2, R.sup.3, R.sup.4 are alkyl etc.; R.sup.5, D, E are alkylene, etc.; G is oxygen etc., as active ingredient.The compound of formula (I) is considered to be useful for the treatment and/or prophylaxis of bone diseases, cancer, systemic granuloma, immunological diseases, allergy, atopy, asthma, gumboil, gingivitis, periodontitis, neurocyte death, Alzheimer's diseases, lungs injury, pulmopathy, acute hepatitis, nephritis, myocardial ischemia, Kawasaki disease, ambustion, ulcerative colitis, Crohn's disease, multiple organ failure, sleeping disorder, platelet aggregation, etc. Excerpt(s): The present invention relates to benzoic acid derivatives. , wherein all symbols have the same meanings as hereafter described, a process for the preparation thereof and a pharmaceutical agent comprising the same as active ingredient. Prostaglandin E.sub.2 (abbreviated as PGE.sub.2) has been known as a metabolite in the arachidonic acid cascade. It has been known that PGE.sub.2 possesses cyto-protective activity, uterine contractile activity, a pain-inducing effect, a promoting effect on digestive peristalsis, an awaking effect, a suppressive effect on gastric acid secretion, hypotensive activity, and diuretic activity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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CRYSTAL FORM OF N-(4-TRIFLUOROMETHYLPHENYL)-5METHYLISOXAZOLE-4-CARBOXAMID- E Inventor(s): Faasch, Holger; (Hochheim, DE), Hedtmann, Udo; (Frankfurt, DE), Paulus, Erich; (Eppstein, DE), Westenfelder, Uwe; (Frankfurt, DE) Correspondence: Finnegan, Henderson, Farabow, Garrett &; Dunner Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20030027851 Date filed: January 19, 2001 Abstract: The invention relates to a crystal modification of the compound of the formula I 1and the processes for the preparation of and use that crystal modifications 1.The invention is used for treating acute immunological episodes, such as sepsis, allergies, graft-versus-host and host-versus-graft-reactions, autoimmune diseases, in particular rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, psoriasis, atopic dermatitis, asthma, urticaria, rhinitis, uveitis, type II diabetes, liver fibrosis, cystic fibrosis, colitis, cancers, such as lung cancer, leukemia, ovarian cancer, sarcomas, Kaposi's sarcoma, meningioma, intestinal cancer, lymphatic cancer, brain tumors, breast cancer, pancreatic cancer, prostate cancer, or skin cancer. Excerpt(s): This case claims benefit under 35 U.S.C.sctn.119 of German priority document 19734438.0 filed on Aug. 8, 1997. This document, as well as German priority document 19756093.8, filed Dec. 17, 1997, are hereby incorporated by reference. The compound of formula I crystallizes in the first crystal modification in the space group P2.sub.1/c with 8 molecules in the unit cell. Molecules of the compound of formula I are present as dimers which originate from the individual molecules by formation of a -C.dbd.O. HN hydrogen bridge bond (2.938.ANG.), the two molecular levels being virtually perpendicular to one another (91.2.degree.). The two molecules have very different conformations. The angles made by the five- and six-membered rings with the central carbonyl group are 5.4.degree. and 2.1.degree. and 23.4.degree. and 23.1.degree., respectively. The latter twist creates the steric preconditions permitting the hydrogen bridge bond between the two molecules. Lines of strong intensity: 16.70; 18.90; 23.00; 23.65; and 29.05 degrees. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Diagnostic and therapeutic compositions and methods related to GPCR 38, a G protein-coupled receptor (GPCR) Inventor(s): Brown, Joseph P.; (Seattle, WA), Burmer, Glenna C.; (Seattle, WA), Kulander, Bruce G.; (Seattle, WA), Roush, Christine L.; (Seattle, WA) Correspondence: Joshua King; Graybeal Jackson Haley Llp; Suite 350; 155-108th Avenue N.E.; Bellevue; WA; 98004-5901; US Patent Application Number: 20030186336 Date filed: July 26, 2002 Abstract: The present invention comprises systems, methods, compositions and the like, such as diagnostics, medicaments and therapeutics, relating to GPR 38 and Alzheimer's disease and Parkinson's disease, inflammatory bowel diseases including ulcerative colitis and Crohn's disease, Hodgkin's disease, glioblastoma and carcinomas including breast, colon, lung (small cell and adenocarcinoma) pancreatic (small cell and

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adenocarcinoma), ovarian, and prostate. Such diagnostics and therapeutics include peptide, protein, antibody and nucleic acid based compositions, including agonists, antagonists, probes, antisense and gene therapy compositions. Excerpt(s): The present application claims priority from PCT patent application PCT/US01/45219, filed Nov. 29, 2001, which application claims priority from U.S. provisional patent application Ser. No. 60/250,251, filed Nov. 29, 2000, and U.S. provisional patent application Ser. No. 60/250,452, filed Nov. 30, 2000, both of which are presently pending. G protein-coupled receptors (GPCRs) are a large group of proteins that transmit signals across cell membranes. In general terms, GPCRs function somewhat like doorbells. When a molecule outside the cell contacts the GPCR (pushes the doorbell), the GPCR changes its shape and activates "G proteins" inside the cell (similar to the doorbell causing the bell to ring inside the house, which in turn causes people inside to answer the door). In addition, GPCRs are like high-security doorbells because each GPCR responds to only one specific kind of signaling molecule (called its "endogenous ligand"). Part of the GPCR is located outside the cell (the "extracellular domain"), part spans the cell's membrane (the "transmembrane domain"), and part is located inside the cell (the "intracellular domain"). GPCRs are embedded in the outer membrane of a cell and recognize and bind certain types of signaling molecules that are present in the spaces surrounding the cell. GPCRs are used by cells to keep an eye on the cells' own activity and environment. In organisms having many cells, the cells use GPCRs to talk to each other. GPCRs are of great interest to the pharmaceutical industry and other industries. For example, many drugs act by binding to specific GPCRs and initiating their intracellular actions, and diagnostics and therapeutics based on GPCRs are becoming increasingly important. Databases, such as LifeSpan BioScience's GPCR Database, help researchers to compare and contrast different GPCRs so that various GPCR functions can be investigated and established. With greater knowledge about the distribution of GPCRs in human tissues and their involvement in disease processes, researchers can design more diagnostics and more effective drugs with fewer side effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Early detection marker for chronic inflammatory associated diseases Inventor(s): Pereira, Heloise Anne; (Edmond, OK) Correspondence: Dunlap, Codding & Rogers P.C.; PO Box 16370; Oklahoma City; OK; 73114; US Patent Application Number: 20030170745 Date filed: March 7, 2003 Abstract: The present invention in one embodiment is an early detection marker for chronic inflammatory-associated diseases, including atherosclerosis, Alzheimer's disease, asthma, rheumatoid arthritis, osteoarthritis, and inflammatory diseases of the bowel such as Crohn's disease, Ulcerative colitis, Irritable bowel syndrome and Inflammatory bowel disease. The method, for example may comprise (1) obtaining a fluid sample from the subject, wherein the subject does not have an acute bacterial or viral infection when the fluid sample is obtained, (2) testing the fluid sample for a circulating or secreted CAP37 protein, and (3) concluding that the subject has a chronic inflammatory-associated disease when the CAP37 protein is detected in the fluid sample. The fluid sample may comprise serum, plasma, or cerebrospinal fluid, for

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example, or any other body fluid exposed to endothelial, vascular, or neuronal secretions. Excerpt(s): This application claims the benefit of U.S. Serial No. 60/363,114, filed Mar. 8, 2002, which is hereby expressly incorporated herein by reference in its entirety. The present invention relates to, but is not limited to, methods for detecting inflammatoryassociated diseases by detecting CAP37 proteins in a body fluid. Cationic Antimicrobial Protein of M.sub.r 37 kDa (CAP37) was originally isolated from granule extracts of human polymorphonuclear leukocytes (PMN) in 1984 (1). The amino acid sequence of PMN-CAP37 revealed its relation to members of the serine protease family that have a conserved catalytic active site consisting of his-57, asp-102 and ser-195 in the charge relay system (2). Of these sites, the conserved histidine and serine of the catalytic triad have been replaced with serine and glycine residues, respectively, rendering CAP37 ineffective as a serine protease (2,3). However, CAP37 has been demonstrated to have a diverse and exciting repertoire of functions. It was first analyzed regarding its bactericidal properties against Gram negative bacteria including, but not limited to, Salmonella typhimurium, Escherichia coli and Pseudomonas aeruginosa (4) and its ability to bind to and neutralize lipopolysaccharide (LPS)(5). Subsequently we showed CAP37 to be a potent chemoattractant for monocytes (6). Additionally, regarding its effects on the monocyte, CAP37 has been reported to stimulate their survival and thrombospondin secretion (7), also to enhance the LPS-stimulated release of prostaglandin E2 (8), interleukin 6 (IL-6)(9) and tumor necrosis factor-alpha (TNF.alpha.)(8-10). To add even further to its extensive range of known functions, CAP37 has been demonstrated to stimulate the reversible contraction of fibroblasts and endothelial cells (7) and to activate endothelial cell protein kinase C (PKC)(11). Recently, CAP37 released from stimulated PMN was reported to be taken up and sequestered in nearby endothelial mitochondria and has been suggested to protect against apoptosis (12). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Fused thiophone derivatives and drugs containing the same as the active ingredient Inventor(s): Katsube, Nobuo; (Osaka, JP), Kishimoto, Tadamitsu; (Osaka, JP), Konishi, Mikio; (Osaka, JP), Konno, Mitoshi; (Osaka, JP) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, NW; Washington; DC; 20037-3213; US Patent Application Number: 20030073706 Date filed: April 23, 2002 Abstract: The present invention relates to a fused thiophene derivative of the formula (I) (wherein all the symbols are defined as described in the specification) and an inhibitor of producing interleukin-6 and/or interleukin-12 comprising the said derivative as an active ingredient.A fused thiophene derivative of the formula (I) is useful as an agent for the prevention and/or treatment of various inflammatory diseases, sepsis, multiple myeloma, plasma cell leukemia, osteoporosis, cachexia, psoriasis, nephritis, renal cell carcinoma, Kaposi's sarcoma, rheumatoid arthritis, gammopathy, Castleman's disease, atrial myxoma, diabetes mellitus, autoimmune diseases, hepatitis, multiple sclerosis, colitis, graft versus host immune diseases, infectious diseases. 1 Excerpt(s): The present invention relates to fused thiophene derivatives and inhibitors of producing Interleukin-6 (abbreviated as IL-6 hereafter) and/or Interleukin-12

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(abbreviated as IL-12 hereafter) containing fused thiophene derivatives as an active ingredient. (wherein all the symbols are as defined hereafter.) and non-toxic salts thereof, novel fused thiophene derivatives of the said formula (IA) or non-toxic salts thereof and methods for preparation thereof. Moreover, the present invention relates to a method for preparation of a compound of the formula (XI) which is an intermediate for the compounds of the formula (I). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Indole derivatives, process for preparation of the same and use thereof Inventor(s): Kobayashi, Kaoru; (Mishima-gun, JP), Nambu, Fumio; (Mishima-gun, JP), Torisu, Kazuhiko; (Mishima-gun, JP) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037; US Patent Application Number: 20030176400 Date filed: December 13, 2002 Abstract: Indole derivatives represented by formula (I): 1(wherein all symbols are described in the description), a process for the preparation of the same and a DP receptor antagonist comprising it as an active ingredient. Since the compounds of formula (I) binds to and are antagonistic to a DP receptor, they are useful in for the prevention and/or treatment of diseases, for example, allergic diseases (allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma, food allergy, etc., systemic mastocytosis; disorders due to systemic mastocyte activation, anaphylactic shock, bronchoconstriction, urticaria, eczema, etc.), diseases accompanied with itching (atopic dermatitis, urticaria, etc.), secondary diseases caused by behaviors (scratching behaviors, beating, etc.) (cataract, retinal detachment, inflammation, infection, sleep disorder, etc.), inflammation, chronic obstructive pulmonary disease, ischemic reperfusion disorder, cerebrovascular disorder, pleuritis complicated by rheumatoid arthritis, ulcerative colitis, and the like. Excerpt(s): The present invention relates to indole derivatives. (wherein all symbols have the same meanings as described below), a process for the preparation of the same and use thereof. Prostaglandin D (hereinafter referred to as "PGD") are known as a metabolite in the arachidonic acid cascade, and are known to have effects of bronchoconstriction, vasodilatation or vasoconstriction and platelet aggregation inhibition. PGD is considered to be produced from mast cells, and the increase of PGD concentration has been recognized among systemic mastocytosis patients (New Eng. J. Med., 303, 1400-1404 (1980)). Also, PGD is considered to relate to neuro activities, especially, sleep and hormone secretion. Furthermore, there are reports suggesting participations in platelet aggregation, glycogen metabolism, ocular tension adjustment and the like. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Isoxazolone compounds useful in treating diseases associated with unwanted cytokine activity Inventor(s): Clark, Michael Philip; (Loveland, OH), De, Biswanath; (Cincinnati, OH), Djung, Jane Far-Jine; (Mason, OH), Laughlin, Steven Karl; (Taylor Mill, KY), Natchus, Michael George; (Alpharetta, GA), Tullis, Joshua Spector; (Broomfield, CO) Correspondence: The Procter & Gamble Company; Intellectual Property Division; Winton Hill Technical Center - Box 161; 6110 Center Hill Avenue; Cincinnati; OH; 45224; US Patent Application Number: 20030096814 Date filed: May 7, 2002 Abstract: Isoxazolone compounds having the generic structure: 1are used to treat disease associated with unwanted cytokine activity, including rheumatoid arthritis, osteoarthritis, diabetes, HIV/AIDS, inflammatory bowel disease, Crohn's disease, ulcerative colitis, congestive heart, hypertension, chronic obstructive pulmonary disease, septic shock syndrome, tuberculosis, adult respiratory distress, asthma, atherosclerosis, muscle degeneration, periodontal disease, cachexia, Reiter's syndrome, gout, acute synovitis, anorexia and bulimia nervosa fever, malaise, myalgia and headaches. Excerpt(s): This application claims priority under Title 35, United States Code 119(e) from Provisional Application Serial No. 60/293,889, filed May 24, 2001. The present invention is directed to certain isoxazolone compounds that inhibit the release of inflammatory cytokines such as interleukin-1 (1L-1) and tumor necrosis factor (TNF) from cells. The compounds of the invention, therefore, are useful in treating diseases involving unwanted cytokine activity. Many cytokine-mediated diseases and conditions are associated with excessive or unregulated production or activity of one or more cytokines such as interleukin 1 (IL-1), tumor necrosis factor (TNF), interleukin 6 (IL-6) and interleukin 8 (IL-8). IL-1 and TNF are important proinflammatory cytokines, which along with several other related molecules, mediate inflammatory cellular response in a wide variety of diseases and conditions. Proinflammatory cytokines such as IL-1 and TNF stimulate other inflammatory mediators such as nitric oxide, cyclooxygenase-2, matrix metalloproteinases. The inhibition of these cytokines is consequently both directly and indirectly beneficial in controlling, reducing and alleviating many of these disease states. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method and apparatus for distinguishing crohn's disease from ulcerative colitis and other gastrointestinal diseases by detecting the presence of fecal antibodies to saccharomyces cerevisiae Inventor(s): Boone, James Hunter; (Christiansburg, VA), Lyerly, David Maxwell; (Radford, VA), Wilkins, Tracy Dale; (Riner, VA) Correspondence: Shook, Hardy & Bacon Llp; 1200 Main Street; Kansas City; MO; 641052118; US Patent Application Number: 20030143649 Date filed: October 25, 2002

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Excerpt(s): This application claims the benefit of priority to U.S. Provisional Application No. 60/335,812 filed on Oct. 26, 2001, the entirety of the disclosure of which is hereby incorporated by reference. Not Applicable. A method and apparatus for the differentiation of Crohn's disease from other gastrointestinal illnesses, such as ulcerative colitis and irritable bowel syndrome, using the presence of fecal anti-Saccharomyces cerevisiae antibodies (ASCA) as a marker for Crohn's disease are provided. The apparatus includes an enzyme-linked immunoassay or other immunoassay that utilizes antibodies specific to human immunoglobulins for the measurement of total endogenous ASCA in a human fecal sample. The method and apparatus may be used by healthcare providers to distinguish Crohn's disease from other gastrointestinal illnesses, such as ulcerative colitis and irritable bowel syndrome. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for the preparation of a pharmaceutical composition comprising 5aminosalicylic acid for use in treatment of ulcerative colitis and crohn's disease Inventor(s): Jepsen, Svenn Kluver; (Holte, DK) Correspondence: Steptoe & Johnson Llp; 1330 Connecticut AVE., NW; Washington; DC; 20036; US Patent Application Number: 20030138495 Date filed: October 11, 2002 Abstract: The present invention concerns a new method of preparing granules comprising 5-aminosalicylic acid and a new method of preparing a pharmaceutical composition for the treatment of ulcerative colitis or Crohn's disease by oral administration comprising as active ingredient 5-aminosalicylic acid. Excerpt(s): The present invention relates to a method of preparing a pharmaceutical composition useful for the treatment of ulcerative colitis and Crohn's disease, currently denominated "inflammatory bowel diseases" (IBD). More particular, the invention relates to a new method of producing granules comprising 5-aminosalisylic acid (5ASA) for use in the preparation of solid oral dosage forms. Ulcerative colitis is a chronic inflammatory disease of the colon of unknown etiology. In its acute stages it resembles an infectious disease, but no microorganism has been definitively established as its cause. The disease causes inflammations of the mucosa of the colon, with extension to the submucosa in severe cases. Typically, not only the colon, but also the rectum is attacked, but only rarely is the ileum involved. The ulcer formation and its extent vary with the developmental stage of the disease, but can often be determined macroscopically (sigmoidoscopy and colonoscopy). The related disease, Crohn's disease, also known as regional enteritis or colitis granulomatosa, is most frequently located in the small intestine (small bowel), especially in the ileum, but may also affect the jejunum and any part of the colon, including the rectum. In the latter case the differentiation of Crohn's disease from ulcerative colitis gives rise to great diagnostic problems. Generally, the inflammation differs from that of ulcerative colitis by progressing to layers deeper than the mucosa and affecting the epithelium to a lesser degree. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods and compositions for treating inflammatory bowel diseases relating to human tumor necrosis factor-gamma-beta Inventor(s): Ni, Jian; (Germantown, MD), Rosen, Craig A.; (Laytonsville, MD), Wei, Ping; (Brookeville, MD), Yu, Guo-Liang; (Berkeley, CA), Zhang, Jun; (San Diego, CA) Correspondence: Human Genome Sciences Inc; 9410 Key West Avenue; Rockville; MD; 20850 Patent Application Number: 20030198640 Date filed: December 6, 2002 Abstract: The present invention encompasses methods for detection, diagnosis, prevention, treatment, and/or amelioration of inflammatory bowel diseases and disorders using TNF-gamma-.beta. and its receptors DR3 and TR6. In particular the invention encompasses methods of using TNF-gamma-.beta., DR3 and TR6 polypeptides, as well as antibodies, and antagonists thereto, in the diagnosis, prognosis and treatment of ulcerative colitis and/or Crohn's disease. Methods of screening for antagonists of the TNF-gamma-.beta. polypeptide, together with therapeutic uses of such antagonists are also disclosed. Excerpt(s): This application, which claims benefit under 35 U.S.C.sctn.119(e) of U.S. Provisional Application No. 60/336,695, filed Dec. 7, 2001, is a Continuation-In-Part of U.S. patent application Ser. No. 10/226,294, filed Aug. 23, 2002; which in turn claims the benefit of priority under 35 U.S.C.sctn.119(e) based on U.S. Provisional Application No. 60/314,381, filed Aug. 24, 2001, and is a Continuation-In-Part of U.S. patent application Ser. No. 09/899,059, filed Jul. 6, 2001; which in turn claims the benefit of priority under 35 U.S.C.sctn.119(e) based on U.S. Provisional Application Nos. 60/278,449 and 60/216,879, filed Mar. 26, 2001 and Jul. 7, 2000 respectively, and is a Continuation-InPart of U.S. patent application Ser. No. 09/559,290, filed Apr. 27, 2000; which in turn claims the benefit of priority under 35 U.S.C.sctn.119(e) based on U.S. Provisional Application Nos. 60/180,908, 60/134,067, 60/132,227 and 60/131,963, filed Feb. 8, 2000, May 13, 1999, May 3, 1999 and Apr. 30, 1999 respectively, and is a Continuation-In-Part of U.S. patent application Ser. No. 09/246,129, filed Feb. 8, 1999; which in turn claims the benefit of priority under 35 U.S.C.sctn.119(e) based on U.S. Provisional Application No. 60/074,047, filed Feb. 9, 1998, and is a Continuation-In-Part of U.S. patent application Ser. No. 09/131,237, filed Aug. 7, 1998; which in turn is a Continuation-In-Part of U.S. patent application Ser. No. 09/005,020, filed Jan. 9, 1998, now abandoned; which in turn is a Continuation-In-Part of U.S. patent application Ser. No. 08/461,246, filed Jun. 5, 1995, now abandoned; which in turn is a Continuation-In-Part of PCT/US94/12880 filed Nov. 7, 1994. The contents of each of the above-identified applications and their associated sequence listings are hereby incorporated by reference in their entireties. The present invention encompasses methods for diagnosis and treatment of inflammatory bowel diseases and disorders using a novel member of the tumor necrosis factor (TNF) family of cytokines. In particular the invention encompasses methods of using TNFgamma-.beta., and/or its receptors DR3 and TR6, in the diagnosis, prognosis and treatment of inflammatory bowel diseases and disorders. Furthermore, the invention encompasses methods of using homomultimeric and heteromultimeric polypeptide complexes comprising TNF-gamma-.beta., and/or its receptors DR3 and TR6, in the diagnosis, prognosis and treatment of inflammatory bowel diseases and disorders. Also encompassed by the invention are methods of using TNF-gamma-.beta., and/or its receptors DR3 and TR6, and/or homomultimeric or heteromultimeric polypeptide complexes containing TNF-gamma-.beta., and/or its receptors DR3 and TR6, in the diagnosis, prognosis and treatment of diseases and/or disorders associated with

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inflammatory bowel diseases and disorders. Also encompassed by the invention are methods of using TNF-gamma-.beta., and/or its receptors DR3 and TR6, and/or homomultimeric or heteromultimeric polypeptide complexes containing TNF-gamma.beta., and/or its receptors DR3 and TR6, in the diagnosis, prognosis and treatment of diseases and/or disorders associated with aberrant interferon gamma secretion and/or activity, including, for example, inflammatory bowel disease. This invention encompasses methods of using polynucleotides, polypeptides encoded by the polynucleotides, antibodies that bind the polypeptides, and antagonists of such polypeptides in the detection, diagnosis, prevention, treatment, and/or amelioration of inflammatory bowel disease. The present invention further encompasses inhibiting the production and function of the polypeptides of the present invention for prevention, treatment, and/or amelioration of inflammatory bowel disease. The cytokine known as tumor necrosis factor-.alpha. (TNF.alpha.; also termed cachectin) is a protein secreted primarily by monocytes and macrophages in response to endotoxin or other stimuli as a soluble homotrimer of 17 kD protein subunits (Smith, R. A. et al., J. Biol. Chem. 262:6951-6954 (1987)). A membrane-bound 26 kD precursor form of TNF has also been described (Kriegler, M. et al., Cell 53:45-53 (1988)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

METHODS FOR TREATING AND PREVENTING ASTHMA AND NON-INVASIVE FUNGUS-INDUCED RHINOSINUSITIS Inventor(s): Ponikau, Jens; (Rochester, MN) Correspondence: Fish & Richardson P.C.; 3300 Dain Rascher Plaza; 60 South Sixth Street; Minneapolis; MN; 55402; US Patent Application Number: 20030091510 Date filed: February 8, 2000 Abstract: The invention involves methods and materials for treating and preventing non-invasive fungus-induced mucositis. Specifically, the invention involves administrating an antifungal agent such that it contact mucus in an amount, at a frequency, and for a duration effective to prevent, reduce, or eliminate non-invasive fungus-induced rhinosinusitis. This invention also provides methods and materials for diagnosing non-invasive fungus-induced rhinosinusitis and culturing non-invasive fungus from a mammalian mucus sample as well as specific antifungal formulations and medical devices for treating and preventing non-invasive fungus-induced rhinosinusitis. In addition, the invention provides methods and materials for treating and preventing other non-invasive fungus-induced mucositis conditions such as chronic otitis media, chronic colitis, and Crohn's disease. Further, the invention involves methods and materials for treating and preventing chronic asthma symptoms. Excerpt(s): This application claims priority from U.S. Provisional Application Serial No. 60/062,709, filed Oct. 22, 1997, U.S. Provisional Application Serial No. 60/063,414, filed Oct. 28, 1997, U.S. Provisional Application Serial No. 60/063,418, filed Oct. 28, 1997, U.S. Provisional Application Serial No. 60/083,272, filed Apr. 28, 1998 and U.S. Provisional Application Serial No. 60/086,397, filed May 22, 1998. The invention relates to methods and materials involved in the treatment and prevention of non-invasive fungus-induced inflammation of mucosal tissue as well as asthma symptoms. Mucositis, the inflammation of mucosal tissue, is a serious medical problem that affects millions of people worldwide. For example, conservative estimates indicate that between 20 to 40

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million Americans suffer from chronic rhinosinusitis, an inflammation of the nasal cavity and/or paranasal sinuses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods of treating ulcerative colitis with chimeric anti-TNF antibodies Inventor(s): Daddona, Peter; (Menlo Park, CA), Ghraveb, John; (Downingtown, PA), Knight, David; (Berwyn, PA), Le, Junming; (Jackson Heights, NY), Siegel, Scott; (Westborough, MA), Vilcek, Jan; (New York, NY) Correspondence: Hamilton, Brook, Smith & Reynolds, P.C.; 530 Virginia Road; P.O. Box 9133; Concord; MA; 01742-9133; US Patent Application Number: 20030198641 Date filed: March 4, 2003 Abstract: Anti-TNF antibodies, fragments and regions thereof which are specific for human tumor necrosis factor-.alpha. (TNF.alpha.) and are useful in vivo diagnosis and therapy of a number of TNF.alpha.-mediated pathologies and conditions, as well as polynucleotides coding for murine and chimeric antibodies, methods of producing the antibody, methods of use of the anti-TNF antibody, or fragment, region or derivative thereof, in immunoassays and immunotherapeutic approaches are provided. Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/756,398, filed Jan. 8, 2001, which is a divisional of U.S. application Ser. No. 09/133,119, filed Aug. 12, 1998, now U.S. Pat. No. 6,277,969, issued Aug. 21, 2001, which is a divisional of U.S. application Ser. No. 08/570,674, filed Dec. 11, 1995, now abandoned, which is a continuation-in-part of U.S. application Ser. No. 08/324,799, filed Oct. 18, 1994, now U.S. Pat. No. 5,698,195, issued Dec. 16, 1997, which is a continuation-in-part of U.S. application Ser. Nos. 08/192,102, now U.S. Pat. No. 5,656,272, issued Aug. 12, 1997, Ser. No. 08/192,861, now U.S. Pat. No. 5,919,452, issued Jul. 6, 1999, and Ser. No. 08/192,093, now U.S. Pat. No. 6,284,471, issued Sep. 4, 2001, all filed on Feb. 4, 1994 which are continuations-in-part of U.S. application Ser. No. 08/010,406, filed Jan. 29, 1993, now abandoned, and U.S. application Ser. No. 08/013,413, filed Feb. 2, 1993, now abandoned, which is a continuation-in-part of U.S. application Ser. No. 07/943,852, filed Sep. 11, 1992, now abandoned, which is a continuation-in-part of U.S. application Ser. No. 07/853,606, filed Mar. 18, 1992, now abandoned, which is a continuation-in-part of U.S. application Ser. No. 07/670,827, filed Mar. 18, 1991, now abandoned. Each of the above applications are entirely incorporated herein by reference. The present invention in the field of immunology and medicine relates to anti-tumor necrosis factor (TNF) antibodies, anti-TNF peptides and nucleic acids encoding therefor, and to pharmaceutical and diagnostic compositions and production, diagnostic and therapeutic methods thereof, and to methods for treating human TNF-mediated pathologies. Monocytes and macrophages secrete cytokines known as tumor necrosis factors (TNF.alpha.) and tumor necrosis factor-.beta. (TNF.beta.) in response to endotoxin or other stimuli. TNF.alpha. is a soluble homotrimer of 17 kD protein subunits (Smith, et al., J. Biol. Chem. 262:6951-6954 (1987)). A membrane-bound 26 kD precursor form of TNF also exists (Kriegler, et al., Cell 53:45-53 (1988)). For reviews of TNF, see Beutler, et al., Nature 320:584 (1986), Old, Science 230:630 (1986), and Le, et al., Lab. Invest. 56:234. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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N-arylsulfonyl aryl aza-bicyclic derivatives as potent cell adhesion inhibitors Inventor(s): Chang, Linda L.; (Wayne, NJ), Hagmann, William K.; (Westfield, NJ), Lin, Linus S.; (Westfield, NJ), Mumford, Richard A.; (Red Bank, NJ), Shah, Shrenik K.; (Metuchen, NJ) Correspondence: Merck And CO Inc; P O Box 2000; Rahway; NJ; 070650907 Patent Application Number: 20020193399 Date filed: March 13, 2002 Abstract: Compounds of Formula I are antagonists of VLA-4 and/or alpha4/beta7, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of AIDS-related dementia, allergic conjunctivitis, allergic rhinitis, Alzheimer's disease, asthma, atherosclerosis, autologous bone marrow transplantation, certain types of toxic and immune-based nephritis, contact dermal hypersensitivity, inflammatory bowel disease including ulcerative colitis and Crohn's disease, inflammatory lung diseases, inflammatory sequelae of viral infections, meningitis, multiple sclerosis, multiple myeloma, myocarditis, organ transplantation, psoriasis, pulmonary fibrosis, restenosis, retinitis, rheumatoid arthritis, septic arthritis, stroke, tumor metastasis, uveititis, and type I diabetes. Excerpt(s): The compounds of the present invention are antagonists of the VLA-4 integrin ("very late antigen-4"; CD49d/CD29; or.alpha.sub.4.beta.sub.1- ), the.alpha.sub.4.beta.sub.7 integrin (LPAM-1 and.alpha.sub.4.beta.sub.p), and/or the.alpha.sub.9.beta.sub.1 integrin, and are useful in the treatment, prevention and suppression of diseases mediated by VLA-4-,.alpha.sub.4.beta.sub.7-, and/or.alpha.sub.9.beta.sub.1-binding and cell adhesion and activation. The present invention relates to potent substituted N-arylsulfonylated-proline derivatives which are useful for the inhibition and prevention of leukocyte adhesion and leukocyte adhesionmediated pathologies. This invention also relates to compositions containing such compounds and methods of treatment using such compounds. Many physiological processes require that cells come into close contact with other cells and/or extracellular matrix. Such adhesion events may be required for cell activation, migration, proliferation and differentiation. Cell-cell and cell-matrix interactions are mediated through several families of cell adhesion molecules (CAMs) including the selectins, integrins, cadherins and immunoglobulins. CAMs play an essential role in both normal and pathophysiological processes. Therefore, the targeting of specific and relevant CAMs in certain disease conditions without interfering with normal cellular functions is essential for an effective and safe therapeutic agent that inhibits cell-cell and cell-matrix interactions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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NKT cell-activating agents containing alpha-glycosylceramides Inventor(s): Kawano, Tetsu; (Chiba, JP), Koezuka, Yasuhiko; (Gunma, JP), Taniguchi, Masaru; (Chiba, JP) Correspondence: Stephen A. Bent; Foley & Lardner; Washington Harbour; 3000 K Street, N.W., Suite 500; Washington; DC; 20007-5143; US Patent Application Number: 20030139351 Date filed: January 2, 2003

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Abstract: An objective of the present invention is to provide NKT cell-activating agents, therapeutic agents for autoimmune diseases (for example, systemic lupus erythematosus, systemic sclerosis, ulcerative colitis, encephalomyelitis, multiple sclerosis and human type I diabetes), and abortifacients. The medicinal compositions according to the present invention comprise.alpha.-glycosylceramides of the following formula (I), or a salt or a solvate thereof as an active ingredient. 1 Excerpt(s): The present invention relates to NKT cell-activating agents, therapeutic agents for autoimmune diseases and agents for inducing abortion. It has been revealed that intermediate TCR cells (TCR.sup.int cells), which express T-cell receptors (TCRs) intermediately, are related to natural killer (NK) cells in terms of their features, for example, showing a large granular lymphocyte (LGL)-like morphology, constantly expressing IL-2R.beta.-chains, and having perforin granules, but they are clearly different from NK cells in terms of having TCRs (Watanabe, H. et al., J. Immunol., 155, 2972 (1995)). Furthermore, among the TCR.sup.int cells activated by interleukin 12 (IL12), NK 1.1-expressing NK 1.1.sup.+TCR.sup.int (NKT) cells have been shown to be important effector cells in controlling hematogenous metastases of tumors to the liver and lung in mice (Hashimoto, W. et al., J. Immunol., 154, 4333 (1995); Anzai, R. et al., Immunol., 88, 82 (1996)). These data suggest that the NKT cells may play an important role in eradicating cancer cells, parasites, protozoans, and intracellular infectious bacteria such as Listeria monocytogenes and Micobacterium tubeculosis (Seki, S. et al., Clin. Immunol., 28, 1069 (1996)). The NKT cells are also known to be closely associated with acute rejection in bone marrow transplantation (Yankelevich, B. et al., J. Immunol., 142, 3423 (1989)) and with controlling of IgE antibody production by controlling Th1/Th2 differentiation of helper T cells (Yoshimoto, T. et al., J. Exp. Med., 179, 1285 (1994)). Thus, the NKT cells are a group of new cells that are currently attracting enormous attention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel phospholipase D polypeptide and DNA sequences Inventor(s): Engebrecht, Joanne; (Stony Brook, NY), Frohman, Michael A.; (Setauket, NY), Morris, Andrew J.; (Mt. Sinai, NY) Correspondence: Gregory Giotta, PH.D.; Vice President & Chief Legal Counsel; Onyx Pharmaceuticals, INC.; 3031 Research Drive; Richmond; CA; 94806; US Patent Application Number: 20030124108 Date filed: April 30, 2002 Abstract: Provided are novel phospholipase D DNA and amino acid sequences. The sequences are useful in methods and compositions for identifying phospholipase D mediator molecules which are in turn useful in therapeutic pharmacuetical compositions for treating rheumatoid arthritis, psoriasis, ulcerative colitis, in wound healing and for treating other diseases or conditions characterized by exhibition of an inflammatory response or in the treatment of cancer and other diseases characterized by pathogenic mitogenicity. Excerpt(s): This invention is in the field of molecular biology and particularly relates to nucleic acid sequences that encode novel phospholipases. The mechanism by which specificity of physiological responses are conferred by a limited number of signal transducing substances, typically enzymes, is poorly understood. Cellular receptors on the surfaces of various cells are involved and initiate multiple signaling pathways. Some

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of the receptors on neutrophils are known: the PAF receptor, the interleukin-8 receptor and the fMetLeuPhe receptor all belong to the super-family of G-protein-linked receptors. A common feature of these receptors is that they span the cell membrane seven times, forming three extracellular and three intracellular loops and a cytoplasmic carboxy-terminal tail. The third loop and the tail exhibit extensive variability in length and sequence, leading to speculation that these parts are responsible for the selective interaction with the various G-proteins. Many of these G-protein-linked receptors stimulate the activation of three phospholipases, phospholipase C (PLC), phospholipase D (PLD) and phospholipase A.sub.2 (PLA.sub.2). These phospholipases constitute a family of regulatory enzymes which trigger various neutrophilic functions, for example adherence, aggregation, chemotaxis, exocytosis of secretory granules and activation of NADPH oxidase, i.e., the respiratory burst. The main substrates for the phospholipases are membrane phospholipids. The primary substrates for PLC are the inositol containing lipids, specifically and typically phosphotidylinositol (PI). PI is phosphorylated by PLC resulting in the formation of PIP, phosphotidylinositol 4phosphate. The primary substrate for PLD and PLA.sub.2 is phosphatidylcholine (PC), a relatively ubiquitous constituent of cell membranes. The activity of cytosolic PLA.sub.2 on PC liberates arachidonic acid, a precursor for the biosynthesis of prostaglandins and leukotrienes and possible intracellular secondary messenger. PLD, on the other hand, catalyzes the hydrolytic cleavage of the terminal phosphate diester bond of glycerophospholipids at the P-O position. PLD activity was originally discovered in plants and only relatively recently discovered in mammalian tissues. PLD has been the focus of recent attention due to the discovery of its activation by fMetLeuPhe in neutrophils. PLD activity has been detected in membranes and in cytosol. Although a 30 kD (kilodalton) and an 80 kD activity have been detected, it has been suggested that these molecular masses represented a single enzyme with varying extents of aggregation. See Cockcroft, Biochimica et Biophysica Acta 1113: 135-160 (1992). One PLD has been isolated, cloned and partially characterized. See Hammond, J. Biol. Chem. 270:29640-43 (1995). Biological characterization of PLD1 revealed that it could be activated by a variety of G-protein regulators, specifically PKC (protein kinase C), ADPribosylation factor (ARF), RhoA, Rac1 and cdc-42, either individually or together in a synergistic manner, suggesting that a single PLD participates in regulated secretion in coordination with ARF and in propagating signal transduction responses through interaction with PKC, PhoA and Rac1. Nonetheless, PKC-independent PLD activation has been associated with Src and Ras oncogenic transformation, leaving open the possibility that additional PLDs might exist. See Jiang, Mol. and Cell. Biol. 14:3676 (1994) and Morris, Trends in Pharmacological Sciences 17: 182-85(1996). The difficulty may arise at least in part from the fact that in the phospholipase family enzymes may or may not be activated by, and catalyze, multiple substances, making sorting, tracking and identification by functional activities impractical. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel synergistic compositions containing aromatic compounds and terpenoids present in Alpinia galanga Inventor(s): Jensen, Nina Worm; (Koge, DK), Petersen, Morten Just; (Verlose, DK), Weidner, Morten Sloth; (Virum, DK) Correspondence: Darby & Darby P.C.; Post Office Box 5257; New York; NY; 10150-5257; US Patent Application Number: 20030157204 Date filed: January 2, 2003 Abstract: Novel compositions of matter containing aromatic compounds and terpenoids which are present in and may preferably be derived from the plant Alpinia galanga (Zingiberaceae) show synergistic effects with respect to immunomodulation, and they significantly suppress hypersensitivity reactions. Thus they are used for preparing medicaments for these purposes and, more specifically, for the treatment or prevention of IgE mediated allergic reactions and conditions, such as asthma, allergic rhinitis, atopic eczema or anaphylaxis, and autoimmune disorders, such as Crohn's disease, ulcerative colitis, rheumatoid arthritis or psoriasis, as well as for the alleviation of pain. They can for example be formulated into pharmaceuticals, cosmetics or dietary supplements. A method of preparing such compositions from Alpinia galanga is also described. Excerpt(s): The present invention relates to novel compositions of matter containing aromatic compounds and terpenoids which are present in and may preferably be derived from the plant Alpinia galanga (Zingiberaceae), and more specifically to novel pharmaceuticals, cosmetics or dietary supplements containing such compositions. Furthermore the invention relates to the use of the compositions for preparing medicaments for the treatment or prevention of hypersensitivity reactions and diseases associated with hypersensitivity reactions. The invention also relates to a method of preparing such compositions from Alpinia galanga. Alpinia galanga (L.), family Zingiberaceae, commonly known as Greater Galangal or Java Galangal, is cultivated and grows wild in Asia. The herb is rhizomatic, 1.8-2.1 m in height with oblong glabrous leaves and greenish white flowers. The fruits are orange-red capsules. The plant is also known under the name Languas galanga, especially in Thailand, and here it is locally called Katuk karohinee. In relation to the present invention the term "Alpinia galanga" refers to any variety of Alpinia galanga or Languas galanga found anywhere in the world. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Nuclear envelope protein recognized by atypical p-ANCA in patients with inflammatory bowel disease and autoimmune liver diseases Inventor(s): Terjung, Birgit; (Swisttal, DE), Worman, Howard J.; (New York, NY) Correspondence: Cooper & Dunham Llp; 1185 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20030003518 Date filed: June 15, 2001 Abstract: The present invention is directed to the molecular characterization of the nuclear antigen recognized by atypical p-antineutrophil cytoplasmic antibodies (p-

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ANCA) in order to better diagnose patients with inflammatory bowel diseases such as ulcerative colitis (UC), and autoimmune liver diseases such as primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Molecular characterization of the target antigen comprises preparing cytoplasmic and nuclear extracts of human neutrophils, human HL-60 and murine 32D myeloid cells. Proteins should then be resolved by 1 and 2 dimensional gel electrophoresis and reactive proteins can then be detected by immunoblotting with sera from individuals, making certain to have both normal and disease controls. Atypical p-ANCA should then be affinity purified against the reactive protein and investigated for their immunofluorescence pattern using confocal microscopy. One could then detect the antigen that atypical p-ANCA can recognize and use that antigen to detect the prescence of atypical p-antineutrophil cytoplasmic antibodies so as to diagnose patients with inflammatory bowel diseases such as ulcerative colitis (UC), and autoimmune liver diseases such as sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Excerpt(s): Throughout this application, various publications are referenced by author and date. Full citations for these publications may be found listed alphabetically at the end of the specification immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein. Atypical "antineutrophil cytoplasmic antibodies" (ANCA) are present in patients with ulcerative colitis (UC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) ANCA represent a family of heterogenous autoantibodies directed against constituents of neutrophilic granulocytes. These autoantibodies have become valuable seromarkers for the diagnostic and therapeutic management of patients with systemic vasculitides such as Wegner granulomatosis and microscopic polyangiitis, in which they recognize well defined cytoplasmic antigens such as proteinase 3 and myeloperoxidase. Two well established ANCA staining patterns can be distinguished on ethanol-fixed neutrophils: a difuse cytoplasmic fluorescence pattern (c-ANCA) and a fine homogeneous labeling of the perinuclear cytoplasm (p-ANCA). Autoantibodies that are similar to p-ANCA in patients with systemic vasculitides are detected in individuals with chronic inflammatory bowel diseases (IBD) such as ulcerative colitis or autoimmune liver disorders such as primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Contrary to systemic vasculitides, the role of ANCA in these disorders is not clear. Various cytoplasmic proteins such as bactericidal/permeability increasing protein, catalase, cathepsin G, enolase, or lactoferrin have been proposed as putative target antigens of ANCA in these disorders, but reactivity to these proteins has only been detected in less than thirty five percent of cases. The predominant target antigen of ANCA in IBD and autoimmune liver disorders has not been identified. Since their target antigens are unknown, p-ANCA in patients with IBD or autoimmune liver disorders are generally referred to as atypical p-ANCA. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Pharmaceutical composition and method of modulating cholinergic function in a mammal Inventor(s): Coe, Jotham W.; (Niantic, CT), Sands, Steven B.; (Stonington, CT) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20030008892 Date filed: March 25, 2002 Abstract: A pharmaceutical composition and method of modulating cholinergic function in a mammal comprising administration of a NRPA compound or a pharmaceutically acceptable salt thereof; and an anti-emetic/anti-nausea agent or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier. The NRPA compound and the anti-emetic/anti-nausea agent are present in amounts that render the composition effective modulating cholinergic function or in the treatment of a diorder or condition selected from inflammatory bowel disease (including but not limited to ulcerative colitis, pyoderma gangrenosum and Crohn's disease), irritable bowel syndrome, spastic dystonia, chronic pain, acute pain, celiac sprue, pouchitis, vasoconstriction, anxiety, panic disorder, depression, bipolar disorder, autism, sleep disorders, jet lag, amyotrophic lateral sclerosis (ALS), cognitive dysfunction, hypertension, bulimia, anorexia, obesity, cardiac arrythmias, gastric acid hypersecretion, ulcers, pheochromocytoma, progressive supranuclear palsy, chemical dependencies and addictions (e.g., dependencies on, or addictions to nicotine (and/or tobacco products), alcohol, benzodiazepines, barbiturates, opioids or cocaine), headache, migraine, stroke, traumatic brain injury (TBI), obsessive-compulsive disorder (OCD), psychosis, Huntington's chorea, tardive dyskinesia, hyperkinesia, dyslexia, schizophrenia, multiinfarct dementia, age-related cognitive decline, epilepsy, including petit mal absence epilepsy, senile dementia of the Alzheimer's type (AD), Parkinson's disease (PD), attention deficit hyperactivity disorder (ADHD) and Tourette's Syndrome. The method of using these compositions is also disclosed. Excerpt(s): The present invention relates to pharmaceutical compositions for modulating cholinergic function in a mammal comprising a nicotinic receptor partial agonist compound in combination with an anti-emetic/anti-nausea agent and a pharmaceutically acceptable carrier. The nicotinic receptor partial agonists (NRPAs) included herein are aryl fused azapolycyclic compounds. NRPAs are not limited to those described here. The term NRPA refers to all chemical compounds which bind at neuronal nicotinic acetylcholine specific receptor sites in mammalian tissue and elicit a partial agonist response. A partial agonist response is defined here to mean a partial, or incomplete functional effect in a given functional assay. Additionally, a partial agonist will also exhibit some degree of antagonist activity by its ability to block the action of a full agonist (Feldman, R. S., Meyer, J. S. & Quenzer, L. F. Principles of Neuropsychopharmacology, 1997; Sinauer Assoc. Inc.). The present invention may be used to treat mammals (e.g. humans) for inflammatory bowel disease (including but not limited to ulcerative colitis, pyoderma gangrenosum and Crohn's disease), irritable bowel syndrome, spastic dystonia, chronic pain, acute pain, celiac sprue, pouchitis, vasoconstriction, anxiety, panic disorder, depression, bipolar disorder, autism, sleep disorders, jet lag, amyotrophic lateral sclerosis (ALS), cognitive dysfunction, hypertension, bulimia, anorexia, obesity, cardiac arrythmias, gastric acid hypersecretion, ulcers, pheochromocytoma, progressive supranuclear palsy, chemical dependencies and addictions (e.g., dependencies on, or addictions to nicotine (and/or tobacco products), alcohol, benzodiazepines, barbiturates, opioids or cocaine), headache, migraine, stroke,

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traumatic brain injury (TBI), obsessive-compulsive disorder (OCD), psychosis, Huntington's chorea, tardive dyskinesia, hyperkinesia, dyslexia, schizophrenia, multiinfarct dementia, age-related cognitive decline, epilepsy, including petit mal absence epilepsy, senile dementia of the Alzheimer's type (AD), Parkinson's disease (PD), attention deficit hyperactivity disorder (ADHD) and Tourette's Syndrome with a decrease in the incidence and severity of unwanted side effects such as nausea and/or stomach upset. The present invention also relates to the combination use of NRPAs and anti-emetic/anti-nausea agents resulting in modulation of cholinergic function without nausea. The combination will provide an improved treatment paradigm than NRPAs alone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pharmacological composition containing yeast cell wall fraction Inventor(s): Nakamura, Tomohiko; (Takasaki-shi, JP), Shirasu, Yoshiharu; (Takasaki-shi, JP), Wakabayashi, Hideyuki; (Takasaki-shi, JP) Correspondence: Venable, Baetjer, Howard And Civiletti, Llp; P.O. Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20030118607 Date filed: October 10, 2002 Abstract: The present invention provides a pharmacological composition as a composition as a raw material capable of preventing or treating the symptoms of inflammatory bowel diseases such as ulcerative colitis, constipation, allergic diseases such as atopic dermatitis, and so on, and which has little side effect and thereby safe, high water dispersibility, and can be ingested easily.A yeast cell wall fraction, which comprises yeast extracts residue and being superior in water dispersibility and swelling properties, is used as an active constituent. As a yeast cell wall fraction, a yeast cell wall fraction obtained with a simple operation of water cleansing of yeast cell after alkali processing yields superior effects for preventing or treating the symptoms of inflammatory bowel diseases such as ulcerative colitis, constipation, allergic diseases such as atopic dermatitis, and so on, as well as such yeast cell wall fraction without foreign taste and odor characteristic to autolysis and suitable for ingestion. Excerpt(s): The present invention generally relates to a pharmacological composition containing cell residue obtained by removing soluble cell substance from enzymegenated yeast, preferably cell residue obtained by conducting water cleansing after alkali treatment, and having as its active constituent a yeast cell wall fraction containing abundant protein and dietary fiber. Particularly, the present invention relates to an agent and/or a food product having as its active constituent the aforementioned yeast cell wall fraction and capable of preventing and/or treating the symptoms of inflammatory bowel diseases such as ulcerative colitis, constipation, allergic diseases such as atopic dermatitis, and so on. Conventionally, as technology directed to a pharmacological composition having as its active constituent yeast or a yeast cell component substance, known are a manufacturing method of a polysaccharide ester sulfate compound and the alkali metal saline thereof having a anti-digestive ulcer agent effect and an anti-arterial sclerosis effect, obtained by sulfating a yeast cell wall in a basic organic solution with chlorosulphonic acid or sulfur trioxide, or sulfating a yeast cell wall by blending it with cooled and levigated strong sulfuric acid and thereafter making it an alkali salt (Japanese Patent Application Laid-Open No. 49-48894); a manufacturing method of a polysaccharide ester sulfate compound and the alkali metal saline thereof

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obtained by sulfating a yeast cell wall in a basic organic solution with chlorosulphonic acid or sulfur trioxide, or sulfating a yeast cell wall by blending it with cooled and levigated strong sulfuric acid and thereafter making it an alkali salt (Japanese Patent Application Laid-Open No. 56-31955); a manufacturing method of a new physiologically active substance peptide mannan A which extracts peptide mannan A from a yeast cell belonging to Saccharomyces and ingests peptide mannan A from such extract (Japanese Patent Laid-Open Publication No. 49-69808); a manufacturing method of a compound protein SP-1 having an anti-ulcer effect and containing amino acids and mannose by making the pepsin act upon the yeast cell wall (Japanese Patent Application Laid-Open No. 62-39527); an anti-allergic agent having as its active constituent mannan deriving from yeast and the like (Japanese Patent Application Laid-Open No.63-119427); an antiulcer agent having as its active constituent dried brewer's yeast with no concern of side effects as it is a natural product (Japanese Patent Application Laid-Open No. 1-313434); a nutrition supplement composition to be administered to mammals and containing a sufficient amount of.beta.-glucan deriving from yeast for supplying a fiber source in foods, fecal-increasing agent, and short-chain fatty acid, and which improves the digestion in mammals, decreases the serum cholesterol level, and fortifies the decrease in weight (Japanese Patent Application Laid-Open No. 4-505997); food, beverage and medical product containing magnesium supplement material which connotes magnesium salt within a yeast cell wall prepared by eluting and separating intercellular cell constituents (Japanese Patent Application Laid-Open No. 9-107919); an inhibitor of antibody-producing cell containing yeast-related polymer, and a composition such as food or medical product for autoimmune disease containing this inhibitor of antibodyproducing cell (Japanese Patent Laid-Open Publication No. 9-188626); and a skin condition improving composition suitable for preventing and treating the likes of atopic dermatitis and containing protease hydrolysate of brewer's yeast and diuretic (Japanese Patent Laid-Open Publication No. 9-227390). Further, conventionally, as technology directed to making the autolytic residue of yeast tasteless and odorless, known are a method of improving the flavor of brewer's yeast by moisture distillation and organic solvation of brewer's yeast (Japanese Patent Application Laid-Open No. 63-22177), a method of decolorizing and deodorizing yeast extract residue, or yeast autolytic residue, wherein yeast extract residue is processed with alkali and acid, high concentration ozone treatment is conducted thereafter, and ethanol treatment is further implemented (Japanese Patent Application Laid-Open No. 4-248968); a method of reducing the foreign taste and odor characteristic to yeast by conducting acid treatment and heat treatment to yeast or a yeast-processed product (Japanese Patent Application Laid-Open No. 6-70751); and a method of making a yeast autolytic insoluble substance tasteless and odorless by suspending a yeast autolytic insoluble substance in ethanol, carrying the stirring treatment under alkaline conditions and eluting the causative agent of foreign taste and odor thereby, and eliminating the eluted material pursuant to centrifugation and eliminating the foreign taste and odor characteristic to a yeast autolytic insoluble substance thereby (Japanese Patent Application Laid-Open No. 9-103266). In addition, as technology directed to the treatment method of yeast cells and yeast cell walls, known is a manufacturing method of a seasoning wherein yeast cells are crushed with a highpressure spray-impact homogenizer, hot water extraction is conducted thereto, and centrifugation is performed to the yeast cell walls which could not be made into particulates (Japanese Patent Application Laid-Open No. 9-117263). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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PLAP polypeptides and methods of producing and using same Inventor(s): Chopra, Ashok K.; (Galveston, TX), Peterson, Johnny W.; (Dickinson, TX), Saini, Shamsher S.; (Galveston, TX), Wood, Thomas G.; (Houston, TX) Correspondence: Mark B. Wilson; Fulbright & Jaworski L.L.P.; Suite 2400; 600 Congress Avenue; Austin; TX; 78701; US Patent Application Number: 20030166548 Date filed: June 19, 2002 Abstract: Synthetic milittin and related peptides derived from the sequence of human phospholipase A.sub.2-activating protein (PLAP), free from the contaminating phospholipase A.sub.2 (PLA.sub.2) and/or present when the peptides are purified from natural sources, show inhibitory activity against PLA.sub.2. Inhibition of this enzyme, responsible for the hydrolysis of arachiodonate, an important precursor of eicosanoids, should lead to a decrease in the inflammatory response. In addition to their use as antiinflammatory therapeutics, compositions containing the synthetic peptides may also be useful therapeutic tools for diagnosing inflammatory diseases (e.g., Crohn's disease, ulcerative colitis, rheumatoid arthritis). Excerpt(s): This application claims priority from U.S. Serial No. 60/049,316, filed Jun. 11, 1997. The present invention relates generally to the fields of diagnosing and treating inflammatory diseases. More particularly, it concerns the uses of synthetic peptide and peptide analog inhibitors of phospholipase A.sub.2. Inflammation is normally a basic host protective mechanism that increases resistance to microorganisms and other foreign antigens. Inflammatory responses are mediated in part by the eicosanoids, C.sub.20 products of the cyclooxygenase and lipooxygenase metabolism of arachidonic acid. The eicosanoids include proinflammatory prostaglandins (e.g., PGE.sub.2) and leukotrienes (e.g., LTB.sub.4). The level of arachidonic acid, itself, is mediated by the action of phospholipase A.sub.2 (PLA.sub.2) a lipophilic enzyme that hydrolyzes arachidonic acid from the sn-2 position of phospholipids located in cell membranes. PLA.sub.2 enzyme activity is increased by a eukaryotic cell protein referred to as phospholipase A.sub.2-activating protein (PLAP), which was initially cloned from murine BC.sub.3H.sub.1 cells (Clark, 1991). Murine PLAP is reported to increase PLA.sub.2 enzyme activity (Bomalaski et al, 1994). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Pyridone-fused azabicyclic- or cytisine derivatives, their preparation and their use in addiction therapy Inventor(s): O'Neill, Brian T.; (Old Saybrook, CT) Correspondence: Paul H. Ginsburg; Pfizer INC.; 20th Floor; 235 East 42nd Street; New York; NY; 10017-5755; US Patent Application Number: 20030065173 Date filed: February 14, 2001 Abstract: Pyridone-fused azabicyclic compounds of the formula 1and their pharmaceutically acceptable salts and prodrugs, wherein R.sup.1, R.sup.2 and R.sup.3 are defined below, intermediates and methods for their preparation. Compositions and methods for using compounds of the formula I in the treatment of neurological and mental disorders related to a decrease in cholinergic function such as nicotine addiction,

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Huntington's Chorea, tardive dyskinesia, hyperkinesia, mania, dyslexia, schizophrenia , analgesia, attention deficit disorder (ADD), multi-infarct demetia, age related cognitive decline, epilepsy, neurological and mental disorders related to a decrease in cholinergic function, senile dementia of the Alzheimer's type, Parkinson's disease, attention deficit hyperactivity disorder (ADHD), anxiety, obesity, Tourette's Syndrome and ulcerative colitis. Excerpt(s): This invention relates to azabicyclic compounds. More particularly it relates to pyridone-fused azabicyclic compounds of the formula I below Compounds of formula I are useful in the treatment of addictive disorders such as the use of tobacco or other nicotine containing products and also for the treatment or prevention of withdrawal symptoms caused by cessation of chronic or long term use of tobacco products. These compounds are also useful in the treatment of Huntington's Chorea, tardive dyskinesia, hyperkinesia, mania, dyslexia, schizophrenia, analgesia, attention deficit disorder (ADD), multi-infarct demetia, age related cognitive decline, epilepsy, neurological and mental disorders related to a decrease in cholinergic function such as Huntington's Chorea, tardive dyskinesia, hyperkinesia, mania, dyslexia, schizophrenia, analgesia, attention deficit disorder (ADD), multi-infarct demetia, age related cognitive decline, epilepsy, neurological and mental disorders related to a decrease in cholinergic function, senile dementia of the Alzheimer's type, Parkinson's disease, attention deficit hyperactivity disorder (ADHD), anxiety, obesity, Tourette's Syndrome and ulcerative colitis. The compounds of this invention may also be used in combination with a antidepressants such as imipramine in order to treat both the cognitive decline and depression associated with AD; in combination with serotonin uptake inhibitors such as Zoloft to treat both the cognitive decline and depression associated with AD; in combination with muscarinic agonists in order to stimulate both central muscarinic and nicotinic receptors; in combination with neurotrophic factors such as NGF in order to maximize cholinergic enhancement; in combination with agents which slow or arrest AD such as amyloid or tau inhibitors. Substances which can deliver pharmacologically relevant amounts of nicotine to the central nervous system are among the most abused substances known. These include, but not are not limited to tobacco cigarettes, and "chewing tobacco" (see J. E. Henningfield, Ph.D, New England Journal of Med., 1196, 1995). Cigarette smoking has been tied to increased risk for lung cancer, emphysema and heart disease and it is estimated 400,000 people will die in 1995 from the combined effects of nicotine abuse in the United States (see J. A. Califano, Jr., New England Journal of Med. 1214, 1995). Nicotine is a highly addicting drug with 40% of those who try smoking later becoming physically dependent upon it. Attempts to quit the use of nicotine, such as in smoking, have been largely ineffective with >80% of such attempts ending in failure. Most attempts to quit end in failure in the first week due to intense withdrawal and craving symptoms. An effective therapy should aid in the cessation or lessening of tobacco use, prevent withdrawal. etc prevent withdrawal symptoms, relieve craving and, simultaneously, antagonize the reinforcing effects of nicotine obtained through smoking. Currently, few therapies are available for smoking cessation and most involve replacement of cigarettes with nicotine in the form of a patch or gum. A high rate of relapse and low overall success in ending nicotine use is evidence of the need for additional and more effective therapies for treatment of nicotine addiction than the nicotine patch or gum. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Regulation of human substance p-like g protein-coupled receptor Inventor(s): Ramakrishnan, Shyam; (Brighton, MA) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20030104435 Date filed: September 11, 2002 Abstract: Reagents which regulate human substance P G protein-coupled receptor (SPGPCR) protein and reagents which bind to human SP-GPCR gene products can play a role in preventing, ameliorating, or correcting dysfunctions or diseases including, but not limited to, urinary incontinence, inflammatory diseases (e.g., arthritis, psoriasis, asthma and inflammatory bowel disease), anxiety, depression or dysthymic disorders, cluster headache, colitis, psychosis, pain, allergies such as eczema and rhinitis, chronic obstructive airways disease, hypersensitivity disorders such as poison ivy, vasospastic diseases such as angina, migraine and Reynaud's disease, fibrosing and collagen diseases such as scleroderma and eosinophilic fascioliasis, reflex sympathetic dystrophy such as shoulder/hand syndrome, addiction disorders such as alcoholism, stress related somatic disorders, peripheral neuropathy, neuralgia, neuropathological disorders such as Alzheimer's disease, AIDS related dementia, diabetic neuropathy and multiple sclerosis, disorders related to immune enhancement or suppression such as systemic lupus erythematosus, and rheumatic diseases such as fibrositis. Excerpt(s): The invention relates to the area of G-protein coupled receptors. More particularly, it relates to the area of human substance P-like G protein-coupled receptor and its regulation. Many medically significant biological processes are mediated by signal transduction pathways that involve G-proteins (Lefkowitz, Nature 351, 353-354, 1991). The family of G-protein coupled receptors (GPCR) includes receptors for hormones, neurotransmitters, growth factors, and viruses. Specific examples of GPCRs include receptors for such diverse agents as dopamine, calcitonin, adrenergic hormones, endothelin, cAMP, adenosine, acetylcholine, serotonin, histamine, thrombin, kinin, follicle stimulating hormone, opsins, endothelial differentiation gene-1, rhodopsins, odorants, cytomegalovirus, G-proteins themselves, effector proteins such as phospholipase C, adenyl cyclase, and phosphodiesterase, and actuator proteins such as protein kinase A and protein kinase C. GPCRs possess seven conserved membranespanning domains connecting at least eight divergent hydrophilic loops. GPCRs (also known as 7TM receptors) have been characterized as including these seven conserved hydrophobic stretches of about 20 to 30 amino acids, connecting at least eight divergent hydrophilic loops. Most GPCRs have single conserved cysteine residues in each of the first two extracellular loops, which form disulfide bonds that are believed to stabilize functional protein structure. The seven transmembrane regions are designated as TM1, TM2, TM3, TM4, TM5, TM6, and TM7. TM3 has been implicated in signal transduction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Remedies for inflammatory bowel diseases Inventor(s): Hirota, Yasushi; (Fukui, JP) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037; US Patent Application Number: 20030212115 Date filed: March 25, 2003 Abstract: Prophylactic and/or therapeutic drugs against ulcerative colitis, which include five-member heterocyclic compounds represented by the formula (I) or these nontoxic salts as active principle, 1(wherein Z represents the group containing.alpha.aminocarbonyl group, R.sup.1 represents (1) substituted alkyl, alkenyl or alkynyl groups, (2) OH, (3) amino, (4) alkylamino, (5) dialkylamino, etc., X and Y represent oxygen atom, sulfur atom or substituted nitrogen atom.) Excerpt(s): The present invention relates to medicines of ulcerative colitis. medicines of ulcerative colitis, which include five-member heterocyclic compounds represented by the formula (I) (all signs in the formula represent the same meanings as postscripts.) and have inhibitory activity against elastase or these nontoxic salts as active principle. Human neutrophil elastase (HNE) is a kind of serine protease, and protein proteinase that is secreted from neutrophils by various inflammatory stimulus and takes a part in connective tissue biolysis. HNE activity is regulated by alpha1-proteinase inhibitor that is inhibitory factor in vivo, and the symptom of tissue destruction appears when unbalance between the enzyme and the inhibitor arise. For example, it is well known that it is involved in pulmonary emphysema, atherosclerosis and arthritis, etc. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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TNF receptor 2 related protein variant Inventor(s): Lal, Preeti G.; (Santa Clara, CA), Warren, Bridget A.; (Cupertino, CA) Correspondence: Incyte Genomics, INC.; 3160 Porter Drive; Palo Alto; CA; 94304; US Patent Application Number: 20030068619 Date filed: July 27, 2001 Abstract: The invention provides a cDNA which encodes a TNFR2PV. It also provides for the use of the cDNA, fragments, complements, and variants thereof and of the encoded protein, portions thereof and antibodies thereto for diagnosis and treatment of cancer and immune disorders, particularly cancer of the prostate, ovary, breast, and brain, or an inflammatory disorder, including rheumatoid arthritis, asthma, and ulcerative colitis. The invention additionally provides expression vectors and host cells for the production of the protein and a transgenic model system. Excerpt(s): This invention relates to a cDNA which encodes a TNF receptor 2 related protein variant and to the use of the cDNA and the encoded protein in the diagnosis and treatment of cancers and immune disorders. Phylogenetic relationships among organisms have been demonstrated many times, and studies from a diversity of prokaryotic and eukaryotic organisms suggest a more or less gradual evolution of molecules, biochemical and physiological mechanisms, and metabolic pathways. Despite different evolutionary pressures, the proteins of nematode, fly, rat, and man have common chemical and structural features and generally perform the same cellular function. Comparisons of the nucleic acid and protein sequences from organisms where

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structure and/or function are known accelerate the investigation of human sequences and allow the development of model systems for testing diagnostic and therapeutic agents for human conditions, diseases, and disorders. Cytokines are a diverse class of extracellular signaling molecules that regulate survival, growth, differentiation, and effector function in a variety of cells. Cytokines include families of signaling molecules such as growth factors, colony-stimulating factors, interleukins, lymphokines, monokines, and interferons. Cytokines are produced by cells that are widespread throughout the body and act in a paracrine or autocrine manner to carry out roles which often involve fighting infection and mediating tissue healing. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Topical formulations for delivery of interleukin-11 Inventor(s): Bedrosian, Camille L.; (Belmont Hills, MA), Keith, James C. JR.; (Andover, MA), Schendel, Paul F.; (Wayland, MA), Schwerschlag, Ullrich S.; (Beverly Farms, MA), Warne, Nicholas W.; (Andover, MA) Correspondence: Mintz, Levin, Cohn, Ferris,; Glovsky And Popeo, P.C.; One Financial Center; Boston; MA; 02111; US Patent Application Number: 20030147849 Date filed: February 7, 2003 Abstract: Provided by the present invention are topical formulations of Interleukin-11 and methods for treating a variety of disorders, including inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis, indeterminate colitis, and infectious colitis), mucositis (e.g., oral mucositis, gastrointestinal mucositis, nasal mucositis, and proctitis), necrotizing enterocolitis, inflammatory skin disorders (e.g., psoriasis, atopic dermatitis, and contact hypersensitivity), aphthous ulcers, pharyngitis, esophagitis, peptic ulcers, gingivitis, periodontitis, and ocular diseases (e.g., conjunctivitis, retinitis, and uveitis). Excerpt(s): This is a continuation-in-part of U.S. patent application Ser. No. 09/179,026 filed Oct. 26, 1998, which is a continuation-in-part of U.S. patent application Ser. No. 08/892,407, filed Jul. 15, 1997, now U.S. Pat. No. 5,948,402, which is a divisional of U.S. patent application Ser. No. 08/495,724, filed Jun. 27, 1995, now U.S. Pat. No. 5,679,339, issued Oct. 21, 1997. The present invention relates generally to novel compositions and methods for topical delivery of interleukin-11 (IL-11). In preferred embodiments, patients are treated employing topical delivery of recombinant human IL-11 for inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis, indeterminate colitis, and infectious colitis), mucositis (e.g., oral mucositis, gastrointestinal mucositis, nasal mucositis, and proctitis), necrotizing enterocolitis, inflammatory skin disorders (e.g., psoriasis, atopic dermatitis, and contact hypersensitivity), aphthous ulcers, pharyngitis, esophagitis, peptic ulcers, gingivitis, periodontitis, and ocular diseases (e.g., conjunctivitis, retinitis, and uveitis). Inflammatory responses include a broad range of host reaction to a variety of insults, such as injury, infection, or rejection. It is the overproduction of mediators that is believed to be associated with a broad range of disorders, including AIDS, arthritis (rheumatoid arthritis, osteoarthritis, spondyloarthropathies), antibiotic-induced diarrheal diseases, multiple sclerosis, osteoporosis, gingivitis, peptic ulcer disease, esophagitis, diabetes, retinitis, uveitis, reperfusion injury after myocardial infarction, cerebral vascular accident, aphthous ulcers (oral), atherosclerosis, tumor metastases, asthma, preeclampsia, pancreatitis, psoriasis, infertility and allergic disorders such as rhinitis, conjunctivitis, and urticaria.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Treatment and diagnosis of macrophage mediated disease Inventor(s): Low, Philip S.; (West Lafavette, IN), Turk, Mary Jo; (New York, NY) Correspondence: Barnes & Thornburg; 11 South Meridian Street; Indianapolis; IN; 46204; US Patent Application Number: 20020192157 Date filed: May 2, 2002 Abstract: The invention relates to a method of treating or monitoring/diagnosing a disease state mediated by activated macrophages. The method comprises the step of administering to a patient suffering from a macrophage mediated disease state an effective amount of a composition comprising a conjugate or complex of the general formulaA.sub.b-Xwhere the group A.sub.b comprises a ligand capable of binding to activated macrophages, and when the conjugate is being used for treatment of the disease state, the group X comprises an immunogen, a cytotoxin, or a compound capable of altering macrophage function, and when the conjugate is being used for monitoring/diagnosing the disease state, X comprises an imaging agent. The method is useful for treating a patient suffering from a disease selected from the group consisting of rheumatoid arthritis, ulcerative colitis, Crohn's disease, inflammation, infections, osteomyelitis, atherosclerosis, organ transplant rejection, pulmonary fibrosis, sarcoidosis, and systemic sclerosis. Excerpt(s): This application claims priority under 35 U.S.C.sctn.119(e) to U.S. Provisional Application Serial No. 60/288,208, filed on May 2, 2001. This invention relates to methods for treating and monitoring disease states mediated by activated macrophages. More particularly, ligands that bind to activated macrophages are complexed with an imaging agent, or an immunogen, a cytotoxin or an agent for altering macrophage function for administration to a diseased host for diagnosis and/or treatment of macrophage mediated disease. The mammalian immune system provides a means for the recognition and elimination of foreign pathogens. While the immune system normally provides a line of defense against foreign pathogens, there are many instances where the immune response itself is involved in the progression of disease. Exemplary of diseases caused or worsened by the host's own immune response are autoimmune diseases such as multiple sclerosis, lupus erythematosus, psoriasis, pulmonary fibrosis, and rheumatoid arthritis and diseases in which the immune response contributes to pathogenesis such as atherosclerosis, inflammatory diseases, osteomyelitis, ulcerative colitis, Crohn's disease, and graft versus host disease often resulting in organ transplant rejection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatment of inflammatory bowel disease Inventor(s): Pfirrmann, Rolf W.; (Lucerne, CH), Redmond, H. Paul; (Wilton, IE) Correspondence: Rothwell, Figg, Ernst & Manbeck, P.C.; 1425 K Street, N.W.; Suite 800; Washington; DC; 20005; US Patent Application Number: 20030119824 Date filed: December 19, 2002

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Abstract: Patients suffering from inflammatory bowel disease such as Crohn's disease or ulcerative colitis are treated either orally or intravenously with methylol transfer agents, such as taurolidine and/or taurultam. These agents can be used in combination with other drugs thereby allowing the use of smaller amounts of the other drugs and limiting unwanted side effects. Excerpt(s): The present application is a continuation of application Ser. No. 09/753,679, filed Jan. 4, 2001, which claims the benefit of U.S. Provisional Application No. 60/174,608, filed Jan. 5, 2000. Inflammatory bowel disease (IBD) is of unknown etiology, although immunological mechanisms play a significant role. The two major disorders involved are ulcerative colitis and Crohn's disease. Both diseases are chronic relapsing disorders. The exact pathogenesis of IBD is unknown. Various factors such as environmental, genetic, smoking and infectious agents have been suggested. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Treatment of inflammatory bowel disease with vitamin d compounds Inventor(s): Cantorna, Margherita T; (State College, PA) Correspondence: Andrus Sceales Starke & Sawall; Suite 1100; 100 East Wisconsin Avenue; Milwaukee; WI; 53202-4178; US Patent Application Number: 20030188756 Date filed: August 19, 2002 Abstract: A method of treating inflammatory bowel disease, particularly ulcerative colitis and Crohn's disease, is disclosed. The method involves administering a vitamin D compound in an amount effective to treat the disease. The administration of a vitamin D compound also prevents the development of or delays the onset of inflammatory bowel disease in susceptible individuals. Excerpt(s): This invention relates to vitamin D compounds, and more particularly to the use of vitamin D compounds to treat inflammatory bowel disease. The natural hormone, 1.alpha.,25-dihydroxyvitamin D.sub.3 and its analog 1.alpha.,25-dihydroxyvitamin D.sub.2 are known to be highly potent regulators of calcium homeostasis in animals and humans, and their activity in cellular differentiation has also been established, Ostrem et al., Proc. Natl. Acad. Sci. USA, 84, 2610 (1987). Many structural analogs of these metabolites have been prepared and tested, including 1.alpha.-hydroxyvitamin D.sub.3, 1.alpha.-hydroxyvitamin D.sub.2, various side chain homologated vitamins and fluorinated analogs. Some of these compounds exhibit an interesting separation of activities in cell differentiation and calcium regulation. This difference in activity may be useful in the treatment of a variety of diseases such as renal osteodystrophy, vitamin Dresistant rickets, osteoporosis, psoriasis, and certain malignancies. Inflammatory bowel diseases (IBD) are immune mediated diseases of unknown etiology affecting the gastrointestinal (GI) tract. There are at least two distinct forms of IBD, ulcerative colitis and Crohn's disease. IBD are chronic recurring illnesses most commonly involving inflammation of the terminal ileum and colon, although these diseases can also affect many sites throughout the alimentary tract. Clearly, genetic factors predispose individuals to development of IBD (Podolosky 1991). In addition, the environment contributes to IBD development, and there is reason to believe that vitamin D may be an environmental factor which affects IBD. Vitamin D from sunlight exposure is less in areas where IBD occurs most often, as IBD is most prevalent in northern climates such as North America and Northern Europe (Podolosky 1991, Sonnenberg et al. 1991). A

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major source of vitamin D results from its manufacture via a photolysis reaction in the skin, and vitamin D available from sunlight exposure is significantly less in northern climates, and especially low during the winter (Clemens et al. 1982, DeLuca 1993). Dietary intake of vitamin D is problematic since there are few foods which are naturally rich in vitamin D. Weight loss occurs in 65-75% of patients diagnosed with Crohn's disease and 1862% of patients with ulcerative colitis (Fleming 1995, Geerling et al. 1998). Vitamin deficiencies in general and vitamin D deficiency in particular have been shown to occur in IBD patients (Andreassen et al. 1998, Kuroki et al. 1993). To date the possible association between vitamin D status and the incidence and severity of IBD in humans or animals has not been studied. The anecdotal information suggests that vitamin D status could be an environmental factor affecting the prevalence rate for IBD and that the correlation warrants investigation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Treatment of ulcerative colitis with tropomyosin isoforms and monoclonal antibodies to tropomyosin isoforms Inventor(s): Das, Kiron M.; (Basking Ridge, NJ) Correspondence: Perkins Coie Llp; Post Office Box 1208; Seattle; WA; 98111-1208; US Patent Application Number: 20030198635 Date filed: May 1, 2003 Abstract: This invention pertains to a method for treating ulcerative colitis. Specifically, the method comprises orally or rectally administering to a human having ulcerative colitis a therapeutically effective amount of an antibody which binds to a tropomyosin isoform associated with ulcerative colitis. In another embodiment, the invention pertains to a method for treating ulcerative colitis in a human which comprises the steps of (a) obtaining from a human a colon epithelial cell extract containing a tropomyosin isoform associated with ulcerative colitis; (b) purifying the tropomyosin isoform until the tropomyosin isoform is substantially homogeneous; (c) developing an antibody which binds to the tropomyosin isoform; and (d) orally or rectally administering to a human having ulcerative colitis a therapeutically effective amount of the antibody to bind to the tropomyosin isoform associated with ulcerative colitis. In yet another embodiment, the invention pertains to a method for treating ulcerative colitis in a human which comprises orally administering to the human a therapeutically effective amount of a tropomyosin isoform associated with ulcerative colitis. Excerpt(s): This Application is a Continuation of U.S. patent application Ser. No. 09/046,049 filed Mar. 23, 1998, and now pending and which is incorporated herein by reference. Priority to this application is claimed under 35 U.S.C.sctn. 120. The disclosures referred to herein to illustrate the background of the invention and to provide additional detail with respect to its practice are incorporated herein by reference and, for convenience, are numerically referenced in the following text and respectively grouped in the appended bibliography. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of il-18 inhibitors Inventor(s): Chvatchko, Yolande; (Confignon, CH), Dinarello, Charles; (Boulder, CO), Kim, Soo-Hyun; (Denver, CO), Novick, Daniela; (Rehovot, IL), Plater-Zyberk, Christine; (Geneva, CH), Rubinstein, Menachem; (Givat Shmuel, IL), Van Deventer, Santer; (Haarlem, NL) Correspondence: David S Resnick; Nixon Peabody; 101 Federal Street; Boston; MA; 02110; US Patent Application Number: 20030157094 Date filed: January 24, 2003 Abstract: The invention relates to the use of inhibitors of IL-18 in the preparation of a medicament for treatment and/or prevention of liver injury. The invention further relates to the use of IL-18 inhibitors in the preparation of a medicament for treatment and/or prevention of arthritis, in particular rheumatoid arthritis. In addition to this, the invention relates to the use of inhibitors of IL-18 in the preparation of a medicament for treatment and/or prevention of inflammatory bowel diseases, in particular of Crohn's disease and ulcerative colitis. Excerpt(s): The present invention relates to the therapeutical use of IL-18 inhibitors in several pathological conditions. More specifically, the invention relates to the treatment and/or prevention of arthritis, to the treatment and/or prevention of liver diseases and to the treatment and/or prevention of inflammatory bowel diseases (IBD). In 1989, an endotoxin-induced serum activity that induced interferon-.gamma. (IFN-.gamma.) obtained from mouse spleen cells was described (Micallef et al., 1996). This serum activity functioned not as a direct inducer of IFN-.gamma. but rather as a co-stimulant together with IL-2 or mitogens. An attempt to purify the activity from post-endotoxin mouse serum revealed an apparently homogeneous 50-55 kDa protein. Since other cytokines can act as co-stimulants for IFN-.gamma. production, the failure of neutralizing antibodies to IL-1, IL4, IL-5, IL-6, or TNF to neutralize the serum activity suggested it was a distinct factor. In 1995, the same scientists demonstrated that the endotoxin-induced co-stimulant for IFN-.gamma. production was present in extracts of livers from mice preconditioned with P. acnes (Novick et al., 1992). In this model, the hepatic macrophage population (Kupffer cells) expand and in these mice, a low dose of bacterial lipopolysaccharide (LPS), which in non-preconditioned mice is not lethal, becomes lethal. The factor, named IFN-.gamma.-inducing factor (IGIF) and later designated interleukin-18 (IL-18), was purified to homogeneity from 1,200 grams of P. acnes-treated mouse livers. Degenerate oligonucleotides derived from amino acid sequences of purified IL-18 were used to clone a murine IL-18 cDNA (Novick et al., 1992). IL-18 is an 18-19 kDa protein of 157 amino acids, which has no obvious similarities to any peptide in the databases. Messenger RNAs for IL-18 and interleukin12 (IL-12) are readily detected in Kupffer cells and activated macrophages. Recombinant IL-18 induces IFN-gamma more potently than does IL-12, apparently through a separate pathway (Novick et al., 1992). Similar to the endotoxin-induced serum activity, IL-18 does not induce IFN-.gamma. by itself, but functions primarily as a co-stimulant with mitogens or IL-2. IL-18 enhances T cell proliferation, apparently through an IL-2dependent pathway, and enhances Th1 cytokine production in vitro and exhibits synergism when combined with IL-12 in terms of enhanced IFN-.gamma. production (Maliszewski et al., 1990). Neutralizing antibodies to mouse IL-18 were shown to prevent the lethality of low-dose LPS in P. acnes pre-conditioned mice. Others had reported the importance of IFN-.gamma. as a mediator of LPS lethality in preconditioned mice. For example, neutralizing anti-IFN-.gamma. antibodies protected

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mice against Shwartzman-like shock (Fantuzzi et al., 1998), and galactosamine-treated mice deficient in the IFN-.gamma. receptor were resistant to LPS-induced death (Bym, 1990). Hence, it was not unexpected that neutralizing antibodies to murine IL-18 protected P. acnes-preconditioned mice against lethal LPS (Novick et al., 1992). Antimurine IL-18 treatment also protected surviving mice against severe hepatic cytotoxicity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with colitis, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “colitis” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on colitis. You can also use this procedure to view pending patent applications concerning colitis. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON COLITIS Overview This chapter provides bibliographic book references relating to colitis. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on colitis include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “colitis” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on colitis: •

Understanding Crohn Disease and Ulcerative Colitis Source: Jackson, MS: University Press of Mississippi. 2000. 116 p. Contact: Available from University Press of Mississippi. 3825 Ridgewood Road, Jackson, MS 39211-6492. (601) 432-6205. Fax (601) 432-6217. E-mail: [email protected]. PRICE: $28.00 plus shipping and handling. ISBN: 1578062039. Summary: Crohn's disease and ulcerative colitis, together known as inflammatory bowel disease (IBD), are chronic illnesses of unknown origin. Written from a patient's perspective, this book provides timely information about how to obtain and maintain the highest quality of life possible while living with IBD. The inflammation within the intestinal tract leads to some or all of these clinical symptoms: diarrhea (with or without blood), abdominal pain, fever, and fatigue. The disease is characterized by periods of flareup and remission. Some individuals, especially those who have ulcerative colitis, may have one acute episode in their lifetime. But most people with IBD have recurrent

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periods of illness. Even in the absence of clinical symptoms there is usually radiological and laboratory evidence of the disease. Current medical treatments reduce symptoms, but do not cure either disease. Because of the unpredictable nature of the disease process, quality of life can be severely impaired. Besides providing basic information, this book describes various medical, surgical, nutritional, and even spiritual treatments. The authors also look at the special situations of IBD in children and in the elderly, and at issues surrounding IBD and reproductive function (in men and in women). The authors stress that patients with IBD can do much to improve their emotional and psychological capabilities for facing the disease, and thus can actively improve their quality of life. The book concludes with appendices of information resources, a glossary of terms, and a subject index. •

Contemporary Diagnosis and Management of Ulcerative Colitis and Proctitis Source: Newtown, PA: Handbooks in Health Care. 1995. 173 p. Contact: Available from Handbooks in Health Care. 9 Pheasant Run, Newtown, PA 18940. (215) 860-9600. PRICE: $9.95 plus $2 shipping (as of 1995). ISBN: 1884065082. Summary: In this handbook, the author provides readers with a detailed overview of the diagnosis and management of ulcerative colitis and proctitis. Fourteen chapters cover epidemiology; etiology, pathogenesis, and pathophysiology; clinical presentation, diagnostic evaluation, and differential diagnosis; commonly used drugs for ulcerative colitis and ulcerative proctitis; potential new drugs and novel therapeutic approaches; the management of ulcerative proctitis; the management of distal ulcerative colitis, leftsided ulcerative colitis, and mild to moderate pancolitis; the management of fulminant ulcerative colitis and toxic megacolon; surgical management; associated extraintestinal disorders; colon cancer surveillance; pregnancy and nursing; the pediatric patient and the elderly patient; and psychosocial and quality of life issues. Each chapter includes figures and tables where appropriate, and brief references; a subject index concludes the handbook.

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Managing Your Child's Crohn's Disease or Ulcerative Colitis Source: New York, NY: MasterMedia Limited. 1996. 163 p. Contact: Available from Crohn's and Colitis Foundation of America, Inc. 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 932-2423 or (212) 685-3440. Fax (212) 779-4098. E-mail: [email protected]. PRICE: $16.95 (members) or $21.95 (nonmembers). Also available from MasterMedia Limited. 17 East 89th Street, New York, NY 10128. (800) 334-8232 or (212) 546-7650. PRICE: $21.95. ISBN: 1571010238. Summary: This book about Crohn's disease and ulcerative colitis provides current information so that parents and children can learn how to handle these inflammatory bowel diseases (IBD). Interviews with children coping with these illnesses add a special insight to the book. Sixteen chapters are presented in three sections: diagnosing IBD, the treatment of IBD, and living with IBD. Topics include symptoms, the first visit to the gastroenterologists, laboratory tests, the causes of IBD, pediatric gastroenterology, surgery, the role of diet, treating slow growth through nutrition, psychosocial factors, school, camp, play and recreation, family life, and pregnancy. The final chapter provides a series of common questions and answers for young patients. The book concludes with a resource section that provides information about the Crohn's and Colitis Foundation of America (CCFA), about the National Digestive Diseases Information Clearinghouse (NDDIC), a guide to medications used in the treatment of IBD, a glossary of terms, and a Children's Legacy Scroll of Honor.

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Angry Gut: Coping with Colitis and Crohn's Disease Source: New York, NY: Plenum Press. 1993. 350 p. Contact: Available from Plenum Publishing. 233 Spring Street, New York, NY 100131578. (800) 221-9369 or (212) 620-8000. Fax (212) 647-1898. E-mail: [email protected]. PRICE: $26.95. ISBN: 0306444704. Summary: This book is intended for patients with inflammatory bowel disease (IBD), their families, and the nurses, primary care physicians, and other health professionals who work with these patients. Twenty-seven chapters are presented in five parts: understanding the anatomy and physiology of IBD; ulcerative colitis; Crohn's disease; special topics related to IBD; and treatments and investigations. Specific topics related to IBD include history; epidemiology; symptoms; diagnosis; treatment;and complications; variant colitis; extraintestinal manifestations; colon cancer; psychological factors and quality of life issues; sex and reproduction; nutrition; drug therapy, including 5-ASA, steroids, immunosuppressives, and antibiotics; surgery; and research. The volume includes some technical language and emphasizes a cooperative, team approach between patient and physician. A subject index is included.

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Crohn's, Colitis, Hemorrhoids, and Me: A Patient's Story of Hope, Humor, and Living with Inflammatory Bowel Disease Source: Laguna Niguel, CA: Anderson Press. 1995. 121 p. Contact: Available from Anderson Press. P.O. Box 6873-001, Laguna Niguel, CA 926076873. (800) 323-1423 or (714) 454-3837. Fax (500) 673-2665. PRICE: $12.95 plus $2 shipping and handling (as of 1996). ISBN: 0964757133. Summary: This is the journal of a woman with Crohn's disease, from her first hospital visit and diagnosis. It will be of particular interest to people newly diagnosed with inflammatory bowel disease (IBD) or facing ostomy surgery. Chapters cover daily living with IBD, surgery (colectomy and ileoanal pull-through), and recoveries. The focus of the book is on maintaining a positive outlook and living life as fully as possible, despite the illness. The book includes a glossary of terms and is illustrated with pencil sketches by the author's husband.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “colitis” at online booksellers’ Web sites, you may discover nonmedical books that use the generic term “colitis” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “colitis” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

A Primate Model for the Study of Colitis and Colonic Carcinoma The Cotton-Top Tamarin (Saguinus oedipus) by Neal K., D.V.M. Clapp (Editor); ISBN: 0849353637; http://www.amazon.com/exec/obidos/ASIN/0849353637/icongroupinterna

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Antibiotic Associated Diarrhea and Colitis: The Role of Clostridium Difficile by S. Peter Borriello (Editor), Peter S. Borriello (Editor) (1984); ISBN: 0898386233; http://www.amazon.com/exec/obidos/ASIN/0898386233/icongroupinterna

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Colitis & Me: A Story of Recovery by Raman Prasad (2003); ISBN: 0972706100; http://www.amazon.com/exec/obidos/ASIN/0972706100/icongroupinterna

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Colitis (Self Help) by Arthur White; ISBN: 0722513186; http://www.amazon.com/exec/obidos/ASIN/0722513186/icongroupinterna

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Colitis (The Experience of Illness) by Michael P. Kelly (1992); ISBN: 0415038391; http://www.amazon.com/exec/obidos/ASIN/0415038391/icongroupinterna

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Contemporary Diagnosis and Management of Ulcerative Colitis and Proctitis by Mark A. Peppercorn; ISBN: 1884065449; http://www.amazon.com/exec/obidos/ASIN/1884065449/icongroupinterna

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Coping With Crohn's Disease and Ulcerative Colitis by Christina Potter (2003); ISBN: 0823939626; http://www.amazon.com/exec/obidos/ASIN/0823939626/icongroupinterna

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Crohn's Disease & Ulcerative Colitis by Fred Saibil, Fredric G. Saibil (1997); ISBN: 1552091147; http://www.amazon.com/exec/obidos/ASIN/1552091147/icongroupinterna

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Crohn's Disease & Ulcerative Colitis: Everything You Need to Know (Your Personal Health) by Fred, Md. Saibil, Fredric G. Saibil (2003); ISBN: 1552977714; http://www.amazon.com/exec/obidos/ASIN/1552977714/icongroupinterna

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Crohn's Disease and Ulcerative Colitis by Canadian Medical Association, Fred Saibil; ISBN: 1552635430; http://www.amazon.com/exec/obidos/ASIN/1552635430/icongroupinterna

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Crohn's Disease and Ulcerative Colitis: Surgical Management by Devinder Kumar, John Alexander-Williams; ISBN: 0387197303; http://www.amazon.com/exec/obidos/ASIN/0387197303/icongroupinterna

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Crohn'S, Colitis, Hemorrhoids, and Me: Kathy's Journal by Kathlene J. O'Leary (1995); ISBN: 0964757133; http://www.amazon.com/exec/obidos/ASIN/0964757133/icongroupinterna

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Day-By-Day Colitis 2000 Calendar by Thomas Masterson (1999); ISBN: 1883205603; http://www.amazon.com/exec/obidos/ASIN/1883205603/icongroupinterna

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Diet Management for Ulcerative Colitis; Menus, Recipes, and Methods of Food Preparation for Anti-Inflammatory Treatment. by Map Hanson; ISBN: 0398023077; http://www.amazon.com/exec/obidos/ASIN/0398023077/icongroupinterna

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Diets to Help Colitis (Diets to Help Series) by Joan Lay; ISBN: 0722517041; http://www.amazon.com/exec/obidos/ASIN/0722517041/icongroupinterna

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Diets to Help Colitis and Irritable Bowel Syndrome: Natural Relief With a Carefully Balanced Regime by J. O. Lay; ISBN: 0722531990; http://www.amazon.com/exec/obidos/ASIN/0722531990/icongroupinterna

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Digestive Health Now: The Four Week Plan to Heal Heartburn, Ulcers, Colitis, Ibs and More by Andrew Gaeddert (2002); ISBN: 155643426X; http://www.amazon.com/exec/obidos/ASIN/155643426X/icongroupinterna

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Dysplasia & Cancer Colitis by Robert H. Riddell (1991); ISBN: 0130537292; http://www.amazon.com/exec/obidos/ASIN/0130537292/icongroupinterna

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Dysplasia and Cancer in Colitis (1991); ISBN: 0444015701; http://www.amazon.com/exec/obidos/ASIN/0444015701/icongroupinterna

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Eating Right for a Bad Gut: The Complete Nutritional Guide to Ileitis, Colitis, Crohn's Disease and Inflammatory Bowel Disease by James Scala; ISBN: 0452267668; http://www.amazon.com/exec/obidos/ASIN/0452267668/icongroupinterna

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Everything You Need to Know About Crohn's Disease and Ulcerative Colitis (Need to Know Library) by Sandra Giddens, Owen Giddens; ISBN: 0823939960; http://www.amazon.com/exec/obidos/ASIN/0823939960/icongroupinterna

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Fundamentals of Colitis by S. J. M. Goulston; ISBN: 0080268625; http://www.amazon.com/exec/obidos/ASIN/0080268625/icongroupinterna

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Gastritis Y Colitis by Abel, Dr Cruz (2001); ISBN: 9706433880; http://www.amazon.com/exec/obidos/ASIN/9706433880/icongroupinterna

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Healthy Digestion: A Natural Approach to Relieving Indigestion, Gas, Heartburn, Constipation, Colitis & More by David Hoffmann, David Hoffman; ISBN: 1580172504; http://www.amazon.com/exec/obidos/ASIN/1580172504/icongroupinterna

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Histopathologic spectrum of regional enteritis and ulcerative colitis by N. Karle Mottet; ISBN: 0721665705; http://www.amazon.com/exec/obidos/ASIN/0721665705/icongroupinterna

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Ibs & Colitis by Jill Wright (2002); ISBN: 185703726X; http://www.amazon.com/exec/obidos/ASIN/185703726X/icongroupinterna

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Intestinal Inflammation (Colitis, Enteritis, Crohn's Disease): Treatment & Therapy Index of New Information by Amer Health Research Institue Staff (1997); ISBN: 0788316028; http://www.amazon.com/exec/obidos/ASIN/0788316028/icongroupinterna

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Intestinal Inflammation (Colitis, Enteritis, Crohn's Disease): Treatment & Therapy: Index of New Information by Amer Health Research Institue Staff, American Health Research Institute (1997); ISBN: 0788316036; http://www.amazon.com/exec/obidos/ASIN/0788316036/icongroupinterna

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Irritable Bowel Syndrome & the Mind-Body/Brain-Gut Connection: 8 Steps for Living a Healthy Life with a Functional Bowel Disorder or Colitis; ISBN: 0965703894; http://www.amazon.com/exec/obidos/ASIN/0965703894/icongroupinterna

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Irritable Bowel Syndrome and the MindBodySpirit Connection: 7 Steps for Living a Healthy Life With a Functional Bowel Disorder, Crohn's Disease or Colitis by William B. Salt II, Neil F. Neimark (2002); ISBN: 0965703851; http://www.amazon.com/exec/obidos/ASIN/0965703851/icongroupinterna

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Living with Your Colitis and Hemorrhoids and Related Disorders [CLV] by Theodore Berland (Author); ISBN: 0312490704; http://www.amazon.com/exec/obidos/ASIN/0312490704/icongroupinterna

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Managing Your Child's Crohn's Disease and Ulcerative Colitis by Keith J. Benkov, Harland S. Winter; ISBN: 1571010238; http://www.amazon.com/exec/obidos/ASIN/1571010238/icongroupinterna

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Medical Approach Vs the Nutritional Approach to Colitis-Crohns Disease; ISBN: 0912582545; http://www.amazon.com/exec/obidos/ASIN/0912582545/icongroupinterna

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Morbus Crohn Colitis Ulcerosa by Guido Adler (1993); ISBN: 0387560327; http://www.amazon.com/exec/obidos/ASIN/0387560327/icongroupinterna

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Mucosal Ulcerative Colitis by David G. Jagelman (Editor); ISBN: 0879932449; http://www.amazon.com/exec/obidos/ASIN/0879932449/icongroupinterna

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Postulating a New Concept of the Etiology, Pathology and Treatment of Chronic Idiopathic Ulcerative Colitis--Is It a Hemorrhagic Disease Caused by mul by N. Phillip Norman; ISBN: 0686875168; http://www.amazon.com/exec/obidos/ASIN/0686875168/icongroupinterna

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Psychotherapy in chronic ulcerative colitis by Aaron Karush; ISBN: 072165293X; http://www.amazon.com/exec/obidos/ASIN/072165293X/icongroupinterna

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Self Help Way To Treat Colitis and Other IBS Conditions, Second Edition by De Lamar, Md. Gibbons, DeLamar Gibbons; ISBN: 0658012177; http://www.amazon.com/exec/obidos/ASIN/0658012177/icongroupinterna

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Self Help-Colitis by Harry Clements; ISBN: 0317072862; http://www.amazon.com/exec/obidos/ASIN/0317072862/icongroupinterna

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Self Treatment for Colitis by Harry Clements, A. White; ISBN: 0722504527; http://www.amazon.com/exec/obidos/ASIN/0722504527/icongroupinterna

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Straight from the Gut: Living With Crohn's Disease & Ulcerative Colitis (PatientCentered Guides) by Cliff Kalibjian (2003); ISBN: 059650005X; http://www.amazon.com/exec/obidos/ASIN/059650005X/icongroupinterna

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The 2002 Official Patient's Sourcebook on Ulcerative Colitis: A Revised and Updated Directory for the Internet Age (Official Patient Guides Series) by Icon Health Publications, Inc. Staff Icon Group International (Compiler) (2002); ISBN: 0597834091; http://www.amazon.com/exec/obidos/ASIN/0597834091/icongroupinterna

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The Angry Gut: Coping With Colitis and Crohn's Disease by W. Grant Thompson (1993); ISBN: 0306444704; http://www.amazon.com/exec/obidos/ASIN/0306444704/icongroupinterna

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The Clinician's Guide to Ulcerative Colitis and Crohn's Disease by P. P. Jewell, et al; ISBN: 0443048037; http://www.amazon.com/exec/obidos/ASIN/0443048037/icongroupinterna

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The Colitis Diet; ISBN: 0849051371; http://www.amazon.com/exec/obidos/ASIN/0849051371/icongroupinterna

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The Crohn's Disease and Ulcerative Colitis Fact Book by Crohn's & Colitis Foundation (Editor), et al (1983); ISBN: 0684179679; http://www.amazon.com/exec/obidos/ASIN/0684179679/icongroupinterna

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The Culinary Couple's Creative Colitis Cookbook by Denise Weale, Ross Weale; ISBN: 0965623904; http://www.amazon.com/exec/obidos/ASIN/0965623904/icongroupinterna

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The Daily Telegraph: Crohn's Disease and Ulcerative Colitis (The Daily Telegraph) by Fred Saibil; ISBN: 1841196711; http://www.amazon.com/exec/obidos/ASIN/1841196711/icongroupinterna

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The First Year---Crohn's Disease and Ulcerative Colitis: An Essential Guide for the Newly Diagnosed by Jill Sklar, Manuel Sklar; ISBN: 1569245320; http://www.amazon.com/exec/obidos/ASIN/1569245320/icongroupinterna

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The Good Gut Guide: Help for Ibs, Ulcerative Colitis, Crohn's Disease, Diverticulitis, Food Allergies, Other Gut Problems by Stephanie Zinser, R. John Nicholls (2003); ISBN: 0007138059; http://www.amazon.com/exec/obidos/ASIN/0007138059/icongroupinterna

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The New Eating Right for a Bad Gut : The Complete Nutritional Guide to Ileitis, Colitis, Crohn's Disease, and Inflammatory Bowel Disease by James Scala; ISBN: 0452279763; http://www.amazon.com/exec/obidos/ASIN/0452279763/icongroupinterna

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The Self-Help Way to Treat Colitis and Other I.B.S. Conditions by Gibbons De Lamar, et al; ISBN: 087983546X; http://www.amazon.com/exec/obidos/ASIN/087983546X/icongroupinterna

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The surgical management of ulcerative colitis by Frank Couper Walker; ISBN: 0407405003; http://www.amazon.com/exec/obidos/ASIN/0407405003/icongroupinterna

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Therapiekonzepte Morbus Crohn / Colitis ulcerosa. by Wolfgang. Fischbach (Author); ISBN: 313106711X; http://www.amazon.com/exec/obidos/ASIN/313106711X/icongroupinterna

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Ulcerative and granulomatous colitis; ISBN: 0398026513; http://www.amazon.com/exec/obidos/ASIN/0398026513/icongroupinterna

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Ulcerative colitis by Michael John Goodman; ISBN: 047148895X; http://www.amazon.com/exec/obidos/ASIN/047148895X/icongroupinterna

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Ulcerative Colitis by Colm A. O'Morain (Editor), et al; ISBN: 0849354986; http://www.amazon.com/exec/obidos/ASIN/0849354986/icongroupinterna

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Ulcerative Colitis (Bailliere's Clinical Gastroenterology) by P. Gibson; ISBN: 0702023108; http://www.amazon.com/exec/obidos/ASIN/0702023108/icongroupinterna

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Ulcerative Colitis and Crohn's Colitis, by Joseph Barnett, Kirsner; ISBN: 0812104803; http://www.amazon.com/exec/obidos/ASIN/0812104803/icongroupinterna

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Ulcerative colitis and Crohn's disease : and other diseases of the alimentary system in childhood; ISBN: 0806715111; http://www.amazon.com/exec/obidos/ASIN/0806715111/icongroupinterna

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Ulcerative Colitis: Focus on Topical Treatment by Stephen B. Hanauer, Philippe Marteau (2000); ISBN: 2742002898; http://www.amazon.com/exec/obidos/ASIN/2742002898/icongroupinterna

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Understanding Crohn Disease and Ulcerative Colitis by Jon Zonderman, et al; ISBN: 1578062039; http://www.amazon.com/exec/obidos/ASIN/1578062039/icongroupinterna

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Vivir con colitis ulcerosa y enfermedad de Crohn by Escarti, Dr Edua, et al; ISBN: 8488066813; http://www.amazon.com/exec/obidos/ASIN/8488066813/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site,

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http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “colitis” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

A comparison of clinical findings and morphologic changes in the peripheral blood in patients with chronic ulcerative colitis. Author: Farmer, Richard G. (Richard Gilbert),; Year: 1967; [Minneapolis] 1960

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Anemia of nontropical sprue and chronic ulcerative colitis studied with radioiron and radiochromium. Author: Giuliani, Emilio R. (Emilio Romolo),; Year: 1970; [Minneapolis] 1962

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Changes in blood coagulation factors associated with chronic ulcerative colitis; with special reference to hypercoagulability. Author: Lee, John Chung Lam,; Year: 1968; [Minneapolis] 1965

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Colitis; mucous and ulcerative stages of constipation, by Charles M. Campbell and Albert K. Detwiller. Author: Campbell, Charles Milton,; Year: 1962; New York, The Educational press [c1935]

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Diagnosis and medical treatment of colitis. Author: Raddin, Joseph Broad,; Year: 1967; Berkeley, Calif., Berkeley Scientific Publications [c1965]

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Diet management for ulcerative colitis; menus, recipes, and methods of food preparation for anti-inflammatory treatment. Author: Hanson, Map.; Year: 1967; Springfield, Ill., Thomas [c1971]

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Help your doctor help you when you have colitis. Author: Alvarez, Walter C. (Walter Clement),; Year: 1970; New York and London, Harper; brothers [c1941]

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How to overcome colitis; a guide to the care and feeding of the crazy colon. Author: Montague, Joseph Franklin,; Year: 1971; New York, Citadel Press [c1956]

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Ileitis following colectomy and ileostomy for mucosal and granulomatous colitis; a clinico-pathologic study of 25 cases. Author: Benjamin, Immanuel,; Year: 1967; [Minneapolis] 1970

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Inflammation in gut; esophagitis, duodenitis, segmental colitis, edited by Z. Maratka and R. Ottenjann. Author: Maratka, Z.; Year: 1965; Basel, New York, Karger, 1970

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Living with your colitis and hemorrhoids, and related disorders Author: Berland, Theodore,; Year: 1969; New York: St. Martin's Press, c1975

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Regional (segmental) colitis; a clinical and pathologic study. Author: Neuman, Harold Wilfred,; Year: 1966; [Minneapolis] 1953

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The management of colitis, by J. Arnold Bargen. edited by Morris Fishbein. Author: Bargen, Jacob Arnold,; Year: 1960; New York, N. Y., National medical book company, inc., 1935

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The modern management of colitis. Author: Bargen, Jacob Arnold,; Year: 1936; Springfield, Ill., C. C. Thomas, 1943

11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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The surgical management of ulcerative colitis. Author: Walker, Frank C. (Frank Couper); Year: 1969; New York, Appleton-Century-Crofts; London, Butterworth [c1969]

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Ulcerative colitis [by] J. C. Goligher [et al.] With a chapter on pathology by B. C. Morson. Author: Goligher, J. C. (John Cedric); Year: 1969; Baltimore, Williams and Wilkins [1968]; ISBN: 702002445

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Ulcerative colitis; the hidden flame. Author: Cohn, Victor,; Year: 1971; [Washington, National Foundation for Research in Ulcerative Colitis, 1961]

Chapters on Colitis In order to find chapters that specifically relate to colitis, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and colitis using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “colitis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on colitis: •

Collagenous and Lymphocytic Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 631-633. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: Collagenous and lymphocytic colitis are clinicopathologic syndromes that represent distinct, possibly autoimmune, forms of idiopathic inflammatory colonic bowel disease. This chapter on collagenous and lymphocytic colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). Both collagenous and lymphocytic colitis present as chronic, watery, noninfectious diarrhea in middle-aged patients with negative radiographic and endoscopic studies. Collagenous colitis predominantly occurs in women; lymphocytic colitis is found equally in both genders. Often there is intermittent, crampy, diffuse abdominal pain, and, not surprisingly, some patients have a previous diagnosis of the irritable bowel syndrome (IBS). In patients with symptomatic collagenous-lymphocytic colitis, several factors should be considered. Since colonic absorption is decreased in all patients and small bowelsecretion has been noted in some patients, dietary secretagogues, such as caffeine-or lactose-containing foods, should be eliminated from the diet. Because of possible association between collagenous colitis and nonsteroidal anti-inflammatory drugs (NSAIDs), these agents should be discontinued. If steatorrhea (excessive amounts of fats in the stool) is documented, a low-fat diet may be helpful. In the presence of bile salt malabsorption, binding resins, such as cholestyramine, have been useful. Some patients are helped by bulking agents and by antidiarrheal medications, such as loperamide hydrochloride (Imodium). The authors conclude that although long term experience is limited, retrospective examination of patients with collagenous lymphocytic colitis reveals a

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benign and chronic course. There is no association between this condition and Crohn's disease or ulcerative colitis. 1 table. 4 references. •

How and Why the Digestive System Malfunctions in People with Crohn Disease or Ulcerative Colitis Source: in Zonderman, J. and Vender, R.S. Understanding Crohn Disease and Ulcerative Colitis. Jackson, MS: University Press of Mississippi. 2000. p. 29-35. Contact: Available from University Press of Mississippi. 3825 Ridgewood Road, Jackson, MS 39211-6492. (601) 432-6205. Fax (601) 432-6217. E-mail: [email protected]. PRICE: $28.00 plus shipping and handling. ISBN: 1578062039. Summary: Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD), are chronic illnesses of unknown origin. This chapter on digestive system malfunction in IBD is from a book that provides timely information about how to obtain and maintain the highest quality of life possible while living with IBD. The authors offer a patient's perspective on coping with IBD. They describe the major pathology of the intestinal tract in a person with CD or UC as chronic inflammation. Inflammation is characterized by four conditions: heat, redness, pain, and swelling. In IBD, inflammation occurs in the inside of the gastrointestinal tract and the inflammatory process also damages the cellular structure of the intestine. In UC, the inflammation affects only the mucosa; in CD, the inflammation can go through the mucosa and involve the full thickness of the bowel wall. Depending on where in the gastrointestinal tract the inflammation occurs, effects include malabsorption of nutrients, bleeding, diarrhea, fever, and pain. The chapter offers statistics on IBD, discusses the possible genetic component in the disease, and considers the role of the immune system.

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Radiation Enterocolitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 635-638. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: Management of radiation injury to the small and large intestine continues to present challenges to gastroenterologists, radiation oncologists, and surgeons alike. This chapter on radiation enterocolitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). With many oncology (cancer therapy) protocols now employing radiation therapy either as adjuvant or curative therapy, the collateral effects of radiation on rapidly proliferating tissues are increasingly important issues. The normal intestinal mucosa and, to a lesser extent, intestinal vascular and interstitial connective tissue compartments are sensitive to ionizing radiation. Consequently, this may be especially problematic in tissues already affected by IBD, because of the varying amount of coincident injury and inflammation as well as the hyperproliferative state of the epithelium. Small and large intestinal complications are dependent on radiation therapy techniques and better use of the modality should enable further reductions in adverse events. Acute complications are correlated with the amount of irradiated bowel and the fraction size. Acute radiation enterocolitis symptoms include diarrhea, nausea,

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abdominal cramps, and tenesmus (fecal urgency) of varying severity. These conditions usually are transient and resolve within a few weeks of completion of radiation treatment. Chronic events also are dependent on the total surface area of bowel irradiated, fraction size, and the total amount of radiation. Prior abdominal surgeries, cholecystectomy, pelvic inflammatory disease (PID), hypertension (high blood pressure), and diabetes mellitus have been documented as risk factors increasing the likelihood of the development of chronic events. The authors conclude with a brief discussion of strategies to prevent radiation enterocolitis. 1 table. 6 references. •

Refractory Distal Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 81-85. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: Patients with refractory distal colitis suffer unrelenting or episodic symptoms of colonic inflammation despite maintenance therapy. This chapter on refractory distal colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). Evaluation of the patient is approached in terms of the symptoms that disrupt their lives and the extent and severity of mucosal inflammation. Although these two issues are integrally related with a positive therapeutic response improving both, optimal management addresses each individually. Refractory colitis is a term with numerous possible interpretations: failure to respond to conventional therapy, partial therapeutic response, extension of the disease, persistent symptoms despite apparent mucosal healing, or control of disease only with doses of medication that induce toxicity. The principal persistent symptoms are rectal bleeding, pain, tenesmus, constipation, increased number of stools, nocturnal diarrhea, fecal incontinence, perineal pain, and systemic symptoms such as fatigue and fever. Management options include mesalamine, glucocorticoids, mercaptopurine and azathioprine, methotrexate, nicotine, metronidazole, heparin, and cyclosporine, as well as surgical intervention. The author concludes by noting that a few patients with left sided UC are disabled by their symptoms and do not respond to medical therapy (drugs); in this select group of patients, surgery is a reasonable approach with less health risk than long term glucocorticoid therapy.

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Current Controversies in the Surgical Management of Ulcerative Colitis Source: Jewell, D.P.; Warren, B.F.; Mortensen, N.J., eds. Challenges in Inflammatory Bowel Disease. Malden, MA: Blackwell Science, Inc. 2001. p.157-165. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail: [email protected]. Website: www.blackwell-science.com. PRICE: $145.95. ISBN: 0632051698. Summary: Proctocolectomy with permanent ileostomy is curative for ulcerative colitis. Since its introduction 50 years ago, subsequent surgical developments have been aimed at avoiding a permanent ileostomy. This chapter on the surgical management of ulcerative colitis is from a book that offers an approach to the subject of inflammatory bowel disease (IBD) that highlights current areas of controversy. The authors note that

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colectomy with ileorectal anastomosis and restorative proctocolectomy are well accepted but controversies remain on the relative indications for these procedures. In addition there is some controversy on the indications for surgery against continued medical treatment and questions relating to technical aspects of the procedures. The authors discuss emergency and elective surgeries separately. 74 references. •

Management of Severe Ulcerative Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 143-147. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: Severe or fulminant ulcerative colitis (UC) is a potentially fatal disease that was associated with a 30 percent mortality rate prior to the introduction of corticosteroids and, in steroid-refractory cases, early surgery. During recent years, the trend has changed from saving lives to improving the quality of life of patients by saving colons or using modern surgical methods. This chapter on the management of severe UC is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and UC, together known as inflammatory bowel disease (IBD). The author discusses the etiology, differential diagnosis, and definition of severe UC. Patients with definite or strongly suspected severe colitis must be admitted to the hospital for intensive treatment. The mainstay of the medical treatment is corticosteroids, taken orally with nothing except small sips of water, and total parenteral nutrition (TPN, outside the gastrointestinal tract). Usually, corticosteroids are administered intravenously in severe colitis, but even in acute colitis, corticosteroids given orally are absorbed completely but somewhat more slowly than those administered intravenously. Colonoscopy, rather than food challenge, is relied on to improve decision making in patients with incomplete or poor response to treatment. The author discusses the indications for using antibiotics, 5 aminosalicylic acid (5 ASA), and immunosuppressives. Beyond the drug therapy, the patient must be monitored carefully. Three or 4 days after initiating therapy, a sigmoidoscopy is of further help in monitoring the response and a biopsy helps to rule out cytomegalovirus. Assessment of response is made mainly on clinical and laboratory grounds, although repeat plain abdominal radiography during ongoing treatment can show signs of impending perforation or definite toxic dilatation that requires surgery. 1 table. 10 references.

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Induction of Remission in Ulcerative Colitis Source: in Williams, C.N., et al., eds. Trends in Inflammatory Bowel Disease Therapy 1999. Boston, MA: Kluwer Academic Publishers. 2000. p. 107-116. Contact: Available from Kluwer Academic Publishers. Customer Service Deparment, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. PRICE: 145.00 plus shipping and handling. ISBN: 0792387627. Summary: Therapy for acute ulcerative colitis (UC) begins with an assessment of disease extent, severity and the response to prior treatments. This chapter on the induction of remission in UC is from a monograph that reprints the presentations given at the Trends in Inflammatory Bowel Disease Therapy Symposium, held in Vancouver, British

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Columbia, Canada, in August 1999. The general objective of the conference was to provide an update in the etiology, pathogenesis, and treatment of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). In this chapter, the author describes care for patients with mild, moderate and severe UC. Mild to moderate activity can be treated with oral mesalamine in the setting of extensive colitis, or topical mesalamine or topical corticosteroids for distal disease. The dose response is relevant for oral mesalamine, but is less important for topical therapy. Moderate to severe extensive colitis requires corticosteroid therapy whereas distal disease can still be treated with topical mesalamine or topical corticosteroids. Severe to fulminant colitis requires hospitalization and parenteral corticosteroids. Significant improvement is anticipated within 3 to 5 days of initiating steroids at doses comparable to 40 to 60 milligrams of prednisolone or 200 to 400 milligrams of hydrocortisone. Patients who do not respond within 7 days are unlikely to improve. Failure to improve on parenteral steroids is indication for either colectomy or treatment with cyclosporin. Cyclosporin will provide prompt improvement in approximately 70 to 80 percent of patients within 3 to 5 days. Failure to respond with a reduction in bowel movements, cessation of bleeding and transfusion requirements, and reduction in erythrocyte sedimentation rate within a week implies treatment failure and is an indication of colectomy. Total parenteral nutrition (TPN, usually intravenous therapy) is adjunctive rather than primary therapy for patients with severe colitis who should be allowed t eat as long as they have an appetite. Narcotic analgesia (painkillers) is contraindicated, as are nonsteroidal antiinflammatory agents (NSAIDs). The author notes that the roles of topical mesalamine, infliximab, and heparin in the setting of fulminant (rapid, sudden, severe) disease or toxic megacolon have not been established. 60 references. •

Aminosalicylates Therapy for Ulcerative Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 123-126. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on aminosalicylates therapy for ulcerative colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). The author cautions that careful attention is necessary in interpreting clinical trials of the aminosalicylates in UC, because of variations in its indications (active disease versus maintenance), therapeutic end points and indices, and duration of treatment. Oral aminosalicylates are the primary maintenance therapy to prevent relapse of colitis after remission has been achieved. There are practical considerations that differentiate sulfasalazine from the non sulfa containing aminosalicylates. There is dose-related efficacy for the maintenance effects of all oral aminosalicylates. With sulfasalazine, the maintenance dose of 2 grams per day is often selected as the best 'balance' between efficacy and side effects. This has led to previous recommendations to reduce the active dose down to 2 grams per day as a maintenance dose. Unfortunately, this precludes use of a more efficacious maintenance dose. In contrast, in the absence of dose-related side effects with mesalamine, the optimal maintenance dose (with respect to efficacy) is the same as the inductive dose. The only constraints are cost and patient compliance. Typically, administration of oral aminosalicylates on a twice-daily schedule is recommended, to enhance compliance.

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Because of variations in gastric emptying and colonic motility among patients, there is no rationale to require administration of oral mesalamine compounds in more than two doses per day. 10 references. •

Colitis and Enteritis in Immunocompromised Individuals Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 639-644. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on colitis and enteritis (inflammation of the large and small intestines, respectively) is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). When patients present with gastrointestinal (GI) disorders that are resistant to conventional therapies (for example, gluten withdrawal in celiac disease) or autoimmune GI disease, which occurs at a young age, immunoglobulin levels should be measured to rule out immunodeficiency as a cause. Because there isa high prevalence of recurrent giardiasis, sprue-like disorder, NLH (nodular lymphoid hyperplasia, or overgrowth), and IBD in immunodeficient patients, patients with these GI diseases should be screened for hypogammaglobulinemia. Early diagnosis and treatment may reduce the morbidity and mortality associated with immunodeficiency. For immunodeficient patients who present with diarrhea or malabsorption, efforts should be made to seek the cause of these problems, because common causes, such as giardiasis and celiac disease, are treatable. There need not be concerns about treating these patients with potentially immunosuppressive agents (steroids or AZA), because the immunodeficiency is generally controlled with intravenous Ig (immunoglobulins). Owing to the increased risk of malignancy (cancer) in immunodeficient patients, periodic GI evaluation in patients with primary immunodeficiency has been advocated, with a view to early detection and treatment of these malignancies. 2 tables. 10 references.

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Colitis in the Elderly Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 619-624. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on colitis in the elderly is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). The spectrum of pathophysiologic conditions associated with diarrhea in the elderly is broad and includes inflammatory diseases of the colon. Colitis in theelderly, defined arbitarily as an age greater than 65 years, merits particular attention because the diagnostic possibilities and the course and prognosis of colitis in the elderly differ from those in younger patients. Typical symptoms include crampy lower abdominal pain and frequent bowel movements, which are characteristically small in volume. Tenesmus (rectal urgency), blood in the stool (microscopic or visible), and fever

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also suggest colonic inflammation. Differentiating among infectious, ischemic, and ulcerative or Crohn's colitis may be particularly difficult in an older patient. Often symptoms of colitis in the elderly do not immediately suggest an inflammatory disorder, let alone IBD, for several reasons, including a blunted response to pain; poor communication owing to impaired cognition, hearing, or vision; fear of the medical system; a focus on cancer as the most likely cause of altered bowel function or gastrointestinal bleeding; and the misconception that IBD rarely has its onset in old age. Physical signs in the elderly may be atypical as a result of altered sensory perception, related in part to the use of a variety of medications or the presence of coexisting systemic disease. The authors caution that a delay in diagnosis is common in older patients with IBD and may result in complications or inappropriate treatment. 1 table. 7 references. •

Crohn's Disease and Indeterminate Colitis Source: in Corman, M.L.; Allison, S.I.; Kuehne, J.P. Handbook of Colon and Rectal Surgery. Philadelphia, PA: Lippincott Williams and Wilkins. 2002. p.777-826. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 223-2300. Fax (301) 223-2365. PRICE: $79.00 plus shipping and handling. ISBN: 0781725860. Summary: This chapter on Crohn's disease and indeterminate colitis is from a handbook that addresses the entire range of diseases affecting the colon, rectum, and anus. The authors consider incidence, epidemiology, etiology, pathogenesis, physical examination, endoscopic examination, radiographic features, specialized laboratory studies, pathology, signs, symptoms, presentations, Crohn's disease in children and adolescents, Crohn's disease in pregnancy, extraintestinal manifestations (including oral, esophageal, gastroduodenal, pancreatic, hepatobiliary, cutaneous, arthritis and rheumatological, ocular, amyloidosis, urologic, and cardiac), the relationship of Crohn's disease to carcinoma (cancer), medical management, surgical management of short bowel syndrome, proctocolectomy, ileostomy, segmental colon resection, management of small bowel Crohn's disease, and indeterminate colitis. The authors stress that the results of surgery for Crohn's disease are less than satisfactory. Therefore, surgical intervention must be limited to those patients who have complications severe enough to justify an operation. 18 figures.

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Dietary Recommendations for Active and Inactive Ulcerative Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 161-164. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on dietary recommendations for active and inactive ulcerative colitis (UC) is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and UC, together known as inflammatory bowel disease (IBD). This chapter discusses the role of diet and nutritional support in ulcerative colitis (UC) in which the catabolic effect (breakdown or loss of body tissue) of inflammation, impaired nutrient absorption, and gastrointestinal (GI) dysfunction can rapidly lead to malnutrition. Inactive UC is a chronic disorder and may be associated with malnutrition, specific elemental

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deficiencies, and specific food intolerances. Patients may not eat enough to meet their nutritional requirements because of anorexia, drug side effects (eg, nausea, headache, and anorexia), food-induced diarrhea, or pain. In lactose intolerant people, production of hydrogen produces bloating, nausea, and flatulence and unabsorbed short-chain fatty acids produce diarrhea. Lactose intolerance may be primary (racial or congenital) or secondary (eg, due to bacterial overgrowth or intestinal mucosal disease or injury). The incidence of UC is not increased in lactose intolerant people, and the incidence of lactose intolerance is not increased in patients with UC. In UC in remission, lactose restriction is important to control symptoms only in those patients documented to have lactose intolerance, presumably on a genetic basis. Active UC involves pathologic and physiologic changes both within the colonic mucosa and systemically. The colonic mucosa is inflamed and associated with loss of fluid, electrolytes, proteins and immunoglobulins, albumin (protein), and hemoglobin (red blood cells). Systemic manifestations of fever and anorexia are associated with reduced oral intake of nutrients. However, the body is in a catabolic state, with increased nutritional requirements and increased energy needs as a result of fever, associated infections, and steroid therapy. In these situations, nutritional support is essential. In such cases, parental or enteral nutrition not only may be of value but may be essential in patient management. 2 tables. 10 references. •

Indeterminate Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 157-160. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on indeterminate colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). Indeterminate colitis is a type of IBD involving the colon that cannot be definitively categorized as either UC or CD. Indeterminate colitis may be merely part of a spectrum, somewhere in between UC and CD. However, it is also possible that indeterminate colitis in the setting of a continued diagnosis of indeterminate colitis after long-term follow-up is a separate disease process, which should be categorized as a specific type of IBD. Therapeutic approaches useful for indeterminate colitis are similar to those for UC or Crohn's colitis. Once medically induced remission has been achieved, long-term medical maintenance of remission for indeterminate colitis includes oral and rectal mesalamine and/or immunomodulators (6-mercaptopurine or Imuran). Although a diagnosis of indeterminate colitis is not an absolute contraindication to an ileal pouchanal anastomosis, both patient and physician should be aware of the increased risk of complications and the lower success rate that can occur. Patients with indeterminate colitis should undergo yearly or bi yearly colonoscopic surveillance beginning 8 years after the initial onset of disease symptoms (to screen for colorectal cancer). 11 references.

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Remission Maintenance in Ulcerative Colitis Source: in Williams, C.N., et al., eds. Trends in Inflammatory Bowel Disease Therapy 1999. Boston, MA: Kluwer Academic Publishers. 2000. p. 117-127.

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Contact: Available from Kluwer Academic Publishers. Customer Service Deparment, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. PRICE: 145.00 plus shipping and handling. ISBN: 0792387627. Summary: This chapter on remission maintenance in ulcerative colitis (UC) is from a monograph that reprints the presentations given at the Trends in Inflammatory Bowel Disease Therapy Symposium, held in Vancouver, British Columbia, Canada, in August 1999. The general objective of the conference was to provide an update in the etiology, pathogenesis, and treatment of inflammatory bowel disease (IBD), including UC and Crohn's disease (CD). In this chapter, the author reports on a large patient cohort from Copenhagen. From this group, it is known that about 50 percent of all patients with UC who are in a continuous supervision program are in remission each year. However, cumulatively, 90 percent of patients have repetitive relapses over time. In this group, 25 percent of patients had undergone colectomy (removal of a portion of the colon) after 10 years; however, more than 90 percent were able to continue to work during this time. These disease characteristics indicate that continuous supervision and remission maintenance contributes to such a generally positive outcome of this disease, with a goal of decreasing the number of relapses and normalization of cancer risk. The newer 5 aminosalicylic acid (5 ASA) releasing drugs have been tested for remission maintenance; they seem to be more or less equally effective (compared to sulphasalazine). For patients who have frequent relapses in spite of drug treatment, or those who can only be brought into remission using azathioprine, this drug has also been used for remission maintenance with a relatively good success rate. The author concludes that currently every patient with a definitive diagnosis of UC in remission should be treated with either sulphasalazine or the newer 5 ASA releasing drugs. The exact duration of such treatment is not yet known; indefinite treatment is normally recommended. Since this will normally not be accepted by the patient, a withdrawal attempt can be made after 3 to 4 years of continuous maintenance treatment. In all patients who are difficut to treat and are having relapses in spite of 5 ASA, azathioprine should be considered. However, it should be kept in mind that surgery can cure the disease, although at a price. 4 figures. 12 tables. 44 references. •

Surgery for Crohn's Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 495-500. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on surgery for Crohn's colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). The surgical treatment of CD affecting the colon and rectum is a particularly challenging endeavor. CD of the colon and rectum manifests with a wide variety of anatomic distributions, diverse complications, and clinical patterns, for which the optimal surgical management must be individualized for each patient's specific situation. The mainstay of therapy for CD is medical management; surgical treatment is required when medical treatment fails and in the presence of septic complications, obstruction, cancer, hemorrhage, and toxic megacolon. Fistulae (abnormal passageways) and abscesses (pockets of infection) requiring surgical management is the indication for

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operation in up to 25 percent of the patients undergoing surgery for CD. The choice of operation for colorectal CD is dependent on multiple variables, including the distribution of disease, the extent of involvement, previous resections, rectal compliance, and adequacy of fecal continence (voluntary control of bowel movements). The authors address concerns regarding the extent of resection, discussing recurrence rates, functional complications, malnutrition, and problems with diarrhea. The authors also report the experience at the University of Chicago with a series of 161 patients who underwent colectomies (removal of a portion of the colon) for CD limited to the colon. 1 table. 14 references. •

Indeterminate Colitis: Surgical Approaches Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 241-244. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on surgery for indeterminate colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). Although the medical treatment for UC and CD is quite similar, restorative proctocolectomy (or ileal pouch-anal anastomosis), now considered the gold standard surgical treatment for UC, usually is contraindicated in known cases of CD due to the high probability of a poor outcome. It is generally agreed that ideally the surgeon should have a clear diagnosis of UC before undertaking restorative proctocolectomy. The term indeterminate colitis has fallen into common use now when a decision (whether the patient has UC or CD) cannot be made on the basis of colonscopy and biopsy appearances. The authors answer common questions on the surgical management of patients with indeterminate colitis. If there is preoperative suspicion of CD, a three stage surgery is advised. A colectomy with ileostomy is performed, giving the pathologist a better opportunity to make an accurate diagnosis. Restorative proctocolectomy may still be performed later. If the diagnosis is more likely to be CD, ileorectal anastomosis may be utilized. The authors emphasize the importance of surgeons and pathologists working closely together to provide the most appropriate care. 1 figure. 14 references.

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Sequential and Combination Therapy of Ulcerative Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 115-118. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the drug therapy of ulcerative colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). UC is a chronic inflammatory disease of unknown cause and incurable with current medications. For palliation, the clinician must choose from an array of oral, per-rectal, and intravenous treatments with many

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dosing options. The medications, doses, and routes of delivery for treatment of active disease may be different from those used for maintenance of remission. Initial treatment of every patient with one drug at a single dose and delivery route (sequential therapy) is the traditional and least complicated way for clinicians and patients to judge the effectiveness and tolerability of a treatment. The compliance with using a single drug is likely to be better than with multiple drugs or delivery routes and the cost probably will be less. If the initial treatment is not effective or tolerable, then the dose can be adjusted, with or without starting other drugs. The main drawback to sequential therapy is that the trial and error method of adding medications may prolong the time to response, compared to starting multiple drugs together, so this approach is most attractive for mildly active disease when controlling symptoms quickly is less critical. Starting multiple treatments at once, either with the same drug or by different delivery routes, or using two or more drugs (combination therapy) may give a combined effect with more prompt onset of action and better efficacy than starting with a single drug and adding others later. The approach is most commonly used for moderate or severe disease when there is urgency to get the symptoms controlled promptly. Drawbacks to combination therapy are the lack of data from controlled trials to confirm the benefits, difficulty identifying the offending drug if an adverse effect occurs with multiple drug therapy, lower patient compliance, and probably higher cost. 2 tables. 7 references. •

Management of Distal Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 69-71. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the management of distal colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). Distal colitis is defined as UC limited to the distal 30 to 50 cm of the large intestine (involving the rectum, sigmoid, and descending colon) and not extending beyond the splenic flexure. Distal colitis is the most common clinical scenario of UC, accounting for 60 to 70 percent of outpatients. From the management perspective, and also due to other physiologic and prognostic features, it is best to separate distal colitis from proctitis, in which the inflammatory process is confined to the rectum. Proctitis often demonstrates more extensive mucosal inflammation, both macroscopic and histologic, compared to more extensive disease (disease in longer parts of the intestines) and thus may require a more prolonged therapeutic approach. Topical treatment is the initial therapy of choice for patients with distal colitis. Enemas are most effective for disease proximal to the rectum, whereas suppositories are both effective and well tolerated in the setting of proctitis. There remains significant controversy and differences of approach regarding dosing, available formulations, and duration of topical versus oral therapy in different parts of the globe. 12 references.

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Management of Ulcerative Colitis in Children Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 153-155.

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Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the management of ulcerative colitis (UC) in children is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and UC, together known as inflammatory bowel disease (IBD). Inflammatory bowel diseases (IBDs) in children are chronic illnesses with symptoms that wax and wane. Although some children may experience a prolonged remission, many have recurrent exacerbations that require ongoing medical evaluation and therapy. In a recent study, children with UC were diagnosed more rapidly than children with CD; however, in both diseases, a significant time elapsed prior to the start of effective therapy. This delay of over 6 months from the time of onset of symptoms to initiation of treatment indicates that more awareness of these diseases is needed among primary care providers. Quality of life is reduced in children with IBD; pediatric gastroenterologists should be aware of the typical psychological patterns in these patients and integrate psychosocial support into the treatment plan. Deciding which medication to use to induce remission in a child with new-onset UC depends on the severity of the disease. Children who have mild disease characterized by bloody diarrhea or abdominal cramps, without fever, anemia, or hypoalbuminemia, usually respond to sulfasalazine, mesalamine, or olsalazine. About 70 percent of children with moderate to severe disease require corticosteroids in the first year of treatment. Characteristics of moderate to severe disease include more than six bloody stools daily, abdominal cramps, awakening at night to defecate, fever, anemia, or hypoalbuminemia (low levels of protein in the blood). The decision to perform a colectomy (removal of part of the colon) in a child with UC should be made by the patient, family, and health care providers all working together to reach consensus. As surgical techniques improve and more is learned about the adaptation of pouches in growing children, patients and providers will be better prepared with information upon which to base a decision. The risks of using potent immunosuppressive agents must be balanced against the potential complications of surgery and the possibility for cure. 1 table. 8 references. •

Therapeutic Expectations: Medical Management of Ulcerative Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 111-113. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the medical management of ulcerative colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). The author stresses that therapeutic expectations for UC must take into consideration the chronic, medically incurable nature of inflammatory bowel disease (IBD), the varied mucosal extent, potential severity, and disease or therapy related complications. It is most useful to consider the therapeutic expectations with regard to inducing remission, maintaining remission, treating symptoms, and treating or preventing complications. Ulcerative colitis can be complicated by intestinal or extra-intestinal complications. Intestinal complications,

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such as bleeding and associated anemia, hypoproteinemia, or electrolyte abnormalities require prompt control with inductive therapies. Thereafter, supplementation with iron and folic acid (with sulfasalazine) should treat and prevent further development of anemia during maintenance therapy. Other intestinal complications, such as toxic megacolon or perforation, can be prevented with aggressive inductive therapies, according to the severity of presentation. Patients should be warned against the use of NSAIDs and to alert their physician when primary care physicians or other specialists prescribe antibiotics or other medications, to be certain they do not induce diarrhea (Clostridium difficile) and are compatible with UC therapy. Controlling colonic inflammation usually prevents extraintestinal complications, such as peripheral arthritis and cutaneous manifestations. In addition, with the advent of pelvic pouch procedures, an additional goal of medical therapy is to treat, and eventually prevent, pouchitis. This chapter serves as an introduction to a section of 12 chapters on UC. 6 references. •

Medical Therapy of Crohn's Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 429-433. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the medical therapy of Crohn's colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and Ulcerative Colitis (UC), together known as inflammatory bowel disease (IBD). The treatment goals for patients with Crohn's disease, irrespective of the sites involved, are to reduce symptoms, induce and maintain remission, improve health-related quality of life (HRQOL), and stimulate mucosal healing. Specific management also is based on patient preferences and the use of the most cost-effective strategies. Selection of treatment for Crohn's colitis is based on several important features of the disease, including the disease site (whether colitis alone or both small and large bowel), extent, severity, presence of complications or extra-intestinal manifestations, prior response to specific drugs, and perhaps disease behavior (inflammatory, fistulizing, stenotic). However, patient characteristics also are extremely important. Adverse effects of treatment; the patient's personality; the presence of anxiety or depression, which may reduce compliance; and the presence of comorbid conditions, which is more prevalent in older patients, also impact upon both the selection of and response to different therapies. The authors offer suggested guidelines for the treatment of active Crohn's colitis. Medical treatment can be classified as supportive or specific. General measures include treatment of dehydration, anemia, nutritional or vitamin deficiencies, and the use of antidiarrheal agents, such as loperamide, or analgesics when needed. Specific measures are directed at the management of inflammation and halting the disease process. More potent drugs are needed in subjects whose disease has been flaring for an extended period without treatment or who respond poorly to initial treatment. Patients are encouraged to optimize their nutritional status, get adequate rest, and minimize stress. The chapter concludes with a brief discussion of maintenance of remission. 1 figure. 2 tables. 11 references.

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Therapeutic Expectations: Surgical Management of Ulcerative Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 171-173. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the surgical management of ulcerative colitis (UC) is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and UC, together known as inflammatory bowel disease (IBD). This chapter focuses on what patients can expect after surgery for medically refractory (not responsive to drug therapy) UC. Almost all patients will be better off after operation than before operation. The operation is safe. Their colitis will be 'cured,' their colitis medications will be discontinued, and their intestinal symptoms will subside. Their physiologic and social functions will generally be preserved or improved, and a feeling of good health and a satisfactory quality of life will return. However, the outcome may not be perfect, and long-term complications can occur. Physicians do their best to achieve an excellent outcome and avoid complications, while providing compassionate, cost-effective, surgical care. Currently, most patients who undergo elective surgery for ulcerative colitis have a proctocolectomy and an ileal pouch-anal canal anastomosis (IPAA). In IPAA, the entire disease colon and rectum are removed, but the anal sphincters are preserved. A new rectum is formed from the terminal ileum (ileal pouch); attaching the pouch to the anal canal restores defecation to the standard transanal route with satisfactory fecal continence. However, proctocolectomy and Brooke ileostomy, proctocolectomy and continent ileostomy (Kock pouch), and colectomy and ileorectostomy still are used, and are also explained to the patient. Indeed, these operations still are the operations of choice for selected patients. 6 references.

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Use of Antibiotics and Other Anti-infectious Agents in Ulcerative Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 149-151. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the use of antibiotics and other anti infectious agents in ulcerative colitis (UC) is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and UC, together known as inflammatory bowel disease (IBD). Abundant evidence suggests that an imbalance between luminal (in the intestines) bacteria and the host inflammatory and immune response plays a central role in the pathogenesis (development) of inflammatory bowel disease (IBD). Development of UC has been observed after enteric (through the gastrointestinal tract) infection with Salmonella, Shigella, and Yersinia species. While these specific pathogens are not considered etiologic (causative) agents of UC, a transient infection may initiate a cascade of inflammatory events that, in predisposed individuals, can lead to UC. Similarly, although many enteric pathogens have been associated with relapse of UC, there is no evidence that persistence of these infections is a cause of the disease. In recent UC

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clinical trials, administration of live non-pathogenic Escherichia coli or a mixture of bifidobacteria, lactobacilli, and streptococci was equivalent to mesalamine in maintenance of remission. Taken together, these data suggest that the beneficial effect of antibiotics may not result from a long-term reduction in total bacterial load but rather from a qualitative alteration of the resident bacterial population. The recent human data further suggest a role for probiotics in the maintenance therapy for UC patients. This topic is also discussed in the chapter on the role of bacteria in CD and the chapter on pouchitis. The authors note that the lack of antibiotic benefits in randomized trials should not completely preclude their use in the management of selected UC patients. In clinical practice, these drugs may benefit patients with an acute flare of the disease, toxic patients with or without megacolon, and subsets of patients with refractory disease. 11 references. •

Immunomodulator Use in Patients with Distal Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 103-106. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the use of immunomodulators for treating distal colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). This chapter outlines an approach to the use of immunomodulators for distal colitis, including both ulcerative colitis (UC) and Crohn's disease (CD). The discussion reviews the decision-making whether to use an immunomodulator, what modulators are available, how to implement and monitor therapy, and duration of therapy. The commonly used immunomodulator agents are azathioprine, 6 mercaptopurine, methotrexate, and infliximab (for CD only). The indications for the use of immunomodulators in IBD includes frequent relapse requiring corticosteroids, corticosteroid dependence, presence of corticosteroid complications, significant contraindications to corticosteroid use, and active disease despite optimal medical management with nonimmunomodulator drugs. The accumulated evidence and experience demonstrating the effectiveness of immumodulators over the last 25 years has led to their widespread use to the benefit of many patients with inflammatory bowel disease (IBD). Therefore, it is important for every gastroenterologist treating patients with IBD to become well educated regarding this class of medications and to develop an efficient approach for their use. There are separate chapters on immunomodulator use in UC and in CD. 5 tables. 4 references.

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Mucosal Protective and Repair Agents in the Treatment of Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 107-110. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the use of mucosal protective and repair agents for treating colitis is from the second edition of a book devoted to the details of medical, surgical,

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and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). The terms 'mucosal protection and repair' in relation to colitis are based on the concept that mechanisms involved in mucosal defense may at times be overwhelmed and the mucosa (the lining of the intestine) damaged. An appreciation of some of the features that protect colonic mucosa may help identify how certain therapeutic agents produce their effect. The agents discussed are carbomers, bismuth, nicotine, lignocaine, probiotics, and shortchain fatty acids. The authors note that an approach to treatment based on the colonic mucosal barrier is superficially attractive, the therapeutic agents that have been examined have not achieved either proven value or commercial availability. With standard therapy of topical or oral 5-aminosalicylates or steroid preparations, remission can be achieved in approximately 80 to 90 percent of patients with distal UC. It is difficult for new alternative treatments to compete with the impressive rate of first-line therapy. A new treatment would have to be at least as effective, better tolerated, and perhaps more economical in order to replace conventional therapy. One possible application for newer agents would be use in those patients who are resistant to conventional therapy or have difficulty because of side effects. At present, it is the authors' clinical practice to reserve agents such as bismuth and nicotine carbomer for such patients, or for clinical trials. 1 figure. 8 references. •

Use of Nicotine and Tobacco in Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 99-101. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the use of nicotine and tobacco for treating colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). Previous epidemiological observations suggested a beneficial effect of smoking in patients with UC and led to the investigational use of nicotine as a therapeutic agent. Ulcerative colitis is a disease of nonsmokers. Treatment with transdermal (skin patch) nicotine appears to be effective for active UC at the highest tolerated dose of nicotine (22 to 25 milligrams every 24 hours ) but it is not effective at low doses as maintenance therapy. Uncontrolled pilot studies showed that nicotine enemas may be of clinical benefit for left-sided colitis. Controlled studies with topical nicotine treatment (enemas or delayed-release oral capsules) are awaited. Adverse reactions are a limiting factor for long-term transdermal nicotine therapy, particularly in life-long nonsmokers, whereas nicotine enemas have low systemic absorption and are well tolerated. At present, transdermal nicotine is not a first-line therapy for UC and should be reserved for patients who have failed other medical therapies. Although smoking is reported to be beneficial for the course of UC, prescription of smoking must be tempered by the significant and potentially fatal consequences of its effects on other body systems; in their clinical practice, the authors strongly discourage patients from smoking. 1 table. 9 references.

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Topically Active Corticosteroids for Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 73-76.

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Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the use of topically active corticosteroids for treating colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). UC universally involves the rectum, but the proximal extent (how far it goes) of the disease is variable. When inflammation is limited to the rectum (proctitis) or to the sigmoid colon (proctosigmoiditis), the symptoms of urgency, tenesmus (straining to defecate), and bleeding cause substantial impact on daily activities, but systemic complications are lower when compared to panulcerative colitis. Topical administration of corticosteroids has been a mainstay of primary therapy for distal ulcerative colitis over several decades and also is a useful adjunct to oral therapy for more extensive disease. However, conventional corticosteroids may be associated with a spectrum of undesirable side effects and thus newer steroid formulations have emerged that provide advantages over conventional steroid preparations. The composite clinical experience indicates that topical 5-ASA (aminosalicylates) preparations will usually provide greater efficacy for distal ulcerative colitis. However, in the patient who is refractory to 5-ASA therapy or shows true 5-ASA sensitivity, topical hydrocortisone foam or budesonide may prove to be useful. Further refinements of the colonic release systems for oral budesonide enterocapsules (taken orally, but the drug is not released from the capsule until it reaches the intestine or colon) may be of benefit to patients with more extensive ulcerative colitis. 11 references. •

Ulcerative Colitis: A Diverse Disease with Diverse Questions and Diverse Solutions Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 119-121. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on ulcerative colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). The author notes that clinicians think of UC as one disease, but it is, in fact, a blend of several conditions whose final common denominator is diffuse inflammation of the colon associated with distortion of crypts on microscopic examination. Clinicians move from one therapy for colitis to another as if UC is a spectrum. First, 5 ASA is tried for one type of UC; if this therapy fails, corticosteroids, either local or systemic, follow for what unspokenly is another type of UC. 6-Mercaptopurine or azathioprine enters therapy for a third type of UC and, finally, surgery cures all. The author discusses the different types of therapy and also considers the cancer risk in patients with UC; surveillance of inflamed colons by means of periodic colonoscopy is the standard of care to address the latter. The author concludes that UC presents, responds to therapy, and has a natural history that suggests that it is a spectrum. The host, the luminal environment, the mucosal border, and the immune system of the lamina propria and vascular walls participate in molding this spectrum. Clinical trials that approach UC

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with these distinct participants in mind may yield more success than outcomes obtained in the past two decades. 10 references.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to colitis have been published that consolidate information across various sources. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:12 •

NACC Directory 2000/01 Source: St. Albans, England: National Association for Colitis and Crohn's Disease (NACC). 2001. 13 p. Contact: Available from National Association for Colitis and Crohn's Disease (NACC). 4 Beaumont House, Sutton Road, St. Albans, Hertfordshire, AL1 5HH. 01727 844296. Email: [email protected]. Website: www.nacc.org.uk. PRICE: Single copy free to members. Summary: This booklet offers the Directory of the National Association for Colitis and Crohn's Disease (NACC), an organization based in England. The purpose of the directory is to provide information about NACC to its members. The directory covers NACC services, group details, involvement and fundraising, and membership. NACC services include support groups, NACC in Contact (a telephone network service), an information line, publications, a website (www.nacc.org.uk), a newsletter, the Welfare Fund, disability benefits, and a counseling project. Involvement and fundraising activities can include attending group meetings, becoming a committee member, offering to be a helper at events or activities, commenting on articles and sharing experiences in the newsletter, helping to raise funds for NACC research and other activities, and offering to share personal experiences with the media. The bulk of the directory lists group chairpeople and committee contacts, organized by location. The final section of the directory describes how to join NACC and the benefits of membership, then lists contact telephone numbers for other sources of help in England.

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Complete Directory for People with Chronic Illness. 4rd ed Source: Lakeville, CT: Grey House Publishing, Inc. 2000. 1047 p. Contact: Available from Grey House Publishing, Inc. Pocket Knife Square, Lakeville, CT 06039. (860) 435-0868. Fax (860) 435-0867. PRICE: $165.00. ISBN: 0939300931. Summary: This directory provides a comprehensive overview of the support services and information resources available for people with any of 80 specific chronic illnesses. It presents information on various organizations, educational materials, publications, and databases. A chapter is devoted to each chronic illness and includes a brief description of it. The digestive diseases covered include celiac disease, Crohn's disease, gastrointestinal disorders, hepatitis, liver disease, substance abuse, and ulcerative

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You will need to limit your search to “Directory” and “colitis” using the "Detailed Search" option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Select your preferred language and the format option “Directory.” Type “colitis” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months.

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colitis. The description of each disease is followed by subchapters that identify national and State associations and agencies, libraries, research centers, reference books, children's books, magazines, newsletters, pamphlets, videotapes and films, support groups and hotlines, and websites. In addition, the directory includes a chapter on death and bereavement, as well as a chapter on Wish Foundations for terminally and chronically ill children.

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CHAPTER 8. MULTIMEDIA ON COLITIS Overview In this chapter, we show you how to keep current on multimedia sources of information on colitis. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on colitis is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “colitis” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “colitis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on colitis: •

What You Really Need to Know About Ulcerative Colitis Source: [Toronto, Ontario, Canada]: Videos for Patients. 1993. (videocassette). Contact: Available from Medical Audio Visual Communications, Inc. Suite 240, 2315 Whirlpool Street, Niagara Falls, NY 14305. Or P.O. Box 84548, 2336 Bloor Street West, Toronto, Ontario M6S 1TO, Canada. (800) 757-4868 or (905) 602-1160. Fax (905) 602-8720. PRICE: $99.00 (Canadian); contact producer for current price in American dollars. Order Number VFP001. Summary: This patient education videotape provides information about ulcerative colitis. The videotape begins with a brief sketch featuring comedian John Cleese and narrator Dr. Robert Buckman illustrating the difficulties sometimes experienced by patients during the traditional doctor's explanation. Topics include a definition of ulcerative colitis (UC); how UC develops; symptoms of UC; classification of UC as mild, moderate, or severe; the advantages and disadvantages of various treatment options, including medications; how and when surgical treatment may be indicated; and how to recognize severe attacks of ulcerative colitis. Dr. Buckman presents the medical facts,

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using models, simple diagrams, and graphics to supplement his explanation, and avoiding medical jargon as much as possible. •

Ulcerative Colitis: The Disease and Enema Therapy Source: Marietta, GA: Solvay Pharmaceuticals, Inc. 1996. (videocassette). Contact: Available from Solvay Pharmaceuticals, Inc. 901 Sawyer Road, Marietta, GA 30062. (800) 354-0026. PRICE: Single copy free. Summary: This videotape program provides information and reassurance for people recently diagnosed with ulcerative colitis (UC). The program notes that UC can have a great impact on a person's life, but that following the prescribed treatment can help relieve symptoms and return a sense of normalcy. The narrator reviews the possible causes of UC, including genetic, infectious, and autoimmune theories, noting that UC is not contagious or caused by stress or food sensitivity. UC is most often found in the developing world, and people are usually diagnosed in their teens or twenties. The program then features brief interviews with six women who describe how they felt when they first received the diagnosis. Reactions ranged from fear and anxiety to relief that they finally had a name for their symptoms. The narrator then lists the common symptoms of UC: diarrhea, rectal bleeding, bloody stool, loss of appetite, anemia, abdominal pain, weight loss, fever, and gas (flatulence). Less common symptoms can include joint pain, skin lesions, and eye inflammation. The program then features a man and two women talking about symptoms, particularly urgency and frequency, and the impact of these symptoms on their lifestyles. The narrator notes that there are rectal agents, oral medications, antibiotics, and combination therapies, but that the video will focus on enema therapy. The program then interviews three patients who use Rowasa (mesalamine in a rectal suspension enema form). The patients talk about enema therapy and the improved quality of life they have found using this form of the drug. The program then uses line drawings to demonstrate how to give oneself an enema. The medication should be given when the patient can stay prone for 30 minutes or, preferably, overnight. The program concludes by encouraging viewers to ask their health care provider to answer any questions they may have. The address and tollfree telephone number (800-343-3637) of the Crohn's and Colitis Foundation of America are also provided.

Bibliography: Multimedia on Colitis The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in colitis (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on colitis: •

A Color supplement to Histopathologic spectrum of regional enteritis and ulcerative colitis [slide] Source: by N. Karle Mottet; Year: 1971; Format: Slide; Philadelphia: Saunders, 1971

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Alternates to a stoma for ulcerative colitis [sound recording] Source: American College of Surgeons; Year: 1982; Format: Sound recording; [Chicago, Ill.]: The College, [1982]

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Antibiotic-associated colitis [slide] Source: John G. Bartlett; Year: 1985; Format: Slide; Garden Grove, Calif.: Medcom, c1985

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Antibiotic-associated colitis [videorecording] Source: Biomedical Media Production Unit, the University of Michigan Medical Center, Office of Educational Resources & Research; Year: 1981; Format: Videorecording; Ann Arbor, Mich.: The University, c1981

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Early diagnosis of ulcerative and granulomatous colitis [slide] Source: the Radiological Society of North America; Year: 1983; Format: Slide; [Chicago, Ill.]: The Society, c1983

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Granulomatous and ulcerative colitis [motion picture]: diagnosis and differential diagnosis Source: Mayo Clinic; Year: 1968; Format: Motion picture; Rochester, Minn.: The Clinic: [for loan by Mayo Foundation, Audiovisual Center], 1968

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Pediatric surgery [sound recording]: ulcerative colitis and Hirschsprung's disease Source: American College of Surgeons; Year: 1986; Format: Sound recording; [Chicago, Ill.]: The College, [1986]

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Single stage proctocolectomy for ulcerative colitis [motion picture] Source: H. Willian Scott, Walter G. Gobbel; produced by Davis & Geck; Year: 1970; Format: Motion picture; Danbury, Conn.: Davis & Geck; [Atlanta: for loan by National Medical Audiovisual Center], 1970

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Synchronous combined proctocolectomy for mucosal ulcerative colitis [videorecording] Source: Videosurgery; Year: 1977; Format: Videorecording; Don Mills, Ont.: Southam Business Publications, c1977

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The early detection and medical management of ulcerative colitis [motion picture] Source: produced by Sturgis-Grant Productions, Inc.; by Nicholas C. Hightower, Jr., A. Compton Broders, Jr., Henry Laurens, Richard D. Haines; from the Section on Gastroenterology,; Year: 1959; Format: Motion picture; United States: Sturgis-Grant, [1959]

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Ulcerative colitis & Crohn's disease [videorecording] Source: presented by the Warren Magnuson Clinical Center, National Institutes of Health, Office of Clinical Reports & Inquiries; a production of AVP Inc; Year: 1985; Format: Videorecording; [Los Angeles, Calif.]: Hospital Satellite Network, c1985

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CHAPTER 9. PERIODICALS AND NEWS ON COLITIS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover colitis.

News Services and Press Releases One of the simplest ways of tracking press releases on colitis is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “colitis” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to colitis. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “colitis” (or synonyms). The following was recently listed in this archive for colitis: •

Epidermal growth factor enema may reduce disease activity of ulcerative colitis Source: Reuters Industry Breifing Date: July 24, 2003

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Protein Design Labs says early data for ulcerative colitis drug look good Source: Reuters Industry Breifing Date: May 19, 2003

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Probiotic therapy can prevent pouchitis after surgery for ulcerative colitis Source: Reuters Medical News Date: May 09, 2003

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Phase II results for new colitis drug promising Source: Reuters Medical News Date: April 09, 2003

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Isis begins second phase II trial of alicaforsen for ulcerative colitis Source: Reuters Industry Breifing Date: April 08, 2003

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Isis starts new phase II ulcerative colitis trial Source: Reuters Industry Breifing Date: November 21, 2002

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Infliximab therapy can be successful in active ulcerative colitis Source: Reuters Industry Breifing Date: November 11, 2002

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Shire acquires rights to ulcerative colitis drug Source: Reuters Industry Breifing Date: October 15, 2002

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Axcan acquires North American rights to mesalamine gel formulation for ulcerative colitis Source: Reuters Industry Breifing Date: October 10, 2002

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Smoking seems to reduce risk of sclerosing cholangitis even in colitis-free patients Source: Reuters Medical News Date: October 08, 2002

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Treatment of AML with idarubicin and cytosine arabinoside carries high risk of neutropenic colitis Source: Reuters Industry Breifing Date: August 16, 2002

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Salix licenses ulcerative colitis drug, restructures leadership Source: Reuters Industry Breifing Date: July 16, 2002

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Hypercoagulation may persist in ulcerative colitis after treatment Source: Reuters Medical News Date: May 21, 2002

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Shire licenses ulcerative colitis drug Source: Reuters Industry Breifing Date: May 03, 2002

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Unique marker for neutrophil activation in ulcerative colitis identified Source: Reuters Medical News Date: May 02, 2002

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Bacterial immunostimulatory DNA prevents and ameliorates colitis in mice Source: Reuters Industry Breifing Date: April 29, 2002

Periodicals and News

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New compound may ease Crohn's, ulcerative colitis Source: Reuters Health eLine Date: March 28, 2002

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C. difficile colitis more deadly than typically thought Source: Reuters Medical News Date: March 11, 2002

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One-stage procedure favored for ulcerative colitis Source: Reuters Medical News Date: January 08, 2002

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Ulcerative colitis procedure tied to decreased fertility in women Source: Reuters Industry Breifing Date: December 28, 2001

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Conductance scanning pinpoints colon "leaks" in ulcerative colitis Source: Reuters Medical News Date: December 26, 2001

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High-dose balsalazide bests low dose, mesalazine in preventing colitis relapse Source: Reuters Industry Breifing Date: November 30, 2001

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Patients with ulcerative colitis likely to have history of depression Source: Reuters Medical News Date: September 27, 2001

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Self-management training reduces office visits by ulcerative colitis patients Source: Reuters Industry Breifing Date: September 21, 2001

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Gene's link to colitis confirmed in whites Source: Reuters Health eLine Date: April 05, 2001

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Link documented between history of appendectomy, low risk of ulcerative colitis Source: Reuters Medical News Date: March 14, 2001

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Incara begins phase II/III trial of ulcerative colitis treatment Source: Reuters Industry Breifing Date: January 30, 2001

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Long-term remission of colitis unlikely with tacrolimus Source: Reuters Industry Breifing Date: January 29, 2001

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IV azathioprine appears safe for severe ulcerative colitis treatment Source: Reuters Industry Breifing Date: January 26, 2001

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Prodromal period identified for Crohn's disease but not ulcerative colitis Source: Reuters Medical News Date: January 22, 2001

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Ursodiol may lower risk of colon cancer in ulcerative colitis patients at high risk Source: Reuters Industry Breifing Date: January 15, 2001

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “colitis” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “colitis” (or synonyms). If you know the name of a company that is relevant to colitis, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “colitis” (or synonyms).

Newsletters on Colitis Find newsletters on colitis using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following


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hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “colitis.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “colitis” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •

IBD Should Not Be Deciding Factor in Pregnancy Source: Crohn's and Colitis Foundation of America, Inc., CCFA News. p. 2. Summer 1992. Contact: Available from CCFA. Greater Washington D.C. Chapter, 901 King Street, Suite 101-A, Alexandria, VA 22314. (703) 739-2548. Summary: A large percentage of patients initially diagnosed with Crohn's disease or ulcerative colitis are in the reproductive years. This brief newsletter article stresses that recent reports are relatively favorable regarding the effects of pregnancy on inflammatory bowel disease (IBD). The author also considers whether IBD adversely affects the outcome of the pregnancy and provides information about drug therapy for IBD during pregnancy.

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Determining the Need for Surgery Source: CCFA Newsletter. Crohn's and Colitis Foundation of America Newsletter. p. 2. Winter 1993. Contact: Available from Crohn's and Colitis Foundation of America. 386 Park Avenue South, 17th Floor, New York, NY 10016. VOICE (800) 932-2423 or (212) 685-3440; FAX (212) 779-4098. Summary: Inflammatory bowel disease (IBD), both ulcerative colitis and Crohn's disease, is a chronic disease affecting a young population, often with significant morbidity and mortality, and often requiring surgery. This brief newsletter article discusses the assessment of complications and the need for surgery. The author reports on the experience of the Cleveland Clinic Foundation, including its extensive long-term follow-up program. The article concludes with a list of indications for surgery in Crohn's disease.

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Evolving Medical Therapies for Inflammatory Bowel Disease Source: Progress in Inflammatory Bowel Disease. 15(2): 1-5. Spring 1994. Contact: Available from Crohn's and Colitis Foundation of America, Inc. 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 343-3637 or (800) 932-2423 or (212) 685-3440. Summary: This newsletter article reviews advances in medical approaches to treating ulcerative colitis and Crohn's disease (collectively, inflammatory bowel disease or IBD). Topics include the use of aminosalicylates, including 5-ASA, mesalamine, sulfasalazine, administration and dosage considerations, and the use of these agents specifically in Crohn's disease; steroid treatment of IBD, including the use of budesonide; immune modifiers, including azathioprine, 6-mercaptopurine, methotrexate, and cyclosporine; and miscellaneous therapies, including immunoinflammatory mediators, lipoxygenase inhibition, and short-chain fatty acids for ulcerative colitis. 22 references.

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•

Rheumatic Manifestations of Gastrointestinal Diseases Source: Bulletin on the Rheumatic Diseases. 51(2): 1-4. 2002. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (800) 268-6942 or (404) 872-7100. Fax (404) 872-9559. Website: www.arthritis.org. Summary: This newsletter provides health professionals with information on the rheumatic manifestations of gastrointestinal diseases. Pathologic changes in the gastrointestinal tract may have a role in the pathogenesis of arthropathies. Impairment of the gastrointestinal barrier function and altered gut permeability may have a role in various diseases, including inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis (UC), celiac sprue, Whipple's disease, and enteric reactive arthritis. Crohn's disease and UC are associated with various extraintestinal chronic inflammatory diseases, including arthritis. The type of arthritis associated with IBDs may be either axial or peripheral. Management of arthritis in patients with IBD requires good control of the underlying gastrointestinal pathology with drugs such as sulfasalazine, azathioprine, glucocorticords, and methotrexate. Low bone mineral density is a complication of IBD, so patients with IBD should be advised to consume adequate vitamin D and calcium and to participate in a regular weight bearing exercise program. Celiac sprue, or gluten enteropathy, is characterized by diffuse damage to the proximal small intestinal mucosa that results in villous atrophy and altered gut permeability. Arthritis is a complication in children and adults. Whipple's disease is a rare multisystemic illness caused by infection with Tropheryma whippelii. Diagnosis is based on duodenal or lymph node biopsy. Recommended treatment is trimethoprim combined with sulfamethoxazole. Reactive arthritis, a common arthritide affecting young adults, usually follows urogenital or intestinal bacterial infection. The mainstays of treatment are analgesics and nonsteroidal antiinflammatory drugs. 2 tables and 37 references.

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “colitis” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on colitis: •

Crohn's Disease and Ulcerative Colitis: Taming Painful Inflammatory Bowel Disease Source: Mayo Clinic Women's Healthsource. 4(6): 4-5. June 2000. Contact: Available from Mayo Foundation for Medical Education and Research. 200 First Street SW, Rochester, MN 55905. Summary: This health newsletter article describes inflammatory bowel disease (IBD), an umbrella term for Crohn's disease and ulcerative colitis (UC). The author notes that the cause of IBD is unclear, but abnormalities of the immune system are associated with these diseases. IBD is an inflammatory disease, and it is this inflammation that results in pain and diarrhea. Symptoms can also include weight loss, fatigue, rectal bleeding, and


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anemia. The location of the inflammation within the digestive tract is one of the features that differentiates Crohn's disease from ulcerative colitis. Crohn's disease can affect any part of the digestive tract, from the mouth to the anus, although inflammation is usually in the small intestine. With UC, inflammation is usually in the large intestine and rectum, and ulcers often form. These disorders may also cause other health complications, including an increased risk for developing colon cancer. The symptoms of Crohn's disease are similar to irritable bowel syndrome (IBS), so diagnostic tests to differentiate the diseases may include blood tests, flexible sigmoidoscopy, colonoscopy, and barium enema. Treatment of IBD depends on the severity of disease and the associated complications. Treatment strategies can include diet, medications, counseling, and surgery. While there is no cure for IBD, some people have long periods of remission when their symptoms are well controlled. One sidebar describes current research efforts on Crohn's disease and ulcerative colitis. 1 figure. •

Ulcerative Colitis: Manageable, With a Brighter Outlook Source: Mayo Clinic Health Letter. 13(12): 1-2. December 1995. Contact: Available from Mayo Clinic Health Letter. Subscription Services, P.O. Box 53889, Boulder, CO 80322-3889. (800) 333-9037. Summary: This newsletter article brings readers up-to-date on the management of ulcerative colitis (UC), a form of inflammatory bowel disease (IBD). The article defines the disease and describes diagnostic tests used to confirm UC. It also includes tips on how to manage flareups of the disease, options for drug therapy, and the role of surgery to treat UC. The article concludes with a brief look at treatments currently in the research stage. 2 figures.

•

Collagenous Colitis Source: Foundation Focus. p. 10-11. April 1995. Contact: Available from Crohn's and Colitis Foundation of America, Inc. 386 Park Avenue South, New York, NY 10016-8804. (800) 343-3637 or (212) 685-3440. Summary: This newsletter article presents information about collagenous colitis, a rare inflammatory disorder that causes chronic watery diarrhea and cramps in the abdomen. Written in a question-and-answer format, the article describes the condition, and then discusses the symptoms, diagnosis, causes, treatment options, and the probable course of the illness. Treatment options include dietary changes, bulking agents, sulfasalazine therapy, and prednisone therapy.

Academic Periodicals covering Colitis Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to colitis. In addition to these sources, you can search for articles covering colitis that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the

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name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for colitis. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with colitis. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to colitis: Balsalazide •

Systemic - U.S. Brands: Colazal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500233.html

Chlordiazepoxide and Clidinium •

Systemic - U.S. Brands: Clindex; Clinoxide; Clipoxide; Librax; Lidox; Lidoxide; Zebrax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202130.html

Corticosteroids •

Rectal - U.S. Brands: Anucort-HC; Anu-Med HC; Anuprep HC; Anusol-HC; Anutone-HC; Anuzone-HC; Cort-Dome; Cortenema; Cortifoam; Hemorrhoidal HC; Hemril-HC Uniserts; Proctocort; Proctosol-HC; Rectosol-HC http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203366.html

Furazolidone •

Oral - U.S. Brands: Furoxone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202252.html

Mesalamine •

Oral - U.S. Brands: Asacol; Pentasa http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202734.html

•

Rectal - U.S. Brands: Canasa; Rowasa http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202351.html

Metronidazole •

Systemic - U.S. Brands: Flagyl; Protostat http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202365.html

Olsalazine •

Oral - U.S. Brands: Dipentum http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202422.html

Sulfasalazine •

Systemic - U.S. Brands: Azulfidine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202537.html

Thiamine (Vitamin B 1 ) •

Systemic - U.S. Brands: Biamine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202560.html

Vancomycin •

Oral - U.S. Brands: Vancocin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202589.html

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Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to colitis by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “colitis” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for

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marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for colitis: •

4-aminosalicylic acid (trade name: Pamisyl (P-D), Rezipas (Squibb)) http://www.rarediseases.org/nord/search/nodd_full?code=499

•

Short chain fatty acid solution http://www.rarediseases.org/nord/search/nodd_full?code=47

•

Bacitracin (trade name: Altracin) http://www.rarediseases.org/nord/search/nodd_full?code=568

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute13: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

13

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.14 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:15 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

14

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 15 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “colitis” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “colitis” (or synonyms) into the “For these words:” box. The following is a sample result: •

Treatment Strategies for OI's and Symptoms: Diarrhea in HIV Infection - Possible Causes, Diagnostic Techniques, and Therapies Contact: Carl Vogel Center, 1012 14th St NW Ste 707, Washington, DC, 20005, (202) 6380750. Summary: This paper discusses treatment strategies for opportunistic infections, more specifically diarrhea, in HIV infection. It also explores possible causes, diagnostic techniques, and therapies. Diarrhea in people living with HIV can have many causes, and ranges in severity. Studies show that examination of diarrhea can lead to the identification of disease-causing organisms. The most severe diarrhea is normally caused by cryptosporidiosis, instigated by a protozoal infection. Isosporiasis, microsporidiosis, cytomegalovirus colitis, and bacterial infections also cause diarrhea. Diarrhea can also be caused by food allergy reactions. The paper goes on to discuss how to diagnose and analyze stool. It talks about parasites including parvum. A number of prescription drugs used for the treatment of diarrhea are described. Candida and parasites are often believed to be present in Persons With AIDS (PWA's) and may cause problems if they remain unrecognized. Mycobacterium Avium Complex (MAC) can cause bodywide infection, but the most common lasting symptom is a chronic, wasting diarrhea.

•

Practical Guide to Topical and Oral 5-ASA Products for the Treatment of Inflammatory Bowel Disease Source: New York, NY: Crohn's and Colitis Foundation of America, Inc. 1993. 14 p. Contact: Available from Crohn's and Colitis Foundation of America, Inc. 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 343-3637 or (800) 932-2423 or (212) 685-3440. PRICE: Single copy free. Summary: This publication includes highlights from a conference on the use of topical and oral 5-ASA drug therapy to treat inflammatory bowel disease (IBD). Four articles address mechanisms of action and sites of delivery of these drug products; acute and maintenance treatment of left-sided colitis and proctitis; acute and maintenance treatment of Crohn's disease and ulcerative colitis; and the use of steroids and immunosuppressive drugs in conjunction with 5-ASA products for Crohn's disease and

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ulcerative colitis. The publication also includes four illustrative case examples. After each article and case example, the faculty and audience members' discussion is reprinted. The publication concludes with a description of the Crohn's and Colitis Foundation of America (CCFA) and its research and educational activities. 22 references.

The NLM Gateway16 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.17 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “colitis” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 35730 360 638 145 0 36873

HSTAT18 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.19 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.20 Simply search by “colitis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

16

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

17

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 18 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 19 20

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists21 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.22 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.23 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Colitis In the following section, we will discuss databases and references which relate to the Genome Project and colitis. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).24 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 21 Adapted 22

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 23 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 24 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “colitis” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for colitis: •

Cutaneous Photosensitivity and Colitis, Lethal Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?219095

•

Enterocolitis Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?226150

•

Ulcerative Colitis, Susceptibility to Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?191390 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome,

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Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html •

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

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Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “colitis” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database25 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database26 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “colitis” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

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Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 26 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on colitis can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to colitis. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to colitis. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “colitis”:

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Other guides Colonic Diseases http://www.nlm.nih.gov/medlineplus/colonicdiseases.html Crohn's Disease http://www.nlm.nih.gov/medlineplus/crohnsdisease.html Digestive Diseases http://www.nlm.nih.gov/medlineplus/digestivediseases.html Ulcerative Colitis http://www.nlm.nih.gov/medlineplus/tutorials/ulcerativecolitisloader.html Ulcerative Colitis http://www.nlm.nih.gov/medlineplus/ulcerativecolitis.html

Within the health topic page dedicated to colitis, the following was listed: •

General/Overviews Inflammatory Bowel Disease Source: American Gastroenterological Association http://www.gastro.org/clinicalRes/brochures/ibd.html Introduction to Ulcerative Colitis Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/aboutuc.html

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Diagnosis/Symptoms Abdominal Pain, Acute: Self-Care Flowcharts Source: American Academy of Family Physicians http://familydoctor.org/flowcharts/527.html Abdominal Pain, Chronic: Self-Care Flowcharts Source: American Academy of Family Physicians http://familydoctor.org/flowcharts/528.html Colonoscopy http://www.nlm.nih.gov/medlineplus/tutorials/colonoscopyloader.html Colonoscopy Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/colonoscopy/index.htm C-Reactive Protein (CRP) Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/crp/test.html Flexible Sigmoidoscopy Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/sigmoidoscopy/index.htm Radiography-Lower GI Tract (Barium Enema “BE”) Source: American College of Radiology, Radiological Society of North America http://www.radiologyinfo.org/content/lower_gi.htm

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Treatment Colostomy http://www.nlm.nih.gov/medlineplus/tutorials/colostomyloader.html Ileostomy, Colostomy and Ileoanal Reservoir Surgery Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/ileostomy/index.htm Laparoscopic Intestinal Surgery: A Guide for Patients Source: Cleveland Clinic Foundation http://www.clevelandclinic.org/health/healthinfo/docs/0900/0962.asp?index=4356 Maintenance Therapy in IBD Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/maintenance.html Surgery for Ulcerative Colitis Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/surgeryuc.html Treatment Options in IBD Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/treatmentoptions.html Types of Medications for Inflammatory Bowel Disease Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/medications.html

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Nutrition Diet and Nutrition Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/diet.html

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Specific Conditions/Aspects Extraintestinal Complications of IBD: Arthritis Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/arthritis.html Extraintestinal Complications: Bone Loss Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/bone.html Extraintestinal Complications: Eye Disorders Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/eye.html Extraintestinal Complications: Kidney Disorders Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/kidney.html Extraintestinal Complications: Liver Disease Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/liver.html

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Extraintestinal Complications: Skin Disorders Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/skin.html Measles Vaccine and Inflammatory Bowel Disease (IBD) Source: National Immunization Program http://www.cdc.gov/nip/vacsafe/concerns/autism/ibd.htm What Is Primary Sclerosing Cholangitis? Source: American Liver Foundation http://www.liverfoundation.org/cgibin/dbs/articles.cgi?db=articles&uid=default&ID=1015&view_records=1 •

Children Inflammatory Bowel Disease Source: Nemours Foundation http://kidshealth.org/parent/medical/digestive/ibd.html Treating IBD in Children and Adolescents Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/kidsmeds.html

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Latest News Environment Plays Role in Bowel Problems Source: 11/14/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14675 .html Picky Eating Common in Kids with Bowel Disease Source: 10/31/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14494 .html

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Organizations American Gastroenterological Association http://www.gastro.org/ Crohn's & Colitis Foundation of America http://www.ccfa.org/ National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ National Institute of Diabetes and Digestive and Kidney Diseases http://www.niddk.nih.gov/

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Pictures/Diagrams Atlas of the Body: The Digestive System Source: American Medical Association http://www.medem.com/MedLb/article_detaillb.cfm?article_ID=ZZZ7C4T46JC&s ub_cat=338

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Research Challenges in IBD Research: Updating the Scientific Agendas 2002 http://www.ccfa.org/medinfo/research/laychallenges.pdf

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Teenagers Inflammatory Bowel Disease Source: Nemours Foundation http://kidshealth.org/teen/diseases_conditions/digestive/ibd.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on colitis. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Q and A. Crohn's Disease and Ulcerative Colitis: Surgery Source: New York, NY: Crohn's and Colitis Foundation of America, Inc. 2002. 12 p. Contact: Available from Crohn's and Colitis Foundation of America, Inc. (CCFA). 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 343-3637 or (800) 9322423 or (212) 685-3440. Fax (212) 779-4098. Website: www.ccfa.org. E-mail: [email protected] PRICE: Single copy free. Summary: About two-thirds to three-fourths of people with Crohn's disease, and about 25 to 40 percent of people with ulcerative colitis will need surgery at some time during their lives. This brochure is written in a question-and-answer format and clearly separates information about Crohn's disease from information about ulcerative colitis. Topics covered include indications for surgery; the role of nutrition in surgical patients with inflammatory bowel disease (Crohn's disease or ulcerative colitis); common surgical procedures; surgical treatment of abscesses and fistulas; recurrence of Crohn's disease following surgery; and selecting the best surgical option for ulcerative colitis.

•

Crohn's and Colitis Foundation of America, Greater Washington, D.C. Chapter: Providing Local Services, a National Effort Source: Washington, DC: Greater Washington, D.C. Chapter, Crohn's and Colitis Foundation of America, Inc. 199x. 2 p.

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Contact: Available from Greater Washington, D.C. Chapter, Crohn's and Colitis Foundation of America, Inc. 901 King Street, Suite 101-A, Alexandria, VA 22314. (703) 739-2548. PRICE: Single copy free. Summary: After a brief explanation of inflammatory bowel disease (IBD), this brochure introduces the local programs and services of the Greater Washington D.C. chapter of the Crohn's and Colitis Foundation of America (CCFA). Topics include the support groups; telephone volunteers; Patient Learning and Understanding Service (PLUS); parent support network; and educational efforts, including meetings, physician referral, books, and the newsletter of the chapter. A final section explains the work of the CCFA, and includes a membership form to join the organization. A list of the early warning signs of IBD is also included. •

Colitis Source: McGaw Park, IL: Baxter Healthcare Corporation. 1990. 4 p. Contact: Available from Baxter Healthcare Corporation. Healthcare Communications, Customer Service, 1500 Waukegan Road, McGaw Park, IL 60085. (800) 766-3646. PRICE: $17.50 for package of 50, or $0.35 each. Order Number HIP 220-030. Summary: Colitis, an inflammation of the colon, is diagnosed when someone is suffering from abdominal cramps and changes in bowel habits, but without signs of serious disease like fever, weight loss, or bleeding. After a brief review of the symptoms of colitis, this general information brochure discusses the causes of colitis and ways to alleviate the symptoms of colitis. The brochure concludes that reducing stress, adding more fruit and fiber to one's diet, exercise, eating at regular times, and increasing fluid intake can help keep the bowel healthy and reduce the effects of colitis.

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Q and A. Crohn's Disease and Ulcerative Colitis: Women's Issues Source: New York, NY: Crohn's and Colitis Foundation of America. 2002. 6 p. Contact: Available from Crohn's and Colitis Foundation of America (CCFA). 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 932-2423. E-mail: [email protected]. Website: www.ccfa.org. PRICE: Single copy free. Summary: Crohn's disease and ulcerative colitis are chronic digestive diseases of the small and large intestines, collectively known as inflammatory bowel disease (IBD). This brochure answers common questions that women with these diseases may have. Symptoms of IBD can include diarrhea, abdominal pain, rectal bleeding, and fever; loss of appetite and weight loss are also common. If medications fail to control the symptoms of the disease, or if certain complications occur, surgery may be required. Yet, in spite of the physical and emotional demands of coping with IBD, most patients are able to lead full, satisfying lives. The brochure covers specific topics including the impact of IBD on menstruation, birth control and conception, dyspareunia (painful sexual intercourse), iron deficiency, pregnancy, drug therapy for IBD during pregnancy and breastfeeding, diagnostic procedures and surgery during pregnancy, pregnancy in women who have had prior bowel surgery, the genetic risks of IBD (passing along the disease to one's child), dietary recommendations for pregnant women with IBD, osteoporosis, and menopause. The brochure includes a brief description of the goals and activities of the Crohn's and Colitis Foundation of American (www.ccfa.org).

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Crohn's Disease or Ulcerative Colitis: How to Choose a Doctor and Hospital for Your Treatment Source: Cleveland, OH: Cleveland Clinic Foundation. 1998. 23 p. Contact: Available from Cleveland Clinic Foundation. Department of Nutrition Services, One Clinic Center, 9500 Euclid Avenue, Cleveland, OH 44195. (216) 444-8950. PRICE: Single copy free. Summary: Selecting a doctor and hospital for treatment of inflammatory bowel disease (IBD, including Crohn's disease and ulcerative colitis) involves making some difficult and important decisions. Patients must carefully consider where to go and what physicians and surgeons are the most qualified to treat IBD. This brochure offers information for patients with IBD, focusing on choosing a doctor and hospital for treatment. The brochure describes the difference between ulcerative colitis and Crohn's disease, how IBD is diagnosed, treatment options (including nonsurgical therapies and surgical procedures), and six points that indicate quality. The six points that patients should consider are credentials, experience, range of services, participation in research and education, patient satisfaction, and outcome indicators. In each area, the brochure offers suggested questions for patients to ask of their health care providers and facilities. Surgical options discussed include pelvic pouch surgery (which allows for nearly normal bowel movements), continent ileostomy (a conversion procedure for old style ileostomy patients to have their external pouch converted to an internal pouch), and strictureplasty (an option for some Crohn's patients, this relieves obstruction but preserves the intestine). The brochure also provides information about the Cleveland Clinic, the producer of the brochure and a nationally known clinic in the treatment of urologic, gynecologic, and colorectal disorders (www.ccf.org ).

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Physician's Guide to Pediatric Crohn's Disease and Ulcerative Colitis Source: New York, NY: Crohn's and Colitis Foundation of America. Boston, MA: Boston University School of Medicine. 1992. 43. Contact: Available from Crohn's and Colitis Foundation of America, Inc. 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 343-3637 or (800) 932-2423 or (212) 685-3440. PRICE: Single copy free. Distribution may be limited to physicians only. Summary: The purpose of this guide is to provide basic information to primary clinicians, pediatricians, and internists, who treat patients with Crohn's disease and ulcerative colitis. As with any chronic disease, there is always a balance between the suppression of disease activity and the consequences of medical and/or surgical therapy. Topics include a review of inflammatory bowel disease (IBD) and how it affects children, clinical aspects of IBD in children, differences between Crohn's disease and ulcerative colitis in adults and children, differential diagnosis in children, medical treatment and management, surgical treatment and management, and quality of life issues. A quiz for continuing medical education credit is included. 16 charts summarize the material presented. 19 figures.

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Q and A. Crohn's Disease and Ulcerative Colitis: Medications Source: New York, NY: Crohn's and Colitis Foundation of America. 2002. 20 p. Contact: Available from Crohn's and Colitis Foundation of America (CCFA). 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 932-2423. E-mail: [email protected]. Website: www.ccfa.org. PRICE: Single copy free.

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Summary: This brochure answers commonly asked questions about the medications used to treat ulcerative colitis and Crohn's disease, two conditions that are collectively called inflammatory bowel disease (IBD). The goals of medical treatment are to suppress the inflammatory response to permit healing of tissue, to improve quality of life, to maintain adequate nutritional status, and to relieve the symptoms of fever, diarrhea, and abdominal pain. Several groups of drugs are used: aminosalicylates, corticosteroids, immune modifiers, and antibiotics. In general, aminosalicylate pills, enemas, and suppositories remain the first line of therapy for people with active IBD, as well as for maintaining remission. Oral aminosalicylates may also prevent Crohn's from recurring after surgery. Oral corticosteroids are usually reserved for individuals who fail to respond to aminosalicylates or who require rapid control of symptoms. Antibiotics may be beneficial in certain clinical situations. Infliximab (a biologic therapy) is appropriate for those with Crohn's disease who fail to respond to conventional medical therapy or who have fistulas. A final section considers the medical treatment for children and adolescents with IBD. All of the medications used for adults are also used for children, and the indications and contraindications are similar. Individualized treatment is required, however, as dosages must be tailored for children, who are of smaller size, and adolescents, who are moving through a period of both physical and psychosocial growth and development. •

Pediatric Crohn's and Colitis Association, Inc Source: Newton, MA: Pediatric Crohn's and Colitis Association, Inc. 199x. 2 p. Contact: Available from Pediatric Crohn's and Colitis Association, Inc. Box 188, Newton, MA 02168-0002. (617) 244-6678. PRICE: Single copy free. Summary: This brochure describes the Pediatric Crohn's and Colitis Association, a group formed to provide information and emotional support to families whose children have been diagnosed as having inflammatory bowel disease (IBD). The brochure describes the activities of the association and includes a form for joining the mailing list. The brochure also includes a list of scientific advisory board members of the association.

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Ulcerative Colitis: Understanding This Chronic Illness Source: San Bruno, CA: StayWell Company. 1998. [2 p.]. Contact: Available from StayWell Company. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 244-4512. PRICE: $ 17.95 for 50 copies; plus shipping and handling; bulk copies available. Order number 9784. Summary: This brochure describes ulcerative colitis (UC), a type of inflammatory bowel disease (IBD). The symptoms of UC can include frequent, loose bowel movements; blood and pus in stools; rectal bleeding; feeling of incomplete bowel movement; urgency; severe straining with bowel movement; joint pain; and rectal pain that comes and goes. Diagnostic tests that may be used to confirm UC include endoscopy, biopsy, blood or stool tests, and xrays of the colon. The brochure reviews treatment options, including medications, dietary strategies, and surgery. One sidebar reviews the anatomy of the digestive tract and how UC can impact the digestive tract. UC is inflammation (irritation and swelling) that occurs in the rectum. It can also affect the colon, but affects only the inside layers of tissue lining the rectum and colon. The brochure concludes by encouraging readers to work closely with their health care providers and to seek out support groups to talk with others who are dealing with IBD. The toll free telephone number of the Crohn's and Colitis Foundation (800-932-2423) is provided. The brochure is illustrated with full color drawings. 6 figures.

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Q and A. About Ulcerative Colitis Source: New York, NY: Crohn's and Colitis Foundation of America, Inc. (CCFA). 2002. 12 p. Contact: Available from Crohn's and Colitis Foundation of America, Inc. (CCFA). 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 343-3637 or (800) 9322423 or (212) 685-3440. Fax (212) 779-4098. Website: www.ccfa.org. E-mail: [email protected] PRICE: Single copy free. Summary: This brochure familiarizes readers with ulcerative colitis, an inflammatory disease of the colon that is characterized by inflammation and ulceration of the innermost lining of the colon. Written in a question and answer format, the brochure describes ulcerative colitis (UC) and covers the incidence of UC, the role of genetics, the symptoms of UC, diagnostic tests used to confirm the condition, medications used to treat UC, the role of surgery in treatment, the importance of nutrition, the role of emotional stress as a trigger for attacks of UC, considerations of everyday life with UC, and theories as to the causes of UC. The booklet concludes with a brief description of the activities of the Crohn's and Colitis Foundation of America (CCFA) and a glossary of terms related to IBD. 1 figure.

•

Q and A. Crohn's Disease and Ulcerative Colitis: A Teacher's Guide Source: New York, NY: Crohn's and Colitis Foundation of America, Inc. 2002. 8 p. Contact: Available from Crohn's and Colitis Foundation of America, Inc. (CCFA). 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 343-3637 or (800) 9322423 or (212) 685-3440. Fax (212) 779-4098. Website: www.ccfa.org. E-mail: [email protected] PRICE: Single copy free. Summary: This brochure is designed to help teachers understand the needs of students and young people who have Crohn's disease or ulcerative colitis. It provides a brief description and explanation of these two kinds of inflammatory bowel diseases (IBD's) and covers the problems of coping with them and their treatment. Potential problems and issues for students include isolation and depression; absence from school; frequent and sudden need to leave the classroom for the bathroom; participation in class trips and sports; and taking medication during school hours. The brochure emphasizes the often crucial role that teachers play in identifying exacerbations of IBD's, and recommends direct communication with medical personnel and parents

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Crohn's Disease, Ulcerative Colitis, and School Source: Newton, MA: Pediatric Crohn's and Colitis Association, Inc. 199x. 6 p. Contact: Available from Pediatric Crohn's and Colitis Association, Inc. Box 188, Newton, MA 02168-0002. (617) 244-6678. PRICE: Single copy free. Summary: This brochure reviews the school-related problems that a young person with inflammatory bowel disease (IBD) may face. Filled with numerous quotes from children with IBD, the brochure discusses the physical ups and downs of IBD; making-up missed school work; changes in appearance; mood swings; physical activities; diet; meeting needs during class time; and activities outside the classroom. The brochure emphasizes that the support, encouragement, and understanding of teachers, friends, and family can make a significant difference in helping children and teenagers to have a productive and satisfying school experience.

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Q and A. Crohn's Disease and Ulcerative Colitis: A Guide for Children and Teenagers Source: New York, NY: Crohn's and Colitis Foundation of America, Inc. 2002. 8 p. Contact: Available from Crohn's and Colitis Foundation of America, Inc. (CCFA). 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 343-3637 or (800) 9322423 or (212) 685-3440. Fax (212) 779-4098. Website: www.ccfa.org. E-mail: [email protected] PRICE: Single copy free. Summary: This pamphlet, written for children and teenagers, discusses Crohn's disease and ulcerative colitis (known together as inflammatory bowel disease or IBD's). The brochure explains the possible causes of IBD; how IBD affects the gastrointestinal tract; treatment; types of medicine and their side effects; the role of diet and nutrition in treatment; physical growth and IBD; tests used to diagnose and monitor IBD; and surgery. The authors also discuss attitudes and habits that may help children and teenagers with IBD to feel better.

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Q and A. Crohn's Disease and Ulcerative Colitis: A Parent's Guide Source: New York, NY: Crohn's and Colitis Foundation of America. 2002. 20 p. Contact: Available from Crohn's and Colitis Foundation of America, Inc. (CCFA). 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 343-3637 or (800) 9322423 or (212) 685-3440. Fax (212) 779-4098. Website: www.ccfa.org. E-mail: [email protected] PRICE: Single copy free. Summary: This pamphlet, written for parents, answers questions about Crohn's disease and ulcerative colitis (together known as inflammatory bowel disease, or IBD) in children. Written in question-and-answer format, the brochure describes the causes, symptoms, and prevalence of IBD; diagnostic tests; inheritance of IBD; the role of surgery; eating habits and nutrition; and special foods and vitamins. The authors point out that children do not grown IBD but that many people enjoy long periods of remission. The common medications used to treat IBD are described in detail. The authors also discuss the emotional and social challenges sometimes presented by IBD's and give parents hints to help their children cope. A glossary of terms is appended.

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Q and A. Crohn's Disease and Ulcerative Colitis: Emotional Factors Source: New York, NY: Crohn's and Colitis Foundation of America, Inc. 2002. 8 p. Contact: Available from Crohn's and Colitis Foundation of America, Inc. (CCFA). 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 343-3637 or (800) 9322423 or (212) 685-3440. Fax (212) 779-4098. Website: www.ccfa.org. E-mail: [email protected] PRICE: Single copy free. Summary: This pamphlet, written in question-and-answer format, answers some of the most commonly asked questions about the role of emotional factors in Crohn's disease and ulcerative colitis (known together as inflammatory bowel disease or IBD's). The authors point out that IBD's are biological disorders of unknown origin and are not caused by tension or anxiety, or more common in people with certain personality types. The brochure clarifies the difference between IBD's and a completely different condition, irritable bowel syndrome, the cause of which does seem to be related to emotional factors. The authors suggest that this brochure be used to explain to friends and family that IBD's are not caused by being 'overly emotional'. Specific topics addressed include the possible role of severe chronic stress in increasing inflammation; emotional difficulties caused by the challenges of living with an IBD; feelings of guilt; ways to cope

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with fears of relapse, attacks in public places, and travel; medications used to cope with psychological difficulties; psychiatric consultation; the special concerns of young people; the emotional effects of ileostomy surgery; and discussion of attitudes which may help IBD patients to better cope with these diseases. •

New Surgical Options for the Treatment of Ulcerative Colitis: Questions and Answers Source: Arlington Heights, IL: American Society of Colon and Rectal Surgeons. 1996. [2 p.]. Contact: Available from American Society of Colon and Rectal Surgeons. 85 West Algonquin Road, Suite 550, Arlington Heights, IL 60005. (800) 791-0001 or (847) 2909184. Fax (847) 290-9203. E-mail: [email protected]. Website: www.fascrs.org. PRICE: Full-text available online at no charge; Single copy free; bulk copies available. Summary: This patient education brochure describes new surgical treatments for ulcerative colitis (UC), an inflammation of the lining of the large bowel (colon). Symptoms of UC include rectal bleeding, diarrhea, abdominal cramps, weight loss, and fever. In addition, patients who have had extensive UC for many years are at an increased risk to develop large bowel cancer. Initial treatment of UC is medical, using antibiotics and antiinflammatory medications. Surgery is indicated for patients who have life threatening complications of inflammatory bowel diseases, such as massive bleeding, perforation, or infection. It may also be necessary for those who have the chronic form of the disease, which fails medical therapy. Historically, the standard operation for UC has been removal of the entire colon, rectum, and anus; this procedure is called a proctocolectomy. This operation requires creation of a Brooke ileostomy and chronic use of an appliance on the abdominal wall to collect waste from the bowel. Another option is the continent ileostomy, in which an internal reservoir is created. The bowel still comes through the abdominal wall, but an external appliance is not required. This option eliminates the risks of cancer and risks of recurrent persistent colitis, but the internal reservoir may begin to leak and require another surgical procedure to revise the reservoir. Some patients may be treated by removal of the colon, with preservation of the rectum and anus. The small bowel can then be reconnected to the rectum and the person retains continence. This avoids the ileostomy, but the risks of ongoing active colitis, increased stool frequency, urgency, and cancer in the retained rectum remain. The brochure then describes the ileoanal procedure, a newer alternative for the management of UC in which all of the colon and rectum are removed, but the anal canal is preserved. The rectum is replaced with a small bowel, which is fashioned to form a small pouch. The pouch acts as a reservoir to help decrease the stool frequency. This maintains a normal route of defecation, but most patients experience 5 to 10 bowel movements per day. The brochure concludes by encouraging readers to educate themselves about these alternatives, so that they can take part in the decisions about their own health care and pursue the highest quality of life. 8 figures.

•

Ulcerative Colitis Source: St. Albans, England: National Association for Colitis and Crohn's Disease (NACC). 1999. 16 p. Contact: Available from National Association for Colitis and Crohn's Disease (NACC). 4 Beaumont House, Sutton Road, St. Albans, Hertfordshire, AL1 5HH. 01727 844296. Email: [email protected]. Website: www.nacc.org.uk. PRICE: Single copy free to members.

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Summary: Ulcerative colitis (UC) is a disease of the lining of the large bowel or colon. This booklet, written for people newly diagnosed with UC, offers an overview of the disease and its treatment. The booklet first describes how the colon works within the digestive system, then discusses how UC affects the working of the colon, the symptoms of the disease, how UC is diagnosed, the causes of UC, dietary impact on the disease, treatment options, drug therapy (antiinflammatory agents, antidiarrheals, analgesics, anemia treatments, nutritional aids), and surgical options (proctocolectomy and ileostomy, colectomy with ileostomy and mucous fistula, colectomy and ileorectal anastomosis, and proctocolectomy with ileal reservoir or pouch). Although the symptoms and signs of UC can disappear for many years, and even for a lifetime, without treatment, the more usual course is one of periodic flareups. The condition is normally managed by drugs, but surgery may become necessary under some circumstances. The booklet concludes with a list of commonly asked questions and answers, covering prognosis, the interrelationship between UC and bowel cancer, UC and pregnancy, the epidemiology of UC, and the role of heredity in UC. 5 figures. 2 tables. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “colitis” (or synonyms). The following was recently posted: •

Management of ulcerative colitis Source: Society for Surgery of the Alimentary Tract, Inc - Medical Specialty Society; 2000 (revised 2001); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2967&nbr=2193&a mp;string=colitis

•

Proctitis, proctocolitis, and enteritis. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 2 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3244&nbr=2470&a mp;string=colitis Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database:

Patient Resources

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Find-a-Doctor (Crohn's and Colitis) Summary: This is a list of physicians, nurses, and other healthcare professionals who are members of Crohn's and Colitis Foundation of America. Source: Crohn's and Colitis Foundation of America http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6800

•

Ulcerative Colitis Summary: In ulcerative colitis, the inner lining of the large intestine (colon or bowel) and rectum becomes inflamed. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=734 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to colitis. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •


•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMD®Health: http://my.webmd.com/health_topics

Associations and Colitis The following is a list of associations that provide information on and resources relating to colitis:

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•

Crohn's and Colitis Foundation of America Telephone: (212) 685-3440 Toll-free: (800) 932-2423 Fax: (212) 779-4098 Email: [email protected] Web Site: http://www.ccfa.org Background: The Crohn s and Colitis Foundation of America is a not-for-profit voluntary health organization dedicated to raising funds for research to determine the cause of and the cure for Crohn s Disease and colitis. Crohn s Disease and ulcerative colitis, collectively known as inflammatory bowel disease, are chronic digestive diseases of unknown cause. While Crohn s Disease may affect any part of the gastrointestinal tract and often results in swelling, soreness, and inflammation of layers of the large and/or small intestinal wall, Ul ulcerative colitis affects only the colon (large intestine), causing inflammation of the inner lining and resulting in diarrhea, often mixed with blood, cramping abdominal pain, and other symptoms. Established in 1967, the Crohn s and Colitis Foundation of America seeks to educate affected individuals, physicians, and the public about these disorders in order to increase awareness about the nature of these chronic disorders and help affected individuals confront their unique problems. In addition, the Foundation establishes support groups, engages in patient advocacy, plays an active role in government legislation, and provides medical referrals. Educational materials produced by the organization include a regular newsletter, reports, and informative brochures. Relevant area(s) of interest: Colitis

•

Crohn's and Colitis Foundation of Canada Telephone: (416) 920-5035 Toll-free: (800) 387-1479 Fax: (416) 929-0364 Email: [email protected] Web Site: http://www.ccfc.ca Background: The Crohn s and Colitis Foundation of Canada (CCFC) is a not-for-profit voluntary health organization dedicated to raising funds for research to determine the cause of and the cure for Crohn s disease and colitis. Crohn s disease and ulcerative colitis, known as inflammatory bowel diseases, are chronic digestive disorders of unknown cause. Crohn s disease may affect any part of the digestive tract and often results in swelling, soreness, and inflammation of layers of the large and/or small intestinal wall. Ulcerative colitis affects the colon (large intestine), causing inflammation of the inner lining and resulting in diarrhea, often mixed with blood, cramping abdominal pain, and other symptoms. Established in 1974, CCFC s mission is to help find the cure for Crohn s disease and ulcerative colitis. The Foundation provides educational programs for affected individuals, their families, health professionals, and the general public. In addition, the Foundation provides educational and awareness initiatives through approximately 75 local CCFC volunteer groups and CCFC community education events, featuring leading IBD specialists. The Foundation publishes a brochure series in both French and English. Titles include 'Surgery and Inflammatory Bowel Disease,' 'Nutrition, Diet and Inflammatory Bowel Disease,' 'Medication for Inflammatory Bowel Disease,' 'Sexuality, Fertility, Pregnancy and Inflammatory Bowel Disease,' and 'Living with Inflammatory Bowel Disease.' 'The Journal,' a regularly published newsletter, is also available.

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National Association for Colitis and Crohn's Disease (UK) Telephone: 44(0) 1727 844296 Fax: 44(0) 1727 862550 Email: [email protected] Web Site: http://www.nacc.org.uk/ Background: The National Association for Colitis and Crohn's Disease (UK) is a national voluntary association in the United Kingdom dedicated to providing information and support services to people who are living with ulcerative colitis or Crohn's disease, which are both forms of inflammatory bowel disease (IBD). The Association is also committed to promoting and supporting research into the medical, health care, social, and psychological aspects of IBD. Ulcerative colitis is characterized by chronic inflammation and ulceration of the large intestine and the rectum. Affected individuals may experience associated pain; episodes of urgent, bloody diarrhea; fatigue; and other symptoms. Crohn's disease may affect any area of the gastrointestinal tract from the mouth to the rectum; however, in most cases, it is characterized by chronic inflammation, ulceration, and scarring of the wall of the small intestine. Associated symptoms and findings may include pain, fatigue, weight loss, episodes of urgent diarrhea, and other symptoms and findings. The National Association for Colitis and Crohn's Disease (UK) was established in 1979 and currently consists of over 27,000 members including affected individuals, their families and friends, health care professionals, and anyone who wishes to support the group's activities. The Association conducts regular meetings; offers local support through its area groups; has a network of trained volunteer counselors who provide telephone support; and offers information and support to families with children affected by IBD through its 'Smilie's People Network.' In addition, the Association has a fund for people in financial difficulty due to IBD and supports local hospitals through its area groups. The National Association for Colitis and Crohn's Disease (UK) also offers brochures, publishes a quarterly newsletter, and has a web site on the Internet.

•

Pediatric Crohn's and Colitis Association, Inc Telephone: (617) 489-5854 Fax: (617) 489-5854 Email: [email protected] Web Site: http://pcca.hypermart.net Background: The Pediatric Crohn s and Colitis Association, Inc. (PCCA) is an international not-for-profit service organization dedicated to providing information and emotional support to families of children with inflammatory bowel disease (IBD) to help ensure that affected children reach their potential in today s society. Crohn s Disease and Ulcerative Colitis, collectively known as Inflammatory Bowel Disease, are chronic digestive diseases of unknown cause. While Crohn s Disease may affect any part of the gastrointestinal tract and often results in swelling, soreness, and inflammation of layers of the large and/or small intestinal wall, Ulcerative Colitis affects only the colon (large intestine), causing inflammation of the inner lining and resulting in diarrhea, often mixed with blood, cramping abdominal pain, and other symptoms. The Association was founded in 1988 by a group of parents with children affected by IBD to address the broad range of issues faced by the pediatric population with these disorders. Currently consisting of over 1,200 members, PCCA is dedicated to promoting pediatric research;

332 Colitis

providing educational, emotional, social, academic, and psychological support; and addressing the role of family dynamics in dealing with a chronic illness. The organization s services include a parent hotline; support groups; patient advocacy; networking services; and medical, educational, and psychological symposia. The organization also provides a variety of educational materials including brochures, pamphlets, an information packet, and a regular newsletter. •

Reach Out for Youth with Ileitis and Colitis, Inc Telephone: (631) 293-3102 Fax: (631) 293-3103 Email: [email protected] Web Site: www.reachoutforyouth.org Background: Reach Out for Youth with Ileitis and Colitis, Inc. is a non-profit support organization dedicated to assisting families whose children have Inflammatory Bowel Disease (IBD) such as Ileitis or Colitis. Ulcerative Colitis is an inflammatory disease of the large intestine and is characterized by diarrhea, abdominal pain, fever, and bleeding from the rectum. Decreased appetite and weight loss may also occur. Ileitis or Crohn s Disease, also an inflammatory bowel disorder, can affect any portion of the digestive system and has symptoms that are similar to those of Colitis. Established in 1979 and consisting of approximately 400 members, the organization has helped hundreds of families cope with the effects of IBD. The group's goals include providing educational materials and emotional support to affected individuals and their families and organizing fundraising efforts to promote research into the causes and treatment of IBD. Educational seminars and a quarterly newsletter entitled 'Inner Circle' assist members by keeping them informed of current activities. A hotline offers interested individuals the opportunity to communicate on a one-to-one basis, especially when acute symptoms are present. Reach Out also continues to support the IBD clinical database established 13 years ago as a crucial research tool. Our educational brochure, 'The Inside Story' is available upon request. Relevant area(s) of interest: Colitis

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to colitis. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with colitis. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about colitis. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.

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Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “colitis” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “colitis”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “colitis” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “colitis” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.27

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

27

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)28: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

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California: Gateway Health Library (Sutter Gould Medical Foundation)

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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

28

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on colitis: •

Basic Guidelines for Colitis Colitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001125.htm

•

Signs & Symptoms for Colitis Abdominal bloating Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003123.htm Abdominal pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm Diarrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003126.htm

•

Diagnostics and Tests for Colitis Abdominal CT scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003789.htm

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Abdominal MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003796.htm Abdominal X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003815.htm Barium enema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003817.htm Colonoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003886.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm Sigmoidoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003885.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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COLITIS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 6-Mercaptopurine: An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Cramps: Abdominal pain due to spasmodic contractions of the bowel. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Accommodation: Adjustment, especially that of the eye for various distances. [EU] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs. Cephalosporin antibiotics are derived from this genus. [NIH] Actin: Essential component of the cell skeleton. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]

Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature

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blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acute-Phase Proteins: Proteins that are secreted into the blood in increased or decreased quantities by hepatocytes in response to trauma, inflammation, or disease. These proteins can serve as inhibitors or mediators of the inflammatory processes. Certain acute-phase proteins have been used to diagnose and follow the course of diseases or as tumor markers. [NIH]

Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenomatous Polyposis Coli: An autosomal dominant polyposis syndrome in which the colon contains few to thousands of adenomatous polyps, often occurring by age 15 to 25. [NIH]

Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adherens Junctions: Anchoring points where the cytoskeleton of neighboring cells are connected to each other. They are composed of specialized areas of the plasma membrane where bundles of microfilaments attach to the membrane through the transmembrane linkers, cadherins, which in turn attach through their extracellular domains to cadherins in the neighboring cell membranes. In sheets of cells, they form into adhesion belts (zonula adherens) that go all the way around a cell. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH]

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Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Uptake Inhibitors: Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (antidepressive agents, tricyclic) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin. [NIH] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and

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stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Alexia: The inability to recognize or comprehend written or printed words. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkalinization: The process by which a substance becomes an alkali. An alkali is the opposite of an acid. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allantois: An embryonic diverticulum of the hindgut of reptiles, birds, and mammals; in man its blood vessels give rise to those of the umbilical cord. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha

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particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [NIH]

Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amoxicillin: A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its

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resistance to gastric acid permits higher serum levels with oral administration. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesics: Compounds capable of relieving pain without the loss of consciousness or without producing anesthesia. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaphylactic: Pertaining to anaphylaxis. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH]

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Anastomosis: A procedure to connect healthy sections of tubular structures in the body after the diseased portion has been surgically removed. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anorectal: Pertaining to the anus and rectum or to the junction region between the two. [EU] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU]

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Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsants: Drugs used to prevent seizures or reduce their severity. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antidiarrheals: Miscellaneous agents found useful in the symptomatic treatment of diarrhea. They have no effect on the agent(s) that cause diarrhea, but merely alleviate the condition. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antimycotic: Suppressing the growth of fungi. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU]

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Antipruritic: Relieving or preventing itching. [EU] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aphakia: Absence of crystalline lens totally or partially from field of vision, from any cause except after cataract extraction. Aphakia is mainly congenital or as result of lens dislocation and subluxation. [NIH] Apheresis: Components plateletpheresis. [NIH]

being

separated

out,

as

leukapheresis,

plasmapheresis,

Aplastic anemia: A condition in which the bone marrow is unable to produce blood cells. [NIH]

Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Appendectomy: An operation to remove the appendix. [NIH] Appendicitis: Acute inflammation of the vermiform appendix. [NIH] Aqueous: Having to do with water. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in

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the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arteriovenous Fistula: An abnormal communication between an artery and a vein. [NIH] Arteritis: Inflammation of an artery. [NIH] Articular: Of or pertaining to a joint. [EU] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Endopeptidases: A sub-subclass of endopeptidases that depend on an aspartic acid residue for their activity. EC 3.4.23. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from

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posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atopic Eczema: Generic term for acute or chronic inflammatory conditions of the skin, typically erythematous, edematous, papular, vesicular, and crusting; often accompanied by sensations of itching and burning. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Autolysis: The spontaneous disintegration of tissues or cells by the action of their own autogenous enzymes. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH]

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Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Baclofen: A GABA derivative that is a specific agonist at GABA-B receptors. It is used in the treatment of spasticity, especially that due to spinal cord damage. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Barbiturates: A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are medically important as sedatives and hypnotics (sedatives, barbiturate), as anesthetics, or as anticonvulsants. [NIH] Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous. [NIH] Barium enema: A procedure in which a liquid with barium in it is put into the rectum and colon by way of the anus. Barium is a silver-white metallic compound that helps to show the image of the lower gastrointestinal tract on an x-ray. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its

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subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [NIH] Beta-Defensins: Defensins found mainly in epithelial cells. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Atresia: Atresia of the biliary tract, most commonly of the extrahepatic bile ducts. [NIH]

Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU]

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Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bismuth: A metallic element that has the atomic symbol Bi, atomic number 83 and atomic weight 208.98. [NIH] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Bladder: The organ that stores urine. [NIH] Blast phase: The phase of chronic myelogenous leukemia in which the number of immature, abnormal white blood cells in the bone marrow and blood is extremely high. Also called blast crisis. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the

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heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bromelain: An enzyme found in pineapples that breaks down other proteins, such as collagen and muscle fiber, and has anti-inflammatory properties. It is used as a meat tenderizer in the food industry. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH]

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Bronchial: Pertaining to one or more bronchi. [EU] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU] Bronchopulmonary Dysplasia: A chronic lung disease appearing in certain newborn infants treated for respiratory distress syndrome with mechanical ventilation and elevated concentration of inspired oxygen. [NIH] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Budesonide: A glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis. [NIH] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Bulking Agents: Laxatives that make bowel movements soft and easy to pass. [NIH] Bullous: Pertaining to or characterized by bullae. [EU] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Cadherins: A group of functionally related glycoproteins responsible for the calciumdependent cell-to-cell adhesion mechanism. They are divided into subclasses E-, P-, and Ncadherins, which are distinct in immunological specificity and tissue distribution. They promote cell adhesion via a homophilic mechanism. These compounds play a role in the construction of tissues and of the whole animal body. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH]

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Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH] Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carboxy: Cannabinoid. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH]

Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH]

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Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Carrier State: The condition of harboring an infective organism without manifesting symptoms of infection. The organism must be readily transmissable to another susceptible host. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Catalyse: To speed up a chemical reaction. [EU] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cathepsins: A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissue. They function optimally within an acidic pH range. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Caveolae: Endocytic/exocytic cell membrane structures rich in glycosphingolipids, cholesterol, and lipid-anchored membrane proteins that function in endocytosis (potocytosis), transcytosis, and signal transduction. Caveolae assume various shapes from open pits to closed vesicles. Caveolar coats are composed of caveolins. [NIH] Caveolins: The main structural proteins of caveolae. Several distinct genes for caveolins have been identified. [NIH] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH]

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Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Membrane Structures: Structures which are part of the cell membrane or have cell membrane as a major part of their structure. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a

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gravitational field generated in a centrifuge. [NIH] Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus Acremonium (Cephalosporium acremonium). They contain the betalactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemokines, C: Group of chemokines without adjacent cysteines that are chemoattractants for lymphocytes only. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. [NIH]

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Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholecystectomy: Surgical removal of the gallbladder. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Choleretic: A choleretic agent. [EU] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Cholestyramine: Strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium as Cl(-) anion. It exchanges chloride ions with bile salts, thus decreasing their concentration and that of cholesterol. It is used as a hypocholesteremic in diarrhea and biliary obstruction and as an antipruritic. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [NIH] Chorion: The outermost extraembryonic membrane. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [NIH] Chronic myelogenous leukemia: CML. A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myeloid leukemia or chronic granulocytic leukemia. [NIH]

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Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic phase: Refers to the early stages of chronic myelogenous leukemia or chronic lymphocytic leukemia. The number of mature and immature abnormal white blood cells in the bone marrow and blood is higher than normal, but lower than in the accelerated or blast phase. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, chymotrypsinogen and carried in the pancreatic juice to the duodenum where it is activated by trypsin. It selectively cleaves aromatic amino acids on the carboxyl side. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clindamycin: An antibacterial agent that is a semisynthetic analog of lincomycin. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of

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inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] Clotrimazole: An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]

Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Colectomy: An operation to remove the colon. An open colectomy is the removal of the colon through a surgical incision made in the wall of the abdomen. Laparoscopic-assisted colectomy uses a thin, lighted tube attached to a video camera. It allows the surgeon to remove the colon without a large incision. [NIH] Coliphages: Viruses whose host is Escherichia coli. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline,

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hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds. EC 3.4.24.-. [NIH] Collagenous Colitis: A type of colitis. Caused by an abnormal band of collagen, a threadlike protein. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colonic flora: The bacteria normally residing within the colon. [EU] Colonic Neoplasms: Tumors or cancer of the colon. [NIH] Colonoscope: A thin, lighted tube used to examine the inside of the colon. [NIH] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [NIH] Colony-Stimulating Factors: Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage colonystimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GMCSF). [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Colorectal Surgery: A surgical specialty concerned with the diagnosis and treatment of disorders and abnormalities of the colon, rectum, and anal canal. [NIH] Colostomy: An opening into the colon from the outside of the body. A colostomy provides a new path for waste material to leave the body after part of the colon has been removed. [NIH] Colostrum: The thin, yellow, serous fluid secreted by the mammary glands during pregnancy and immediately postpartum before lactation begins. It consists of immunologically active substances, white blood cells, water, protein, fat, and carbohydrates. [NIH]

Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Commensal: 1. Living on or within another organism, and deriving benefit without injuring or benefiting the other individual. 2. An organism living on or within another, but not causing injury to the host. [EU] Common Variable Immunodeficiency: Heterogeneous group of immunodeficiency syndromes characterized by hypogammaglobulinemia of most isotypes, variable B-cell defects, and the presence of recurrent bacterial infections. [NIH] Compassionate: A process for providing experimental drugs to very sick patients who have no treatment options. [NIH]

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Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compulsive Behavior: The behavior of performing an act persistently and repetitively without it leading to reward or pleasure. The act is usually a small, circumscribed behavior, almost ritualistic, yet not pathologically disturbing. Examples of compulsive behavior include twirling of hair, checking something constantly, not wanting pennies in change, straightening tilted pictures, etc. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray

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machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Conjunctivitis, Allergic: Conjunctivitis due to hypersensitivity to various allergens. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contact dermatitis: Inflammation of the skin with varying degrees of erythema, edema and vesinculation resulting from cutaneous contact with a foreign substance or other exposure. [NIH]

Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continence: The ability to hold in a bowel movement or urine. [NIH] Continent Ileostomy: An operation to create a pouch from part of the small intestine. Stool that collects in the pouch is removed by inserting a small tube through an opening made in

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the abdomen. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Ulcer: Loss of epithelial tissue from the surface of the cornea due to progressive erosion and necrosis of the tissue; usually caused by bacterial, fungal, or viral infection. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD

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results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Crowding: Behavior with respect to an excessive number of individuals, human or animal, in relation to available space. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cycasin: Carcinogenic and neurotoxic glycoside occurring in a number of plant species, including Cycas revoluta. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU]

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Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cysteine Endopeptidases: Endopeptidases which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by sulfhydryl reagents. EC 3.4.22. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH]

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Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Defecation: The normal process of elimination of fecal material from the rectum. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Demyelinating Diseases: Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

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Dental Plaque: A film that attaches to teeth, often causing dental caries and gingivitis. It is composed of mucins, secreted from salivary glands, and microorganisms. [NIH] Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatitis Herpetiformis: Rare, chronic, papulo-vesicular disease characterized by an intensely pruritic eruption consisting of various combinations of symmetrical, erythematous, papular, vesicular, or bullous lesions. The disease is strongly associated with the presence of HLA-B8 and HLA-DR3 antigens. A variety of different autoantibodies has been detected in small numbers in patients with dermatitis herpetiformis. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] Descending Colon: The part of the colon where stool is stored. Located on the left side of the abdomen. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Dextran Sulfate: Long-chain polymer of glucose containing 17-20% sulfur. It has been used as an anticoagulant and also has been shown to inhibit the binding of HIV-1 to CD4+ Tlymphocytes. It is commonly used as both an experimental and clinical laboratory reagent and has been investigated for use as an antiviral agent, in the treatment of hypolipidemia, and for the prevention of free radical damage, among other applications. [NIH] DHEA: Dehydroepiandrosterone. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH]

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Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Dietary Fiber: The remnants of plant cell walls that are resistant to digestion by the alimentary enzymes of man. It comprises various polysaccharides and lignins. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diosmin: A bioflavonoid that strengthens vascular walls. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU]

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Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Distention: The state of being distended or enlarged; the act of distending. [EU] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]

Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH]

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Duct: A tube through which body fluids pass. [NIH] Ductus Arteriosus: A fetal blood vessel connecting the pulmonary artery with the descending aorta. [NIH] Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [NIH]

Duodenitis: An irritation of the first part of the small intestine (duodenum). [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysentery: Any of various disorders marked by inflammation of the intestines, especially of the colon, and attended by pain in the abdomen, tenesmus, and frequent stools containing blood and mucus. Causes include chemical irritants, bacteria, protozoa, or parasitic worms. [EU]

Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]

Ecosystem: A dynamic complex of plant, animal and micro-organism communities and their non-living environment interacting as a functional unit. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Educational Status: Educational attainment or level of education of individuals. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and

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hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electroacupuncture: A form of acupuncture using low frequency electrically stimulated needles to produce analgesia and anesthesia and to treat disease. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Electroporation: A technique in which electric pulses of intensity in kilovolts per centimeter and of microsecond-to-millisecond duration cause a temporary loss of the semipermeability of cell membranes, thus leading to ion leakage, escape of metabolites, and increased uptake by cells of drugs, molecular probes, and DNA. Some applications of electroporation include introduction of plasmids or foreign DNA into living cells for transfection, fusion of cells to prepare hybridomas, and insertion of proteins into cell membranes. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emetic: An agent that causes vomiting. [EU] Emetine: The principal alkaloid of ipecac, from the ground roots of Uragoga (or Cephaelis) ipecacuanha or U. acuminata, of the Rubiaceae. It is used as an amebicide in many different preparations and may cause serious cardiac, hepatic, or renal damage and violent diarrhea and vomiting. Emetine inhibits protein syntheis in eucaryotic but not prokaryotic cells. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH]

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Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH]

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Enema: The injection of a liquid through the anus into the large bowel. [NIH] Energetic: Exhibiting energy : strenuous; operating with force, vigour, or effect. [EU] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Enteral Nutrition: Nutritional support given via the alimentary canal or any route connected to the gastrointestinal system (i.e., the enteral route). This includes oral feeding, sip feeding, and tube feeding using nasogastric, gastrostomy, and jejunostomy tubes. [NIH] Enteric bacteria: Single-celled microorganisms that lack chlorophyll. Some bacteria are capable of causing human, animal, or plant diseases; others are essential in pollution control because they break down organic matter in the air and in the water. [NIH] Enteric Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small intestine; see also enterocolitis. [EU] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]

Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Eosinophilic Gastroenteritis: Infection and swelling of the lining of the stomach, small intestine, or large intestine. The infection is caused by white blood cells (eosinophils). [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH]

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Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Episcleritis: Inflammation of the episclera and/or the outer layers of the sclera itself. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Nodosum: An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring or atrophy. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagitis, Peptic: Inflammation of the esophagus caused by reflux of gastric juice and/or stomach and duodenal contents. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a

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peripheral sense organ. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expert Systems: Computer programs based on knowledge developed from consultation with experts on a problem, and the processing and/or formalizing of this knowledge using these programs in such a manner that the problems may be solved. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Faecal: Pertaining to or of the nature of feces. [EU] Fallopian Tubes: Two long muscular tubes that transport ova from the ovaries to the uterus. They extend from the horn of the uterus to the ovaries and consist of an ampulla, an infundibulum, an isthmus, two ostia, and a pars uterina. The walls of the tubes are composed of three layers: mucosal, muscular, and serosal. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fascioliasis: Helminth infection of the liver caused by species of Fasciola. [NIH]

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Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fecal Incontinence: Failure of voluntary control of the anal sphincters, with involuntary passage of feces and flatus. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Fetal Membranes: Thin layers of tissue which surround the embryo or fetus and provide for its nutrition, respiration, excretion and protection; they are the yolk sac, allantois, amnion, and chorion. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibrositis: Aching, soreness or stiffness of muscles; often caused by inexpedient work postures. [NIH] Fish Oils: Oils high in unsaturated fats extracted from the bodies of fish or fish parts, especially the livers. Those from the liver are usually high in vitamin A. The oils are used as dietary supplements, in soaps and detergents, as protective coatings, and as a base for other food products such as vegetable shortenings. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Flatulence: Production or presence of gas in the gastrointestinal tract which may be expelled through the anus. [NIH] Flatus: Gas passed through the rectum. [NIH]

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Flexor: Muscles which flex a joint. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or

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asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungistatic: Inhibiting the growth of fungi. [EU] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines,

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characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastroenterologist: A doctor who specializes in diagnosing and treating disorders of the digestive system. [NIH] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastroscopy: Endoscopic examination, therapy, or surgery of the interior of the stomach. [NIH]

Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gelatinases: A class of enzymes that catalyzes the degradation of gelatin by acting on the peptide bonds. EC 3.4.24.-. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germfree: Free from all living micro-organisms. [NIH] Germ-free: Free of bacteria, disease-causing viruses, and other organisms that can cause

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infection. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Ginger: Deciduous plant rich in volatile oil (oils, volatile). It is used as a flavoring agent and has many other uses both internally and topically. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal

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kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Gonadal: Pertaining to a gonad. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the

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recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Granule: A small pill made from sucrose. [EU] Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. [NIH] Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Granulomatous Colitis: Another name for Crohn's disease of the colon. [NIH] Granulomatous Disease, Chronic: A recessive X-linked defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]

Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH]

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Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Hematogenous: Originating in the blood or spread through the bloodstream. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

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Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Hesperidin: Predominant flavonoid in lemons and sweet oranges. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU]

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Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Housekeeping: The care and management of property. [NIH] Human Genome Project: A coordinated effort of researchers to map and sequence the human genome. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydration: Combining with water. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU]

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Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxamic Acids: A class of weak acids with the general formula R-conhoh. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hygienic: Pertaining to hygiene, or conducive to health. [EU] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hyperkinesia: Abnormally increased motor function or activity; hyperactivity. [EU] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersecretion: Excessive secretion. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypogammaglobulinemia: The most common primary immunodeficiency in which antibody production is deficient. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idarubicin: An orally administered anthracycline antibiotic. The compound has shown

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activity against breast cancer, lymphomas and leukemias, together with potential for reduced cardiac toxicity. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileitis: Inflammation of the ileum. [EU] Ileoanal Pull-Through: An operation to remove the colon and inner lining of the rectum. The outer muscle of the rectum is not touched. The bottom end of the small intestine (ileum) is pulled through the remaining rectum and joined to the anus. Stool can be passed normally. Also called ileoanal anastomosis. [NIH] Ileoanal Reservoir: An operation to remove the colon, upper rectum, and part of the lower rectum. An internal pouch is created from the remaining intestine to hold stool. The operation may be done in two stages. The pouch may also be called a J-pouch or W-pouch. [NIH]

Ileostomy: Surgical creation of an external opening into the ileum for fecal diversion or drainage. Loop or tube procedures are most often employed. [NIH] Ileum: The lower end of the small intestine. [NIH] Ileus: Obstruction of the intestines. [EU] Image Cytometry: A technique encompassing morphometry, densitometry, neural networks, and expert systems that has numerous clinical and research applications and is particularly useful in anatomic pathology for the study of malignant lesions. The most common current application of image cytometry is for DNA analysis, followed by quantitation of immunohistochemical staining. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [NIH]

Immaturity: The state or quality of being unripe or not fully developed. [EU] Immune Complex Diseases: Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides serum sickness and the arthus reaction, evidence supports a pathogenic role for immune complexes in many other systemic immunologic diseases including glomerulonephritis, systemic lupus erythematosus and polyarteritis nodosa. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer

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factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]

Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]

Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunomodulator: New type of drugs mainly using biotechnological methods. Treatment of cancer. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Immunotoxins: Semisynthetic conjugates of various toxic molecules, including radioactive isotopes and bacterial or plant toxins, with specific immune substances such as immunoglobulins, monoclonal antibodies, and antigens. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds,

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wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU]

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Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insufflation: The act of blowing a powder, vapor, or gas into any body cavity for experimental, diagnostic, or therapeutic purposes. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical

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patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Intensive Care Units: Hospital units providing continuous surveillance and care to acutely ill patients. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interferon-beta: One of the type I interferons produced by fibroblasts in response to stimulation by live or inactivated virus or by double-stranded RNA. It is a cytokine with antiviral, antiproliferative, and immunomodulating activity. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-10: Factor that is a coregulator of mast cell growth. It is produced by T-cells and B-cells and shows extensive homology with the Epstein-Barr virus BCRFI gene. [NIH] Interleukin-11: Lymphohematopoietic cytokine that has the ability to modulate antigenspecific antibody responses, potentiate megakaryocytes, and regulate bone marrow adipogenesis. [NIH] Interleukin-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-15: Cytokine that stimulates the proliferation of T-lymphocytes and shares biological activities with IL-2. IL-15 also can induce B-lymphocyte proliferation and differentiation. [NIH] Interleukin-18: Cytokine which resembles IL-1 structurally and IL-12 functionally. It enhances the cytotoxic activity of NK cells and CTLs, and appears to play a role both as neuroimmunomodulator and in the induction of mucosal immunity. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-3: A multilineage cell growth factor secreted by lymphocytes, epithelial cells, and astrocytes which stimulates clonal proliferation and differentiation of various types of blood and tissue cells. Also called multi-CSF, it is considered one of the hematopoietic colony stimulating factors. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and T-

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lymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Flora: The bacteria, yeasts, and fungi that grow normally in the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport

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can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ipecac: A syrup made from the dried rhizomes of two different species, Cephaelis ipecacuanha and C. acuminata, belonging to the Rubiaciae family. They contain emetine, cephaeline, psychotrine and other isoquinolines. Ipecac syrup is used widely as an emetic acting both locally on the gastric mucosa and centrally on the chemoreceptor trigger zone. [NIH]

Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic Colitis: Decreased blood flow to the colon. Causes fever, pain, and bloody diarrhea. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Jejunostomy: Surgical formation of an opening through the abdominal wall into the jejunum, usually for enteral hyperalimentation. [NIH] Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] Jet lag: Symptoms produced in human beings by fast travel through large meridian difference. [NIH]

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Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratinocyte growth factor: A substance that stimulates the growth of epithelial cells that line the surface of the mouth and intestinal tract. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratoconus: A disorder characterized by an irregular corneal surface (cone-shaped) resulting in blurred and distorted images. [NIH] Ketotifen: A cycloheptathiophene that interferes with the release of inflammatory mediators and blocks histamine H1 receptors. It has been proposed as an anti-asthmatic and for the treatment of rhinitis, skin allergies, and anaphylaxis. [NIH] Kidney Cortex: The outer zone of the kidney, beneath the capsule, consisting of kidney glomerulus; kidney tubules, distal; and kidney tubules, proximal. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lactation: The period of the secretion of milk. [EU] Lactose Intolerance: The disease state resulting from the absence of lactase enzyme in the musocal cells of the gastrointestinal tract, and therefore an inability to break down the disaccharide lactose in milk for absorption from the gastrointestinal tract. It is manifested by indigestion of a mild nature to severe diarrhea. It may be due to inborn defect genetically conditioned or may be acquired. [NIH] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Laparotomy: A surgical incision made in the wall of the abdomen. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH]

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Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leucovorin: The active metabolite of folic acid. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. [NIH] Leukapheresis: The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lichen Planus: An inflammatory, pruritic disease of the skin and mucous membranes, which can be either generalized or localized. It is characterized by distinctive purplish, flattopped papules having a predilection for the trunk and flexor surfaces. The lesions may be discrete or coalesce to form plaques. Histologically, there is a "saw-tooth" pattern of epidermal hyperplasia and vacuolar alteration of the basal layer of the epidermis along with

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an intense upper dermal inflammatory infiltrate composed predominantly of T-cells. Etiology is unknown. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Lincomycin: (2S-trans)-Methyl 6,8-dideoxy-6-(((1-methyl-4-propyl-2pyrrolidinyl)carbonyl)amino)-1-thio-D-erythro-alpha-D-galacto-octopyranoside. An antibiotic produced by Streptomyces lincolnensis var. lincolnensis. It has been used in the treatment of staphylococcal, streptococcal, and Bacteroides fragilis infections. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH]

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Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Local therapy: Treatment that affects cells in the tumor and the area close to it. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Loperamide: 4-(p-Chlorophenyl)-4-hydroxy-N.N-dimethyl-alpha,alpha-diphenyl-1piperidine butyramide hydrochloride. Synthetic anti-diarrheal agent with a long duration of action; it is not significantly absorbed from the gut, has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally. [NIH] Loperamide hydrochloride: An antidiarrheal drug. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lupus Nephritis: Glomerulonephritis associated with systemic lupus erythematosus. It is classified into four histologic types: mesangial, focal, diffuse, and membranous. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH]

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Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells. [NIH] Lymphocyte Transformation: Morphologic alteration of small lymphocytes in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by interleukins, mitogens such as phytohemagglutinins, and by specific antigens. It may also occur in vivo, as in graft rejection and chronic myelogenous leukemia. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphocytosis: Excess of normal lymphocytes in the blood or in any effusion. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malabsorption syndrome: A group of symptoms such as gas, bloating, abdominal pain, and diarrhea resulting from the body's inability to properly absorb nutrients. [NIH] Malaise: A vague feeling of bodily discomfort. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and

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spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Mastocyte: A mast cell. [EU] Mastocytosis: A group of diseases resulting from proliferation of mast cells. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medroxyprogesterone: (6 alpha)-17-Hydroxy-6-methylpregn-4-ene-3,20-dione. A synthetic progestational hormone used in veterinary practice as an estrus regulator. [NIH] Medroxyprogesterone Acetate: An injectable contraceptive, generally marketed under the name Depo-Provera. [NIH]

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Megacolon: Pathological enlargement of the colon. [NIH] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningioma: A type of tumor that occurs in the meninges, the membranes that cover and protect the brain and spinal cord. Meningiomas usually grow slowly. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercaptopurine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be

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absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metalloendopeptidases: Endopeptidases which use a metal, normally zinc, in the catalytic mechanism. This group of enzymes is inactivated by metal chelators. EC 3.4.24. [NIH] Metallothionein: A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylazoxymethanol Acetate: The aglycone of cycasin. It acts as a potent carcinogen and neurotoxin and inhibits hepatic DNA, RNA, and protein synthesis. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms

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include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

Microsporidiosis: Infections with protozoa of the phylum Microspora. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milk Thistle: The plant Silybum marianum in the family Asteraceae containing the bioflavonoid complex silymarin. For centuries this has been used traditionally to treat liver disease. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]

Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [NIH]

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Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Monokines: Soluble mediators of the immune response that are neither antibodies nor complement. They are produced largely, but not exclusively, by monocytes and macrophages. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morbillivirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. MEASLES VIRUS is the type species. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Neurons: Neurons which activate muscle cells. [NIH] Mouth Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucosal Lining: The lining of GI tract organs that makes mucus. [NIH] Mucosal Ulceration: Skin ulceration in workers who work with lime and lime solutions. [NIH]

Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution.

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[NIH]

Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Multiple Organ Failure: A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscarinic Agonists: Drugs that bind to and activate muscarinic cholinergic receptors (receptors, muscarinic). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculoskeletal Diseases: Diseases of the muscles and their associated ligaments and other connective tissue and of the bones and cartilage viewed collectively. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myenteric: On stimulation of an intestinal segment, the segment above contracts and that below relaxes. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the

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blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]

Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Obstruction: Any hindrance to the passage of air into and out of the nose. The obstruction may be in the nasal vestibule, fossae, or other areas of the nasal cavity. [NIH] Nasal Septum: The partition separating the two nasal cavities in the midplane, composed of cartilaginous, membranous and bony parts. [NIH] Nasogastric: The process of passing a small, flexible plastic tube through the nose or mouth into the stomach or small intestine. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes

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(LGL). [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Nearsightedness: The common term for myopia. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Necrotizing Enterocolitis: A condition in which part of the tissue in the intestines is destroyed. Occurs mainly in under-weight newborn babies. A temporary ileostomy may be necessary. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH]

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Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]

Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neurotrophins: A nerve growth factor. [NIH] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH]

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Neutrophil: A type of white blood cell. [NIH] Neutrophil Activation: The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cellsurface receptors on the neutrophil. [NIH] Neutrophil Infiltration: The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Niche: The ultimate unit of the habitat, i. e. the specific spot occupied by an individual organism; by extension, the more or less specialized relationships existing between an organism, individual or synusia(e), and its environment. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitrosamines: A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties. [NIH] Nitrosation: Conversion into nitroso compounds. An example is the reaction of nitrites with amino compounds to form carcinogenic N-nitrosamines. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [NIH]

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Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleoproteins: Proteins conjugated with nucleic acids. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH]

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Oncology: The study of cancer. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]

Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal

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osteoporosis and age-related (or senile) osteoporosis. [NIH] Ostomy: Surgical construction of an artificial opening (stoma) for external fistulization of a duct or vessel by insertion of a tube with or without a supportive stent. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovarian Cysts: General term for cysts and cystic diseases of the ovary. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxazolone: Immunologic adjuvant and sensitizing agent. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA

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bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pallor: A clinical manifestation consisting of an unnatural paleness of the skin. [NIH] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Ducts: Ducts that collect pancreatic juice from the pancreas and supply it to the duodenum. [NIH] Pancreatic Insufficiency: Absence of or reduced pancreatic exocrine secretion into the duodenum and resultant poor digestion of lipids, vitamins, nitrogen, and carbohydrates. [NIH]

Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Pancytopenia: Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the

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frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Paratuberculosis: An infectious disease caused by Mycobacterium paratuberculosis. Characteristics include chronic debilitation and weight loss. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Patent ductus arteriosus: Abnormal persistence of the opening in the arterial duct that connects the pulmonary artery to the descending aorta; this opening normally closes within 24 hours of birth. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH]

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Patient Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] Patient Care Management: Generating, planning, organizing, and administering medical and nursing care and services for patients. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Satisfaction: The degree to which the individual regards the health care service or product or the manner in which it is delivered by the provider as useful, effective, or beneficial. [NIH] Pediatric Gastroenterologist: A doctor who treats children with digestive diseases. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvic inflammatory disease: A bacteriological disease sometimes associated with intrauterine device (IUD) usage. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins. [NIH] Peptide Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU]

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Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Perineal: Pertaining to the perineum. [EU] Perineum: The area between the anus and the sex organs. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]

Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peristalsis: The rippling motion of muscles in the intestine or other tubular organs characterized by the alternate contraction and relaxation of the muscles that propel the contents onward. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Periventricular Leukomalacia: Rare form of epilepsy. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the

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close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharyngitis: Inflammation of the throat. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipases A: Phosphatide acylhydrolases. Catalyze the hydrolysis of one of the acyl groups of phosphoglycerides or glycerophosphatidates. Phospholipase A1 hydrolyzes the acyl group attached to the 1-position (EC 3.1.1.32) and phospholipase A2 hydrolyzes the acyl group attached to the 2-position (EC 3.1.1.4). [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH]

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Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Phycocyanin: The metal-free blue phycobilin pigment in a conjugated chromoprotein of blue-green algae. It functions as light-absorbing substance together with chlorophylls. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Phytohemagglutinins: Mucoproteins isolated from the kidney bean (Phaseolus vulgaris); some of them are mitogenic to lymphocytes, others agglutinate all or certain types of erythrocytes or lymphocytes. They are used mainly in the study of immune mechanisms and in cell culture. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plana: The radiographic term applied to a vertebral body crushed to a thin plate. [NIH] Plant Diseases: Diseases of plants. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Exchange: Removal of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (PPF), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and

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other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Platelet Activating Factor: A phospholipid derivative formed by platelets, basophils, neutrophils, monocytes, and macrophages. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including hypotension, thrombocytopenia, neutropenia, and bronchoconstriction. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]

Plateletpheresis: The preparation of platelet concentrates with the return of red cells and platelet-poor plasma to the donor. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or

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veins. [EU] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polyp: A growth that protrudes from a mucous membrane. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government

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agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Preleukemia: Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria. [NIH] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal ends of the three polypeptide chains. Protocollagen, a precursor of procollagen consists of procollagen peptide chains in which proline and lysine have not yet been hydroxylated. [NIH] Proctocolectomy: An operation to remove the colon and rectum. Also called coloproctectomy. [NIH] Proctocolectomy, Restorative: A surgical procedure involving the excision of the colon and rectum and the formation of an ileoanal reservoir (pouch). In patients with intestinal

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diseases, such as ulcerative colitis, this procedure avoids the need for an ostomy by allowing for transanal defecation. [NIH] Proctocolitis: Inflammation of the rectum and colon. [NIH] Proctosigmoiditis: Irritation of the rectum and the sigmoid colon. [NIH] Proctosigmoidoscopy: An examination of the rectum and the lower part of the colon using a thin, lighted tube called a sigmoidoscope. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane).

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The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Protein Subunits: Single chains of amino acids that are the units of a multimeric protein. They can be identical or non-identical subunits. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH]

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Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoal: Having to do with the simplest organisms in the animal kingdom. Protozoa are single-cell organisms, such as ameba, and are different from bacteria, which are not members of the animal kingdom. Some protozoa can be seen without a microscope. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Proxy: A person authorized to decide or act for another person, for example, a person having durable power of attorney. [NIH] Pruritic: Pertaining to or characterized by pruritus. [EU] Pseudomembranous Colitis: Severe irritation of the colon. Caused by Clostridium difficile bacteria. Occurs after taking oral antibiotics, which kill bacteria that normally live in the colon. [NIH] Pseudotumor Cerebri: A condition marked by raised intracranial pressure and characterized clinically by headaches; nausea; papilledema, peripheral constriction of the visual fields, transient visual obscurations, and pulsatile tinnitus. Obesity is frequently associated with this condition, which primarily affects women between 20 and 44 years of age. Chronic papilledema may lead to optic nerve injury (optic nerve diseases) and visual loss (blindness). [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU]

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Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Psyllium: Dried, ripe seeds of Plantago psyllium, P. indica, and P. ovata (Plantaginaceae). Plantain seeds swell in water and are used as demulcents and bulk laxatives. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Emphysema: Condition of the lungs characterized by increase beyond normal in the size of air spaces distal to the terminal bronchioles, either from dilatation of the alveoli or from destruction of their walls. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial infection. [EU] Pyoderma: Any purulent skin disease (Dorland, 27th ed). [NIH] Pyoderma Gangrenosum: An idiopathic, rapidly evolving, and severely debilitating disease occurring most commonly in association with chronic ulcerative colitis. It is characterized by the presence of boggy, purplish ulcers with undermined borders, appearing mostly on the legs. The majority of cases are in people between 40 and 60 years old. Its etiology is unknown. [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a

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thin fluid called liquor puris). [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Quinoxaline: AMPA/Kainate antagonist. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation oncologist: A doctor who specializes in using radiation to treat cancer. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of

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diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Reassurance: A procedure in psychotherapy that seeks to give the client confidence in a favorable outcome. It makes use of suggestion, of the prestige of the therapist. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Muscarinic: One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for muscarine over nicotine. There are several subtypes (usually M1, M2, M3.) that are characterized by their cellular actions, pharmacology, and molecular biology. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Fusion Proteins: Proteins that are the result of genetic engineering. A regulatory part or promoter of one or more genes is combined with a structural gene. The fusion protein is formed after transcription and translation of the fused gene. This type of fusion protein is used in the study of gene regulation or structure-activity relationships. They might also be used clinically as targeted toxins (immunotoxins). [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflective: Capable of throwing back light, images, sound waves : reflecting. [EU] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH]

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Refractive Power: The ability of an object, such as the eye, to bend light as light passes through it. [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regional enteritis: Inflammation of the intestines, but usually only of the small intestine. Also called Crohn's disease. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal Osteodystrophy: Decalcification of bone due to hyperparathyroidism secondary to chronic kidney disease. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Resected: Surgical removal of part of an organ. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together,

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separately visible; thus revealing the structure of an object. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Burst: A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (granulomatous disease, chronic) often die as a result of recurrent bacterial infections. [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restitution: The restoration to a normal state. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Detachment: Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Retinal detachment occurs more commonly in men than in women, in eyes with degenerative myopia, in aging and in aphakia. It may occur after an uncomplicated cataract extraction, but it is seen more often if vitreous humor has been lost during surgery. (Dorland, 27th ed; Newell, Ophthalmology: Principles and Concepts, 7th ed, p310-12). [NIH] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH]

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Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodentia: A mammalian order which consists of 29 families and many genera. [NIH] Rosiglitazone: A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones. [NIH] Rotator: A muscle by which a part can be turned circularly. [NIH] Saccharomyces: A genus of ascomycetous fungi of the family Saccharomycetaceae, order

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saccharomycetales. [NIH] Saccharomyces cerevisiae: A species of the genus Saccharomyces, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. [NIH] Saccharomycetales: An order of fungi in the phylum Ascomycota that multiply by budding. They include the telomorphic ascomycetous yeasts which are found in a very wide range of habitats. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salvage Therapy: A therapeutic approach, involving chemotherapy, radiation therapy, or surgery, after initial regimens have failed to lead to improvement in a patient's condition. Salvage therapy is most often used for neoplastic diseases. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior five-

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sixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Scleritis: Refers to any inflammation of the sclera including episcleritis, a benign condition affecting only the episclera, which is generally short-lived and easily treated. Classic scleritis, on the other hand, affects deeper tissue and is characterized by higher rates of visual acuity loss and even mortality, particularly in necrotizing form. Its characteristic symptom is severe and general head pain. Scleritis has also been associated with systemic collagen disease. Etiology is unknown but is thought to involve a local immune response. Treatment is difficult and includes administration of anti-inflammatory and immunosuppressive agents such as corticosteroids. Inflammation of the sclera may also be secondary to inflammation of adjacent tissues, such as the conjunctiva. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedatives, Barbiturate: Those derivatives of barbituric or thiobarbituric acid that are used as hypnotics or sedatives. The structural class of all such derivatives, regardless of use, is barbiturates. [NIH] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH]

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Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [NIH] Seminal vesicles: Glands that help produce semen. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Senna: Preparations of Cassia senna L. and C. angustifolia of the Leguminosae. They contain sennosides, which are anthraquinone type cathartics and are used in many different preparations as laxatives. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serine Endopeptidases: Any member of the group of endopeptidases containing at the active site a serine residue involved in catalysis. EC 3.4.21. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serotonin Uptake Inhibitors: Compounds that specifically inhibit the reuptake of serotonin in the brain. This increases the serotonin concentration in the synaptic cleft which then activates serotonin receptors to a greater extent. These agents have been used in treatment of depression, panic disorder, obsessive-compulsive behavior, and alcoholism, as analgesics, and to treat obesity and bulimia. Many of the adrenergic uptake inhibitors also inhibit serotonin uptake; they are not included here. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serrata: The serrated anterior border of the retina located approximately 8.5 mm from the limbus and adjacent to the pars plana of the ciliary body. [NIH] Serrated: Having notches or teeth on the edge as a saw has. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins

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have been removed. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Short Bowel Syndrome: A malabsorption syndrome resulting from extensive operative resection of small bowel. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoid Colon: The lower part of the colon that empties into the rectum. [NIH] Sigmoidoscope: A thin, lighted tube used to view the inside of the colon. [NIH] Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silymarin: A mixture of flavonoids extracted from seeds of the milk thistle, Silybum marianum. It consists primarily of three isomers: silicristin, silidianin, and silybin, its major component. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin Aging: The process of aging due to changes in the structure and elasticity of the skin over time. It may be a part of physiological aging or it may be due to the effects of ultraviolet radiation, usually through exposure to sunlight. [NIH]

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Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Soaps: Sodium or potassium salts of long chain fatty acids. These detergent substances are obtained by boiling natural oils or fats with caustic alkali. Sodium soaps are harder and are used as topical anti-infectives and vehicles in pills and liniments; potassium soaps are soft, used as vehicles for ointments and also as topical antimicrobials. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spasmodic: Of the nature of a spasm. [EU] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in

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spastic paralysis or in cerebral palsy. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Sphincters: Any annular muscle closing an orifice. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprue: A non febrile tropical disease of uncertain origin. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Steatorrhea: A condition in which the body cannot absorb fat. Causes a buildup of fat in the stool and loose, greasy, and foul bowel movements. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH]

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Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stoma: A surgically created opening from an area inside the body to the outside. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stool test: A test to check for hidden blood in the bowel movement. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a

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smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Suppurative: Consisting of, containing, associated with, or identified by the formation of pus. [NIH] Supraspinal: Above the spinal column or any spine. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH]

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Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] Synovitis: Inflammation of a synovial membrane. It is usually painful, particularly on motion, and is characterized by a fluctuating swelling due to effusion within a synovial sac. Synovitis is qualified as fibrinous, gonorrhoeal, hyperplastic, lipomatous, metritic, puerperal, rheumatic, scarlatinal, syphilitic, tuberculous, urethral, etc. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the

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skull, and containing the organs of hearing. [NIH] Tenesmus: Straining, especially ineffectual and painful straining at stool or in urination. [EU] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators

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of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymoma: A tumor of the thymus, an organ that is part of the lymphatic system and is located in the chest, behind the breastbone. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Ticlopidine: Ticlopidine is an effective inhibitor of platelet aggregation. The drug has been found to significantly reduce infarction size in acute myocardial infarcts and is an effective antithrombotic agent in arteriovenous fistulas, aorto-coronary bypass grafts, ischemic heart disease, venous thrombosis, and arteriosclerosis. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Titre: The quantity of a substance required to produce a reaction with a given volume of another substance, or the amount of one substance required to correspond with a given amount of another substance. [EU] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU]

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Tonicity: The normal state of muscular tension. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell

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to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Triad: Trivalent. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Trinitrobenzenesulfonic Acid: A reagent that is used to neutralize peptide terminal amino groups. [NIH] Trophic: Of or pertaining to nutrition. [EU] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH]

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Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Unsaturated Fats: A type of fat. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH]

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Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urogenital System: All the organs involved in reproduction and the formation and release of urine. It includes the kidneys, ureters, bladder, urethra, and the organs of reproduction ovaries, uterus, fallopian tubes, vagina, and clitoris in women and the testes, seminal vesicles, prostate, seminal ducts, and penis in men. [NIH] Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Varices: Stretched veins such as those that form in the esophagus from cirrhosis. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH]

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Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villous: Of a surface, covered with villi. [NIH] Villus: Cell found in the lining of the small intestine. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vinorelbine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH]

452 Colitis

Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitamin D: The vitamin that mediates intestinal calcium absorption, bone calcium metabolism, and probably muscle activity. It usually acts as a hormone precursor, requiring 2 stages of metabolism before reaching actual hormonal form. It is isolated from fish liver oils and used in the treatment and prevention of rickets. [NIH] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitreous Humor: The transparent, colorless mass of gel that lies behind the lens and in front of the retina and fills the center of the eyeball. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Volvulus: A twisting of the stomach or large intestine. May be caused by the stomach being in the wrong position, a foreign substance, or abnormal joining of one part of the stomach or intestine to another. Volvulus can lead to blockage, perforation, peritonitis, and poor blood flow. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH]

Dictionary 453

X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yolk Sac: An embryonic membrane formed from endoderm and mesoderm. In reptiles and birds it incorporates the yolk into the digestive tract for nourishing the embryo. In placental mammals its nutritional function is vestigial; however, it is the source of most of the intestinal mucosa and the site of formation of the germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

455

INDEX 6 6-Mercaptopurine, 15, 276, 285, 297, 343 A Abdominal Cramps, 271, 280, 322, 327, 343 Aberrant, 28, 49, 53, 99, 212, 241, 343 Ablation, 81, 343 Abscess, 58, 117, 343 Acatalasia, 343, 360 Acceptor, 343, 402, 417 Accommodation, 343, 411 Acetylcholine, 103, 248, 253, 343, 363, 403, 414 Acne, 209, 210, 343 Acoustic, 175, 343 Acremonium, 343, 362 Actin, 58, 71, 83, 343, 407, 448 Action Potentials, 208, 343 Acute leukemia, 106, 343, 426 Acute myelogenous leukemia, 104, 123, 343, 344 Acute myeloid leukemia, 104, 343, 344 Acute nonlymphocytic leukemia, 343, 344 Acute renal, 344, 389 Acute-Phase Proteins, 112, 344 Acyl, 344, 422 Adaptability, 344, 361 Adaptation, 210, 280, 344 Adenine, 344, 430 Adenocarcinoma, 33, 86, 94, 234, 344 Adenomatous Polyposis Coli, 110, 344 Adenosine, 58, 221, 253, 344, 358, 392, 422 Adherens Junctions, 87, 344 Adipocytes, 344, 368, 401 Adjustment, 237, 343, 344 Adjuvant, 62, 270, 344, 385, 417 Adoptive Transfer, 37, 70, 76, 83, 344 Adrenal Cortex, 345, 370, 391, 427 Adrenal Glands, 345, 348 Adrenal Medulla, 345, 360, 380, 414 Adrenergic, 253, 345, 375, 380, 403, 438, 443 Adrenergic Uptake Inhibitors, 345, 438 Adsorption, 110, 345 Adsorptive, 110, 345 Adverse Effect, 25, 66, 196, 279, 345, 375, 439 Aerobic, 345, 408, 417

Aetiology, 213, 345 Afferent, 345, 401 Affinity, 73, 247, 345, 402, 404, 407, 440 Agar, 345, 366, 370, 423 Age Groups, 28, 345 Age of Onset, 72, 200, 345 Aged, 80 and Over, 345 Agonist, 70, 75, 140, 143, 147, 150, 248, 345, 354, 375, 414 Agoraphobia, 346, 393, 418 Airway, 48, 346 Albumin, 21, 276, 346, 417, 423 Aldehydes, 346, 452 Alertness, 346, 358 Alexia, 346, 376 Algorithms, 346, 356 Alkaline, 250, 346, 347, 354, 359 Alkalinization, 218, 346 Alkaloid, 346, 365, 377, 414 Allantois, 346, 382 Alleles, 53, 81, 346, 402 Allergen, 74, 346, 373 Allergic Rhinitis, 226, 229, 237, 246, 346, 358 Allogeneic, 104, 346, 387 Allogeneic bone marrow transplantation, 104, 346 Allograft, 38, 225, 226, 346 Allylamine, 346, 347 Alopecia, 346, 371 Alpha Particles, 346, 431 Alternative medicine, 296, 347 Alveoli, 347, 430, 451 Ambulatory Care, 347 Amebiasis, 347, 407 Ameliorated, 139, 146, 347 Ameliorating, 218, 253, 347 Amine, 211, 225, 347, 390 Amino Acid Sequence, 209, 210, 223, 236, 244, 259, 347, 350, 381, 385, 426 Amino Acid Substitution, 34, 347 Amino-terminal, 347, 426 Ammonia, 58, 347, 387 Amnion, 347, 382 Amniotic Fluid, 347, 386 Amoxicillin, 7, 185, 347 Amphetamines, 345, 348, 365 Ampicillin, 7, 185, 347, 348

456 Colitis

Amplification, 55, 215, 348 Ampulla, 348, 378, 381 Amyloid, 111, 252, 348 Amyloidosis, 275, 348 Anaemia, 99, 348, 406 Anaesthesia, 348, 395 Analgesics, 232, 281, 298, 328, 348, 438 Analog, 251, 257, 348, 364, 383, 384 Analogous, 348, 375, 425, 447 Analytes, 318, 348 Anaphylactic, 237, 348, 424 Anaphylatoxins, 348, 367 Anaphylaxis, 226, 246, 348, 400 Anatomical, 35, 349, 353, 368, 394, 437 Androgens, 345, 349, 370 Anemia, 132, 209, 268, 280, 281, 290, 299, 314, 328, 349, 383, 410 Anesthesia, 346, 348, 349, 377, 378 Anesthetics, 349, 354, 380 Angina, 253, 349 Angiogenesis, 76, 82, 212, 225, 230, 231, 349, 405 Angioplasty, 225, 349, 411 Animal model, 23, 30, 32, 36, 38, 48, 53, 57, 60, 61, 66, 70, 127, 131, 157, 349 Anions, 346, 349, 399 Anomalies, 45, 349 Anorectal, 22, 349 Anorexia, 230, 238, 248, 276, 348, 349, 385, 449 Antagonism, 349, 358 Anthracycline, 349, 392 Anthrax, 81, 349 Antiallergic, 349, 370 Antibacterial, 349, 364, 441, 450 Antibody, 4, 24, 27, 34, 38, 47, 96, 108, 175, 197, 202, 205, 213, 215, 216, 223, 235, 242, 244, 250, 258, 345, 350, 357, 367, 380, 389, 390, 391, 392, 393, 394, 395, 397, 399, 405, 409, 431, 441, 453 Anticoagulant, 204, 350, 373, 428 Anticonvulsants, 350, 354 Antidepressant, 350, 393 Antidiarrheals, 328, 350 Antidote, 350, 401 Antifungal, 217, 241, 350 Antigen-Antibody Complex, 350, 367 Antigen-presenting cell, 75, 350, 372 Anti-infective, 350, 391, 440 Anti-Inflammatory Agents, 350, 352, 370 Antimetabolite, 343, 350, 383 Antimicrobial, 16, 236, 350, 364, 373

Antimycotic, 350, 365 Antineoplastic, 343, 350, 359, 370, 371, 383, 418, 451 Antioxidant, 14, 66, 78, 161, 165, 350, 352, 417, 439 Antiproliferative, 350, 397 Antipruritic, 351, 363 Antithrombotic, 351, 428, 446 Antiviral, 351, 373, 394, 397, 420 Anus, 275, 299, 327, 348, 349, 351, 353, 354, 357, 379, 382, 393, 421, 432 Anxiety, 198, 209, 248, 252, 253, 281, 290, 326, 351, 418 Anxiety Disorders, 351, 418 Aorta, 351, 376, 419, 451 Aphakia, 351, 434 Apheresis, 107, 110, 351 Aplastic anemia, 134, 351 Apolipoproteins, 351, 402 Apoptosis, 26, 54, 68, 69, 73, 84, 94, 221, 223, 231, 236, 351 Appendectomy, 8, 10, 21, 295, 351 Appendicitis, 9, 10, 21, 351 Aqueous, 351, 354, 360, 371, 391, 401 Arachidonate 12-Lipoxygenase, 351, 402 Arachidonate 15-Lipoxygenase, 351, 402 Arachidonate Lipoxygenases, 351, 402 Arachidonic Acid, 37, 212, 220, 233, 237, 245, 251, 351, 376, 401, 427 Arginine, 158, 176, 348, 352, 414, 448 Aromatic, 226, 246, 352, 364, 407, 422 Arterial, 249, 346, 352, 363, 369, 392, 419, 428, 444 Arteries, 351, 352, 357, 369, 403, 407, 411, 430, 445, 449 Arterioles, 214, 352, 357, 359, 407, 411 Arteriolosclerosis, 352 Arteriosclerosis, 214, 228, 352, 446 Arteriovenous, 352, 407, 446 Arteriovenous Fistula, 352, 446 Arteritis, 134, 352 Articular, 352, 416 Ascorbic Acid, 138, 145, 352, 392 Aseptic, 130, 352, 416, 442 Aspartic, 352, 378 Aspartic Endopeptidases, 352, 378 Asphyxia, 84, 352 Aspirin, 28, 124, 352 Assay, 28, 50, 68, 224, 248, 352, 394, 435, 449 Astrocytoma, 352, 386

Index 457

Asymptomatic, 7, 10, 86, 94, 343, 347, 352, 418 Ataxia, 314, 352, 391, 445 Atmospheric Pressure, 353, 392 Atopic, 211, 213, 214, 219, 225, 229, 234, 237, 246, 249, 255, 353 Atopic Eczema, 246, 353 Atresia, 210, 353, 355 Atrial, 236, 353, 369, 448 Atrioventricular, 353, 369 Atrium, 353, 369, 448, 451 Atrophy, 95, 298, 313, 314, 353, 380, 413 Attenuated, 95, 161, 353 Atypical, 95, 108, 246, 247, 275, 353 Autacoids, 353, 395 Autoantibodies, 29, 64, 209, 247, 353, 373 Autoantigens, 35, 353 Autodigestion, 353, 418 Autoimmune disease, 53, 209, 210, 211, 216, 219, 234, 236, 244, 250, 256, 353, 410, 423 Autoimmune Hepatitis, 247, 353 Autoimmunity, 64, 83, 227, 353 Autologous, 224, 225, 243, 353 Autologous bone marrow transplantation, 224, 225, 243, 353 Autolysis, 249, 353 Autonomic, 343, 353, 414, 421 Axonal, 49, 353 Axons, 354, 398, 416, 421 B Bacillus, 106, 349, 354, 358 Baclofen, 129, 354 Bacterial Infections, 310, 354, 361, 366, 388, 434 Bacterial Physiology, 344, 354 Bacterial toxin, 80, 82, 354 Bactericidal, 236, 247, 354, 380 Bacteriophage, 30, 80, 354, 423, 447 Bacterium, 354, 389 Barbiturates, 248, 354, 437 Barium, 15, 19, 197, 299, 318, 342, 354 Barium enema, 15, 197, 299, 342, 354 Basal Ganglia, 353, 354, 363, 386 Basal Ganglia Diseases, 353, 354, 363 Base, 44, 72, 201, 280, 344, 354, 371, 372, 382, 383, 385, 400, 444, 449 Base Sequence, 354, 383, 385 Basement Membrane, 37, 110, 230, 354, 381, 400 Basophils, 355, 388, 401, 424

Benign, 16, 18, 120, 127, 270, 352, 355, 389, 412, 431, 437 Benzene, 355 Benzodiazepines, 248, 355 Benzoic Acid, 233, 355 Bereavement, 287, 355 Beta-Defensins, 114, 355 Beta-pleated, 348, 355 Beta-Thromboglobulin, 355, 398 Bilateral, 11, 355, 380, 434 Bile, 63, 96, 143, 150, 171, 178, 269, 355, 362, 363, 384, 390, 391, 402, 442, 444, 450 Bile Acids, 143, 150, 178, 355, 442, 444 Bile Acids and Salts, 355 Bile Ducts, 355, 384 Biliary, 29, 45, 129, 355, 359, 363, 390, 418 Biliary Atresia, 45, 355 Biliary Tract, 29, 355, 359, 418 Bilirubin, 346, 355, 384 Bioassay, 8, 355 Bioavailability, 203, 355 Bioavailable, 66, 356 Biochemical, 34, 47, 52, 63, 67, 90, 144, 151, 161, 179, 254, 346, 350, 356, 383, 401, 416, 438 Biological response modifier, 356, 397 Biological therapy, 356, 388 Biopsy, 4, 5, 17, 19, 21, 26, 31, 55, 103, 112, 135, 198, 200, 272, 278, 298, 324, 356 Biopsy specimen, 5, 55, 356 Biosynthesis, 212, 245, 352, 356, 365, 438 Biotechnology, 87, 92, 268, 296, 309, 312, 313, 314, 315, 356 Bipolar Disorder, 248, 356 Bismuth, 14, 284, 356 Bivalent, 356, 407 Bladder, 356, 371, 395, 410, 413, 428, 449, 450 Blast phase, 356, 364 Blastocyst, 356, 368, 423 Bloating, 276, 341, 356, 395, 399, 404 Blood Coagulation, 268, 356, 359, 435, 445 Blood Coagulation Factors, 268, 356 Blood Glucose, 356, 389, 396 Blood Platelets, 356, 406, 424, 438, 445 Blood pressure, 271, 356, 359, 362, 392, 409, 430, 440 Blood transfusion, 17, 357 Blot, 71, 357, 394 Blotting, Western, 357, 394 Body Composition, 205, 357

458 Colitis

Body Fluids, 224, 357, 358, 376, 383, 415, 440, 448 Bone Marrow Transplantation, 37, 168, 244, 357 Bone scan, 357, 436 Bowel Movement, 26, 273, 274, 278, 323, 324, 327, 357, 358, 368, 374, 441, 442 Brachytherapy, 357, 398, 399, 431, 453 Bradykinin, 357, 414, 424 Branch, 116, 339, 357, 385, 403, 419, 441, 445 Breakdown, 275, 357, 374, 384, 416 Breeding, 86, 357 Broad-spectrum, 347, 348, 357, 362 Bromelain, 182, 357 Bronchi, 357, 358, 380, 447 Bronchial, 237, 358, 390 Bronchioles, 347, 358, 430 Bronchiseptica, 358, 421 Bronchitis, 211, 358, 364 Bronchoconstriction, 237, 358, 424 Bronchopulmonary, 68, 358 Bronchopulmonary Dysplasia, 68, 358 Bronchus, 358 Buccal, 358, 403 Budesonide, 5, 23, 24, 96, 97, 174, 213, 285, 297, 358 Bulimia, 238, 248, 358, 438 Bulking Agents, 5, 269, 299, 358 Bullous, 117, 358, 373 Bypass, 358, 411, 446 C Cachexia, 211, 221, 229, 230, 236, 238, 358 Cadherins, 225, 243, 344, 358 Caffeine, 5, 269, 358, 430 Calcification, 352, 358 Calcium, 29, 257, 298, 358, 359, 367, 401, 405, 411, 419, 428, 439, 448, 452 Calculi, 359, 387 Cannabidiol, 42, 359 Cannabinoids, 42, 359 Cannabinol, 359 Capillary, 212, 357, 359, 451 Capsules, 5, 144, 151, 226, 246, 284, 359, 375, 385 Carbohydrate, 220, 359, 370, 387, 425 Carbon Dioxide, 359, 372, 423, 434 Carboplatin, 170, 359 Carboxy, 245, 359 Carboxy-terminal, 245, 359 Carcinogen, 359, 407 Carcinogenesis, 61, 127, 160, 194, 359, 362

Carcinogenic, 355, 359, 370, 396, 414, 415, 427, 442 Carcinoma, 22, 26, 40, 61, 103, 116, 117, 124, 161, 176, 236, 263, 275, 359 Cardiac, 97, 225, 226, 248, 275, 346, 358, 359, 369, 377, 380, 384, 393, 411, 442 Cardiovascular, 78, 221, 359, 401, 438 Cardiovascular disease, 78, 359 Carnitine, 176, 359 Carotene, 359, 434 Carrier Proteins, 360, 423 Carrier State, 7, 347, 360 Case report, 21, 108, 113, 116, 117, 129, 132, 136, 141, 148, 160, 166, 168, 176, 177, 360, 364 Case series, 116, 360, 364 Case-Control Studies, 13, 67, 360 Catalase, 247, 343, 360 Catalyse, 208, 360 Cataract, 237, 351, 360, 434 Catecholamine, 360, 375, 422 Cathepsins, 52, 360 Catheterization, 349, 360, 411 Cations, 360, 399 Caudal, 360, 374, 392, 425 Causal, 21, 53, 360, 398, 438, 445 Caveolae, 58, 360 Caveolins, 360 Cecum, 57, 227, 360, 400 Celiac Disease, 4, 215, 274, 286, 361 Cell Adhesion, 101, 216, 224, 243, 358, 361, 396 Cell Adhesion Molecules, 216, 225, 243, 361 Cell Cycle, 361, 364, 429 Cell Death, 42, 351, 361, 386, 412 Cell Differentiation, 53, 219, 257, 361, 439 Cell Division, 313, 354, 361, 388, 406, 408, 423, 427 Cell membrane, 208, 216, 223, 235, 245, 251, 344, 360, 361, 365, 373, 377, 381, 384, 398, 422 Cell Membrane Structures, 360, 361 Cell proliferation, 24, 215, 259, 352, 361, 398, 439 Cell Respiration, 361, 408, 417, 434 Cell Size, 361, 383 Cell Survival, 79, 361, 388 Cellulose, 361, 384, 423 Central Nervous System Infections, 361, 389, 391 Centrifugation, 250, 361, 444

Index 459

Cephalosporins, 7, 186, 362 Ceramide, 209, 362 Cerebellar, 353, 362, 432 Cerebral, 139, 146, 215, 255, 353, 354, 362, 369, 380, 386, 391, 441, 445 Cerebral hemispheres, 354, 362, 386 Cerebral Palsy, 362, 441 Cerebrospinal, 235, 362, 391 Cerebrospinal fluid, 235, 362, 391 Cerebrovascular, 237, 354, 359, 362, 445 Cerebrum, 362, 448 Character, 362, 372, 387 Chemokines, 31, 33, 35, 54, 70, 76, 362 Chemokines, C, 76, 362 Chemopreventive, 41, 135, 362 Chemoreceptor, 362, 399 Chemotactic Factors, 362, 367, 414 Chemotaxis, 76, 245, 362 Chemotherapy, 104, 142, 149, 159, 160, 161, 166, 170, 173, 179, 181, 362, 436 Chenodeoxycholic Acid, 138, 145, 362, 450 Chimeras, 77, 363 Chlorophyll, 363, 379, 384 Cholangitis, 63, 95, 97, 99, 103, 134, 135, 247, 294, 320, 363 Cholecystectomy, 271, 363 Cholera, 90, 210, 363, 438, 451 Choleretic, 362, 363, 450 Cholesterol, 250, 355, 360, 363, 364, 369, 384, 402, 403, 442 Cholesterol Esters, 363, 402 Cholestyramine, 269, 363 Cholinergic, 248, 251, 252, 363, 410, 414, 432 Chorea, 248, 249, 252, 363 Choreatic Disorders, 363 Chorion, 363, 382 Chorioretinitis, 363, 434 Choroid, 363, 434, 450 Chromatin, 351, 363 Chromosomal, 53, 81, 348, 363 Chromosome, 53, 67, 88, 93, 112, 363, 389, 402 Chronic Disease, 6, 25, 55, 297, 323, 358, 363, 366 Chronic lymphocytic leukemia, 363, 364 Chronic myelogenous leukemia, 356, 363, 364, 404 Chronic Obstructive Pulmonary Disease, 225, 229, 237, 238, 364 Chronic phase, 213, 364 Chronic renal, 364, 425, 449

Chylomicrons, 364, 402 Chymotrypsin, 209, 364 Ciliary, 364, 409, 438, 450 Ciliary Body, 364, 438, 450 Ciprofloxacin, 24, 186, 364 Circulatory system, 232, 364, 378 CIS, 51, 364, 434 Cisplatin, 161, 364 Citrus, 352, 364 Clamp, 36, 364 Clindamycin, 7, 30, 186, 364 Clinical Medicine, 70, 113, 140, 147, 164, 364, 426 Clinical study, 143, 144, 150, 151, 159, 202, 364, 369 Clone, 259, 364 Cloning, 356, 365 Clot Retraction, 365, 424 Clotrimazole, 195, 196, 365 Coagulation, 81, 356, 365, 389, 424, 446 Coca, 365 Cocaine, 248, 365 Cochlea, 365, 396 Coenzyme, 352, 365 Cofactor, 365, 428, 445 Cognition, 275, 365 Coliphages, 354, 365 Collagen disease, 253, 366, 391, 437 Collagenases, 230, 366 Collapse, 348, 357, 366 Colloidal, 346, 366, 377 Colonic flora, 39, 366 Colonic Neoplasms, 139, 146, 366 Colonoscope, 40, 366 Colony-Stimulating Factors, 255, 366, 388 Colorectal, 5, 13, 24, 26, 28, 40, 41, 45, 61, 78, 93, 99, 102, 103, 110, 111, 112, 113, 116, 127, 129, 141, 148, 161, 162, 165, 183, 194, 276, 278, 323, 366 Colorectal Cancer, 13, 24, 28, 41, 45, 61, 93, 99, 102, 112, 183, 276, 366 Colorectal Surgery, 13, 141, 148, 366 Colostomy, 18, 319, 366 Colostrum, 135, 182, 366 Combination Therapy, 278, 279, 366 Commensal, 29, 62, 82, 366 Common Variable Immunodeficiency, 95, 366 Compassionate, 282, 366 Complement, 38, 41, 81, 112, 348, 367, 385, 396, 404, 409, 424 Complement Activation, 38, 81, 348, 367

460 Colitis

Complementary and alternative medicine, 155, 192, 367 Complementary medicine, 6, 155, 367 Complete remission, 367, 433 Compulsive Behavior, 367, 438 Computational Biology, 309, 312, 367 Computed tomography, 367, 368, 436 Computerized axial tomography, 368, 436 Conception, 322, 368, 369, 382, 442 Concomitant, 17, 49, 99, 106, 368 Cone, 55, 368, 400, 443 Congestion, 368, 380 Congestive heart failure, 8, 229, 230, 368 Conjugated, 174, 355, 362, 368, 371, 414, 415, 423 Conjunctiva, 368, 437 Conjunctivitis, 214, 224, 225, 237, 243, 255, 368 Conjunctivitis, Allergic, 224, 225, 243, 368 Connective Tissue Cells, 368 Consciousness, 348, 368, 372, 374 Constipation, 5, 35, 98, 249, 265, 268, 271, 368, 399, 421 Constitutional, 368, 434 Constriction, 8, 368, 399, 429, 450 Constriction, Pathologic, 368, 450 Consultation, 198, 327, 368, 381 Consumption, 368, 373, 385, 415, 434 Contact dermatitis, 18, 213, 368 Contamination, 65, 368, 390 Continence, 108, 278, 282, 327, 368 Continent Ileostomy, 18, 25, 282, 323, 327, 368 Contraceptive, 16, 369, 405 Contraindications, ii, 283, 324, 369 Control group, 42, 369, 431 Controlled clinical trial, 10, 369 Controlled study, 126, 156, 195, 369 Conventional therapy, 271, 284, 369 Conventional treatment, 369 Convulsions, 369, 376, 426 Coordination, 245, 369, 410 Cor, 103, 369 Cornea, 369, 437, 450 Corneal Ulcer, 230, 369 Coronary, 359, 369, 370, 407, 411, 446 Coronary Arteriosclerosis, 369, 411 Coronary heart disease, 359, 369 Coronary Thrombosis, 370, 407, 411 Corpus, 212, 370, 420, 427, 445 Corpus Luteum, 212, 370, 427 Cortex, 353, 370, 380, 416, 432

Cortical, 370, 381, 437, 445 Corticosteroid, 22, 34, 273, 283, 370, 426, 442 Cortisol, 346, 370 Cortisone, 370, 426 Cranial, 370, 380, 389, 398, 413, 416, 419, 421, 441 Craniocerebral Trauma, 354, 370, 389, 391, 445, 446 Crowding, 40, 370 Cryptosporidiosis, 310, 370 Culture Media, 65, 345, 370 Cultured cells, 50, 370 Curative, 15, 18, 25, 270, 271, 370, 414, 435, 445 Cutaneous, 57, 275, 281, 313, 349, 368, 370, 399, 403 Cycasin, 370, 407 Cyclic, 211, 225, 358, 370, 388, 414, 422, 428, 437 Cyclophosphamide, 130, 371 Cyclosporine, 12, 17, 19, 24, 115, 126, 129, 271, 297, 371 Cysteine, 52, 253, 362, 371, 378, 443 Cysteine Endopeptidases, 371, 378 Cystine, 52, 371 Cystitis, 141, 148, 371 Cytochrome, 371, 434 Cytochrome b, 371, 434 Cytomegalovirus, 12, 90, 99, 100, 105, 113, 129, 132, 161, 203, 253, 272, 310, 371, 384 Cytomegalovirus Infections, 371, 384 Cytoplasm, 247, 351, 355, 361, 371, 379, 388, 407, 435, 444 Cytosine, 104, 123, 294, 371 Cytoskeleton, 58, 71, 75, 83, 344, 371, 396, 408 Cytotoxic, 83, 371, 394, 397, 431, 439 Cytotoxicity, 162, 260, 346, 364, 371 D Databases, Bibliographic, 309, 372 Decarboxylation, 372, 390 Decidua, 372, 423 Decision Making, 272, 372 Defecation, 36, 174, 282, 327, 372, 427 Defense Mechanisms, 39, 372, 396 Degenerative, 68, 221, 229, 230, 372, 390, 404, 416, 434, 435 Dehydration, 26, 281, 363, 372 Deletion, 33, 51, 73, 77, 351, 372 Delusions, 372, 429

Index 461

Dementia, 224, 229, 243, 248, 249, 252, 253, 372 Demyelinating Diseases, 230, 372 Denaturation, 82, 372 Dendrites, 372, 413 Dendritic, 34, 35, 47, 53, 100, 372, 406 Dendritic cell, 34, 35, 47, 53, 100, 372 Density, 56, 79, 298, 361, 372, 383, 402, 416, 440 Dental Caries, 372, 373, 383 Dental Plaque, 209, 210, 373 Depersonalization, 373, 418, 436 Depolarization, 373, 439 Deprivation, 60, 373 Derealization, 373, 418 Dermal, 224, 225, 243, 373, 402 Dermatitis, 208, 211, 213, 214, 219, 225, 229, 234, 237, 249, 255, 373, 376 Dermatitis Herpetiformis, 208, 373 Dermatology, 41, 101, 124, 373 Dermatosis, 101, 117, 373 Descending Colon, 109, 279, 373 Desensitization, 49, 58, 75, 373 Detergents, 373, 382 Deuterium, 373, 391 Developed Countries, 8, 41, 52, 373 DHEA, 187, 373 Diabetes Mellitus, 34, 68, 211, 236, 271, 373, 374, 386, 389 Diabetic Retinopathy, 212, 230, 374, 423 Diagnostic procedure, 207, 296, 322, 374 Diarrhoea, 98, 374, 385 Diastolic, 374, 392 Diencephalon, 374, 392, 445 Dietary Fiber, 176, 178, 249, 374 Diffusion, 374, 395, 399, 414 Digestion, 124, 165, 178, 250, 265, 346, 355, 357, 374, 395, 398, 402, 418, 420, 442, 450 Digestive system, 206, 270, 328, 332, 374, 385, 409 Digestive tract, 299, 324, 330, 374, 440, 453 Dihydroxy, 212, 374 Dilatation, 272, 349, 374, 426, 430 Dilation, 214, 357, 374, 391 Dimethyl, 374, 403 Diosmin, 158, 374 Diploid, 374, 423 Direct, iii, 43, 66, 77, 85, 259, 301, 325, 364, 374, 375, 386, 425, 432, 443 Disinfectant, 374, 380 Disparity, 8, 374 Dissociation, 345, 374, 399

Distention, 8, 375 Diuresis, 358, 375 Diuretic, 233, 250, 375 Dizziness, 375, 418, 451 Docetaxel, 159, 160, 161, 375 Domesticated, 375, 388 Dopamine, 253, 365, 375, 422 Dosage Forms, 239, 375 Drive, ii, vi, 5, 7, 9, 10, 15, 21, 29, 40, 137, 138, 145, 375, 399 Drug Design, 59, 303, 304, 375 Drug Interactions, 303, 375 Drug Resistance, 60, 375 Drug Tolerance, 375, 446 Drug Toxicity, 13, 375 Duct, 218, 348, 360, 363, 376, 381, 417, 419, 436 Ductus Arteriosus, 376 Duodenal Ulcer, 73, 232, 376 Duodenitis, 22, 268, 376 Duodenum, 23, 233, 355, 364, 376, 378, 384, 399, 418, 442 Dura mater, 376, 406, 418 Dyes, 348, 355, 376, 383, 443 Dysentery, 60, 347, 376 Dyskinesia, 248, 249, 252, 376 Dyslexia, 248, 249, 252, 376 Dyspareunia, 322, 376 Dysplasia, 15, 24, 26, 39, 41, 69, 102, 107, 132, 142, 149, 163, 179, 264, 265, 314, 376 Dyspnea, 376, 418, 430 Dystonia, 248, 376 Dystrophy, 221, 253, 313, 376 E Eclampsia, 355, 376, 426 Ecosystem, 82, 376 Eczema, 213, 226, 237, 253, 376 Edema, 42, 57, 81, 368, 374, 376, 398, 411, 412, 426, 449 Educational Status, 8, 376 Effector, 29, 31, 33, 52, 53, 58, 71, 84, 131, 244, 253, 255, 343, 367, 376, 413, 422 Effector cell, 244, 376, 413 Effusion, 376, 404, 444 Eicosanoids, 28, 37, 54, 251, 376 Elasticity, 352, 369, 377, 439 Elastin, 228, 365, 377, 381 Elective, 7, 20, 272, 282, 377 Electroacupuncture, 163, 377 Electrocardiogram, 198, 377 Electrocoagulation, 365, 377

462 Colitis

Electrolyte, 51, 58, 281, 370, 377, 383, 408, 415, 425, 440, 449 Electrons, 350, 354, 377, 399, 417, 431 Electrophoresis, 82, 247, 377 Electroplating, 377, 443 Electroporation, 30, 377 Embolism, 97, 377 Embryo, 347, 356, 361, 377, 382, 395, 425, 449, 453 Emetic, 248, 377, 399 Emetine, 377, 399 Emollient, 377, 387, 415 Emphysema, 252, 364, 377 Empirical, 15, 377 Encapsulated, 35, 377 Encephalitis, 377, 378 Encephalomyelitis, 53, 244, 378 Endarterectomy, 349, 378 Endemic, 363, 378, 441 Endocrine System, 378, 413 Endocytosis, 75, 218, 360, 378 Endometrium, 212, 372, 378, 406 Endopeptidases, 230, 352, 360, 371, 378, 407, 420, 438 Endoscope, 40, 198, 378 Endoscopic, 11, 14, 17, 18, 20, 21, 24, 26, 40, 55, 102, 269, 275, 366, 378, 385, 439 Endoscopy, 5, 8, 9, 18, 100, 107, 109, 111, 116, 134, 135, 170, 176, 324, 378 Endothelial cell, 50, 76, 82, 87, 236, 378, 382, 398, 445 Endothelium, 50, 57, 78, 82, 87, 378, 414, 424 Endothelium, Lymphatic, 378 Endothelium, Vascular, 378 Endothelium-derived, 378, 414 Endotoxic, 221, 225, 226, 378, 402 Endotoxin, 241, 242, 259, 378, 448 End-stage renal, 364, 378, 425 Enema, 170, 196, 199, 200, 204, 290, 293, 318, 379 Energetic, 67, 379 Energy balance, 379, 401 Enkephalin, 49, 379 Enteral Nutrition, 111, 142, 143, 149, 151, 220, 276, 379 Enteric bacteria, 29, 55, 60, 66, 74, 379 Enteric Nervous System, 27, 65, 379 Enteritis, 42, 64, 142, 149, 159, 208, 265, 274, 328, 379 Enteropeptidase, 379, 448 Environmental Exposure, 379, 415

Environmental Health, 53, 308, 310, 379 Enzymatic, 359, 367, 372, 379, 390, 434 Enzyme Inhibitors, 379, 424 Eosinophil, 44, 74, 379, 388 Eosinophilic, 74, 104, 125, 142, 149, 215, 253, 379 Eosinophilic Gastroenteritis, 74, 215, 379 Epidemic, 379, 441 Epidemiological, 52, 121, 284, 379 Epidermal, 76, 105, 201, 293, 379, 400, 401, 406 Epidermis, 379, 400, 401, 430 Epigastric, 379, 418 Epinephrine, 345, 375, 380, 414, 449 Episcleritis, 380, 437 Epithelium, 18, 29, 33, 37, 39, 41, 43, 45, 58, 76, 79, 84, 239, 270, 354, 378, 380, 384, 434 Epitope, 71, 88, 380 Erythema, 19, 106, 183, 368, 380, 450 Erythema Nodosum, 19, 106, 380 Erythrocytes, 60, 348, 349, 357, 380, 418, 423, 432 Escalation, 34, 130, 380 Esophageal, 40, 63, 275, 380 Esophagitis, 203, 214, 215, 255, 268, 380 Esophagitis, Peptic, 214, 255, 380 Esophagus, 40, 45, 353, 374, 380, 385, 422, 432, 442, 450 Essential Tremor, 313, 380 Estrogen, 16, 17, 44, 380 Ethanol, 36, 247, 250, 380 Ethmoid, 380, 419 Eukaryotic Cells, 380, 395, 416 Evacuation, 368, 380, 384, 401 Evoke, 380, 442 Excitation, 40, 348, 362, 381, 383 Excitatory, 49, 354, 381, 387 Exocrine, 381, 418 Exocytosis, 52, 218, 245, 381 Exogenous, 42, 44, 47, 73, 77, 345, 376, 381 Exon, 6, 381 Expert Systems, 381, 393 Extensor, 381, 429 External-beam radiation, 381, 399, 431, 453 Extracellular Matrix, 52, 81, 93, 216, 225, 243, 368, 381, 382, 396, 405 Extracellular Matrix Proteins, 381, 405 Extracellular Space, 381 Extracorporeal, 106, 128, 381 Extraction, 63, 250, 351, 381, 434

Index 463

Extrapyramidal, 375, 381 F Faecal, 106, 131, 168, 171, 374, 381 Fallopian Tubes, 381, 450 Family Planning, 309, 381 Fascioliasis, 253, 381 Fatigue, 19, 261, 271, 298, 331, 382, 389 Febrile, 382, 441 Fecal Incontinence, 271, 382, 395 Feces, 8, 368, 381, 382, 442 Fertilizers, 382, 443 Fetal Membranes, 230, 382 Fetus, 218, 382, 423, 426, 449, 450 Fibrin, 356, 365, 382, 421, 424, 445, 446 Fibrinogen, 382, 423, 424, 445 Fibroblast Growth Factor, 121, 382 Fibroblasts, 44, 236, 368, 382, 397, 398 Fibronectin, 224, 382 Fibrosis, 48, 58, 80, 209, 210, 217, 218, 229, 234, 314, 346, 382, 430, 436, 437 Fibrositis, 253, 382 Fish Oils, 180, 382 Fistula, 9, 328, 382, 384 Flatulence, 276, 290, 382 Flatus, 382, 384 Flexor, 381, 383, 401 Flow Cytometry, 55, 68, 383 Fluid Therapy, 383, 415 Fluorescence, 40, 64, 107, 247, 383 Fluorescent Dyes, 383 Fluorine, 157, 383 Fluorouracil, 124, 161, 383 Folate, 24, 153, 163, 166, 172, 383 Fold, 40, 45, 53, 55, 61, 383, 407 Folic Acid, 153, 178, 179, 281, 383, 401 Foramen, 383, 421 Forearm, 357, 383 Fractionation, 383, 444 Frameshift, 67, 383, 449 Frameshift Mutation, 67, 383, 449 Fungi, 233, 350, 383, 384, 388, 398, 407, 408, 435, 436, 453 Fungistatic, 355, 384 Fungus, 217, 241, 362, 384 G Gallbladder, 103, 343, 355, 363, 374, 384, 385 Gallstones, 355, 362, 384, 450 Gamma Rays, 384, 431 Ganciclovir, 132, 203, 384 Ganglia, 49, 343, 354, 379, 384, 412, 421 Gangrenous, 141, 148, 384, 438

Gap Junctions, 384, 443, 444 Gas, 12, 265, 290, 347, 359, 374, 382, 383, 384, 391, 395, 396, 399, 404, 414, 450, 451 Gastric, 63, 71, 225, 226, 232, 233, 248, 274, 348, 353, 359, 375, 380, 384, 390, 399, 420 Gastric Acid, 233, 248, 348, 384 Gastric Emptying, 274, 384 Gastric Juices, 384, 420 Gastric Mucosa, 384, 399, 420 Gastrin, 384, 391 Gastritis, 73, 87, 89, 107, 179, 217, 232, 265, 384 Gastroduodenal, 275, 384 Gastroenteritis, 210, 384 Gastroenterologist, 20, 283, 385 Gastroscopy, 40, 385 Gastrostomy, 379, 385 Gelatin, 222, 370, 385, 387, 443, 445 Gelatinases, 230, 385 Gene Expression, 31, 37, 40, 56, 101, 140, 147, 178, 221, 231, 314, 385 General practitioner, 13, 385 Genetic Code, 385, 415 Genetic Engineering, 356, 365, 385, 432 Genetic Markers, 6, 385 Genetics, 33, 40, 46, 80, 112, 113, 325, 385, 408 Genital, 364, 385, 450 Genitourinary, 385, 450 Genotype, 385, 422 Germ Cells, 385, 406, 417, 440, 445, 453 Germfree, 82, 91, 385 Germ-free, 71, 385 Gestation, 107, 201, 386, 423 Gestational, 76, 86, 386 Gestational Age, 76, 86, 386 Giant Cells, 386, 436 Giardiasis, 274, 386, 407 Ginger, 179, 188, 386 Gland, 345, 370, 386, 403, 405, 418, 419, 423, 428, 437, 442, 446 Glioblastoma, 234, 386 Glomerular, 57, 230, 386, 433 Glomeruli, 386, 430 Glomerulonephritis, 87, 110, 386, 393, 403 Glomerulus, 386, 400, 412 Glottis, 386, 422 Glucocorticoid, 86, 115, 271, 358, 386, 391, 426 Glucose, 86, 99, 313, 352, 356, 361, 373, 386, 387, 389, 396, 436 Glucose Intolerance, 373, 386

464 Colitis

Glucuronic Acid, 386, 390 Glutamate, 387 Glutamic Acid, 203, 383, 387, 427 Glutamine, 110, 175, 188, 387 Glutathione Peroxidase, 78, 387, 437 Gluten, 274, 298, 361, 387 Glycerol, 42, 387, 422 Glycerophospholipids, 245, 387, 422 Glycine, 236, 355, 362, 387, 438 Glycogen, 237, 387 Glycoprotein, 216, 382, 386, 387, 388, 400, 404, 445, 448 Goblet Cells, 85, 387 Gonadal, 387, 442 Gout, 238, 387 Governing Board, 387, 426 Grade, 16, 67, 102, 107, 132, 387 Grading, 40, 387 Graft, 110, 225, 226, 229, 230, 234, 236, 256, 387, 388, 391, 394, 404, 410, 411 Graft Rejection, 229, 230, 387, 394, 404 Grafting, 388, 395 Graft-versus-host disease, 110, 388, 410 Gram-negative, 41, 225, 226, 358, 378, 388, 451 Gram-Negative Bacteria, 378, 388 Granule, 45, 236, 388, 435 Granulocyte Colony-Stimulating Factor, 366, 388 Granulocyte-Macrophage ColonyStimulating Factor, 366, 388 Granulocytes, 247, 366, 388, 401, 410, 439, 452 Granuloma, 110, 233, 388 Granulomatous Colitis, 55, 161, 267, 268, 291, 388 Granulomatous Disease, Chronic, 388, 434 Grasses, 383, 388 Growth factors, 37, 48, 253, 255, 388 Guanylate Cyclase, 388, 414 Guinea Pigs, 164, 388 H Habitat, 388, 414 Half-Life, 73, 389 Haploid, 389, 423 Haplotypes, 6, 389 Haptens, 345, 389 Headache, 248, 253, 276, 358, 389, 391 Headache Disorders, 389 Health Services, iv, 27, 46, 311, 389 Heart attack, 359, 389 Heart failure, 230, 389, 430

Heartbeat, 26, 389 Hematogenous, 244, 389 Hemoglobin, 19, 21, 276, 349, 380, 389, 401 Hemoglobinuria, 313, 389 Hemolytic, 41, 57, 73, 79, 80, 81, 83, 88, 90, 127, 132, 389 Hemorrhage, 19, 22, 26, 41, 68, 105, 277, 370, 377, 389, 411, 430, 442, 452 Hemorrhoids, 209, 210, 215, 263, 264, 265, 268, 389 Hemostasis, 389, 396, 438 Heparin, 24, 204, 271, 273, 390, 424 Hepatic, 259, 346, 377, 390, 407 Hepatitis, 90, 91, 111, 233, 236, 247, 286, 390 Hepatitis A, 91, 390 Hepatobiliary, 275, 390 Hepatocytes, 344, 390 Hepatovirus, 390 Hereditary, 81, 363, 387, 390, 413, 424, 434 Heredity, 328, 385, 390 Herpes, 111, 209, 390 Herpes Zoster, 390 Hesperidin, 158, 390 Heterodimers, 216, 390, 396 Heterogeneity, 345, 390 Heterogenic, 390 Heterogenous, 247, 390 Heterotrophic, 383, 390 Histamine, 112, 140, 147, 253, 348, 390, 400, 403 Histidine, 236, 390 Histology, 5, 37, 140, 147, 390 Homeostasis, 84, 86, 231, 257, 390 Homogeneous, 50, 247, 258, 259, 352, 390, 422 Homologous, 75, 81, 224, 346, 356, 390, 444 Hormonal, 353, 370, 391, 452 Host, 28, 30, 31, 33, 42, 43, 47, 49, 50, 54, 56, 60, 62, 64, 65, 66, 70, 79, 91, 110, 131, 214, 215, 225, 226, 233, 234, 236, 251, 254, 255, 256, 282, 285, 354, 360, 365, 366, 391, 393, 394, 401, 451 Housekeeping, 40, 391 Human Genome Project, 40, 315, 391 Humoral, 47, 64, 387, 391 Humour, 391 Hybrid, 365, 391 Hybridization, 79, 391, 408 Hybridoma, 71, 391 Hydration, 8, 391

Index 465

Hydrocephalus, 391, 398 Hydrocortisone, 15, 273, 285, 391 Hydrogen Peroxide, 35, 63, 360, 387, 391, 402 Hydrolysis, 251, 352, 364, 391, 399, 420, 422, 425, 428, 448 Hydrophilic, 253, 373, 391 Hydrophobic, 222, 253, 373, 387, 392, 402 Hydroxamic Acids, 229, 230, 392 Hydroxylysine, 366, 392 Hydroxyproline, 366, 392 Hygienic, 49, 392 Hyperaemia, 174, 368, 392 Hyperbaric, 93, 156, 168, 177, 180, 392 Hyperbaric oxygen, 93, 156, 168, 177, 180, 392 Hyperkinesia, 248, 249, 252, 392 Hyperplasia, 90, 100, 274, 392, 401 Hypersecretion, 248, 392 Hypertension, 17, 156, 184, 238, 248, 271, 352, 359, 392, 398, 426, 449 Hypertrophy, 231, 369, 392, 448 Hyperuricemia, 387, 392 Hypogammaglobulinemia, 274, 366, 392 Hypotension, 369, 392, 424 Hypotensive, 233, 392 Hypothalamic, 77, 392 Hypothalamus, 77, 374, 379, 392, 423, 440, 445 Hypoxanthine, 392, 452 Hypoxia, 69, 84, 163, 176, 392, 445 I Id, 152, 183, 328, 329, 338, 340, 392 Idarubicin, 104, 123, 294, 392 Idiopathic, 5, 12, 14, 16, 36, 52, 66, 223, 266, 269, 393, 430, 436 Ileitis, 195, 208, 265, 267, 268, 332, 393 Ileoanal Pull-Through, 263, 393 Ileoanal Reservoir, 108, 319, 393, 426 Ileostomy, 7, 9, 15, 18, 20, 22, 23, 25, 90, 268, 271, 275, 278, 282, 319, 323, 327, 328, 393, 412 Ileum, 9, 15, 69, 112, 239, 257, 282, 360, 393, 399 Ileus, 4, 393 Image Cytometry, 99, 393 Imidazole, 208, 365, 390, 393 Imipramine, 252, 393 Immaturity, 85, 393 Immune Complex Diseases, 350, 393, 423 Immune function, 6, 11, 32, 393, 394 Immune Sera, 393

Immunity, 33, 48, 50, 59, 67, 127, 131, 134, 393, 394, 397, 404, 415, 447 Immunization, 57, 320, 344, 393, 394 Immunoassay, 4, 86, 90, 239, 394 Immunoblotting, 247, 394 Immunodeficiency, 83, 88, 274, 313, 366, 392, 394 Immunodeficiency syndrome, 366, 394 Immunofluorescence, 247, 394 Immunogen, 256, 394 Immunogenic, 394, 402 Immunoglobulin, 4, 57, 274, 350, 394, 409 Immunohistochemistry, 51, 93, 394 Immunologic, 210, 344, 362, 386, 393, 394, 417, 431 Immunomodulator, 283, 394 Immunosuppressant, 343, 383, 394 Immunosuppressive Agents, 19, 22, 219, 220, 274, 280, 394, 437 Immunosuppressive therapy, 9, 11, 26, 100, 394 Immunotherapy, 344, 356, 373, 394 Immunotoxins, 394, 432 Impairment, 39, 298, 352, 376, 394, 406, 429 Implant radiation, 394, 398, 399, 431, 453 Implantation, 129, 213, 368, 395 In situ, 37, 51, 64, 162, 395 In Situ Hybridization, 38, 51, 64, 395 In vitro, 28, 31, 33, 36, 38, 39, 40, 43, 47, 52, 53, 61, 62, 65, 73, 86, 259, 395, 435, 444, 446 Incision, 365, 395, 398, 400 Incontinence, 253, 391, 395 Incubation, 395, 421 Incubation period, 395, 421 Indicative, 263, 395, 419, 450 Indigestion, 265, 395, 400 Indomethacin, 123, 395 Induction, 11, 12, 27, 34, 38, 41, 48, 77, 79, 85, 89, 104, 125, 138, 145, 203, 219, 272, 349, 395, 397 Infancy, 157, 395, 435 Infant, Newborn, 345, 395 Infarction, 391, 395, 433, 446 Infertility, 215, 218, 255, 395 Infiltration, 5, 10, 44, 67, 386, 395 Infusion, 34, 129, 396, 411, 447 Ingestion, 5, 57, 65, 164, 167, 249, 349, 396, 425 Initiation, 68, 76, 84, 280, 396, 447 Initiator, 396, 397

466 Colitis

Inlay, 396, 434 Inner ear, 11, 396, 450 Inorganic, 208, 364, 396, 409 Inositol, 245, 396, 437 Inotropic, 375, 396 Insight, 28, 33, 50, 54, 67, 75, 262, 396 Insufflation, 102, 106, 396 Insulator, 396, 410 Insulin, 48, 80, 86, 167, 229, 230, 396, 435 Insulin-dependent diabetes mellitus, 396 Insulin-like, 48, 80, 167, 396 Integrins, 71, 216, 225, 243, 396 Intensive Care, 62, 98, 177, 396, 397 Intensive Care Units, 62, 397 Interferon, 11, 12, 53, 89, 115, 198, 202, 219, 241, 259, 397 Interferon-alpha, 397 Interferon-beta, 53, 198, 397 Interleukin-1, 35, 70, 78, 89, 91, 109, 142, 149, 171, 180, 214, 232, 236, 238, 255, 259, 397 Interleukin-10, 78, 89, 91, 142, 149, 171, 180, 397 Interleukin-11, 214, 255, 397 Interleukin-12, 236, 259, 397 Interleukin-15, 232, 397 Interleukin-18, 109, 259, 397 Interleukin-2, 213, 397 Interleukin-3, 366, 397 Interleukin-6, 236, 397 Interleukin-8, 76, 89, 225, 245, 397 Interleukins, 255, 394, 398, 404 Intermittent, 11, 269, 383, 398 Internal radiation, 398, 399, 431, 453 Interneurons, 49, 398 Interstitial, 87, 141, 148, 270, 357, 381, 398, 399, 412, 433, 453 Intervention Studies, 57, 398 Intestinal Flora, 49, 80, 398 Intoxication, 398, 452 Intracranial Hypertension, 120, 389, 391, 398, 446 Intraepithelial, 27, 120, 398 Intramuscular, 398, 419 Intrathecal, 129, 398 Intravenous, 6, 8, 15, 17, 20, 22, 24, 118, 129, 169, 201, 203, 273, 274, 278, 396, 398, 419 Intrinsic, 56, 80, 81, 345, 354, 398 Invasive, 31, 33, 41, 52, 55, 60, 64, 90, 217, 241, 393, 398, 404

Involuntary, 354, 363, 380, 382, 398, 411, 432, 440 Ion Channels, 208, 398, 413, 444 Ion Transport, 61, 92, 398, 408 Ionization, 399 Ionizing, 270, 347, 379, 399, 431 Ions, 208, 354, 363, 374, 377, 391, 398, 399, 428 Ipecac, 167, 377, 399 Irradiation, 84, 168, 399, 453 Irritable Bowel Syndrome, 5, 128, 184, 239, 248, 264, 265, 269, 299, 326, 399 Irritants, 376, 399 Ischemia, 8, 19, 28, 157, 221, 353, 399, 411, 433 Ischemic Colitis, 8, 16, 17, 97, 118, 120, 133, 144, 151, 223, 399 Isozymes, 78, 399 J Jejunostomy, 379, 399 Jejunum, 239, 399 Jet lag, 248, 399 Joint, 100, 230, 290, 324, 352, 364, 383, 400, 416, 443, 444 K Kb, 53, 308, 400 Keratinocyte growth factor, 130, 400 Keratinocytes, 398, 400 Keratoconus, 230, 400 Ketotifen, 125, 400 Kidney Cortex, 400, 407 Kidney Disease, 195, 200, 201, 206, 308, 314, 320, 329, 400, 433 Kinetic, 399, 400 L Labile, 367, 400 Labyrinth, 365, 396, 400, 438, 451 Laceration, 400, 445 Lactation, 366, 400 Lactose Intolerance, 276, 400 Lag, 400 Laminin, 354, 381, 400 Laparotomy, 10, 45, 116, 129, 133, 400 Latency, 4, 400 Latent, 400, 426 Lavage, 99, 401 Laxative, 345, 362, 401 Least-Squares Analysis, 401, 433 Lectin, 119, 401, 406 Lens, 351, 360, 401, 433, 452 Leprosy, 209, 210, 401 Leptin, 77, 210, 401

Index 467

Lesion, 56, 227, 388, 401, 403, 409, 444, 449 Lethal, 31, 81, 84, 259, 313, 354, 401 Leucine, 401, 420 Leucocyte, 379, 401 Leucovorin, 124, 401 Leukapheresis, 198, 351, 401 Leukemia, 159, 219, 234, 236, 313, 343, 363, 401, 426 Leukocytes, 76, 84, 87, 214, 236, 355, 357, 362, 388, 395, 397, 398, 401, 418, 448 Leukocytosis, 16, 19, 401 Leukotrienes, 60, 170, 245, 251, 351, 352, 376, 401 Library Services, 338, 401 Lichen Planus, 136, 401 Life cycle, 384, 402 Ligament, 402, 428 Ligands, 143, 150, 224, 256, 361, 396, 402 Likelihood Functions, 402, 433 Lincomycin, 364, 402 Linear Models, 402, 433 Linkage, 46, 53, 66, 67, 385, 402 Linkage Disequilibrium, 46, 67, 402 Lipid, 28, 165, 169, 178, 231, 351, 352, 360, 387, 396, 402, 410, 418, 448 Lipid A, 28, 178, 402 Lipid Peroxidation, 165, 402, 418 Lipophilic, 251, 402 Lipopolysaccharide, 90, 236, 259, 388, 402 Lipoprotein, 79, 388, 402, 403 Lipoxygenase, 24, 212, 297, 351, 401, 402 Liver scan, 402, 436 Liver Transplantation, 63, 403 Local therapy, 222, 223, 403 Localization, 27, 39, 46, 51, 62, 79, 394, 403 Locomotion, 403, 423 Logistic Models, 403, 433 Loop, 245, 393, 403 Loperamide, 269, 281, 403 Loperamide hydrochloride, 269, 403 Low-density lipoprotein, 402, 403 Lumen, 12, 58, 218, 233, 378, 403 Lupus, 100, 210, 219, 256, 403, 444 Lupus Nephritis, 100, 403 Lymph, 90, 298, 364, 378, 391, 403, 436 Lymph node, 298, 403, 436 Lymphatic, 234, 378, 395, 403, 407, 424, 440, 441, 446 Lymphatic system, 403, 440, 441, 446 Lymphocyte, 32, 33, 65, 87, 216, 244, 350, 397, 403, 404, 405 Lymphocyte Subsets, 33, 404

Lymphocyte Transformation, 65, 404 Lymphocytic, 4, 14, 18, 112, 118, 119, 139, 142, 143, 146, 149, 150, 163, 269, 404 Lymphocytosis, 139, 146, 404 Lymphoid, 56, 100, 274, 350, 401, 404 Lymphokines, 255, 404 Lymphoma, 160, 232, 313, 404 Lysine, 392, 404, 426, 448 Lytic, 80, 404, 438 M Macrophage, 47, 52, 54, 256, 259, 366, 388, 397, 404 Macrophage Colony-Stimulating Factor, 366, 404 Macula, 404 Macula Lutea, 404 Macular Degeneration, 221, 230, 404 Magnetic Resonance Imaging, 404, 436 Maintenance therapy, 25, 26, 203, 271, 273, 281, 283, 284, 404 Major Histocompatibility Complex, 389, 404 Malabsorption, 184, 269, 270, 274, 313, 361, 404, 439 Malabsorption syndrome, 404, 439 Malaise, 238, 404 Malignancy, 15, 22, 55, 274, 404 Malignant, 110, 160, 313, 344, 350, 352, 386, 393, 404, 405, 410, 412, 431, 436 Malignant tumor, 405, 410 Malnutrition, 275, 278, 346, 353, 358, 405, 410 Mammary, 366, 405 Mania, 252, 405 Manic, 356, 405, 429 Manic-depressive psychosis, 405, 429 Manifest, 26, 219, 353, 405 Mannans, 384, 405 Mastitis, 405, 438 Mastocyte, 237, 405 Mastocytosis, 237, 405 Matrix metalloproteinase, 229, 230, 238, 405 Maxillary, 405, 419 Measles Virus, 100, 405 Meat, 57, 61, 357, 405 Medial, 352, 380, 405, 416, 441 Mediate, 38, 48, 52, 85, 238, 361, 375, 405 Mediator, 28, 48, 60, 69, 84, 134, 169, 194, 244, 259, 397, 405, 424, 438 Medical Records, 198, 405 Medicament, 259, 405, 443

468 Colitis

MEDLINE, 309, 312, 314, 405 Medroxyprogesterone, 215, 405 Medroxyprogesterone Acetate, 215, 405 Megacolon, 4, 8, 15, 19, 22, 98, 113, 262, 273, 277, 281, 283, 406 Megakaryocytes, 397, 406 Megaloblastic, 383, 406 Meiosis, 356, 406, 444 Melanin, 406, 422, 449 Melanocytes, 406 Melanoma, 313, 406 Membrane Proteins, 360, 406 Memory, 53, 211, 349, 372, 406 Meninges, 361, 370, 376, 406 Meningioma, 234, 406 Meningitis, 214, 224, 225, 243, 406 Menopause, 322, 406, 425 Menstrual Cycle, 406, 427 Menstruation, 322, 372, 406 Mental Disorders, 206, 251, 252, 406, 429 Mentors, 33, 44, 406 Mercaptopurine, 19, 22, 26, 271, 283, 406 Mercury, 13, 20, 383, 406 Mesenchymal, 81, 93, 388, 404, 407 Mesenteric, 90, 120, 231, 407 Mesentery, 407, 421 Meta-Analysis, 53, 407 Metabolic disorder, 387, 407 Metabolite, 233, 237, 374, 401, 407, 427 Metalloendopeptidases, 378, 407 Metallothionein, 140, 147, 164, 407 Metastasis, 216, 224, 225, 230, 243, 361, 405, 407 Metastatic, 160, 213, 407, 437 Methionine, 374, 407, 443 Methylazoxymethanol Acetate, 160, 407 Metronidazole, 4, 8, 189, 271, 302, 407 MI, 161, 225, 342, 407 Microbe, 407, 447 Microbiology, 30, 64, 65, 75, 80, 344, 353, 407 Microcirculation, 165, 407, 424 Microfilaments, 344, 407 Microorganism, 239, 365, 407, 419, 452 Micro-organism, 233, 372, 376, 385, 408, 438 Microscopy, 51, 79, 247, 354, 408 Microspheres, 35, 408 Microsporidiosis, 310, 408 Microtubules, 408, 418 Migration, 31, 47, 58, 71, 214, 224, 243, 408 Milk Thistle, 408, 439

Mineralocorticoids, 345, 370, 408 Mitochondria, 236, 408, 411, 416 Mitochondrial Swelling, 408, 412 Mitosis, 351, 408 Mitotic, 375, 408 Mitotic inhibitors, 375, 408 Mobility, 51, 408 Modeling, 40, 46, 375, 408 Modification, 47, 234, 385, 408, 431 Molecular mass, 245, 408 Molecular Probes, 377, 408 Molecule, 42, 54, 83, 101, 221, 224, 235, 350, 354, 365, 367, 374, 376, 378, 380, 381, 391, 401, 408, 409, 415, 417, 424, 431, 432, 439, 450 Monitor, 56, 198, 283, 326, 409, 414 Monoclonal, 34, 73, 175, 197, 202, 223, 258, 394, 399, 409, 431, 453 Monoclonal antibodies, 34, 73, 202, 258, 394, 409 Monocyte, 52, 76, 106, 110, 236, 404, 409 Monokines, 255, 409 Mononuclear, 29, 388, 404, 409, 448 Morbillivirus, 405, 409 Morphological, 172, 377, 384, 406, 409 Morphology, 32, 37, 244, 360, 409 Motility, 36, 274, 395, 409, 438 Motion Sickness, 409, 412 Motor Neurons, 49, 409 Mouth Ulcer, 19, 409 Mucins, 373, 387, 409, 436 Mucociliary, 409, 439 Mucosal Lining, 9, 25, 409 Mucosal Ulceration, 42, 409 Mucositis, 214, 217, 241, 255, 409 Mucus, 217, 241, 376, 409, 449 Multicenter study, 5, 135, 409 Multiple Myeloma, 224, 236, 243, 410 Multiple Organ Failure, 213, 233, 410 Muscarinic Agonists, 252, 410 Muscle Fibers, 410, 448 Muscular Atrophy, 313, 410 Muscular Dystrophies, 376, 410 Musculoskeletal Diseases, 74, 410 Mutagenesis, 67, 75, 410 Mutagenic, 61, 410, 414 Mutagens, 383, 410 Myalgia, 238, 410 Mycophenolate mofetil, 105, 410 Mydriatic, 374, 410 Myelin, 372, 410 Myelodysplastic syndrome, 68, 410, 440

Index 469

Myelogenous, 410 Myeloid Cells, 247, 410 Myeloma, 391, 410 Myenteric, 49, 410 Myocardial infarction, 215, 228, 255, 355, 370, 407, 410, 411 Myocardial Ischemia, 233, 411 Myocardial Reperfusion, 411, 433 Myocardial Reperfusion Injury, 411, 433 Myocarditis, 224, 225, 243, 411 Myocardium, 407, 410, 411 Myopia, 230, 411, 412, 432, 434 Myotonic Dystrophy, 313, 411 N Naive, 53, 411 Nasal Cavity, 217, 242, 411, 418 Nasal Obstruction, 217, 411 Nasal Septum, 411 Nasogastric, 379, 411 Natural killer cells, 397, 411 Nausea, 18, 248, 270, 276, 375, 385, 395, 412, 418, 429, 449 NCI, 1, 39, 205, 307, 364, 412 Nearsightedness, 411, 412 Neonatal, 45, 59, 62, 76, 84, 99, 102, 104, 123, 125, 164, 173, 180, 412 Neonatal period, 76, 412 Neoplasia, 24, 61, 99, 120, 214, 313, 412 Neoplasm, 412, 436, 449 Neoplastic, 20, 37, 95, 172, 193, 391, 404, 412, 436 Nephritis, 38, 87, 224, 225, 226, 233, 236, 243, 412 Nephropathy, 400, 412 Nephrosis, 412 Nephrotic, 113, 141, 148, 168, 412 Nephrotic Syndrome, 113, 141, 148, 168, 412 Nephrotoxic, 38, 412 Nerve Endings, 412, 444 Nerve Growth Factor, 412, 413 Nervous System, 27, 86, 229, 230, 252, 313, 343, 345, 348, 355, 358, 361, 365, 384, 386, 387, 401, 403, 405, 410, 412, 413, 416, 421, 438, 443, 444 Networks, 212, 393, 413 Neural, 49, 221, 345, 348, 391, 393, 413, 434 Neural Pathways, 49, 413 Neuralgia, 253, 413 Neurodegenerative Diseases, 221, 354, 413 Neuroendocrine, 65, 413 Neurogenic, 10, 413

Neurologic, 386, 391, 413 Neuromuscular, 343, 413, 449 Neuromuscular Junction, 343, 413 Neuronal, 48, 68, 77, 221, 236, 248, 413, 421 Neurons, 27, 49, 77, 365, 372, 381, 384, 398, 409, 412, 413, 414, 443, 444 Neuropathy, 253, 413, 421 Neuropeptide, 75, 413 Neuroretinitis, 413, 434 Neurotoxin, 407, 413 Neurotransmitters, 49, 253, 413 Neurotrophins, 48, 413 Neutralization, 85, 228, 413 Neutrons, 346, 399, 413, 431 Neutropenia, 413, 424 Neutrophil, 28, 31, 42, 43, 44, 54, 57, 128, 254, 294, 414 Neutrophil Activation, 294, 414 Neutrophil Infiltration, 42, 44, 414 Niacin, 414, 448 Niche, 39, 40, 414 Nicotine, 17, 24, 101, 103, 248, 251, 252, 271, 284, 414, 432 Nitric Oxide, 69, 73, 118, 124, 165, 177, 238, 414 Nitrogen, 61, 211, 254, 346, 347, 349, 371, 381, 387, 408, 414, 418, 448 Nitrosamines, 414 Nitrosation, 61, 414 Norepinephrine, 65, 345, 375, 414 Nosocomial, 4, 414 Nuclear, 11, 54, 61, 67, 155, 157, 221, 231, 246, 354, 377, 380, 384, 386, 412, 414 Nuclear Proteins, 221, 414 Nuclei, 40, 77, 221, 346, 377, 385, 404, 408, 413, 415, 416, 429 Nucleic acid, 209, 235, 242, 244, 254, 343, 354, 371, 385, 391, 392, 395, 410, 414, 415, 430 Nucleic Acid Hybridization, 391, 415 Nucleoproteins, 414, 415 Nucleus, 351, 354, 355, 363, 370, 371, 373, 380, 384, 406, 409, 413, 414, 415, 427, 429, 442, 445 Nursing Care, 415, 420 Nutritional Status, 6, 281, 324, 415 Nutritional Support, 220, 275, 385, 415 O Observational study, 118, 415 Ocular, 214, 230, 237, 255, 275, 415 Odds Ratio, 415, 433

470 Colitis

Odour, 352, 415, 449 Office Visits, 295, 415 Ointments, 375, 415, 440 Omega-3 fatty acid, 28, 160, 415 Oncogene, 313, 415 Oncogenic, 245, 396, 415, 429 Oncologist, 415 Oncology, 125, 161, 167, 173, 179, 270, 416 Opacity, 360, 372, 416 Operon, 80, 416, 433 Opportunistic Infections, 310, 416 Opsin, 416, 434 Optic Chiasm, 392, 416 Optic Disk, 374, 404, 416 Optic Nerve, 413, 416, 418, 429, 434, 437 Organ Culture, 416, 446 Organ Transplantation, 224, 225, 243, 416 Organelles, 361, 371, 406, 416 Osmotic, 346, 408, 416 Ossification, 416, 435 Osteoarthritis, 215, 221, 229, 230, 232, 235, 238, 255, 416 Osteomyelitis, 256, 416 Osteoporosis, 125, 211, 215, 221, 236, 255, 257, 322, 416 Ostomy, 24, 108, 263, 417, 427 Otitis, 217, 241, 417 Otitis Media, 217, 241, 417 Outpatient, 126, 417 Ovalbumin, 71, 139, 146, 417 Ovarian Cysts, 119, 417 Ovarian Follicle, 370, 417 Ovaries, 381, 417, 450 Ovary, 224, 254, 370, 417, 425 Overdose, 141, 148, 417 Overexpress, 81, 417 Ovum, 370, 372, 386, 402, 417, 427, 453 Oxazolone, 74, 127, 174, 417 Oxidants, 39, 52, 66, 417 Oxidation, 61, 79, 343, 350, 351, 371, 387, 402, 417, 418 Oxidation-Reduction, 417 Oxidative metabolism, 401, 417 Oxidative Stress, 164, 417 P P53 gene, 41, 418 Pachymeningitis, 406, 418 Paclitaxel, 170, 171, 176, 418 Palliative, 9, 418, 445 Pallor, 19, 418 Palsy, 248, 418

Pancreas, 218, 343, 364, 374, 385, 396, 418, 440, 448 Pancreatic, 218, 234, 275, 313, 359, 364, 418 Pancreatic cancer, 234, 313, 418 Pancreatic Ducts, 218, 418 Pancreatic Insufficiency, 218, 418 Pancreatic Juice, 218, 364, 418 Pancreatitis, 18, 94, 127, 215, 217, 255, 418 Pancytopenia, 96, 418 Panic, 248, 393, 418, 438 Panic Disorder, 248, 393, 418, 438 Paralysis, 418, 441 Paranasal Sinuses, 217, 242, 418, 439 Parasite, 19, 60, 419, 448 Parasitic, 49, 209, 370, 376, 419 Parathyroid, 419, 435 Parathyroid Glands, 419, 435 Paratuberculosis, 64, 419 Parenteral, 12, 15, 168, 210, 272, 273, 419 Parenteral Nutrition, 12, 15, 210, 272, 273, 419 Paresthesias, 418, 419 Parotid, 419, 436 Paroxysmal, 313, 389, 419, 421, 452 Partial remission, 419, 433 Particle, 78, 419, 440, 447 Patch, 36, 252, 284, 419, 447 Patent ductus arteriosus, 123, 419 Pathogen, 7, 30, 34, 43, 57, 65, 73, 82, 89, 91, 205, 215, 233, 395, 419 Pathologic, 29, 55, 57, 84, 157, 268, 276, 298, 351, 356, 369, 392, 419, 425, 429 Pathologic Processes, 351, 419 Pathologies, 83, 224, 225, 242, 243, 419 Pathophysiology, 7, 16, 59, 119, 169, 262, 419 Patient Advocacy, 330, 332, 420 Patient Care Management, 8, 420 Patient Compliance, 273, 279, 420 Patient Education, 6, 289, 321, 327, 336, 338, 342, 420 Patient Satisfaction, 108, 323, 420 Pediatric Gastroenterologist, 43, 59, 280, 420 Pelvic, 7, 20, 271, 281, 323, 420, 428 Pelvic inflammatory disease, 271, 420 Penicillin, 189, 348, 349, 420 Penis, 420, 450 Pepsin, 250, 420 Pepsin A, 250, 420 Peptic, 72, 184, 215, 255, 420 Peptic Ulcer, 72, 184, 215, 255, 420

Index 471

Peptide, 28, 71, 75, 104, 109, 130, 216, 222, 223, 235, 250, 251, 259, 366, 378, 379, 382, 385, 401, 420, 425, 426, 428, 448 Peptide Fragments, 216, 420 Peptide Hydrolases, 378, 420 Peptide T, 420, 448 Perception, 86, 93, 275, 368, 373, 420, 436 Perforation, 9, 19, 22, 93, 98, 108, 116, 122, 123, 131, 272, 281, 327, 383, 420, 452 Perfusion, 392, 421, 446 Pericardium, 421, 444 Perineal, 271, 421 Perineum, 421 Periodontal disease, 68, 230, 238, 421 Periodontitis, 214, 233, 255, 421 Peripheral blood, 29, 31, 64, 268, 397, 421, 426 Peripheral Nerves, 401, 421 Peripheral Nervous System, 372, 413, 418, 421, 440, 443 Peripheral Neuropathy, 253, 421 Peristalsis, 233, 421 Peritoneal, 45, 233, 421 Peritoneal Cavity, 233, 421 Peritoneum, 407, 421 Peritonitis, 100, 131, 184, 421, 452 Periventricular Leukomalacia, 68, 421 Pertussis, 86, 421, 452 Phagocyte, 404, 417, 422 Phagocytosis, 60, 64, 422 Pharmaceutical Preparations, 361, 380, 385, 422 Pharmaceutical Solutions, 375, 422 Pharmacokinetic, 67, 144, 151, 203, 422 Pharmacologic, 61, 174, 349, 353, 389, 422, 446, 447 Pharmacotherapy, 178, 223, 422 Pharyngitis, 214, 255, 422 Pharynx, 411, 422 Phenotype, 33, 35, 47, 52, 86, 422 Phenylalanine, 420, 422, 449 Phosphodiesterase, 211, 229, 253, 422 Phospholipases, 244, 422, 439 Phospholipases A, 245, 422 Phospholipids, 220, 245, 251, 382, 396, 402, 422 Phosphorus, 359, 419, 422, 423 Phosphorylated, 245, 365, 423 Phosphorylation, 75, 423 Photocoagulation, 365, 423 Phycocyanin, 138, 145, 423

Physical Examination, 19, 26, 197, 198, 275, 386, 423 Physiologic, 62, 276, 279, 282, 346, 356, 389, 406, 423, 427, 432 Physiology, 27, 44, 48, 51, 62, 71, 80, 122, 162, 166, 263, 385, 423, 451 Phytohemagglutinins, 404, 423 Pigment, 355, 406, 423, 434 Pilot study, 12, 63, 72, 114, 142, 149, 158, 169, 181, 200, 423 Pituitary Gland, 370, 382, 423 Placenta, 212, 423, 427, 449 Plana, 423, 438 Plant Diseases, 379, 423 Plants, 245, 346, 357, 359, 364, 365, 386, 401, 409, 414, 423, 425, 436, 447 Plaque, 230, 349, 423 Plasma cells, 350, 410, 423 Plasma Exchange, 107, 423 Plasma protein, 118, 214, 346, 378, 423, 428 Plasmapheresis, 351, 424 Plasmids, 81, 377, 424 Plasmin, 81, 424 Plasminogen, 424 Plasminogen Activators, 424 Platelet Activating Factor, 84, 424 Platelet Activation, 424, 439 Platelet Aggregation, 233, 237, 348, 414, 424, 445, 446 Platelet Factor 4, 398, 424 Plateletpheresis, 351, 424 Platelets, 351, 355, 414, 418, 424, 446 Platinum, 364, 403, 424 Plexus, 49, 424 Poisoning, 183, 375, 385, 398, 407, 412, 425 Pollen, 64, 425 Polycystic, 314, 425 Polymerase, 6, 221, 425, 433 Polyp, 217, 425 Polypeptide, 224, 240, 244, 347, 359, 365, 382, 391, 420, 424, 425, 426, 428, 440, 453 Polyposis, 37, 109, 217, 344, 366, 425 Polysaccharide, 249, 350, 361, 425, 428 Polyunsaturated fat, 28, 161, 162, 164, 165, 180, 425, 446 Posterior, 348, 353, 363, 418, 425, 436, 441 Postmenopausal, 416, 425 Postoperative, 15, 22, 116, 410, 425 Postoperative Complications, 15, 22, 425 Postsynaptic, 425, 439, 443, 444 Post-synaptic, 425, 444 Potassium, 208, 408, 425, 440

472 Colitis

Potentiate, 44, 89, 397, 425 Potentiating, 58, 425 Potentiation, 58, 425, 439 Practice Guidelines, 16, 21, 311, 328, 425 Precancerous, 20, 40, 362, 426 Precipitating Factors, 8, 389, 426 Preclinical, 83, 426 Predisposition, 50, 426 Prednisolone, 11, 14, 99, 114, 126, 273, 426 Prednisone, 17, 22, 130, 299, 426 Preeclampsia, 215, 255, 426 Pregnancy Tests, 386, 426 Preleukemia, 410, 426, 440 Premalignant, 426 Prenatal, 68, 85, 123, 377, 426 Presynaptic, 412, 426, 443, 444 Prevalence, 4, 8, 46, 52, 66, 128, 181, 258, 274, 326, 415, 426 Probe, 40, 87, 426 Procollagen, 104, 426 Proctocolectomy, 7, 10, 20, 22, 23, 25, 104, 110, 116, 118, 119, 129, 130, 220, 271, 275, 278, 282, 291, 327, 328, 426 Proctocolectomy, Restorative, 20, 426 Proctocolitis, 111, 129, 162, 328, 427 Proctosigmoiditis, 26, 285, 427 Proctosigmoidoscopy, 19, 21, 197, 427 Prodrug, 140, 147, 427 Progesterone, 215, 427, 442 Prognostic factor, 4, 12, 427 Progression, 41, 63, 66, 67, 80, 161, 193, 216, 230, 256, 349, 427 Progressive, 63, 91, 248, 352, 361, 364, 369, 372, 375, 380, 388, 410, 411, 412, 413, 416, 424, 427, 430, 433, 449 Projection, 372, 398, 414, 416, 427, 432 Proline, 243, 365, 392, 426, 427 Promoter, 34, 38, 51, 109, 427, 432 Prone, 290, 427 Prophase, 356, 427, 444 Prophylaxis, 11, 178, 233, 427 Proportional, 44, 427 Prospective study, 82, 129, 427 Prostaglandin, 92, 233, 236, 237, 427, 445 Prostaglandins A, 60, 245, 395, 427, 428 Prostaglandins D, 428 Prostate, 234, 235, 254, 313, 428, 448, 450 Protease, 81, 105, 236, 250, 254, 366, 428 Protein C, 33, 44, 51, 253, 346, 347, 351, 354, 402, 428, 448 Protein Conformation, 347, 428

Protein S, 79, 210, 241, 242, 253, 254, 268, 314, 356, 377, 385, 407, 428, 435 Protein Subunits, 241, 242, 428 Proteins, 30, 31, 38, 39, 43, 45, 58, 64, 71, 76, 79, 82, 86, 107, 131, 139, 146, 202, 208, 209, 216, 235, 236, 245, 247, 253, 254, 276, 344, 347, 348, 350, 351, 352, 356, 357, 360, 361, 363, 365, 367, 371, 377, 381, 384, 390, 391, 397, 405, 406, 409, 414, 415, 420, 423, 428, 429, 431, 432, 438, 445, 447, 451 Proteinuria, 230, 410, 412, 426, 428 Proteoglycans, 228, 354, 381, 428 Proteolytic, 81, 367, 379, 382, 424, 428 Prothrombin, 428, 445 Protocol, 5, 197, 428 Protons, 346, 391, 399, 429, 431 Proto-Oncogene Proteins, 418, 429 Proto-Oncogene Proteins c-mos, 418, 429 Protozoa, 376, 408, 429 Protozoal, 310, 429 Proximal, 14, 218, 220, 279, 285, 298, 375, 400, 411, 426, 429 Proxy, 167, 429 Pruritic, 373, 376, 401, 429 Pseudomembranous Colitis, 4, 7, 30, 91, 96, 100, 106, 109, 131, 157, 228, 429 Pseudotumor Cerebri, 398, 429 Psychiatric, 327, 406, 429 Psychiatry, 100, 121, 429, 451 Psychosis, 248, 249, 253, 386, 429 Psychotherapy, 266, 430, 432 Psychotropic, 42, 430 Psyllium, 190, 430 Public Policy, 309, 430 Publishing, 18, 19, 21, 25, 26, 88, 263, 286, 430 Pulmonary Artery, 356, 376, 419, 430, 451 Pulmonary Emphysema, 228, 254, 430 Pulmonary Fibrosis, 224, 243, 256, 430 Pulmonary hypertension, 369, 430 Pulse, 101, 409, 430 Pupil, 369, 374, 410, 430 Purifying, 258, 373, 430 Purines, 354, 430, 438, 452 Purpura, 107, 208, 430 Purulent, 343, 430 Pyelonephritis, 87, 430 Pyoderma, 176, 248, 430 Pyoderma Gangrenosum, 248, 430 Pyogenic, 416, 430, 438

Index 473

Q Quiescent, 10, 82, 120, 431 Quinoxaline, 225, 431 R Race, 408, 431 Radiation oncologist, 270, 415, 431 Radiation therapy, 270, 381, 383, 392, 398, 399, 431, 436, 453 Radioactive, 357, 389, 391, 394, 395, 398, 399, 402, 408, 409, 414, 415, 431, 436, 453 Radiography, 19, 272, 318, 386, 431 Radiolabeled, 357, 399, 431, 453 Radiological, 20, 138, 145, 262, 291, 318, 431 Radiology, 138, 144, 145, 151, 318, 431 Radiotherapy, 357, 399, 431, 453 Random Allocation, 431 Randomization, 11, 431 Reactive Oxygen Species, 215, 431 Reagent, 373, 432, 448 Reality Testing, 429, 432 Reassurance, 290, 432 Receptors, Muscarinic, 410, 432 Receptors, Serotonin, 432, 438 Recombinant, 29, 38, 54, 70, 71, 73, 214, 255, 259, 432, 450 Recombinant Fusion Proteins, 71, 432 Recombination, 385, 432 Recurrence, 10, 11, 171, 278, 321, 356, 405, 432 Red blood cells, 276, 380, 389, 432, 436 Red Nucleus, 353, 432 Refer, 1, 358, 367, 375, 384, 390, 398, 403, 404, 411, 413, 414, 429, 432 Reflective, 218, 432 Reflex, 48, 74, 253, 432 Reflux, 380, 432 Refraction, 411, 432, 441 Refractive Power, 411, 433 Regeneration, 382, 433 Regimen, 6, 17, 22, 376, 420, 422, 433, 435 Regional enteritis, 239, 265, 290, 433 Regression Analysis, 69, 433 Relapse, 11, 19, 30, 60, 100, 125, 173, 213, 252, 273, 282, 283, 295, 327, 433 Relative risk, 10, 53, 433 Renal failure, 221, 433 Renal Osteodystrophy, 257, 433 Reperfusion, 28, 214, 215, 221, 225, 226, 230, 237, 255, 411, 433 Reperfusion Injury, 28, 214, 215, 221, 225, 226, 230, 255, 433

Repressor, 416, 433 Resected, 18, 35, 433 Resection, 8, 9, 18, 22, 76, 210, 275, 278, 433, 439 Resolving, 106, 433 Respiration, 359, 362, 382, 409, 417, 434 Respiratory Burst, 245, 434 Respiratory distress syndrome, 225, 228, 358, 434 Response rate, 12, 15, 434 Restitution, 56, 58, 71, 434 Restoration, 47, 411, 433, 434, 452 Retina, 363, 364, 374, 401, 404, 411, 413, 416, 434, 435, 438, 450, 452 Retinal, 221, 237, 368, 374, 416, 434, 452 Retinal Detachment, 237, 374, 434 Retinitis, 214, 224, 225, 243, 255, 434, 435 Retinoblastoma, 313, 434 Retinol, 434 Retinopathy, 230, 374, 435 Retreatment, 4, 91, 435 Retrospective, 4, 6, 269, 435 Reversion, 435, 449 Rheumatic Diseases, 104, 117, 214, 253, 298, 435 Rheumatism, 435 Rhinitis, 215, 224, 225, 234, 243, 253, 255, 358, 400, 435, 438 Ribose, 67, 221, 344, 435 Ribosome, 435, 447 Rickets, 257, 435, 452 Rigidity, 423, 435 Risk factor, 41, 44, 46, 76, 84, 107, 113, 271, 403, 427, 433, 435 Risk patient, 24, 435 Ristocetin, 435, 450 Rod, 354, 364, 435 Rodentia, 74, 435 Rosiglitazone, 195, 435 Rotator, 86, 435 S Saccharomyces, 5, 93, 156, 175, 177, 178, 181, 238, 239, 250, 435, 436, 453 Saccharomyces cerevisiae, 177, 238, 239, 436, 453 Saccharomycetales, 436 Salicylate, 14, 436 Saline, 249, 423, 436 Saliva, 77, 436 Salivary, 76, 371, 373, 374, 418, 436 Salivary glands, 371, 373, 374, 436 Salvage Therapy, 115, 436

474 Colitis

Saponins, 436, 442 Sarcoidosis, 64, 256, 436 Sarcoma, 234, 236, 436 Scans, 53, 217, 436 Schizoid, 436, 452 Schizophrenia, 248, 249, 252, 436, 452 Schizotypal Personality Disorder, 373, 436, 452 Sclera, 363, 368, 380, 436, 437, 450 Scleritis, 208, 437 Scleroderma, 208, 253, 352, 437 Sclerosis, 12, 42, 53, 68, 198, 210, 211, 215, 219, 224, 225, 229, 230, 232, 234, 236, 243, 244, 248, 249, 253, 255, 256, 313, 352, 366, 410, 437 Screening, 9, 10, 24, 45, 46, 55, 68, 197, 208, 240, 364, 437 Second Messenger Systems, 413, 437 Secondary tumor, 407, 437 Secretory, 27, 58, 218, 245, 437, 443, 444 Sedative, 198, 393, 437 Sedatives, Barbiturate, 354, 437 Segmental, 268, 275, 437 Segmentation, 437 Seizures, 350, 386, 419, 437 Selenium, 78, 437 Semen, 428, 438 Semicircular canal, 396, 438 Seminal vesicles, 438, 450 Semisynthetic, 347, 364, 394, 438 Senescence, 221, 438 Senile, 248, 249, 252, 417, 438 Senna, 190, 438 Sepsis, 16, 20, 98, 106, 175, 205, 211, 225, 226, 229, 230, 234, 236, 438 Septic, 213, 221, 224, 225, 226, 229, 230, 238, 243, 277, 352, 438 Septicaemia, 131, 438 Sequencing, 53, 82, 102, 438 Serine, 52, 81, 236, 254, 364, 378, 429, 438, 448 Serine Endopeptidases, 378, 438 Serologic, 133, 394, 438 Serotonin, 252, 253, 345, 422, 432, 438, 448 Serotonin Uptake Inhibitors, 252, 438 Serotypes, 31, 438 Serous, 366, 378, 438 Serrata, 140, 147, 164, 186, 364, 438 Serrated, 438 Sex Determination, 314, 439 Shock, 8, 39, 64, 213, 221, 225, 226, 229, 230, 237, 238, 260, 348, 391, 439, 448

Short Bowel Syndrome, 210, 275, 439 Side effect, 5, 11, 18, 19, 22, 24, 25, 26, 199, 220, 227, 235, 249, 250, 257, 273, 276, 284, 285, 301, 304, 326, 345, 356, 371, 392, 439, 443, 447 Sigmoid, 35, 279, 285, 427, 439 Sigmoid Colon, 35, 285, 427, 439 Sigmoidoscope, 427, 439 Sigmoidoscopy, 17, 19, 21, 195, 196, 239, 272, 299, 318, 342, 439 Signal Transduction, 36, 70, 79, 84, 245, 253, 360, 396, 439 Signs and Symptoms, 10, 95, 433, 439, 449 Silymarin, 141, 148, 165, 408, 439 Sinusitis, 217, 439 Skeletal, 221, 349, 364, 410, 439, 448 Skeleton, 343, 400, 427, 439, 440 Skin Aging, 221, 230, 439 Skull, 370, 440, 445 Small cell lung cancer, 166, 440 Smoldering leukemia, 410, 440 Smooth muscle, 47, 49, 346, 348, 353, 358, 368, 390, 410, 440, 443 Sneezing, 421, 440 Soaps, 382, 440 Social Environment, 431, 440 Soft tissue, 357, 439, 440 Solid tumor, 82, 230, 349, 440 Solvent, 355, 380, 387, 416, 422, 440 Soma, 440 Somatic, 253, 391, 406, 408, 421, 440 Somatostatin, 49, 440 Sound wave, 432, 440 Soybean Oil, 425, 440 Spasmodic, 343, 422, 440 Spastic, 248, 399, 440 Spasticity, 354, 440, 441 Specialist, 13, 332, 374, 441 Specificity, 4, 33, 69, 244, 345, 351, 358, 378, 426, 441, 446 Spectrum, 16, 32, 41, 265, 274, 276, 285, 290, 365, 441 Sperm, 349, 363, 425, 441 Sphenoid, 419, 441 Sphincters, 282, 382, 441 Spinal cord, 198, 352, 354, 361, 362, 363, 376, 378, 379, 398, 406, 412, 413, 418, 421, 432, 441 Spleen, 259, 348, 371, 391, 403, 436, 441 Sporadic, 37, 41, 94, 132, 413, 434, 441 Sprue, 87, 139, 146, 248, 268, 274, 298, 441 Staging, 436, 441

Index 475

Standard therapy, 53, 284, 441 Statistically significant, 11, 441 Steatorrhea, 5, 269, 441 Steel, 364, 441 Stem Cells, 346, 388, 441 Stent, 417, 441 Sterile, 352, 419, 442 Sterility, 371, 395, 442 Steroid therapy, 11, 22, 126, 201, 276, 442 Stimulant, 259, 358, 390, 442 Stimulus, 215, 254, 375, 376, 381, 398, 400, 419, 432, 442, 445 Stoma, 18, 290, 417, 442 Stool test, 198, 324, 442 Strand, 208, 221, 425, 442 Streptococci, 283, 442 Stricture, 16, 442 Stroke, 206, 221, 224, 225, 226, 243, 248, 308, 359, 442 Stromal, 109, 442 Structure-Activity Relationship, 432, 442 Subacute, 395, 439, 442 Subarachnoid, 389, 442 Subclinical, 68, 395, 437, 442 Subcutaneous, 344, 376, 384, 419, 442 Subspecies, 441, 442 Substance P, 75, 250, 253, 407, 435, 437, 443 Substrate, 221, 245, 379, 443 Sulfur, 153, 249, 254, 373, 381, 407, 443 Sulfuric acid, 249, 443 Superoxide, 66, 434, 443 Support group, 286, 287, 322, 324, 330, 332, 443 Supportive care, 57, 80, 443 Suppositories, 279, 324, 385, 443 Suppression, 36, 76, 82, 86, 179, 224, 243, 253, 323, 370, 443 Suppressive, 39, 144, 151, 219, 233, 443 Suppurative, 10, 384, 443 Supraspinal, 354, 443 Surfactant, 218, 443 Sympathomimetic, 375, 380, 414, 443 Symphysis, 428, 443 Symptomatic, 5, 9, 15, 232, 269, 350, 418, 443 Symptomatic treatment, 5, 232, 350, 443 Synapses, 413, 443 Synapsis, 444 Synaptic, 49, 208, 414, 438, 439, 443, 444 Synaptic Transmission, 208, 414, 444 Synaptosomes, 49, 444

Synergistic, 48, 226, 245, 246, 444 Synovial, 232, 444 Synovial Membrane, 444 Synovitis, 238, 444 Systemic, 26, 27, 42, 48, 107, 196, 214, 219, 233, 234, 237, 244, 247, 253, 256, 271, 275, 276, 284, 285, 302, 348, 351, 357, 366, 380, 393, 395, 398, 399, 403, 424, 426, 431, 436, 437, 444, 447, 448, 453 Systemic disease, 275, 444 Systemic lupus erythematosus, 214, 234, 244, 253, 366, 393, 403, 444 Systolic, 392, 444 T Tachycardia, 19, 26, 444 Tacrolimus, 12, 103, 295, 444 Tardive, 248, 249, 252, 444 Taurine, 355, 362, 444 Telangiectasia, 314, 444 Temporal, 28, 389, 404, 444 Tenesmus, 17, 19, 21, 26, 271, 274, 285, 376, 445 Testicular, 142, 149, 173, 445 Testis, 445 Tetani, 445 Tetanic, 445 Tetanus, 81, 445 Tetrahydrocannabinol, 359, 445 Thalamic, 353, 445 Thalamic Diseases, 353, 445 Third Ventricle, 392, 445 Thorax, 343, 445 Threonine, 420, 429, 438, 445 Threshold, 392, 445 Thrombin, 253, 382, 424, 428, 445 Thrombocytopenia, 424, 445 Thrombomodulin, 428, 445 Thrombosis, 225, 226, 355, 396, 428, 442, 445 Thromboxanes, 352, 376, 445 Thrombus, 86, 370, 395, 411, 424, 446, 451 Thymoma, 110, 446 Thymus, 224, 394, 403, 446 Thyroid, 219, 419, 446, 449 Thyroid Gland, 419, 446 Thyroiditis, 68, 446 Thyroxine, 346, 422, 446 Ticlopidine, 142, 149, 446 Tin, 421, 424, 446 Tinnitus, 417, 429, 446 Tissue Culture, 8, 84, 88, 446 Tissue Distribution, 358, 446

476 Colitis

Titre, 4, 446 Tolerance, 143, 151, 208, 344, 386, 446 Tonicity, 376, 447 Tooth Preparation, 344, 447 Toxaemia, 426, 447 Toxicity, 9, 17, 24, 50, 67, 122, 221, 271, 375, 393, 407, 435, 447 Toxicology, 67, 310, 447 Toxins, 4, 42, 50, 57, 71, 79, 81, 90, 91, 214, 350, 377, 387, 394, 395, 409, 432, 447 Trace element, 14, 140, 147, 164, 383, 446, 447 Trachea, 357, 358, 422, 446, 447 Traction, 364, 447 Transcription Factors, 29, 38, 54, 231, 447 Transdermal, 17, 24, 101, 103, 284, 447 Transduction, 36, 78, 79, 253, 439, 447 Transfection, 87, 356, 377, 447 Transfer Factor, 394, 447 Transfusion, 273, 447 Transgenes, 78, 447 Translation, 32, 79, 432, 447 Translational, 40, 447 Translocation, 67, 447 Transmitter, 343, 375, 398, 405, 414, 443, 447 Transplantation, 63, 105, 221, 364, 394, 404, 448 Trauma, 98, 214, 221, 344, 380, 412, 418, 448 Treatment Failure, 273, 448 Triad, 236, 448 Trichomoniasis, 407, 448 Tricuspid Atresia, 369, 448 Tricyclic, 345, 393, 448 Trigger zone, 399, 448 Triglyceride, 142, 149, 448 Trinitrobenzenesulfonic Acid, 140, 147, 448 Trophic, 49, 448 Tropomyosin, 29, 258, 448 Troponin, 448 Trypsin, 209, 364, 379, 448 Tryptophan, 62, 366, 438, 448 Tuberculosis, 64, 238, 368, 403, 448 Tuberous Sclerosis, 314, 448 Tumor marker, 344, 448 Tumor Necrosis Factor, 12, 24, 60, 70, 88, 96, 219, 236, 238, 240, 242, 448 Tumor suppressor gene, 418, 449 Tumour, 175, 211, 449 Typhimurium, 29, 31, 88, 91, 131, 236, 449

Typhoid fever, 131, 449 Tyrosine, 69, 219, 375, 449 U Ulcer, 179, 225, 226, 232, 239, 249, 376, 420, 449 Ulceration, 8, 12, 21, 60, 87, 325, 331, 409, 449 Ultrasonography, 386, 449 Umbilical Arteries, 449 Umbilical Cord, 50, 346, 449 Unconscious, 349, 372, 392, 449 Unsaturated Fats, 382, 449 Uraemia, 418, 449 Uremia, 433, 449 Ureters, 449, 450 Urethra, 420, 428, 449, 450 Uric, 387, 392, 430, 449 Urinary, 106, 175, 233, 253, 359, 364, 371, 385, 391, 395, 410, 449, 450, 452 Urinary tract, 175, 233, 450 Urinary tract infection, 175, 450 Urine, 165, 198, 356, 366, 368, 375, 389, 395, 428, 449, 450 Urogenital, 232, 298, 385, 450 Urogenital System, 232, 450 Ursodeoxycholic Acid, 63, 138, 145, 450 Urticaria, 100, 215, 234, 237, 255, 348, 450 Uterus, 370, 372, 378, 381, 406, 417, 427, 450 Uvea, 450 Uveitis, 214, 215, 234, 255, 450 V Vaccine, 34, 80, 320, 344, 428, 450 Vacuoles, 378, 416, 450 Vagina, 406, 450 Vancomycin, 4, 8, 100, 181, 203, 302, 450 Varices, 63, 450 Vascular endothelial growth factor, 82, 450 Vasculitis, 117, 418, 450 Vasoconstriction, 237, 248, 380, 450 Vasodilatation, 237, 450 Vasodilator, 357, 375, 390, 411, 450 VE, 46, 87, 88, 450 Vector, 77, 447, 450 Vein, 198, 352, 398, 414, 419, 449, 451 Venous, 139, 146, 352, 355, 389, 428, 446, 448, 451 Venous Thrombosis, 139, 146, 355, 446, 451 Ventilation, 358, 451 Ventricle, 353, 369, 430, 444, 445, 448, 451

Index 477

Ventricular, 369, 391, 411, 448, 451 Venules, 214, 357, 359, 378, 407, 451 Vertebrae, 441, 451 Vertigo, 417, 451 Vesicular, 353, 373, 390, 451 Vestibule, 365, 396, 411, 438, 451 Veterinary Medicine, 141, 148, 309, 451 Vibrio, 81, 131, 363, 451 Vibrio cholerae, 131, 363, 451 Villi, 391, 451 Villous, 298, 361, 451 Villus, 69, 451 Vinca Alkaloids, 451 Vinorelbine, 135, 181, 182, 451 Viral, 49, 78, 80, 209, 224, 225, 235, 243, 369, 377, 386, 415, 447, 451 Viral vector, 78, 451 Virulence, 30, 31, 34, 60, 65, 88, 89, 353, 447, 451 Virus, 78, 88, 111, 354, 361, 385, 386, 397, 423, 447, 451, 452 Viscera, 407, 440, 452 Visual Acuity, 437, 452 Vitamin A, 396, 434, 452 Vitamin D, 257, 281, 435, 452 Vitreous Hemorrhage, 374, 452 Vitreous Humor, 434, 452

Vivo, 30, 31, 34, 36, 38, 39, 42, 45, 47, 48, 52, 54, 62, 65, 67, 73, 83, 86, 169, 242, 254, 390, 395, 404, 417, 444, 445, 452 Volvulus, 210, 452 W White blood cell, 197, 350, 356, 363, 364, 366, 379, 401, 403, 404, 409, 410, 411, 413, 414, 423, 452 Whooping Cough, 422, 452 Windpipe, 358, 422, 446, 452 Withdrawal, 20, 252, 274, 277, 452 Wound Healing, 80, 212, 230, 244, 361, 382, 396, 405, 452 X Xanthine, 69, 452 Xanthine Oxidase, 69, 452 Xenograft, 134, 349, 452 X-ray, 12, 21, 180, 197, 342, 354, 367, 368, 383, 384, 399, 414, 431, 436, 452, 453 X-ray therapy, 399, 453 Y Yeasts, 383, 384, 398, 422, 436, 453 Yolk Sac, 382, 453 Z Zygote, 368, 453 Zymogen, 364, 428, 453

478 Colitis

Index 479

480 Colitis

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