Inflammatory Bowel Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

INFLAMMATORY BOWEL DISEASE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERE...

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INFLAMMATORY BOWEL DISEASE 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 Ó2004 by ICON Group International, Inc. Copyright Ó2004 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., 1960Inflammatory Bowel Disease: 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: 0-597-84465-8 1. Inflammatory Bowel Disease-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 inflammatory bowel disease. 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 INFLAMMATORY BOWEL DISEASE ............................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Inflammatory Bowel Disease....................................................... 32 E-Journals: PubMed Central ....................................................................................................... 92 The National Library of Medicine: PubMed ................................................................................ 95 CHAPTER 2. NUTRITION AND INFLAMMATORY BOWEL DISEASE ................................................ 141 Overview.................................................................................................................................... 141 Finding Nutrition Studies on Inflammatory Bowel Disease ..................................................... 141 Federal Resources on Nutrition ................................................................................................. 148 Additional Web Resources ......................................................................................................... 149 CHAPTER 3. DISSERTATIONS ON INFLAMMATORY BOWEL DISEASE............................................ 151 Overview.................................................................................................................................... 151 Dissertations on Inflammatory Bowel Disease .......................................................................... 151 Keeping Current ........................................................................................................................ 152 CHAPTER 4. CLINICAL TRIALS AND INFLAMMATORY BOWEL DISEASE ...................................... 153 Overview.................................................................................................................................... 153 Recent Trials on Inflammatory Bowel Disease .......................................................................... 153 Keeping Current on Clinical Trials ........................................................................................... 157 CHAPTER 5. PATENTS ON INFLAMMATORY BOWEL DISEASE ...................................................... 159 Overview.................................................................................................................................... 159 Patents on Inflammatory Bowel Disease.................................................................................... 159 Patent Applications on Inflammatory Bowel Disease................................................................ 180 Keeping Current ........................................................................................................................ 205 CHAPTER 6. BOOKS ON INFLAMMATORY BOWEL DISEASE .......................................................... 207 Overview.................................................................................................................................... 207 Book Summaries: Federal Agencies............................................................................................ 207 Book Summaries: Online Booksellers......................................................................................... 211 Chapters on Inflammatory Bowel Disease ................................................................................. 217 Directories.................................................................................................................................. 237 CHAPTER 7. MULTIMEDIA ON INFLAMMATORY BOWEL DISEASE ............................................... 239 Overview.................................................................................................................................... 239 Video Recordings ....................................................................................................................... 239 CHAPTER 8. PERIODICALS AND NEWS ON INFLAMMATORY BOWEL DISEASE ............................ 241 Overview.................................................................................................................................... 241 News Services and Press Releases.............................................................................................. 241 Newsletters on Inflammatory Bowel Disease............................................................................. 245 Newsletter Articles .................................................................................................................... 245 Academic Periodicals covering Inflammatory Bowel Disease.................................................... 248 CHAPTER 9. RESEARCHING MEDICATIONS................................................................................... 249 Overview.................................................................................................................................... 249 U.S. Pharmacopeia..................................................................................................................... 249 Commercial Databases ............................................................................................................... 250 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 255 Overview.................................................................................................................................... 255 NIH Guidelines.......................................................................................................................... 255 NIH Databases........................................................................................................................... 257 Other Commercial Databases..................................................................................................... 259 The Genome Project and Inflammatory Bowel Disease ............................................................. 259 APPENDIX B. PATIENT RESOURCES ............................................................................................... 265

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Overview.................................................................................................................................... 265 Patient Guideline Sources.......................................................................................................... 265 Finding Associations.................................................................................................................. 275 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 277 Overview.................................................................................................................................... 277 Preparation................................................................................................................................. 277 Finding a Local Medical Library................................................................................................ 277 Medical Libraries in the U.S. and Canada ................................................................................. 277 ONLINE GLOSSARIES ................................................................................................................ 283 Online Dictionary Directories ................................................................................................... 283 INFLAMMATORY BOWEL DISEASE DICTIONARY.......................................................... 285 INDEX .............................................................................................................................................. 389

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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 inflammatory bowel disease is indexed in search engines, such as www.google.com or others, a non-systematic 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 inflammatory bowel disease, 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 inflammatory bowel disease, 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 inflammatory bowel disease. Abundant guidance is given on how to obtain free-ofcharge 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 inflammatory bowel disease, 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 inflammatory bowel disease. 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 INFLAMMATORY BOWEL DISEASE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on inflammatory bowel disease.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and inflammatory bowel disease, 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 “inflammatory bowel disease” (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: ·

Biologic Therapy of Inflammatory Bowel Disease Source: Gastroenterology. 122(6): 1592-1608. 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: Advancing knowledge regarding the biology of chronic inflammation has led to the development of specific biologic therapies that mechanistically target individual inflammatory pathways. This article explores the many biologic therapies that are being evaluated for the treatment of the chronic inflammatory bowel diseases (IBD): Crohn's disease and ulcerative colitis. Biologic compounds proven to be effective for Crohn's disease include monoclonal antibodies to tumor necrosis factor (infliximab and CDP571)

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and to the leukocyte adhesion molecule alpha 4 integrin (natalizumab). Other biologic compounds for which there is insufficient evidence to judge efficacy for IBD include: p55 tumor necrosis factor (TNF) binding protein (onercept); interferon alpha; interferon beta-1a; anti-interferon gamma antibody; anti-interleukin 12 antibody; p65 anti-sense oligonucleotide granulocyte colony stimulating factor, and granulocyte macrophage colony stimulating factor; anti-interleukin 2 receptor antibody; epidermal growth factor; keratinocyte growth factor 2 (repifermin); human growth hormone; anti-CD4 antibody; and anti-alpha4beta7 antibody. Biologic therapies that have been proven ineffective for inflammatory bowel disease include: interleukin 10; interleukin 11; antisense intercellular adhesion molecule 1; and the TNF receptor fusion protein etanercept. The authors conclude that based on the early successes of infliximab, CDP571 and natalizumab, it seems certain that biologic therapy will play an important role in the future treatment of IBD. 4 figures. 2 tables. 144 references. ·

Exercise Guidelines for Patients with Inflammatory Bowel Disease Source: Gastroenterology Nursing. Society of Gastroenterology Nurses and Associates. 21(3): 108-111. May-June 1998. Contact: Available from Williams and Wilkins, 351 West Camden Street, Baltimore, MD 21201-2436. Summary: Aerobic exercise can be beneficial for people with inflammatory bowel disease (IBD), because it tends to reverse muscle weakness and wasting and prevents the loss of calcium and protein that may commonly occur with IBD. Exercise is especially beneficial for people taking glucocorticoid medications; steroids may cause muscle atrophy and weakness, osteoporosis, and bone loss, which increases the risk for fracture. This article discusses five components that need to be included in an exercise program: mode of activity, intensity of exercise, frequency and duration of training, and progression. The signs and symptoms of potential complications are reviewed. The article emphasizes that people with IBD can benefit from a well-rounded exercise program that includes aerobic activities, such as brisk walking, jogging, swimming, cycling, or step aerobics, and resistance training with free weights, bands, or pulleys. To derive maximum benefit, aerobic activities must be performed 20 to 60 minutes a day, 3 to 5 days a week. 2 tables. 17 references.

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Nutritional Issues in Inflammatory Bowel Disease Source: Gastroenterology Clinics of North America. 27(2): 435-451. June 1998. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Although significant advances have been made in understanding the pathogenesis and treatment of Crohn's disease and ulcerative colitis, few standards of care exist for using nutrition as primary or adjunctive therapy to treat these diseases. The data concerning its benefits are conflicting, however. Nutritional therapy that has been used in the treatment of inflammatory bowel diseases (IBD) includes total parenteral nutrition (TPN), and elemental, peptide, polymeric, and exclusion diets. This article apprises the clinician of the role of these various forms of nutrition, with emphasis on the results of controlled studies. The most important clinical consequences of malnutrition in IBD are growth retardation in children; weight loss and decreased functional capacity; and, if the association is causative, perioperative morbidity. Proteincalorie, folic acid, vitamin B12, niacin, and zinc deficiencies can cause diarrhea and could therefore contribute to disease activity in IBD. Current evidence indicates that

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patients with IBD, except for patients with lactose intolerance, patients with strictures in the gastrointestinal tract, and patients with extensive ileal resection or disease, should be encouraged to eat a normal, healthy diet. The article concludes with a brief section on the use of alternative therapy, including medicinal herbs. 4 tables. 106 references. ·

Review Article: The Treatment of Inflammatory Bowel Disease with 6Mercaptopurine or Azathioprine Source: Alimentary Pharmacology and Therapeutics. 15(11): 1699-1708. November 2001. 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: Azathioprine is a prodrug of 6-mercaptopurine that is further metabolized by various enzymes present in the liver and gut. Azathioprine and 6-mercaptopurine have been used in the treatment of inflammatory bowel disease (IBD, which includes ulcerative colitis and Crohn's disease) for more than 30 years. However, widespread use of these drugs is a more recent phenomenon, due to a long standing debate on the efficacy of these agents in IBD. Both drugs are slow acting, which is why clinical efficacy cannot be expected until several weeks or even months of treatment have elapsed. Consequently, these drugs have no place as monotherapy (single drugs) in the treatment of acute relapsing IBD. This review article suggestions guidelines for the application of azathioprine and 6-mercaptopurine in the treatment of IBD. The clinical effects of these drugs are probably identical, although their exact mode of action is still unknown. In Crohn's disease, these drugs are indicated in chronic active disease that fails to respond to glucocorticoids, or when the prednisolone dosage cannot be reduced below 10 to 15 milligrams, particularly if adverse effects are problematic. The drugs should be used to maintain remission, but only in patients with previous extensive or troublesome chronic active disease. In ulcerative colitis, patient indications for these drugs include chronic unresponsive glucocorticoid-dependent disease and frequent relapses (more than three in 2 years). 1 table. 74 references.

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Colonoscopy Plus Biopsy in the Inflammatory Bowel Diseases Source: Gastrointestinal Endoscopy Clinics of North America. 10(4): 755-774. October 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Biopsy of the colon is an important diagnostic tool in the investigation of the inflammatory bowel diseases (IBD). Colon biopsies are critical in helping to diagnose diarrhea, to distinguish different forms of colitis, to determine the extent of disease, and to determine if neoplasia (including cancer) has arisen in the setting of chronic colitis. This article reviews a number of scenarios where colon biopsies are of particular importance, such as biopsies in the patient with undiagnosed diarrhea, distinguishing different forms of inflammatory bowel disease (IBD), assessing disease extent and activity, differential diagnosis of and diagnosing other disorders superimposed on inflammatory bowel disease, neoplasia in patients with IBD, and colonic biopsy as a mirror of generalized gastrointestinal or systemic disease. One table summarizes the recommended locations and numbers of biopsies for different scenarios. The author concludes that to use colon biopsies most appropriately in patient management and to get the most mileage from them usually requires frequent clinician-pathologist

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interaction, often repeat endoscopy with biopsies at a different time, and the assessment of the biopsies in the clinical context. 1 figure. 3 tables. 94 references. ·

Iron and Inflammatory Bowel Disease Source: Alimentary Pharmacology and Therapeutics. 15(4): 429-438. April 2001. 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: Both anemia of iron deficiency and anemia of chronic disease are frequently encountered in patients with inflammatory bowel disease (IBD, consisting of Crohn's disease or ulcerative colitis). Anemia of iron deficiency is mostly due to inadequate intake or loss of iron. Anemia of chronic disease probably results from decreased erythropoiesis (creation of the hormone erythropoietin, which helps the body use oxygen), secondary to increased levels of proinflammatory cytokines, reactive oxygen metabolites, and nitric oxide. This article reviews the problem of iron in patients with IBD. The authors note that assessment of the iron status in a condition association with inflammation, such as IBD, is difficult. The combination of serum transferrin receptor with ferritin concentrations, however, allows a reliable assessment of the iron deficit. The best treatment for anemia of chronic disease is the cure of the underlying disease. Erythropoietin reportedly may increase hemoglobin levels in some of these patients. The anemia of iron deficiency is usually treated with oral iron supplements. Iron supplementation may lead to an increased inflammatory activity through the generation of reactive oxygen species. To date, data from studies in animal models of IBD support the theoretical disadvantage of iron supplementation in this respect. However, the results cannot be easily generalized to the human situation, because the amount of supplemented iron in these experiments was much higher than the does used in patients with iron deficiency. 2 figures. 97 references.

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Bone Mineral Density Assessment in Children with Inflammatory Bowel Disease Source: Gastroenterology. 114(5): 902-911. May 1998. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Children with inflammatory bowel disease (IBD) are at risk for osteoporosis because of undernutrition, delayed puberty, and prolonged use of corticosteroids. This article reports on a study that compared bone mineral density (BMD) in children with IBD with that in normal children and assessed the effects of nutritional and hormonal factors and corticosteroid dosages on BMD. A total of 162 subjects (99 with IBD and 63 healthy sibling controls) were enrolled in the study. Patients underwent anthropometric assessment, pubertal staging, bone age radiography, and BMD assessment by dual energy x-ray absorptiometry of the lumbar spine, femoral neck, and radius. The study also included laboratory evaluations. BMD Z scores at the lumbar spine and femoral neck were lower in patients with IBD, and lower in those with Crohn's disease in general than in those with ulcerative colitis (UC). Low BMD persisted after correction for bone age in girls with Crohn's disease. Cumulative corticosteroid dose was a significant predictor of reduced BMD. BMD did not correlate with measures of calcium homeostasis, except with elevated serum phosphate and urine calcium levels in girls. The authors conclude that low BMD occurs in children with IBD (more in Crohn's disease than in UC), especially in pubertal and postpubertal girls. Cumulative

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corticosteroid dose is a predictor of low BMD, but other factors in Crohn's disease remain undetermined. 2 figures. 6 tables. 46 references. (AA-M). ·

Psychiatric Predictors of Noncompliance in Inflammatory Bowel Disease: Psychiatry and Compliance Source: Journal of Clinical Gastroenterology. 32(1): 66-68. January 2001. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: Compliance with medications is very important in the management of many gastrointestinal disorders; in inflammatory bowel disease (IBD), controlled trials have shown the benefit of prophylactic (preventive) medical treatment in lowering the risk of recurrences. In this article, the authors appraised the association between current psychiatric disorders and medication adherence in an unselected consecutive group of outpatients with IBD. In 85 unselected consecutive outpatients with IBD, a professional structured diagnostic interview and a psychiatric assessment were carried out. In analyses, compliance correlated positively with disease duration and inversely with both disease severity and presence of psychiatric disorders. The relationship between the degree of compliance and the duration of the disease may be justified by the progressively increased awareness of having a chronic illness. This involves a gradual change in coping strategies, from avoidance to acceptance, and some years are needed to reach this goal. Thus, in the early phases, patients are prone to conform carefully to medical prescriptions only during relapses and to be less attentive during remissions. The authors note that only recurrent or serious flares seem able to confirm the real chronicity of the disease and the necessity of therapy. The authors conclude that in patients with IBD, preventive liaison psychiatry interventions seem indicated. 1 table. 26 references.

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Inflammatory Bowel Disease: Short-and Long-Term Treatments Source: Disease-A-Month. 44(4): 145-172. April 1998. Contact: Available from Mosby, Inc. 11830 Westline Industrial Drive, St. Louis, MO 631446-3318. (800) 453-4351 or (314) 453-4351. Fax (314) 432-1158. E-mail: [email protected]. Website: www.mosby.com/Mosby/Periodicals. Summary: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the digestive tract, known together as inflammatory bowel disease (IBD). The true cause or causes of IBD are unknown, although abnormal function of the immune system is clearly involved. Proposed causes include chronic infection, genetic abnormality, environmental factors, autoimmunity, and other abnormalities of immunoregulatory mechanisms. Each factor might play a role as a triggering or perpetuating cause. The chronic nature of these diseases and their tendency for spontaneous relapse and flareup have made study and treatment of these diseases complex. This article discusses standard and novel therapies for IBD and includes some review of what is known about the pathophysiology and manifestations of these diseases as a framework for understanding the rationale behind the treatment options. The section on UC discusses short-term therapy, including antibiotics, glucocorticoids, immunosuppressive therapy; nicotine; specialized nutritional therapy, including parenteral nutrition and defined diets; and specific micronutrient supplements, as well as long-term therapy. The section on Crohn's disease defines steroid-refractory and steroid-dependent disease and then discusses short-term therapy, including sulfasalazine, antibiotics, glucocorticoids, budesonide, immunosuppressive therapy,

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methotrexate, and cyclosporine; specialized nutritional therapy for CD, including defined diets, parenteral nutrition, and specific micronutrient supplements; and longterm therapy for CD, notably drug therapy. The next section of the article considers novel immunomodulatory treatments in IBD, including cytokines and cytokine blockade, T-cell apheresis and T-cell inhibition, and inhibition of adhesion molecules. The final section discusses special considerations in IBD, notably pouchitis in UC, and fistulas in CD. The authors conclude that although surgery should not be considered a failure of medical therapy, the fact that two thirds of patients with CD still require surgery to manage their disease suggests that advances in treatment are needed. 3 figures. 2 tables. 150 references. ·

Evolving Treatment Strategies for Inflammatory Bowel Disease Source: in Coggins, C.H.; Hancock, E.W., Eds. Annual Review of Medicine: Selected Topics in the Clinical Sciences, Volume 52. Palo Alto, CA: Annual Reviews Inc. 2001. p. 299-318. Contact: Available from Annual Reviews Inc. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (800) 523-8635. Fax: (415) 855- 9815. PRICE: $47. ISBN: 0824305450. Summary: Crohn's disease and ulcerative colitis (collectively known as inflammatory bowel disease or IBD) are idiopathic (of unknown cause) inflammatory bowel diseases characterized by dysregulated intestinal immune responses in genetically susceptible hosts. This article explains how conventional approaches to the medical therapy of ulcerative colitis and Crohn's disease can now be directed at either induction or maintenance of remission to improve therapeutic efficacy while minimizing complications. Newer approaches have expanded the utility of conventional therapies by improving both safety and efficacy and highlight the importance of specific targets along the immunoinflammatory pathways. Agents discussed include aminosalicylates, corticosteroids, antibiotics, azathioprine, 6 mercaptopurine, methotrexate, mycophenolate, cyclosporine, tacrolimus (FK 506), infliximab, and investigational therapies, including CDP571, etanercept, thalidomide, interleukins, adhesion molecules, heparin, probiotics, and nicotine. The combination of conventional and novel approaches now offers the potential of modifying the natural history of these diseases. 2 tables. 143 references.

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Long-term Risk of Malignancy After Treatment of Inflammatory Bowel Disease With Azathioprine Source: Alimentary Pharmacology and Therapeutics. 16(7): 1225-1232. 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: Data from renal (kidney) transplant and rheumatoid arthritis (RA) patients suggest that there is an increased risk of malignancy after treatment with azathioprine. Whether this is true for patients with inflammatory bowel disease (IBD) remains uncertain. This article reports on a retrospective review of clinical notes: azathioprine was given to 626 of 2,204 patients (885 with Crohn's disease and 1,349 with ulcerative colitis). The mean total duration of azathioprine was 27 months. The mean follow up from diagnosis was 13.7 years and the mean follow up from the start of azathioprine was 6.9 years. Thirty-one cancers were observed in 30 patients treated with azathioprine (4.5 percent of the population) and 77 cancers were observed in 70 patients not treated with azathioprine (4.5 percent). Logistic regression analysis (including in the model the

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age, sex, diagnosis, and extent of disease) showed that treatment with azathioprine did not significantly affect the risk of development of cancer. Eight patients had lymphoma; three had been given azathioprine. For patients with ulcerative colitis, the number of colorectal cancers in patients given azathioprine was 8 of 355 (2.2 percent) compared with 28 of 994 (2.8 percent) for patients not given azathioprine (not a significant difference). The authors conclude that no increased risk of cancer diagnosis following azathioprine treatment was observed. 1 figure. 6 tables. 24 references. ·

Medical Therapy for Inflammatory Bowel Disease Source: Gastroenterology Clinics of North America. 28(2): 297-321. June 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Despite advances in the understanding of Crohn's disease (CD) and ulcerative colitis (UC), the origins of inflammatory bowel disease (IBD) remain elusive. The therapeutic modalities used to treat CD and UC work at various sites along the immunoinflammatory cascades. This article reviews the pharmacology, mechanisms of action, clinical efficacy, and adverse effects of traditional therapies, such as aminosalicylates and corticosteroids, and examines the expanding number of immunomodulatory agents used in the management of IBD. Traditional therapies, such as aminosalicylates and corticosteroids, continue to be cornerstones in managing of IBD. However, immunomodulators, such as azathioprine and 6 mercaptopurine (6MP), are demonstrating increasing importance in the setting of steroid resistant and steroid dependent disease. Further, postoperative prophylaxis with certain antibiotics (e.g., metronidazole), aminosalicylates, or immunomodulators may be beneficial in preventing recurrence after resection in some patients with CD. In addition, immunosuppressive agents previously reserved for organ transplantation (e.g., cyclosporine) have expanded the number of medical therapies as advances in molecular engineering techniques are already heralding the development of a novel class of biologic therapies available for certain subgroups of patients. 5 tables. 252 references. (AA-M).

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10-Year Survey of Inflammatory Bowel Diseases: Drug Therapy, Costs and Adverse Reactions Source: Alimentary Pharmacology and Therapeutics. 15(4): 475-481. April 2001. 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: Drug therapy for Crohn's disease and ulcerative colitis (together termed inflammatory bowel disease, or IBD) is based on antiinflammatory and immunomodulating drugs, nutritional support, and surgical resection (removal of part of the intestine). Recently, new drugs have been introduced to combat IBD. This article reports on a study undertaken to consider drug prescriptions, costs, and adverse reactions in IBD patients in Sweden between 1988 and 1997. The annual drug exposure for Crohn's disease was 0.55 million daily doses per million population, mainly supplementation and aminosalicylic acids. Mesalazine and olsalazine had 61 percent within this group. For ulcerative colitis (UC), drug exposure was 0.61 million daily doses per million per year and aminosalicylic acids fell from 70 percent to 65 percent. For IBD patients, corticosteroid use and nutritional supplementation were common. The annual average cost for IBD drugs was $7.0 million (United States dollars). Annually, 32

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adverse drug reactions were reported, mainly hematological reactions such as agranulocytosis and pancytopenia (60 percent), followed by skin reactions. Only 2 deaths were reported. Aminosalicylic acids were the most commonly reported compounds. The authors conclude that drug use for IBD in the pre-biologic agent era rested on aminosalicylic acid drugs and corticosteroids with stable levels, proportions, and costs. The level of adverse drug reactions was low, but hematological (blood) reactions support the monitoring of IBD patients. 6 tables. 26 references. ·

Dysplasia in Inflammatory Bowel Diseases: Definition and Clinical Impact Source: Canadian Journal of Gastroenterology. 13(8): 671-678. October 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: Dysplasia is a morphological term that means malformation; this article reviews the definition of dysplasia in inflammatory bowel diseases (IBD) and its clinical impact. For the definition of IBD related dysplasia, the nature and origin of the malformation are stressed and the lesion is defined as an epithelial malformation that is unequivocally neoplastic but noninvasive. The use of a precise definition is necessary because of the clinical consequences related to the finding of dysplasia in IBD. The authors note that the microscopic diagnosis of dysplasia, however, remains difficult. Clinically, it is important to make a proper differential diagnosis between polypoid IBD related dysplasia and sporadic adenoma occurring in IBD, and between therapy related pseudodysplasia and genuine dysplasia. When dysplasia is diagnosed, a second opinion may be indicated because of the clinical consequences. Additional techniques to search for genetic defects associated with carcinogenesis can help to support the diagnosis. These techniques can identify changes in DNA content and molecular changes resulting from defects of genes controlling cell proliferation and death or tissue structure. These changes can be absent, appear early or late in the transition from normalcy toward dysplasia and cancer, or appear during repair. Positive findings indicate an increased cancer risk, but the magnitude of the risk remains to be defined. A positive diagnosis of genuine dysplasia necessitates clinical action, either followup of the patient or treatment. The authors conclude that, in practice, treatment means surgery because dysplasia can be a precursor or a marker of malignancy, except for sporadic adenomas, which can be removed locally. 5 figures. 44 references.

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Role of Endoscopy in Inflammatory Bowel Disease Source: Gastrointestinal Endoscopy Clinics of North America. 11(4): 641-657. October 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Ever since its introduction into clinical use in the 1960s, flexible fiberoptic endoscopy has progressively become an indispensable tool to diagnose and treat gastrointestinal (GI) disorders. In addition to permitting visualization and biopsy sampling of much of the gastrointestinal tract, endoscopy can also be used therapeutically, to localize and treat bleeding, dilate strictures, and remove tumors. Ileal and colonic biopsies are critical to establish the cause of chronic diarrhea, to help distinguish between different forms of colitis, to determine the extent of disease, and to determine if neoplastic changes have arisen in the setting of chronic colitis. This article reviews the expanding use of endoscopy in inflammatory bowel disease (IBD) in the pediatric age group. The author summarizes a practical approach to endoscopic

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procedures in pediatric patients, including preparation for colonoscopy, sedation, choice of endoscope, and safety concerns. 1 figure. 2 tables. 85 references. ·

Influence of Sex and Disease on Illness-Related Concerns in Inflammatory Bowel Disease Source: Canadian Journal of Gastroenterology. 13(9): 728-732. November 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: Identifying the normal concerns of people with ulcerative colitis (UC) and Crohn's disease (CD) can facilitate a comprehensive approach to their medical care. Clinically, it can be easily appreciated that the concerns of men and women with inflammatory bowel disease (IBD) may differ and that this may have a substantial impact on both coping and treatment decisions. This article reports on a study undertaken to discover the influence of sex and disease on illness related concerns in people with IBD. The 343 subjects in the study answered 25 items on a Rating Form of IBD Patient Concerns (RFIPC). Compared with men, women reported higher levels of IBD symptom severity and higher overall RFIPC scores. Women were more concerned than men about feelings related to their bodies, attractiveness, feeling alone, and having children. There was an interaction between disease and sex regarding concern about sexual performance and intimacy. In both cases, men with CD reported less concern than the other comparison group. The illness concerns that differ between sexes are not the most intense concerns in either sex. These results confirm that gender has a significant influence on a number of illness concerns, particularly concerns related to self image and relationships. The interaction of disease type and sex with respect to concern over sexual performance and intimacy is open to several potential explanations and requires further research. The authors conclude by encouraging clinicians to inquire into these sex specific concerns with which their patients may be struggling. 3 figures. 2 tables. 10 references.

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Inflammatory Bowel Disease: Current and Future Therapeutic Options Source: Postgraduate Medicine. 103(5): 86-88, 90, 95-97, 101-102. May 1998. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: Inflammatory bowel disease (IBD) usually presents as a complicated spectrum of flares and remissions, but the underlying course of the disease is chronic. This article, the second of two on IBD, presents an overview of the available treatment options, including both conventional methods and promising investigative approaches. Some of the most commonly used conventional agents used to treat IBD are the 5aminosalicylic acids, sulfasalazine, mesalamine, and olsalazine sodium. Corticosteroids and immunomodulating agents are also often used. The folic acid antagonist methotrexate and the antibiotics metronidazole, ciprofloxacin, and clarithromycin are other familiar components of conventional therapy. The authors also discuss some alternative approaches, including enema therapy (with introduction of a corticosteroid or a short-chain fatty acid) and nutritional therapy (elemental diets or glutamine supplementation). Because of the chronic nature of their condition, patients with IBD often become quite sophisticated in their understanding of treatment methods so they should be told of new options for controlling their disease. 2 tables. 28 references. (AAM).

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Inflammatory Bowel Disease in Minorities: Fiction or Fact? Source: Practical Gastroenterology. 26(3): 54, 56, 59, 60, 62, 64, 66. March 2002. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: Inflammatory bowel disease (IBD, consisting of ulcerative colitis and Crohn's disease) has traditionally been considered as 'a disease of the whites.' Limited data is available on the racial differences in the occurrence of IBD. Both ulcerative colitis and Crohn's disease are thought to be rare in minorities. This article reviews the emerging evidence suggesting that the incidence in blacks, Asians, and Hispanics, is higher than previously recognized. Studies of immigrants from low incidence to high incidence regions of the world support the hypothesis that environmental factors play a role in the development of IBD, and may account for its low prevalence in countries with predominantly nonwhite populations. There are also data suggesting differences in clinical features and disease outcomes among minority groups. Whether the differences reflect genetic heterogeneity or sociocultural factors is incompletely defined. The authors conclude that it is important to recognize in this new millennium that IBS can occur in minority populations, and its incidence in them is higher than previously recognized. 2 tables. 37 references.

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Impact of Diet on Inflammatory Bowel Disease Source: Digestive Health and Nutrition. p. 9-11. January-February 2002. Contact: Available from American Gastroenterological Association. 7910 Woodmont Avenue, 7th Floor, Bethesda, MD 20814. (877) DHN-4YOU or (301) 654-2055, ext. 650. Email: [email protected]. Summary: Inflammatory bowel disease (IBD, including ulcerative colitis and Crohns disease) can be debilitating, but many people with IBD find ways to manage their illness through a combination of medications and diet. This article describes the impact of diet on the management of IBD. The author begins with two case reports, one of a patient with ulcerative colitis and one of a patient with Crohns disease. The author then reviews several foods that are known to cause aggravating symptoms for IBD patients: high fiber foods, milk and milk products, fried foods, greasy foods, and large meals. Patients are cautioned that because of the intestinal elimination of proteins and other nutrients from the body, people with IBD may lack essential nutrients; in addition, too many dietary restrictions can contribute to dehydration and malnutrition. People with IBD must be sure to compensate the body sufficiently by following the advice of a physician and nutritionist and eating the right foods and multivitamins. Children and teenagers with IBD must be monitored even more closely because inadequate nutrition and loss of essential vitamins may threaten physical growth as well as behavioral and cognitive development. The author also discusses the impact of drug therapy on the symptoms of IBD and possible interactions between drugs and nutrition. One sidebar summarizes the possible indications for surgery for IBD. The article concludes with two web site addresses for additional information.

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Measles Vaccination a Risk Factor for Inflammatory Bowel Disease? Source: Gastroenterology Nursing. 23(4): 168-171. July-August 2000. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (410) 528-8555.

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Summary: It has been suggested that measles virus or receipt of the measles vaccination may pose a risk of developing inflammatory bowel disease (IBD). This article presents a review of the literature discussing the measles virus as a possible risk factor for IBD. The author concludes that no data have confirmed this suspicion, and vaccination from measles should be strongly encouraged. Measles is a life threatening childhood illness that can lead to sterility in adult years. Even if an association between the measles virus and IBD exists (a remote possibility, based on the research to date), the author stresses that the benefits of a vaccine against a crippling childhood disease have to be weighed against the risk of developing a chronic, nonfatal illness. 1 figure. 13 references. ·

Quality-of-Life Factors in Adolescent Inflammatory Bowel Disease Source: Inflammatory Bowel Diseases. 4(1): 6-11. February 1998. Contact: Available from Lippincott Raven Publishers. 12107 Insurance Way, P.O. Box 1580, Hagerstown, MD 21741-1580. (800) 777-2295 or (301) 714-2300. Fax (301) 824-7390. E-mail: [email protected]. Summary: Little is known about the specific psychosocial factors that influence quality of life in adolescents with newly diagnosed inflammatory bowel disease (IBD). This article reports on a study in which the authors used a model to assess adolescent adjustment to recent-onset IBD. Thirty adolescent-parent pairs completed a set of standardized questionnaires. Adolescents were 12 to 18 years of age and had Crohn's disease or ulcerative colitis of less than 5 years duration. Adolescents health-related quality of life scores significantly correlated with satisfaction and degree of closeness with their social support members, such as parents. An unexpected finding was that the adolescents included more extended family than peers in their social support networks. Also of note was that parental coping styles rather than adolescent coping styles significantly correlated with adolescents quality of life health scores. Severity of illness did not correlate with adolescent quality of life health scores. There was significant agreement between adolescent and parental quality of life health scores and stressful event ratings. Adolescents with recent-onset IBD rely more on family members than their peers for emotional support, and they depend more on their parents coping skills than on their own. These findings may indicate lags in normal adolescent development. Adolescents and parents do communicate and share concerns with each other. The authors conclude that support programs for adolescents with IBD should reinforce existing coping skills and parent-adolescent communication while promoting development. 4 tables. 25 references. (AA-M).

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Nutritional Issues and Therapy in Inflammatory Bowel Disease Source: Seminars in Gastrointestinal Disease. 9(1): 21-30. January 1998. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 654-2452 or (407) 345-4000. Summary: Nutritional issues in inflammatory bowel disease (IBD) often receive inadequate attention both in regard to therapy and nutritionally related complications of IBD. This article reviews much of the research that has evaluated the role of diet in the causation, primary treatment, and adjunctive therapy of both ulcerative colitis (UC) and Crohn's disease (CD). Elemental or polymeric diets have proved beneficial for treating acute flareups of CD and maintenance of IBD. A careful team approach can overcome problems in implementing nutritional therapy. Nutrition also has a critical benefit in postoperative CD and perioperative UC. Easily corrected nutritional abnormalities are often overlooked in patients with IBD, which may have significant consequences.

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Therapeutic nutritional interventions as primary therapy are of some benefit in Crohn's disease but patient selection is tremendously important. Elemental diets appear useful for at least a distinct subset of patients who require an alternative to steroids, and the best response is seen in those with mild to moderate, nonstricturing, predominantly small bowel disease without bloody diarrhea. Polymeric diets are cheaper, better tolerated, and probably as efficacious as elemental diets. Total parenteral nutrition (TPN) has a demonstrated benefit for nutritional improvement and a clear use in active Crohn's disease. The authors conclude that nutritional therapy may have a central place in the hierarchy of treatment in IBD and further research is critical to better define its benefits. Appended to the article is a relevant case history, with commentary by one of the authors and three additional physicians. 1 table. 30 references. (AA-M). ·

Inflammatory Bowel Disease in Pediatric and Adolescent Patients Source: Gastroenterology Clinics of North America. 28(2): 445-458. June 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Once considered rare in pediatric practice, chronic inflammatory bowel disease (IBD) is now being recognized with increasing frequency in children of all ages. This article reviews IBD in pediatric and adolescent patients. In addition to the usual gastrointestinal symptoms of diarrhea, abdominal pain, weight loss, anemia, joint symptoms, and rectal bleeding, children may exhibit prominent extraintestinal manifestations such as growth failure and delayed puberty. Other problems unique to pediatrics include the lack of controlled clinical trials and the lack of medications available for and tested in children, as well as the psychological issues that occur in children and adolescents with IBD. The authors stress that these unique problems necessitate a different medical approach than is used for adult onset IBD. A critical factor in the successful management of this disease is the willingness of the patient to cooperate with the multidisciplinary care team. Parents and patients must be educated and supported to treat these disorders effectively. 1 table. 61 references. (AA-M).

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Presenting Symptoms and Diagnostic Lag in Children with Inflammatory Bowel Disease Source: Inflammatory Bowel Diseases. 5(3): 158-160. August 1999. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030. Fax (301) 824-7390. Summary: Presenting symptoms and their duration may affect the time that elapses prior to definitive diagnosis of inflammatory bowel disease (IBD). This article reports on a study undertaken to determine the mean duration of presenting symptoms and diagnostic lag in children with IBD. The medical records of all patients less than 19 years of age diagnosed with IBD at the pediatric gastroenterology clinic of Children's Hospital of Wisconsin between 1990 and 1995 were reviewed. The age at diagnosis, gender, presenting symptoms and duration, disease location, and diagnostic lag were analyzed. There were 91 children (49 male) diagnosed with IBD. Crohn's disease (CD) was diagnosed in 58 children, ulcerative colitis (UC) in 24, and indeterminate colitis in 9. The mean ages at diagnosis were 11.4 years for CD, 9.7 years for UC, and 7.8 years for indeterminate colitis. The most frequent presenting symptoms were abdominal pain, diarrhea, hematochezia, and weight loss. The average lag in diagnosis of CD was 7.1 months, which varied by disease location: small intestine 10.5 months, ileocolonic 7.5 months, and colonic 6.4 months. The average lag in diagnosis was 6.7 months for UC

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and 14 months for indeterminate colitis. Children presenting with growth failure had the longest diagnostic lag. The authors conclude that the elapsed time between symptom onset and the diagnosis of CD has decreased. The diagnostic lag in CD decreases with distal colonic involvement. Following onset of symptoms, UC was diagnosed only slightly more rapidly than CD. 5 tables. 10 references. ·

Inflammatory Bowel Disease is Not Associated with an Increased Risk of Lymphoma Source: Gastroenterology. 121(5): 1080-1087. November 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: Previous studies of the risk of lymphoma in inflammatory bowel disease (IBD) patients have provided conflicting results. This study examines the risk of Hodgkin's and non Hodgkin's lymphoma among patients with inflammatory bowel disease. The authors performed a retrospective cohort study using the General Practice Research Database. Inflammatory bowel disease patients were matched to randomly selected controls on age, sex, and primary care practice. Lymphoma rates were also compared with published age and sex specific rates. The study included 6,605 patients with Crohn's disease; 10,391 with ulcerative colitis (UC); and 60,506 controls followed for an average of 3.7, 3.9, and 4.4 years, respectively. The incidence of lymphoma was not increased in patients with IBD. In subgroup analyses, an increased risk was not observed among patients with Crohn's disease or UC. Compared with IBD patients not treated with azathioprine or 6MP, the relative risk of lymphoma among the 1,465 IBD patients treated with these medications was 1.27. The authors conclude that patients with IBD do not have an increased risk of lymphoma as compared with the general population. Although the authors cannot completely rule out a modest increased risk of lymphoma with azathioprine of 6MP therapy, an increased risk was not observed in this cohort. 4 tables. 48 references.

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Novel Therapies for Inflammatory Bowel Disease Source: Gastroenterology Clinics of North America. 28(2): 323-351. June 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Recent advances in the understanding of the basic processes that contribute to inflammatory bowel disease (IBD) have led to the identification of new targets for therapy. Agents in development and those newly introduced for clinical use, include both traditional compounds and a growing number of biologic response modifiers. This review article places these novel therapies within a pathophysiologic framework, highlighting completely new targets and therapeutic modalities. Innovations in drug delivery have provided additional benefits from time tested agents such as corticosteroids and 5 aminosalicylic acid in IBD. Newly developed agents, particularly biologic therapies, have begun to assume a prominent role. These include chimeric and humanized monoclonal antibodies, recominant cytokines, recombinant immunoadhesins, oligopeptide receptor agonists and antagonists, and antisense oligonucleotides. The facility with which these agents may be developed, their specificity of action, and their rapid adoption in clinical trials have greatly accelerated the pace of discovery. The author concludes that cell based and gene based therapies will be tested as better vectors for DNA transfer to the gastrointestinal tract are developed and critical targets are pinpointed. 3 figures. 220 references. (AA-M).

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Genetics of Inflammatory Bowel Disease Source: Alimentary Pharmacology and Therapeutics. 15(6): 731-748. June 2001. 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: Recent epidemiological, clinical and molecular studies have provided strong evidence that inherited predisposition is important in the pathogenesis (development) of chronic inflammatory bowel diseases (IBD). This article reviews these studies on the genetics of IBD. The authors note that the model most consistent with the epidemiological data suggests that Crohn's disease and ulcerative colitis (the two types of IBD) are related polygenic diseases, sharing some but not all susceptibility genes. Investigators throughout the world have applied the complementary techniques of genome wide scanning and candidate gene analysis. Four areas of linkage have been widely replicated on chromosomes 16 (IBD1), 12 (IBD2), 6 (IBD3, the HLA region), and most recently on chromosome 14. Fine mapping of these regions is under way. Of the positional candidate genes, most attention has centered on the genes of the major histocompatibility complex. Genes within this region may determine disease susceptibility, behavior, complications, and response to therapy. A glossary of genetics terms is appended to the article. 1 appendix. 1 figure. 4 tables. 132 references.

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Use of Community Resources Before Inflammatory Bowel Disease Surgery Is Associated with Postsurgical Quality of Life Source: Canadian Journal of Gastroenterology. 14(2): 95-98. February 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: Research in chronic illness shows that community resources can have a lasting influence on the course of the illness; however, little research has been done to evaluate the community agencies that specifically address the needs of inflammatory bowel disease (IBD) patients. This article reports on a study undertaken to survey awareness of community agency resources among patients who have surgery for IBD, and to analyze the association between using these resources and qualitative postsurgical outcomes. The subjects were 92 patients who had surgery over a 12 month period; each person completed the Inflammatory Bowel Disease Questionnaire (IBDQ), and a self report instrument used to probe awareness and use of local community resources. Community resources were divided into two groups: those involving primarily social and educational participation, and those involving some individualized attention, usually from a professional or a trained lay facilitator. Results showed that almost all subjects were aware of at least one available resource. Participation in resources before surgery was variable, but 50 percent of the sample participated in at least one social or educational resource and 46.9 percent participated in at least one professional or individual support. For the 92 subjects who completed both the IBDQ and a survey of resources, analysis revealed a main effect of professional or individual resource use on postsurgical quality of life but no main effect of social or educational resources and no interaction. The authors conclude that the association between presurgical participation in professional or individualized community resources and better subjective outcome of IBD surgery may be explained by a positive contribution of participation to coping with surgery for IBD. 3 tables. 9 references.

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Inflammatory Bowel Disease in the Elderly Source: Gastroenterology Clinics of North America. 30(2): 409-426. June 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32821-9816. (800) 654-2452. Summary: Roughly 15 percent of all patients with inflammatory bowel disease (IBD) first develop symptoms after age 65. As the number of elderly in the population continues to grow, clinicians should see a greater number of elderly IBD patients. This article, from a special issue on gastrointestinal (GI) disorders in the elderly, addresses IBD in the older patient. In general, the presenting features of IBD are similar to those encountered in younger patients, but the broad differential diagnosis of colitis in the elderly can make definitive diagnosis more challenging. Despite many advances in cellular and molecular biology, the precise cause of IBD is elusive. The elderly are particularly susceptible to GI infection, suggesting a possible compromise of the mucosal immune system with age. The presentation and course of both ulcerative colitis (UC) and Crohn's disease (CD) in older patients is similar to that in younger patients. Differential diagnosis can include infection, ischemic colitis, diverticular disease, microscopic colitis, medications, and other conditions (lymphoma, radiation enterocolitis, vasculitis, amyloidosis). Whereas most therapies for IBD have not been studied specifically in the elderly, as a general rule, medical and surgical treatment options are the same irrespective of age. The authors stress that osteoporosis (abnormal loss of bone density), a condition generally associated with aging, should be managed aggressively in patients with IBD because many older persons already have a substantial baseline risk for accelerated bone loss. 1 figure. 2 tables. 123 references.

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Inflammatory Bowel Disease After Liver Transplantation: The Effect of Different Immunosuppressive Regimens Source: Alimentary Pharmacology and Therapeutics. 18(1): 33-44. July 2003. Summary: Seemingly conflicting results have been reported on the prevalence and severity of inflammatory bowel disease (IBD) after liver transplantation. Regimens with different combinations of drugs can be used for immunosuppression after transplantation. This article reports on a retrospective study of the prevalence of IBD after liver transplantation and the possible relationship with maintenance immunosuppressive regimens. The study included 78 patients with end stage primary sclerosing cholangitis (48 patients) or autoimmune cirrhosis (30 patients), transplanted between 1979 and July 2001, and with a follow up of at least 1 year. The median follow up after transplantation was 7.2 years. Nine of 25 patients with pre-transplant IBD experienced flare-ups after transplantation. Six of 53 patients without pre-transplant IBD developed de novo IBD after transplantation. The IBD-free survival was significantly higher in patients not receiving tacrolimus versus those receiving tacrolimus, in those receiving azathioprine versus those not receiving azathioprine, and in patients taking the regimen prednisolone-azathioprine-cyclosporin A versus those tacking tacrolimusprednisolone. Pretransplant IBD and the use of tacrolimus were found to be independent predictors for IBD after transplantation. Azathioprine appears to have a protective effect. 2 figures. 4 tables. 20 references.

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Incidence of Fracture Among Patients with Inflammatory Bowel Disease: A Population-Based Cohort Study Source: Annals of Internal Medicine. 133(10): 795-799. November 21, 2000.

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Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org. Summary: The clinical significance of the high prevalence of osteopenia (a condition of subnormally mineralized bone) in inflammatory bowel disease (IBD) is unclear. This article reports on a study undertaken to determine whether persons with IBD have increased incidence of fracture. Patients with IBD in the University of Manitoba IBD Database (n = 6,027) were matched to 10 randomly selected persons in the general population without IBD (n = 60,270) by year, age, sex, and postal area of residence. The incidence of hospitalization for hip fracture was determined on the basis of hospital discharge abstracts. Outpatient medical billing records and hospital discharge abstracts were used to calculate the incidence of spine, rib, and forearm fractures. Persons with IBD had significantly increased incidence of fractures at the spine, hip, wrist or forearm, and rib. The authors conclude that the incidence of fracture among persons with IBD is 40 percent greater than that in the general population. The authors note that other factors may also play a role; studies have shown that patients with Crohn's disease are more likely to smoke and patients with IBD may have lower levels of sex hormones and ingest less than the recommended daily amount of calcium and vitamin D. The authors call for clinical studies to identify which patients with IBD are at increased risk and which therapeutic interventions might benefit them. 2 tables. 20 references. ·

Bone Mineral Metabolism In Pediatric Inflammatory Bowel Disease Source: Inflammatory Bowel Diseases. 5(3): 192-199. August 1999. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030. Fax (301) 824-7390. Summary: The development of reliable techniques to measure bone densitometry and evolving effective drug treatment have created great interest in the diagnosis and treatment of osteoporosis in adults with inflammatory disease. This clinical review article considers a number of studies that have examined the prevalence of abnormal bone mineral metabolism in children and adolescents. Studies conducted over the past decade indicate a greater likelihood of clinically significant problems in Crohn's disease than in ulcerative colitis. Corticosteroids have been proven to impair bone mineral status. The author notes that it is increasingly clear that inflammation and other factors play a bigger role than malabsorption of minerals or vitamin D in most patients. As the use of the bisphosphonate class of drugs is limited in pediatric patients, there is a need to emphasize the role of diet and exercise in children and teenagers, particularly in those affected by inflammatory bowel disease (IBD). 5 tables. 86 references.

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Inflammatory Bowel Disease: Origins, Presentation, and Course Source: Postgraduate Medicine. 103(5): 77-80, 83-84. May 1998. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: The exact cause of inflammatory bowel disease (IBD) remains unknown, but its destructive nature is clearly recognized. This article, the first of two on IBD, summarizes the pathogenesis and epidemiology of ulcerative colitis (UC) and Crohn's disease. Ways to distinguish between these two facets of IBD, both clinically and pathologically, are explained, as are disorders that may mimic IBD. The incidence and prevalence of IBD vary greatly with geographic location and ethnic background. The

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greatest risk factor is a family history of IBD and immunopathologic alterations culminating in IBD have only recently been described. UC is by definition confined to the colonic mucosa. Inflammation virtually always involves the rectum and is continuous and confluent to its proximal margin. The upper gastrointestinal tract and small bowel are not significantly involved; such involvement suggests Crohn's disease. Common presenting signs of UC include rectal bleeding, diarrhea, abdominal pain, and tenesmus. Crohn's disease is characterized by transmural inflammation. Any part of the gastrointestinal tract can be inflamed, but certain locations are more commonly involved than others. Transmural inflammation can lead to complications not often seen with UC, such as stricture formation, obstruction, fistulas, and abscesses. IBD can have hepatobiliary, rheumatologic, dermatologic, and ocular complications as well. 4 tables. 32 references. (AA-M). ·

Bone and Joint Diseases in Inflammatory Bowel Disease Source: Alimentary Pharmacology and Therapeutics. 12(5): 397-404. May 1998. 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 intestinal and articular (joints) systems are closely linked in inflammatory bowel disease (IBD). Clinical and immunological studies support an important etiopathogenetic link between intestinal and articular inflammation. There is increasing evidence for a negative link between bone mass density and intestinal inflammation. This article focuses on the prevalence, etio-pathogenesis, and treatment of arthritis (peripheral, sacroiliitis, and spondylitis) and osteoporosis in patients with IBD. Peripheral arthritis is most frequently seen in patients with extensive ulcerative colitis (UC) and in patients with Crohn's disease (CD). Especially in UC, a distinct relationship between attacks of arthritis and flareups of bowel disease is observed. One section discusses gut inflammation in spondyloarthropathy, defined as a group of related inflammatory joint diseases that share similar clinical features and a strong association with HLA B27. Entities include not only inflammatory bowel disease but also ankylosing spondylitis, reactive arthritis triggered by a urogenital or enterogenic infection, some form of psoriatic arthritis, and a group of undifferentiated spondyloarthropathies. The latter half of the article addresses bone mass density and IBD, particularly osteoporosis. Osteoporosis is a systemic skeletal disease characterized by a low bone mass and a micro-architectural deterioration leading to increased bone fragility and susceptibility to fracture. The article concludes that identifying the inflammatory mechanisms that reduce bone mass density should help to prevent and treat this IBD-related morbidity. 1 table. 65 references. (AA-M).

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Palliative Care in Inflammatory Bowel Disease: An Evidence-Based Approach Source: Inflammatory Bowel Diseases. 6(3): 228-243. 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 management of the patient with inflammatory bowel disease (IBD) is challenging for both the physician and the patient. IBD imposes both a physical and emotional burden on patients' lives. Palliative care is important for IBD patients because it focuses on improving quality of life. While palliative care does not change the natural history of the disease, it provides relief from pain and other distressing symptoms. This article focuses on various aspects of care for IBD patients, including pain control,

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management of oral and skin ulcerations, stomal problems in IBD patients, control of nausea and vomiting, management of chronic diarrhea and pruritis ani (itching of the anus), evaluation of anemia, treatment of steroid related bone disease, and treatment of psychological problems associated with IBD. Each of these areas is discussed from an evidence based approach. The authors categorize the evidence discussed in five groups: category A refers to evidence from clinical trials that are randomized and well controlled; category B evidence refers to evidence from cohort or case controlled studies; category C is evidence from case reports or flawed clinical trials; category D evidence is limited to the clinical experience of the authors; evidence labeled as category E refers to situations where there is insufficient evidence available to form an opinion. The authors also present algorithms for the management of pain and nausea in patients with IBD. 2 figures. 2 tables. 193 references. ·

Critical Assessment of New Therapies in Inflammatory Bowel Disease Source: Journal of Gastroenterology and Hepatology. 17 (Supplement): S176-S185. February 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: The only disease modifying therapy for inflammatory bowel disease (IBD), until recently, was immunosuppression with azathioprine. Other 'standard' therapies for IBD were merely symptomatic. This review article offers a critical assessment of new therapies for IBD. With the advent of biological therapies, especially the chimeric monoclonal anti-TNF antibody infliximab, treatment starts to target specific pathogenic disease mechanisms, which allow thorough suppression of the disease process and healing of the bowel in the long term. Moreover, infliximab is the only drug up to the present that allows short-term healing of fistulizing Crohn's disease (one type of IBD). This therapy is associated with problems of immunogenicity. The formation of antibodies to infliximab jeopardizes the efficacy and is associated with infusion reactions. The author contends that optimization of anti-TNG strategies will occur in the coming years. Another promising therapy is antagonization of alpha4 integrins and hence, of migration of inflammatory cells to the intestine. The author expects that more simple therapies using small molecules that inhibit the key cytokines or proinflammatory processes will take over in the next decade. In the current and future approach to IBD therapy, immunosuppression with azathioprine or 6-MP and methotrexate play a central role. At the present time, the combination of infliximab with azathioprine or methotrexate can be regarded as the new standard for the therapy of refractory Crohn's disease. In ulcerative colitis (UC, another type of IBD), much less progress has been made and the value of biological therapy as well as of long term management with immunosuppression remains controversial. Probiotics are an attractive treatment option for IBD, but studies so far are small and data are not yet convincing. 2 figures. 5 tables. 59 references.

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Inflammatory Bowel Disease: Progress Toward a Gene Source: Canadian Journal of Gastroenterology. 14(3): 207-218. March 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: The pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD) is still unknown, but the importance of genetic susceptibility has been clearly shown by

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epidemiological data from family and twin studies. This article reports on research progress toward identifying the genetic basis of these inflammatory bowel diseases (IBD). Linkage studies have identified two susceptibility loci for IBD on chromosomes 12 and 16. More important, these linkages have been replicated by independent investigators, and studies of positional candidates within these regions continue, together with fine mapping strategies. Regions of 'suggestive' linkage on chromosomes 1, 3, 4, 6, 7, 10, 22, and X have also been reported in individual studies. Other important candidate genes investigated include the interleukin 1 receptor antagonist, MUC3, and genes of the human leukocyte antigen (HLA) system. The apparently conflicting data in different studies from around the world may be explained by ethnic differences, case mix, and genetic heterogeneity. Animal studies have provided insights from targeted mutations and quantitative trait locus analysis. The goals of continuing research include narrowing the regions of linkages and analysis of candidate genes and possibly applying newly developed methods using single nucleotide polymorphisms. Advances in IBD genetics hold the potential to provide knowledge about disease pathogenesis at the molecular level, with ensuing benefits for clinical practice. 2 figures. 2 tables. 144 references. ·

Polyunsaturated Fatty Acids and Inflammatory Bowel Disease Source: American Journal of Clinical Nutrition. 71(1 Supplement): 339S-342S. January 2000. Contact: Available from American Journal of Clinical Nutrition. Production Office, 9650 Rockville Pike, Bethesda, MD 20814. (301) 530-7038. Fax (301) 571-8303. Website: www.ajcn.org. Summary: The rationale for supplementation with n-3 fatty acids to promote the health of the gastrointestinal (GI) tract lies in the antiinflammatory effects of these lipid (fat) compounds. The first evidence of the importance of dietary intake of n-3 polyunsaturated fatty acids was derived from epidemiological observations of the low incidence of inflammatory bowel disease (IBD) in Eskimos. This article briefly reviews the literature on the use of n-3 fatty acids in IBD (ulcerative colitis and Crohn disease), the results of which are controversial. The discrepancies between studies may reside in the different study designs used as well as in the various formulations and dosages used, some of which may lead to a high incidence of side effects. Choosing a formulation that lowers the incidence of side effects, selecting patients carefully, and paying strict attention to experimental design are critical when investigating further the therapeutic potential of these lipids in inflammatory bowel disease. 1 figure. 27 references.

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'Modern Life' in the Epidemiology of Inflammatory Bowel Disease: A Case-Control Study with Special Emphasis on Nutritional Factors Source: European Journal of Gastroenterology and Hepatology. 10(3): 243-249. March 1998. Contact: Available from Rapid Science Publishers. 400 Market Street, Suite 750, Philadelphia, PA 19106. (800) 552-5866 or (215) 574-2210. Summary: The rising incidence of inflammatory bowel disease (IBD) since the second World War coincides with profound changes in dietary patterns. This article reports on a case control study that investigated the possible pathogenic role of some characteristic modern dietary factors in IBD. The study focused on risk factors in 688 recently diagnosed cases of IBD (290 with Crohn's disease and 398 with ulcerative colitis)

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compared with 616 population controls. Smoking, age, gender, and education were taken into account by using logistic regression analysis. There was a positive association between the development of Crohn's disease and cola drinks, chewing gum, and chocolate consumption, and a negative association with consumption of citrus fruit. Consumption of cola drinks and chocolate were also positively associated with developing ulcerative colitis. There was a negative association between the intake of citrus fruits and 'having a stuffed pet' for a period longer than 5 years during childhood and developing. No association with the frequency of toothbrushing and developing IBD was found. The authors conclude that these nutritional items may be true risk factors or they might simply be the expression of a modern lifestyle also involving other risk factors for IBD that at present are still unknown. 4 tables. 39 references. (AA-M). ·

Current Theories on the Causes of Inflammatory Bowel Disease Source: Gastroenterology Clinics of North America. 28(2): 283-296. June 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: The understanding of the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) has greatly expanded over the past decade. This review article discusses current theories on the causes of inflammatory bowel disease (IBD), the collective term used for CD and UC. The presence of abnormalities in the immune system, the contribution of nonimmune cells in the intestinal mucosa, a variety of genetic risk determinants, and random environmental factors may all be necessary to induce what clinically presents as IBD. The authors conclude that several agents likely initiate an immune response that finally leads to pathology in the intestinal microenvironment and genetic background of a particular patient. The authors also predict what future directions are most likely to yield useful information and how understanding of these diseases will evolve within the next few years. 1 figure. 96 references. (AA-M).

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Effects of Inflammatory Bowel Disease on Adolescents Source: Gastroenterology Nursing. 23(2): 63-66. March-April 2000. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (410) 528-8555. Summary: This article considers the effects of inflammatory bowel disease (IBD) on adolescents. Adolescence is a time of profound change for individuals; a time that can witness biologic, social, and psychological change in the individual as well as role changes within the family and peer groups. Compounding these difficult transitions with the onset of inflammatory bowel disease leads to additional problems with adolescence adjustment. In the limited studies that have addressed the adolescent and IBD, several key concepts emerge that point to ways for successfully dealing with these adolescent adjustment problems. The author explains how Roy's Adaptation Model can provide a foundation for identifying and selecting interventions in working with adolescents and chronic illness. This model features three steps: assessment of the client's behavior in each of the adaptive modes; selection of the areas of concern that need reinforcing, either maladaptive or adaptive behaviors; and for each of the behaviors, determination of the focal, contextual, and residual stimuli that shapes the behaviors. The author uses a hypothetical case study to demonstrate the application of this model. 15 references.

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Genetics of Inflammatory Bowel Disease: A Guide for the Clinician Source: Practical Gastroenterology. 21(9): 25-26, 29-30, 32. September 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: This article explains why the inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, are fundamentally genetic disorders. IBD genes are being identified and genetic markers and serum antibodies are being used to define clinical subgroups. IBD disorders have a higher prevalence in certain ethnic groups, are inherited within families, and are associated with particular genetic syndromes. To locate IBD genes, researchers have combined two different approaches. The first is a genomewide search, in which the entire human genome is screened for genes linked within IBD families. The second is the candidate gene approach, where immunologically relevant genes are tested for associations within IBD populations and families. These two strategies have led to considerable progress in identifying potential genes, but no single gene has yet been linked to a specific functional defect in IBD. However, candidate genes in combination with serum immunologic markers can be used to stratify patients into clinically important subgroups. In this way; these markers may eventually guide the clinician in diagnosis and treatment. 2 tables. 8 references. (AA-M).

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Clinical Economics Review: Medical Management of Inflammatory Bowel Disease Source: Alimentary Pharmacology and Therapeutics. 13(1): 15-25. January 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: This article provides a clinical economics review of the medical management of inflammatory bowel disease (IBD). Inflammatory bowel diseases, although uncommon and rarely fatal, typically present during the period of economically productive adult life. Patients may require extensive therapeutic intervention as a result of the chronic, relapsing nature of the diseases. Their medical management includes oral and topical 5 amino salicylic acid derivatives and corticosteroids, as well as antibiotics and immunosuppressive therapies. Assessing the cost effectiveness of rival treatments requires valid, reliable, global assessments of outcome that consider quality of life, as well as the usual clinical end points. Macroeconomic studies of the overall impact of IBD on health care systems have so far been largely confined to North America, where the total annual U.S. costs, both direct and indirect, incurred by the estimated 380,000 to 480,000 people with IBD have been put at approximately $2 billion. Drugs were estimated to account for only 10 percent of total costs, whereas surgery and hospitalization account for approximately half. Studies from Europe suggest that the proportion of patients with Crohn's disease and ulcerative colitis who are capable of full time work is 75 percent and 90 percent, respectively. However, while only a minority of IBD patients suffer chronic ill health and their life expectancy is normal, obtaining life insurance may be problematic, suggesting a misconception that IBD frequently results in a major impact on an individual's economic productivity. 1 figure. 3 tables. 43 references. (AA).

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Complementary and Alternative Medicine Use by Patients with Inflammatory Bowel Disease: An Internet Survey Source: Canadian Journal of Gastroenterology. 13(4): 327-332. May 1999.

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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 to determine the degree and related factors of the use of complementary and alternative medicine (CAM) by patients with inflammatory bowel disease (IBD). The study involved the use of the Internet and the authors compare the results found with those found by using a similar survey in patients attending gastroenterology clinics in Calgary, Alberta. The study was a cross sectional survey of 263 patients with IBD conducted as a World Wide Web based, structured questionnaire. Complementary therapies had been used by 46 percent of the patients in the previous two years. Current use was reported by 34 percent. Vitamins, herbal products, and natural health practices were the most commonly reported therapies. Side effects and lack of effectiveness of standard therapies were the most commonly cited reasons for seeking complementary medicine. However, despite this, respondents who had previously received surgery, or intravenous or oral steroids were less likely to be current CAM users. Important differences between the determinants of and reasons for CAM use in the present study and those of a similar study of IBD patients in a local tertiary care setting were noted. For example, the local care setting patients were more likely to use CAM when they had factors associated with a worse disease course (use of IV or oral steroids and previous hospitalization or surgery); in contrast, these factors were associated with a lower likelihood of using CAM in the Internet sample. The authors discuss the pros and cons of conducting IBD related research on the Internet, but conclude that their observations show, at a minimum, substantive differences in terms of both disease severity and health beliefs between the Internet sample and the local care setting sample. 4 tables. 11 references. ·

Natural History of Corticosteroid Therapy for Inflammatory Bowel Disease: A Population-Based Study Source: Gastroenterology. 121(2): 255-260. August 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 reports on a study undertaken to determine the 1 year outcome after the first course of corticosteroids in an inception cohort of patients with inflammatory bowel disease (IBD, which includes ulcerative colitis and Crohn's disease). All patients in Olmsted County, Minnesota, diagnosed with Crohn's disease (n = 173) or ulcerative colitis (n = 185) from 1970 to 1993 who were treated with systemic corticosteroids were identified (4 patients denied research authorization for records review). Immediate outcome (30 days) and 1 year outcome after the first course of corticosteroids were determined. Results showed that 74 (43 percent) patients with Crohn's disease (CD) and 63 (34 percent) patients with ulcerative colitis (UC) were treated with corticosteroids. Immediate outcomes for CD were complete remission in 43 patients (58 percent), partial remission in 19 patients (26 percent), and no response in 12 patients (16 percent). Immediate outcomes for UC were complete remission in 34 patients (54 percent), partial remission in 19 patients (30 percent), and no response in 10 patients (16 percent). One year outcomes for CD were prolonged response in 24 patients (32 percent), corticosteroid dependence in 21 patients (28 percent), operation in 28 patients (38 percent), and lost to follow up (1 patient, 1 percent). One year outcomes for UC were prolonged response in 31 patients (49 percent), corticosteroid dependence in 14 patients (22 percent), and operation in 18 patients (29 percent). The authors conclude that most patients with CD and UC initially respond to corticosteroids. At 1 year, 32

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percent of patients with CD and 48 percent with UC are corticosteroid free without operation. 3 figures. 4 tables. 23 references. ·

Trends in Inflammatory Bowel Disease Therapy Source: Canadian Journal of Gastroenterology. 13(9): 775-776. November 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 reviews advances in gene therapy for treating inflammatory bowel disease (IBD). The authors contend that it is possible that genetic information may be shown to predict disease behavior and response to targeted therapy. Because of the family incidence of IBD of approximately one person in six, the regions of linkage are being narrowed with the use of studies of affected sibling pairs or multiple affected families and family based association studies. There appears to be a multigene basis of IBD, with multiple pathways leading to inflammation, ranging from intrinsic changes in the immune system to alterations in the intestinal barrier function. IBD is categorized into ulcerative colitis (UC) and Crohn's disease (CD) by its description of disease patterns, prediction of outcomes, and direction of appropriate treatment strategies, but not on pathogenetic mechanisms. The authors review newer investigational methods for IBD, including color Doppler sonography (ultrasound) and assays to detect antibodies. A final section discusses optimizing therapy for IBD. The authors caution that UC in the elderly tends to have a greater tendency for distal involvement, with a more severe initial attack, and with a possibly higher risk of complications due to prolonged steroid use. Mesalamine remains the standard of care for the treatment of mild attacks of UC or CD. IBD itself as well as its therapy with glucocorticosteroids are risk factors for osteopenia and osteoporosis.

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Early Diagnosis of Inflammatory Bowel Disease: Article Five in the Series Source: Practical Gastroenterology. 23(1): 22, 24, 26-28, 31-33, 37-38. January 1999. 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: This article reviews the early diagnosis of inflammatory bowel disease (IBD), the collective term for Crohn's disease (CD) and ulcerative colitis (UC). The cause is incompletely understood. IBD usually develops in the second or third decades of life, but may affect all age groups. Although patients with IBD usually present with diarrhea and crampy abdominal pain, constitutional symptoms such as weight loss and extraintestinal symptoms involving the eye, hepatobiliary (liver) system, joints, skin, and other organ systems are common. Many of the extraintestinal manifestations may predate intestinal involvement by years. Diagnosing IBD can be challenging because of this broad array of possible presentations. However, radiologic, serologic (blood), microbiologic, and endoscopic testing should help the physician make an early diagnosis when IBD is suspected. 5 tables. 27 references. (AA).

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Hepatobiliary Manifestations of Inflammatory Bowel Disease Source: Gastroenterology Clinics of North America. 28(2): 491-513. June 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000.

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Summary: This article reviews the hepatobiliary manifestations of inflammatory bowel disease (IBD). A large number of hepatobiliary abnormalities have been described in association with IBD, including primary sclerosing cholangitis (PSC), pericholangitis, chronic hepatitis, cryptogenic cirrhosis, cholangiocarcinoma (gallbladder cancer), and cholelithiasis (gallstones). PSC is the most common of these hepatobiliary diseases. This high degree of association with IBD suggests a common pathogenic mechanism; however, no causal relationship has been established. Medical therapy has not proven successful in slowing disease progression or prolonging survival. PSC usually progresses insidiously and eventually leads to cirrhosis. Endoscopic manipulation is recommended for treating complications of recurrent cholangitis or worsening jaundice in the setting of a dominant stricture, but endoscopic approaches have not been shown to improve survival or decrease the need for liver transplantation. Liver transplantation is life saving for patients with advanced PSC. Pericholangitis, gallstones, and chronic hepatitis are additional disorders noted in association with IBD, but they are much less common and easier to manage than PSC. 3 figures. 6 tables. 140 references. (AA-M). ·

Inflammatory Bowel Disease and Pregnancy Source: Gastroenterology Clinics of North America. 27(1): 213-224. March 1998. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: This article reviews the interplay of inflammatory bowel disease (IBD) and pregnancy. The author begins by cautioning that many of the research studies are somewhat dated and often did not distinguish between the subtypes of IBD. However, general implications for practice can be ascertained. Topics include fertility, inheritance and IBD, the influence of ulcerative colitis (UC) on fetal outcome, the influence of Crohn's disease on fetal outcome, the influence of pregnancy on the course of UC and of Crohn's disease, episiotomy in IBD, the influence of drug therapy on the pregnant woman and the fetus, smoking, the effect of surgery for IBD on subsequent pregnancies, and the management of IBD during pregnancy. Drugs discussed include 5aminosalicylic acid agents (mesalamine, olsalazine), corticosteroids, immunosuppressives, cyclosporine, methotrexate, and antibiotics. Rates of healthy babies, congenital abnormalities, stillbirths, and spontaneous abortions are roughly the same in women with UC and Crohn's disease as in the normal population. The presence of UC did not influence the mode of delivery (vaginal versus cesarean section) or the incidence of preeclampsia during gestation. However, if a severe exacerbation requiring surgery occurs during pregnancy, the fetal mortality is high. 71 references.

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Management of Inflammatory Bowel Disease Source: American Family Physician. 57(1): 57-68. January 1, 1998. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: This article reviews the management of inflammatory bowel disease (IBD). Patients with an inflammatory bowel disease, such as ulcerative colitis or Crohn's disease, have recurrent symptoms with considerable morbidity. Patient involvement and education are necessary components of effective management. Mild disease requires only symptomatic relief and dietary manipulation. Mild to moderate disease can be managed with 5-aminosalicylic acid compounds, including olsalazine and mesalamine. Mesalamine enemas and suppositories are useful in treating proctosigmoiditis. Antibiotics such as metronidazole may be required in patients with

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Crohn's disease. Corticosteroids are beneficial in patients with more severe symptoms, but side effects limit their use, particularly for chronic therapy. Immunosuppressant therapy may be considered in patients with refractory disease that is not amenable to surgery. IBD in pregnant women can be managed with 5 aminosalicylic acid compounds and corticosteroids. Since longstanding IBD (especially ulcerative colitis) is associated with an increased risk of colon cancer, periodic colonoscopy is warranted. Two patient care management algorithms are presented. 2 figures. 1 table. 50 references. (AA-M). ·

Muscoloskeletal Manifestations in Inflammatory Bowel Disease Source: Canadian Journal of Gastroenterology. 15(6): 399-403. June 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: This article reviews the musculoskeletal manifestations of inflammatory bowel disease (IBD), the most common extraintestinal complications of the condition. Wide ranges in prevalence have been reported, depending on the criteria used to define spondylarthropathy. In 1991, the European Spondylarthropathy Study Group developed classification criteria that included previously neglected cases of undifferentiated spondylarthropathies, which had been ignored in most of the oldest epidemiological studies on IBD. The spectrum of musculoskeletal manifestations in IBD patients includes all of the clinical features of spondylarthropathies: peripheral arthritis, inflammatory spinal pain, dactylitis, enthesitis (Achilles tendinitis and plantar fasciitis), buttock pain, and anterior chest wall pain. Radiological evidence of sacroiliitis is common, but not obligatory. The articular manifestations begin either at the same time or subsequent to the bowel disease; however, the onset of spinal disease often precedes the diagnosis of IBD. The prevalence of the different musculoskeletal manifestations is similar in ulcerative colitis and Crohn's disease (the two categories of IBD). Symptoms usually disappear after proctocolectomy (removal of the affected portion of the colon). The pathogenetic mechanisms (how the disease causes the complications) that produce the musculoskeletal manifestations in IBD are unclear. Several arguments favor an important role of the intestinal mucosa in the development of spondylarthropathy. The natural history of the disease is characterized by periods of flares and remission; therefore, the efficacy of treatment is difficult to establish. Most patients respond to rest, physical therapy, and nonsteroidal antiinflammatory drugs (NSAIDs), but these drugs may activate the bowel disease. Sulfasalazine may be recommended in some patients; however, there is no indication for the systemic use of steroids. 6 tables. 43 references.

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Nutrition and Inflammatory Bowel Disease Source: Gastroenterology Clinics of North America. 28(2): 423-443. June 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: This article reviews the nutritional aspects of inflammatory bowel disease (IBD), including the mechanisms and manifestations of malnutrition and the efficacy of nutritional therapies. Nutrient deficiencies in patients with IBD occur via several mechanisms and may complicate the course of the disease. Up to 85 percent of patients hospitalized with exacerbations of IBD have protein energy malnutrition. This form of malnutrition also occurs between flareups of the disease, particularly in patients with Crohn's disease (CD), in whom the development of nutrient deficiencies is often insidious. Nutritional status is assessed by clinical examination and the use of

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nutritional indices such as the Subjective Global Assessment of nutritional status. Nutritional intervention may improve outcomes in certain people; however, because of the costs and complications of such therapy, careful selection is warranted, especially in patients presumed to need parenteral nutrition. Clinical trials have established the efficacy of enteral formulations in nutritional repletion and reduction of disease activity in CD. Studies have shown the efficacy of nutrients with trophic effects, such as short chain fatty acids, glutamine, epidermal growth factor, nucleotides, and nutrients with immunomodulatory properties, such as omega 3 fatty acids and gamma linoleic acids, as therapy for IBD. 1 figure. 6 tables. 160 references. (AA-M). ·

Watching for and Managing Joint Problems in Inflammatory Bowel Disease Source: Journal of Musculoskeletal Medicine. 13(11):28-30,33-34; November 1996. Summary: This journal article for health professionals discusses the nature and prevalence of peripheral joint arthritis and of spondylitis and sacroiliitis in ulcerative colitis and Crohn's disease. These rheumatic manifestations are the most common ones to accompany inflammatory bowel disease. The bowel and joint symptoms may or may not occur at the same time. Similarly, bowel and joint symptoms may or may not respond to the same treatment. Treatment of peripheral joint arthritis is directed toward controlling the bowel disease, and it includes corticosteroids and immunosuppressives. Joint injections and analgesics may provide symptomatic relief. The course of sacroiliitis and spondylitis is independent of the bowel disease. Treatment is aimed at limiting joint damage, and aggressive physical therapy and exercise are the mainstays. 8 references, 1 figure, and 3 tables. (AA-M).

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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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Review Article: Bone and Joint Diseases in Inflammatory Bowel Disease Source: Alimentary Pharmacology and Therapeutics. 12(5): 397-404. May 1998. Summary: This review article provides health professionals with information on the prevalence, etiopathogenesis, and treatment of arthritis and osteoporosis in

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inflammatory bowel disease. The intestinal and articular systems are closely linked in inflammatory bowel disease. Spondyloarthropathy is the most common extraintestinal manifestation of inflammatory bowel disease. Either a peripheral arthritis or a spondylitis may occur. The peripheral arthritis is pauciarticular and asymmetrical and mainly involves the large and small joints of the lower limbs. Peripheral arthritis is most frequently seen in patients with extensive ulcerative colitis or Crohn's colitis. The axial involvement includes sacroiliitis and spondylitis. Clinical and immunologic studies support an important etiopathogenetic link between intestinal and articular inflammation. Treatment options for patients with a spondyloarthropathy include a short course of nonsteroidal anti-inflammatory drugs, sulfasalazine, azathioprine-6mercaptopurine, and methotrexate. Osteoporosis is a systemic skeletal disease characterized by a low bone mass and microarchitectural deterioration leading to increased bone fragility and susceptibility to fracture. Bone mass density can be measured by several methods, including dual energy x-ray absorptiometry. Bone turnover can also be estimated by biochemical markers. The pathogenesis of osteoporosis in inflammatory bowel disease is likely to be multifactorial. There is increasing evidence of a negative link between bone mass density and intestinal inflammation. Treatment options include hormones and biphosphonates. The article concludes that further elucidation of the mechanisms of recirculation, adhesion, and disease inducing features will help in understanding the etiopathogenesis of extraintestinal manifestations of inflammatory bowel disease. 1 table and 65 references. (AA-M) ·

Inflammatory Bowel Disease: Immunodiagnostics, Immunotherapeutics, and Ecotherapeutics Source: Gastroenterology. 120(3): 622-635. February 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: Treatment options for inflammatory bowel disease (IBD) reflect a continuing shift from empiricism to strategies based on improved understanding of the pathophysiology of disease. This article reviews the use of immunodiagnostics, immunotherapeutics, and ecotherapeutics for managing inflammatory bowel disease (Crohn's disease and ulcerative colitis). In susceptible individuals, IBD appears to be the result of defective regulation of mucosal immune interactions with the enteric microflora. This has prompted research directed at the interface of the traditional disciplines of immunology, microbiology, and epithelial cell biology. Whereas immunodiagnostics have been of limited clinical value in IBD, assessments of mucosal rather than systemic immune function are promising. For therapy, there is an increasing trend toward more aggressive and earlier use of immunomodulatory agents, particularly for prevention of relapse, with cytokine manipulation as a bridge therapy to achieve remission in patients with acute severe disease. Although most drug treatments are directed toward altering the host response, the rational for manipulating the enteric flora (i.e., the resident bacteria in the intestinal tract) appears sound and will be the basis of additional future therapeutic strategies. The author concludes that notwithstanding the widening range of options for drug therapy in IBD, other outcome modifiers and well established principles of managing chronic disease are as important as ever. 1 figure. 4 tables. 124 references.

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Epidemiology and the Natural Course of Inflammatory Bowel Disease Source: Gastroenterology Clinics of North America. 28(2): 255-281. June 1999.

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Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory disorders of the gastrointestinal tract that are distributed unevenly within populations and throughout the world. This review article considers epidemiology and the natural course of inflammatory bowel disease (IBD). Although its exact causes remain unknown, epidemiology has provided insight into its pathogenesis. The authors examine geographic, ethnic, and other trends in IBD; risk factors (including genetic and environmental factors); and its natural history. The authors caution that performance of epidemiologic studies of IBD that are similar and easily compared has been hampered by lack of universally adopted diagnostic criteria for these disorders. A study from Baltimore has suggested that the incidence of IBD in African Americans is lower than in American whites. Studies of the incidence of IBD in populations that emigrate to high risk geographic areas suggest that the rate rises in these groups. Several studies have suggested that within a specified geographic area, the incidence of IBD is two to fourfold higher in Jews than in other ethnic groups. Several studies have found a trend toward increased rates of IBD in urban communities compared to rural ones. Both ulcerative colitis and Crohn disease are more frequent in high socioeconomic and white collar populations than in lower socioeconomic and blue collar populations. The authors review the extent and severity of disease, disease course, complications, cancer risks, survival (prognosis), and quality of life in UC and CD. The article concludes with a brief description of IBD in the pediatric population and in the elderly. 4 figures. 3 tables. 125 references. (AA-M). ·

Review Article: Potential Therapeutic Applications and Mechanisms of Action of Heparin in Inflammatory Bowel Disease Source: Alimentary Pharmacology and Therapeutics. 14(11): 1403-1409. November 2000. 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: Unfractioned heparin was recently reported to be beneficial in the treatment of inflammatory bowel disease (IBD). This article reviews the potential therapeutic applications and mechanisms of action of heparin in IBD. The available uncontrolled data show that the drug may be effective in steroid resistant ulcerative colitis (UC) with a percent of complete clinical remission of over 70 percent, after an average of 4 to 6 weeks of therapy. The administration of unfractioned heparin is not currently justified by the very limited available data. The worsening of rectal bleeding is infrequent in treated UC patients and only rarely does it require blood transfusion or a colectomy (removal of part of the colon). Low molecular weight heparin was used in a single trial in patients with steroid refractory UC, with results similar to those observed with unfractioned heparin. Since a prothrombotic state has been described in IBD, and microvascular intestinal occlusion (blockage of the smallest blood vessels in the intestine) seems to play a role in the pathogenesis of IBD, it is reasonable that part of the beneficial effects of unfractioned heparin in IBD may result from its anticoagulant properties. However, beyond its well known anticoagulant activity, unfractioned heparin also exhibits a broad spectrum of immunomodulating and anti inflammatory properties, by inhibiting the recruitment of neutrophils and reducing pro inflammatory cytokines. Moreover, heparin can restore the high affinity receptor binding of basic fibroblast growth factor; this would aid healing of the ulcerated mucosa. The authors conclude that unfractioned heparin may represent a safe therapeutic option for severe,

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steroid resistant UC, although randomized, controlled trials are needed to confirm this data. 1 figure. 2 tables. 71 references. ·

Oxidative Stress as Pathogenic Factor in Inflammatory Bowel Disease: Radicals or Ridiculous? Source: Alimentary Pharmacology and Therapeutics. 16(12): 1997-2015. December 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: Virtually all inflammatory mediators investigated to date seem to be dysregulated in the inflamed intestinal mucosa of patients with inflammatory bowel disease (IBD). However, which of these are actually involved in the initiation and perpetuation of intestinal tissue damage is still not fully understood. Among these mediators are the reactive oxygen metabolites, produced in large amounts by the massively infiltrating leucocytes. These reactive oxygen metabolites are believed to constitute a major tissue-destructive force and may contribute significantly to the pathogenesis (development) of IBD. This article provides a concise overview of reactive oxygen metabolite biochemistry, the types of cell and tissue damage potentially inflicted by them, and the endogenous antioxidants which should prevent these harmful effects. The authors note that reactive oxygen metabolite-mediated injury is important in both the primary and downstream secondary pathophysiological mechanisms underlying intestinal inflammation. Nonetheless, how the individual components of the mucosal antioxidant enzymatic cascade respond to inflammatory conditions is a neglected area of research. 1 figure. 1 table. 264 references.

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Use of Cytotoxic Agents and Cyclosporine in the Treatment of Autoimmune Disease. Part 2: Inflammatory Bowel Disease, Systemic Vasculitis, and Therapeutic Toxicity Source: Annals of Internal Medicine. 129(1): 49-58. July 1, 1998. Summary: When cytotoxic (cell-damaging) agents were introduced, their ability to disrupt nucleic acid and protein synthesis led to their effective use for the treatment of neoplastic disease (cancer). It then became apparent that these agents also suppress the immune system. This usually unwelcome effect was subsequently studied and beneficially directed toward treating non-neoplastic diseases in which autoimmune mechanisms play a role. This article discusses the use of cytotoxic agents and cyclosporine in the treatment of inflammatory bowel disease (IBD) and systemic vasculitis, and reviews the toxic effects of these agents. The authors caution that because these medications can cause treatment-induced illness or even death, it is imperative to weigh the benefits and risks of cytotoxic therapy when treating a non-neoplastic disease. The authors review research studies that investigated the use of these drugs. Drugs used for IBD include azathioprine and 6-mercaptopurine, methotrexate, and cyclosporine. These drugs are frequently used in combination with other agents and require careful monitoring. The authors stress that the optimal use of various drug combinations requires not only a knowledge of appropriate indications and dosage but also a thorough assessment of patient expectations and quality of life, a careful weighing of the various risks of medical and surgical therapies, the judicious use of other supportive measures, and extensive patient education. The section on toxicity discusses cyclophosphamide, chlorambucil, methotrexate, azathioprine, 6-mercaptopurine, and cyclosporine. The authors caution that infection is still an important cause of illness and

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death that is largely related to the nonspecific actions of these agents on the immune response. 3 tables. 75 references. ·

Immunosuppressive Drugs in the Treatment of Inflammatory Bowel Disease Source: Seminars in Gastrointestinal Disease. 9(1): 2-9. January 1998. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 654-2452 or (407) 345-4000. Summary: With increasing experience, the threshold for using immunosuppressive drugs in inflammatory bowel disease (IBD) has fallen. There is a tendency now to use them in a greater proportion of patients and at an earlier stage of the disease. This article provides an overview of the agents in common use and highlights their role in the management of IBD. The principal drugs used in clinical practice at this time include: azathioprine (AZA) and its metabolite 6-mercaptopurine (6-MP), methotrexate, and cyclopsporin A. AZA and 6-MP are generally considered the first line immunosuppressive agents. These drugs are effective and generally well tolerated by most patients and enable many patients to avoid the predictable side effects of steroid therapy. The major concerns associated with IS therapy, malignancy, and opportunistic infection have not been significant problems with either AZA or 6-MP in the context of IBD treatment. The toxicities associated with AZA and 6-MP can be divided into allergic-type reactions that are dose-independent (pancreatitis, fever, rash, arthralgias, malaise, nausea, and diarrhea) and non-allergic type reactions that are dose dependent (leukopenia, thrombocytopenia, and hepatitis). Because of the extensive use of immunosuppressive drugs, it is important that clinicians involved in caring for patients with IBD be familiar with them. Appended to the article are two relevant case histories, with commentary by one of the authors and three additional physicians. 38 references. (AA-M).

Federally Funded Research on Inflammatory Bowel Disease The U.S. Government supports a variety of research studies relating to inflammatory bowel disease. 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 inflammatory bowel disease. 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 inflammatory bowel disease. The following is typical of the type of information found when searching the CRISP database for inflammatory bowel disease:

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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Project Title: ANTI-INFLAMMATORY INFLAMMATION

LIPIDS

IN

ACUTE

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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 pro-inflammatory 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 ·

Project Title: AUTOIMMUNITY CENTERS OF EXCELLENCE Principal Investigator & Institution: Diamond, Betty A.; Professor; Microbiology and Immunology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The Autoimmunity Center of Excellence at the Albert Einstein College of Medicine will encompass research projects, an infrastructure for clinical trials and an administrative core. This Center reflects an interdisciplinary approach to autoimmune disease. It involves a collaboration of clinicians and basic scientists that is focused on translational studies to develop new therapeutic strategies. The research component will be directed by Betty Diamond and includes three research projects. Each project has the goal of developing new targets for therapy in autoimmune disease. The first project (PI: Anne Davidson) is a study of the effects of statins alone or in conjunction with CTLA-4Ig in the NZB/W mouse model of lupus. This project will

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include a study of the effect of statins on peripheral blood mononuclear cells of lupus patients. The second project (PI: Betty Diamond) is a study of the effect of CD22 overexpression on B cell development and on autoantibody production in murine models of SLE and includes a study of a CD22 polymorphism reported to associate with lupus. Overall it will explore whether inhibition of CD22 represents a useful therapeutic strategy. The third project (PI: Stanley Nathenson) is a biophysical study of the polymorphism of murine two microglobulin that is required for the expression of diabetes in NOD mice. This study will provide a comprehensive biophysical characterization of the features of TCR/MHC-peptide complexes that are directly relevant to eliciting diabetes. These studies promise to provide the atomic and molecular mechanisms responsible for disease development and thus may lead to novel strategies for the design of therapeutics that will limit disease-associated T cell reactivity. A clinical infrastructure is described (Clinical Director: Cynthia Aranow) that is capable of performing clinical trials in autoimmune rheumatic diseases, type 1 diabetes, autoimmune hematologic diseases, and inflammatory bowel disease. In addition, there are proposals for a clinical trial of DNase I in serologically active, clinically inactive lupus and for a trial of statin therapy as a steroid sparing agent in rheumatoid arthritis. Finally, the Center will include an administrative core for coordination and implementation of Center activities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: B220+DN INFLAMMATION

TCELLS

IN

MUCOSAL

TOLERANCE

AND

Principal Investigator & Institution: Hamad, Abdel R.; Instructor of Pathology; Pathology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2004; Project Start 21-JAN-2004; Project End 31-DEC-2005 Summary: (provided by applicant): Ulcerative colitis and Crohn's' disease, collectively referred to as Inflammatory Bowel disease (IBD), are chronic spontaneously relapsing disorders of the gastrointestinal tract. IBD is mediated at least in part by autoimmune mechanisms that are not completely understood. Studies of well-defined animal models of IBD have implicated several types of regulatory T cells, including CD4+CD25+ T cells, Tr1 and Th3 cells, in regulation of mucosal tolerance. However, none of these regulatory cells is known to naturally reside in the gastrointestinal tract. We have identified B220+ DN T cells as a new type of regulatory T cells that suppress polyclonal T cell activation in vitro and prevent T cell-mediated colitis in the SCID-transfer model of the disease. The mechanism of suppression involves inhibition of IL-2 transcription and inhibition of CD25 upregulation. These findings were obtained by analysis of B220+ DN T cells that accumulate in mice deficient in Fas or FasL genes. However, phenotypically similar B220+DN T cells exist in significant numbers at intraepithelial sites of the appendix, colon, cecum and in the liver, but their function has not been defined. Three Specific Aims are proposed to understand the cellular mechanisms of DN T cell-mediated suppression and the potential role of B220+ DN T cells that reside at the intraepithelial sites of the large intestine and the liver in regulating mucosal tolerance. The three Specific Aims are: 1) Characterize the cellular mechanism by which B220+ DN T cells suppress colitis 2) Define the role of the Fas pathway in controlling regulatory T cell function 3) Characterize the function of intraepithelial (IELs) and hepatic B220+ DN T cells. These studies may provide novel insights into how immune responses of the colon and liver are regulated and mucosol tolerance is maintained. In addition, they lay the groundwork for the analysis of B220+ DN T cell in healthy individuals and IBD patients.

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

Project Title: BETA2 INTEGRIN SIGNALING IN HUMAN NEUTROPHILS Principal Investigator & Institution: Takami, Mimi S.; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 15-MAY-1999; Project End 31-MAR-2004 Summary: A variety of gastrointestinal disorders, that include H. pylori, NSAID induced gastritis and inflammatory bowel disease, involve the recruitment of leukocytes from the circulation to the site of injury. The severity of the mucosal injury in these disease processes has been directly correlated with the extent of the neutrophil infiltration. In addition, the persistent neutrophil infiltrate which is the hallmark of chronic H. pylori infection, has been implicated as a possible mechanism facilitating malignant transformation in the gastric mucosa. Central to the modulation of adhesion and migration of leukocytes in inflammatory processes such as these, is a subfamily of cell surface receptors, the beta2 integrins. Adhesion through beta2 integrins is a complex process that involves activation of the integrin through an inside out signaling mechanism, triggered by the engagement of well characterized receptors such as the chemokine receptors, IL-8, C5a, and N-Formylmethionlleucyl- phenylalanine (FMLP), cytokine receptors, such as TNF, and activation of Protein Kinase C. Integrin activation results in enhanced binding to ligand, and subsequently, generation of an outside-in signal cascade that may lead to changes in gene expression and cytoskeletal rearrangement, enabling the leukocyte to migrate to sites of injury, and facilitating the physiologic response of the cell. Recent reports have identified Interleukin-8 as an important epithelial-derived inflammatory mediator in both IBD and H. pylori gastritis. In neutrophils, I1-8 has been shown to induce chemotaxis, respiratory burst and granule release, and to enhance cellular adhesion. However, the specific effects of IL-8 on beta2 integrin activation and ligand binding have not been closely examined. In addition, while recent reports indicate that IL-8 activates the MAPK pathway through Ras/Rafmediated events, the relationship of these events to beta2 integrin function has yet to be elucidated. Our goal, within this proposal, is to delineate the signal transduction cascades involved in beta2 integrin activation, with a particular focus on the physiologic stimulus at the chemokine receptor. In addition, we will examine post-ligand-binding events, including protein tyrosine phosphorylation and protein-protein interactions that are central to the outside-in signaling cascade initiated by engagement of beta2 integrins on human neutrophils. We will examine the relationship of these events to the complex shape changes involved in aggregation and transmigration. And, as a biological model, we will explore the way in which exposure to Helicobacter pylori, may impact these signals and affect neutrophil adhesion and migration on epithelial surfaces. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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 2002; 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

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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 ·

Project Title: CHEMOKINE SIGNALING AND COLITIS IN GIA2 DEFICIENT MICE Principal Investigator & Institution: Edwards, Robert A.; Pathology; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 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

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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: CLASS I MOLECULES AND AUTOIMMUNITY Principal Investigator & Institution: Roopenian, Derry C.; Senior Staff Scientist; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2003; Project Start 01-MAY-1999; Project End 31-JUL-2007 Summary: (provided by applicant): IgG is the major antibody isotype responsible for a wide diversity of autoimmune diseases. A major goal would thus be to understand how one controls the levels of pathogenic IgG antibodies in individuals with autoimmune disease. Studies culminating in our recent gene targeting and transgenic experiments have suggested that the MHC class I-like IgG protection receptor, FcRn, plays a key role in maintaining endogenous IgG concentrations in mammals of all ages. Our studies indicate that FcRn is a key control point for IgG-mediated immune responses. The overall goal of the proposed studies is thus to elucidate the biology and function of FcRn in normal and autoimmune states. Our new results provide the first direct evidence that FcRn is an important molecule for humoral autoimmunity. Aim 1 will determine which autoimmune diseases are ameliorated (or exacerbated) by an FcRn deficiency in a variety of autoimmune diseases. The results will suggest the diseases in which increased serum IgG concentrations are deleterious or protective. In doing so, it should define the autoimmune diseases that might be amenable to anti-FcRn therapeutic strategies. While FcRn protein is detected only at low levels in healthy adult mice, our new results indicate that FcRn protein increases substantially as mice develop SLE. Aim 2 will thus determine whether an increased level of FcRn expression contributes to autoimmune disease. These results should provide important insights into why FcRn is upregulated and whether FcRn upregulation is a major factor in establishing and maintaining hypergammaglobulinemia. While the IgG conserving function of FcRn is well established, the difficulties in monitoring FcRn in vivo have impeded the resolution of major issues concerning its in vivo biology. To determine the tissue sites in which FcRn expresses and operates to protect IgG from catabolism under normal and autoimmune situations, Aim 3 will thus employ Cre-Lox technology to replace the normal FcRn gene with an FcRn-GFP fusion construct. The expression of this construct under normal regulation and under tissue specific regulation will clarify the anatomy of FcRnmediated protection of IgG, and, more generally, will facilitate many other aspects of investigation into the physiology of FcRn. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLASS II FUNCTION IN INTESTINAL EPITHELIAL CELLS Principal Investigator & Institution: Hershberg, Robert M.; Infectious Disease Research Institute 1124 Columbia St, Ste 600 Seattle, Wa 98104 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: The single layer of polarized intestinal epithelial cells (IECs) which line the entire gastrointestinal tract express low levels of class II antigens constitutively, with elevated levels seen in a variety of autoimmune and inflammatory conditions including Inflammatory Bowel Disease (IBD). The long term goal of this grant proposal is to understand the mechanisms and significance of class II antigen processing by intestinal epithelial cells (IECs). We hypothesize that the class II mediated processing and presentation of luminal antigens by IECs contributes to the maintenance of CD4+ T cell compartments in the intestinal mucosa, and may contribute to the exaggerated mucosal CD4+ T responses that result in intestinal inflammation, including IBD. We have demonstrated that class II expressing IECs display unique features of class II processing and presentation related to their polarized phenotype and can function as potent antigen presenting cells to CD4+ T cells. This proposal outlines strategies to both define the molecular determinants of the polarized class II pathways operational in IEC, and to determine the biological relevance of IEC class II expression with regards to mucosal CD4+ T cell development and intestinal inflammation. We will examine the role of antigen denaturation, receptor mediated endocytosis, and the recycling of class II from the plasma membrane, respectively, on the class II antigen processing initiated from the apical or basolateral surface of polarized IEC. Experiments are proposed to define the molecular targeting signals that both direct the highly polarized expression of class II molecules at the basolateral surface and direct the localization of class II molecules in intracellular compartments in polarized IEC. Moreover, we describe the development of a novel model system in which the expression of class II molecules is targeted to IEC in either the small intestine or colon of transgenic mice. We plan to use these mice to determine the biological relevance of IEC class II expression to the development and function of normal and pathological CD4+ T cell populations in the intestinal mucosa. We anticipate that the experiments outlined in this grant proposal will highlight the IEC as an important therapeutic target in the modulation of mucosal immune and inflammatory responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLINICAL COMPONENT Principal Investigator & Institution: Kotzin, Brian L.; Professor and Head; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: The Denver Autoimmunity Center of Excellence encompasses a wide array of clinical investigators involved in studies of autoimmune diseases. The Denver ACE includes groups doing clinical investigation on type 1 diabetes, systemic lupus erythematosus and lupus nephritis, rheumatoid arthritis, systemic sclerosis, multiple sclerosis, autoimmune pulmonary diseases including interstitial lung disease and granulomatous lung disease, celiac disease, inflammatory bowel diseases, autoimmune polyendocrine syndromes and Addison's disease, and autoimmune skin diseases including vitiligo, pemphigus, and lupus-related rashes. These disease groups, involving multiple clinical specialties, departments, and institutions are part of the Denver ACE and have pledged their interest and support. In the original application and this renewal application, diseases being studied in individual clinical projects have

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included type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis, Addison's disease and autoimmune polyendocrine syndromes, celiac disease, and vitiligo. Among the different clinical components of the Denver ACE is the Barbara Davis Center for Childhood Diabetes, which is well known for its role in innovative research in the treatment and prevention of type 1 diabetes. The Denver ACE also includes a number of groups interested in the investigation of systemic lupus and two large Centers of multiple sclerosis patients. An important addition to the current renewal application is the addition of the rheumatology group at the University of Nebraska Medical Center and the Rheumatoid Arthritis Investigational Network (RAIN) of clinical rheumatologists and other personnel directed to the study of RA. In the preceding funding period, the Denver ACE has been involved in the design of clinical trials investigating the use of parenteral insulin for the prevention of islet cell autoimmunity and type 1 diabetes in high risk children, the use of a monoclonal antibody to complement component C5 in the treatment of lupus nephritis, and the use of mycophenolate with daclizumab in new onset type 1 diabetes. The Denver Center is also a collaborating site for ACE studies of anti-CD20 in systemic lupus. Two novel Phase II randomized, double-blind, and placebo-controlled protocols are included in the current renewal application. The first investigates the use of an insulin peptide B9-23 altered peptide ligand to prevent development of disease in patients with prediabetes. The second involves the use of a monoclonal antibody to CD20 (rituximab) in the treatment of patients with early (recent-onset) rheumatoid arthritis. Both trials will also involve considerable mechanistic studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: COMMENSAL BACTERIA IN REGULATION OF T GONDII INDUCED IBD Principal Investigator & Institution: Kasper, Lloyd H.; Professor; Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: The proposed studies investigate the interaction of Toxoplasma gondii and commensal bacterial flora in the immune regulation of an experimental model of pathogen-driven inflammatory bowel disease (IBD). The hypothesis to be tested is that specific bacterial products derived from commensal intestinal flora can interact with the parasite-infected host and prevent the development of experimental IBD. We have observed that germ free mice are more susceptible to an acute necrotizing condition of the ileum and colon than conventional mice following oral parasite infection suggesting that intestinal microflora or their derived products are required to prevent the development of Toxoplasma induced IBD. In the first specific aim, we will compare intestinal tissue samples (phenotyping, chemokines cytokines production) in germ-free strains of resistant (BALB/c) and susceptible (C57BL/6) mice following oral Toxoplasma infection to conventional mice. We have identified a specific capsular polysaccharide of B. fragilis that can modulate the gut inflammatory process. Treatment of conventional mice with capsular polysaccharide (PS A) derived from Bacteroides fragilis prevents the development of T. gondii induced IBD. The mucosal tissue and more specifically lymphoid cells from the lamina propria, Peyer's patches and other organs from PS A treated conventional and germ free mice will be assessed for immunohistologic differences. Mechanisms (IL-10, TGF-b production) of immunomodulation induced by the PS A will be further investigated. As suggested by our preliminary data, particular attention will focus on TGF-b producing CD8+ intraepithelial lymphocytes (IEL) and on a population of IL-10 dependent CD4

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regulatory T cells (CD45RB low, CD25). We will evaluate for the expression of these regulatory CD4+ T cells in the lamina propria and Peyer's patches of PS A treated mice and determine whether this cell population can be adaptively transferred to naive mice and prevent toxoplasma-driven IBD. NKT cells are also important regulatory cells that respond to polysaccharides. We will evaluate whether PS A treatment can induce a population of NKT cells that exert effector and immunoregulatory activity. 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; Internal Medicine; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 01-APR-1984; Project End 31-JUL-2003 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: CONTROL OF MICROVASCULAR FUNCTION BY OXYGEN Principal Investigator & Institution: Jackson, William F.; Professor; Biomedical Sciences; Western Michigan University 1903 W Michigan Ave Kalamazoo, Mi 49008 Timing: Fiscal Year 2002; Project Start 31-OCT-1989; Project End 31-MAR-2007 Summary: (provided by the applicant): Blood flow to the body's organs and tissues is regulated to meet their metabolic demands. O2-dependent control of arteriolar tone has been implicated in this regulatory process for over a century. However, the cellular site where changes in PO2 are sensed, and how changes in PO2 are coupled to changes in arteriolar muscle tone remain unclear. Therefore, the overall aims of the research proposed are to 1.) identify the cellular location of the sensorthat mediates arteriolar O2 reactivity, and 2.) establish the mechanism of action of O2 on these microvessels. The focus of this proposal will be on arteriolar O2 reactivity, in the hamster cheek pouch, a

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common microcirculatory model. We are in a unique position to study arteriolar function in this tissue from the level of single ion channels in isolated arteriolar muscle cells in vitro, to responses of intact arterioles in the living microcirculation. The proposed studies will: acquire new information on the cellular location where changes in PO2 are sensed; establish the ionic basis of O2-induced changes in arteriolar tone; and improve our understanding of the mechanism of action of cysteinyl-leukotrienes (cysLTs) on arterioles in the microcirculation. These data will not only aid in understanding the basic physiology of blood flow regulation in the microcirculation, but may also provide new clues to the etiology or consequences of diseases that impact the microcirculation such as hypertension, diabetes, and atherosclerosis and well as diseases such as asthma, inflammatory bowel disease, psoriasis, renal disease, and eosinophilic inflammation in which cysLTs are implicated. The specific aimsof the research are to test five hypotheses concerning the site and mechanism of action of O2 on hamster cheek pouch arterioles. They are: 1. Cells that synthesize cysLTs (the signaling molecules that we propose mediated arteriolar O2 reactivity in the cheek pouch) are distributed, extravascularly along arterioles, 2. O2 and cysLTs depolarize, elevate [Ca2+], and contract arteriolar muscle cells by stimulating Ca2+ influx through L-type Ca2+ channels, which subsequently activate Ca2+-dependent Cl-efflux through Ca2+activated C1 about channels, 3. O2- and cysLT-induced depolarization and constriction are limited by activation of Ca2+activated K+ channels, 4. cysLTs initiate vasoconstriction that can be conducted along arterioles through an arteriolar muscle cell pathway and 5. 02-induced constriction is conducted along arterioles through an arteriolar muscle cell pathway. These hypotheses will be tested by integration of stateof-the-art methodologies including immunohistochemistry; laser scanning confocal microscopy; intravital videomicroscopy, ratiometric calcium measurements, enzymatic isolation of arteriolar muscle cells; single-channel and whole-cell patch clamp recording; and conventional microelectrode recording in cheek pouch arterioles from golden Syrian hamsters. 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 2002; 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, TNF-

42


alpha, 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 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 nonimmune 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: CYTOKINE RESTITUTION

REGULATION

OF

INTESTINAL

EPITHELIAL

Principal Investigator & Institution: Polk, D. Brent.; Associate Professor of Pediatrics and Ce; Pediatrics; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 15-AUG-1999; Project End 31-JUL-2004 Summary: Maintenance of an intact intestinal epithelium is critical for intestinal growth, development, wound healing and prevention of disease. Restitution, the initial phase of epithelial wound repair, is regulated by a number of peptides, including cytokines such as tumor necrosis factor (TNF)alpha and epidermal growth (EGF). In spite a clear role for TNFalpha in the pathogenesis of inflammatory bowel disease, surprisingly little information is known about its role in the process of restitution. This proposal has evolved out of our long term studies on the mechanisms of growth factor regulated intestinal growth and development. Based on the synthesis of our preliminary and reported data, evidence from animal models of inflammatory bowel disease and on human clinical trials, the hypothesis being tested in this proposal is that TNFalpha specifically regulates intestinal epithelial restitution through signal transduction pathways required for cell migration and proliferation. We have established specific aims to address the following questions: (l) What are the principal mechanisms of TNFalpha regulation of intestinal epithelial cell migration? (2) What are the principal mechanisms of TNFalpha regulation of intestinal epithelial cell proliferation? and (3) How does TNFalpha interfere with EGF receptor signal transduction? To answer these questions we will use cellular transfection of the two human TNFalpha receptors (TNFalphaR1 and TNFalphaR2) and a series of constructs into the young adult mouse colon (YAMC) or mouse small intestinal epithelial (MSIE) cell lines. Using speciesspecific reagents we will investigate the function of TNFalphaR1 and TNFalphaR1 in the migration, proliferation and EGF receptor signal transduction of intestinal epithelial cells. Mutational analysis of the respective receptors will be used to determine regulatory domains effecting these processes. Once identified, regulatory domains will

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be placed in "bait" plasmid constructs for screening in the yeast two-hybrid assay for interacting proteins. To enhance the likelihood of recovering functional interacting proteins, we will develop GST-fusion proteins using the domains to screen intestinal cell-derived cDNA libraries and for purification of proteins, from YAMC and MSIE cell lysates, for amino acid sequence analysis. Antibodies will be generated against novel proteins to characterize the nature and function of these protein-protein interactions. The proposed studies should enhance our understanding of mechanisms of cytokine regulation of epithelial restitution and the prioritization of signal transduction when multipleligands, such as TNFalpha and EGF, are simultaneously activating their cognate receptors. The findings will have broad implications on intestinal biology, from normal growth and development, to tumorigenesis and metastasis, to the chronic mucosal ulceration state of inflammatory bowel disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: CYTOKINE TRAFFICKING AND SECRETION IN MACROPHAGES Principal Investigator & Institution: Stow, Jennifer L.; University of Queensland Cumbrae Stewart Building Brisbane, Queensland, 4072 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Tumour necrosis factor alpha (TNFalpha) is a proinflammatory, clinically-important cytokine secreted by activated macrophages. TNFalpha has widespread roles in host defence, tumour ceil killing and homeostasis. However, excess secretion of TNFa is a major cause of tissue damage in chronic inflammatory diseases such as Crohn's disease, arthritis and in cancer. Cytokine secretion in macrophages is poorly understood at the molecular and cellular level. The goal of these studies is to generate an understanding of how TNFalpha is trafficked to the cell surface for secretion by macrophages. Recent findings have revealed a specific tSNARE, (Syntaxin4/SNAP-23/Munc18c), a vesicle docking and fusion complex, as a key regulator of TNFa trafficking in macrophages. The proposed studies will further investigate t-SNARE expression and function in macrophages and in inflammation. The studies have three specific aims. First, to address how SNARE proteins are regulated in macrophages. LPS-responsive transcriptional and post-translational mechanisms will be studied at the level of gene and protein regulation using microarrays, then defining changes in protein modifications. Secondly, in vitro and in vivo approaches will be used to explore the function of Syntaxin4 as a rate-limiting 'rheostat' for TNFalpha secretion. Syntaxin4 levels will be titrated by expression of wild type or mutant cDNAs in cells and in transgenic mice. A mouse model will be used to investigate the roles of macrophages, TNFalpha and Syntaxin4 in inflammatory bowel disease. The third aim uses a combination of techniques -fluorescence imaging in live cells, immunolabeling and proteomics - to characterize the TNFalpha transport vesicles and secretory pathways in macrophages. Taken together this work will generate important insights into the pathobiology of macrophages and TNFalpha. Defining the function of the Syntaxin4 t-SNARE in macrophages will be a major advance in understanding trafficking. Finally, trafficking proteins - in particular Syntaxin4 - offer potential as drug targets for novel anti-TNFalpha therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 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: CYTOKINES AND MUCOSAL IMMUNE REGULATION Principal Investigator & Institution: Ma, Averil I.; Assistant Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 30-SEP-1996; Project End 31-JUL-2006 Summary: (Applicant's Abstract): A critical step in inciting intestinal inflammation is the elaboration of proinflammatory factors such as TNF. TNF activates NF-kappa-B and JNK signaling pathways, which induce the expression of other genes in a proinflammatory cascade. While it is clear that dysregulated expression of TNF can cause intestinal inflammation, it is not clear how TNF signals are normally down-regulated or controlled in vivo. To better understand the molecular mechanisms by which TNF signals are regulated, the investigator is studying A20, a novel molecule thought to regulate cellular responses to TNF. The PI has generated A20 deficient (A20-/-) mice

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and these mice develop spontaneous bowel inflammation, which is dramatically worsened after exposure to TNF. These remarkable physiological problems are associated with molecular defects in regulating TNF induced NF-kappa-B activity and cellular resistance to programmed cell death (PCD). This compelling preliminary data highlights A20's pivotal role in terminating TNF responses in vivo. It also provides a unique opportunity to interrogate the molecular mechanisms by which such control is normally achieved. Thus, the investigator proposes to: (1) delineate the role of A20 in regulating both spontaneous and TNF induced intestinal inflammation; (2) determine both the requirement and the contribution of A20-/-lymphocytes to mediating intestinal activation in these mice; (3) define the relative contributions of nonlymphoid (myeloid) hematopoietic cells versus non-hematopoietic cells; and (4) define the role of A20 in regulating TNF induced NF-kappa-B and PCD responses in intestinal tissue. Understanding both the cellular and molecular mechanisms by which A20 regulates TNF responses will provide unique insights into how TNF induced inflammation is normally terminated, and may also lead to novel therapies for human IBD patients. 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

46


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 ·

Project Title: DEVELOPMENT AND CHARACTERIZATION OF CD14 DEFICIENT MICE Principal Investigator & Institution: Freeman, Mason W.; Chief; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted from the applicant's abstract): CD14 is a 55 kDa glycosyl phosphatidylinositol-linked protein that is also present in a soluble form in serum. CD14 binds lipopolysaccharides (LPSs) derived from the outermost layer of Gram-negative bacteria and activates a signaling cascade that results in the production of inflammatory cytokines that include tumor necrosis factor alpha, interleukin-6, and interleukin-1. This response has been shown to be important in the pathogenesis of septic shock following Gram- negative septicemia. Recent data have also suggested that a similar response may play a role in accelerating atherosclerotic plaque development and in enhancing the formation of the macrophage foam cell, the histologic hallmark of the early atheroma. Several lines of evidence also implicate this pathway in the pathogenesis of PID, a leading cause of infertility in the developed world, and in the phagocytosis of apoptotic cells, an essential event in tissue remodeling and development. Investigators working on inflammatory bowel disease, periodontal disease, and a variety of inflammatory pulmonary disorders have also postulated an important role for CD14 in these conditions. Given the widespread interest in understanding the contributions of CD14 to normal physiology and pathologic conditions, the applicant's laboratory has generated homologous recombinant mice lacking this protein. This grant application proposes to generate a breeding colony of these animals and to distribute these mice to the many investigators that have requested them. These investigators, working on diseases supported by a diverse group of NIH Institutes, can then utilize these animals in experiments that explore the biological processes in which CD14 activity has been implicated. In addition to developing the breeding colony of CD14 deficient mice, this application proposes to characterize the utility of these animals as models for diseases that represent major human health problems in which the principal investigators of the grant have established research efforts. Thus, the CD14 deficient animals will be bred into mouse strains that are susceptible to atherosclerosis in order to explore the role of Chlamydial infections in the pathogenesis of cardiovascular disease. In addition, CD14null mice will also be used to explore the role of the endotoxin signaling pathway in mouse models of PID. This work is intended to broaden the applicability of CD14 deficient mice to research involving acute and chronic inflammatory disease and to make a critical animal resource available to the investigative community at large. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EGF, OXIDANTS & INTESTINAL BARRIER INTEGRITY Principal Investigator & Institution: Banan, Ali; Rush University Medical Center Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: Broad, long-term goal: To prevent or reverse the acute attack in inflammatory bowel disease (IBD). Strategy: If we knew the mechanism by which endogenous growth factors (GF) prevent oxidant-induced intestinal injury, we could

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47

develop GF-mimetics or enhancers for prevention/treatment of IBD. Background: Disruption of barrier integrity by oxidative stress is a major contributor to intestinal inflammation. Using monolayers of intestinal cells, we established a novel disruptive and protective mechanism-cytoskeletal damage and stability. We further reported that i) damage is caused by nitration of tubulin and actin and disassembly of cytoskeletal filaments by oxidative products of iNOS / NO upregulation; ii) pretreatment with GF (e.g., EGF) prevented damage via activation of PKC-beta1 and PKC- zeta (zetu) isoforms. Our recent Preliminary Data suggest a unifying fundamental mechanism: a) oxidants may upregulate iNOS by activating NF-kappaB (oxidants degraded NFkappaB's inhibitor, I-kappaBalpha, and translocated NF-kappaB to the nucleus; transfection of a mutant I-kappaBalpha prevented oxidant effects on I-kappaBalpha, NFkappaB, NO and barrier function); b) GFs protect via PKC isoforms inhibiting NFkappaB activation (early pilot data suggest that transfection of anti-sense to PKC-beta1 prevents GF's effects on I-kappaBalpha and NF-kappaB). This shared mechanism of damage and protection-modulation of NF-kappaB activation-led to our working Hypothesis: Growth factors in GI epithelial cells protect against oxidant-induced cytoskeletal disruption and loss of barrier integrity by preventing oxidant- induced upregulation of iNOS. Protection is mediated by activation of specific PKC isoforms that stabilize 1-kappaBalpha, prevent translocation and activation of NF-kappaB, and inhibit iNOS upregulation. Aim 1. To determine whether NF-kappaB inactivation is a key molecular event mediating GF-induced prevention of oxidant-induced effects: a) iNOS upregulation, b) microtubule disassembly; c) barrier disruption. Aim 2. To determine whether protection of cytoskeletal and barrier integrity by GF is mediated by increased signaling via PKC isoforms that is linked to downstream stabilization of I-kappaBalpha, inactivation of NF-kappaB and down-regulation of iNOS. Aims will involve strategies from both pharmacology (activators/ inhibitors) and molecular biology (transfection); monolayers will be used under conditions in which a) oxidants cause iNOS upregulation and cytoskeletal nitration and disassembly and barrier disruption, and b) preincubation with GF prevents this oxidative damage. Significance. Our studies will: i) yield new insights into fundamental protective mechanisms by GF against the oxidative stress of proinflammatory conditions; ii) substantially improve understanding of IBD pathophysiology and suggest new targets for novel anti-IBD drugs; iii) explain intestinal barrier instability during inflammation; iv) establish PKC isoform signaling as crucial in protection against inflammation. 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-AG-

48


type 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 ·

Project Title: ENDOTHELIAL LATERAL JUNCTIONS AND LEUKOCYTE EGRESS Principal Investigator & Institution: Goldberg, Peter L.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): A critical event during an inflammatory response is the recruitment of blood leukocytes to the site of injury, immune response, or infection, resulting in transendothelial migration (TEM). Dysregulation of the inflammatory response is a factor in many diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis, atherosclerosis, asthma, and psoriasis. The TEM of leukocytes from the vasculature into the neighboring tissues has been studied extensively. However, there is limited information regarding the endothelium-dependant mechanisms that may contribute to leukocyte egress at endothelial cell (EC) lateral junctions. The focus of this application is to examine leukocyte egress at endothelial cell-cell junctions, concentrating on the mechanisms that allow the rapid formation of inter-endothelial cell, claps by VE-cadherin during leukocyte TEM. Throughout this study we will make use of the a variety of in vitro molecular, biochemical, immunological, and biological techniques, including adenoviral constructs, fluorescence recovery after photobleaching and leukocyte TEM in flow chamber assays. Specifically, we will determine the 1) the lateral mobility of wild type VE-cadherin and a tailless mutant VE-cadherin in vascular endothelium and 2) examine the lateral mobility of these proteins during leukocyte TEM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 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: FUNCTION OF NUP475 IN THE GASTROINTESTINAL TRACK Principal Investigator & Institution: Worthington, Mark T.; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: (provided by applicant): AU-rich elements (AREs) are critical regulators of cytokine and proto-oncogene messenger RNAs, preventing aberrant inflammation and uncontrolled growth. The protein Nup475 (also known at tristetraprolin and TIS11) is the prototype of a family of ARE-binding proteins with a common structural motif, the Cys3His domain, which we have proven has a novel structure distinct from the classical zinc finger. Nup475 destabilizes mRNAs by deadenylation of the polyA tail, as well as with effects on transcriptional activation and to promote apoptosis. This proposal will define determinants of Nup475 binding and potential mechanisms for its action, including the role of this protein in a mouse model of inflammatory bowel disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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 2002; 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

50


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 ·

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 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: GLUCOSE-SENSING AND INTESTINAL FEEDBACK INHIBITION Principal Investigator & Institution: Raybould, Helen E.; Professor; Anatomy; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The ability of nutrients in the intestinal lumen to initiate changes in secretory and motor function in the gastrointestinal tract is well established. The precise nature of the "sensors" is not well characterized. Dietary carbohydrate in the intestinal lumen is well established to inhibit gastric emptying and food intake. The hypothesis to be tested is that dietary carbohydrate-induced inhibition of gastric emptying is dependent on binding of glucose to the sodium-glucose cotransporter SGLT on enterochromaffin (EC) cells, leading to release of 5hydroxytryptamine (5-HT) that activates 5-HT3 receptors on extrinsic afferent nerve terminals in the intestinal mucosa. To test this hypothesis, studies are proposed to determine that (1) inhibition of gastric emptying by glucose is dependent on binding of glucose to SGLT; (2) glucose-induced release of 5-HT from EC cells is dependent on

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binding of glucose to SGLT; (3) activation of vagal and spinal afferents in response to glucose is dependent on SGLT and 5-HT3 receptor activation and (4) to demonstrate the expression of 5-HT3 receptors on vagal and spinal afferent terminals innervating the duodenum and their association with EC cells. The role of SGLT-1 and 5-HT release in glucose-induced inhibition of gastric emptying will be determined in awake rats by intestinal perfusion of analogues of glucose that are or are not substrates for SGLT, and the role of binding to SGLT will be determined by infusion of phloridzin that binds but is not internalized. Finally, the role of sodium ions or protons will be determined by alteration of their concentrations in intestinal glucose perfusates. 5-HT secretion will be measured in vitro from BON cells, a model for native EC cells, to determine that glucose acts directly on EC cells. The expression of SGLT by BON cells and native EC cells will be determined by measurement of expression of SGLT protein by Western blot and by immunocytochemistry. Duodenal vagal and spinal afferent discharge will be measured to determine whether glucose activates extrinsic afferent fiber activity and whether this is mediated by SGLT and a 5-HT3-receptor pathway. The cellular sites of expression of 5-HT3 receptors in the intestinal wall and their origins will be determined in immunohistochemical studies using antisera raised to the 5-HT3 receptor in tissue from intact, capsaicin-treated and extrinsically denervated rats. The relationship between primary afferent nerve terminals expressing 5-HT3 receptors and EC cells expressing 5HT will be determined in double labeling experiments. These studies address sensory transduction in the gastrointestinal tract, which is important in the regulation of normal digestive function. There is evidence that sensory function of the intestine is altered in pathological conditions such as inflammatory bowel disease, functional bowel disease and obesity. A greater understanding of these sensory mechanisms will help in understanding the pathophysiology of these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: GREEN TEA POLYPHENOLS: A NOVEL APPROACH TO IBD Principal Investigator & Institution: Oz, Helieh S.; Internal Medicine; Rush University Medical Center Chicago, Il 60612 Timing: Fiscal Year 2004; Project Start 15-FEB-2004; Project End 31-JAN-2006 Summary: (provided by applicant): Crohn's disease and Ulcerative Colitis are chronic idiopathic inflammatory disease of the gastrointestinal tract (IBD). Current medical intervention of IBD consists of anti-inflammatory and immunosuppressive agents. Despite medical intervention, many patients remain refractory. Clearly, new therapeutic modalities are needed to minimize the destructive nature of IBD. Use of alternative medicine is widespread and on the rise in the United States. Patients with IBD frequently use alternative medicine and consider it an important form of therapy. There are a number of alternative medicine therapies that may prove beneficial. These include therapies that have anti-inflammatory properties or alter the bacterial flora in the bowel. However, the scientific evidence for the use of alternative medicines is often lacking or weak, and safety generally has not been assessed. Thus, there is a great need to establish the effectiveness and safety of alternative medicines used in patients. Green tea has potent anti-inflammatory properties. We present evidence that green tea polyphenols decrease the disease activity in interleuken-2 mice model of autoimmunity and IBD. The transcription factor, NF-KappaB and NF-KappaB-inducible inflammatory mediators (e.g. TNF-alpha, interleukin-1) play a critical role in the intestinal injury and the clinical/biochemical abnormalities observed in IBD. We recently showed that polyphenols extracted from green tea are potent inhibitors of NF-KappaB. We have compelling preliminary data showing that the green tea polyphenol and its extract (-)-

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epigallocatechin-3-gallate (EGCG), inhibit the activity of I-KB kinase (IKK), a pivotal enzyme in the NF-KappaB activation pathway. The overall objectives of this project are to determine whether green tea polyphenols (in doses ranging from functional foods to pharmacological) and/or EGCG modulate intestinal injury and immune cell responses in the Dextran Sulfate Sodium (DSS) model of Ulcerative Colitis. We will also confirm our findings using another IBD model, the interleukin-10 (IL-10) deficient mice that develop spontaneous enterocolitis (similar to Crohn's disease). These studies should provide evidence supporting green tea polyphenols/EGCG as potent anti-inflammatory therapy and provide the basis for a green tea polyphenols/EGCG intervention trials in patients with Inflammatory Bowel Disease. 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 Aob 104 Airport Drive Cb#1350 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: GROWTH REGULATION IN SURGICAL DISEASES OF THE GUT Principal Investigator & Institution: Ko, Tien C.; Surgery; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-MAY-2006 Summary: (Provided by Applicant): The specific focus of this proposal is to define the transforming growth factor-n (TGF-B) signaling pathway in gut epithelial cells. The human gut epithelium is maintained by a continuous process of self-renewal, which

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requires a balance between cell division and apoptosis. Alteration in gut renewal is a hallmark of many diseases of the gut, such as neoplastic growth and inflammatory bowel diseases, all of which contribute to a major health care burden for the United States' population. Progress in the treatment of these diseases has been hampered by the lack of insight into the molecular mechanisms regulating gut renewal. TGF-B is a most important physiological regulator of gut renewal. TGF-B signal is transduced from the receptor complex to the nucleus through a novel class of proteins, the Smads. The goal of this proposal is to determine whether TGF-f3 regulation of cell division and apoptosis is mediated through Smad proteins. We have planned experiments with the following two specific aim. In specific aim 1, we will characterize the role of Smads in TGF-B regulation of cell division. We will determine 1) which endogenous Smads are activated by TGF-B in gut epithelial cells 2) whether endogenous Smads are essential for TGF-B signaling in gut epithelial cells, and 3) whether endogenous Smads are essential for TGF-B inhibition of cyclin Dl expression, Cdk4 activity and cell cycle progression. In specific aim 2, we will characterize the role of Smads in TGF-B-induced apoptosis. We will determine 1) whether Smad3 expression correlates with sensitivity to TGF-Binduced apoptosis, 2) whether Smad3 is essential for TGF-B-induced apoptosis in gut epithelial cells, 3) which domain(s) of Smad3 is required for TGF-B-induced apoptosis, 4) which structural differences between Smad2 and Smad3 are responsible for different apoptosis responses, and 5) the changes in gene expression in TGF-B-induced apoptosis. The studies in the current proposal will extend our previous findings by further delineating the molecular mechanisms that mediate TGF-B's effects in the gut. By delineating the role of Smads in the gut, we hope to determine whether they are potential therapeutic targets for the management of human diseases of the gut. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HEPCIDIN EXPRESSION IN THE ANEMIA OF CHRONIC DISEASE Principal Investigator & Institution: Weinstein, David A.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The pathogenesis of the anemia of chronic disease is not understood. A recently identified peptide, hepcidin, has been found to be aberrantly expressed in hepatic adenomas in GSD (GSD), resulting in an iron-resistant irondeficiency anemia similar to that seen in the anemia of chronic disease. Hepcidin is postulated to be involved in the pathogenesis of the anemia of chronic disease, and these investigations are aimed at characterizing the role of hepcidin in both normal iron homeostasis and in subjects with the anemia of chronic disease. The specific aims are the following: 1) To evaluate the relationship between adenoma tumor burden and anemia; 2) To characterize iron absorption and distribution in normal controls, anemic patients, and patients with GSD Type 1 at (GSD1a; 3) To compare hepcidin expression in normal individuals and patients with GSD1a, and 4) To determine the role of hepcidin as a mediator of the anemia of chronic disease in patients with other inflammatory conditions. Methodology: The relationship between iron homeostasis and hepcidin expression will be studied in normal and pathologic states including GSD1a, juvenile rheumatoid arthritis, and inflammatory bowel disease. As inappropriate hepcidin expression has been demonstrated in hepatic adenomas in patients with GSD, direct observational studies in this population will be performed to allow further clinical correlation between these lesions and indices of erythropoiesis and iron status. Oral absorption of iron will be investigated in all subjects to define the relationship between hepcidin and iron absorption. For the inflammatory disorders, the oral iron challenge

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tests and direct measurement of hepcidin will be performed during periods of disease remission and exacerbation. The relationship between hepcidin and inflammatory markers will also be investigated. Through these studies, the role of hepcidin as a mediator of anemia of chronic disease will be elucidated. Improved understanding of the pathophysiology of the anemia of chronic disease will lay the foundation for new treatments for anemia and disorders of iron homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: IBD RESEARCH--JUNIOR FACULTY SYMPOSIUM Principal Investigator & Institution: Barrett, Terrence A.; Associate Professor of Medicine and Micr; Medicine; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 17-JAN-2002; Project End 31-DEC-2002 Summary: provided by applicant): The Principal Investigator proposes to convene a symposium geared towards the development of junior faculty in the area of inflammatory bowel disease research from 1/11/2002 to 1/13/2002 in Chicago, IL at Northwestern Memorial Hospital of the Northwester University Medical School. The purpose of the symposium will be to provide a forum for junior faculty to present their research, network with peers and obtain feedback on their planned research proposals. All presenters will be junior faculty who will present work intended for submission to external funding agencies such as the National Institutes of Health. The talks will be presented in two sections. In the first section, the speaker will present in the following format: 1) a brief introduction, 2) novelty and biologic relevance of the model, 3) results of data from the investigator's lab, and 4) conclusions. In the second section, the speaker will present the rational and hypothesis-driven goals of a research proposal being considered for submission. The presentation will be followed by an open discussion by members of the audience selected for their expertise and experience as grant reviewers. Two members of the audience will be specifically assigned to provide a written critique to the speaker during the meeting along with a priority score based on the NIH scale (1 to 5). The basic science talks will be divided into sessions in the following categories: 1) epithelial cell differentiation and neoplasia, 2) epithelial cell immune activation, 3) mechanisms of mucosal immune responses, and 4) inflammatory bowel disease models. A dinner program will feature a keynote address on mechanisms in human IBD with the remainder of the evening devoted to a poster session with presentations by fellows and junior faculty not speaking during the day. The poster session will be attended by speakers as well as senior faculty. An important purpose of the evening session will be to provide time for speakers to meet other junior faculty as well as senior investigators. The goals of the symposium will be to 1) provide exposure for junior faculty, 2) provide scientific review for projects in their early development, and 3) provide an atmosphere for networking for junior and senior investigators. It is our proposition that the bringing together of junior faculty with their peers as well as senior investigators will generate a dialogue helpful to the development of their research as well as begin their incorporation into the scientific community of inflammatory bowel disease research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 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 2002; 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 (IFNbeta), 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 IFN-beta 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-

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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 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 IFN-beta (Aim #2). In addition, murine models will be used to examine the role of both IFN-beta 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

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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 ·

Project Title: IL-16 IN PULMONARY CRYPTOCOCCOSIS Principal Investigator & Institution: Kornfeld, Hardy; Professor; Medicine; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Interleukin-16 (IL- 16) is a structurally unique cytokine that uses CD4 as a receptor to signal diverse biological activities in target cells including but not limited to T cells, monocytes, dendritic cells and eosinophils. Initially described as a chemoattractant factor for CD4+ T cells, IL-16 was later found to upregulate IL-2Rcz and HLADR expression, and to cause reversible anergy of CD4+ T cells in vitro. A role for IL-16 in pathological immune responses is suggested by its presence in a variety of diseases characterized by CD4+ T cell accumulation including asthma, sarcoidosis, inflammatory bowel disease, and rheumatoid arthritis. In some disease states, epithelial cells or fibroblasts express IL-16. A role for IL-16 in host defense is suggested by elevated blood levels in HIV-infected hosts, and by its expression in tuberculous granulomas. The biological activities described for IL-16 in vitro suggest that it could function either as a pro-inflammatory or anti-inflammatory cytokine in vivo. We cloned the murine IL-16 gene and used it to create an IL- 16 knockout mouse. In this application, we propose to challenge the IL-16 knockout mouse by experimental infection with Cryptococcus neoformans to learn how IL-16 functions within the integrated immune response in vivo. Preliminary data suggest that IL-16-/- mice fail to control pulmonary C. neoformans infection despite mounting an exuberant inflammatory response. We will investigate the specific deficits displayed by IL-16-/mice in both the T cell and macrophage components of cell-mediated immunity, and we will examine the role of IL-16 expression by bronchial epithelial cells in host defense. Our research plan capitalizes on a well-characterized mouse model of cryptococcal infection that provides an excellent basis to study normal and abnormal cell mediated immune responses in the lung. The project will contribute new basic knowledge about the role of IL-16 in immunity, and it will provide additional understanding of protective immunity against the important AIDS co-pathogen C. neoformans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNE DIFFERENTIATION

MODULATION

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INTESTINAL

CELL

Principal Investigator & Institution: Wu, Gary D.; Associate Professor of Medicine; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUL-1995; Project End 31-MAY-2005 Summary: Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear hormone receptor superfamily originally shown to play a critical role in adipocyte differentiation and glucose homeostasis, has recently been implicated as a regulator of cellular proliferation and inflammatory responses. Ligands for PPARgamma include prostanoids such as 15-deoxy-delta 12,14 prostaglandin J, (15dPGJ,), polyunsaturated fatty acids, a variety of non-steroidal anti-inflammatory drugs (NSAIDS), and a new class of oral antidiabetic agents, the thiazolidinediones (TZDs).

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Colonic epithelial cells, which express high levels of PPARgamma protein, have the ability to produce inflammatory cytokines that may play a role in inflammatory bowel disease (IBD). In preliminary data, we show that PPARgamma ligands dramatically attenuate cytokine gene expression in colon cancer cell lines by inhibiting IkappaB-alpha phosphorylation and activation of Nuclear Factor Kappa B (NF-kappaB); a mechanism that requires the activation of new gene transcription and protein synthesis. These same ligands also induce the expression of the anti-inflammatory protein, annexin I (lipocortin I). Moreover, we show that thiazolidinedione ligands for PPARgamma markedly reduce colonic inflammation in a mouse model of IBD. Ligands for PPARgamma may therefore have promise as novel therapeutic agents for the treatment of patients with IBD. The overall goal of this grant proposal is to identify and characterize candidate molecular mechanisms by which TZD and prostanoid ligands for PPARgamma inhibit the intestinal inflammatory response. We hypothesize that PPARgamma ligands inhibit the intestinal immune response by the activation of gene transcription through a PPARgamma dependent mechanism. Based on this hypothesis, three specific aims will be pursued: 1) To determine the role that PPARgamma and its post-translational modification plays in the regulation of the intestinal epithelial immune response through cell culture models, 2) To clone the PPARgamma Ligand dependent Inhibitor of IkappaB-alpha Phosphorylation (PLIP) as well as identify its kinase target, and 3) To identify the molecular mechanisms by which these ligands activate annexin I expression in vitro as well as determine its pattern of expression in vivo. Ultimately, the studies described in this grant proposal may provide novel insights into mechanisms by which nuclear hormone receptors and their ligands modulate the intestinal inflammatory response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: IMPACT OF CO-RECEPTOR AND HIV VIRAL BURDEN ON GUT MUCOSA Principal Investigator & Institution: Anton, Peter A.; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: (adapted from the application's abstract): This application requests funds to allow the principal investigator, Dr. Peter Anton, to pursue clinical research on the quantification of mucosal viral loads and the characterization of mononuclear cells present in focal infections of HIV-1 in the intestinal mucosa. This work is based on newly developed methods in Dr. Anton's group to reproducibly isolate mucosal lympoid tissue. There are three specific aims. In Aim 1, Dr. Anton will continue with the optimization of the technique for isolation and characterization of mucosal lymphoid tissue to test the hypothesis that HIV infection is associated with mucosal inflammation. This part of the application will focus on the isolation of mononucelar cells and on quantitative methods to measure tissue RNA/DNA for HIV-1. In Aim 2, a study will be carried out to examine the correlation between CCR5 co-receptor expression and enhanced susceptibility to infection with HIV-1. Additionally, the relationship between HIV infection and D- chemokine expression (as a marker of inflammation) will be sought to test this hypothesis. In Aim 3, a clinical study will be executed to test the hypothesis that inflammation is a clinically significant feature of HIV persistence. This will be done by looking for decreased mucosal viral burden and evidence of immune reconstitution after therapeutic intervention. 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: INHIBITION OF IMMUNE RESPONSES BY CD8ALPHAALPHA-TL Principal Investigator & Institution: Cheroutre, Hilde; La Jolla Institute for Allergy/Immunolgy 10355 Science Center Dr San Diego, Ca 921211118 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2005 Summary: (provided by applicant): T cells in the intestinal mucosa face continual antigenic challenge from the contents of the intestine. Therefore, specific mechanisms of immune regulation must have evolved to prevent uncontrolled immune responsiveness in the gut. In fact, there is evidence that loss of proper immune regulation in the intestine leads to inflammatory bowel disease (IBD). Many T cells in the intestinal mucosa of mice express a homodimer form of CD8a chains instead of an W13 heterodimer. Evidence presented in the Preliminary Results section shows that the TL antigen, a class I molecule which is expressed almost exclusively by intestinal epithelial cells in mice, strongly prefers to bind to CD8cw. By contrast, other class I molecules show preference for binding CD8ab. Our data further suggests that the interaction between CD8aa and TL can inhibit immune reactivity. Our overall hypothesis is that the TL-mediated engagement of CD8aa, separately from the TCR-MHC complex, down regulates TCR-mediated signal transduction and thus prevents chronic stimulation. The experiments outlined are designed to explore the TL-CD8acz interaction. In aim I, the functional consequences, in terms of T cell proliferation, cytotoxicity and cytokine release, will be analyzed in vitro using TL positive presenting cells. In aim 2, the consequences of this interaction will be explored in vivo. Several transgenic and gene knock out strains, that differ with regard to their TL-CD8aa interactions, will be

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analyzed for mucosal T cell number and function. In aim 3, the biochemical basis for preferential binding of the TL antigen to CD8aa will be characterized. In aim 4, the membrane proximal signal transduction events altered by CD8 aa engagement will be analyzed. The experiments in this application therefore will characterize a novel regulatory mechanism for mucosal T cells. As regulation of and by intestinal T cells is crucial in controlling intestinal inflammation and preventing IBD, in the induction of oral tolerance, and in the surveillance for cancers of epithelial cells, the results from these studies could have important ramifications for understanding normal homeostasis and treatment of pathological conditions in the intestinal mucosa. Furthermore, in mice and humans, CD8aa can be expressed by activated T cells and NK cells, and in vitro studies show that engaging CD8aa on systemic T cells can be inhibitory. Therefore, the mechanisms outlined here could have implications for cancer and other diseases that extend beyond the mucosa. 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: 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 2002; 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 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

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Project Title: INTESTINAL EPITHELIAL TIGHT JUNCTION STRUCTUREFUNCTION Principal Investigator & Institution: Nusrat, Asma; Associate Professor; Pathology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Inflammatory bowel disease (IBD) is characterized by relapsing intestinal inflammation and altered epithelial permeability resulting in fluid/electrolyte loss and systemic exposure to luminal antigens. Permeability changes have, in turn, been attributed to defective tight junction (TJ) structure/function. Details of epithelial TJ composition and its relationship to gate/fence function are still rudimentary. We have recently shown enrichment TJ proteins in "raft" like membrane microdomains. The major objective of this proposal is to define functionally relevant structural elements in TJs of epithelial cells with the following two specific aims. Specific Aim 1: To identify novel intercellular junction proteins involved in regulation of intestinal epithelial permeability using a monoclonal antibody approach. We have utilized TJ-enriched membrane fractions to generate four monoclonal antibodies that recognize unique epitopes in TJs of epithelial cell lines and native intestinal epithelial

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cells. The primary focus will be on defining the antigens for these antibodies. Epitope modulation by cytokines (IFN-gamma, HGF) important in inflammation/repair will be determined. Expression of their respective antigens in native normal and inflamed intestinal tissues will be analyzed. Specific Aim 2: To define molecular targets for tight junction proteins key in regulating intestinal epithelial permeability using a bait-peptide approach. We will capture protein components in the TJ complex using novel bait peptides representing segments of the TJ transmembrane protein, occludin. Biotinylated, photoactive bait peptides have been generated to recapitulate: 1) a 27 aa coiled-coil region in the cytoplasmic tail; and 2) 21 aa regions in the first and second extracellular loops. Peptide protein complexes in epithelial cells will be captured using a solid matrix of avidin. Functional consequences of peptide protein binding on TJ gate/fence function will be explored. Information from these studies should reveal important mechanistic insights into the structure/function of TJs and should provide novel insights into potential therapeutic targets for the prevention or correction of epithelial permeability defects associated with IBD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: INTESTINAL INFLAMMATION ORCHESTRATED BY PATHOGENS Principal Investigator & Institution: Mc Cormick, Beth A.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: The active phase of both Salmonella-associated gastroenteritis and chronic states of inflammatory bowel disease IBD), such as ulcerative colitis and Crohn's disease, is characterized histologically by polymorphonuclear leukocyte (PMN) migration into and across the epithelial lining of the intestine. These events result in acute inflammation of the epithelium and subsequent epithelial dysfunction. The degree of PMN transmigration into intestinal crypts and the formation of crypt abscesses is indicative of disease severity and is used clinically to evaluate the activity of IBD. It is unclear what triggers directional movement of PMN across the intestinal epithelium. Towards this end, we have recently shown that epithelial cells themselves can send such signals to underlying PMN and these signals are regulated by enteric flora, such as S. typhimurium. The broad long term objectives of this proposal are to investigate the molecular mechanism by which epithelial cells in response to microbial pathogens can signal to PMN and orchestrate their directed migration. Once we begin to understand the basis of such transcellular signaling important in promoting disease flares of S. typhimurium pathogenesis, it may be possible to develop novel therapeutic strategies aimed at treatments for and ameliorating IBD. The specific aims are ultimately directed at achieving this goal, and are three-fold. Specific Aim 1 is designed to determine the nature of S. typhimurium virulence factors and define their contribution to the epithelial orchestration of mucosal inflammation. Specifically, we will delineate how S. typhimurium SipA, SopB, and SopA secreted proteins interfere with the signaling pathways which lead to epithelial orchestration of mucosal inflammation by expression of these proteins in epithelial cells using adenoviral expression vectors. Functional effect of expression of these proteins on orchestration of proinflammatory events which govern PMN transepithelial migration will be correlated with morphological consequences by both confocal and electron microscopy. Specific Aim 2 is designed to identify the signal transduction cascades which lead to the release of the proinflammatory chemoattractant PEEC and will employ several different approaches which include determining the relationship between S. typhimurium invasion and the apical epithelial release of PEEC, examination of the role of the JNK-pathway,

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determining the effects of small GTPase (cdc42, rac-1, and Arf6) expression on the ability of S. Typhimurium to induce PMN transepithelial migration by expression of dominant inhibitory mutants using adenoviral expression vectors, examining the role of phosphinositide signaling, and determining whether the ability of S. typhimurium to elicit PEEC secretion correlates with their ability to induce an increase in intracellular calcium in model intestinal epithelia. Specific Aim 3 is designed to characterize a recently identified pro-inflammatory PMN chemoattractant. The first part of this aim will elucidate the structure of PEEC utilizing HPLC purification, NMR analysis, mass spectrometry and sequence analysis, while the second part of this aim will define PEEC's relationship to other PMN chemoattractants including its ranking in the PMN chemoattractant hierarchy, will determine whether PEEC is able to activate other immune-type cells as well as assess the role of PEEC in inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: INTESTINAL MECHANISMS OF TOLERANCE Principal Investigator & Institution: Newberry, Rodney D.; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-DEC-2003 Summary: The gastrointestinal tract contains the largest number of lymphocytes in the body that experience the greatest exposure to antigen. Central to our well being is the ability of the gastrointestinal immune system to mount an effective immune response to pathogenic bacteria and viruses, and at the same time display an immunologic hyporesponsiveness, or tolerance, to absorbed nutrients. The occurrence of tolerance to ingested antigens is well documented, however the mechanisms by which this tolerance occurs remain a mystery. Breakdown in the mechanisms of tolerance in the gastrointestinal immune system may result in diseases such as inflammatory bowel disease or celiac sprue. We believe that the intestinal lamina propria represents a specialized environment for the development and maintenance of a subset of immunoregulatory T- lymphocytes responsible for tolerance to ingested soluble antigens. We believe that macrophage tolerance to lipopolysaccharide and the immunoregulatory cytokines interleukin 10 and transforming growth factor beta are crucial to the induction and maintenance of tolerance in the gastrointestinal tract. Our preliminary data supports the hypothesis that when T lymphocytes in the lamina propria, in contrast to T lymphocytes from classical secondary lymphoid tissues, are stimulated by antigen, they exert a down regulatory effect on the immune response. We further hypothesize that development and maintenance of these immunoregulatory T lymphocytes is dependent upon the specialized environment of the intestinal lamina propria. To gain a better understanding of how the T-lymphocytes and antigen presenting cells in the lamina propria may regulate the immune response to ingested soluble antigens we propose the following specific aims: 1) Determine the role of macrophage tolerance to LPS in the induction and maintenance of tolerance in the gastrointestinal immune system. 2) Investigate the in vitro immunoregulatory capacity of the lamina propria lymphocytes. 3) Assess the ability of lamina propria lymphocytes to act in an immunoregulatory capacity in vivo in models of intestinal inflammation, lamina propria lymphocytes. We believe that understanding how the gastrointestinal immune system maintains a state of tolerance to ingested soluble antigens is of paramount importance in understanding the pathogenesis of gastrointestinal inflammatory diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LYMPHOTOXIN ALPHA BETA AND LIGHT CYTOKINE SYSTEMS Principal Investigator & Institution: Ware, Carl F.; Head Division Molecular Immunology; La Jolla Institute for Allergy/Immunolgy 10355 Science Center Dr San Diego, Ca 921211118 Timing: Fiscal Year 2003; Project Start 01-AUG-1994; Project End 31-DEC-2007 Summary: (provided by applicant): Lymphotoxin(LT)-alphabeta LIGHT cytokine systems have emerged as critical factors regulating the development and effector functions of innate and adaptive immune systems. This project period is focused on the actions of LIGHT and LTalphabeta as regulators of lymphocyte activation and survival. Beyond the recognized role of LTalphabeta in lymphoid organogenesis, new results indicate that LTalphabeta and LIGHT are essential for survival of T and B lymphocytes in response to a viral pathogen. Constitutive expression of LIGHT as a transgene in T cells leads to a profound cell-mediated, intestinal inflammatory disease, but with lymphoid abnormalities. Further, LIGHT is a candidate susceptibility locus for inflammatory bowel disease in humans providing strong circumstantial evidence linking these cytokines to a human autoimmune disease. Additionally, ligation of HVEM leads to negative regulation of T cell responses that can override CD28 costimulation. Three specific aims are proposed to elucidate their roles in T cell activation and survival. The first aim develops a transferable model of intestinal inflammation by expression of LIGHT in splenic T cells via a feline immunodeficiency virus (FIV; lentivirus) vector. T cells are adoptively transferred into HVEM-/- and LTbetaR-/- mice to determine the receptor basis of the inflammatory phenotype. The functionality of the distinct physical forms of LIGHT will be examined with this FIV model. The regulatory elements and mutations/polymorphisms that control human LIGHT gene expression and protein function will be defined using bioinformatic and molecular genetic approaches. Monoclonal Abs to mouse HVEM and LTbetaR were developed that function as immune modulators. The second aim focuses on the use of these antibodies to directly probe the functions of HVEM in physiological settings, including the 5CC7 TCR-Tg mice and the CD4+CD45Rb(hi) adoptive transfer model of inflammatory mucosal disease. Finally, the signaling pathways induced by HVEM will be investigated using biochemical and genetic systems to elucidate the mechanism of negative signaling in T cells. The specific effector molecules induced by LTbetaR and HVEM signaling pathways, identified by their functional properties or through DNA array analysis, will be tested using virus infection and LIGHT-induced intestinal inflammation models. Together these aims will provide new insight into the physiologic role of the LTalphabeta and LIGHT cytokine systems in cell-mediated inflammatory reactions and pathogenesis of human autoimmune disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MASSIVELY PARALLEL GENE EXPRESSION ANALYSIS Principal Investigator & Institution: Quigg, Richard J.; Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 25-JUN-2001; Project End 31-MAY-2004 Summary: The research proposed in this application will develop and utilize massively parallel gene analysis technology. Both commercially available microarrays from Affymetrix and arrays custom-made in this facility will be used. The basic strategy for these experiments is to identify genes that are relevant for individual experimental projects. These finite gene sets will be included on arrays made in our facility, which will be customized for the individual user. The advantages of such an approach are that

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multiple experiments will then be performed cost effectively, allowing appropriate statistical analyses of data, as well as systematic variations and manipulations. Ongoing studies are those from NIDDK-funded investigators examining disease processes and models in humans, animals and homogenous cells: 1) Nephropathy occurring during the course of experimental diabetes mellitus in mice; 2) Lymphocytic abnormalities in mice with experimental inflammatory bowel disease (IBD); 3) Molecular basis of intestinal epithelial adaptation to altered luminal sodium load; 4) Activation defects in monocytes from patients with IBD; 5) Effects of steroids on muscle and adipocyte gene expression in polycystic ovary syndrome; 6) Analysis of signaling defects in mouse models of thyroid hormone resistance; 7) Analysis of signaling defects in patients with thyroid hormone resistance; 8) Analyses of mRNA changes in human pancreatic islets prepared for transplantation; 9) Effects of high glucose exposure to pancreatic beta cells; and, 10) Neuronal gene expression in response to gonadotropin-releasing hormone. These analyses will permit the identification of relevant genes that are upregulated or downregulated in these various conditions. Pilot and feasibility studies will be to: 1) Develop cDNA microarrays from pituitary, pancreatic islets and renal glomeruli to allow gene profiling from these anatomically unique sites; and 2) Utilize laser capture microdissection microscopy to obtain glomerular RNA from animal models and human tissue specimens of lupus nephritis, and subsequently apply microarray technology to identify gene changes in this disease. If this NIDDK-sponsored core facility is funded, innovative work investigating gene expression in a variety of renal, endocrinologic and gastrointestinal disease models and processes will be performed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MECHANISMS OF COLONIC RESPONSES TO NEUROTENSIN Principal Investigator & Institution: Pothoulakis, Charalabos; Associate Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: The pathophysiology of inflammatory bowel disease (IBD), and Clostridium difficile toxin-associated colitis, two common GI clinical entities with significant morbidity and mortality, is not completely understood. Recent evidence indicate that binding of neuropeptides to receptors on intestinal epithelial cells plays a critical role in the pathogenesis of colonic inflammation. We showed that neurotensin (NT), a neuropeptide released in the colon in response to several stimuli, triggers NF-kappaB activation and release of proinflammatory cytokines from the colonic mucosa. Moreover, high affinity NT receptors are expressed on colonic epithelial cells and are upregulated in IBD and C. difficile toxin-mediated enterocolitis. However, the molecular and biochemical mechanism(s) by which NT binding triggers these responses are not known. Our hypothesis is that the peptide NT, acting through G -protein coupled type 1 receptors (NTR1) on colonic epithelial cells, stimulates signal transduction pathways involving PKC, MAPK and NF-kappaB leading to IL-8 release. Aim 1 will examine the role of the NF- kappaB/IkappaB system in IL-8 gene expression following neurotensin stimulation in colonic epithelial cells. Experiments in this aim will elucidate the role of MAP kinase pathways in NTR1-induced NF-kappaB activation and IL-8 gene expression and examine the importance of PKC-epidermal growth factor communication in MAP kinase activation following NTR1 stimulation. Aim 2 will determine the functional role of the Rho family of small GTP binding proteins RhoA, Rac, and Cdc42 in NT- induced IL-8 expression and determine whether NT binding to NTR1 activates the Rho family proteins. Experiments in this aim will also identify which heterotrimeric G protein receptor subtype is involved in NTR1-induced NF-kappaB activation and IL-8 gene

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expression, as well as activation of Rho family proteins. Studies described in aim 3 will identify the structural determinants of NTR1 that mediate NT-induced IL-8 expression. Specifically, we will examine the role of the third intracellular loop and the C-terminus of NTR1 in NT signaling and IL-8 expression in human colonocytes. Studies are also proposed to identify the critical residues within the third intracellular loop and the Cterminus involved in NTR1-mediated IL-8 production. Our results will provide important insights on the role of NT and its high affinity receptor in colonic inflammation and may lead to novel therapeutic approaches for the treatment of intestinal inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MICROECOLOGY-MURINE GUT-INITIATION & PROGRESSION OF IBD Principal Investigator & Institution: Fox, James G.; Director and Professor; Div of Comparative Medicine; Massachusetts Institute of Technology Room E19-750 Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant): Genetically engineered mice with immune dysregulation have been used with increasing success in attempting to unravel and comprehend IBD in humans. IBD is considered to be the result of a combination of genetic and environmental factors. Microbial flora are undoubtedly an important component of the disease process, in which microbial antigens are thought to initiate and promote inflammation, particularly in the presence of immune dysregulation or an impaired mucosal barrier in the susceptible host. The understanding of the complex microecology of the distal intestine is extremely limited because of the tedious nature of identifying individual bacterial species and strains by conventional methods, and the inability to culture many fastidious commensal organisms. To circumvent this lack of bacterial speciation, gnotobiotic animals colonized with known microbiota have been used to great advantage. A standardized microbiota used in colonizing germfree rodents referred to "Altered Schaedler Flora" (ASF) was developed. Because of the limitations of an in vivo monitoring system used to identify the 8 anaerobic bacterial species in ASF, we recently characterized their phylogenetic positions relative to known bacteria by utilizing 16S rRNA sequence analysis. This proposal will use molecular techniques, based on quantitative PCR of ASF 1 6S rRNA, to screen the microbial diversity of the murine gut and ascertain how microflora dynamics, under defined experimental conditions, with and without helicobacters, influence initiation and progression of IBD in the mouse. Specifically we will 1) characterize, using molecular techniques, the identification, quantification and distribution of Altered Schaedler's Flora (ASF) in the gastrointestinal tract of the IL-1O-/- and the C57BL mouse. 2) Determine how enteropathogenic Helicobacter spp. associated typhlocolitis in the lL1O-/- mice alters the microecology of the lower bowel and correspondingly, ascertain whether and how individual species in ASF influence the progression or attenuation of chronic intestinal inflammation. 3) Determine microbial dynamics of ASF after physiological and anatomical perturbation of the lower bowel in mice as well as altering host genotype an how these changes influence subsequent induction of typhlocolitis and possibly colonic adenocarcinoma induced by Helicobacter spp. 4) Determine perturbations of ASF and Helicobacter spp. prior and subsequent to oral vaccination with Helicobacter spp. antigens and mucosal adjuvants, elucidate how these vaccine strategies influence microflora dynamics and impact gut cytokine responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MICROENVIRONMENT IN ENTERIC NEURON DEVELOPMENT Principal Investigator & Institution: Gershon, Michael D.; Professor and Chairman; Anatomy and Cell Biology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-DEC-1979; Project End 31-JAN-2005 Summary: (From the Applicant's Abstract): The enteric nervous system (ENS) is the largest, most complex, and functionally independent division of the PNS. It develops from precursors that migrate to the bowel from specific regions of the neural crest; however, the developmental program of the population is not set before it reaches the gut. Instead, that program is orchestrated within the bowel, and involves both the lineage-determined genes expressed by crest-derived cells and signaling molecules (growth factors and guidance molecules) in the enteric microenvironment. This application tests the following hypotheses: (i) HAND2, a basic helix-loop-helix (bHLH) transcription factor, recently found to be expressed early in the developing ENS and to be "proneural," commits enteric crest-derived precursors to the neuronal lineage. Experiments will include gain and loss of HAND2 function (HAND2-/- mice; antisense oligonucleotide blockade). (ii) HAND1, a related bHLH factor that is normally expressed in sympathoadrenal (SA) but not in enteric neurons, causes the phenotype of common Mash-1-dependent SA-enteric progenitors to become SA (stably catecholaminergic/express TrkA) rather than enteric. (iii) Both NT-3/TrkC and BDNF/TrkB are essential for the formation of specific subsets of enteric neurons (which we will identify by molecular, immunocytochemical, and in vitro experiments). (iv) BDNF/TrkB signaling partially ameliorates ENS defects in mice lacking NT-3/TrkC. (v) TrkC is expressed before TrkB and NT-3 (and/or a neuropoietic cytokine) induce TrkB expression. (vi) NT-3 and BDNF exert trophic influences on synapses in the mature ENS, thereby altering enteric neurotransmission and enhancing propulsive motility (for which NT-3/BDNF are undergoing testing as prokinetic drugs). (vii) Chemoattraction, mediated by netrins/DCC, is important in the formation of the submucosal plexus and in the migration of crest-derived precursors from the bowel to form the pancreatic ganglia. (viii) Slit proteins (ligands) and Robo receptors, which are expressed in the fetal gut, repel migrating enteric crest-derived cells and thus help to prevent them from reaching incorrect destinations. Congenital defects of the ENS are relatively common and may not all be as evident as congenital megacolon (Hirschsprung's disease; aganglionosis of the terminal bowel) or pseudoobstruction. Some may be subtle and contribute to functional or inflammatory bowel disease in later life, in which the ENS component is not currently appreciated, but may be revealed (and ultimately treated) by understanding ENS development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR ETIOLOGY OF FAMILIAL MEDITERRANEAN FEVER Principal Investigator & Institution: Gumucio, Deborah L.; Associate Professor; Cell and Developmental Biology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Patients with the autosomal recessive disease, Familial Mediterranean fever (FMF), suffer periodic, unpredictable attacks of fever associated with severe pain; the pain is localized most commonly in joints (arthritis), abdomen (peritonitis) or chest (pleuritis). Occasionally, this disease presents with skin manifestations (erysipeloid erythema), pericarditis, vasculitis, or myalgia. In many patients, amyloidosis is a complication, and if untreated, this can be life-threatening.

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FMF is caused by missense mutations in pyrin, a protein of unknown function expressed in neutrophils, monocytes, eosinophils, dendritic cells, synovial cells and skin and peritoneal fibroblasts. Pyrin expression in these cells is induced by proinflammatory cytokines and by LPS. Thus, it has been speculated that pyrin modulates the inflammatory response. Evolutionary studies of the pyrin molecule indicate that it has been under positive Darwinian selection during evolution of the primates. Moreover, the high frequency of mutant pyrin alleles in several human ethnic groups supports a heterozygote (selective) advantage for the mutant allele. Mutant forms of pyrin may enhance the body's ability to clear important pathogen(s). Indeed, acute phase reactants, important agents of innate immunity, are up-regulated not only in patients but in carriers of mutant alleles. Structural analysis of the pyrin molecule revealed that exon 1 encodes a death-domain related structural motif (known as the pyrin domain or PyD) that is found in a growing family of proteins involved in inflammation and innate immunity. Identification of pyrin-interacting proteins as well as additional functional studies reveal that pyrin is linked directly to apoptotic and cytoskeletal signaling cascades, and that it modulates cytokine secretion. Experiments described in this proposal are designed to further explore these functions of pyrin and determine the effects of pyrin mutations on apoptosis (Aim 1); cytoskeletal signaling (Aim 2); and cytokine production (Aim 3). Recently identified pyrin isoforms will also be examined in these functional assays, since preliminary studies indicate that the various isoforms may function differently. Such studies could provide clues to understanding of the molecular pathogenesis of FMF, and may reveal new information about inflammatory pathways in general. In fact, pyrin-interacting proteins and pyrin domain-containing family members have already been connected to several human diseases, including inflammatory bowel disease, PAPA syndrome, Muckle-Wells syndrome, familial cold urticaria, Blau syndrome and Bechet's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MUCIN SECRETION IN COLUMNAR EPITHELIAL CELLS Principal Investigator & Institution: Kuver, Rahul P.; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 15-APR-1999; Project End 31-DEC-2003 Summary: Mucins are high molecular weight glycoproteins which form a viscous gel lining epithelial surfaces forming a physical barrier between the host and the environment. All columnar epithelial cells secrete mucins, as do specialized goblet cells lining the gastrointestinal tract. A mechanistic understanding of mucin secretion has clinical relevance for a number of diseases including cystic fibrosis (CF), inflammatory bowel disease and peptic ulcer disease. Prior work on mucin secretion has been performed in neoplastic cells. Furthermore, much of the knowledge in this field is derived from the study of goblet cells. Whether the same processes apply to nonneoplastic columnar epithelial cells is not known. We propose to employ cystic fibrosis as a disease model to probe structural and functional aspects of mucin secretion in columnar epithelial cells. Thick mucus is a phenotypic hallmark and causes much of the morbidity of CF. Studies by our group and others show a complex relationship between CFTR, the chloride channel defective in CF patients, and the processes by which mucin glyproteins are secreted by columnar epithelial cells. We hypothesize that in CF columnar epithelial cells, post-translational processing of mucin glycoproteins and mucin granule exocytosis are altered. The specific aims are to: 1. Characterize the signal transduction pathways involved in mucin secretion in columnar epithelial cells, and determine whether mucin secretion is dependent on chloride ion movements. 2.

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Investigate mucin post-translational processing in columnar epithelial cells. 3. Determine whether CFTR is functionally involved in mucous granule exocytosis in columnar epithelial cells. 4. Determine whether isolated mucous granules contain functional CFTR This proposal will provide a structured framework of research training for the candidate. The sponsor's group's expertise in biliary cell biology will ensure a supportive and stimulating environment for the candidate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MUCOSAL HIV AND IMMUNOBIOLOGY CENTER Principal Investigator & Institution: Smith, Phillip D.; Professor of Medicine; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): This application is for the establishment of a University of Alabama at Birmingham (UAB) Digestive Diseases Research Development Center (DDRDC), focusing on the interaction between microbes and the host in mucosal tissues. Principal among the microbes to be studied will be HIV-1, which enters the host through the gastrointestinal and genital tract mucosae; Helicobacter pylori, the most common cause of gastric inflammatory disease; and the commensal bacterial flora, which plays a critical role in the pathogenesis of inflammatory bowel disease. UAB's mucosal immunologists, recognized for their leadership in the study of mucosal pathogens and mucosal ceil immunobiology, have heretofore collaborated individually in an informal, project-oriented manner. We believe that a DDRDC will synergize the research efforts of these investigators into a world-class, program-oriented, mucosal immunology research group more capable of accomplishing breakthroughs in digestive diseases research. Accordingly, the goals for a DDRDC at UAB are the following: (1) Provide an efficient and effective mechanism for expediting, expanding and fostering research in the interaction between microbes, especially HIV-t, H. pylori and the commensal flora, mucoal [sic] epithelium and mucosal innate and adaptive immune cells. (2) Coordinate and pool University-wide resources otherwise not available to individual UAB mucosal immunoogists [sic] in a cost-effective, user-friendly Center. (3) Provide a resource-, expertise- and intellectual-rich environment to generate new concepts in mucosal HIV-1, H. pylori and commensal microbe immunobiology, resulting in new initiatives inte [sic] and investigators in digestive diseases research. These goals will be accomplished through three Cores, including a (1) GeneticallyDefined [sic] Microbe and Expression Core, (2) Cell and Molecular Pathology Core, and (3) Gnotobiotic and Genetically-Engineered [sic] Mouse Core. These Cores will promote digestive disease research at UAB and enhance the goals of the DDRDC program. Since the space and equipment for each Core are largely in place, this application seeks funding to staff, supply and run the Cores. In summary, the goals and components described above define the proposed UAB DDRDC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MUCOSAL T-CELLS IN EARLY&LATE PEDIATRIC CROHN'S DISEASE Principal Investigator & Institution: Kugathasan, Subra; Pediatrics; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: PROPOSAL (Adapted from the applicant's abstract): The overall goal of this project is to functionally and phenotypically characterize gut mucosal T-cells in children

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with new onset as well as longstanding Crohn's disease (CD), and use this information in guiding the development of new strategies for CD diagnosis, patient substratification and early medical intervention. CD is a devastating lifelong chronic inflammatory destruction of the gastrointestional tract that is most frequently diagnosed in adolescents and young adults. Because the cause of CD remains undefined, diagnosis relies on the identification of destructive mucosal changes identified on x-ray, endoscopy and/or tissue histology. Recent clinical trials suggest that early immunomodulator therapy results in an improved clinical outcome in CD children, but early medical intervention may be hindered by a lag in diagnosis of up to 18 months. Basic investigation also suggests significant differences exist in cellular and molecular mechanisms between "early" and "late" phases of chronic inflammation in the intestine, further emphasizing the need for investigation both at the time of diagnosis as well as in longstanding CD. Over the past four years, the investigators have conducted a systematic investigation of mucosal T-cells isolated from endoscopic biopsies in children with CD as well as non-inflammatory bowel disease (IBD) inflammation and normal controls. They have defined unique patterns of in vitro T-cell growth and proliferation in response to interleukin-2 (IL-2), where CD, mucosal T- cells demonstrate significantly enhanced in vitro growth (J. Peds., 133: 675- 81, 1998). Recent flow cytometric analysis of mucosal T-cell phenotype has shown that markers of immunologic memory (CD45RA, CD45RO) and homing (L- selectin) differentiate "early" and "late" phases of chronic inflammation in CD children. Thus, the central hypothesis of this proposal is: Characterization of mucosal T-cell function and phenotype will allow for prompt diagnosis as well as substratification into "early" and "late" phases of chronic inflammation in pediatric CD. This hypothesis will be tested with the following three specific aims. Aim 1 is the characterization of mucosal T-cell in vitro growth in the early diagnosis of CD, with cross-sectional validation, longitudinal follow-up, and evaluation of children at risk. Aim 2 is the characterization of mucosal T-cell phenotype and function during early and late CD with analysis of mucosal T-cell subsets and cytokine production. Aim 3 is to assess the impact of early immunomodulatory therapy on clinical outcome and correlate with mucosal T-cell phenotype and function in newly diagnosed CD patients over a 24-month longitudinal follow-up. Thus, the K23 Mentored Patient-Oriented Clinical Research Career Development Award will not only define fundamental areas of immunopathogenesis in the under-researched area of pediatric CD, it will also allow the applicant to obtain critical training and expertise required to perform high caliber translational research. 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 12443 Research Pky, Ste 207 Orlando, Fl 32828 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

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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 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

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Project Title: NEUROIMMUNE MECHANISMS OF VISCERAL HYPERALGESIA Principal Investigator & Institution: Pezzone, Michael A.; Assistant Professor; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 15-APR-1999; Project End 31-JAN-2004 Summary: The applicant for this Mentored Clinical Scientist Development Award is currently completing a Fellowship in Gastroenterology and Hepatology at the University of Pittsburgh Medical Center. During his training to obtain combined M.D. and Ph.D. degrees under the mentorship of Bruce Rabin, M.D., Ph.D., the candidate investigated extensively the neural and neuroendocrine mechanisms of stressor-induced immune alterations int he rat, focusing specifically on stress-activated CNS pathways that may modulate lymphocyte function. In these studies, the candidate identified stress-activated neurons in the rat CNS by using c-FOS expression as a marker of neuronal stimulation following acute footshock and conditioned stress. To further his career in academic medicine and to further develop his expertise in neuro-immune interactions and stress, the candidate has designed this research proposal to assess the roles of stress and intestinal inflammation in the development of visceral hyperalgesia in the gut. This model of colonic inflammation (trinitrobenzenesulfonic acid in ethanol) appears to be propagated by cells of the immune system and is subsequently modulated by stress. Understanding the pathophysiologic roles of these factors in the sensitization of gastrointestinal afferents will help further provide important information regarding the etiology and clinical course (including relapse) of painful bowel disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Methods encompassing intestinal electrophysiology, neuropharmacology, histology, and mast cell growth factors will be used to evaluate, in a hapten- induced model of colonic inflammation, the chemical dialog between afferent nerves and inflammatory/immune cells is likely to contribute to the sensitization of gastrointestinal afferents in pathological conditions such as IBS and IBD. This dialog may be modulated by activity in autonomic pathways to the gut and/or by chemicals released from the pituitary gland during stress. Combining these new skills with those previously acquired, the applicant will be well-suited to study a variety of gastrointestinal disease states in addition to characterization of the neuroimmune mechanisms of visceral hyperalgesia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEW ORALLY ACTIVE AGENTS FOR CANCER PREVENTION Principal Investigator & Institution: Honda, Tadashi; Chemistry; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): This project provides novel orally active tricyclicbis-enone derivatives (TBEs) for prevention and/or treatment of cancer, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, Alzheimer's disease, Parkinson's disease and other diseases whose pathogenesis may involve excessive production of nitric oxide (NO) and/or prostaglandins. On the basis of the structure of a synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), which is an extremely potent inhibitor of the de novo synthesis of inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in macrophages and of proliferation of many human tumor cell lines, we designed TBEs to address the inadequacies (low oral potency in vivo, low water solubility, high cost of production, and so on) of CDDO. Our rationale for exploring the TBEs is as follows. (1) Because TBEs could be synthesized from commercially available small molecules, TBEs with

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various functionalities at different positions can be obtained. Such "diversity oriented synthesis" of TBEs could lead to totally new cancer chemopreventive and antiinflammatory drugs that are orally active and water-soluble for ease of administration and formulation, and that are low in cost for large scale synthesis. (2) This structural flexibility might provide us with new structure-activity relationships (SARs) and different compounds that are appropriate and specialized for each therapeutic area. (3) Some of the activities of CDDO might be absent because of the delineation of the pharmacophore of CDDO (Increase of selectivity). In our preliminary studies, we have found that TBE-9 shows high inhibitory activity (IC50 = 1 nM level) against production of NO induced by interferon-((IFN-gamma) in mouse macrophages, and is orally active at 15 mg/kg (single administration) in an in vivo study using mouse peritoneal inflammation induced by thioglycollate and IFN-gamma amongst TBEs initially synthesized. The present investigation thus will design and synthesize new orally active TBEs on the basis of our preliminary SARs, to improve their potency (in vitro and in vivo), to study their mechanism of action as anti-inflammatory and anti-proliferative agents, and to study these new TBEs in vivo for blocking inflammation and for growth inhibition and prevention of cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: NF-KAPPAB REGULATION BY ANDROGEN RECEPTOR Principal Investigator & Institution: Baldwin, Albert S.; Associate Director, Professor; Biochemistry and Biophysics; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The androgen receptor (AR) is a member of the steroid receptor superfamily of transcription factors. Like other members of the family, AR is regulated primarily through interactions with a specific ligand. Thus androgens bind to AR leading to nuclear translocation, interaction with transcriptional coactivators, and control of gene expression through binding to androgen receptor response elements (AREs) in the promoters of relevant genes to stimulate specific gene expression. Interestingly, androgens have been shown to inhibit gene expression but the mechanisms associated with this process are poorly understood. While there is growing evidence of complex regulation of AR function which occurs independent of androgens, less is known about the ability of AR to affect distinct regulatory pathways that may impact growth or oncogenesis. In this regard, prostate cancer develops as an androgendependent cancer. Androgen ablation remains the only effective form of systemic therapy for patients with advanced prostate cancer due to the ineffectiveness of standard forms of cancer therapy. Unfortunately, progression to androgen-independent cancer occurs within a few years of androgen withdrawal and this is associated with extremely poor therapeutic options and with negative prognosis. Because AR-mediated gene activation appears to occur in both androgen-dependent and androgenindependent cancer, it is assumed that aberrant AR responses contribute to the recurrent, androgen-independent tumor. The transcription factor NF-kappaB is considered a key modulator of the immune and inflammatory response through its ability to control expression of genes encoding cytokines, cytokine receptors, and chemokines. Additionally NF-kappaB is a potent inhibitor of apoptosis and can promote cell proliferation through the upregulation of genes such as cyclin D1. Consistent with these points, NF-kappaB is considered a key effector of inflammatory diseases such as arthritis and inflammatory bowel disease. Importantly, NF-kappaB is now recognized as important in a number of cancers including squamous cell carcinoma, breast cancer,

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and multiple myeloma. The activity of NF-kappaB is controlled at two levels. One mechanism involves interactions with an inhibitory protein known as IkappaB and another mechanism involves direct phosphorylation of the p65 subunit of NF-kappaB which controls transactivation potential. In each case, the IkappaB kinase (IKK) controls the activity of NF-kappaB through its ability to phosphorylate IkappaB, leading to its ubiquitination and degradation, and through its ability to phosphorylate p65 on serine 536. Our preliminary data indicate that androgens potently suppress NF-KB activation through a mechanism which involves inhibition of IkappaBalpha degradation. Additionally, we provide evidence that the phosphorylation of p65 on serine 536, a process associated with IKK and with enhanced transactivation potential, is upregulated in androgen-receptor null cells and in androgen-independent prostate cancer samples. The underlying hypothesis of this proposal is that androgen-activated AR normally functions to suppress NF-kappaB activation through control of IkappaB-alpha degradation and inhibition of phosphorylation of p65. Based on the findings, we also hypothesize that the transition to androgen-independent prostate cancer is associated with a loss of this control on NF-kappaB function, allowing the oncogenic mechanisms associated with NF-kappaB to be manifested. The goals of the application are to determine how androgen activated AR blocks NF-kappaB, with a focus on direct regulation of IKK and on upstream signaling components, and to determine if NFkappaB is functionally upregulated in androgen-independent prostate cancer. The experiments have the potential to identify a new target in the regulatory cascade associated with androgen/AR signaling and to possibly identify a new target for treatment of androgen-independent cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

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 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

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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: NON-ADDICTING CANNABINOID MEDICATIONS Principal Investigator & Institution: Malan, Thomas P.; Professor; Anesthesiology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2006 Summary: (provided by applicant): As a physician, I see many patients with medical conditions for which adequate therapy is not available. CB2 cannabinoid receptorselective agonist medications may prove useful in treating some of these disease states. One is moderate-to-severe pain, where the use of opioid medications, the most effective therapy, is often limited due to concerns over addiction. In addition, opioids prescribed as analgesics are subject to diversion and abuse. We have shown that CB2 receptorselective agonists produce strong antinociceptive effects in animal models, suggesting that they may be useful as analgesic medications for humans. Unlike cannabinoids with agonist activity at CB1 receptors, CB2 receptor-selective agonists are predicted not to produce the rewarding properties associated with drug abuse, since CB2 receptors are not found in the CNS. By reducing the need for opioids, CB2 receptor-selective medications would diminish the problem of addiction with its severe individual and social costs. CB2 receptor-selective agonists, however, are likely to have important medical applications beyond analgesia. In this proposal, we hypothesize that CB2 receptor-selective agonists will be useful in the treatment of the prevalent and challenging problems of urinary incontinence; irritable bowel syndrome, inflammatory bowel disease and visceral hypersensitivity; and opioid resistant neuropathic pain. Our goal is to combine state-of-the-art chemistry and biology to develop CB2 receptorselective agonists as medications. Aim one will test the hypothesis that CB2 receptorselective agonists will have therapeutically desirable properties beyond analgesic effects. We will explore the activity of CB2 receptor-selective agonists in experimental models relevant to urinary incontinence; inflammatory bowel disease and other conditions associated with sensitization or increased activity of C-fibers. We will also test the hypothesis that CB2 receptor-selective agonists will not produce a withdrawal syndrome or provide reward. Aim two will use a lead optimization strategy to improve the medicinal properties of AM1241, our structural lead compound. This will be accomplished by a structure-activity relationship study involving the systematic manipulation of each of the molecule's pharmacophoric groups using drug design principles. Novel compounds will be evaluated for their affinity at and selectivity for CB2 cannabinoid receptors in vitro and for desired properties in vivo. The successful completion of these aims will provide physicians a therapeutic option that may provide

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relief for patients with difficult medical conditions and decrease the use of opioids, minimizing opportunities for abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: NONINVASIVE TEST FOR MANAGEMENT OF NONULCER DYSPEPSIA Principal Investigator & Institution: Craine, Brian L.; Western Research Company, Inc. 3275 W Ina Rd, Ste 215 Tucson, Az 85741 Timing: Fiscal Year 2002; Project Start 01-NOV-1999; Project End 31-JUL-2004 Summary: (Applicant's abstract): Nonulcer dyspepsia is a highly prevalent medical condition affecting up to 30 percent of the Western population, accounting for 2-5 percent of all visits to primary care physicians and leads to over one billion dollars worth of upper endoscopy procedures per year. In an attempt to lower this tremendous burden on the health care system the general practice currently is to attempt to avoid endoscopy in the majority of patients, which are low risk, by an initial empiric trial of medication. Endoscopy can then be performed on those that fail initial therapy. Unfortunately, empiric treatment is only effective in about 40-50 percent of cases since it is difficult to determine in advance the most effective treatment. Consequently the high cost of endoscopy continues to be a problem. The overall goal of this project is to develop an inexpensive, non-invasive test for the objective and quantitative categorization of nonulcer dyspepsia patients with the purpose of providing the most effective initial treatment. The effectiveness of objective patient categorization will be tested with respect to ability to predict which patients will be responders to acid suppression therapy and which will be responsive to prokinetic treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHOGENESIS OF HELICOBACTER HEPATICUS Principal Investigator & Institution: Beckwith, Catherine S.; Comparative Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (Provided by applicant): Catherine Beckwith, D.V.M, Ph.D., Diplomate, American College of Laboratory Animal Medicine, received her doctoral training with Dr. Lela Riley at the University of Missouri where her research focused on development of diagnostic assays, identification of virulence factors, and characterization of the pathogenesis of rodent Helicobacter infections. With the SERCA, Dr. Beckwith will build upon her background in research and obtain additional training that will allow her to develop into an independently funded research investigator. Dr. Beckwith will train in the rich intellectual environment of SU where Dr. Stanley Falkow, an internationally renowned leader in bacterial pathogenesis research, will mentor her. Dr. Beckwith is co-sponsored by Linda Cork, D.V.M., Ph.D., a veterinary pathologist and the Department Chair of Comparative Medicine, who will ensure that she has the resources and time to carry out her research. Clinical and teaching responsibilities will be only as sufficient to maintain her clinical skills. Dr. Beckwith will conduct an in-depth research project, present her research at national scientific meetings, participate in laboratory meetings, attend specialized courses at Cold Spring Harbor Laboratory, and attend seminars and journal clubs related to bacterial pathogenesis. Dr. Beckwith's research will use a molecular and genetic approach to identify and characterize virulence factors in H. hepaticus, the cause of IBD, chronic active hepatitis, and hepatocellular tumors in mice. The H. hepaticus-infected mouse is an animal model of

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chronic bacterial infection, which closely mimics human hepatobiliary and inflammatory bowel diseases. Dr. Beckwith will create a transposon library in H. hepaticus and identify virulence factors through negative selection in mice. Novel virulence factors and the host response will be characterized using traditional and cutting edge techniques including global gene expression analysis with microarrays. Characterization of virulence factors is essential to understanding the pathogenesis of IBD and hepatitis caused byH. hepaticus. Recent evidence suggests a link between helicobacters and chronic hepatobiliary diseases in humans. The long-term goal of the proposal is to develop new strategies for prevention and treatment of chronic liver and intestinal disease in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: PATHWAYS OF INTESTINAL T CELL DEVELOPMENT Principal Investigator & Institution: Camerini, Victoria N.; Associate Professor; Pediatrics; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 15-FEB-2000; Project End 31-JAN-2005 Summary: There is considerable evidence that a subset of intestinal intraepithelial lymphocytes (IEL) develop extrathymically in mice, leading to the hypothesis that the intestine functions as a primary lymphoid organ in the development of these T cells. We, and others, have characterized cells found in lymphoid aggregates called, cryptopatches (CP) and T cell receptor negative (TCR-) cells, dispersed within the epithelium of mice, which have several phenotypic and functional characteristics of T cell progenitors. Nevertheless, the lineage relationships between these cells and the mechanisms by which putative progenitors develop into TCR+ IEL in vivo is presently unknown. Recent data in mice transgenic for the male, H-Y specific alphabeta T cell receptor (H-Y TCR), indicate that H-Y TCR+ IEL are present only in male mice, while female mice lack H-Y TCR+ transgenic IEL. This suggests that the development of IEL in male mice is antigen driven, while female mice fail to develop H-Y TCR+ IEL due to the lack of the cognate antigen. The central hypothesis of this proposal is H-Y TCR+ IEL arise via a distinct pathway of T cell development centered in the small intestine and that establishment of these T cells is self-antigen driven. We propose that bone marrow stem cells form cryptopatch aggregates early in neonatal life and that precursor IEL (pre-IEL) derived from these aggregates continue their differentiation within the intestinal epithelium establishing TCR+ IEL in response to antigen encountered in the gut. In the First Specific Aim we will investigate the origin of cells resident within cryptopatch aggregates and determine the dependence of these aggregates on the thymus and other key factors. In the Second Specific Aim we will determine the developmental potential of pre-IEL and the lineage relationships between these cells and TCR+ IEL. And finally, in the Third Specific Aim we will determine the requirements for selection and expansion of H-Y TCR+ IEL and determine the functional specificity of these cells. The studies in this application, are focused on the H-Y TCR transgenic mouse line. This system will allow us to define the developmental pathway and functional specificity of intestinal T cells driven by self-antigen reactivity in the gut. Defining the developmental pathways of T cells in the intestine will shed light on their role in immune homeostasis in the intestine and in the pathogenesis of inflammatory bowel disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHWAYS TO INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Terhorst, Cornelis P.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215

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Timing: Fiscal Year 2003; Project Start 30-SEP-1997; Project End 31-DEC-2007 Summary: (provided by applicant): Studies with genetically well-defined mouse models of Inflammatory Bowel Diseases, i.e. experimental colitis, lead to a general notion that several perturbations of the finely tuned balance between the immune system and the vast antigenic load of the colon can result in disease. Aggressor CD4+ T helper1 cells accumulate in the lamina propria followed by initiation of destructive cascades in the intestinal mucosa. Bacterial antigens or mouse antigens encoded by genes induced by colonic bacteria are presented to these T cell subsets by professional Antigen Presenting Cells (APC), macrophages, dendritic cells and M cells. In healthy mice the aggressor Th1 cells are prevented from expanding and thus initiating the destructive cascades by Suppressor (TS) T cells. Our general hypothesis is that the pathogenesis of colitis is the result of aberrant regulation of the innate and adaptive immune systems. The first hypothesis of this application is that the SLAM family of adhesion molecules in macrophage/dendritic cell CD4+ T cell interactions determine the induction and effector functions of aggressor T cells in the periphery. The second hypothesis is that well defined monoclonal antigen specific TS cells act via a bystander mechanism in colitis. The third hypothesis is that TS cells are educated in the thymus and act in the periphery, but can also prevent thymic destruction by aggressor T cells. The genetically well-defined mutant mouse strains that will be used in the experiments designed to prove these three hypotheses in turn will provide further evidence for the general hypothesis. The experiments proposed in this application are grouped into the following specific aims: 1). To study the role of the SLAM family of adhesion molecules which govern the interactions between macrophages and colitis inducing aggressor T cells. 2). Further define CD4+CD25+ TS cells that suppress colitis in the periphery via bystander suppression. 3). Test the hypothesis that CD4+CD25+ TS cells that suppress colitis are educated in the thymus and can prevent thymic destruction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: EPITHELIUM

PHYSIOLOGY

OF

NF-KB

SIGNALING

IN

INTESTINAL

Principal Investigator & Institution: Kagnoff, Martin F.; Professor of Medicine and Director; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: Intestinal epithelial cells are a major site of contact between the host and microbes, microbial products, and other environmental agents that cause epithelial cell injury. Our long-term objective is to define the mechanisms by which intestinal epithelial cells play a role in host mucosal defense by signaling the onset of innate and adaptive immune and inflammatory responses in the intestinal mucosa. In vitro studies indicate the importance of the transcription factor NF-kappaB as a central regulator of the intestinal epithelial cell response to microbial infection, yet little is known regarding the functional importance in vivo of epithelial cell NF-kappaB for mucosal innate immunity and epithelial cell survival. Studies in Specific Aim 1 will determine the functional importance of intestinal epithelial cell NF-kappaB in vivo by testing the hypothesis that activation of NF-kappaB in intestinal epithelial cells has a key role in signaling the onset of the mucosal inflammation in response to microbial and chemical injury, and in protecting epithelial cells from undergoing apoptosis in response to gamma radiation. These in vivo studies will use mice in which Cre recombinase under the control of the villin promoter was used to generate progeny with a conditional intestinal epithelial cell knockout of the beta subunit of the IkappaB kinase (IKK) that is

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essential for signal induced activation of NF-kappaB. Specific Aim 2 will study the importance of epithelial cell NF-kappaB for epithelial cell migration in an in vitro model of epithelial cell restitution. Epithelial cell restitution is the process wherebyintestinal epithelial cells migrate to seal a superficial wound in the early period following epithelial cell injury. In preliminary studies we discovered that NF-kappaB is activated at the wound edge and that NF-kappaB is essential for subsequent epithelial cell migration. Studies in Aim 2 will further test the hypothesis that NF-kappaB plays a central role in regulating epithelial cell migration following epithelial cell wound injury. The proposed studies focus on the proximal signaling mechanisms that lead to NFkappaB activation following epithelial cell wound injury and the NF-kappaB responsive genes that play a central role in this model of epithelial cell injury. The proposed studies have marked significance for understanding the mechanisms that initiate and regulate intestinal mucosal inflammation and epithelial cell survival, and for elucidating mechanisms that are important for re-epithelialization of mucosal surfaces during microbial or toxic intestinal injuries and in inflammatory bowel diseases and celiac 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; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-JUL-2007 Summary: (provided by applicant): The overall goal of this grant is to understand why polyamines are essential to the migration of GI mucosal cells during the early mucosal restitution component of healing. Experiments supported during the past 15 years this project has been active have shown that: 1) polyamines are essential to the healing of gastric and duodenal mucosa, 2) polyamines are required for mucosal restitution which depends on cell migration, 3) polyamines are essential to cell migration, 4) polyamines are necessary for the normal functioning of several components of the cytoskeleton involved in cell migration, 5) migration of IEC-6 cells is regulated by the Rho GTPases, and 6) polyamines influence the levels and activities of the Rho GTPases. The first set of specific aims will determine the effect of polyamines on the Rho family of GTPases during the migration of IEC-6 cells. IEC-6 cells stably transfected with constitutively active and dominant negative RhoA, Rac1 and Cdc42 will be used to determine their hierarchy of activation and where the polyamines interact. Preliminary data indicate that both RhoA and Raci are essential for cell migration but that only Rac1 activity is sufficient for migration. The second set of specific aims will determine the role of polyamines in integrin signaling by examining ccli attachment and spreading. The same clones and polyamine depletion will be used to examine the roles of Rho, Rac and Cdc42. Polyamine depletion will be used to determine the role of polyamines in the distribution and phosphorylation of proteins involved in the formation of focal adhesions and in cell spreading. In the third set of specific aims a highly specific polyamine antibody will be used to determine the cellular localization of polyamines during the processes of spreading and migration and to determine the colocalization of polyamines with cytoskeletal proteins and those regulating cytoskeletal transformations. These studies will provide the first description of the involvement of the Rho-GTPases in epithelial cell migration and spreading and how the activities of these proteins are regulated by polyamines. They also will provide the first studies of polyamine localization during dynamic cell processes and define the mechanisms by which polyamines regulate those processes. This work will increase our understanding of cell

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function basic to many clinical conditions in which cell migration is a major component. These include peptic ulcer disease, cancer, and inflammatory bowel disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: PPARS: TRANSCRIPTIONAL REGULATORS OF METABOLISM Principal Investigator & Institution: Evans, Ronald M.; Senior Member; Keystone Symposia Drawer 1630, 221 Summit Pl #272 Silverthorne, Co 80498 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2003 Summary: (provided by applicant): Academic, pharmaceutical and clinical studies on the PPARs have been increasing at an exponential rate. The PPARs include a group of three related nuclear hormone receptors, (alpha, beta, and gamma) that have been implicated in many aspects of metabolic disease, particularly in the development of adult onset (Type II) diabetes, obesity, hypertension, and atherosclerosis. These receptors are also seen as potential therapeutic targets in the treatment of inflammatory bowel disease, Crohn's disease, colon cancer, prostate cancer and breast cancer. Of prominent interest for the upcoming meeting are: 1) defining the roles of the PPARs in various physiological and pathological settings such as diabetes, cardiovascular disease and immune cell function. 2) Identifying new ligands, both biological and synthetic that will help open new avenues of investigation and therapeutic intervention. 3) Define longterm benefits and risks of PPAR active drugs, including Actos, Avandia and the fibrates. 4) Identifying new coactivator/repressor proteins and in particular, determining which of these components are associated with specific biological programs. 5) Developing specific molecular links between the PPARs and other nuclear receptors including LXR, FXR, and PXR. These orphan receptors help to coordinate metabolic function and may act in a cascade fashion to impact on PPAR action. This meeting will bring together experts from the pharmaceutical, academic and biotechnology industries. Although the PPARs are routinely discussed at meetings focused on nuclear receptors, diabetes, obesity or gene transcription, this conference promotes a unique confluence of all of these areas by bringing in experts who approach the field with differing backgrounds and interests. It is believed that this synergy will push this exciting field forward at an accelerated pace. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 ·

Project Title: REGULATION OF EPITHELIAL CELL MOTILITY BY VILLIN Principal Investigator & Institution: Khurana, Seema; Associate Professor; Physiology; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): The PI proposes to determine and characterize the role of villin and its ligands (phosphatidylinositol 4,5- bisphosphate (PIP2) and actin) in epithelial cell motility. Active cell motility regulates many important intestinal epithelial cell functions, including: ion transport proteins via endocytosis and exocytosis, crucial for absorption of nutrients; intestinal restitution, important to maintain homeostasis in the presence of large osmotic and mechanical stress; the movement of cells along the crypt-villus axis; the invasion and propagation of enteropathogens; immune surveillance and inflammation; as well as neoplastic tumor cell dissemination and metastasis. Villin is an actin nucleating, capping, severing, and bundling protein. Villin binds and regulates two ligands that are known to regulate cell motility, phospholipase C-gamma1 (PLC-gamma1) as well as the substrate of the lipase namely, phosphatidylinositol 4,5-bisphosphate (PIP2). Recent studies with villin knock out mice have demonstrated that villin is necessary to regulate epithelial cell motility. In addition, villin shares sequence homology with other proteins of its family including gelsolin, which have been shown to regulate cell motility in vivo. Our working hypothesis is that villin's ability to regulate phosphoinositide-mediated signal transduction pathways and the actin cytoskeleton is important to epithelial cell physiology and pathophysiology involving changes in cell motility. To accomplish our overall study objectives we will characterize the villin-PIP2 interaction using the following approaches: reconstitution in vitro using recombinant villin proteins; endogenous villin expression in the intestinal epithelial cell line, Caco-2; and over expression of villin and enzymes that regulate intracellular PIP2 levels, in the villin null intestinal cell line, IEC-6 using a tetracyclineregulated system. To determine unequivocally the role of villin in the epithelial cell motility, we will use villin knock out mice. These studies promise the prospect of modifying motility for enhancement of normal physiology and for amelioration of disease. Inhibition of epithelial cell motility can be significant in several diseases, including inflammatory bowel disease, celiac disease, and colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RNA BINDING PROTEIN CUGBP2 IN INTESTINAL EPITHELIUM Principal Investigator & Institution: Anant, Shrikant; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: Regulated expression of certain genes in the intestinal epithelial cells is controlled at the posttranscriptional levels of mRNA stability and mRNA translation. Dysregulation in either one could lead to various pathophysiological conditions including colon cancer and inflammatory bowel disease. An important cis-acting element controlling these functions is the AU-rich sequence elements, which is present in the 3'untranslated region of many tightly regulated genes. We have recently identified a novel AU-rich RNA binding protein, CUGBP2, which is induced in intestinal epithelial cells after radiation injury, coincident with the cells undergoing apoptosis. Furthermore COX-2 mRNA rapidly accumulates in the intestine after radiation injury, however, COX-2 mRNA translation is inhibited. We have now determined that CUGBP2 binds 3' untranslated region of COX-2 mRNA and stabilizes the mRNA, but inhibits its translation. Accordingly, the three aims of the current application are (a) to investigate the mechanism by which CUGBP2 binds and stabilizes AU-rich mRNAs, (b) to determine the mechanism by which CUGBP2 affects mRNA translation, and (c) to determine the effects of CUGBP2 expression on intestinal epithelial cell apoptosis. These experimental approaches should lead to a better understanding and significance of mucosal gene expression induced by injury, and advance our knowledge of posttranscriptional control of gene expression in intestine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF GALECTIN-4 IN COLITIS Principal Investigator & Institution: Mizoguchi, Atsushi; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2004; Project Start 15-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): Inflammatory bowel disease (IBD) is a group of chronic, relapsing and remitting inflammatory conditions that affect individuals throughout the life. Although the status of IBD as a canonical autoimmune disease has risen steadily by accumulated studies, it is not known whether the intestinal epithelial cell-derived proteins are involved in the pathogenesis of IBD. Recently, we have identified a mammalian lectin, galectin-4, as a colonic epithelial cell-derived pathogenic mediator in the exacerbation of colitis by using serological analysis of recombinant cDNA expression libraries (SEREX) in which cDNA libraries generated from colonic epithelial cells from T cell receptor alpha knockout (TCRalpha KO) mice were screened by using purified immunoglobulins from the TCRalpha KO mice. This discovery provides us a great opportunity to more closely examine the role of self-lectin originating from colonic epithelial cells in the pathogenesis of colitis. Based on our preliminary studies, we hypothesize that the colonic epithelial cell-derived galectin-4 contributes to the exacerbation of colitis by cross-linking the specific glycoreceptors and stimulating interleukin (IL)-6 production by the pathogenic T cells. In this application, we will initially plan to define our hypothesis by administration of recombinant galectin-4 into chronic colitis prone mice. We also plan to examine the therapeutic beneficial of in rive neutralization of galectin-4 activity on the chronic colitis by administration of galectin-4-specific monoclonal antibodies. In addition, the characteristic of galectin- 4/pathogenic T cell interaction and the involvement of immunological synapse and alpha2,3-sialyltransferase-I in galectin-4-induced IL-6

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expression will be examined. These studies will not only enhance understanding of the pathogenic mechanisms of IBD but also provide important information to develop new therapeutic approaches for human IBD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ROLE OF IL-10 IN THE REGULATION OF AUTOIMMUNE DISEASE Principal Investigator & Institution: Flavell, Richard A.; Professor and Chairman; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: It has become clear that immune regulation is a major mechanism which prevents the development of autoimmunity. Indeed, human individuals that are genetically identical to autoimmune patients rarely develop diseases that afflict their siblings. Immune regulation can be defined by regulatory or suppressor T cells and the regulatory cytokines TGF-b and IL-10. The relationship between these important cytokines and the cells that regulate the immune response is not clear. Moreover, the mechanisms whereby these cytokines act on other cell types, through well characterized in vitro, have not been connected mechanistically to the regulation of two autoimmune diseases, EAE and IBD. We will first generate a novel reporter mouse that will use the eGFP marker to visualize IL-1O production during the autoimmune response. Specifically, in IL-10 knock-in mouse will be generated wherein an IRES-eGFP cistron is placed downstream of the IL-10 gene. This will be part of the same IL-10 transcription unit and most cells expressing IL-10 will express eGFP. Mice carrying this reporter knock-in will be used to show when and where IL-10 is expressed and what the consequence of immune regulation are on IL-10 gene expression during the development and resolution of EAE and IBD. To elucidate the cell types that are the target of IL-10 mediated inhibition of immune responses we will employ transgenic mice in which a dominant negative IL-10 receptor is directed to either T cells or various antigen presenting cells/inflammatory cells. Thus, the CD4 promoter will be used to direct the synthesis of the dnIL-10R1. T cells from these transgenic mice are nonresponsive to IL-10 and therefore autoaggressive T cells cannot be inhibited by IL-10. Similarly, if IL-10 acts to induce regulatory T cells this will not be possible in mice that carry this transgene. We will investigate both possibilities for the function of IL-10 in a similar vein, we will generate transgenic mice in which the dnIL-10R1 is expressed on dendritic cells, macrophages and B cells by using different promoters to direct the synthesis of the transgene. Using these mice, we will elucidate which antigen presenting cells or inflammatory cells are the target of IL-10 mediated signaling during the development and resolution of the two diseases, EAE and IBD. In collaboration with Dr. Janeway, we will also use our approaches to elucidate the role of IL-1O in the protection provided by the therapeutic vaccine being studied in the role of IL-10 in that system. We believe that these approaches should substantially advance our understanding of the role of IL-10 in immunoregulation and autoimmune disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 ·

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 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

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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: SECOND INTERNATIONAL CONFERENCE ON NADPH OXIDASES Principal Investigator & Institution: Griendling, Kathy K.; Professor; Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 31-MAR-2005 Summary: (provided by applicant): With this application, we request funding to support the "Second International Conference on NADPH Oxidases" (http://www.noxlI.emory.edu/index.htm). The conference will be held at Callaway Gardens in Pine Mountain, Georgia, March 27-31, 2004, and will be organized by Drs. Kathy Griendling and J. David Lambeth, both of whom are leaders in the field. This biannual meeting is the second in a series, which focuses on a newly discovered family of enzymes--the Nox and Duox enzymes. These enzymes play key roles in diseases in which oxidative stress plays a pathological role, including hypertension, atherosclerosis, heart failure, pathological vascular remodeling, cancer, diabetes, inflammatory bowel disease, shock lung, and immune diseases such as arthritis. The meeting will bring together basic scientists and clinicians from all over the world to facilitate exchange, in an informal setting, of state-of-the-art information on the biological importance of these enzymes. Attendance will be limited to 150 conferees to encourage free discussion of ideas and information. We have amassed an outstanding list of internationally recognized speakers who will form the core of the meeting, and who have agreed to present their newest data on Nox enzymes. The meeting format will involve formal lectures, poster sessions, and time for informal, unstructured interactions. Understanding these enzymes is directly relevant to fundamental biological questions relating to the missions of several NIH institutes, including the National Heart, Lung and Blood Institute and the National Cancer Institute, and will thus further our understanding of basic disease mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SMAD3 AS AN INHIBITOR OF ATHEROGENESIS Principal Investigator & Institution: Jain, Mukesh K.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2005 Summary: (provided by applicant): Recent studies have highlighted the importance of inflammation as a contributor to the pathogenesis of a number of chronic disease states

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such as rheumatoid arthritis, cirrhosis, glomerulosclerosis, inflammatory bowel disease and atherosclerosis. The infiltration of monocytes/macrophages is a characteristic feature seen in chronic inflammatory disease states. Indeed, experimental, clinical, and pathologic studies have established an essential role for the monocyte in the development of atherosclerotic lesions. As such, identification of mechanism(s) regulating monocyte/macrophage activation are of considerable interest. Transforming growth factor beta (TGFb1) is a potent inhibitor of inflammation and immune cell activation. Definitive evidence for this role is derived from the fact that mice deficient in this factor succumb to a systemic inflammatory wasting syndrome. TGFb1 is expressed in human atherosclerotic lesions and its levels correlate inversely with the severity of clinical disease. The mechanism(s) by which TGFb1 is able to inhibit immune cells remains poorly understood. Recently, a family of proteins termed Smads have been identified as effectors of TGFb1 signaling. We hypothesized that members of this family may regulate TGFb1?s inhibitory effects on monocytes. Indeed, we found that one of these factors, termed Smad3, was able to recapitulate the inhibitory properties of TGFb1 with respect to monocyte/macrophage activation. These studies also suggest that inhibition occurs through a novel mechanism involving competition for rate-limiting quantities of critical cellular regulatory factors (co-activator competition). Thus, the goals of this study are to define the role of Smad3 in monocyte biology. First, we will dissect the molecular mechanisms governing Smad3 mediated inhibition in macrophages. Second, we will overexpress Smad3 in macrophages and assess effects on specific effector functions such as elaboration of cytokines, matrix degrading enzymes and lipid uptake. Third, we will assess the effect of Smad3 deficiency on the development of atherosclerosis in mice. Collectively, these studies should provide insight into the role of Smad3 in mononuclear cell biology both in vitro and in vivo. Furthermore, these results may serve as the basis of novel strategies to limit mononuclear cell activation and inflammation in a number of human disease states, including atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: THE GENETICS OF MULTIPLE AUTOIMMUNITY SYNDROME Principal Investigator & Institution: Spritz, Richard A.; Professor and Director; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: Multiple autoimmune disease is characterized by the co-occurrence of two or more of various autoimmune disorders in individuals, and often also in their family members. Perhaps the most common form of multiple autoimmune disease is so-called 'autoimmune polyendocrine syndrome type 2' (APS2), classically characterized by the co-occurrence of Addison's disease, autoimmune thyroid disease (Graves' disease and hypothyroidism), type 1 diabetes mellitus, celiac disease, hypogonadism, vitiligo, alopecia, pernicious anemia, and myasthenia gravis, but occasionally systemic lupus erythematosus, juvenile rheumatoid arthritis, multiple sclerosis, and other disorders. APS2 appears to represent a constellation of disorders controlled by multiple genes that predispose to autoimmunity, most likely acting at several different biological levels, in concert with environmental factors. We have defined a sub-group of multiple autoimmune disease, which we term 'multiple autoimmunity syndrome', which includes a specific constellation of associated disorders; vitiligo, autoimmune thyroid disease, pernicious anemia, Addison's disease, lupus and perhaps inflammatory bowel disease. We have ascertained a large number of multiple autoimmunity syndrome

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families in which different individuals have different combinations of these specific diagnoses. In these families, susceptibility to this specific constellation of autoimmune diseases appears to be inherited as an autosomal dominant trait with reduced penetrance. We plan to collect samples from these families and carry out genome-wide genotyping and genetic linkage analyses for the purpose of mapping the genetic loci that predispose to this form of multiple autoimmune disease. We will then carry out more detailed mapping to define the genetic intervals, and subsequently screen positional candidate genes for pathologic mutations. The effects of these mutations will be tested in functional analyses that will provide ultimate confirmation of gene identification. The genes that predispose to this constellation of associated diseases will likely be different from those associated with susceptibility to the individual components of this group of diseases. We anticipate that these studies will shed light on the mechanisms of autoimmunity itself, as well as the autoimmune mechanisms that underlie these individual autoimmune diseases. 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 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

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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 REGULATION OF MUCOSAL INFLAMMATION Principal Investigator & Institution: Fiona, Powrie; Keystone Symposia Drawer 1630, 221 Summit Pl #272 Silverthorne, Co 80498 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2003 Summary: (provided by applicant): This Keystone Symposium will focus on the rapidly expanding and topical field of mucosal inflammation and its regulation and will consider mechanisms of inflammation relative to all mucosal surfaces. A particular strength of this meeting is that it will be run jointly with a meeting on Hygiene, Allergy and Asthma, allowing a comprehensive examination of genetic, environmental and immune pathological factors involved in inflammation at different mucosal surfaces. In the first part of the Symposium factors that control the overall development of the mucosal immune system will be considered as well as the mechanism of tolerance induction in the mucosal immune system. These topics will provide the theoretical basis for the understanding of mucosal inflammation. Next there will be a plenary session held jointly with the "sister" Symposium that will focus on dendritic cell function in the gastrointestinal and pulmonary tracts followed by an examination of effector and regulatory mechanisms underlying mucosal inflammation. In the latter half there will be a second joint plenary session in this case considering regulatory (suppressor) mechanism in the gastrointestinal and pulmonary tracts concluding with an examination of new murine models of mucosal inflammation. Epithelial cell function and mucosal homeostasis will also be examined. This is a subject that meshes well with the discussion of environmental factors in pulmonary inflammation being considered in the "sister" Symposium. Finally there will be presentations on homing of leukocytes to mucosal surfaces and the chemokine system. With this agenda, this Keystone Symposium will provide a keen examination of the major outstanding questions in the area of mucosal inflammation and will be an invaluable source of information for students and postdocs working in this area. It is expected that review of these topics will provide major insights into the mechanisms underlying mucosal inflammatory diseases such as inflammatory bowel disease and asthma. 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

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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 ·

Project Title: TOLL-LIKE RECEPTOR-COMPLEX IN INTESTINAL EPITH. CELLS Principal Investigator & Institution: Abreu, Maria T.; Director, Basic & Translational Research; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 900481804 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant): The intestinal epithelium is continually exposed to a high concentration of diverse bacteria. In spite of the density of commensal bacteria, the normal intestine is not inflamed. Idiopathic inflammatory bowel disease in humans and animals is characterized by aberrant host-microbial interactions. We wished to understand the mechanism by which the normal epithelium guards against chronic inflammation in the presence of commensal flora and thus understand how this may be perturbed in idiopathic inflammatory bowel disease. Gut commensal flora consists of mixed gram-positive and gram-negative organisms (Naidu et al. 1999; Dunne 2001). The cell wall of gram-negative bacteria contains lipopolysaccharide (LPS), a potent proinflammatory molecule (Aderem and Ulevitch 2000). Cellular responses to LPS are mediated by the interaction of LPS with toll-like receptor 4 (TLR4) and transduced via the IL- 1 receptor signaling complex to activate NF-kappaB and pro-inflammatory cytokine secretion (Zhang et al. 1999; Bowie and O'Neill 2000; Jiang et al. 2000; da Silva Correia et al. 2001). Data demonstrate that a novel, secreted protein, MD-2, is required for TLR4 function (Shimazu et al. 1999; Yang et al. 2000). We hypothesize that the TLR co-receptor MD-2 is normally down regulated in intestinal epithelial cells limiting proinflammatory gene expression in the presence of LPS. We further hypothesize that increased expression of MD-2 in response to Th1 cytokines perpetuates bacterial hyperreactivity in inflammatory bowel disease. Others and we have recently described that intestinal epithelial cells are unresponsive to purified, protein-free LPS as measured by NF-kappaB activation and IL-8 secretion (Abreu et al. 2001; Naik et al. 2001). LPS

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unresponsiveness in intestinal epithelial cells is due to low expression of TLR4 and MD2. Preliminary data demonstrate that MD-2 expression is low in normal intestinal epithelial cells in vivo and increased in patients with inflammatory bowel disease. The cytokines increase expression of MD-2 and restore LPS responsiveness in intestinal epithelial cells. Cloning of the MD-2 promoter demonstrates that MD-2 is transcriptionally regulated by IFN-gamma via the STAT pathway. In this proposal, we will explore the molecular mechanisms by which MD-2 is transcriptionally regulated in intestinal epithelial cells and the effect of this regulation on the function of toll-like receptor signaling. The results of our studies have important implications for understanding host-microbial interactions and the inter-relationship between the innate and adaptive immune systems in the gut. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: TREATMENT OF DEPRESSED ADOLESCENTS WITH PHYSICAL ILLNESS Principal Investigator & Institution: Szigethy, Eva M.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The identification and treatment of depressive disorders in adolescents with chronic physical illness is an understudied area. The purpose of this Mentored Patient-Oriented Research Development Award (K23) is to enable the candidate to become an independent clinical researcher in the area of innovative approaches to evaluation and treatment of depression in adolescents facing physical illnesses. The proposal will focus on patients with inflammatory bowel disease (IBD). The project will be conducted at Children's Hospital Boston (CHB), where a large population of adolescents with IBD is available. William R. Beardslee, MD, with expertise in depressive disorders and prevention, will serve as the primary mentor. John March, MD, MPH and John Weisz, PhD, experts in clinical psychiatric outcome research and psychotherapy interventions, will serve as co-sponsors. Research plan: The aims are: 1) Conduct randomized comparison trial of cognitive behavioral therapy (CBT) enhanced with physical illness narrative, family education, and social skills components (n=24) to standard of community care treatment (n=24) in depressed adolescents with IBD, and 2) Investigate underlying neurobehavioral changes in adolescents with depression and IBD. Career development plan: The training will emphasize skills necessary for conducting comparative clinical trials in the treatment of depression in adolescents with chronic physical illness and begin to explore underlying neurological mechanisms of the disease process. Didactic work in intervention research design and statistics, developmental psychopathology, and assessment of methodologies for biological and neurobehavioral correlates of treatment response will complement supervision by the program consultants. With a sound understanding of pathobiology and change mechanisms, the long-term goals of the candidate are to develop and evaluate cognitive-behavioral and pharmacological treatments for physically ill children and adolescents with depression and to investigate neurobiological correlates of treatment effect. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: UT GASTROENTEROLOGY/HEPATOLOGY RESEARCH TRAINING PROGRAM Principal Investigator & Institution: Dietschy, John Maurice.; Chief, Division of Gastroenterology; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-JAN-1997; Project End 31-DEC-2006 Summary: (provided by applicant): Training in the UT Gastroenterology/Hepatology Research Training Program takes place in the laboratories of the Division of Digestive and Liver Diseases and in the laboratories of several basic science departments at The University of Texas Southwestern Medical Center and the Dallas Veteran's Affairs Medical Center campuses. Under the direction of Drs. John M. Dietschy, Stuart J. Spechler and Dwain L. Thiele, applicants are carefully screened and interviewed. Each successful applicant will undertake a major research project for two to four years under the direct supervision of one or more members of the Senior Research Faculty. In addition, each trainee will have close interactions with other Senior Research Faculty and with members of various basic science departments. The projects that are ongoing in the laboratories of these faculty members are very diverse and involve a wide variety of techniques in cellular and molecular biology. Representative projects include detailed studies into the nature of alternative biochemical pathways for the biosynthesis of bile acids, the role of orphan nuclear receptors in the control of bile acid synthesis and sterol transport, an analysis of new treatments for hepatitis C, the role of cytotoxic lymphocytes in diseases such as hepatitis and inflammatory bowel disease and the role of newly described cholesterol 24 hydroxylase and the ABCA1 protein in biliary cholesterol secretion. Initially all trainees attend formal lectures in the performance of ethical biological research and, throughout the year, participate in regular research conferences and clinical conferences in the division. In addition, there is a two-year cycle of lectures devoted to the physiology, molecular biology and cell biology of the organs of the gastrointestinal tract. Throughout this two to four year course of intense research work, the trainees will learn to utilize a variety of basic laboratory procedures common to molecular and cell biology. If the trainee is engaged in clinical investigation, he/she will participate in a year long formal course in various aspects of human research. The progress of all trainees is monitored on a regular basis and, at the end of this intense period of research, each trainee will also have the opportunity of completing his/her clinical training. There are formal courses in the use of animals in medical research and in the special problems of ethical human investigation. There is an active program for recruiting underrepresented minorities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: WNT SIGNALING IN IBD-RELATED COLON CANCER Principal Investigator & Institution: Holcombe, Randall F.; Medicine; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2004; Project Start 15-FEB-2004; Project End 31-JAN-2006 Summary: (provided by applicant): Wnt ligands induce a signaling cascade by binding to cell surface frizzled receptors. This leads to increases in cellular beta-catenin and, ultimately, the induction of transcription of growth promoting genes. This process, mimicked by mutations in the APC gene, is integrally associated with the process of sporadic colon carcinogenesis. Mutations in APC and beta-catenin appear to be rare in inflammatory bowel disease (IBD)-related tumors. However, abnormal expression of other components of the Wnt pathway, including frizzled receptors, SARP1 and

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disheveled (dvl) have been described. In this proposal, the expression of upstream elements of the Wnt signal transduction pathway, frizzled receptors and frizzled inhibitory molecules will be defined in normal, dysplastic and malignant colonic tissues from patients with IBD. First, we will examine the expression of Fz receptors by immunohistochemistry in IBD-associated colon cancer tissues and compare this expression to adjacent mucosal tissues and sporadic colon cancers. In situ hybridization with anti-sense RNA probes specific for each of the ten Fz receptor subtypes as well as for specific frizzled-inhibitory proteins (FIPs) will then be utilized to define their expression in these tissues. Next, colon biopsies of normal and dysplastic mucosa will be obtained prospectively from patients with IBD undergoing surveillance colonoscopy. These tissues will be evaluated for expression of frizzled receptor subtypes and FIPs and also for activation of Wnt signaling, indicated by nuclearization of beta-catenin and increased expression and activity of a downstream pathway component, LEF1. Finally, the role of specific Fz receptor subtypes in the initiation and propagation of Wnt pathway signals will be defined utilizing a novel, in vitro, co-culture expression system. Those Fz receptor subtypes which exhibit differential expression in IBD tissues will be evaluated in this system. Expression constructs for individual Fz receptor subtypes will be utilized for more in-depth analysis in colon cancer cell lines. The precise effects of FIPs on Wnt signaling will be defined in vitro, with attention to the potentially disparate responses of different, specific, Fz receptor subtypes. 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 unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “inflammatory bowel disease” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for inflammatory bowel disease in the PubMed Central database: ·

A national survey on the patterns of treatment of inflammatory bowel disease in Canada. by Hilsden RJ, Verhoef MJ, Best A, Pocobelli G.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166136

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An important regulatory role for CD4 +CD8[alpha][alpha] T cells in the intestinal epithelial layer in the prevention of inflammatory bowel disease. by Das G, Augustine MM, Das J, Bottomly K, Ray P, Ray A.; 2003 Apr 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154344

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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. 5 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.

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Antibodies detectable by counterimmunoelectrophoresis against Bacteroides antigens in serum of patients with inflammatory bowel disease. by Helphingstine CJ, Hentges DJ, Campbell BJ, Butt J, Barrett JT.; 1979 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=273033

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Assessing health-related quality of life in patients with inflammatory bowel disease, in Crete, Greece. by Pallis AG, Vlachonikolis IG, Mouzas IA.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65681

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Bacteroides ovatus as the Predominant Commensal Intestinal Microbe Causing a Systemic Antibody Response in Inflammatory Bowel Disease. by Saitoh S, Noda S, Aiba Y, Takagi A, Sakamoto M, Benno Y, Koga Y.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=119885

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Citrobacter rodentium Infection in Mice Elicits a Mucosal Th1 Cytokine Response and Lesions Similar to Those in Murine Inflammatory Bowel Disease. by Higgins LM, Frankel G, Douce G, Dougan G, MacDonald TT.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96617

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Clinical Aspects and Pathophysiology of Inflammatory Bowel Disease. by Hendrickson BA, Gokhale R, Cho JH.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=118061

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Connecting the dots from Toll-like receptors to innate immune cells and inflammatory bowel disease. by Boone DL, Ma A.; 2003 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154457

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Correlation of Cecal Microflora of HLA-B27 Transgenic Rats with Inflammatory Bowel Disease. by Onderdonk AB, Richardson JA, Hammer RE, Taurog JD.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108765

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Differential Alteration in Intestinal Epithelial Cell Expression of Toll-Like Receptor 3 (TLR3) and TLR4 in Inflammatory Bowel Disease. by Cario E, Podolsky DK.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97811

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Distinct Elevation of Levels of Anti-Caenorhabditis elegans Antibody in Sera of Patients with Inflammatory Bowel Disease. by Oshitani N, Hato F, Kitagawa S, Watanabe K, Fujiwara Y, Higuchi K, Matsumoto T, Arakawa T.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193898

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Effects of chronic inflammatory bowel diseases on left ventricular structure and function: a study protocol. by Cioffi U, Ciulla MM, De Simone M, Paliotti R, Pierini A, Magrini F, Botti F, Contessini-Avesani E.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128828

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Evidence for a NOD2-independent susceptibility locus for inflammatory bowel disease on chromosome 16p. by Hampe J, Frenzel H, Mirza MM, Croucher PJ, Cuthbert A, Mascheretti S, Huse K, Platzer M, Bridger S, Meyer B, Nurnberg P, Stokkers P, Krawczak M, Mathew CG, Curran M, Schreiber S.; 2002 Jan 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117559

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Helicobacter bilis-induced inflammatory bowel disease in scid mice with defined flora. by Shomer NH, Dangler CA, Schrenzel MD, Fox JG.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175697

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Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: Evidence for epistasis between 1p and IBD1. by Cho JH,

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Nicolae DL, Gold LH, Fields CT, LaBuda MC, Rohal PM, Pickles MR, Qin L, Fu Y, Mann JS, Kirschner BS, Jabs EW, Weber J, Hanauer SB, Bayless TM, Brant SR.; 1998 Jun 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22666 ·

Inflammatory bowel disease: an immunity-mediated condition triggered by bacterial infection with Helicobacter hepaticus. by Cahill RJ, Foltz CJ, Fox JG, Dangler CA, Powrie F, Schauer DB.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175441

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Investigation of association of mycobacteria with inflammatory bowel disease by nucleic acid hybridization. by Yoshimura HH, Graham DY, Estes MK, Merkal RS.; 1987 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265821

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Molecular Cloning of a Bacteroides caccae TonB-Linked Outer Membrane Protein Identified by an Inflammatory Bowel Disease Marker Antibody. by Wei B, Dalwadi H, Gordon LK, Landers C, Bruckner D, Targan SR, Braun J.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98733

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Neglect of growth and development in the clinical monitoring of children and teenagers with inflammatory bowel disease: review of case records. by Ghosh S, Drummond HE, Ferguson A.; 1998 Jul 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28604

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Open access follow up for inflammatory bowel disease: pragmatic randomised trial and cost effectiveness study. by Williams JG, Cheung WY, Russell IT, Cohen DR, Longo M, Lervy B.; 2000 Feb 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27297

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Potential role of microorganisms isolated from periodontal lesions in the pathogenesis of inflammatory bowel disease. by Van Dyke TE, Dowell VR Jr, Offenbacher S, Snyder W, Hersh T.; 1986 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=260846

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Prevalence of inflammatory bowel disease in British 26 year olds: national longitudinal birth cohort. by Montgomery SM, Morris DL, Thompson NP, Subhani J, Pounder RE, Wakefield AJ.; 1998 Apr 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28509

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Results of Multiple Diagnostic Tests for Mycobacterium avium subsp. paratuberculosis in Patients with Inflammatory Bowel Disease and in Controls. by Collins MT, Lisby G, Moser C, Chicks D, Christensen S, Reichelderfer M, Hoiby N, Harms BA, Thomsen OO, Skibsted U, Binder V.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87608

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Treatment with Neurokinin-1 Receptor Antagonist Reduces Severity of Inflammatory Bowel Disease Induced by Cryptosporidium parvum. by Sonea IM, Palmer MV, Akili D, Harp JA.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=119952

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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 inflammatory bowel disease, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “inflammatory bowel disease” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for inflammatory bowel disease (hyperlinks lead to article summaries): ·

A case of SAPHO syndrome with pyoderma gangrenosum and inflammatory bowel disease masquerading as Behcet's disease. Author(s): Yamasaki O, Iwatsuki K, Kaneko F. Source: Advances in Experimental Medicine and Biology. 2003; 528: 339-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12918720

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A population- and family-based study of Canadian families reveals association of HLA DRB1*0103 with colonic involvement in inflammatory bowel disease. Author(s): Silverberg MS, Mirea L, Bull SB, Murphy JE, Steinhart AH, Greenberg GR, McLeod RS, Cohen Z, Wade JA, Siminovitch KA. Source: Inflammatory Bowel Diseases. 2003 January; 9(1): 1-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12656131

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A potent human C5a receptor antagonist protects against disease pathology in a rat model of inflammatory bowel disease. Author(s): Woodruff TM, Arumugam TV, Shiels IA, Reid RC, Fairlie DP, Taylor SM. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 November 15; 171(10): 5514-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607958

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A report on efficacy and safety of azathioprine in a group of inflammatory bowel disease patients in northwest Greece. Author(s): Christodoulou D, Katsanos K, Baltayannis G, Tzabouras N, Tsianos EV. Source: Hepatogastroenterology. 2003 July-August; 50(52): 1021-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12845970

6 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.

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Acquired microvascular dysfunction in inflammatory bowel disease: Loss of nitric oxide-mediated vasodilation. Author(s): Hatoum OA, Binion DG, Otterson MF, Gutterman DD. Source: Gastroenterology. 2003 July; 125(1): 58-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12851871

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Activated platelets are the source of elevated levels of soluble CD40 ligand in the circulation of inflammatory bowel disease patients. Author(s): Danese S, Katz JA, Saibeni S, Papa A, Gasbarrini A, Vecchi M, Fiocchi C. Source: Gut. 2003 October; 52(10): 1435-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12970136

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Active inflammatory bowel disease: evaluation with 99mTc (V) DMSA scintigraphy. Author(s): Koutroubakis IE, Koukouraki SI, Dimoulios PD, Velidaki AA, Karkavitsas NS, Kouroumalis EA. Source: Radiology. 2003 October; 229(1): 70-4. Epub 2003 August 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12925713

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Age and family history at presentation of pediatric inflammatory bowel disease. Author(s): Weinstein TA, Levine M, Pettei MJ, Gold DM, Kessler BH, Levine JJ. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 November; 37(5): 60913. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581806

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Allergens, dysbiosis and immune dysregulation: case studies on inflammatory bowel disease. Author(s): Lukaczer D, Lerman RH. Source: Alternative Therapies in Health and Medicine. 2003 May-June; 9(3): 136, 130-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12776484

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Alpha 4 integrin blockade in inflammatory bowel disease. Author(s): Ghosh S. Source: Annals of the Rheumatic Diseases. 2003 November; 62 Suppl 2: Ii70-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532154

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Altered glycosylation in inflammatory bowel disease: a possible role in cancer development. Author(s): Campbell BJ, Yu LG, Rhodes JM. Source: Glycoconjugate Journal. 2001 November-December; 18(11-12): 851-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12820718

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An open-label trial of the selective cyclo-oxygenase-2 inhibitor, rofecoxib, in inflammatory bowel disease-associated peripheral arthritis and arthralgia. Author(s): Reinisch W, Miehsler W, Dejaco C, Harrer M, Waldhoer T, Lichtenberger C, Vogelsang H. Source: Alimentary Pharmacology & Therapeutics. 2003 June 1; 17(11): 1371-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786631

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Anti-neutrophil cytoplasmic antibodies in Brazilian patients with inflammatory bowel disease. Author(s): Cabral VL, Miszputen SJ, Catapani WR. Source: Hepatogastroenterology. 2003 March-April; 50(50): 412-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12749235

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Anti-Saccharomyces cerevisiae antibodies in Japanese patients with inflammatory bowel disease: diagnostic accuracy and clinical value. Author(s): Hisabe T, Matsui T, Sakurai T, Murakami Y, Tanabe H, Matake H, Yao T, Kamachi S, Iwashita A. Source: Journal of Gastroenterology. 2003; 38(2): 121-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12640524

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Apoptosis, inflammatory bowel disease and carcinogenesis: overview of international and Greek experiences. Author(s): Kountouras J, Kouklakis G, Zavos C, Chatzopoulos D, Moschos J, Molyvas E, Zavos N. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 April; 17(4): 249-58. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12704469

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Assessment of disease activity in inflammatory bowel disease; relevance for clinical trials. Author(s): Naber AH, de Jong DJ. Source: The Netherlands Journal of Medicine. 2003 April; 61(4): 105-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12852718

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Association between K469E allele of intercellular adhesion molecule 1 gene and inflammatory bowel disease in different populations. Author(s): Papa A, Danese S, Armuzzi A, Gaetani E, Flex A, Pola P, Gasbarrini A. Source: Gut. 2003 August; 52(8): 1227-8; Author Reply 1228. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12865290

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Association between p47phox pseudogenes and inflammatory bowel disease. Author(s): Harbord M, Hankin A, Bloom S, Mitchison H. Source: Blood. 2003 April 15; 101(8): 3337. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12672696

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Association of extraintestinal manifestations of inflammatory bowel disease in a province of western Hungary with disease phenotype: results of a 25-year follow-up study. Author(s): Lakatos L, Pandur T, David G, Balogh Z, Kuronya P, Tollas A, Lakatos PL. Source: World Journal of Gastroenterology : Wjg. 2003 October; 9(10): 2300-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562397

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Association of TNF-alpha-857C with inflammatory bowel disease in the Australian population. Author(s): O'Callaghan NJ, Adams KE, van Heel DA, Cavanaugh JA. Source: Scandinavian Journal of Gastroenterology. 2003 May; 38(5): 533-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12795465

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B2 microglobulin: is it a reliable marker of activity in inflammatory bowel disease? Author(s): Zissis M, Afroudakis A, Galanopoulos G, Palermos L, Boura X, Michopoulos S, Archimandritis A. Source: The American Journal of Gastroenterology. 2001 July; 96(7): 2177-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11467650

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Bacteroides ovatus as the predominant commensal intestinal microbe causing a systemic antibody response in inflammatory bowel disease. Author(s): Saitoh S, Noda S, Aiba Y, Takagi A, Sakamoto M, Benno Y, Koga Y. Source: Clinical and Diagnostic Laboratory Immunology. 2002 January; 9(1): 54-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11777829

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Bartonella hensela in inflammatory bowel disease. Author(s): Numazaki K, Chiba S, Ueno H. Source: Lancet. 2001 June 16; 357(9272): 1974-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11430386

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Bartonella henselae and inflammatory bowel disease. Author(s): Massei F, Massimetti M, Messina F, Macchia P, Maggiore G. Source: Lancet. 2000 October 7; 356(9237): 1245-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11072951

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Basic coating polymers for the colon-specific drug delivery in inflammatory bowel disease. Author(s): Leopold CS, Eikeler D. Source: Drug Development and Industrial Pharmacy. 2000 December; 26(12): 1239-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11147124

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Benefit of anti-TNFalpha treatment for nephrotic syndrome in a patient with juvenile inflammatory bowel disease associated spondyloarthropathy complicated with amyloidosis and glomerulonephritis. Author(s): Verschueren P, Lensen F, Lerut E, Claes K, De Vos R, Van Damme B, Westhovens R. Source: Annals of the Rheumatic Diseases. 2003 April; 62(4): 368-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12634242

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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/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12656695

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Biochemical markers and bone densitometry in inflammatory bowel disease. Author(s): Ledro Cano D, Torres Dominguez Y, Castro Laria L, Saenz Dana M, Herrerias Esteban JM, Herrerias Gutierrez JM. Source: Rev Esp Enferm Dig. 2000 September; 92(9): 595-600. English, Spanish. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11138241

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Biodegradable microparticles as a two-drug controlled release formulation: a potential treatment of inflammatory bowel disease. Author(s): Lamprecht A, Rodero Torres H, Schafer U, Lehr CM. Source: Journal of Controlled Release : Official Journal of the Controlled Release Society. 2000 December 3; 69(3): 445-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11102684

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Biodegradable microspheres targeting mucosal immune-regulating cells: new approach for treatment of inflammatory bowel disease. Author(s): Nakase H, Okazaki K, Tabata Y, Chiba T. Source: Journal of Gastroenterology. 2003 March; 38 Suppl 15: 59-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698874

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Biologic therapy of inflammatory bowel disease. Author(s): Sandborn WJ, Targan SR. Source: Gastroenterology. 2002 May; 122(6): 1592-608. Review. Erratum In: Gastroenterology 2002 August; 123(2): 656. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12016425

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Biological and novel therapies for inflammatory bowel disease in children. Author(s): Mamula P, Mascarenhas MR, Baldassano RN. Source: Pediatric Clinics of North America. 2002 February; 49(1): 1-25. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11826800

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Biological therapies of inflammatory bowel disease. Author(s): van Deventer SJ. Source: Acta Gastroenterol Belg. 2001 April-June; 64(2): 177-81. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11475130

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Biotechnologically manufactured drugs for inflammatory bowel disease. Author(s): Petersen JA, Rasmussen SN. Source: Scandinavian Journal of Gastroenterology. 2001 December; 36(12): 1233-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11761010

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Blockade of NF-kappaB activation and donation of nitric oxide: new treatment options in inflammatory bowel disease? Author(s): Dijkstra G, Moshage H, Jansen PL. Source: Scandinavian Journal of Gastroenterology. Supplement. 2002; (236): 37-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12408502

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Body composition in patients with an ileostomy and inflammatory bowel disease: validation of bio-electric impedance spectroscopy (BIS). Author(s): Carlsson E, Bosaeus I, Nordgren S. Source: European Journal of Clinical Nutrition. 2002 July; 56(7): 680-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12080410

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Body composition in patients with inflammatory bowel disease: a population-based study. Author(s): Jahnsen J, Falch JA, Mowinckel P, Aadland E. Source: The American Journal of Gastroenterology. 2003 July; 98(7): 1556-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873577

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Bone density in a population-based cohort of premenopausal adult women with early onset inflammatory bowel disease. Author(s): Bernstein CN, Leslie WD, Taback SP. Source: The American Journal of Gastroenterology. 2003 May; 98(5): 1094-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809833

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Bone mineral density in patients with inflammatory bowel disease. Author(s): Martin JP, Tonge KA, Bhonsle U, Jacyna MR, Levi J. Source: European Journal of Gastroenterology & Hepatology. 1999 May; 11(5): 537-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10755258

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Bone morphogenetic protein-7 reduces the severity of colon tissue damage and accelerates the healing of inflammatory bowel disease in rats. Author(s): Maric I, Poljak L, Zoricic S, Bobinac D, Bosukonda D, Sampath KT, Vukicevic S. Source: Journal of Cellular Physiology. 2003 August; 196(2): 258-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12811818

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Campylobacter jejuni enterocolitis presenting as inflammatory bowel disease. Author(s): Quondamcarlo C, Valentini G, Ruggeri M, Forlini G, Fenderico P, Rossi Z. Source: Techniques in Coloproctology. 2003 October; 7(3): 173-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14628162

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CARD15 genotyping in inflammatory bowel disease patients by multiplex pyrosequencing. Author(s): Palmieri O, Toth S, Ferraris A, Andriulli A, Latiano A, Annese V, Dallapiccola B, Vecchi M, Devoto M, Surrey S, Fortina P. Source: Clinical Chemistry. 2003 October; 49(10): 1675-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14500598

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Cerebral venous thrombosis in acute inflammatory bowel disease. Author(s): Singh G, Sarkar S, Manoj K, Shorrock C, Isaacs P. Source: Gut. 2004 February; 53(2): 161, 206. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724141

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Changing pattern of paediatric inflammatory bowel disease in northern Stockholm 1990-2001. Author(s): Hildebrand H, Finkel Y, Grahnquist L, Lindholm J, Ekbom A, Askling J. Source: Gut. 2003 October; 52(10): 1432-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12970135

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Chronic sinonasal disease in patients with inflammatory bowel disease. Author(s): Book DT, Smith TL, McNamar JP, Saeian K, Binion DG, Toohill RJ. Source: American Journal of Rhinology. 2003 March-April; 17(2): 87-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12751702

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Clinical aspects and pathophysiology of inflammatory bowel disease. Author(s): Hendrickson BA, Gokhale R, Cho JH. Source: Clinical Microbiology Reviews. 2002 January; 15(1): 79-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11781268

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Cognitive function in people with chronic illness: inflammatory bowel disease and irritable bowel syndrome. Author(s): Attree EA, Dancey CP, Keeling D, Wilson C. Source: Applied Neuropsychology. 2003; 10(2): 96-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12788684

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Colon carcinogenesis in inflammatory bowel disease: applying molecular genetics to clinical practice. Author(s): Itzkowitz S. Source: Journal of Clinical Gastroenterology. 2003 May-June; 36(5 Suppl): S70-4; Discussion S94-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12702969

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Color Doppler transabdominal ultrasonography for the assessment of the patients with inflammatory bowel disease during treatment. Author(s): Rogoveanu I, Saftoiu A, Cazacu S, Ciurea T. Source: Rom J Gastroenterol. 2003 December; 12(4): 277-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14726971

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Colorectal cancer in patients with inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis. Author(s): Vera A, Gunson BK, Ussatoff V, Nightingale P, Candinas D, Radley S, Mayer AD, Buckels JA, McMaster P, Neuberger J, Mirza DF. Source: Transplantation. 2003 June 27; 75(12): 1983-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12829898

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Colorectal mass lesions masquerading as chronic inflammatory bowel disease on mucosal biopsy. Author(s): Gupta J, Shepherd NA. Source: Histopathology. 2003 May; 42(5): 476-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12713625

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Comparison of multidetector CT and barium studies of the small bowel: inflammatory bowel disease in children. Author(s): Jamieson DH, Shipman PJ, Israel DM, Jacobson K. Source: Ajr. American Journal of Roentgenology. 2003 May; 180(5): 1211-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12704025

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Complementary alternative medicine in patients with inflammatory bowel disease: use and attitudes. Author(s): Quattropani C, Ausfeld B, Straumann A, Heer P, Seibold F. Source: Scandinavian Journal of Gastroenterology. 2003 March; 38(3): 277-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12737442

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Complementary and alternative medicine use by Canadian patients with inflammatory bowel disease: results from a national survey. Author(s): Hilsden RJ, Verhoef MJ, Best A, Pocobelli G. Source: The American Journal of Gastroenterology. 2003 July; 98(7): 1563-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873578

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Connecting the dots from Toll-like receptors to innate immune cells and inflammatory bowel disease. Author(s): Boone DL, Ma A. Source: The Journal of Clinical Investigation. 2003 May; 111(9): 1284-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12727919

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Contraceptive choices for women with inflammatory bowel disease. Author(s): Faculty of Family Planning & Reproductive Health Care, Clinical Effectiveness Unit. Source: The Journal of Family Planning and Reproductive Health Care / Faculty of Family Planning & Reproductive Health Care, Royal College of Obstetricians & Gynaecologists. 2003 July; 29(3): 127-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12885304

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Corticosteroids and immunomodulators: postoperative infectious complication risk in inflammatory bowel disease patients. Author(s): Aberra FN, Lewis JD, Hass D, Rombeau JL, Osborne B, Lichtenstein GR. Source: Gastroenterology. 2003 August; 125(2): 320-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12891531

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Cryptosporidium parvum in intestinal mucosal biopsies from patients with inflammatory bowel disease. Author(s): Chen W, Chadwick V, Tie A, Harp J. Source: The American Journal of Gastroenterology. 2001 December; 96(12): 3463-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11774987

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Cytokine and anti-cytokine therapies for inflammatory bowel disease. Author(s): Ogata H, Hibi T. Source: Current Pharmaceutical Design. 2003; 9(14): 1107-13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12769750

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Cytokine network in inflammatory bowel disease. Author(s): Fuss IJ. Source: Current Drug Targets. Inflammation and Allergy. 2003 June; 2(2): 101-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561161

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Defining subtypes of Crohn's disease patients: the ground work for translational research in inflammatory bowel disease. Author(s): Abreu MT, Yang H. Source: Journal of Clinical Gastroenterology. 2003 January; 36(1): 3-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12488696

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Delayed puberty associated with inflammatory bowel disease. Author(s): Ballinger AB, Savage MO, Sanderson IR. Source: Pediatric Research. 2003 February; 53(2): 205-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12538776

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Detection of Chlamydia pneumoniae by polymerase chain reaction-enzyme immunoassay in intestinal mucosal biopsies from patients with inflammatory bowel disease and controls. Author(s): Chen W, Li D, Wilson I, Chadwick VS. Source: Journal of Gastroenterology and Hepatology. 2002 September; 17(9): 987-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12167120

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Determinants of bone loss in inflammatory bowel disease: a new role for interleukin6 polymorphisms? Author(s): Hurlstone DP. Source: Scandinavian Journal of Gastroenterology. 2002 August; 37(8): 987. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12229978

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Developments in understanding and management of inflammatory bowel disease. Author(s): Hershman MJ. Source: Hosp Med. 2003 December; 64(12): 702. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14702779

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Diagnosis and misdiagnosis of inflammatory bowel disease. Author(s): Papadakis KA, Tabibzadeh S. Source: Gastrointest Endosc Clin N Am. 2002 July; 12(3): 433-49. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12486937

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Diagnostic problems and advances in inflammatory bowel disease. Author(s): Odze R. Source: Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 2003 April; 16(4): 347-58. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12692200

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Diagnostic role of anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic antibodies in patients with inflammatory bowel disease. Author(s): Kim BG, Kim YS, Kim JS, Jung HC, Song IS. Source: Diseases of the Colon and Rectum. 2002 August; 45(8): 1062-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12195191

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Diagnostic value of anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies for inflammatory bowel disease: high prevalence in patients with celiac disease. Author(s): Damoiseaux JG, Bouten B, Linders AM, Austen J, Roozendaal C, Russel MG, Forget PP, Tervaert JW. Source: Journal of Clinical Immunology. 2002 September; 22(5): 281-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12405161

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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/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12063968

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Differential mucosal expression of three superoxide dismutase isoforms in inflammatory bowel disease. Author(s): Kruidenier L, Kuiper I, van Duijn W, Marklund SL, van Hogezand RA, Lamers CB, Verspaget HW. Source: The Journal of Pathology. 2003 September; 201(1): 7-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950012

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Diminished efficacy of colonic adaptation to lactulose occurs in patients with inflammatory bowel disease in remission. Author(s): Szilagyi A, Rivard J, Shrier I. Source: Digestive Diseases and Sciences. 2002 December; 47(12): 2811-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12498306

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Discriminant histological features in the diagnosis of chronic idiopathic inflammatory bowel disease: analysis of a large dataset by a novel data visualisation technique. Author(s): Cross SS, Harrison RF. Source: Journal of Clinical Pathology. 2002 January; 55(1): 51-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11825925

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Discussion on inflammatory bowel disease is not associated with an increased risk of lymphoma. Author(s): Bernatsky S. Source: Gastroenterology. 2002 August; 123(2): 653. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12145829

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Discussion on the biologic therapy of inflammatory bowel disease. Author(s): Merger M, Herfarth H, Scholmerich J, Andus T, Farber L. Source: Gastroenterology. 2003 June; 124(7): 2005-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12812200

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Discussion on the safety of 6-mercaptopurine for childbearing patients with inflammatory bowel disease: a retrospective cohort study. Author(s): Yacyshyn BR, Pilarski LM. Source: Gastroenterology. 2003 November; 125(5): 1562; Author Reply 1562. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14628819

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Does monitoring prevent cancer in inflammatory bowel disease? Author(s): Loftus EV Jr. Source: Journal of Clinical Gastroenterology. 2003 May-June; 36(5 Suppl): S79-83; Discussion S94-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12702971

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Does the use of 5-aminosalicylates in inflammatory bowel disease prevent the development of colorectal cancer? Author(s): Bernstein CN, Blanchard JF, Metge C, Yogendran M. Source: The American Journal of Gastroenterology. 2003 December; 98(12): 2784-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14687833

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Dysbiosis in inflammatory bowel disease. Author(s): Tamboli CP, Neut C, Desreumaux P, Colombel JF. Source: Gut. 2004 January; 53(1): 1-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684564

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Dysplasia in inflammatory bowel disease. Author(s): Greenson JK. Source: Semin Diagn Pathol. 2002 February; 19(1): 31-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11936264

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Effect of liver transplantation on inflammatory bowel disease in patients with primary sclerosing cholangitis. Author(s): Dvorchik I, Subotin M, Demetris AJ, Fung JJ, Starzl TE, Wieand S, AbuElmagd KM. Source: Hepatology (Baltimore, Md.). 2002 February; 35(2): 380-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11826412

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Effect of nicotine on inflammatory bowel disease. Author(s): Naser SA, Ghobrial G, Miles H. Source: The American Journal of Gastroenterology. 2001 December; 96(12): 3455-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11774981

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Effects of duodenal seal oil administration in patients with inflammatory bowel disease. Author(s): Arslan G, Brunborg LA, Froyland L, Brun JG, Valen M, Berstad A. Source: Lipids. 2002 October; 37(10): 935-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12530551

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Efficacy of Pentasa tablets for the treatment of inflammatory bowel disease. Author(s): Wong JM, Wei SC. Source: J Formos Med Assoc. 2003 September; 102(9): 613-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14625605

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Endoscopy in the pregnant patient with inflammatory bowel disease. Author(s): Katz JA. Source: Gastrointest Endosc Clin N Am. 2002 July; 12(3): 635-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12486949

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Enhanced endoscopy in inflammatory bowel disease. Author(s): Jacobson BC, Van Dam J. Source: Gastrointest Endosc Clin N Am. 2002 July; 12(3): 573-87. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12486945

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Environmental influences on inflammatory bowel disease manifestations. Lessons from epidemiology. Author(s): Timmer A. Source: Digestive Diseases (Basel, Switzerland). 2003; 21(2): 91-104. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571108

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Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study. Author(s): Kugathasan S, Judd RH, Hoffmann RG, Heikenen J, Telega G, Khan F, Weisdorf-Schindele S, San Pablo W Jr, Perrault J, Park R, Yaffe M, Brown C, RiveraBennett MT, Halabi I, Martinez A, Blank E, Werlin SL, Rudolph CD, Binion DG; Wisconsin Pediatric Inflammatory Bowel Disease Alliance. Source: The Journal of Pediatrics. 2003 October; 143(4): 525-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571234

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Epstein-Barr virus infection in colorectal neoplasms associated with inflammatory bowel disease: detection of the virus in lymphomas but not in adenocarcinomas. Author(s): Wong NA, Herbst H, Herrmann K, Kirchner T, Krajewski AS, Moorghen M, Niedobitek F, Rooney N, Shepherd NA, Niedobitek G. Source: The Journal of Pathology. 2003 October; 201(2): 312-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14517849

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Epstein-Barr virus-positive lymphoma in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine. Author(s): Dayharsh GA, Loftus EV Jr, Sandborn WJ, Tremaine WJ, Zinsmeister AR, Witzig TE, Macon WR, Burgart LJ. Source: Gastroenterology. 2002 January; 122(1): 72-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11781282

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Erythrocyte mean corpuscular volume as a surrogate marker for 6-thioguanine nucleotide concentration monitoring in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine. Author(s): Thomas CW Jr, Lowry PW, Franklin CL, Weaver AL, Myhre GM, Mays DC, Tremaine WJ, Lipsky JJ, Sandborn WJ. Source: Inflammatory Bowel Diseases. 2003 July; 9(4): 237-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12902847

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Evaluation of 99mTc-HMPAO leukocyte scintigraphy in the investigation of pediatric inflammatory bowel disease. Author(s): Grahnquist L, Chapman SC, Hvidsten S, Murphy MS. Source: The Journal of Pediatrics. 2003 July; 143(1): 48-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915823

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Evaluation of bone mineral density in inflammatory bowel disease: current safety focus. Author(s): Lichtenstein GR. Source: The American Journal of Gastroenterology. 2003 December; 98(12 Suppl): S2430. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14697915

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Evaluation of bone mineral density in patients with inflammatory bowel disease. Author(s): Cuffari C, Lichtenstein GR. Source: Current Gastroenterology Reports. 2003 August; 5(4): 261-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12864952

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Evaluation of educational programs in inflammatory bowel disease. Author(s): Quan H, Present JW, Sutherland LR. Source: Inflammatory Bowel Diseases. 2003 November; 9(6): 356-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14671484

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Evaluation of Helicobacter species in inflammatory bowel disease. Author(s): Bell SJ, Chisholm SA, Owen RJ, Borriello SP, Kamm MA. Source: Alimentary Pharmacology & Therapeutics. 2003 September 1; 18(5): 481-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950420

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Evaluation of new therapies for inflammatory bowel disease. Author(s): Carty E, Rampton DS. Source: British Journal of Clinical Pharmacology. 2003 October; 56(4): 351-61. Review. Erratum In: Br J Clin Pharmacol. 2003 November; 56(5): 584. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12968979

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Expression and regulation of tissue inhibitor of metalloproteinase-1 and matrix metalloproteinases by intestinal myofibroblasts in inflammatory bowel disease. Author(s): McKaig BC, McWilliams D, Watson SA, Mahida YR. Source: American Journal of Pathology. 2003 April; 162(4): 1355-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12651627

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Expression of platelet-derived endothelial cell growth factor in inflammatory bowel disease. Author(s): Saito S, Tsuno NH, Sunami E, Hori N, Kitayama J, Kazama S, Okaji Y, Kawai K, Kanazawa T, Watanabe T, Shibata Y, Nagawa H. Source: Journal of Gastroenterology. 2003; 38(3): 229-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12673445

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Expression, localization, and functional activity of TL1A, a novel Th1-polarizing cytokine in inflammatory bowel disease. Author(s): Bamias G, Martin C 3rd, Marini M, Hoang S, Mishina M, Ross WG, Sachedina MA, Friel CM, Mize J, Bickston SJ, Pizarro TT, Wei P, Cominelli F. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 November 1; 171(9): 486874. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14568967

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Factor V Leiden and prothrombin gene mutation in inflammatory bowel disease in a Mediterranean area. Author(s): Turri D, Rosselli M, Simioni P, Tormene D, Grimaudo S, Martorana G, Siragusa S, Mariani G, Cottone M, Siracusa S. Source: Dig Liver Dis. 2001 October; 33(7): 559-62. Erratum In: Dig Liver Dis 2002 March; 34(3): 212. Siracusa S [corrected to Siragusa S]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11816544

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Factor XIII and tissue transglutaminase antibodies in coeliac and inflammatory bowel disease. Author(s): Sjober K, Eriksson S, Tenngart B, Roth EB, Leffler H, Stenberg P. Source: Autoimmunity. 2002 August; 35(5): 357-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12515290

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Factors affecting health related quality of life of patients with inflammatory bowel disease. Author(s): Casellas F, Lopez-Vivancos J, Casado A, Malagelada JR. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2002 December; 11(8): 775-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12482161

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Factors affecting surgical risk in elderly patients with inflammatory bowel disease. Author(s): Page MJ, Poritz LS, Kunselman SJ, Koltun WA. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2002 July-August; 6(4): 606-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12127128

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Faecal calprotectin levels in infants with infantile colic, healthy infants, children with inflammatory bowel disease, children with recurrent abdominal pain and healthy children. Author(s): Olafsdottir E, Aksnes L, Fluge G, Berstad A. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(1): 45-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11883817

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Failure to yield: drug resistance in inflammatory bowel disease. Author(s): Tremaine WJ. Source: Gastroenterology. 2002 April; 122(4): 1165-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11910368

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Familial and sporadic inflammatory bowel disease: comparison of clinical features and serological markers in a genetically homogeneous population. Author(s): Halme L, Turunen U, Helio T, Paavola P, Walle T, Miettinen A, Jarvinen H, Kontula K, Farkkila M. Source: Scandinavian Journal of Gastroenterology. 2002 June; 37(6): 692-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12126248

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Familial and sporadic inflammatory bowel disease: different entities? Author(s): Peeters M, Cortot A, Vermeire S, Colombel JF. Source: Inflammatory Bowel Diseases. 2000 November; 6(4): 314-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11149564

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Familial occurrence of inflammatory bowel disease in celiac disease. Author(s): Cottone M, Marrone C, Casa A, Oliva L, Orlando A, Calabrese E, Martorana G, Pagliaro L. Source: Inflammatory Bowel Diseases. 2003 September; 9(5): 321-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14555916

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Family history as a risk factor for colorectal cancer in inflammatory bowel disease. Author(s): Askling J, Dickman PW, Karlen P, Brostrom O, Lapidus A, Lofberg R, Ekbom A. Source: Gastroenterology. 2001 May; 120(6): 1356-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11313305

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Fecal calprotectin as a measure of disease activity in childhood inflammatory bowel disease. Author(s): Bunn SK, Bisset WM, Main MJ, Golden BE. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 February; 32(2): 171-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11321388

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Fecal calprotectin: validation as a noninvasive measure of bowel inflammation in childhood inflammatory bowel disease. Author(s): Bunn SK, Bisset WM, Main MJ, Gray ES, Olson S, Golden BE. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 July; 33(1): 14-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11479402

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Fertility and pregnancy in inflammatory bowel disease. Author(s): Alstead E. Source: World Journal of Gastroenterology : Wjg. 2001 August; 7(4): 455-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11819810

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Fibromyalgia and chronic widespread pain in patients with inflammatory bowel disease: a cross sectional population survey. Author(s): Palm O, Moum B, Jahnsen J, Gran JT. Source: The Journal of Rheumatology. 2001 March; 28(3): 590-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11296964

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Fine mapping of the chromosome 3p susceptibility locus in inflammatory bowel disease. Author(s): Hampe J, Lynch NJ, Daniels S, Bridger S, Macpherson AJ, Stokkers P, Forbes A, Lennard-Jones JE, Mathew CG, Curran ME, Schreiber S. Source: Gut. 2001 February; 48(2): 191-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11156639

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Food for thought in managing inflammatory bowel disease. Author(s): Phillips S. Source: Community Nurse. 2000 December; 6(11): 13-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11982170

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Frequency of extraintestinal manifestations in patients with inflammatory bowel disease in Northwest Greece and review of the literature. Author(s): Christodoulou DK, Katsanos KH, Kitsanou M, Stergiopoulou C, Hatzis J, Tsianos EV. Source: Dig Liver Dis. 2002 November; 34(11): 781-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12546513

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Frequency of use and standards of care for the use of azathioprine and 6mercaptopurine in the treatment of inflammatory bowel disease: a systematic review of the literature and a survey of Canadian gastroenterologists. Author(s): Wallace TM, Veldhuyzen van Zanten SJ. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2001 January; 15(1): 21-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11173323

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Functional bowel disorders in inflammatory bowel disease. Author(s): Pezzone MA, Wald A. Source: Gastroenterology Clinics of North America. 2002 March; 31(1): 347-57. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12122742

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Fundamental mechanisms of growth failure in inflammatory bowel disease. Author(s): Ballinger A. Source: Hormone Research. 2002; 58 Suppl 1: 7-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12373006

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Gender issues in the management of inflammatory bowel disease and irritable bowel syndrome. Author(s): Kane S. Source: Int J Fertil Womens Med. 2002 May-June; 47(3): 136-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12081259

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Gene transfer approaches for the treatment of inflammatory bowel disease. Author(s): Wirtz S, Neurath MF. Source: Gene Therapy. 2003 May; 10(10): 854-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12732871

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Genetic and nutritional predictors of hyperhomocysteinemia in inflammatory bowel disease. Author(s): Papa A, Danese S, Gasbarrini G, Gasbarrini A. Source: The American Journal of Gastroenterology. 2002 February; 97(2): 490-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11866298

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Genetic aspects of inflammatory bowel disease. Author(s): Hugot JP. Source: Nestle Nutr Workshop Ser Clin Perform Programme. 1999; 2: 23-37; Discussion 37-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11490625

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Genetic determinants of IL-6 expression levels do not influence bone loss in inflammatory bowel disease. Author(s): Schulte C, Goebell H, Roher HD, Schulte KM. Source: Digestive Diseases and Sciences. 2001 November; 46(11): 2521-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11713964

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Genetic dissection of the cellular pathways and signaling mechanisms in modeled tumor necrosis factor-induced Crohn's-like inflammatory bowel disease. Author(s): Kontoyiannis D, Boulougouris G, Manoloukos M, Armaka M, Apostolaki M, Pizarro T, Kotlyarov A, Forster I, Flavell R, Gaestel M, Tsichlis P, Cominelli F, Kollias G. Source: The Journal of Experimental Medicine. 2002 December 16; 196(12): 1563-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12486099

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Genetic refinement and physical mapping of a chromosome 16q candidate region for inflammatory bowel disease. Author(s): Zouali H, Chamaillard M, Lesage S, Cezard JP, Colombel JF, Belaiche J, Almer S, Tysk C, Montague S, Gassull M, Christensen S, Finkel Y, Gower-Rousseau C, Modigliani R, Macry J, Selinger-Leneman H, Thomas G, Hugot JP; GETAID. Source: European Journal of Human Genetics : Ejhg. 2001 October; 9(10): 731-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11781683

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Genetic variation in the IGSF6 gene and lack of association with inflammatory bowel disease. Author(s): King K, Moody A, Fisher SA, Mirza MM, Cuthbert AP, Hampe J, SutherlandCraggs A, Sanderson J, MacPherson AJ, Forbes A, Mansfield J, Schreiber S, Lewis CM, Mathew CG. Source: European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics. 2003 June; 30(3): 187-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786995

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Genetics of inflammatory bowel disease. Author(s): Karban A, Eliakim R, Brant SR. Source: Isr Med Assoc J. 2002 October; 4(10): 798-802. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12389344

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Genetics of inflammatory bowel disease: from bench to bedside? Author(s): Satsangi J. Source: Acta Odontologica Scandinavica. 2001 June; 59(3): 187-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11501890

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Genetics of inflammatory bowel disease: scientific and clinical implications. Author(s): Satsangi J, Morecroft J, Shah NB, Nimmo E. Source: Best Practice & Research. Clinical Gastroenterology. 2003 February; 17(1): 3-18. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12617879

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Genetics of inflammatory bowel disease: the beginning of the end or the end of the beginning? Author(s): Annese V, Latiano A, Andriulli A. Source: Dig Liver Dis. 2003 June; 35(6): 442-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12868683

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Genetics of inflammatory bowel disease--an update. Author(s): van Heel DA, Jewell DP. Source: Acta Gastroenterol Belg. 2001 April-June; 64(2): 160-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11475126

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Genome-wide search in Finnish families with inflammatory bowel disease provides evidence for novel susceptibility loci. Author(s): Paavola-Sakki P, Ollikainen V, Helio T, Halme L, Turunen U, Lahermo P, Lappalainen M, Farkkila M, Kontula K. Source: European Journal of Human Genetics : Ejhg. 2003 February; 11(2): 112-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12634858

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Genomic structure, chromosome mapping and expression analysis of the human AVIL gene, and its exclusion as a candidate for locus for inflammatory bowel disease at 12q13-14 (IBD2). Author(s): Tumer Z, Croucher PJ, Jensen LR, Hampe J, Hansen C, Kalscheuer V, Ropers HH, Tommerup N, Schreiber S. Source: Gene. 2002 April 17; 288(1-2): 179-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12034507

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Genotype-phenotype correlations: how many disorders constitute inflammatory bowel disease? Author(s): Gasche C, Alizadeh BZ, Pena AS. Source: European Journal of Gastroenterology & Hepatology. 2003 June; 15(6): 599-606. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12840669

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Glucocorticoid resistance in inflammatory bowel disease. Author(s): Farrell RJ, Kelleher D. Source: The Journal of Endocrinology. 2003 September; 178(3): 339-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12967327

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Growth failure in the child with inflammatory bowel disease. Author(s): Stephens M, Batres LA, Ng D, Baldassano R. Source: Semin Gastrointest Dis. 2001 October; 12(4): 253-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11726079

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Growth hormone has anabolic effects in glucocorticosteroid-dependent children with inflammatory bowel disease: a pilot study. Author(s): Mauras N, George D, Evans J, Milov D, Abrams S, Rini A, Welch S, Haymond MW. Source: Metabolism: Clinical and Experimental. 2002 January; 51(1): 127-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11782884

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Guidelines for screening and surveillance of asymptomatic colorectal cancer in patients with inflammatory bowel disease. Author(s): Eaden JA, Mayberry JF; British Society for Gastroenterology; Association of Coloproctology for Great Britain and Ireland. Source: Gut. 2002 October; 51 Suppl 5: V10-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12221032

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Health-related quality of life and psychological distress in a population-based sample of Swedish patients with inflammatory bowel disease. Author(s): Nordin K, Pahlman L, Larsson K, Sundberg-Hjelm M, Loof L. Source: Scandinavian Journal of Gastroenterology. 2002 April; 37(4): 450-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11989837

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Helicobacter pylori infection in patients with inflammatory bowel disease. Author(s): Guslandi M. Source: The American Journal of Gastroenterology. 2003 November; 98(11): 2570-1; Author Reply 2571-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638369

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Hepatic manifestations of gastrointestinal diseases. Inflammatory bowel disease, celiac disease, and Whipple's disease. Author(s): Smyth C, Kelleher D, Keeling PW. Source: Clinics in Liver Disease. 2002 November; 6(4): 1013-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12516204

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Hepatobiliary alterations in patients with inflammatory bowel disease. Author(s): Caserta L, Riegler G. Source: Archives of Internal Medicine. 2002 June 10; 162(11): 1312; Author Reply 1312-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12038955

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Hepatobiliary disease in inflammatory bowel disease. Author(s): Ahmad J, Slivka A. Source: Gastroenterology Clinics of North America. 2002 March; 31(1): 329-45. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12122741

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Heterogeneity of HPLC profiles of human class II MHC-bound peptides isolated from intestine with inflammatory bowel disease. Author(s): Oshitani N, Hato F, Jinno Y, Sawa Y, Hara J, Nakamura S, Matsumoto T, Arakawa T, Kitano A, Kitagawa S, Kuroki T. Source: Digestive Diseases and Sciences. 2002 September; 47(9): 2088-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12353860

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High prevalence of fatigue in quiescent inflammatory bowel disease is not related to adrenocortical insufficiency. Author(s): Minderhoud IM, Oldenburg B, van Dam PS, van Berge Henegouwen GP. Source: The American Journal of Gastroenterology. 2003 May; 98(5): 1088-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809832

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High prevalence of Mycoplasma pneumoniae in intestinal mucosal biopsies from patients with inflammatory bowel disease and controls. Author(s): Chen W, Li D, Paulus B, Wilson I, Chadwick VS. Source: Digestive Diseases and Sciences. 2001 November; 46(11): 2529-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11713965

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High resolution MIC genotyping: design and application to the investigation of inflammatory bowel disease susceptibility. Author(s): Ahmad T, Marshall SE, Mulcahy-Hawes K, Orchard T, Crawshaw J, Armuzzi A, Neville M, van Heel D, Barnardo M, Welsh KI, Jewell DP, Bunce M. Source: Tissue Antigens. 2002 August; 60(2): 164-79. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12392511

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High-dose azathioprine in children with inflammatory bowel disease. Author(s): Fuentes D, Torrente F, Keady S, Thirrupathy K, Thomson MA, Walker-Smith JA, Murch SH, Heuschkel RB. Source: Alimentary Pharmacology & Therapeutics. 2003 April 1; 17(7): 913-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12656694

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Hip fractures in patients with inflammatory bowel disease and their relationship to corticosteroid use: a population based cohort study. Author(s): Card T, West J, Hubbard R, Logan RF. Source: Gut. 2004 February; 53(2): 251-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724159

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Histologic changes in defunctioned rectums in patients with inflammatory bowel disease: a clinicopathologic study of 82 patients with long-term follow-up. Author(s): Asplund S, Gramlich T, Fazio V, Petras R. Source: Diseases of the Colon and Rectum. 2002 September; 45(9): 1206-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12352238

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HLA antigens and anti-neutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease. Author(s): Garcia Herola A, Nos P, Hinijosa J, Hoyos M, Moles JR, Carmona E, Puig N, Sanchez-Cuenca JM, Ponce J, Berenguer J. Source: Rev Esp Enferm Dig. 2003 November; 95(11): 760-4, 755-9. English, Spanish. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14640873

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Home total parenteral nutrition: an alternative to early surgery for complicated inflammatory bowel disease. Author(s): Evans JP, Steinhart AH, Cohen Z, McLeod RS. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2003 May-June; 7(4): 562-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12763417

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Homing of mucosal lymphocytes to the liver in the pathogenesis of hepatic complications of inflammatory bowel disease. Author(s): Grant AJ, Lalor PF, Salmi M, Jalkanen S, Adams DH. Source: Lancet. 2002 January 12; 359(9301): 150-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11809275

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Homocysteine, cysteine, and glutathione in human colonic mucosa: elevated levels of homocysteine in patients with inflammatory bowel disease. Author(s): Morgenstern I, Raijmakers MT, Peters WH, Hoensch H, Kirch W. Source: Digestive Diseases and Sciences. 2003 October; 48(10): 2083-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627359

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Human beta-defensin 2 but not beta-defensin 1 is expressed preferentially in colonic mucosa of inflammatory bowel disease. Author(s): Wehkamp J, Fellermann K, Herrlinger KR, Baxmann S, Schmidt K, Schwind B, Duchrow M, Wohlschlager C, Feller AC, Stange EF. Source: European Journal of Gastroenterology & Hepatology. 2002 July; 14(7): 745-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12169983

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Hyperhomocysteinaemia, coagulation pathway activation and thrombophilia in patients with inflammatory bowel disease. Author(s): Bjerregaard LT, Nederby NJ, Fredholm L, Brandslund I, Munkholm P, Hey H. Source: Scandinavian Journal of Gastroenterology. 2002 January; 37(1): 62-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11843038

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Hyperhomocystinemia in children with inflammatory bowel disease. Author(s): Nakano E, Taylor CJ, Chada L, McGaw J, Powers HJ. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 November; 37(5): 58690. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581802

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Hypothalamic digoxin, hemispheric chemical dominance, and inflammatory bowel disease. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 September; 113(9): 1221-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12959741

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Identification of novel polymorphisms in the beta7 integrin gene: family-based association studies in inflammatory bowel disease. Author(s): van Heel DA, Carey AH, Jewell DP. Source: Genes and Immunity. 2001 December; 2(8): 455-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11781713

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IgA and IgG tissue transglutaminase antibody prevalence and clinical significance in connective tissue diseases, inflammatory bowel disease, and primary biliary cirrhosis. Author(s): Bizzaro N, Villalta D, Tonutti E, Doria A, Tampoia M, Bassetti D, Tozzoli R. Source: Digestive Diseases and Sciences. 2003 December; 48(12): 2360-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14714625

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Immunodulation with tacrolimus (FK506): results of a prospective, open-label, noncontrolled trial in patients with inflammatory bowel disease. Author(s): de Oca J, Vilar L, Castellote J, Sanchez Santos R, Pares D, Biondo S, Osorio A, del Rio C, Jaurrieta E, Marti Rague J. Source: Rev Esp Enferm Dig. 2003 July; 95(7): 465-70, 459-64. English, Spanish. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14515846

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Impaired synthesis or cellular storage of norepinephrine, dopamine, and 5hydroxytryptamine in human inflammatory bowel disease. Author(s): Magro F, Vieira-Coelho MA, Fraga S, Serrao MP, Veloso FT, Ribeiro T, Soares-da-Silva P. Source: Digestive Diseases and Sciences. 2002 January; 47(1): 216-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11837726

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Inflammatory bowel disease (IBD). Author(s): Rayhorn N. Source: Nursing. 2003 November; 33(11): 54-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14597818

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Inflammatory bowel disease activity assessment with biologic markers and 99mTcWBC scintigraphy: are there different trends in ileitis versus colitis? Author(s): Charron M. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 October; 44(10): 1586-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14530471

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Inflammatory bowel disease and the eye. Author(s): Ghanchi FD, Rembacken BJ. Source: Survey of Ophthalmology. 2003 November-December; 48(6): 663-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14609712

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Inflammatory bowel disease and the risk of fracture. Author(s): van Staa TP, Cooper C, Brusse LS, Leufkens H, Javaid MK, Arden NK. Source: Gastroenterology. 2003 December; 125(6): 1591-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724810

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Inflammatory bowel disease emergencies. Author(s): Cheung O, Regueiro MD. Source: Gastroenterology Clinics of North America. 2003 December; 32(4): 1269-88. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14696307

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Inflammatory bowel disease in African Americans. Author(s): Reddy SI, Burakoff R. Source: Inflammatory Bowel Diseases. 2003 November; 9(6): 380-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14671487

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Inflammatory bowel disease in early childhood and adolescence: special considerations. Author(s): Mamula P, Markowitz JE, Baldassano RN. Source: Gastroenterology Clinics of North America. 2003 September; 32(3): 967-95, Viii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562584

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Inflammatory bowel disease in Estonia: a prospective epidemiologic study 1993-1998. Author(s): Salupere R. Source: World Journal of Gastroenterology : Wjg. 2001 June; 7(3): 387-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11819795

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Inflammatory bowel disease in pregnancy. Author(s): Alstead EM. Source: Postgraduate Medical Journal. 2002 January; 78(915): 23-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11796867

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Inflammatory bowel disease support groups: a primer for gastroenterology nurses. Author(s): Leshem RN. Source: Gastroenterology Nursing : the Official Journal of the Society of Gastroenterology Nurses and Associates. 2003 November-December; 26(6): 246-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14676612

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Inflammatory bowel disease versus irritable bowel syndrome: a hospital-based, casecontrol study of disease impact on quality of life. Author(s): Pace F, Molteni P, Bollani S, Sarzi-Puttini P, Stockbrugger R, Porro GB, Drossman DA. Source: Scandinavian Journal of Gastroenterology. 2003 October; 38(10): 1031-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14621276

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Inflammatory bowel disease. Author(s): Marteau P. Source: Endoscopy. 2002 January; 34(1): 63-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11778131

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Inflammatory bowel disease. Author(s): Keighley MR, Stockbrugger RW. Source: Alimentary Pharmacology & Therapeutics. 2003 November; 18 Suppl 3: 66-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531744

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Inflammatory bowel disease-associated gene expression in intestinal epithelial cells by differential cDNA screening and mRNA display. Author(s): Fukushima K, Yonezawa H, Fiocchi C. Source: Inflammatory Bowel Diseases. 2003 September; 9(5): 290-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14555912

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Issues and experience around the Paediatric Register of Inflammatory Bowel Disease. Author(s): Taylor L, Casson D, Platt MJ. Source: Archives of Disease in Childhood. 2003 October; 88(10): 891-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14500309

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K-ras mutations in sera of patients with colorectal neoplasias and long-standing inflammatory bowel disease. Author(s): Borchers R, Heinzlmann M, Zahn R, Witter K, Martin K, Loeschke K, Folwaczny C. Source: Scandinavian Journal of Gastroenterology. 2002 June; 37(6): 715-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12126252

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Lack of association between the C3435T MDR1 gene polymorphism and inflammatory bowel disease in two independent Northern European populations. Author(s): Croucher PJ, Mascheretti S, Foelsch UR, Hampe J, Schreiber S. Source: Gastroenterology. 2003 December; 125(6): 1919-20; Author Reply 1920-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14727637

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Lack of relationship of calcium and vitamin D intake to bone mineral density in premenopausal women with inflammatory bowel disease. Author(s): Bernstein CN, Bector S, Leslie WD. Source: The American Journal of Gastroenterology. 2003 November; 98(11): 2468-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638350

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Laparoscopic surgery for inflammatory bowel disease. Author(s): Bullen TF, Hershman MJ. Source: Hosp Med. 2003 December; 64(12): 724-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14702784

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Laparoscopic surgery for inflammatory bowel disease: results of the past decade. Author(s): Gurland BH, Wexner SD. Source: Inflammatory Bowel Diseases. 2002 January; 8(1): 46-54. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11837938

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Laparoscopic-assisted bowel resection in pediatric/adolescent inflammatory bowel disease: laparoscopic bowel resection in children. Author(s): Simon T, Orangio G, Ambroze W, Schertzer M, Armstrong D. Source: Diseases of the Colon and Rectum. 2003 October; 46(10): 1325-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14530669

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Leukocytapheresis as an adjunct to conventional medication for inflammatory bowel disease. Author(s): Sawada K. Source: Diseases of the Colon and Rectum. 2003 October; 46(10 Suppl): S66-77. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14530661

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Linkage of ulcerative colitis to the pericentromeric region of chromosome 16 in Italian inflammatory bowel disease families is independent of the presence of common CARD15 mutations. Author(s): Annese V, Latiano A, Palmieri O, Li HH, Forabosco P, Ferraris A, Andriulli A, Vecchi M, Ardizzone S, Cottone M, Dallapiccola B, Rappaport E, Fortina P, Devoto M. Source: Journal of Medical Genetics. 2003 November; 40(11): 837-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627676

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Listeria monocytogenes and inflammatory bowel disease: detection of Listeria species in intestinal mucosal biopsies by real-time PCR. Author(s): Huijsdens XW, Linskens RK, Taspinar H, Meuwissen SG, VandenbrouckeGrauls CM, Savelkoul PH. Source: Scandinavian Journal of Gastroenterology. 2003 March; 38(3): 332-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12737451

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Low dose methotrexate in inflammatory bowel disease: current status and future directions. Author(s): Schroder O, Stein J. Source: The American Journal of Gastroenterology. 2003 March; 98(3): 530-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12650783

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Low vitamin B(6) plasma levels, a risk factor for thrombosis, in inflammatory bowel disease: role of inflammation and correlation with acute phase reactants. Author(s): Saibeni S, Cattaneo M, Vecchi M, Zighetti ML, Lecchi A, Lombardi R, Meucci G, Spina L, de Franchis R. Source: The American Journal of Gastroenterology. 2003 January; 98(1): 112-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12526945

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Macrophages in inflammatory bowel disease. Author(s): Grip O, Janciauskiene S, Lindgren S. Source: Current Drug Targets. Inflammation and Allergy. 2003 June; 2(2): 155-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561168

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Maintenance therapy for inflammatory bowel disease. Author(s): Feagan BG. Source: The American Journal of Gastroenterology. 2003 December; 98(12 Suppl): S6S17. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14697913

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Management issues in women with inflammatory bowel disease. Author(s): Reddy SI, Wolf JL. Source: J Am Osteopath Assoc. 2001 December; 101(12 Suppl Pt 2): S17-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11794750

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Management of neoplastic polyps in inflammatory bowel disease. Author(s): Friedman S, Odze RD, Farraye FA. Source: Inflammatory Bowel Diseases. 2003 July; 9(4): 260-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12902849

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MDR1 Ala893 polymorphism is associated with inflammatory bowel disease. Author(s): Brant SR, Panhuysen CI, Nicolae D, Reddy DM, Bonen DK, Karaliukas R, Zhang L, Swanson E, Datta LW, Moran T, Ravenhill G, Duerr RH, Achkar JP, Karban AS, Cho JH. Source: American Journal of Human Genetics. 2003 December; 73(6): 1282-92. Epub 2003 November 07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14610718

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Mesenteric vein thrombosis after proctocolectomy for inflammatory bowel disease. Author(s): Lambley J, Ho YH. Source: Diseases of the Colon and Rectum. 2003 December; 46(12): 1715. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14668602

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Mortality in inflammatory bowel disease: a population-based cohort study. Author(s): Card T, Hubbard R, Logan RF. Source: Gastroenterology. 2003 December; 125(6): 1583-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724808

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Mortality in inflammatory bowel disease: peril and promise. Author(s): Loftus EV Jr. Source: Gastroenterology. 2003 December; 125(6): 1881-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724840

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Mucosal flora in inflammatory bowel disease. Author(s): Swidsinski A, Ladhoff A, Pernthaler A, Swidsinski S, Loening-Baucke V, Ortner M, Weber J, Hoffmann U, Schreiber S, Dietel M, Lochs H. Source: Gastroenterology. 2002 January; 122(1): 44-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11781279

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Multiparticulate systems in the treatment of inflammatory bowel disease. Author(s): Lamprecht A. Source: Current Drug Targets. Inflammation and Allergy. 2003 June; 2(2): 137-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561166

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Neuroendocrine cell secretory granules are not bacteria in inflammatory bowel disease. Author(s): Dvorak AM. Source: Gastroenterology. 2003 October; 125(4): 1288. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14552323

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Neutrophil derived human S100A12 (EN-RAGE) is strongly expressed during chronic active inflammatory bowel disease. Author(s): Foell D, Kucharzik T, Kraft M, Vogl T, Sorg C, Domschke W, Roth J. Source: Gut. 2003 June; 52(6): 847-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740341

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New biological therapies in inflammatory bowel disease. Author(s): van Deventer SJ. Source: Best Practice & Research. Clinical Gastroenterology. 2003 February; 17(1): 11930. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12617887

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New developments in aetiological mechanisms of inflammatory bowel disease. Author(s): Scholmerich J. Source: European Journal of Gastroenterology & Hepatology. 2003 June; 15(6): 585-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12840666

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Nitric oxide in inflammatory bowel disease. Author(s): Cross RK, Wilson KT. Source: Inflammatory Bowel Diseases. 2003 May; 9(3): 179-89. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12792224

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Nitric oxide-releasing mesalamine: potential utility for treatment of inflammatory bowel disease. Author(s): Wallace JL. Source: Dig Liver Dis. 2003 May; 35 Suppl 2: S35-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12846442

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NOD2/CARD15 and the Paneth cell: another piece in the genetic jigsaw of inflammatory bowel disease. Author(s): Aldhous MC, Nimmo ER, Satsangi J. Source: Gut. 2003 November; 52(11): 1533-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570717

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Non-invasive investigation of inflammatory bowel disease. Author(s): Tibble JA, Bjarnason I. Source: World Journal of Gastroenterology : Wjg. 2001 August; 7(4): 460-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11819811

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Novel approaches to treating inflammatory bowel disease: targeting alpha-4 integrin. Author(s): Sandborn WJ, Yednock TA. Source: The American Journal of Gastroenterology. 2003 November; 98(11): 2372-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638336

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Nutritional and metabolic issues in inflammatory bowel disease. Author(s): Cabre E, Gassull MA. Source: Current Opinion in Clinical Nutrition and Metabolic Care. 2003 September; 6(5): 569-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12913675

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O brother, where art thou? The case for siblings, environment, and inflammatory bowel disease. Author(s): Su C. Source: Inflammatory Bowel Diseases. 2003 May; 9(3): 211-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12797350

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Ocular myasthenia gravis and inflammatory bowel disease: a case report and literature review. Author(s): Foroozan R, Sambursky R. Source: The British Journal of Ophthalmology. 2003 September; 87(9): 1186-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12928296

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Of germs in inflammatory bowel disease and of how to fight them. Author(s): Guslandi M. Source: Journal of Gastroenterology and Hepatology. 2003 January; 18(1): 115-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12519238

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Optimization and individualization of thiopurine therapy in inflammatory bowel disease: the great variability among drug responses. Author(s): Scherl E, Subbaramiah K. Source: The Pharmacogenomics Journal. 2003; 3(2): 66-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12746731

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Optimizing the therapeutic potential of azathioprine/6-mercaptopurine in the treatment of inflammatory bowel disease. Author(s): Papadakis KA. Source: Journal of Clinical Gastroenterology. 2003 May-June; 36(5): 379-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12702974

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Optimizing treatment with thioguanine derivatives in inflammatory bowel disease. Author(s): Louis E, Belaiche J. Source: Best Practice & Research. Clinical Gastroenterology. 2003 February; 17(1): 37-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12617881

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Oral iron therapy in inflammatory bowel disease: usage, tolerance, and efficacy. Author(s): de Silva AD, Mylonaki M, Rampton DS. Source: Inflammatory Bowel Diseases. 2003 September; 9(5): 316-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14555915

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Oral signs and symptoms in relation to disease activity and site of involvement in patients with inflammatory bowel disease. Author(s): Katz J, Shenkman A, Stavropoulos F, Melzer E. Source: Oral Diseases. 2003 January; 9(1): 34-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12617256

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Osteoporosis in inflammatory bowel disease. Author(s): Compston J. Source: Gut. 2003 January; 52(1): 63-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12477761

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Oxidative stress and antioxidant capacity in patients with inflammatory bowel disease. Author(s): Tuzun A, Erdil A, Inal V, Aydin A, Bagci S, Yesilova Z, Sayal A, Karaeren N, Dagalp K. Source: Clinical Biochemistry. 2002 October; 35(7): 569-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12493587

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Platelet-derived growth factor and its receptors are expressed in areas of both active inflammation and active fibrosis in inflammatory bowel disease. Author(s): Kumagai S, Ohtani H, Nagai T, Funa K, Hiwatashi NO, Shimosegawa, Nagura H. Source: The Tohoku Journal of Experimental Medicine. 2001 September; 195(1): 21-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11780721

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Presenting features of inflammatory bowel disease in Great Britain and Ireland. Author(s): Sawczenko A, Sandhu BK. Source: Archives of Disease in Childhood. 2003 November; 88(11): 995-1000. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14612366

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Prevalence of amebiasis in inflammatory bowel disease in Turkey. Author(s): Ustun S, Dagci H, Aksoy U, Guruz Y, Ersoz G. Source: World Journal of Gastroenterology : Wjg. 2003 August; 9(8): 1834-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12918132

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Prevalence of inflammatory bowel disease in an insured population in Puerto Rico during 1996. Author(s): Torres EA, De Jesus R, Perez CM, Inesta M, Torres D, Morell C, Just E. Source: P R Health Sci J. 2003 September; 22(3): 253-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14619451

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Previous experience and quiality of life in patients with inflammatory bowel disease during relapse. Author(s): Casellas F, Lopez Vivancos J, Malagela JR. Source: Rev Esp Enferm Dig. 2003 July; 95(7): 476-9, 471-5. English, Spanish. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12952508

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Probiotics in inflammatory bowel disease: a critical review. Author(s): Tamboli CP, Caucheteux C, Cortot A, Colombel JF, Desreumaux P. Source: Best Practice & Research. Clinical Gastroenterology. 2003 October; 17(5): 805-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14507590

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Profile of the inflammatory bowel disease patient with depressive disorders. Author(s): Acosta-Ramirez D, Pagan-Ocasio V, Torres EA, Rodriguez M, Caro O. Source: P R Health Sci J. 2001 September; 20(3): 215-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11776721

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Proliferation of D2-40-expressing intestinal lymphatic vessels in the lamina propria in inflammatory bowel disease. Author(s): Fogt F, Pascha TL, Zhang PJ, Gausas RE, Rahemtulla A, Zimmerman RL. Source: International Journal of Molecular Medicine. 2004 February; 13(2): 211-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14719125

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Pulmonary function tests and high-resolution CT in the detection of pulmonary involvement in inflammatory bowel disease. Author(s): Songur N, Songur Y, Tuzun M, Dogan I, Tuzun D, Ensari A, Hekimoglu B. Source: Journal of Clinical Gastroenterology. 2003 October; 37(4): 292-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506385

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Pyrosequencing of TPMT alleles in a general Swedish population and in patients with inflammatory bowel disease. Author(s): Haglund S, Lindqvist M, Almer S, Peterson C, Taipalensuu J. Source: Clinical Chemistry. 2004 February; 50(2): 288-95. Epub 2003 December 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14656901

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Quality of health care in inflammatory bowel disease: development of a reliable questionnaire (QUOTE-IBD) and first results. Author(s): van der Eijk I, Sixma H, Smeets T, Veloso FT, Odes S, Montague S, Fornaciari G, Moum B, Stockbrugger R, Russel M; European Collaborative Study Group on IBD. Source: The American Journal of Gastroenterology. 2001 December; 96(12): 3329-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11774945

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Quality of life in Chinese patients with inflammatory bowel disease: validation of the Chinese translation of the Inflammatory Bowel Disease Questionnaire. Author(s): Leong RW, Lee YT, Ching JY, Sung JJ. Source: Alimentary Pharmacology & Therapeutics. 2003 March 1; 17(5): 711-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12641521

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Quality of life in inflammatory bowel disease in remission: the impact of IBS-like symptoms and associated psychological factors. Author(s): Simren M, Axelsson J, Gillberg R, Abrahamsson H, Svedlund J, Bjornsson ES. Source: The American Journal of Gastroenterology. 2002 February; 97(2): 389-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11866278

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Quality of life in inflammatory bowel disease: a cross-cultural comparison of English and Canadian children. Author(s): Richardson G, Griffiths AM, Miller V, Thomas AG. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 May; 32(5): 573-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11429519

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Quality of life in Korean patients with inflammatory bowel diseases: ulcerative colitis, Crohn's disease and intestinal Behcet's disease. Author(s): Kim WH, Cho YS, Yoo HM, Park IS, Park EC, Lim JG. Source: International Journal of Colorectal Disease. 1999 February; 14(1): 52-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10207731

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Quality of life in paediatric inflammatory bowel disease measured by a generic and a disease-specific questionnaire. Author(s): Loonen HJ, Grootenhuis MA, Last BF, Koopman HM, Derkx HH. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(3): 348-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12022311

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Quality of life in patients with inflammatory bowel disease: translation, data quality, scaling assumptions, validity, reliability and sensitivity to change of the Norwegian version of IBDQ. Author(s): Bernklev T, Moum B, Moum T; Inflammatory Bowel South-Eastern Norway (IBSEN) Group of Gastroenterologists. Source: Scandinavian Journal of Gastroenterology. 2002 October; 37(10): 1164-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12408521

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Quality of life of Greek patients with inflammatory bowel disease. Validation of the Greek translation of the inflammatory bowel disease questionnaire. Author(s): Pallis AG, Vlachonikolis IG, Mouzas IA. Source: Digestion. 2001; 63(4): 240-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11435724

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Quality of life of parents and siblings of children with inflammatory bowel disease. Author(s): Akobeng AK, Miller V, Firth D, Suresh-Babu MV, Mir P, Thomas AG. Source: Journal of Pediatric Gastroenterology and Nutrition. 1999 April; 28(4): S40-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10204524

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Quality of life rapidly improves with budesonide therapy for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group. Author(s): Irvine EJ, Greenberg GR, Feagan BG, Martin F, Sutherland LR, Thomson AB, Nilsson LG, Persson T. Source: Inflammatory Bowel Diseases. 2000 August; 6(3): 181-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10961590

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Radiolabeled leukocyte imaging in inflammatory bowel disease: a prospective blinded evaluation. Author(s): Lachter J, Isseroff HN, Yasin K, Keidar Z, Israel O. Source: Hepatogastroenterology. 2003 September-October; 50(53): 1439-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571757

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Recent indications and methods of surgery for inflammatory bowel disease. Author(s): Ohki S, Terashima S, Sekikawa K, Takenoshita S, Gotoh M. Source: Current Drug Targets. Inflammation and Allergy. 2003 June; 2(2): 113-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561162

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Reduced migration of fibroblasts in inflammatory bowel disease: role of inflammatory mediators and focal adhesion kinase. Author(s): Leeb SN, Vogl D, Gunckel M, Kiessling S, Falk W, Goke M, Scholmerich J, Gelbmann CM, Rogler G. Source: Gastroenterology. 2003 November; 125(5): 1341-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14598250

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Reducing psychological distress in patients with inflammatory bowel disease by cognitive-behavioural treatment: exploratory study of effectiveness. Author(s): Mussell M, Bocker U, Nagel N, Olbrich R, Singer MV. Source: Scandinavian Journal of Gastroenterology. 2003 July; 38(7): 755-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12889563

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Relationship between the tumor necrosis factor alpha polymorphism and the serum C-reactive protein levels in inflammatory bowel disease. Author(s): Vatay A, Bene L, Kovacs A, Prohaszka Z, Szalai C, Romics L, Fekete B, Karadi I, Fust G. Source: Immunogenetics. 2003 July; 55(4): 247-52. Epub 2003 June 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12811429

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Review article: inherited thrombophilia in inflammatory bowel disease. Author(s): Papa A, Danese S, Grillo A, Gasbarrini G, Gasbarrini A. Source: The American Journal of Gastroenterology. 2003 June; 98(6): 1247-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12818264

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Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease. Author(s): Allgayer H. Source: Alimentary Pharmacology & Therapeutics. 2003 September; 18 Suppl 2: 10-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950415

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Review article: the data supporting a role for aminosalicylates in the chemoprevention of colorectal cancer in patients with inflammatory bowel disease. Author(s): Eaden J. Source: Alimentary Pharmacology & Therapeutics. 2003 September; 18 Suppl 2: 15-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950416

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Review article: the expanding role of biological agents in the treatment of inflammatory bowel disease - focus on selective adhesion molecule inhibition. Author(s): Rutgeerts P, Van Deventer S, Schreiber S. Source: Alimentary Pharmacology & Therapeutics. 2003 June 15; 17(12): 1435-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823145

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Review article: the incidence and prevalence of colorectal cancer in inflammatory bowel disease. Author(s): Munkholm P. Source: Alimentary Pharmacology & Therapeutics. 2003 September; 18 Suppl 2: 1-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950413

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Selective cyclooxygenase-2 inhibitors and relapse of inflammatory bowel disease. Author(s): Biancone L, Tosti C, De Nigris F, Fantini M, Pallone F. Source: Gastroenterology. 2003 August; 125(2): 637-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12891585

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Seroprevalence of Schistosoma mansoni in Puerto Ricans with inflammatory bowel disease. Author(s): Torres EA, Acosta H, Cruz M, Weinstock J, Hillyer GV. Source: P R Health Sci J. 2001 September; 20(3): 211-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11776720

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Serum human cartilage glycoprotein 39 as a marker of arthritis associated with inflammatory bowel disease. Author(s): Punzi L, Podswiadek M, D'Inca R, Zaninotto M, Bernardi D, Plebani M, Sturniolo GC. Source: Annals of the Rheumatic Diseases. 2003 December; 62(12): 1224-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14644865

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Serum laminin and collagen IV in inflammatory bowel disease. Author(s): Koutroubakis IE, Petinaki E, Dimoulios P, Vardas E, Roussomoustakaki M, Maniatis AN, Kouroumalis EA. Source: Journal of Clinical Pathology. 2003 November; 56(11): 817-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14600124

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Shared care in gastroenterology: GPs' views of open access to out-patient follow-up for patients with inflammatory bowel disease. Author(s): Cheung WY, Dove J, Lervy B, Russell IT, Williams JG. Source: Family Practice. 2002 February; 19(1): 53-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11818350

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Spatial distribution and histogenesis of colorectal Paneth cell metaplasia in idiopathic inflammatory bowel disease. Author(s): Tanaka M, Saito H, Kusumi T, Fukuda S, Shimoyama T, Sasaki Y, Suto K, Munakata A, Kudo H. Source: Journal of Gastroenterology and Hepatology. 2001 December; 16(12): 1353-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11851832

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Stratification by CARD15 variant genotype in a genome-wide search for inflammatory bowel disease susceptibility loci. Author(s): Shaw SH, Hampe J, White R, Mathew CG, Curran ME, Schreiber S. Source: Human Genetics. 2003 November; 113(6): 514-21. Epub 2003 September 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13680363

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Strong telomerase activity of B lymphocyte from mesenteric lymph nodes of patients with inflammatory bowel disease. Author(s): Takagi S, Kinouchi Y, Chida M, Hiwatashi N, Noguchi M, Takahashi S, Shimosegawa T. Source: Digestive Diseases and Sciences. 2003 October; 48(10): 2091-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627360

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Study of animal-borne infections in the mucosas of patients with inflammatory bowel disease and population-based controls. Author(s): Bernstein CN, Nayar G, Hamel A, Blanchard JF. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 4986-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605128

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Surgery for inflammatory bowel disease. Author(s): Bullen TF, Hershman MJ. Source: Hosp Med. 2003 December; 64(12): 719-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14702783

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Telomerase activity in chronic inflammatory bowel disease. Author(s): Kleideiter E, Friedrich U, Mohring A, Walker S, Horing E, Maier K, Fritz P, Thon KP, Klotz U. Source: Digestive Diseases and Sciences. 2003 December; 48(12): 2328-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14714621

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The genetics of inflammatory bowel disease. Author(s): Baburajan B, Parkes M. Source: Hosp Med. 2003 October; 64(10): 599-602. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14584240

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The presentation and management of juvenile-onset chronic inflammatory bowel disease in Northeastern Scotland. Author(s): Watson AJ, Johnston AT, Barker PM, Youngson GG, Bisset WM, Mahomed AA. Source: Journal of Pediatric Surgery. 2002 January; 37(1): 83-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11781993

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The serum concentrations of zinc, copper and selenium in children with inflammatory bowel disease. Author(s): Ojuawo A, Keith L. Source: Cent Afr J Med. 2002 September-October; 48(9-10): 116-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562534

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The value of serological and genetic markers in inflammatory bowel disease; strength and weakness of the studies. Author(s): Pena AS. Source: Rev Esp Enferm Dig. 2003 November; 95(11): 752-4, 749-51. English, Spanish. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14640872

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The vascular contribution in the pathogenesis of inflammatory bowel disease. Author(s): Hatoum OA, Miura H, Binion DG. Source: American Journal of Physiology. Heart and Circulatory Physiology. 2003 November; 285(5): H1791-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561675

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Three-dimensional ultrasonography, virtual coloscopy and endorectal magnetic resonance imaging in the diagnosis of complicated inflammatory bowel disease. Author(s): Szilvas A, Szekely G, Tarjan Z, Fornet B. Source: Endoscopy. 2002 January; 34(1): 94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11778139

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Toxicity of mycophenolate mofetil in patients with inflammatory bowel disease. Author(s): Skelly MM, Logan RF, Jenkins D, Mahida YR, Hawkey CJ. Source: Inflammatory Bowel Diseases. 2002 March; 8(2): 93-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11854606

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Treatment of inflammatory bowel disease: safety and tolerability issues. Author(s): Navarro F, Hanauer SB. Source: The American Journal of Gastroenterology. 2003 December; 98(12 Suppl): S1823. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14697914

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Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Author(s): Summers RW, Elliott DE, Qadir K, Urban JF Jr, Thompson R, Weinstock JV. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 2034-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14499784

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Uncoupling of the sympathetic nervous system and the hypothalamic-pituitaryadrenal axis in inflammatory bowel disease? Author(s): Straub RH, Herfarth H, Falk W, Andus T, Scholmerich J. Source: Journal of Neuroimmunology. 2002 May; 126(1-2): 116-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12020963

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Unsettling facts of life: bacterial commensalism, epithelial adherence, and inflammatory bowel disease. Author(s): Braun J. Source: Gastroenterology. 2002 January; 122(1): 228-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11781298

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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/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12120183

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Upper gastrointestinal tract endoscopy in inflammatory bowel disease. Author(s): Isaacs KL. Source: Gastrointest Endosc Clin N Am. 2002 July; 12(3): 451-62, Vii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12486938

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Upregulation of interleukin-12 and -17 in active inflammatory bowel disease. Author(s): Nielsen OH, Kirman I, Rudiger N, Hendel J, Vainer B. Source: Scandinavian Journal of Gastroenterology. 2003 February; 38(2): 180-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12678335

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Urinary excretion of N-methylhistamine as a marker of disease activity in inflammatory bowel disease. Author(s): Winterkamp S, Weidenhiller M, Otte P, Stolper J, Schwab D, Hahn EG, Raithel M. Source: The American Journal of Gastroenterology. 2002 December; 97(12): 3071-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12492192

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Urinary patterns of patients with renal stones associated with chronic inflammatory bowel disease. Author(s): Trinchieri A, Lizzano R, Castelnuovo C, Zanetti G, Pisani E. Source: Arch Ital Urol Androl. 2002 June; 74(2): 61-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12161938

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Use of probiotics in the treatment of inflammatory bowel disease. Author(s): Hart AL, Stagg AJ, Kamm MA. Source: Journal of Clinical Gastroenterology. 2003 February; 36(2): 111-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12544192

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Utility of measuring 6-methylmercaptopurine and 6-thioguanine nucleotide levels in managing inflammatory bowel disease patients treated with 6-mercaptopurine in a clinical practice setting. Author(s): Mardini HE, Arnold GL. Source: Journal of Clinical Gastroenterology. 2003 May-June; 36(5): 390-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12702978

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Uveitis and erythema nodosum in inflammatory bowel disease: clinical features and the role of HLA genes. Author(s): Orchard TR, Chua CN, Ahmad T, Cheng H, Welsh KI, Jewell DP. Source: Gastroenterology. 2002 September; 123(3): 714-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12198697

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Val34Leu factor XIII polymorphism in Italian patients with inflammatory bowel disease. Author(s): Saibeni S, Vecchi M, Faioni EM, Franchi F, Rondonotti E, Borsi G, de Franchis R. Source: Dig Liver Dis. 2003 January; 35(1): 32-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12725605

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Validation of the EuroQol questionnaire in patients with inflammatory bowel disease. Author(s): Konig HH, Ulshofer A, Gregor M, von Tirpitz C, Reinshagen M, Adler G, Leidl R. Source: European Journal of Gastroenterology & Hepatology. 2002 November; 14(11): 1205-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12439115

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Validation of the inflammatory bowel disease questionnaire in Swedish patients with ulcerative colitis. Author(s): Hjortswang H, Jarnerot G, Curman B, Sandberg-Gertzen H, Tysk C, Blomberg B, Almer S, Strom M. Source: Scandinavian Journal of Gastroenterology. 2001 January; 36(1): 77-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11218243

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Validity and completeness of the General Practice Research Database for studies of inflammatory bowel disease. Author(s): Lewis JD, Brensinger C, Bilker WB, Strom BL. Source: Pharmacoepidemiology and Drug Safety. 2002 April-May; 11(3): 211-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12051120

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Value of rectosigmoidoscopy with biopsies for diagnosis of inflammatory bowel disease in children. Author(s): Escher JC, ten KF, Lichtenbelt K, Schornagel I, Buller H, Derkx B, Taminiau J. Source: Inflammatory Bowel Diseases. 2002 January; 8(1): 16-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11837934

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Variations in initial assessment and management of inflammatory bowel disease across Great Britain and Ireland. Author(s): Sawczenko A, Lynn R, Sandhu BK. Source: Archives of Disease in Childhood. 2003 November; 88(11): 990-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14612365

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Vascular smooth muscle cells and pericytes express MMP-1, MMP-9, TIMP-1 and type I procollagen in inflammatory bowel disease. Author(s): Arihiro S, Ohtani H, Hiwatashi N, Torii A, Sorsa T, Nagura H. Source: Histopathology. 2001 July; 39(1): 50-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11454044

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Venous thromboembolism in inflammatory bowel disease. Author(s): Solem CA, Loftus EV, Tremaine WJ, Sandborn WJ. Source: The American Journal of Gastroenterology. 2004 January; 99(1): 97-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14687149

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Villous and serrated adenomatous growth bordering carcinomas in inflammatory bowel disease. Author(s): Rubio CA, Befrits R, Jaramillo E, Nesi G, Amorosi A. Source: Anticancer Res. 2000 November-December; 20(6C): 4761-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11205214

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Vitamin D status, parathyroid hormone and bone mineral density in patients with inflammatory bowel disease. Author(s): Jahnsen J, Falch JA, Mowinckel P, Aadland E. Source: Scandinavian Journal of Gastroenterology. 2002 February; 37(2): 192-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11843057

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Well-adjusted children: an alternate view of children with inflammatory bowel disease and functional gastrointestinal complaints. Author(s): Gold N, Issenman R, Roberts J, Watt S. Source: Inflammatory Bowel Diseases. 2000 February; 6(1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10701143

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What are the major arguments in favour of the genetic susceptibility for inflammatory bowel disease? Author(s): Tamboli CP, Cortot A, Colombel JF. Source: European Journal of Gastroenterology & Hepatology. 2003 June; 15(6): 587-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12840667

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What do eosinophils tell us in biopsies of patients with inflammatory bowel disease? Author(s): Yang GY, West AB. Source: Journal of Clinical Gastroenterology. 2003 February; 36(2): 93-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12544188

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What do patients with irritable bowel syndrome dream about? A comparison with inflammatory bowel disease. Author(s): Lal S, Whorwell PJ. Source: Dig Liver Dis. 2002 July; 34(7): 506-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12236484

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What is the association of primary sclerosing cholangitis with sex and inflammatory bowel disease in Turkish patients? Author(s): Bayraktar Y, Arslan S, Saglam F, Uzunalimoglu B, Kayhan B. Source: Hepatogastroenterology. 1998 November-December; 45(24): 2064-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9951867

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What's good for the goose should be good for the gander--6-MP use in fathers with inflammatory bowel disease. Author(s): Kane SV. Source: The American Journal of Gastroenterology. 2000 March; 95(3): 581-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10710042

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Why children with inflammatory bowel disease are diagnosed at a younger age than their affected parent. Author(s): Lee JC, Bridger S, McGregor C, Macpherson AJ, Jones JE. Source: Gut. 1999 June; 44(6): 808-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10323881

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Work losses related to inflammatory bowel disease in Canada: results from a National Population Health Survey. Author(s): Longobardi T, Jacobs P, Wu L, Bernstein CN. Source: The American Journal of Gastroenterology. 2003 April; 98(4): 844-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738466

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Work losses related to inflammatory bowel disease in the United States: results from the National Health Interview Survey. Author(s): Longobardi T, Jacobs P, Bernstein CN. Source: The American Journal of Gastroenterology. 2003 May; 98(5): 1064-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809829

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YKL-40 as a marker of joint involvement in inflammatory bowel disease. Author(s): Bernardi D, Podswiadek M, Zaninotto M, Punzi L, Plebani M. Source: Clinical Chemistry. 2003 October; 49(10): 1685-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14500601

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CHAPTER 2. NUTRITION AND INFLAMMATORY BOWEL DISEASE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and inflammatory bowel disease.

Finding Nutrition Studies on Inflammatory Bowel Disease 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 “inflammatory bowel disease” (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 inflammatory bowel disease: ·

Nutritional support in chronic inflammatory bowel disease. Source: Kirschner, B.S. Nutrition-and-the-M.D (USA). (February 1986). volume 12(2) page 1-2.

Additional consumer oriented references include: ·

Diet for inflammatory bowel disease. Source: Hershman, J.M. Nutr-M.D. Van Nuys, Calif. : Nutrition & the M.D. May 1988. volume 14 (5) page 7-8. 0732-0167

The following information is typical of that found when using the “Full IBIDS Database” to search for “inflammatory bowel disease” (or a synonym): ·

Bone mineral density and nutritional status in children with chronic inflammatory bowel disease. Author(s): Department of Paediatrics, Division of Endocrinology, Erasmus University and University Hospital Rotterdam/Sophia Children' s Hospital, Rotterdam (Netherlands) Source: Boot, A.M. Bouquet, J. Krenning, E.P. Muinck Keizer Schrama, S.M.P.F. de (United-Kingdom). (1998). volume 42(2) page 188-194.

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Lipid treatment of inflammatory bowel disease. Author(s): Medizinische Klinik, Klinikum Innenstadt, University of Munich, Ziemssenstrasse 1, 80336 Munich (Germany) Source: Endres, S. Lorenz, R. Loeschke, K. Current-Opinion-in-Clinical-Nutrition-andMetabolic-Care (United Kingdom). (1999). volume 2(2) page 117-120.

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Risk of inflammatory bowel disease attributable to smoking, oral contraception and breastfeeding in Italy: a nationwide case-control study. Author(s): Department of Statistics, Chair of Medical Statistics and Epidemiology, University of Milan, Milan (Italy) Source: Corrao, G. Tragnone, A. Caprilli, R. Trallori, G. Papi, C. Andreoli, A. Paolo, M. di Riegler, G. Rigo, G.P. Ferrau, O. Mansi, C. Ingrosso, M. Valpiani, D. InternationalJournal-of-Epidemiology (United Kingdom). (1998). volume 27(3) page 397-404.

Additional physician-oriented references include: ·

5-ASA-glutamate protects rats from inflammatory bowel disease induced by intracolonic administration of trinitrobenzensulfonic acid. Author(s): Gastroenterology and Endoscopy Clinic, University of Perugia, Italy. Source: Clerici, C Gentili, G Pellicciari, R Gresele, P Mezzasoma, A M Giansanti, M Clementi, M Bartoli, G Balo, S Modesto, R Aburbeh, A G Morelli, O Morelli, A Ital-JGastroenterol-Hepatol. 1998 August; 30(4): 385-90 1125-8055

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A new treatment for inflammatory bowel disease. Author(s): Bay Area Veterinary Internal Medicine Service, Oakland, CA. Source: Stewart, A. North-American-Veterinary-Conference (USA). (1996). volume 10 page 199. dogs cats steroids therapy inflammation

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All patients with inflammatory bowel disease should have bone density assessment: con. Author(s): Department of Medicine, St. Boniface General Hospital, Winnipeg, Manitoba, Canada. [email protected] Source: Leslie, W D Inflamm-Bowel-Dis. 2001 May; 7(2): 163-7; discussion 168-9 10780998

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Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: potential therapeutic use in the treatment of inflammatory bowel disease. Author(s): Haematology Department, Women's and Children's Hospital, North Adelaide, South Australia. [email protected] Source: Hodge, G Hodge, S Han, P Cytometry. 2002 August 1; 48(4): 209-15 0196-4763

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Antioxidants and mucosa protectives: realistic therapeutic options in inflammatory bowel disease? Author(s): Department of Gastroenterology and Hepatology, Leiden University Medical Center, The Netherlands. Source: Kruidenier, L Verspaget, H W Mediators-Inflamm. 1998; 7(3): 157-62 0962-9351

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Bone mineral metabolism in pediatric inflammatory bowel disease. Author(s): Children's Hospital, Hamilton Health Sciences Corporation, McMaster University Medical Centre, Ontario, Canada. Source: Issenman, R M Inflamm-Bowel-Dis. 1999 August; 5(3): 192-9 1078-0998

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Can glucose-insulin-potassium regimen suppress inflammatory bowel disease? Author(s): EFA Sciences LLC, Suite #266, 1420 Providence Highway, Norwood, MA 02062, USA. [email protected] Source: Das, U N Med-Hypotheses. 2001 August; 57(2): 183-5 0306-9877

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Carrageenan-induced intestinal injury in the rat--a model for inflammatory bowel disease. Author(s): Department of Pathology, University of Saskatchewan, Saskatoon, Canada. Source: Moyana, T N Lalonde, J M Ann-Clin-Lab-Sci. 1990 Nov-December; 20(6): 420-6 0091-7370

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Chemoprevention of colorectal cancer in inflammatory bowel disease? A potential role for folate. Author(s): Gastroenterology Department, University Hospital, Heraklion, Greece. [email protected] Source: Mouzas, I A Papavassiliou, E Koutroubakis, I Ital-J-Gastroenterol-Hepatol. 1998 August; 30(4): 421-5 1125-8055

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Concanavalin A induced suppressor activity exerted by peripheral blood mononuclear cells--with special reference to chronic inflammatory bowel disease. Author(s): Medical Department C, Herlev Hospital, University of Copenhagen, Denmark. Source: Davidsen, B D Dan-Med-Bull. 1988 June; 35(3): 201-22 0907-8916

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Congenital Guillain-Barre syndrome associated with maternal inflammatory bowel disease is responsive to intravenous immunoglobulin. Author(s): Department of Neurology, Columbia University College of Physicians and Surgeons, Neurological Institute, New York, NY 10032, USA. [email protected] Source: Bamford, N S Trojaborg, W Sherbany, A A De Vivo, D C Eur-J-Paediatr-Neurol. 2002; 6(2): 115-9 1090-3798

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Dietary fats and inflammatory bowel disease in Asians. Author(s): Gastrointestinal Research Unit, Leicester General Hospital, UK.

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Source: Chuah, S Y Jayanthi, V Lee, C N McDonald, B Probert, C S Mayberry, J F Ital-JGastroenterol. 1992 September; 24(7): 386-8 0392-0623 ·

Dysregulation of intestinal mucosal immunity: implications in inflammatory bowel disease. Author(s): Departments of Molecular and Cellular Physiology and Medicine, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932. Source: Laroux, F S Pavlick, K P Wolf, R E Grisham, M B News-Physiol-Sci. 2001 December; 16: 272-7 0886-1714

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Effect of short-term topical corticosteroid treatment on mucosal enzyme systems in patients with distal inflammatory bowel disease. Author(s): Department of General Internal Medicine, University of Bonn, Germany. Source: Scheurlen, C Allgayer, H Hardt, M Kruis, W Hepatogastroenterology. 1998 SepOctober; 45(23): 1539-45 0172-6390

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Epidemiology of inflammatory bowel disease. Author(s): Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden. Source: Ekbom, A Nestle-Nutr-Workshop-Ser-Clin-Perform-Programme. 1999; 2: 7-18; discussion 18-21 1422-7584

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Etiology and pathophysiology of inflammatory bowel disease--environmental factors. Author(s): Klinik und Poliklinik fur Innere Medizin I, Klinikum der Universitat, Regensburg, Germany. [email protected] Source: Andus, T Gross, V Hepatogastroenterology. 2000 Jan-February; 47(31): 29-43 0172-6390

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Evaluation of oral administration of folic and folinic acid to prevent folate deficiency in patients with inflammatory bowel disease treated with salicylazosulfapyridine. Author(s): First Medical Clinic, University of Bologna, Italy. Source: Pironi, L Cornia, G L Ursitti, M A Dallasta, M A Miniero, R Fasano, F Miglioli, M Barbara, L Int-J-Clin-Pharmacol-Res. 1988; 8(2): 143-8 0251-1649

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Examination, prevention and treatment of osteoporosis in patients with inflammatory bowel disease: recommendations and reality. Author(s): First Department of Medicine/Gastroenterology, General Hospital, Grieskirchnerstrasse 42, A-4600 Wels. [email protected] Source: Kirchgatterer, A Wenzl, H H Aschl, G Hinterreiter, M Stadler, B Hinterleitner, T A Petritsch, W Knoflach, P Acta-Med-Austriaca. 2002; 29(4): 120-3 0303-8173

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Feline inflammatory bowel disease: treatment, prognosis, and new developments. Source: Krecic, M.R. Compend-contin-educ-pract-vet. Trenton, N.J. : Veterinary Learning Systems. November 2001. volume 23 (11) page 964-973. 0193-1903

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High prevalence of hyperchomocysteinemia in patients with inflammatory bowel disease: a pathogenic link with thromboembolic complications? Author(s): A. Bianchi Bonomi Hemophilia and Thrombosis Center, and Department of Internal Medicine, IRCCS Ospedale Maggiore, University of Milano, Italy. [email protected] Source: Cattaneo, M Vecchi, M Zighetti, M L Saibeni, S Martinelli, I Omodei, P Mannucci, P M de Franchis, R Thromb-Haemost. 1998 October; 80(4): 542-5 0340-6245

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Immune potentiation of ultrafine dietary particles in normal subjects and patients with inflammatory bowel disease. Author(s): Gastrointestinal Laboratory, The Rayne Institute, St Thomas' Hospital, London, SE1 7EH, UK. [email protected]

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Source: Powell, J J Harvey, R S Ashwood, P Wolstencroft, R Gershwin, M E Thompson, R P J-Autoimmun. 2000 February; 14(1): 99-105 0896-8411 ·

Immunology of inflammatory bowel disease. Author(s): Department of Medicine, Washington University School of Medicine, St. Louis, Mo. Source: Stenson, W F MacDermott, R P Year-Immunol. 1989; 4286-95 0256-2308

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Immunopharmacology of 5-aminosalicylic acid and of glucocorticoids in the therapy of inflammatory bowel disease. Author(s): 1st Department of Medicine, Christian Albrechts University, Kiel, Germany. Source: Nikolaus, S Folscn, U Schreiber, S Hepatogastroenterology. 2000 Jan-February; 47(31): 71-82 0172-6390

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Increased intracellular Th1 cytokines in scid mice with inflammatory bowel disease. Author(s): Department of Medical Anatomy, Panum Institute, University of Copenhagen, Denmark. [email protected] Source: Bregenholt, S Claesson, M H Eur-J-Immunol. 1998 January; 28(1): 379-89 00142980

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Inflammatory bowel disease and pregnancy. Author(s): Department of Surgery, St.Peter's Hospital, Surrey, [email protected] Source: Lamah, M Scott, H J Int-J-Colorectal-Dis. 2002 July; 17(4): 216-22 0179-1958

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Inflammatory mediators and the pathogenesis of inflammatory bowel disease. Author(s): Department of Medicine, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel. Source: Eliakim, R Rachmilewitz, D Ital-J-Gastroenterol. 1992 Jul-August; 24(6): 361-8 0392-0623

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Interleukin-10 (IL-10) genotypes in inflammatory bowel disease. Author(s): School of Biological Sciences, University of Manchester, UK. Source: Tagore, A Gonsalkorale, W M Pravica, V Hajeer, A H McMahon, R Whorwell, P J Sinnott, P J Hutchinson, I V Tissue-Antigens. 1999 October; 54(4): 386-90 0001-2815

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Intestinal microflora as a therapeutic target in inflammatory bowel disease. Author(s): Second Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. Source: Mitsuyama, K Toyonaga, A Sata, M J-Gastroenterol. 2002 November; 37 Suppl 14: 73-7 0944-1174

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Lipid treatment in inflammatory bowel disease. Author(s): Department of Emergency Medicine, S. Orsola Hospital, Bologna, Italy. Source: Belluzzi, A Nestle-Nutr-Workshop-Ser-Clin-Perform-Programme. 1999; 2: 199211; discussion 211-5 1422-7584

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Management of bone loss in inflammatory bowel disease. Author(s): Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA. [email protected] Source: Lichtenstein, G R Semin-Gastrointest-Dis. 2001 October; 12(4): 275-83 1049-5118

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Mechanism of the uricosuric action of the anti-inflammatory drug E3040 used to treat inflammatory bowel disease I: study using a rat model of hyperuricemia. Author(s): Department of Pharmacy, The University of Tokyo Hospital, The University of Tokyo, Japan. [email protected]

UK,

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Source: Yamada, H Kotaki, H Furitsu, H Sawada, Y Iga, T Biopharm-Drug-Dispos. 1999 March; 20(2): 77-83 0142-2782 ·

Mechanisms of immune cell-mediated tissue injury in inflammatory bowel disease (Review). Author(s): Departments of Microbiology and Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. Source: Baumgart, D C McVay, L D Carding, S R Int-J-Mol-Med. 1998 February; 1(2): 315-32 1107-3756

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Metabolism of vitamin A in inflammatory bowel disease. Author(s): Department of Gastroenterology and Metabolism, Medical Center of Postgraduate Education, Warsaw, Poland. Source: Janczewska, I Bartnik, W Butruk, E Tomecki, R Kazik, E Ostrowski, J Hepatogastroenterology. 1991 October; 38(5): 391-5 0172-6390

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Microbiological and immunological strategies for treatment of inflammatory bowel disease. Author(s): Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and Ghent University, KL. Ledeganckstraat 35, B-9000, Gent, Belgium. [email protected] Source: Steidler, L Microbes-Infect. 2001 November; 3(13): 1157-66 1286-4579

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New developments in the pharmacotherapy of inflammatory bowel disease. Author(s): Oosterschelde Hospital Foundation, Goes, The Netherlands. Source: Harting, J W Pharm-Weekbl-Sci. 1992 August 21; 14(4A): 275-86 0167-6555

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Nutrition in chronic inflammatory bowel disease. Source: Motil, K.J. Grand, R.J. Pediatric nutrition : theory and practice / edited by Richard J. Grand, James L. Sutphen, William H. Dietz. Boston : Butterworths, c1987. page 465-479. ill., charts. ISBN: 0409951110

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Nutritional and metabolic advances in inflammatory bowel disease. Author(s): Department of Gastroenterology and Hepatology, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104 (USA) Source: Burke, A. Lichtenstein, G.R. Rombeau, J.L. Current-Opinion-in-ClinicalNutrition-and-Metabolic-Care (United Kingdom). (1998). volume 1(5) page 387-390. mankind digestive system diseases malnutrition diet nutrient intake body weight unsaturated fatty acids dietary fibres health colitis

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Nutritional issues and therapy in inflammatory bowel disease. Author(s): Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA. Source: Husain, A Korzenik, J R Semin-Gastrointest-Dis. 1998 January; 9(1): 21-30 10495118

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Nutritional support in patients with inflammatory bowel disease. Author(s): Department of Medicine, University of Louisville School of Medicine, KY 40292. Source: Lowen, C C Greene, L M McClave, S A Postgrad-Med. 1992 April; 91(5): 407-14 0032-5481

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Potato glycoalkaloids adversely affect intestinal permeability and aggravate inflammatory bowel disease. Author(s): Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

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Source: Patel, B Schutte, R Sporns, P Doyle, J Jewel, L Fedorak, R N Inflamm-Bowel-Dis. 2002 September; 8(5): 340-6 1078-0998 ·

Potential role of glutamine administration in inflammatory bowel disease. Author(s): Department of Medicine, Division of Endocrinology and Metabolism, Nutrition and Health Sciences Program, Emory University School of Medicine, Atlanta, Ga., USA. Source: Jonas, C R Ziegler, T R Nestle-Nutr-Workshop-Ser-Clin-Perform-Programme. 1999; 2: 217-30; discussion 230-5 1422-7584

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Preillness non dietary factors and habits in inflammatory bowel disease. Author(s): Department of Gastroenterology, Tel-Aviv Sourasky Medical Centre, Israel. Source: Klein, I Reif, S Farbstein, H Halak, A Gilat, T Ital-J-Gastroenterol-Hepatol. 1998 June; 30(3): 247-51 1125-8055

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Probiotics and inflammatory bowel disease: is there a scientific rationale? Author(s): Department of Medicine, University College Cork, National University of Ireland. Source: Shanahan, F Inflamm-Bowel-Dis. 2000 May; 6(2): 107-15 1078-0998

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Probiotics--role in inflammatory bowel disease. Author(s): IBD Unit, Department of Internal Medicine and Gastroenterology, University of Bologna, Italy. [email protected] Source: Gionchetti, P Amadini, C Rizzello, F Venturi, A Palmonari, V Morselli, C Romagnoli, R Campieri, M Dig-Liver-Dis. 2002 September; 34 Suppl 2: S58-62 1590-8658

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Probiotics--scope and promise in inflammatory bowel disease. Author(s): Institute of Gastroenterology, Rambam Medical Center, Haifa, Israel. [email protected] Source: Chermesh, Irit Eliakim, Rami Isr-Med-Assoc-J. 2002 May; 4(5): 353-6 1565-1088

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Reduced bone mineral density and unbalanced bone metabolism in patients with inflammatory bowel disease. Author(s): Department of Internal Medicine, University of Essen, Germany. Source: Schulte, C Dignass, A U Mann, K Goebell, H Inflamm-Bowel-Dis. 1998 November; 4(4): 268-75 1078-0998

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Retrograde spread of therapeutic enemas in patients with inflammatory bowel disease. Author(s): Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands. Source: van Buul, M M Mulder, C J Wiltink, E H van Royen, E A Tytgat, G N Hepatogastroenterology. 1989 August; 36(4): 199-201 0172-6390

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Self-care for the inflammatory bowel disease patient: what can the professional recommend? Author(s): Section of Gastroenterology, Boston Medical Center, MA 02118, USA. Source: Oviedo, J Farraye, F A Semin-Gastrointest-Dis. 2001 October; 12(4): 223-36 10495118

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Smoking and nicotine in inflammatory bowel disease: good or bad for cytokines? Author(s): Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands. [email protected] Source: Zijlstra, F J Mediators-Inflamm. 1998; 7(3): 153-5 0962-9351

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Soluble adhesion molecules in inflammatory bowel disease. Author(s): Departments of Clinical Medicine and Gastroenterology, Trinity College and St James's Hospital, Dublin, Ireland. Source: Goggins, M G Goh, J O'Connell, M A Weir, D G Kelleher, D Mahmud, N Ir-JMed-Sci. 2001 Apr-June; 170(2): 107-11 0021-1265

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The relationship between habits of food consumption and reported reactions to food in people with inflammatory bowel disease--testing the limits. Author(s): School of Nursing, University of British Columbia, Vancouver, Canada. [email protected] Source: Joachim, G Nutr-Health. 1999; 13(2): 69-83 0260-1060

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Therapeutic potential of infliximab in inflammatory bowel disease. Author(s): University of Pennsylvania Medical Center, Crohn's and Colitis Comprehensive Care Program, USA. Source: Hurd, L B Lichtenstein, G R Gastroenterol-Nurs. 1999 Sep-October; 22(5): 199208 1042-895X

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Transepithelial transport processes at the intestinal mucosa in inflammatory bowel disease. Author(s): Department of General Surgery, Westfalian Wilhelms University, Munster, Germany. [email protected] Source: Schurmann, G Bruwer, M Klotz, A Schmid, K W Senninger, N Zimmer, K P IntJ-Colorectal-Dis. 1999 February; 14(1): 41-6 0179-1958

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Treating inflammatory bowel disease. Author(s): Chesterfield and North Derbyshire Royal Hospital NHS Trust. Source: Shepherd, M Nurs-Times. 2000 August 3; 96(31 Suppl): 18 0954-7762

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Treatment of the extraintestinal manifestations of inflammatory bowel disease. Author(s): Inflammatory Bowel Disease Clinical and Research Centre, University of Manitoba, John Buhler Research Centre, 804F-715 McDermot Avenue, Winnipeg, Manitoba, Canada R3E 3P4. [email protected] Source: Bernstein, C N Curr-Gastroenterol-Repage 2002 December; 4(6): 513-6 1522-8037

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Two cases of severe iron-deficiency anaemia due to inflammatory bowel disease in the dog. Source: Ristic, J.M.E. Stidworthy, M.F. J-small-anim-pract. London : British Veterinary Association. February 2002. volume 43 (2) page 80-83. 0022-4510

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Use of macro- and micronutrients for nutrition support in inflammatory bowel disease. Author(s): Department of Medicine/Gastroenterology, Washington University School of Medicine, St. Louis, Mo., USA. Source: Alpers, D H Nestle-Nutr-Workshop-Ser-Clin-Perform-Programme. 1999; 2: 15567; discussion 167-70 1422-7584

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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WebMDÒHealth: 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 inflammatory bowel disease; 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 Vitamin A Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10066,00.html

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Minerals Biotin Source: Healthnotes, Inc.; www.healthnotes.com Zinc Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10071,00.html

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CHAPTER 3. DISSERTATIONS ON INFLAMMATORY BOWEL DISEASE Overview In this chapter, we will give you a bibliography on recent dissertations relating to inflammatory bowel disease. 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 “inflammatory bowel disease” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on inflammatory bowel disease, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Inflammatory Bowel Disease 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 inflammatory bowel disease. 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: ·

Establishing the Validity and Reliability of the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) by Konieczny, Terra Ann; MSN from Medical College of Ohio at Toledo, 2003, 111 pages http://wwwlib.umi.com/dissertations/fullcit/1413729

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Followup Study of Inflammatory Bowel Disease: Effect of Stress and Biological Markers by Duffy, Linda Claire, PhD from State University of New York at Buffalo, 1987, 303 pages http://wwwlib.umi.com/dissertations/fullcit/8718533

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Formulation Development and In-vitro Evaluation of a Polysaccharide-Based ColonSpecific Drug Delivery System (CSDDS) for the Treatment of Inflammatory Bowel Disease by Singh, Brahma N.; PhD from St. John's University (New York), School of Pharmacy, 2003, 191 pages http://wwwlib.umi.com/dissertations/fullcit/3080556

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Impact of Inflammatory Bowel Disease on Family Functioning As Reported by Mothers by Silverstein, Barbara Sue, PhD from Saint Louis University, 1994, 115 pages http://wwwlib.umi.com/dissertations/fullcit/9503005

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Inflammatory Bowel Disease As a Cultural Artifact an Ethnography of the Politics of Suffering by Foulds, John Simon; PhD from The University of British Columbia (Canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NL20600

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Inflammatory Bowel Disease As a Cultural Artifact: an Ethnography of the Politics of Suffering by Foulds, John Simon, PhD from The University of British Columbia (Canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/f1933605

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It Isn't Allowed Out: Perceived Stress and Health in British and Asian Inflammatory Bowel Disease Patients by Barone, Timi Lynne, PhD from Case Western Reserve University, 1997, 350 pages http://wwwlib.umi.com/dissertations/fullcit/9813007

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The Effect of Physiological Stress on Mucosal Mast Cells in Patients with Inflammatory Bowel Disease by Farhadi, Ashkan; MS from Rush University, 2003, 57 pages http://wwwlib.umi.com/dissertations/fullcit/1414958

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 4. CLINICAL TRIALS AND INFLAMMATORY BOWEL DISEASE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning inflammatory bowel disease.

Recent Trials on Inflammatory Bowel Disease The following is a list of recent trials dedicated to inflammatory bowel disease.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

8

These are listed at www.ClinicalTrials.gov.

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Clotrimazole Enemas for Pouchitis in Children and Adults Condition(s): Ulcerative Colitis; Pouchitis; Ileitis; Inflammatory Bowel Disease 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 anti-inflammatory 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

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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

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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, 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 ·

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

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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. Study Type: Observational Contact(s): James M Perrin, MD [email protected]; Aziz Chughtai, MPH Web Site: http://clinicaltrials.gov/ct/show/NCT00061737 ·

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 no longer 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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A pharmacokinetic study to determine the oral bioavailability of methotrexate in patients with inflammatory bowel disease Condition(s): Inflammatory Bowel Disease Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Crohn's and Colitis Foundation Purpose - Excerpt: Patients with inflammatory bowel disease (IBD) who require methotrexate (MTX)for treatment currently receive this drug by injection. MTX is also available as a pill that can be given by mouth but it is not known how well the drug enters the body in patients with Crohn's disease or ulcerative colitis. This study is being done to compare how much MTX enters the body when the drug is taken by mouth compared to when it is given by injection. If the drug is well absorbed, it may allow patients to receive the drug by mouth. Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035074

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 “inflammatory bowel disease” (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 5. DISEASE

PATENTS ON INFLAMMATORY BOWEL

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 “inflammatory bowel disease” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on inflammatory bowel disease, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Inflammatory Bowel Disease By performing a patent search focusing on inflammatory bowel disease, 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 9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We 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 inflammatory bowel disease: ·

Amide therapeutics and methods for treating inflammatory bowel disease Inventor(s): Flitter; William D. (Mountain View, CA), Garland; William A. (Los Gatos, CA), Greenwood Van-Meerveld; Beverly (Oklahoma City, OK), Irwin; Ian (Palo Alto, CA) Assignee(s): Centaur Pharmaceuticals, Inc. (sunnyvale, Ca) Patent Number: 6,486,349 Date filed: November 17, 2000 Abstract: Disclosed are methods for treating or preventing inflammatory bowel disease (IBD) using amide and related compounds. Pharmaceutical compositions containing amide compounds which are useful for the treatment or prophylaxis of IBD are also disclosed. Excerpt(s): This invention relates to the treatment of inflammatory bowel disease (IBD). More specifically, this invention is directed to methods for treating or preventing IBD using amide compounds. This invention is also directed to pharmaceutical compositions containing amide compounds which are useful for the treatment or prophylaxis of IBD. The term inflammatory bowel disease ("IBD") describes a group of chronic inflammatory disorders of unknown causes involving the gastrointestinal tract ("GI tract"). The prevalence of IBD in the US is estimated to be about 200 per 100,000 population or approximately 500,000 people. Patients with IBD can be divided into two major groups, those with ulcerative colitis ("UC") and those with Crohn's disease ("CD"). In patients with UC, there is an inflammatory reaction primarily involving the colonic mucosa. The inflammation is typically uniform and continuous with no intervening areas of normal mucosa. Surface mucosal cells as well as crypt epithelium and submucosa are involved in an inflammatory reaction with neutrophil infiltration. Ultimately, this situation typically progresses to epithelial damage with loss of epithelial cells resulting in multiple ulcerations, fibrosis, dysplasia and longitudinal retraction of the colon. Web site: http://www.delphion.com/details?pn=US06486349__

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Antagonists of MCP-1 function and methods of use thereof Inventor(s): Anuskiewicz; Steven E. (San Bruno, CA), Inagaki; Hideaki (Anjoh, JP), Ishiwata; Yoshiro (Aichi-gun, JP), Jomori; Takahito (Nagoya, JP), Kakigami; Takuji (Inabe-gun, JP), Laborde; Edgardo (Foster City, CA), Matsumoto; Yukiharu (Gifu, JP), Matsushima; Kouji (Matsudo, JP), Meng; Fanying (San Francisco, CA), Peterson; Brian T. (San Francisco, CA), Robinson; Louise (San Carlos, CA), Villar; Hugo O. (La Jolla, CA), Yokochi; Shoji (Inabe-gun, JP) Assignee(s): Sanwa Kagaku Kenkyusho Co., Ltd. (jp), Telik, Inc. (palo Alto, Ca) Patent Number: 6,677,365 Date filed: March 25, 2002

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Abstract: Chemical compounds which are antagonists of Monocyte Chemoattractant Protein-1 (MCP-1) function, pharmaceutical compositions comprising these compounds, methods of treatment employing these compounds and compositions, and processes for preparing these compounds. The compounds are useful in the prevention or treatment of chronic or acute inflammatory or autoimmune diseases, especially those associated with aberrant lymphocyte or monocyte accumulation such as arthritis, asthma, atherosclerosis, diabetic nephropathy, inflammatory bowel disease, Crohn's disease, multiple sclerosis, nephritis, pancreatitis, pulmonary fibrosis, psoriasis, restenosis, and transplant rejection. Excerpt(s): The present invention relates to chemical compounds, pharmaceutical compositions comprising said compounds, uses of said compounds and compositions, methods of treatment employing said compounds and compositions, and processes for preparing said compounds. Specifically, this invention relates to novel compounds which are antagonists of Monocyte Chemoattractant Protein-1 (MCP-1) function and are useful in the prevention or treatment of chronic or acute inflammatory or autoimmune diseases, especially those associated with aberrant lymphocyte or monocyte accumulation such as arthritis, asthma, atherosclerosis, diabetic nephropathy, inflammatory bowel disease, Crohn's disease, multiple sclerosis, nephritis, pancreatitis, pulmonary fibrosis, psoriasis, restenosis, and transplant rejection. More specifically, the invention is related to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases. The migration of leukocytes from blood vessels into diseased tissues is an important process in the initiation of normal inflammatory responses to certain stimuli or insults to the immune system. However, this process is also involved in the onset and progression of life-threatening inflammatory and autoimmune diseases; blocking leukocyte recruitment in these disease states, therefore, can be an effective therapeutic strategy. The mechanism by which leukocytes leave the bloodstream and accumulate at inflammatory sites involves three distinct steps: (1) rolling, (2) arrest and firm adhesion, and (3) transendothelial migration [Springer, Nature 346:425-433 (1990); Lawrence and Springer, Cell 65:859-873 (1991); Butcher, Cell 67:1033-1036 (1991)]. The second step is mediated at the molecular level by chemoattractant receptors on the surface of leukocytes which bind chemoattractant cytokines secreted by proinflammatory cells at the site of damage or infection. Receptor binding activates leukocytes, increases their adhesiveness to the endothelium, and promotes their transmigration into the affected tissue, where they can secrete inflammatory and chemoattractant cytokines and degradative proteases that act on the subendothelial matrix, facilitating the migration of additional leukocytes to the site of injury. Web site: http://www.delphion.com/details?pn=US06677365__ ·

Antibodies to cytokines in the prevention and treatment of inflammatory bowel disease Inventor(s): Kink; John A. (Madison, WI), Stafford; Douglas C. (Madison, WI), Worledge; Katherine L. (Madison, WI) Assignee(s): Promega Corp. (madison, Wi) Patent Number: 6,663,864 Date filed: June 4, 1999 Abstract: Methods are described for treating inflammatory bowel disease in animals, including humans. Specific avian polyclonal antibodies directed to proinflammatory

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cytokines (such as IL-6 and TNF) are shown to have a beneficial effect in animal models predictive of human therapy for the treatment of colitis, including Crohn's disease. Excerpt(s): The present invention relates to therapeutics for the prevention and treatment of inflammatory bowel disease, and in particular the prevention and treatment of inflammatory bowel disease in humans as well as other animals through the use of antibodies to inflammatory mediators including but not limited to proinflammatory cytokines. Inflammatory bowel diseases (IBD) are defined by chronic, relapsing intestinal inflammation of obscure origin. IBD refers to two distinct disorders, Crohn's disease and ulcerative colitis (UC). Both diseases appear to result from the unrestrained activation of an inflammatory response in the intestine. This inflammatory cascade is thought to be perpetuated through the actions of proinflammatory cytokines and selective activation of lymphocyte subsets. In patients with IBD, ulcers and inflammation of the inner lining of the intestines lead to symptoms of abdominal pain, diarrhea, and rectal bleeding. Ulcerative colitis occurs in the large intestine, while in Crohn's, the disease can involve the entire GI tract as well as the small and large intestines. For most patients, IBD is a chronic condition with symptoms lasting for months to years. It is most common in young adults, but can occur at any age. It is found worldwide, but is most common in industrialized countries such as the United States, England, and northern Europe. It is especially common in people of Jewish descent and has racial differences in incidence as well. The clinical symptoms of IBD are intermittent rectal bleeding, crampy abdominal pain, weight loss and diarrhea. Diagnosis of IBD is based on the clinical symptoms, the use of a barium enema, but direct visualization (sigmoidoscopy or colonoscopy) is the most accurate test. Protracted IBD is a risk factor for colon cancer, and treatment of IBD can involve medications and surgery. Some patients with UC only have disease in the rectum (proctitis). Others with UC have disease limited the rectum and the adjacent left colon (proctosigmoiditis). Yet others have UC of the entire colon (universal IBD). Symptoms of UC are generally more severe with more extensive disease (larger portion of the colon involved with disease). Web site: http://www.delphion.com/details?pn=US06663864__ ·

Artificial proteoglycans Inventor(s): Aruffo; Alejandro A. (Belle Mead, NJ), Bennett; Kelly L. (Skillman, NJ), Greenfield; Brad W. (Edmonds, WA), Wolff; Edith A. (Plainsboro, NJ) Assignee(s): Bristol-myers Squibb Co. (princeton, Nj) Patent Number: 6,559,287 Date filed: January 21, 1999 Abstract: Novel articifial proteoglycans containing a GAG assembly site and a control sequence required for assembly, method for enhancing the biological activity of a glycosaminoglycan binding protein using artificial proteoglycans, DNA constructs of artificial proteoglycans. The artificial proteoglycans of the present invention are useful for preparations of adjuvants for vaccination, for targeting of chemokines to nonimmunogenic tumor cells to enhance cellular anti-tumor response, for preparations designed to help promote wound healing, and for treatment of immunological disorders,including rheumatoid arthritis, asthma, chronic obstructive pulmonary disorder, Lupus, inflammatory bowel disease, psoriasis, osteoarthritis, and HIV infection.

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Excerpt(s): Heparan sulfate (HS) and chondroitin sulfate (CS) are glycosaminoglycans. Heparan sulfate and chondroitin sulfate modified proteoglycans have been shown to play an important role in regulating the function of a number of glycosaminoglycan (GAG) binding proteins which include growth factors and chemokines. For example, binding of basic fibroblast growth factor (b-FGF) to HS modified proteoglycans has been shown to increase local concentrations of the growth factor and prolong its half life. In addition, it appears that growth factor binding to the proteoglycan changes its conformation and facilitates its interaction with its receptor and also leads to receptor oligomerization enhancing signal transduction. An example of a proteoglycan of current interest is CD44. CD44 is a widely distributed type I membrane protein which is capable of binding hyaluronan (HA), other extracellular matrix components and osteopontin. The interaction between CD44 and its ligands has been shown to participate in cell migration and activation. The exons encoding the CD44 gene can be variably spliced to give rise to multiple protein isoforms. Expression of these CD44 isoforms can be tissue specific, developmentally regulated and/or regulated by cell activation. Most of these isoforms arise from the variable splicing of exons encoding polypeptide fragments located in the extracellular region of CD44, downstream of the HA binding domain. Changes in the pattern of glycosylation of CD44 resulting from the addition of variably spliced exons, which are modified extensively with O-linked carbohydrates, can effectively modulate the HA binding activity of CD44. Likewise, different CD44 isoforms are modified with different GAG polymers including HS and CS. (b) a second targeting polypeptide. Web site: http://www.delphion.com/details?pn=US06559287__ ·

Benzyl compounds which inhibit leukocyte adhesion mediated by VLA-4 Inventor(s): Dappen; Michael S. (640 Topaz St., Redwood City, CA 94061), Dressen; Darren B. (3110 Casa De Campo #2, San Mateo, CA 94403), Grant; Francine S. (3735 Sacromento St., San Francisco, CA 94118), Konradi; Andrei W. (95 Cervantes #105, San Francisco, CA 94123), Lombardo; Louis John (412 S. Woods Rd., Belle Mead, NJ 08502), Pleiss; Michael A. (848 Stella Ct., Sunnyvale, CA 94087), Semko; Christopher M. (2361 Carpenter Ct., Fremont, CA 94539), Thorsett; Eugene D. (571 Buena Vista, Moss Beach, CA 94038) Assignee(s): None Reported Patent Number: 6,586,602 Date filed: January 14, 2002 Abstract: Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, wherein the disease may be, for example, asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis. Excerpt(s): This invention relates to compounds which inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. All of the above publications, patents and patent applications are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety.

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Intercellular adhesion mediated by VLA-4 and other cell surface receptors is associated with a number of inflammatory responses. At the site of an injury or other inflammatory stimulus, activated vascular endothelial cells express molecules that are adhesive for leukocytes. The mechanics of leukocyte adhesion to endothelial cells involves, in part, the recognition and binding of cell surface receptors on leukocytes to the corresponding cell surface molecules on endothelial cells. Once bound, the leukocytes migrate across the blood vessel wall to enter the injured site and release chemical mediators to combat infection. For reviews of adhesion receptors of the immune system, see, for example, Springer.sup.3 and Osborn.sup.4. Web site: http://www.delphion.com/details?pn=US06586602__ ·

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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Compositions and methods comprising helicobacter antigens for treatment and prevention of inflammatory bowel disease Inventor(s): Fox; James J. (Harvard, MA), Lee; Adrian (Lane Cove, AU), Schauer; David (Newton, MA), Whary; Mark (Pepperell, MA) Assignee(s): Massachusetts Institute of Technology (cambridge, Ma) Patent Number: 6,599,509 Date filed: August 28, 1998 Abstract: The treatment of IBD in mammals, including humans, is described. More particularly, the present invention relates to compositions and methods for the treatment of IBD associated with Helicobacter or other bacterial infections in mammals, including humans, and to vaccine compositions and antibodies suitable for use in such treatment. Excerpt(s): The present invention relates to the treatment of Inflammatory Bowel Disease in mammals, including humans. More particularly, the present invention relates to immunogens and immunization with bacterial antigens, including but not limited to Helicobacter antigens, to prevent or treat Inflammatory Bowel Disease. Inflammatory Bowel Disease (IBD) refers to a group of gastrointestinal disorders characterized by a chronic non-specific inflammation of portions of the gastrointestinal tract. Ulcerative colitis and Crohn's Disease are the most prominent examples of IBD in humans. They are associated with many symptoms and complications, including growth retardation in children, rectal prolapse, blood in stools (e.g., melena and/or hematochezia), wasting, iron deficiency, and anemia (e.g. iron deficiency anemia and anemia of chronic disease or of chronic inflammation). The etiology (or etiologies) and pathogenesis of IBD are still unclear. Previous understanding of the pathogenesis was limited to a three-stage process: (a) an irritant, which could be an immune process or infectious agent, activates (b) leukocytes which release enzymes such as proteases and inflammatory mediators such as histamine, serotonin and prostaglandins, and (c) these products cause edema, pain, heat and loss of function. See Wyngaarden and Smith (eds.) Cecil's Textbook of Medicine (W. B. Saunders Co. 1985), Berkow (ed.). The Merck Manual of Diagnosis and Therapy (Merck Sharp & Dohme Research Laboratories, 1982), and Harrison's Principles of Internal Medicine, 12th Ed., McGraw-Hill, Inc. (1991). Web site: http://www.delphion.com/details?pn=US06599509__

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Fgl-2 knockout mice Inventor(s): Fung; Laisum (Toronto, CA), Levy; Gary (Thornhill, CA), Marsden; Philip (Toronto, CA) Assignee(s): Trillium Therapeutics Inc. (toronto, Ca) Patent Number: 6,642,433 Date filed: October 13, 2000 Abstract: A knockout mouse in which the Fgl-2 gene has been suppressed is described. The mouse is useful in studying the role of Fgl-2 in normal and disease states including viral hepatitis, allograph rejection, fetal loss, inflammatory bowel disease, lupus glomerulonephritis; acute respiratory disease syndrome, Whipple's disease, cancer and for developing therapies to treat these diseases.

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Excerpt(s): The present invention relates to mammals and cell lines in which the expression of the Fgl-2 gene has been suppressed. The invention also includes constructs that are useful in preparing the mammals and cell lines. Fulminant viral hepatitis is characterized by the rapid appearance of jaundice, coagulopathy and encephalopathy and reflects severe hepatocellular dysfunction and necrosis. Thrombosis is a common feature of fulminant hepatitis and may occur in viral infections complicated by disseminated intravascular coagulation. Monocytes/macrophages respond to infection with hepatitis viruses by generating procoagulant activity (PCA) and also produce monokines such as TNF and IL-2, which in turn can induce other cells like endothelial cells to produce PCA. Activation of the coagulation pathways is an important part of immune and inflammatory reactions and accounts for the fibrin deposition in these reactions. Furthermore, the inventors have shown that the elaboration of PCA by monocytes/macrophages parallels the susceptibility to fulminant hepatitis caused by murine hepatitis virus strain 3 (MHV-3). As described in applicant's co-pending application Ser. No. 09/442,143, which is incorporated herein by reference in its entirety, the applicant's identified the MHV-3 induced procoagulant as a direct prothrombinase Fgl-2 and the mouse and human sequences have been sequenced. Clinical conditions other than hepatitis in which Fgl-2 is implicated include allograft rejection, fetal loss, inflammatory bowel disease lupus glomerulonephritis, acute respiratory disease syndrome, Whipple's disease, and cancer. In view of the role of Fgl-2 in various diseases it is useful to prepare an Fgl-2 knockout model in order to further elucidate its function in these diseases and importantly to develop therapies to treat the diseases. Web site: http://www.delphion.com/details?pn=US06642433__ ·

Heterocycle amides as cell adhesion inhibitors Inventor(s): Chang; Linda L. (Wayne, NJ), Delaszlo; Stephen E. (Rumson, NJ), Doherty; George (Princeton, NJ), Hagmann; William K. (Westfield, NJ), Yang; Ginger X. (Jersey City, NJ) Assignee(s): Merck & Co., Inc. (rahway, Nj) Patent Number: 6,420,418 Date filed: August 14, 2000 Abstract: Compounds of Formula I are antagonists of VLA-4 and/or.alpha.4.beta.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.4.beta.1), the.alpha.4.beta.7 integrin (LPAM-1 and.alpha.4.beta.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

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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 VLA4,.alpha.4.beta.7-, and/or.alpha.9.beta.1-binding and cell adhesion and activation, such as AIDS-related dementia, allergic 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, vascular occlusion following angioplasty. The present invention relates to oxygen and sulfur heterocyclic amide 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 selecting, 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=US06420418__ ·

Inhibitor of platelet activating factor Inventor(s): Mahuran; Don (Toronto, CA), Reynaud; Denis (Toronto, CA), Rigat; Brigitte (Abingdon-Oxon, GB) Assignee(s): Hsc Research and Development Limited Partnership (ca) Patent Number: 6,423,680 Date filed: October 30, 1998 Abstract: An anti-inflammatory composition is provided. The composition comprises GM.sub.2 activator protein or a peptide derived from the GM.sub.2 activator protein which is capable of inhibiting platelet activating factor (PAF). The composition is useful in the treatment of inflammatory conditions such as inflammatory bowel disease and asthma. Excerpt(s): The present invention relates to anti-inflammatory compositions. More particularly, the present invention relates to an anti-inflammatory composition comprising GM.sub.2 activator protein. Inflammation is generally a protective response triggered by tissue injury or destruction. It is characterized physically by pain, heat, redness, swelling and loss of function, and histologically by a complex series of events which include dilatation of arterioles, leakage in capillaries and venules, exudation of plasma and other fluids, and migration of leukocytes into the inflammatory focus. Although characterized as a protective response, disorders exist in which prolonged or chronic inflammation is undesirable because it causes extreme discomfort as well as extensive tissue damage. Examples of such inflammatory disorders include autoimmune disease, hypersensitivity, rheumatism (such as rheumatoid arthritis), vasculitis,

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asthma, allergies, rhinitis, gout and tissue-specific conditions such as glomerulonephritis and hepatitis. Many "anti-inflammatory" drugs exist today which are used to treat the symptoms associated with inflammatory disorders. Treatments including both steroidal and non-steroidal (NSAIDS) drugs are known. Unfortunately, undesirable side effects are commonly encountered with the use of either of these treatments. NSAIDS, such as the salicylates and related compounds, for example, exhibit toxicity, and can cause gastric and intestinal ulceration, disturbances in platelet function and changes in renal function. Steroidal treatments also exhibit toxicity, and have been found to adversely effect infant growth, development and immune response, and cause bone fragility in older patients. Web site: http://www.delphion.com/details?pn=US06423680__ ·

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. Web site: http://www.delphion.com/details?pn=US06630444__

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Medical use for atypical.beta.-adrenoceptor agonists Inventor(s): Bahl; Ashwani Kumar (Ware, GB) Assignee(s): Glaxo Group Limited (greenford, Gb) Patent Number: 6,696,486 Date filed: February 14, 1996 Abstract: The present invention relates to the use of compounds which act as agonists at atypical beta-adrenoceptors, for the treatment of gastrointestinal disorders, especially peptic ulceration, oesophagitis, gastritis and duodenitis, intestinal ulcerations, including inflammatory bowel disease, and gastrointestinal ulcerations, especially when induced by non-steroidal anti-inflammatory drugs or corticosteroids. Excerpt(s): This invention relates to a new medical use for certain chemical compounds and pharmaceutical compositions containing them. In particular it relates to the use in the treatment of gastrointestinal disorders of compounds which act as agonists at atypical beta-adrenoceptors (also known as beta-3-adrenoceptors). Such receptors have been described for example by J R S Arch et. al., Nature, 309, 163-165 (1984); C Wilson et. al., Eur. J. Pharmacol., 100, 309-319 (1984); L J Emorine et. al., Science, 245, 1118-1121 (1989); and A. Bianchetti et. al. Br. J. Pharmacol., 100, 831-839 (1990). Atypical betaadrenoceptors belong to the family of adrenoceptors which mediate the physiological actions of the hormones adrenaline and noradrenaline. Sub-types of the adrenoceptors,.alpha.sub.1 -,.alpha.sub.2 -,.beta.sub.1 -,.beta.sub.2 - and.beta.sub.3 (atypical) can be identified on the basis of their pharmacological properties and physiological effects. Chemical agents which stimulate or block these receptors (but not.beta.sub.3) are widely used in clinical medicine. More recently, emphasis has been placed upon specific receptor selectivity in order to reduce side effects caused, in part, by interactions with other receptors. Atypical beta-adrenoceptors are known to occur in adipose tissue and the gastrointestinal tract. Compounds which act as agonists at atypical beta-adrenoceptors may be identified using standards tests (see for instance C Wilson et. al., supra). Web site: http://www.delphion.com/details?pn=US06696486__

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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 injury, bacterial pneumonia, inflammatory bowel disease, rheumatoid arthritis, asthma, ulcerative colitis and Crohn's disease.

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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, 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

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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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Methods for treatment of inflammatory bowel disease Inventor(s): Alila; Hector W. (North Wales, PA), Earle; Keith A. (North Wales, PA) Assignee(s): Osi Pharmaceuticals, Inc. (melville, Ny) Patent Number: 6,699,894 Date filed: September 23, 2002 Abstract: Substituted condensation products of N-benzyl-3-indenylacetamides with heterocyclic aldehydes and other such inhibitors are useful for the treatment of inflammatory bowel disease. Excerpt(s): This invention relates to the treatment of inflammatory bowel disease. Inflammatory bowel disease ("IBD") refers to two chronic diseases that cause inflammation of the intestines: ulcerative colitis and Crohn's disease. Ulcerative colitis and Crohn's disease are different diseases that manifest similar symptoms. Up to 2,000,000 Americans are estimated to suffer from IBD. Both diseases are chronic and most frequently have their onset in early adult life. Some patients have alternating periods of remission alternating with periods of relapse or flare. Other patients have continuous symptoms from continued inflammation. The severity of the diseases varies widely between individuals. Some suffer only mild symptoms, but others have severe and disabling symptoms. Medical science has not yet discovered a cause or cure. Web site: http://www.delphion.com/details?pn=US06699894__

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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). 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

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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__ ·

Models of chronic and acute inflammatory diseases Inventor(s): Ehrhardt; Rolf (San Francisco, CA), Hong; Kenneth (El Cerrito, CA) Assignee(s): Bioseek, Inc. (burlingame, Ca) Patent Number: 6,593,511 Date filed: May 9, 2001 Abstract: Methods and compositions are provided for the creation and screening of nonhuman animal models having chronic inflammation. Immunocompromised host animals are injected with a population of immunocompetent effector cells, depleted of CD25+ T cells. The effector cells are tolerant of the host major histocompatibility antigens, but reactive to at least one antigen present in the host animal. The transferred cells are preferably stimulated and localized by administration of an immunostimulant at a local site. The animals are useful for a variety of screening assays and for investigation into disease causes and pathways. A variety of chronic inflammatory diseases may be studied with this model, including psoriasis, rheumatoid arthritis, diabetes, inflammatory bowel disease and multiple sclerosis. Excerpt(s): Despite recent advances in genomic sequencing efforts, as well as in the fields of pre-clinical drug screening/development and clinical trial design, the transfer of existing "pre-clinical" knowledge into the clinic is still very difficult. This is mainly due to the sparse knowledge of the events that occur during the initiation, the perpetuation and the maintenance of inflammatory disease states in humans. The reasons for such incomplete and often low quality information are numerous: humans cannot intentionally be studied in the pre-clinical phase, cell isolation is difficult from human tissue, the starting events of an autoimmune reaction occur without notice, and patients with autoimmune or other inflammatory diseases may not wish to be treated as experimental subjects. As a result, there is a lack of reliable information on which to base decisions about clinical trials. When clinical symptoms arise and treatment is required, rational selection from among the many potential anti-inflammatory compounds or combinations thereof is difficult. In order to identify new and useful drugs, screening assays must be able to provide biologically relevant information, so that there is a good correlation between the information generated by the screening assay and the pharmaceutical effectiveness of the compound. Some of the more important features for

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pharmaceutical effectiveness are specificity for the targeted cell or disease, a lack of toxicity at relevant dosages, and specific activity of the compound against its molecular or cellular target. Web site: http://www.delphion.com/details?pn=US06593511__ ·

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) Assignee(s): The Trustees of Columbia University in the City of New York (new York, Ny) Patent Number: 6,627,458 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 (pANCA) 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.

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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://www.delphion.com/details?pn=US06627458__ ·

Pharmaceutical compositions for inhibition of cytokine production and secretion Inventor(s): Bencherif; Merouane (Winston-Salem, NC), Caldwell; William Scott (Winston-Salem, NC), Dobson; Grayland Page (Winston-Salem, NC), Dull; Gary Maurice (Lewisville, NC) Assignee(s): Targacept, Inc. (winston-salem, Nc) Patent Number: 6,489,349 Date filed: September 6, 2000 Abstract: Pharmaceutical compositions incorporate compounds that affect cytokine production and/or secretion. Such compounds include aryl substituted olefinic amine compounds, pyridyloxylalkylamines and phenoxyalkylamines, and aryl substituted amine compounds, such as 3-aminophenyl amine compounds. Such pharmaceutical compositions can be used for treating a wide variety of conditions, diseases and disorders, and particularly those associated with dysfunction of cytokine production and/or secretion. Of particular interest are pharmaceutical compositions useful for preventing and treating conditions, diseases and disorders associated with undesirably high levels of cytokine production and/or secretion. Such pharmaceutical compositions are useful for treating the effects of inflammatory bowel disease, inflammation, arthritis, cachexia in neoplastics diseases or associated with AIDS, and autoimmune diseases. Excerpt(s): The present invention relates to pharmaceutical compositions, and particularly pharmaceutical compositions incorporating compounds that affect cytokine production and/or secretion. The present invention also relates to methods for treating a wide variety of conditions, diseases and disorders, and particularly those associated with dysfunction of cytokine production and/or secretion. Of particular interest are pharmaceutical compositions useful for preventing and treating conditions, diseases and disorders associated with undesirably high levels of cytokine production and/or secretion. Cytokines are polypeptides that affect cell function and modulate interactions between cells associated with immune, inflammatory or hematopoietic responses. Cytokines include monokines (which are generally produced and secreted by mononuclear cells, such as macrophages and monocytes) and lymphokines (which are generally produced and secreted by lymphocytes). Examples of cytokines include interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor (TNF, which includes TNF-alpha and TNF-beta). Cytokines have been recognized as having numerous functions, particularly with regards to immune system and inflammatory responses. See, Ebadi et al., Neurochem. Int., 30(4-5): 347-374 (1997). However, excessive or unregulated cytokine production and secretion has been implicated in mediating or exacerbating various diseases and disorders, particularly those associated with deficiencies in immunoregulation and physiological conditions (e.g., inflammation). See, for example, Tamaka, Jap. J. Clin. Med., 56(1): 97-101 (1998);

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Dinarello, J. Biol. Regul. Homeostat. Ag., 11(3): 91-103 (1997); Moldawer et al., Sem. Oncol., 25(1): 73-81 (1998); Balkwill, J. Viral Hepat., 4(2): 6-15 (1997); Martin et al., Eur. Resp. J., 10(9): 2139-2146 (1997) and PCT WO 98/25619. For example, pro-inflammatory cytokines are produced by a variety of cell types, play major roles in the regulation of host immune responses, and have been implicated in diverse pathologies. Exemplary pro-inflammatory cytokines include interleukin species, prostaglandin species, colony stimulating factor and tumor necrosis factor. Web site: http://www.delphion.com/details?pn=US06489349__ ·

Stimulating neutrophil function to treat inflammatory bowel disease Inventor(s): Dieckgraefe; Brian (Chesterfield, MO), Korzenik; Joshua (St. Louis, MO) Assignee(s): The Washington University (st. Louis, Mo) Patent Number: 6,500,418 Date filed: August 11, 2000 Abstract: Immune stimulatory amounts of hematopoietic colony stimulating factors are administered to patients with inflammatory bowel disease. The factors include G-CSF and GM-CSF. These factors induce and maintain remission of the disease and its manifestations, whether within the intestine or without. Excerpt(s): Crohn's disease persists as an enigma: without a deciphered etiology and without adequate therapy. Prevailing explanations of the pathogenesis of Crohn's disease (Crohn's Disease) hold that the characteristic chronic intestinal inflammation results from an aberrant, activated immune response generated against ubiquitous bacteria or bacterial products that gain access to the lamina propria, perhaps through a more permeable intestinal barrier. The abnormal reaction has been suggested to be mediated principally by T-cells enhanced by an intrinsic imbalance in pro-inflammatory and contra-inflammatory mediators. Thus, most therapy aims to counteract that inflammatory state with increasingly potent and sophisticated immune suppressants. Current therapy, mostly directed at suppressing the inflammatory process, remains inadequate both for the treatment of flares and maintenance of remission. Steroids can be effective in short term use but produce dependency in a significant proportion of patients. While certain antibiotics appear promising, data are limited. Thus there is a need in the art for effective method for treating inflammatory bowel diseases. It is an object of the invention to provide a method of treating Crohn's Disease. Web site: http://www.delphion.com/details?pn=US06500418__

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T-cell antigens, and their use in diagnosis and treatment of T-cell mediated conditions Inventor(s): Vandenbark; Arthur A. (8328 NW. Ridgetop Ct., Portland, OR 97229), Weinberg; Andrew D. (3266 SW. Fairmount Blvd., Portland, OR 97201) Assignee(s): None Reported Patent Number: 6,566,082 Date filed: June 6, 1995 Abstract: The OX-40 antigen is characterized and claimed together with variants and derivatives thereof. Also described are binding agents for the antigen and the use of

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these in diagnosis and therapy. Examples of such use include a method for the selective depletion of activated CD4.sup.+ T-cells in vivo by using immunotoxins comprising an OX-40 antibody conjugated to a toxic molecule (such as Ricin-A chain). The administration of these specific immunotoxins is used therapeutically to deplete autoimmune reactive CD4.sup.+ T-cells which have been implicated in diseases including Multiple Sclerosis, Rheumatoid Arthritis, Sarcoidosis, and Autoimmune Uveitis as well as inflammatory bowel disease and graft-versus-host disease. This type of therapy is also beneficial for eradicating CD4.sup.+ T-cell lymphomas and alloreactive CD4.sup.+ T-cells involved with a transplantation reaction. The use of the human form of the OX-40 antibody will also help in the early diagnosis of all the diseases mentioned above. Excerpt(s): This invention relates to methods for the specific depletion of activated Tlymphocytes particularly those belonging to the CD4.sup.+ subclass. Such activated Tlymphocytes e.g. CD4.sup.+ T-lymphocytes, are implicated in a number of conditions in humans including multiple sclerosis and transplant rejection. In particular, this invention provides a treatment in which activated T-lymphocytes e.g. CD4.sup.+ T-cells involved in a particular disease or condition are depleted while the non-activated Tlymphocyte e.g. CD4.sup.+ T-cells repertoire is unaffected. The CD4.sup.+ Tlymphocyte (herein referred to as the CD4.sup.+ T-cell) is the central player in the immune system because of the "help" it provides to other leukocytes in fighting off infection and potential cancerous cells. CD4.sup.+ T-cells play essential roles in both humeral and cell-mediated immunity and additionally they act during parasite infection to promote the differentiation of eosinophils and mast cells. If the CD4.sup.+ T-cell population is depleted (as is the case in AIDS patients) the host is rendered susceptible to a number of pathogens and tumours that do not ordinarily pose a threat to the host. While CD4.sup.+ T-cells thus play an important beneficial role in disease prevention, the aberrant function of these cells can produce serious problems. In some individuals, the aberrant function of CD4.sup.+ T-cells leads to autoimmunity and other disease states (Swanborg, R. H., 1984; Cush, J. J., and Lipsky, P. E., 1988; Caspi et al., 1988). Autoimmune diseases in which CD4.sup.+ T-cells have been implicated include multiple sclerosis, rheumatoid arthritis and autoimmune uveitis (see generally, Steinman, L., 1993). In essence these diseases involve an aberrant immune response in which the immune system is subverted from its normal role of attacking invading pathogens and instead attacks the host body tissues, leading to illness and even death. The targeted host tissues vary between autoimmune diseases, for example, in multiple sclerosis the immune system attacks the white matter of the brain and spinal cord, in rheumatoid arthritis the immune system attacks the synovial lining of the joints. Activated CD4.sup.+ T-cells have also been implicated in other illnesses, including rejection of transplant tissues and organs and in the development of CD4.sup.+ T-cell lymphomas. Web site: http://www.delphion.com/details?pn=US06566082__ ·

Treatment for inflammatory bowel disease with a vcam-1/1gG fusion protein Inventor(s): Burkly; Linda C. (West Newton, MA), Lobb; Roy R. (Westwood, MA) Assignee(s): Biogen, Inc. (cambridge, Ma) Patent Number: 6,482,409 Date filed: September 21, 1998

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Abstract: A method for the treatment of inflammatory bowel disease (IBD) is disclosed. The method comprises administration of a VCAM-1/IgG fusion protein. Excerpt(s): The present invention relates to a treatment for inflammatory bowel disease (IBD). More particularly, this invention relates to the use of antibodies recognizing the integrin VLA-4 (very late antigen-4) in the treatment of IBD. Inflammatory bowel disease, or IBD, is a collective term encompassing ulcerative colitis and Crohn's disease (ileitis), which are chronic inflammatory disorders of the gastrointestinal tract. Ulcerative colitis is confined to the large intestine (colon) and rectum, and involves only the inner lining of the intestinal wall. Crohn's disease may affect any section of the gastrointestinal tract (i.e., mouth, esophagus, stomach, small intestine, large intestine, rectum and anus) and may involve all layers of the intestinal wall. Both diseases are characterized by abdominal pain and cramping, diarrhea, rectal bleeding and fever. The symptoms of these diseases are usually progressive, and sufferers typically experience periods of remission followed by severe flareups. Severe side effects are associated with the drugs commonly prescribed for IBD, including nausea, dizziness, changes in blood chemistry (including anemia and leukopenia), skin rashes and drug dependence; and the surgical treatments are radical procedures that often profoundly alter the everyday life of the patient. Accordingly, there is a great need for treatments for IBD that are effective yet less severe in their side effects and are less invasive of the IBD sufferer's body and quality of life. Web site: http://www.delphion.com/details?pn=US06482409__ ·

Treatment of Inflammatory bowel disease by inhibiting binding and/or signalling through.alpha. 4.beta. 7 and its ligands and madcam Inventor(s): Newman; Walter (Boston, MA), Picarella; Dominic (Boston, MA), Ringler; Douglas J. (Revere, MA) Assignee(s): Millennium Pharmaceuticals, Inc. (cambridge, Ma) Patent Number: 6,551,593 Date filed: February 10, 1995 Abstract: The invention relates to the treatment of individuals suffering from a disease associated with leukocyte recruitment to the gastrointestinal tract or other tissues as a result of binding of leukocytes to gut-associated endothelium expressing the molecule MAdCAM (such as inflammatory bowel disease), comprising administering to the individual an effective amount of an antibody which inhibits the binding of leukocytes to endothelial MAdCAM. Excerpt(s): Inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's disease, for example, can be a debilitating and progressive disease involving inflammation of the gastrointestinal tract affecting an estimated two million people in the United States. Symptoms include abdominal pain, cramping, diarrhea and rectal bleeding. IBD treatments have included anti-inflammatory drugs (such as, corticosteroids and sulfasalazine), immunosuppressive drugs (such as, 6mercaptopurine, cyclosporine and azathioprine) and surgery (such as, colectomy). Podolsky, The New England Journal of Medicine, 325:928-937 (1991) and Podolsky, The New England Journal of Medicine, 325:1008-1016 (1991). Some studies have suggested that the cell adhesion molecule, ICAM-1, mediates leukocyte recruitment to inflammatory sites through adhesion to leukocyte surface ligands, i.e. Mac-1, LFA-1 or.alpha.4.beta.2 (Springer, Nature, 346:425-434 (1990)). In addition, vascular cell

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adhesion molecule-1 (VCAM-1), recognizing the.alpha.4.beta.1 integrin (VLA-4), has been reported to play a role in in vivo leukocyte recruitment as well (Silber et al., J. Clin. Invest. 93:1554-1563 (1994)). It has been proposed that IBD can be treated by blocking the interaction of ICAM-1 with LFA-1 or Mac-1 or VCAM-1 with.alpha.4.beta.1 (e.g., WO 93/15764). However, these therapeutic targets are likely involved in inflammatory processes in multiple organs, and a functional blockade would likely result in systemic immune dysfunction. Mucosal addressin MAdCAM, a mucosal vascular adhesion molecule, is a 58-66K glycoprotein adhesion receptor for lymphocytes which is distinct from VCAM-1 and ICAM-1 (Briskin et al., Nature, 363:461-463 (1993)). In contrast to VCAM-1 and ICAM-1, MAdCAM is preferentially expressed in the gastrointestinal tract, binds the.alpha.4.beta.7 integrin (also called LPAM-1 and CD49d/CD.sup.-) found on lymphocytes, and participates in the homing of these cells to mucosal sites, such as Peyer's patches in the intestinal wall (Hamann et al., Journal of Immunology, 152:32823293 (1994)). The use of inhibitors to the binding of MAdCAM to the receptor,.alpha.4.beta.7, in the treatment of diseases such as IBD has not been suggested. Web site: http://www.delphion.com/details?pn=US06551593__ ·

Treatment of inflammatory bowel disease with IFN-.gamma. inhibitors Inventor(s): Ashkenazi; Avi J. (San Mateo, CA), Ward; Rebecca H. R. (San Francisco, CA) Assignee(s): Genentech, Inc. (south San Francisco, Ca) Patent Number: 6,558,661 Date filed: February 22, 1994 Abstract: The invention concerns a method for the prevention or treatment of inflammatory bowel disease by administering an interferon-.gamma. inhibitor. The invention further concerns pharmaceutical compositions and bispecific molecules useful in such method. Excerpt(s): The invention concerns the prevention or treatment of inflammatory bowel disease by administering an interferon-gamma (IFN-.gamma.) inhibitor. Inflammatory bowel disease (IBD) is a collective term for ulcerative colitis (UC) and Crohn's disease, which are considered as two different entities, but have many common features and probably share at least some pathologic mechanisms. There is sufficient overlap in the diagnostic criteria for UC and CD that it is sometimes impossible to say which a given patient has; however, the type of lesion typically seen is different, as is the localization. UC mostly appears in the colon, proximal to the rectum, and the characteristic lesion is a superficial ulcer of the mucosa; CD can appear anywhere in the bowel, with occasional involvement of stomach, esophagus and duodenum, and the lesions are usually described as extensive linear fissures. The aetiology of these diseases is unknown and the initial lesion has not been clearly defined; however, patchy necrosis of the surface epithelium, focal accumulations of leukocytes adjacent to glandular crypts, and an increased number of intraepithelial lymphocytes and certain macrophage subsets have been described as putative early changes, especially in Crohn's disease. Web site: http://www.delphion.com/details?pn=US06558661__

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Patent Applications on Inflammatory Bowel Disease 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 inflammatory bowel disease: ·

1,6-Fused uracil derivatives as matrix metalloproteinase inhibitors Inventor(s): Roark, William Howard; (Ann Arbor, MI) Correspondence: Warner-lambert Company; 2800 Plymouth RD; Ann Arbor; MI; 48105; US Patent Application Number: 20040034009 Date filed: August 5, 2003 Abstract: This invention provides compounds defined by Formula I 1or a pharmaceutically acceptable salt thereof,wherein R.sup.1, Q, Y.sup.6, Y.sup.8, R.sup.2, R.sup.4, and R.sup.7 are as defined in the specification. The invention also provides pharmaceutical compositions comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, as defined in the specification, together with a pharmaceutically acceptable carrier, diluent, or excipient. The invention also provides methods of inhibiting an MMP-13 enzyme in an animal, comprising administering to the animal a compound of Formula I, or a pharmaceutically acceptable salt thereof. The invention also provides methods of treating a disease mediated by an MMP-13 enzyme in a patient, comprising administering to the patient a compound of Formula I, or a pharmaceutically acceptable salt thereof, either alone or in a pharmaceutical composition. The invention also provides methods of treating diseases such as heart disease, multiple sclerosis, osteo- and rheumatoid arthritis, arthritis other than osteo- or rheumatoid arthritis, cardiac insufficiency, inflammatory bowel disease, heart failure, age-related macular degeneration, chronic obstructive pulmonary disease, asthma, periodontal diseases, psoriasis, atherosclerosis, and osteoporosis in a patient, comprising administering to the patient a compound of Formula I, or a pharmaceutically acceptable salt thereof, either alone or in a pharmaceutical composition. The invention also provides combinations, comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, together with another pharmaceutically active component as described in the specification. Excerpt(s): This application claims benefit of priority from U.S. Provisional Patent Application No. 60/403,074, filed Aug. 13, 2002. This invention relates to 1,6-fused uracil derivatives which inhibit matrix metalloproteinase enzymes and thus are useful for treating diseases resulting from MMP-mediated tissue breakdown such as heart disease, cardiac insufficiency, inflammatory bowel disease, multiple sclerosis, osteo- and rheumatoid arthritis, arthritis other than osteo- or rheumatoid arthritis, heart failure, age-related macular degeneration, chronic obstructive pulmonary disease, asthma, periodontal diseases, psoriasis, atherosclerosis, and osteoporosis. Matrix metalloproteinases (sometimes referred to as MMPs) are naturally occurring enzymes found in most mammals. Over-expression and activation of MMPs, or an imbalance between MMPs and inhibitors of MMPs, have been suggested as factors in the pathogenesis of diseases characterized by the breakdown of extracellular matrix or connective tissues.

10

This has been a common practice outside the United States prior to December 2000.

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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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Anti-inflammatory and psoriasis treatment and protein kinase inhibition by hydroxyltilbenes and novel stilbene derivatives and analogues Inventor(s): Chen, Genhui; (Burnaby, CA), Hu, Kaiji; (Burnaby, CA), Li, Jianxiong; (Port Moody, CA), Webster, John M.; (North Vancouver, CA), Zhu, Jiang; (Burnaby, CA) Correspondence: Pennie & Edmonds; 1155 Avenue OF The Americas; New York; NY; 10036-2711; US Patent Application Number: 20030171429 Date filed: October 28, 2002 Abstract: Disclosed herein are compositions containing hydroxylstilbenes or their derivatives or analogues. The compositions are useful to inhibit protein kinease, and for the treatment of inflammatory diseases, including psoriasis, multiple sclerosis, rhumatoid arthritis, restinosis, inflammatory bowel disease, and inflammatory lung disease. They are also useful to treat surgical adhesions and graft rejection. Novel derivatives and analogues are also disclosed. Excerpt(s): The stilbenes isolated from Photorhabdus species bacteria are known to have antibiotic activity. See V. J. Paul, S. Frautschv, W. Fenical, and K. H. Nealson, Journal of Chemical Ecology, 7: 589-597 (1981), and K. Hu, J. Li, W. Wang, H. Wu, H. Lin and J. M. Webster, Canadian Journal of Microbiology. 44: 1072-1077 (1998). However, these compounds have not been shown to have other biological activity. A similar compound, resveratrol, has been disclosed as having cancer preventive (Jang et al. 1997) and protein kinase C inhibitory (Garcia-Garcia et. al., 1999) activities. There are many common conditions that cannot be treated successfully by antibiotics. Some of these are inflammatory diseases. The compounds of the invention possess specific antiinflammatory properties. Inflammatory diseases, whether of a chronic or acute nature, represent a substantial problem in the healthcare industry. Chronic inflammation is considered to be inflammation of a prolonged duration (weeks or months) in which active inflammation, tissue destruction and attempts at healing are proceeding simultaneously (Robbins Pathological Basis of Disease by R. S. Cotran, v. Kumar, and S. L. Robbins, W. B, Saunders Co., p. 75, 1989). Although chronic inflammation can follow an acute inflammatory episode, it can also begin as an insidious process that progresses with time, for example, as a result of a persistent infection (e.g., tuberculosis, syphilis, fungal infection) which causes a delayed hypersensitivity reaction, prolonged exposure to endogenous (e.g., elevated plasma lipids) or exogenous (e.g., silica, asbestos, cigarette tar, surgical sutures) toxins, or, autoimmune reactions against the body's own tissues (e.g., rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, psoriasis). Chronic inflammatory diseases therefore, include many common medical conditions such as rheumatoid arthritis, restenosis, psoriasis, multiple sclerosis, surgical adhesions, tuberculosis, and chronic inflammatory lung and airway diseases (e.g., asthma, pneumoconiosis, chronic obstructive pulmonary disease, nasal polyps and pulmonary fibrosis). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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·

Bifidobacteriumin the treatment of inflammatory disease Inventor(s): Collins, John Kevin; (Doughcloyne, IE), O'Mahony, Liam; (Cork, IE), O'Sullivan, Gerald Christopher; (Cork, IE), Shanahan, Fergus; (Kinsale, IE) Correspondence: Jacobson Holman Pllc; 400 Seventh Street N.W.; Suite 600; Washington; DC; 20004; US Patent Application Number: 20030215467 Date filed: March 17, 2003 Abstract: A strain of Bifidobacterium isolated from resected and washed human gastrointestinal tract is significantly immunomodulatory following oral consumption in humans. The strain is useful in the prophylaxis and/or treatment of undesirable inflammatroy activity, especially gastrointestinal inflammatory activity such as inflammatory bowel disease or irritable bowel syndrome. The inflammatory activity may also be due to cancer. Excerpt(s): This invention relates to probiotic Bifidobacterium strains which have various applications in foodstuffs and in medicine. More particularly, the invention relates to probiotic strains of bifidobacteria which are capable of beneficially modifying and consequently alleviating observable symptoms in inflammatory disease. Consumers are becoming increasingly aware of matters which may be necessary for maintenance of their environment, health and nutrition. In response, scientific research has focussed upon the roles that diet, stress, and modern medical practices (e.g. antibiotics and radiotherapy) may play in threatening human health. In particular, population dynamics shifting towards older societies are increasing the incidence of illnesses which may be caused by deficient or compromised microflora such as gastrointestinal tract (GIT) infections, constipation, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD)--Crohn's disease and ulcerative colitis, food allergies, antibiotic-induced diarrhoea, cardiovascular disease, and certain cancers (e.g. colorectal cancer). Probiotics have been defined as live microbial food supplements which beneficially affect the host by improving the intestinal microbial balance, or more broadly, as living microorganisms, which upon ingestion in certain numbers, exert health effects beyond inherent basic nutrition. Cocktails of various micro-organisms, particularly species of Lactobacillus and Streptococcus, have traditionally been used in fermented dairy products to promote health. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

·

Compositions and methods for the therapy and diagnosis of inflammatory bowel disease Inventor(s): Hersberg, Robert M.; (US), Hosken, Nancy Ann; (US), Lodes, Michael J.; (US), Mohamath, Raodoh; (US) Correspondence: Corixa Corporation; 1124 Columbia Street; Suite 200; Seattle; WA; 98104; US Patent Application Number: 20040043931 Date filed: May 30, 2003 Abstract: Compositions and methods for the therapy and diagnosis of Inflammatory Bowel Disease (IBD), including Crohn's Disease and Ulcerative Colitis, are disclosed. Illustrative compositions comprise one or more bacterial polypeptides, immunogenic

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portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of IBD. Excerpt(s): This application is a continuation in part of PCT Application No. PCT/US02/40422, filed on Dec. 16, 2002, which is related to U.S. Provisional Patent Application No. 60/426,835, filed Nov. 15, 2002, No. 60/396,242, filed Jul. 16, 2002, and No. 60/341,830, filed Dec. 17, 2001, which are all incorporated herein in their entirety. The present invention relates generally to therapy and diagnosis of Crohn's Disease and Ulcerative Colitis (collectively referred to as Inflammatory Bowel Disease, or IBD). The invention is more particularly related to polypeptides comprising at least a portion of a protein that is recognized, and to which individuals with IBD mount an aberrant immune response, and to polynucleotides encoding such polypeptides. Such polypeptides and polynucleotides are useful in pharmaceutical compositions, e.g., vaccines, and other compositions for the diagnosis and treatment of IBD. Crohn's Disease and Ulcerative Colitis (collectively referred to as Inflammatory Bowel Disease, or IBD) are chronic, inflammatory diseases of the gastrointestinal tract. While the clinical features vary somewhat between these two disorders, both are characterized by abdominal pain, diarrhea (often bloody), a variable group of `extra-intestinal` manifestations (such as arthritis, uveitis, skin changes, etc) and the accumulation of inflammatory cells within the small intestine and colon (observed in pathologic biopsy or surgical specimens). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Compositions comprising a substituted immunomediated inflammatory disorders

benzimidazole

useful

for

treating

Inventor(s): Church, Timothy J.; (Redwood City, CA), Cutshall, Neil Scott; (San Mateo, CA), Gangloff, Anthony R.; (Pacifica, CA), Jenkins, Thomas E.; (La Honda, CA), Linsell, Martin S.; (Foster City, CA), Litvak, Joane; (Oakland, CA), Rice, Kenneth D.; (Sausalito, CA), Spencer, Jeffrey R.; (San Mateo, CA), Wang, Vivian R.; (Redwood City, CA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030212120 Date filed: March 14, 2003 Abstract: Novel compounds, compositions and methods effective for the prevention and treatment of mast-cell mediated inflammatory disorders are described. The compounds, compositions and methods are effective for the prevention and treatment of inflammatory diseases associated with the respiratory tract, such as asthma and allergic rhinitis, as well as other types of immunomediated inflammatory disorders, such as rheumatoid arthritis, conjunctivitis and inflammatory bowel disease, various dermatological conditions, as well as certain viral conditions. The compounds comprise potent and selective inhibitors of the mast cell protease tryptase. The compositions for treating these conditions include oral, inhalant, topical and parenteral preparations as well as devices comprising such preparations. Excerpt(s): This application is a continuation-in-part of application Ser. No. 08/833,674, filed Apr. 07, 1997, which is a continuation-in-part of application Ser. No. 08/357,491, filed Dec. 14, 1994, which are herein incorporated by reference, and relates to

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compounds and compositions for treating diseases associated with serine protease, particularly tryptase, activity. Tryptase, the predominant protease secreted from human mast cells, is thought to be involved in neuropeptide processing and tissue inflammation. Tryptase concentrations are elevated in the bloodstream for several hours following anaphylaxis (Schwartz et al. (1987) N. Eng. J. Med. 316:1622-1626), are increased in nasal and lung lavage fluid from atopic subjects following specific antigen challenge (Castells et al. (1988) J. Allerg. Clin. Immunol. 141:563-568) and are elevated in lung lavage fluid of atopic asthmatics after endobronchial allergen challenge. Smokers often have striking elevations of bronchoalveolar lavage fluid tryptase levels, a finding that provides some support for the hypothesis that release of proteinase from activated mast cells could contribute to lung destruction in smoker's emphysema. (Celenteron et al. (1988) Chest 94:119-123). In addition, tryptase has been shown to be a potent mitogen for fibroblasts, suggesting that it is involved in pulmonary fibrosis and interstitial lung disease (Ross et al. (1991) J. Clin. Invest. 88:493-499). Asthma is recognized as an inflammatory disorder (Hood et al. (1984) In: Benjamin-Cummings, ed. Immunology 2nd ed.) and frequently is characterized by progressive development of hyperresponsiveness of the trachea and bronchi to both immunospecific allergens and generalized chemical or physical stimuli. The disease involves multiple biochemical mediators in both its acute and chronic stages. The hyper-responsiveness of asthmatic bronchiolar tissue is believed to be the result of chronic inflammatory reactions, which irritate and damage the epithelium lining the airway wall and promote pathological thickening of the underlying tissue. Bronchial biopsies in patients with only mild asthma have features of inflammation in the airway wall. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Compounds and methods Inventor(s): Bondinell, William E.; (Collegeville, PA), Neeb, Michael J.; (Collegeville, PA) Correspondence: Smithkline Beecham Corporation; Corporate Intellectual Property-us, Uw2220; P. O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20040038982 Date filed: February 5, 2003 Abstract: This invention relates to substituted heterocyclic compounds which are modulators, agonists or antagonists, of the CCR5 receptor. In addition, this invention relates to the treatment and prevention of disease states mediated by CCR5, including, but not limited to, asthma and atopic disorders (for example, atopic dermatitis and allergies), rheumatoid arthritis, sarcoidosis, or idiopathic pulmonary fibrosis and other fibrotic diseases, atherosclerosis, psoriasis, autoimmune diseases such as multiple sclerosis, treating and/or preventing rejection of transplanted organs, and inflammatory bowel disease, all in mammals, by the use of substituted heterocyclic compounds which are CCR5 receptor antagonists. Furthermore, since CD8+ T cells have been implicated in COPD, CCR5 may play a role in their recruitment and therefore antagonists to CCR5 could provide potential therapeutic in the treatment of COPD. Also, since CCR5 is a co-receptor for the entry of HIV into cells, selective receptor modulators may be useful in the treatment of HIV infection. Excerpt(s): This invention relates to substituted heterocyclic compounds which are modulators, agonists or antagonists, of the CC chemokine receptor CC-CKR5 now designated as CCR5 (Nature Medicine 1996, 2, 1174-8). In addition, this invention relates to the treatment and prevention of disease states mediated by CCR5. T cells are not only

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key regulators of the immune response to infectious agents but are believed critical for the initiation and maintenance of the inflammatory reaction in a variety of chronic diseases. Increased numbers or enhanced activation state of T cells, especially CD4+ T cells, have been demonstrated in the synovium of individuals with rheumatoid arthritis (M. J. Elliott and R. N. Maini, Int. Arch. Allergy Immunol. 104: 112-1125, 1994), in the bronchial mucosa of asthmatics (C. J. Corrigan and A. B. Kay, Immunol. Today 13:501506, 1992), in the lesions of multiple sclerosis (R. Martin and H. F. McFarland, Crit. Rev. Clin. Lab. Sci. 32: 121-182, 1995), in psoriatic lesions (J. L. Jones, J. Berth-Jone, A. Fletcher and P. E. Hutchinson, J. Pathol. 174: 77-82, 1994) and in the fatty streaks of atherosclerosis (R. Ross, Annu. Rev. Physiol. 57: 791-804, 1995). T cells, as well as other inflammatory cells, will migrate into tissues in response to the production of a variety of chemotactic factors. Among these factors are a superfamily of 8-12 kDa proteins known as the chemokines. These proteins share structural features such as the presence of 3-4 conserved cysteine residues. RANTES, which stands for Regulated upon Activation Normal T cell Expressed and Secreted, is an 8 kDa protein member of CC branch of the chemokine family. These proteins recruit and activate immune and inflammatory cells through an interaction with G-protein coupled receptors. The CC branch is defined by the absence of an intervening amino acid residue between the first two cysteine residues and members of this family predominately elicit the migration of mononuclear cells, eosinophils and basophils (M. Baggiolini, B. Dewald, and B. Moser, Adv. Immunol. 55: 97-179, 1994; and J. J. Oppenheim, C. O. C. Zachariae, N. Mukaida, and K. Matsushima, Annu. Rev. Immunol. 9: 617-648, 1991). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Compounds and methods for treatment of asthma, allergy and inflammatory disorders Inventor(s): Cai, Xiong; (Belmont, MA), Chatelain, Pierre; (Woluwe Saint Pierre, BE), Differding, Edmond; (Louvain-La-Neuve, BE), Ellis, James; (Boxford, MA), Grewal, Gurmit; (Natick, MA), Hussoin, Sajjat; (Lexington, MA), Lassoie, Marie-Agnes; (BraineLe-Chateau, BE), Lewis, Timothy; (Marlborough, MA), Scannell, Ralph; (Hopkinson, MA), Toy-Palmer, Anna; (Arlington, MA), Young, Michelle; (Belmont, MA) Correspondence: Michael S. Greenfield; Mcdonnell Boehnen Hulbert & Berghoff; 32nd Floor; 300 S. Wacker Drive; Chicago; IL; 60606; US Patent Application Number: 20030220347 Date filed: September 12, 2002 Abstract: The present invention provides 1,4 substituted piperazines, 1,4 substituted piperidines, and 1-substituted,4-alkylidenyl piperidines compounds. The compounds of the invention are dual acting molecules having both leukotriene inhibition properties as well as antihistaminergic properties. The compounds of the invention are useful for treating conditions in which there is likely to be a histamine and/or leukotriene component. These conditions include preferably asthma, seasonal and perennial allergic rhinitis, sinusitus, conjunctivitis, food allergy, scombroid poisoning, psoriasis, urticaria, pruritus, eczema, rheumatoid arthritis, inflammatory bowel disease, chronic obstructive pulmonary disease, thrombotic disease and otitis media. Also provided are methods of treating asthma and rhinitis by administering an effective asthma and rhinitis-relieving amount of the compounds to a subject in need thereof. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/126,521, filed Mar. 26, 1999. The invention relates to the field of 1,4 substituted

Patents 187

piperazines, 1,4 substituted piperidines, and 1-substituted, 4-alkylidenyl piperidines. Leukotrienes are potent local mediators, playing a major role in inflammatory and allergic responses including arthritis, asthma, psoriasis, and thrombotic disease. Leukotrienes are straight chain eicosanoids produced by the oxidation of arachidonic acid by lipoxygenases. Arachidonic acid is oxidized by 5-lipoxygenase and ultimately converted to leukotrienes A4, B4, C4, D4 or E4. 15-Lipoxygenase is responsible for the conversion of arachidonic acid to various biologically active metabolites including 15hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE). Both of these mediators have been implicated in the pathogenesis of airway and allergic diseases such as asthma by contributing to bronchoconstriction, mucus secretion, and eosinophil migration. A mixture of one or more of such leukotrienes are known to be potent bronchoconstrictors. Thus, leukotrienes have been shown to play an important role in the pathology of asthma. Rigorous proof for the role of leukotrienes in asthma has been provided by several pivotal clinical trials in which orally administered 5-lipoxygenase (5-LO) inhibitors (or LTD4 receptor antagonists) produce clear therapeutic benefit in asthma patients. These benefits include reduction in the use of classic asthma therapies such as beta agonists and corticosteroids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Compounds which inhibit leukocyte adhesion mediated by VLA-4 Inventor(s): Baudy, Reinhardt Bernhard; (Doylestown, PA), Grant, Francine S.; (San Francisco, CA), Konradi, Andrei W.; (San Francisco, CA), Kreft, Anthony; (Langhorne, PA), Pleiss, Michael A.; (Sunnyvale, CA), Sarantakis, Dimitrios; (Newtown, PA), Semko, Christopher M.; (Fremont, CA), Thorsett, Eugene D.; (Moss Beach, CA) Correspondence: Gerald F. Swiss; Burns, Doane, Swecker & Mathis, L.L.P.; P.O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20040006093 Date filed: March 7, 2003 Abstract: Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/______, which was converted pursuant to 37 C.F.R.sctn.1.53(c)(2)(i) from U.S. patent application Ser. No. 08/904,423, filed Jul. 31, 1997, which application is incorporated herein by reference in its entirety. This invention relates to compounds which inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. All of the above publications, patents and patent applications are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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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 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

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Immunoregulatory compounds and derivatives and methods of treating diseases therewith Inventor(s): Ekwuribe, Nnochiri Nkem; (Cary, NC), Riggs-Sauthier, Jennifer A.; (Raleigh, NC) Correspondence: Myers Bigel Sibley & Sajovec; PO Box 37428; Raleigh; NC; 27627; US Patent Application Number: 20030191186 Date filed: May 23, 2003 Abstract: Compounds are disclosed having the structure of Formula I: 1where R.sup.1, R.sup.3, and R.sup.4 are independently hydrogen or C.sub.1 to C.sub.4 alkyl, and R.sup.2 is: 2where R.sup.5 is selected from the group consisting of hydrogen and C.sub.1 to C.sub.4 alkyl, or 3where R.sup.6, R.sup.7 and R.sup.8 are independently hydrogen or C.sub.1 to C.sub.4 alkyl; or the esters or pharmacologically acceptable salts thereof. Such compounds may be utilized for the prophylaxis or treatment of various diseases, particularly inflammatory conditions of the GI tract.Methods of treating inflammatory conditions of the GI tract such as inflammatory bowel disease using compounds having the following formula are also disclosed: 4where R.sup.9, R.sup.10 and R.sup.11 are independently selected from the group consisting of hydrogen and C.sub.1 to C.sub.4 alkyl, and R.sup.12 is selected from the group consisting of hydrogen and --C(O)R.sup.13, where R.sup.13 is a C.sub.1 to C.sub.6 alkyl or an aryl group. Excerpt(s): This application is a divisional application of, and claims priority to, U.S. patent application Ser. No. 09/942,464, filed Aug. 29, 2001, allowed, which claims priority to U.S. Provisional Application No. 60/228,683, filed Aug. 29, 2000, the disclosures of each of which are incorporated herein by reference in their entireties. The present invention relates to immunoregulatory compounds and methods of treating diseases therewith. Many people suffer from inflammatory bowel disease (IBD). IBD is a generic term used to refer to two inflammatory diseases, ulcerative colitis and Crohn's disease. Ulcerative colitis is a chronic inflammatory disease of unknown etiology that affects various portions of the gastrointestinal (GI) tract, particularly the lower GI tract, and more particularly the colon and/or rectum. Crohn's disease is a serious inflammatory disease of the GI tract. It predominates in the small intestine (ileum) and the large intestine (colon). Various medications are being used to treat inflammatory bowel disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method and composition for treatment of inflammatory bowel disease Inventor(s): Bergeron, Raymond J. JR.; (Gainesville, FL) Correspondence: Miles & Stockbridge P.C.; Suite 500; 1751 Pinnacle Drive; Mclean; VA; 22102-3833; US Patent Application Number: 20030211978 Date filed: June 12, 2003 Abstract: A composition in unit dosage form for the inhibition, prevention or treatment of inflammatory bowel disease comprising an effective amount of a compound having the formula: 1and a pharmaceutically acceptable carrier therefor. Also disclosed is a method for the inhibition, prevention or treatment of inflammatory bowel disease

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comprising administering to a human or non-human mammal in need thereof an effective amount of a compound having the formula: 2 Excerpt(s): The present invention relates to the treatment of inflammatory bowel diseases. Inflammatory bowel disorders or diseases (IBD) encompass a spectrum of overlapping clinical diseases that appear to lack a common etiology. IBD, however, are characterized by chronic inflammation at various sites in the gastrointestinal (GI) tract. Illustrative IBD are regional enteritis (or Crohn's disease), idiopathic ulcerative colitis, idiopathic proctocolitis and infectious colitis. Most hypotheses regarding the pathogenesis of IBD concern the implication of immunologic, infectious and dietary factors. IBD are characterized histopathologically by ulceration, pseudomembranes, radiologically visible lesions, edema and the build-up of inflammatory cells; symptoms involve diarrhea, abdominal pain, weight loss and hypoproteinemia. Descriptions in the literature include Northfield, Drugs, Vol. 14, pages 198-206 (1977); Blaker et al, Eur. J. Pediatr., Vol. 139, pages 162-164 (1982); Singleton, The Gastroenterology Annual, pages 268-310 (1983); Saco et al, J. Amer. Acad. Dermatol., Vol. 4, pages 619-629 (1981); Prantera et al, Ital. J. Gastroenterol., Vol. 13, pages 24-27 (1981); Sales et al, Arch. Int. Med., Vol. 143, pages 294-299 (1983); and Ament, Inflammatory Bowel Diseases, Martinus Nijhoff Publ., Boston, Mass., pages 254-268 (1982). Less frequent, but also possible, are mucosal inflammation of other sections of the GI tract, such as duodenitis, jejunitis and proctitis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Method for treating inflammation Inventor(s): Blumberg, Hal; (Seattle, WA), Chandrasekher, Yasmin A.; (Mercer Island, WA), Eagan, Maribeth A.; (Seattle, WA), Foster, Donald C.; (Lake Forest Park, WA), Jaspers, Stephen R.; (Edmonds, WA), Kelly, James D.; (Mercer Island, WA), Madden, Karen L.; (Bellevue, WA), Novak, Julia E.; (Bainbridge Island, WA), Sprecher, Cindy A.; (Seattle, WA), Thompson, Penny; (Snohomish, WA), Xu, Wenfeng; (Mukilteo, WA) Correspondence: Shelby J. Walker; Zymogenetics, INC.; 1201 Eastlake Avenue East; Seattle; WA; 98102; US Patent Application Number: 20040005320 Date filed: April 28, 2003 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 injury, bacterial pneumonia, inflammatory bowel disease, rheumatoid arthritis, asthma, ulcerative colitis and Crohn's disease. Excerpt(s): The present application is a divisional application of U.S. application Ser. No. 09/746,359, filed Dec. 22, 2000, which claims priority under 35 U.S.C.sctn.119(e) to U.S. Provisional Patent Application 60/171,969, filed Dec. 23, 1999 and U.S. Provisional Application No. 60/213,341 filed Jun. 22, 2000. 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

Patents 191

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. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Method for treating inflammatory bowel disease and other forms of gastrointestinal inflammation Inventor(s): Rachmilewitz, Daniel; (Tel Aviv, IL), Raz, Eyal; (Del Mar, CA) Correspondence: Bozicevic, Field & Francis Llp; 200 Middlefield RD; Suite 200; Menlo Park; CA; 94025; US Patent Application Number: 20030176389 Date filed: April 11, 2003 Abstract: The invention provides a method for ameliorating gastrointestinal inflammation, particularly chronic gastrointestinal inflammation such as inflammatory bowel disease (IBD), in a subject. In one embodiment, the method comprises administering an immunomodulatory nucleic acid to a subject suffering from or susceptible to gastrointestinal inflammation. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/184,256, filed Feb. 23, 2000, which application is incorporated herein by reference in its entirety. The invention relates to a method for ameliorating inflammation of the gastrointestinal tract, such as that associated with inflammatory bowel disease, in a subject. The method involves administering a nucleic acid comprising an immunomodulatory nucleotide sequence to the subject. The immunomodulatory sequence can be administered alone or together with an additional therapeutic agents. Gastrointestinal inflammation is one of the most common types of inflammatory process which affects humans (for a review, see, e.g., Bamford, FEMS Immunol Med Microbiol (1999) 24(2):161-8). Inflammatory bowel disease (IBD), a form of chronic gastrointestinal inflammation, includes a group of chronic inflammatory disorders of generally unknown etiology, e.g., ulcerative colitis (UC) and Crohn's disease (CD). Clinical and experimental evidence suggest that the pathogenesis of IBD is multifactorial involving susceptibility genes and environmental factors (Sartor Am J Gastroenterol. (1997) 92:5S-11S). The interaction of these factors with the immune system leads to intestinal inflammation and dysregulated mucosal immunity against commensal bacteria, various microbial products (e.g., LPS) or antigens (Mayer et al. Current concept of IBD: Etiology and pathogenesis. In "Inflammatory Bowel Disease" 5.sup.th edition 2000, Kirsner JB editor. W. B. Sanunders Company, pp 280-296; for a discussion of IBD in children see, e.g., Walker-Smith, Postgrad Med J (2000) 76(898):46972). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of treating anemia Inventor(s): Creasy, Caretha; (Erdenheim, PA), Dillon, Susan B.; (Chester Springs, PA), Lord, Kenneth A.; (Collegeville, PA) Correspondence: Ratner & Prestia; P.O. Box 980; Valley Forge; PA; 19482-0980; US Patent Application Number: 20030176375 Date filed: May 14, 2001 Abstract: hYAK3-2 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing hYAK3-2 polypeptides and polynucleotides in the design of protocols for the treatment of bone loss including osteoporosis; inflammatory diseases such as Adult Respiratory Disease Syndrome (ARDS), Rheumatoid arthritis, Osteoarthritis, Inflammatory Bowel Disease (IBD), psoriasis, dermatitis, asthma, allergies; infections such as bacterial, fungal, protozoan and viral infections, particularly infections caused by HIV-1 or HIV-2; HIV-associated cachexia and other immunodeficiency disorders; septic shock; pain; injury; cancers including testicular cancer; anorexia; bulimia; neutropenia; cytopenia; anemias, including anemias due to renal insufficiency or to chronic disease, such as autoimmunity or cancer, and drug-induced anemias; polycythemia; myelosuppression; Parkinson's disease; cardiovascular disease including restenosis, atherosclerosis, acute heart failure, myocardial infarction; hypotension; hypertension; urinary retention; angina pectoris; ulcers; benign prostatic hypertrophy; and psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, delirium, dementia, severe mental retardation and dyskinesias, such as Huntington's disease or Gilles dela Tourett's syndrome., among others, and diagnostic assays for such conditions. Excerpt(s): This application claims priority to U.S. Ser. No. 60/118,045 filed Feb. 1, 1999, which is incorporated by reference in its entirety. This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to a serine/threonine protein kinase, hereinafter referred to as hYAK3-2. The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. A number of polypeptide growth factors and hormones mediate their cellular effects through a signal transduction pathway. Transduction of signals from the cell surface receptors for these ligands to intracellular effectors frequently involves phosphorylation or dephosphorylation of specific protein substrates by regulatory protein serine/threonine kinases (PSTK) and phosphatases. Serine/threonine phosphorylation is a major mediator of signal transduction in multicellular organisms. Receptor-bound, membranebound and intracellular PSTKs regulate cell proliferation, cell differentiation and signalling processes in many cell types. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of treating inflammatory conditions with progesterone or progesterone analogs Inventor(s): Schreiber, Alan D.; (Philadelphia, PA) Correspondence: Finnegan, Henderson, Farabow, Garrett & Dunner; Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20040038954 Date filed: June 24, 2003 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 application claims priority to U.S. Provisional Patent Application No. 60/156,434, filed Sep. 28, 1999. 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. "Inflammatory bowel disease" (IBD) encompasses the idiopathic, chronic inflammatory bowel diseases ulcerative colitis (UC), Crohn's disease (CD), and proctitis. Researchers do not know the cause of these diseases, but believe that they involve genetic and immunologic influences on the gastrointestinal tract's ability to distinguish foreign from self-antigens and/or to alter the mucosal immune response. They share many overlapping epidemiological, clinical, and therapeutic features IBD affects up to 1,000,000 Americans and disease symptoms can be so severe as to prevent the patient from carrying on a normal life. The total cost of the disease, including lost productivity, in the US is two billion dollars per year. Ward et al., Clinical economics review: medical management of inflammatory bowel disease; Ailment Pharmacol Ther 13:15-25 (1999). Drug therapies that allow patients to avoid surgical intervention could reduce the cost significantly. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods and compositions relating to modulation of A20 Inventor(s): Boone, David; (Chicago, IL), Lee, Eric; (Torrance, CA), Ma, Averil; (Chicago, IL) Correspondence: Robert E. Hanson; Fulbright & Jaworski L.L.P.; Suite 2400; 600 Congress Avenue; Austin; TX; 78701; US Patent Application Number: 20030171253 Date filed: April 18, 2002 Abstract: The invention provides compositions and methods for treating diseases characterized by aberrant programmed cell death and/or inflammation, comprising mediating A20 function in the subject. Such diseases include Crohn's disease, inflammatory bowel disease, a disease associated with ischemic injury, a toxin-induced

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liver disease and cancer. The invention further provides methods and compositions for assays for modulators of A20. Excerpt(s): This application claims the priority of U.S. Provisional Patent Application Serial No. 60/285,427, filed Apr. 19, 2001, the entire disclosure of which is specifically incorporated herein by reference. The present invention relates generally to the field of medicine. More particularly, it concerns compositions and methods for treating disease conditions comprising modulating A20. Intestinal inflammatory responses to microbial pathogens must be delicately balanced to effectively eliminate pathogens while preventing autoimmunity. The critical roles of cytokines in maintaining this balance have been demonstrated in both experimental models such as gene targeted transgenic mice and in human IBD patients. (Sadlock et al., 1993; Willerford et al., 1995; Kuhn et al., 1993; Blumberg et al., 1999; Fiocchi, 1999). One of the most important cytokines for regulating intestinal inflammation is tumor necrosis factor (TNF). The critical roles of TNF in this regard are highlighted both by animal studies showing that TNF overexpression by targeted deletion of TNF 3' untranslated mRNA stability elements leads to ileitis and arthritis (TNF.sup.DELTA.ARE mice) (Kontoyiannis et al., 1999), and by human studies and clinical experience showing that IBD patients express high levels of TNF and frequently respond to anti-TNF therapy (Targan et al., 1997; Rutgeerts et al., 1999). These observations indicate that TNF is a critical regulator of immune homeostasis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Novel human gene relating to respiratory diseases, obesity, and inflammatory bowel disease Inventor(s): Allen, Kristin; (Hopkinton, MA), Del Mastro, Richard G.; (Norfolk, MA), Dupuis, Josee; (Newton, MA), Eerdewegh, Paul Van; (Weston, MA), Keith, Tim; (Bedford, MA), Little, Randall D.; (Newtonville, MA), Pandit, Sunil; (Gaithersburg, MD), Simon, Jason; (Westfield, NJ) Correspondence: Morgan & Finnegan, L.L.P.; 345 Park Avenue; New York; NY; 10154; US Patent Application Number: 20040002470 Date filed: October 17, 2002 Abstract: This invention relates to genes identified from human chromosome 20p13-p12, which are associated with various diseases, including asthma. The invention also relates to the nucleotide sequences of these genes, isolated nucleic acids comprising these nucleotide sequences, and isolated polypeptides or peptides encoded thereby. The invention further relates to vectors and host cells comprising the disclosed nucleotide sequences, or fragments thereof, as well as antibodies that bind to the encoded polypeptides or peptides. Also related are ligands that modulate the activity of the disclosed genes or gene products. In addition, the invention relates to methods and compositions employing the disclosed nucleic acids, polypeptides or peptides, antibodies, and/or ligands for use in diagnostics and therapeutics for asthma and other diseases. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 10/126,022 filed Apr. 19, 2002, which is a continuation-in-part of U.S. application Ser. No. 09/834,597 filed Apr. 13, 2001, which is a continuation-in-part of U.S. application Ser. No. 09/548,797, filed Apr. 13, 2000, which are hereby incorporated by reference

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herein in their entirety. This invention relates to genes identified from human chromosome 20p13-p12, including Gene 216, which are associated with asthma, obesity, inflammatory bowel disease, and other human diseases. The invention also relates to the nucleotide sequences of these genes, including genomic DNA sequences, cDNA sequences, single nucleotide polymorphisms, alleles, and haplotypes. The invention further relates to isolated nucleic acids comprising these nucleotide sequences, and isolated polypeptides or peptides encoded thereby. Also related are expression vectors and host cells comprising the disclosed nucleic acids or fragments thereof, as well as antibodies that bind to the encoded polypeptides or peptides. The present invention further relates to ligands that modulate the activity of the disclosed genes or gene products. In addition, the invention relates to diagnostics and therapeutics for various diseases, including asthma, utilizing the disclosed nucleic acids, polypeptides or peptides, antibodies, and/or ligands. Mouse chromosome 2 has been linked to a variety of disorders including airway hyperesponsiveness and obesity (DeSanctis et al., 1995, Nature Genetics, 11:150-154; Nagle et al., 1999, Nature, 398:148-152). This region of the mouse genome is homologous to portions of human chromosome 20 including 20p13p12. Although human chromosome 20p13-12p has been linked to a variety of genetic disorders including diabetes insipidus, neurohypophyseal, congenital endothelial dystrophy of cornea, insomnia, neurodegeneration with brain iron accumulation 1 (Hallervorden-Spatz syndrome), fibrodysplasia ossificans progressive, alagille syndrome, hydrometrocolpos (McKusick-Kaufman syndrome), Creutzfeldt-Jakob disease and Gerstmann-Straussler disease (see NCBI; National Center for Biotechnology Information, National Library of Medicine, 38A, 8N905, 8600 Rockville Pike, Bethesda, Md. 20894; at www (world wide web) ncbi.nlm.nih.gov) the genes affecting these disorders have yet to be discovered. There is a need in the art for identifying specific genes relating to these disorders, as well as genes associated with obesity, lung disease, particularly, inflammatory lung disease phenotypes such as Chronic Obstructive Lung Disease (COPD), Adult Respiratory Distress Syndrome (ARDS), and asthma. Identification and characterization of such genes will make possible the development of effective diagnostics and therapeutic means to treat lung-related disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

NOVEL MUCOSAL VASCULAR ADDRESSINS Inventor(s): BRISKIN, MICHAEL J.; (LEXINGTON, MA) Correspondence: Hamilton, Brook, Smith & Reynolds, P.C.; 530 Virginia Road; P.O. Box 9133; Concord; MA; 01742-9133; US Patent Application Number: 20040023373 Date filed: September 1, 1995 Abstract: The present invention relates to isolated and/or recombinant nucleic acids which encode primate MAdCAMs, and to proteins or polypeptides referred to herein as isolated and/or recombinant primate MAdCAMs. The invention further relates to recombinant nucleic acid constructs, comprising a nucleic acid which encodes a primate MAdCAM of the present invention, a portion thereof, or a variant; to host cells comprising such constructs, useful for the production of recombinant proteins; the use of nucleic acids and/or proteins in assays to identify inhibitors (e.g., antagonists) of primate MAdCAM function; and to antibodies reactive with primate MAdCAM, which are useful in in vitro methods, diagnostic and/or therapeutic application.The invention also relates to the treatment of individuals, particularly humans, suffering from a

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disease (e.g., inflammatory bowel disease) associated with leukocyte recruitment to the intestinal tract or other tissues as a result of binding of leukocytes to cells expressing the molecule MAdCAM (gut-associated endothelium), comprising administering to the individual an effective amount of an agent, such as an antibody which inhibits the binding of leukocytes to MAdCAM. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 08/386,857 (Attorney Docket No. LKS94-04), filed Feb. 10, 1995, which is incorporated herein by reference in its entirety. Lymphocyte homing from the circulation to the lymphoid tissues and migration to sites of inflammation is regulated by interaction with receptors expressed in postcapillary venules, including high endothelial venules (HEV) found in secondary lymphoid tissues (e.g., mesenteric lymph nodes, Peyer's Patches (PP)) (Bevilacqua, M. P., Annu. Rev. Immunol., 11:767-804 (1993); Butcher, E. C., Cell, 67: 1033-1036 (1991); Picker, L. J., et al., Annu. Rev. Immunol., 10:561-591 (1992); and Springer, T. A., Cell, 76: 301-314 (1994)). These interactions are tissue specific in nature. Inflammation (e.g., chronic inflammation) is characterized by infiltration of the affected tissue by leukocytes, such as lymphocytes, lymphoblasts, and mononuclear phagocytes. The remarkable selectivity by which leukocytes preferentially migrate to various tissues during both normal circulation and inflammation results from a series of adhesive and activating events involving multiple receptor-ligand interactions as proposed by Butcher and others (Butcher, E. C., Cell, 67: 1033-1036 (1991); vonAndrain, U. H., et al., Proc. Natl. Acad. Sci. USA, 88:7538 (1991); Mayadas, T. N., et al., Cell, 74:541 (1993); (Springer, T. A., Cell, 76:301 (1994)). As an initial step, there is a transient, rolling interaction between leukocytes and endothelium, which results from the interaction of selectins (and by.alpha.4 integrins in some instances) with their carbohydrate ligands. This interaction which is characterized by rolling in the direction of flow can be assessed by known methods (Lawrence, M. B. and T. A. Springer, Cell, 65:859 (1991); WO 92/21746, Springer et al., (Dec. 10, 1992)). This is followed by activation events mediated by chemoattractants such as chemokines and their receptors, which cause activation of integrin adhesiveness and influence the direction of migration of leukocytes through vascular walls. Such secondary signals in turn trigger the firm adhesion of leukocytes to endothelium via leukocyte integrins and their endothelial ligands (Ig-like receptors and the ECM), and subsequent transendothelial migration from the circulation across the vascular endothelium. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Novel thiocarbamic acid derivatives and the pharmaceutical compositions containing the same Inventor(s): Kim, Hee Doo; (Seoul, KR), Lee, Jee Woo; (Seoul, KR), Oh, Uh Taek; (Kyunggi-do, KR), Park, Hyeung Geun; (Seoul, KR), Park, Young Ho; (Seoul, KR), Suh, Young Ger; (Kyunggi-do, KR), Yi, Jung Bum; (Kyunggi-do, KR) Correspondence: Finnegan, Henderson, Farabow, Garrett & Dunner; Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20030203944 Date filed: February 3, 2003 Abstract: The present invention relates to an antagonist against vanilloid receptor and the pharmaceutical compositions containing the same. As diseases associated with the activity of vanilloid receptor, pain, acute pain, chronic pain, neuropathic pain, postoperative pain, migraine, arthralgia, neuropathies, nerve injury, diabetic neuropathy,

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neurodegeneration, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, irritable bowel syndrome, a respiratory disorder such as asthma or chronic obstructive pulmonary disease, irritation of skin, eye or mucous membrane, fevescence, stomachduodenal ulcer, inflammatory bowel disease and inflammatory diseases can be enumerated. The present invention provides a pharmaceutical composition for prevention or treatment of these diseases. Excerpt(s): The present invention relates to thiocarbamic acid derivatives and the pharmaceutical compositions containing the same, and particularly, to novel thiocarbamic acid derivatives as an antagonist against vanilloid receptor (VR) and the pharmaceutical compositions thereof. As diseases associated with the activity of vanilloid receptor, pain, acute pain, chronic pain, neuropathic pain, post-operative pain, migraine, arthralgia, neuropathies, nerve injury, diabetic neuropathy, neurodegeneration, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, irritable bowel syndrome, a respiratory disorder such as asthma or chronic obstructive pulmonary disease, irritation of skin, eye or mucous membrane, fervescence, stomachduodenal ulcer, inflammatory bowel disease and inflammatory diseases can be enumerated. The present invention provides pharmaceutical compositions for prevention or treatment of these diseases. Yet, the diseases described above are only for enumeration, not to limit the scope of clinical application of vanilloid receptor antagonist. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Piperidine derivatives useful as CCR5 antagonists Inventor(s): Miller, Michael W.; (Westfield, NJ), Palani, Anandan; (Bridgewater, NJ), Scott, Jack D.; (Springfield, NJ) Correspondence: Schering-plough Corporation; Patent Department (k-6-1, 1990); 2000 Galloping Hill Road; Kenilworth; NJ; 07033-0530; US Patent Application Number: 20040010008 Date filed: August 28, 2002 Abstract: The present invention provides a compound of the formula 1or a pharmaceutically acceptable salt or solvate thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.9, R.sup.10, A and B are as defined in the specification. The present invention also provides pharmaceutical compositions containing the compound of this invention, and methods of treatment using the compound of this invention. The invention also relates to the use of a combination of a compound of this invention and one or more antiviral or other agents useful in the treatment of Human Immunodeficiency Virus (HIV). The invention further relates to the use of a compound of this invention, alone or in combination with another agent, in the treatment of solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/315683, filed Aug. 29, 2001. The present invention relates to piperidine derivatives useful as selective CCR5 antagonists, pharmaceutical compositions containing the compound of this invention, and methods of treatment using the inventive compounds. The invention also relates to the use of a combination of the compound of this invention and one or more antiviral or other agents useful in the treatment of Human Immunodeficiency Virus (HIV). The invention further relates to the use of the

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compound of this invention, alone or in combination with another agent, in the treatment of solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis. The global health crisis caused by HIV, the causative agent of Acquired Immunodeficiency Syndrome (AIDS), is unquestioned. While recent advances in drug therapies have been successful in slowing the progression of AIDS, there is still a need to find a safer, more efficient, less expensive way to control the virus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Recombinant anti-VLA-4 antibody molecules Inventor(s): Carr, Frank J.; (Balmedie, GB), Lobb, Roy R.; (Westwood, MA), Tempest, Philip R.; (Royston, GB) Correspondence: Fish & Richardson PC; 225 Franklin ST; Boston; MA; 02110; US Patent Application Number: 20030185819 Date filed: May 2, 2003 Abstract: The present invention disclosed recombinant anti-VLA-4 antibody molecules, including humanized recombinant anti-VLA-4 antibody molecules. These antibodies are useful in the treatment of specific and non-specific inflammation, including asthma and inflammatory bowel disease. In addition, the humanized recombinant anti-VLA-4 antibodies disclosed can be useful in methods of diagnosing and localizing sites of inflammation. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 08/004,798, filed Jan. 12, 1993 and PCT/US94/00266, filed Jan. 7, 1994. The present invention relates to recombinant anti-VLA-4 antibody molecules, including humanized recombinant anti-VLA-4 antibody molecules. Natural immunoglobulins have been known for many years, as have the various FRAGMENTS thereof, such as the Fab, (Fab').sub.2 and Fe fragments, which can be derived by enzymatic cleavage. Natural immunoglobulins comprise generally a Y-shaped molecule having an antigen-binding site towards the free end of each upper arm. The remainder of the structure, and particularly the stem of the Y, mediates the effector functions associated with immunoglobulins. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Reverse-turn mimetics and methods relating thereto Inventor(s): Eguchi, Masakatsu; (Seattle, WA), Kahn, Michael; (Kirkland, WA), Kim, Hwa-Ok; (Redmond, WA), Stasiak, Marcin; (Seattle, WA) Correspondence: Seed Intellectual Property Law Group Pllc; 701 Fifth Ave; Suite 6300; Seattle; WA; 98104-7092; US Patent Application Number: 20040029868 Date filed: February 7, 2003 Abstract: Conformationally constrained compounds which mimic the secondary structure of reverse-turn regions of biologically active peptides and proteins are disclosed. Such reverse-turn mimetics have utility in the treatment of cell adhesion-

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indicated diseases, such as multiple sclerosis, atherosclerosis, asthma and inflammatory bowel disease. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 08/846,432, filed Apr. 30, 1997, which is a continuation in part of U.S. application Ser. No. 08/549,007, filed Oct. 27, 1995. The present invention relates generally to reverseturn mimetics, including inhibitors of cell adhesion-mediated disease, as well as to a chemical library of reverse-turn mimetics. Cell adhesion is critical to the viability of living organisms. Adhesion holds multicellular tissues together and directs embryonic development. It plays important roles in wound healing, eradication of infection and blood coagulation. Integrins are a family of cell surface proteins intimately involved in all of these functions. They have been found in nearly every type of human cell except red blood cells. Abnormalities in integrin function contribute to a variety of disorders including inflammatory diseases, heart attack, stroke, and cancer. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Sodium salt of an azo derivative of 5-aminosalicylic acid Inventor(s): Carceller, Elena; (Barcelona, ES), Escamilla, Jose Ignacio; (Barcelona, ES), Forn, Javier; (Barcelona, ES), Ramis, Joaquim; (Barcelona, ES), Salas Solana, Jorge; (Barcelona, ES) Correspondence: Burns Doane Swecker & Mathis L L P; Post Office Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030176401 Date filed: May 6, 2003 Abstract: The present invention relates to the sodium salt of (Z)-2-hydroxy-5-[[4-[3-[4[(2-methyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl]-1-piperidinyl]-3-oxo-1-phenyl-1propenyl]phenyl]azo]benzoic acid, as well as to the pharmaceutical compositions containing it, to a procedure for its preparation and to its use. for the manufacture of medicaments for the treatment or prevention of inflammatory bowel disease. Excerpt(s): The present invention relates to a new salt of an azo derivative of 5aminosalicylic acid, and more particularly to the sodium salt of (Z)-2-hydroxy-5-[[4-[3[4-[(2-methyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl- ]-1-piperidinyl]-3-oxo-1-phenyl-1propenyl]phenyl]azo]benzoic acid. The present invention also relates to the pharmaceutical compositions containing it, to a procedure for its preparation and to its use for the manufacture of medicaments useful for the treatment or prevention of inflammatory bowel disease. Inflammatory bowel disease is a chronic inflammatory disease of the intestine, whose etiology is still unknown. The most prevalent forms of this disease are ulcerative colitis and Crohn's disease. The authors of the present invention have found that the levels of azoreduction observed with this compound are low when studies on the metabolization of said azo bond are carried out. Since this kind of compounds are precisely designed to be metabolized and deliver in the colon 5-ASA and the PAF antagonist, which are the active molecules, the problem arises of finding compounds that are metabolized in the colon to a greater extent. This problem is solved with the new salt that is the object of the present invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Sphingolipid derivatives and their methods of use Inventor(s): Bhalla, Kapil N.; (Atlanta, GA), Keane, Thomas E.; (Dunwoody, GA), Liotta, Dennis C.; (McDonough, GA), Merrill, Alfred H. JR.; (Dunwoody, GA), Schmelz, Eva M.; (Atlanta, GA) Correspondence: King & Spalding; 191 Peachtree Street, N.E.; Atlanta; GA; 30303-1763; US Patent Application Number: 20040039212 Date filed: August 25, 2003 Abstract: Derivatives of sphingolipids of the formula: 1are provided wherein the substituents are as defined in the specification and wherein there is at least one R.sup.2 substituent in the sphingolipid derivative. The compounds are useful in the treatment of of abnormal cell proliferation, including benign and malignant tumors, the promotion of cell differentiation, the induction of apoptosis, the inhibition of protein kinase C, and the treatment of inflammatory conditions, psoriasis, inflammatory bowel disease as well as proliferation of smooth muscle cells in the course of development of plaques in vascular tissue. The invention also includes a method for triggering the release of cytochrome c from mitochondria that includes administering an effective amount of a sphingolipid or its derivative or prodrug to a host in need thereof. Further, the invention provides a method for treating bacterial infections, including those that influence colon cancer and other disorders of the intestine, that includes administering an effective amount of one of the active compounds identified herein. Excerpt(s): This application is in the area of pharmaceutical chemistry, and in particular includes sphingolipid derivatives, prodrugs and pharmaceutical compositions and salts thereof for the treatment of abnormal cell proliferation, including benign and malignant tumors, the promotion of cell differentiation, the induction of apoptosis, the inhibition of protein kinase C, and the treatment of inflammatory conditions, psoriasis, inflammatory bowel disease as well as proliferation of smooth muscle cells in the course of development of plaques in vascular tissue. The invention also includes a method for triggering the release of cytochrome c from mitochondria that includes administering an effective amount of a sphingolipid or its derivative or prodrug to a host in need thereof. Further, the invention provides a method for treating bacterial infections, including those that influence colon cancer and other disorders of the intestine, that includes administering an effective amount of one of the active compounds identified herein. Mammalian sphingolipid compounds typically vary in the presence or absence of: (I) the 4,5-trans-double bond (for example, sphingosine has a double bond whereas sphinganine (also referred to as dihydrosphingosine) does not); (ii) double bond(s) at other positions, such as position 8; (iii) a hydroxyl group at position 4 (D-1hydroxysphinganine, also called "phytosphingosine") or elsewhere (Robson et al., J. Lipid Res. 35:2060-2068, 1994); (iv) methyl group(s) on the alkyl side chain or on the amino group, such as N,N,-dimethylsphingosine; and (v) acylation of the amino group (for example ceramide (also referred to as N-acylsphingosine), and dihydroceramide (also referred to as N-acyl-sphinganine)). The 4-hydroxysphinganines are the major long-chain bases of yeast (Wells, G. B. and Lester, R. L., J. Biol. Chem., 258:10200-10203, 1983), plants (Lynch, D. V., Lipid Metabolism in Plants (T. S. Moore, Jr., ed.), pp. 285308, CRC Press, Boca Raton, Fla. 1993), and fungi (Merrill et al., Fungal Lipids (R. Prasad and M. Ghanoum, eds.), CRC Press, Boca Raton, Fla., 1995a), but are also made by mammals (Crossman and Hirschberg, J. Biol. Chem, 252:5815-5819, 1977). Other modifications of the long-chain base backbone include phosphorylation at the hydroxyloxygen of carbon I (Buehrer and Bell, Adv. Lipid Res. 6:59-67, 1993), and

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acylation (Merrill and Wang, Methods Enzymol,. 209:427-437, 1992) (Igarashi and Hakomori, Biochim. Biophys. Res. Commun. 164:1411-1416, 1989; Felding-Habermann et al., Biochemistry 29:6314-6322, 1990) of the amino group. Each of these compounds can be found in various alkyl chain lengths, with 18 carbons predominating in most sphingolipids, but other homologs can constitute a major portion of specific sphingolipid (as exemplified by the large amounts of C.sub.20 sphingosine in brain gangliosides) (Valsecchi et al., J. Neurochem., 60:193-196, 1993) and in different sources (e.g., C.sub.16 sphingosine is a substantial component of milk sphingomyelin) (Morrison, Biochim. Biophys. Acta., 176:537-546, 1969). One difficulty in studying these compounds is that relatively few are commercially available in chemically-pure form. For example, most of the sphinganine that can be purchased from various vendors is a mixture of the D and L enantiomers (therefore, commercially available dihydroceramides are also mixtures) and the metabolism, and some of the functions, of these compounds are sensitive to stereochemistry (Stroffel and Bister, Hoppe-Seyler's Z. Physiol. Chem. 354:169-181, 1973; Buehrer and Bell, J. Biol. Chem. 267:3154-3159, 1992; Adv. Lipid Res. 26:59-67, 1993; Hauser et al., J. Biol. Chem. 269:6803-6809, 1994; Olivera et al., J. Biol. Chem. 269:17924-17930, 1994). For example, sphingosine kinase (which forms the signaling compound sphingosine 1-phosphate) will act only on the erythro stereoisomers--the threo stereoisomers are inhibitors of the enzyme (Buehrer and Bell, J. Biol. Chem. 267:3154-3159, 1992; Adv. Lipid Res. 26:59-67, 1993). Release of intracellular calcium is limited to D-(+)-erythro-sphingosine 1-phosphate. Sphingosines and other long-chain bases are cationic amphiphiles, which distinguishes them from most other naturally occurring lipids, which are neutral (including zwitterionic) or anionic. In the protonated form, they affect the phase behavior of both zwitterionic (Koiv et al., Chem. Phys. Lipids. 66:123-134, 1993; Lpez-Garcia et al., Biochim. Biophys. Acta., 1194:281-288, 1994) and acidic (Koiv et al., Chem. Phys. Lipids, 66:123-134, 1993; Lpez-Garcia et al., Biochim. Biophys. Acta. 1194:281-288, 1994) phospholipids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Therapeutic applications of T-BAM (CD40L) technology to treat diseases involving smooth muscle cells Inventor(s): Chess, Leonard; (Scarsdale, NY), Karpusas, Mihail N.; (Roslindale, MA), Thomas, David W.; (Wellesley, MA), Yellin, Michael J.; (Montclair, NJ) Correspondence: Fish & Neave; 1251 Avenue OF The Americas; 50th Floor; New York; NY; 10020-1105; US Patent Application Number: 20030219437 Date filed: November 15, 2002 Abstract: Activation of smooth muscle cells bearing CD40 on their cell surface by CD40 ligand is inhibited by contacting the smooth muscle cells with an anti-T-BAM (CD40L) antibody capable of inhibiting the interactions between CD40 ligand and the CD40bearing smooth muscle cells, in an amount effective to inhibit activation of the smooth muscle cells. Activation of smooth muscle cells bearing CD40 on their surface by CD40 ligand in a subject is inhibited by administering to the subject an anti-T-BAM (CD40L) antibody capable of inhibiting the interaction between CD40 ligand and the smooth muscle cells, in an amount effective to inhibit activation of the cells. Conditions dependent on CD40 ligand-induced activation of CD40-bearing cells smooth muscle cells are treated, in particular inflammatory bowel disease.

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Excerpt(s): This application claims the priority of U.S. patent application Ser. No. 08/677,730, filed Jul. 8, 1996 the contents of which is hereby incorporated by reference into the present application. Throughout this application, various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citation for these references may be found in the text or listed by number following the Experimental Details section. CD40 is a cell surface molecule expressed on a variety of cells and interacts with a 30-33 kDa activation-induced CD4+ T cell counterreceptor termed CD40L. CD40L-CD40 interactions have been extensively studied in T cell-B cell interactions and are essential for T cell dependent B cell differentiation and IgG, IgA and IgE production. CD40 is also expressed on monocytes, dendritic cells, epithelial cells, endothelial cells and fibroblasts. CD40 expression on these cells is upregulated in vitro by cytokines, most notably IFN.gamma. Interestingly, in vivo studies have demonstrated markedly upregulated CD40 expression in inflammatory sites, such as rheumatoid arthritis synovial membrane or psoriatic plaques. In vitro studies utilizing anti-CD40 mAb or CD40L+ cells demonstrate that CD40 is functionally expressed on monocytes, dendritic cells, epithelial cells, endothelial cells and fibroblasts. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Treatment of inflammatory bowel disease using growth factors Inventor(s): Boldog, Ferenc L.; (North Haven, CT), Burgess, Catherine E.; (Wethersfield, CT), Fernandes, Elma R.; (Branford, CT), Jeffers, Michael E.; (Branford, CT), LaRochelle, William J.; (Madison, CT), Lichenstein, Henri S.; (Guilford, CT), Peterson, Jeffrey; (Brookfield, CT), Prayaga, Sudhirdas K.; (O'Fallon, MO), Rittman, Beth; (Colchester, CT), Shimkets, Juliette B.; (Guilford, CT), Shimkets, Richard A.; (Guilford, CT), Yang, Meijia; (East Lyme, CT) Correspondence: Mintz, Levin, Cohn, Ferris, Glovsky; And Popeo, P.C.; One Financial Center; Boston; MA; 02111; US Patent Application Number: 20040006015 Date filed: December 16, 2002 Abstract: The present invention is based upon methods of treating inflammatory conditions in the intestinal tract of mammals using growth factor related polypeptides. The invention includes methods of reducing the mortality rate or delaying mortality in a subject suffering from an inflammatory pathology. Methods of using fibroblast growth factor-CX (FGF-CX) polynucleotides sequences and the FGF-CX polypeptides encoded by such nucleic acid sequence, or variants, fragments and homologs thereof, are claimed in the invention. Similarly, methods of using FCTRX polynucleotide sequences and the FCTRX polypeptides encoded by such nucleic acid sequences, or variants, fragments and homologs thereof, alone or in combination, are also claimed in the invention. FCTRX collectively refers to any of six variant FCTRX sequences, variously designated FCTR1, FCTR2, FCTR3, FCTR4, FCTR5 and FCTR6. Excerpt(s): This application claims the benefit of priority from U.S. Provisional application Ser. No. 60/246,206, filed Nov. 6, 2000, U.S. Non-Provisional application Ser. No. 09/992,840, filed Nov. 6, 2001, U.S. Non-Provisional application Ser. No. 10/011,364, filed Nov. 16, 2001, and U.S. Provisional application Ser. No. 60/386,545, filed Jun. 6, 2002, the contents of which are incorporated herein in its entirety. The present invention generally relates to methods of treatment of inflammatory conditions in the intestinal

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tract of mammals using growth factor related polypeptides. More specifically, the polypeptides employed in the methods of the invention are related to a member of the fibroblast growth factor family and to a member of the platelet derived growth factor family. Inflammatory bowel disease comprises two distinct subsets: ulcerative colitis and Crohn's disease. In 1999, approximately 1.7 million people were diagnosed with this debilitating disease. Satisfactory treatment of IBD is an unmet medical need, as existing therapeutics have not been successful in curtailing the disease and preventing surgeries. Up to forty percent of all ulcerative colitis patients undergo surgery, which typically includes the removal of part of the large intestine or a full colostomy. Such surgery is not curative for Crohn's disease, as 75% of all patients undergo at least one surgery in their lifetime, and up to 90% of these patients require additional surgeries. Consequently a therapeutic that can successfully treat inflammatory bowel disease will have the beneficial effects of improving a patient's quality of life, while potentially saving the healthcare system millions of dollars in costs associated with invasive surgical procedures. 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.,25dihydroxyvitamin 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 D-resistant 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

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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 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 by introducing CEP antigen composition Inventor(s): Das, Kiron M.; (Baskin Ridge, NJ) Correspondence: Perkins Coie Llp; Post Office Box 1208; Seattle; WA; 98111-1208; US Patent Application Number: 20040029786 Date filed: May 8, 2003 Abstract: One aspect of the invention pertains to a method for treating ulcerative colitis and Crohn's disease by administering a composition comprising colonic epithelial protein (CEP) to induce tolerance. Another aspect of the invention provides for a composition comprising a colon epithelial cell extract, a LS-180 human colon cancer cell extract, a normal colon cell extract and T lymphocytes of a subject fed with the colon epithelial cell extract in the treatment of inflammatory bowel disease and/or inflammation. Yet another aspect of the invention is directed to methods for treating inflammatory bowel disease and/or inflammation by administering the aforementioned compositions to a subject. Excerpt(s): This application claims the benefit of priority to U.S. Provisional Patent Application No. 60/379,379, filed May 8, 2002, which is hereby incorporated by reference in its entirety as if fully set forth herein. This invention relates to the field of gastroenterology. Specifically it relates to the treatment of inflammatory bowel disease and/or inflammation. Inflammatory bowel disease (IBD) describes a number of gastrointestinal disorders. Of these diseases, Crohn's disease and ulcerative colitis are two of the main disease entities. Crohn's disease is a serious inflammatory disease of the gastrointestinal tract. It predominates in the ileum of the small intestine and the large intestine (colon), but may occur in any section of the gastrointestinal tract. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Tricyclic-bis-enone derivatives and methods of use thereof Inventor(s): Favaloro, Frank G.; (Norfolk, MA), Gribble, Gordon W.; (Lebanon, NH), Honda, Tadashi; (Hanover, NH), Sporn, Michael B.; (Tunbridge, VT), Suh, Nanjoo; (White River Junction, VT) Correspondence: Fulbright & Jaworski L.L.P.; A Registered Limited Liability Partnership; Suite 2400; 600 Congress Avenue; Austin; TX; 78701-3271; US Patent Application Number: 20030232786 Date filed: January 15, 2003 Abstract: Novel tricyclic-bis-enone derivatives (TBEs) as well as the process for the preparation of such TBEs are provided. Also provided are methods for prevention and/or treatment of cancer, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotropic lateral sclerosis, rheumatoid arthritis, inflammatory bowel disease, and all other diseases whose pathogenesis is believed to involve excessive production of either nitric oxide (NO) or prostaglandins or the overexpression of iNOS or COX-2 genes or gene products. Further, methods for the synthesis of the TBE compounds of the invention utilize cheap commercially available reagents and are highly cost effective and amenable to scale-up. Additional high efficiency synthetic methods that utilize novel intermediates as well as the synthesis of these intermediates are also provided. Furthermore, the invention also provides methods for designing novel and watersoluble TBEs. Excerpt(s): The present application claims priority to provisional U.S. Patent Application Serial No. 60/348,594 filed Jan. 15, 2002; provisional U.S. Patent Application Serial No. 60/376,040, filed Apr. 26, 2002 and provisional U.S. Patent Application Serial No. 60/402,966, filed Aug. 13, 2002. The entire text of each of the above referenced applications is incorporated herein by reference and without disclaimer. The present invention provides novel tricyclic-bis-enone derivatives (TBEs), as well as the process for the preparation of such TBEs, for prevention and/or treatment of cancer, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotropic lateral sclerosis, rheumatoid arthritis, inflammatory bowel disease, and other diseases whose pathogenesis is believed to involve excessive production of either nitric oxide (NO) or prostaglandins. One of the major needs in clinical oncology is the development of effective and safe new agents for chemoprevention. In particular, there is a need for chemopreventative agents targeted at mechanisms known to be involved in the process of carcinogenesis. In recent years, there has been a resurgence of interest in the study of mechanisms of inflammation that relate to carcinogenesis and in the use of such mechanisms as the basis for development of new chemopreventative agents. 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 inflammatory bowel disease, 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 “inflammatory bowel disease” (or synonyms) into the “Term 1” box. After clicking on the search button,

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scroll down to see the various patents which have been granted to date on inflammatory bowel disease. You can also use this procedure to view pending patent applications concerning inflammatory bowel disease. 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 6. BOOKS ON INFLAMMATORY BOWEL DISEASE Overview This chapter provides bibliographic book references relating to inflammatory bowel disease. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on inflammatory bowel disease 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 “inflammatory bowel disease” (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 inflammatory bowel disease: ·

Clinician's Guide to Inflammatory Bowel Disease Source: Thorofare, NJ: SLACK Incorporated. 2003. 336 p. Contact: Available from SLACK Incorporated. 6900 Grove Road, Thorofare, NJ 080869447. (856) 848-1000. Fax (856) 853-5991. Website: www.slackbooks.com. PRICE: $44.95; plus shipping and handling. ISBN: 556425546. Order number: 75546. Summary: Although the term inflammatory bowel disease (IBD) describes a wide range of inflammatory states, it generally refers to ulcerative colitis (UC) and Crohn's disease. This handbook presents an up to date guide on selected topics in IBD, focusing on those clinically important areas that have undergone recent changes or discoveries. The book offers 18 chapters: epidemiology, imaging in IBD, clinical features of UC, clinical features of Crohn's disease, postoperative recurrence of Crohn's disease, extraintestinal manifestations of IBD, cancer in IBD, complications of the ileal pouch-

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anal anastomosis, nutritional support considerations, pregnancy and fertility with IBD, indications for surgery in IBD, surgical therapy for IBD, medical therapy for Crohn's disease, medical therapy for UC, disease modifiers in IBD, evaluation of the patient suspected of having IBD, special considerations for pediatric and adolescent patients with IBD, and the medical approach to the patient with IBD. Each chapter includes references and a subject index concludes the volume. ·

If This Is A Test, Have I Passed Yet?: Living With Inflammatory Bowel Disease. 2nd ed Source: Toronto, Ontario, Canada: Macmillan Canada. 1994. 152 p. Contact: Available from Fern Publications. P.O. Box 16893, St. Louis, MO 63105. (314) 994-0052. PRICE: $12.95. ISBN: 0771590466. Summary: This book chronicles the author's life with Crohn's disease. Written in a friendly, easy-to-read style, the book takes the reader through the author's journey with the disease: the years of illness before diagnosis; the impact of learning that she had a chronic and incurable disease; the effect of Crohn's disease on her relationships with her family and friends; the fear of surgery; and the frustration and dehumanization of frequent hospitalizations. She focuses on providing practical advice about each topic as she discusses it. Two final chapters depart from the autobiographical format: one is written by her husband and provides the spouse's perspective; the other, directed at health care practitioners, offers advice on providing care to people who are chronically ill. The book concludes with a glossary and a recommended reading list.

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Challenges in Inflammatory Bowel Disease Source: Malden, MA: Blackwell Science, Inc. 2001. 294 p. 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: This book offers an approach to the subject of inflammatory bowel disease (IBD) that highlights current areas of controversy. Divided into six sections, the book covers epidemiology; etiology and pathogenesis; diagnosis and assessment; management; surveillance for colorectal cancer; long-term complications; and prognosis. The 23 chapters cover topics including chances in the incidence of IBS, the differences between familial disease and sporadic disease, the role of genetics, controversies in histopathological diagnosis, diagnostic tools, the use of mesalazine, nutritional therapy, antibiotics in treating Crohn's disease, immunosuppression and immunomodulation, the surgical management of ulcerative colitis, the causes and treatment of ileoanal pouch dysfunction, the recognition of dysplasia, cancer surveillance in colitis, the case against surveillance for colorectal cancer, growth retardation in children with IBD, osteopenia, and prognosis in IBD. Each chapter includes references and a subject index concludes the text.

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Ask Audrey: The Author's Personal and Professional Experience in the Day-to-Day Living with Inflammatory Bowel Disease Source: Detroit, MI: Audrey Kron. 1992. 156 p. Contact: Available from Center for Coping with Chronic Illness. 7466 Pebble Lane, West Bloomfield, MI 48322. (810) 626-6960. Also available from CCFA Michigan Chapter.

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31313 Northwestern Highway, Suite 209, Farmington Hills, MI 48334. (810) 737-0900. Fax (810) 737-0904. PRICE: $15 including shipping and handling. ISBN: 0963387707. Summary: This book, written by a medical psychotherapist with inflammatory bowel disease (IBD), presents practical guidelines for coping with IBD. After an introduction in which the author shares her life story, she provides chapters on general information about chronic illness; practical suggestions; relationships; emotions and IBD; and coping techniques. Practical suggestions are provided on dealing with diarrhea; choosing a doctor; going to the hospital; controlling pain; taking blood tests; travelling; total parenteral nutrition (TPN); living with TPN; deciding on an ostomy; getting out of bed; having fun despite weakness; and enjoying the holidays. Much of the information in the book is based on the Ask Audrey columns that originally appeared in the Crohn's and Colitis Foundation of America's Michigan Chapter CCFA Newsletter. ·

Inflammatory Bowel Disease. 5th ed Source: Saint Louis, MO: W.B. Saunders Company. 1999. 832 p. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department, 11830 Westline Industrial Drive, Saint Louis, MO 63146-9988. (800) 545-2522. Fax (800) 568-5136. E-mail: [email protected]. Website: www.wbsaunders.com. PRICE: $145.00 plus shipping and handling. ISBN: 0721676162. Summary: This comprehensive textbook describes all the latest scientific and clinical advances in the field of inflammatory bowel disease (IBD), including etiology and pathogenesis, evaluation and classification, medical and surgical therapies, and patient care management. Specific topics include homeostasis of the bowel in health and disease, the intestinal epithelium, the epidemiology of IBD, the genetics of Crohn's disease and ulcerative colitis, the pathogenesis of IBD, differential diagnosis, idiopathic IBD in the elderly, psychosocial factors in IBD, fertility and pregnancy in IBD, gastrointestinal malignancies in IBD, the other colitides (collagenous, lymphocytic, diversion, ischemic infections, clostridium difficile), endoscopy and radiography in IBD, medical therapy in IBD, the nutritional aspects of dealing with IBD, indications for surgery, the surgical management of patients with IBD, enterostomal care for patients with IBD, and prognostic considerations in IBD. The textbook integrates new therapeutic guidelines on the principles of induction, maintenance, and sustained control of remissions as well as discussions of current indications for surgery, the latest surgical technologies, and possible consequences of surgery. Each chapter is written by authorities in the field and includes illustrations and extensive references. The text concludes with a detailed subject index.

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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,

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despite the illness. The book includes a glossary of terms and is illustrated with pencil sketches by the author's husband. ·

Advanced Therapy of Inflammatory Bowel Disease Source: Hamilton, Ontario: B.C. Decker Inc. 2001. 670 p. 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 is 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 editors note that most readers of the text will be experienced digestive disease specialists who have already made the correct diagnosis and are now looking for another opinion regarding a new or controversial treatment modality. The text includes 138 chapters, each written by experts in the field, arranged in eleven categories: introduction, diagnostic methodology, proctosigmoiditis, ulcerative colitis, surgery for UC, complications of IBD, Crohn's disease, surgery for Crohn's disease, patient support services, behavioral therapy, and special situations. The latter sections cover IBD genetics, managing patients' concerns, lifestyle issues, the role of the IBD nurse advocate, the Crohn's and Colitis Foundation of America, pediatrics and family support, nutritional consultation and guidance, insurance and disability advocacy issues, sexual adjustments and body image, the role of clergy, psychiatric complications of IBD, stress management, behavioral pain management, fitness program, alternative patient care methods, fertility and pregnancy in IBD, colitis in the elderly, radiation enterocolitis, colitis and enteritis in immunocompromised individuals, lymphoma in IBD, and Behcet's disease. Each chapter includes a list of references and a list of supplemental reading suggestions, and is illustrated with black and white photographs, figures, and tables. A detailed subject index concludes the volume. Accompanying the text is a CD ROM version of the entire volume, with search features that enable increased access to the information in the text.

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Inflammatory Bowel Disease: A Guide for Patients and Their Families. 2nd ed Source: Philadelphia, PA: Lippincott-Raven Publishers. 1999. 235 p. Contact: Available from Crohn's and Colitis Foundation of America. 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 932-2423. Fax (212) 779-4098. E-mail: [email protected]. Website: www.ccfa.org. PRICE: $17.00 for members; $22.00 for nonmembers; plus shipping and handling. ISBN: 0397517718. Summary: This text is the official patient guide of the Crohn's and Colitis Foundation of America (CCFA). The text was written specifically for people with inflammatory bowel disease (IBD) and their families, physicians, and other health care professionals. IBD is the collective term for ulcerative colitis and Crohn's disease. Ulcerative colitis is an inflammatory disease of the large intestine (the colon), that is characterized by inflammation and ulceration of its inner lining. By contrast, Crohn's disease can affect any area of the gastrointestinal tract, including the small intestine, and there can be areas of normal intestine as well. The guide provides an extensive overview of IBD, including types, distinguishing features, and complications. Fourteen chapters discuss the anatomy and function of the digestive system, the cause of IBD, ulcerative colitis, Crohn's disease, extraintestinal complications, IBD and pregnancy, diet and nutrition,

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medical and surgical therapies, IBD in children and adolescents, special considerations for older patients, the emotional impact of IBD, alternative medicine, and the role of the CCFA. Each chapter is written by an expert in the field; most conclude with a list of references. The book also contains a glossary of medical terms, a glossary of surgical terms, and a subject index. ·

Therapy of Inflammatory Bowel Disease: New Medical and Surgical Approaches Source: New York, NY: Marcel Dekker, Inc. 1990. 304 p. Contact: Available from Marcel Dekker, Inc. P.O. Box 5005, Monticello, NY 12701-5185. (800) 228-1160 or (212) 696-9000. Fax (914) 796-1772. E-mail: [email protected]. PRICE: $190.00. ISBN: 0824781694. Summary: With the proliferation of new drugs, new nutritional considerations, and ileostomy alternatives, those who care for patients with inflammatory bowel disease (IBD) need a resource that comprehensively but concisely reviews and updates the latest in IBD therapy. This book attempts to provide such a resource. Part I details the pharmacology, clinical utility, modes of action, and toxicity of the various therapeutic agents, with specific recommendations for usage included. Part I concludes with chapters on nutrition and ileostomy alternatives designed to complement the sections on the individual drugs. Part II provides information dealing with certain general conditions, including extraintestinal and malignant complications; the pediatric patient; pregnancy and nursing; and psychosocial issues. The last chapter deals with specific patient presentations commonly faced by the clinician. This chapter enables the reader to learn how experienced clinicians apply the tools described in earlier chapters to the office and bedside practice of IBD. Each chapter includes figures, tables, and illustrations, as well as lengthy reference lists. A detailed subject index is appended. 976 references.

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 PrintÒ). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “inflammatory bowel disease” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “inflammatory bowel disease” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “inflammatory bowel disease” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): ·

A Meditaion to Help With Irritable Bowel Syndrome & Inflammatory Bowel Disease by Belleruth Naparstek (2002); ISBN: 1881405605; http://www.amazon.com/exec/obidos/ASIN/1881405605/icongroupinterna

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Advanced Therapy of Inflammatory Bowel Disease (Book with CD-ROM) by Theodore M. Bayless (Editor), et al (2000); ISBN: 1550091220; http://www.amazon.com/exec/obidos/ASIN/1550091220/icongroupinterna

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Advances in Inflammatory Bowel Diseases by P. Rutgeerts (Editor), et al; ISBN: 0792387503; http://www.amazon.com/exec/obidos/ASIN/0792387503/icongroupinterna

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Animal Models of Inflammatory Bowel Disease: Contribution to the 1st International Conference on Inflammatory Bowel Disease Animal Models, Berlin, December 2001 by M. Zeitz (Editor) (2003); ISBN: 380557522X; http://www.amazon.com/exec/obidos/ASIN/380557522X/icongroupinterna

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Ask Audrey: The Author's Personal & Professional Experience in the Day-To-Day Living With Inflammatory Bowel Disease by Audrey Kron (1999); ISBN: 0963387723; http://www.amazon.com/exec/obidos/ASIN/0963387723/icongroupinterna

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Challenges in Inflammatory Bowel Disease by D. P. Jewell (Editor), et al; ISBN: 0632051698; http://www.amazon.com/exec/obidos/ASIN/0632051698/icongroupinterna

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Chronic Inflammatory Bowel Disease in Childhood (BIPR: Gastroenterology - 8.1) by Walker-Smith, MacDonald; ISBN: 0702018430; http://www.amazon.com/exec/obidos/ASIN/0702018430/icongroupinterna

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Chronic Inflammatory Bowel Disease: Proceedings of the Falk Symposium Held in Lubeck, Germany, 4-5 March, 1994 by E.-F. Stange (Editor), E. F. Strange (1995); ISBN: 0792388763; http://www.amazon.com/exec/obidos/ASIN/0792388763/icongroupinterna

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Chronic inflammatory bowel disease by James L. Achord; ISBN: 0846301547; http://www.amazon.com/exec/obidos/ASIN/0846301547/icongroupinterna

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Clinical Challenges in Inflammatory Bowel Diseases: : Diagnosis, Prognosis & Treatment by M. Campieri (Editor), et al (1998); ISBN: 0792387333; http://www.amazon.com/exec/obidos/ASIN/0792387333/icongroupinterna

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Current Management of Inflammatory Bowel Disease (Medical Titles in the Current Therapy Series) by Theodore M. Bayless (Editor); ISBN: 1556640579; http://www.amazon.com/exec/obidos/ASIN/1556640579/icongroupinterna

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Cytokines in Inflammatory Bowel Disease by Claudio Fiocchi (1996); ISBN: 1570591245; http://www.amazon.com/exec/obidos/ASIN/1570591245/icongroupinterna

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Genetics and Epidemiology of Inflammatory Bowel Disease (Frontiers of Gastrointestinal Research, Vol 11) by R. McConnell (Editor), et al (1986); ISBN: 3805542658; http://www.amazon.com/exec/obidos/ASIN/3805542658/icongroupinterna

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Glucocorticoid Therapy in Chronic Inflammatory Bowel Disease: From Basic Principles to Rational Therapy (Falk Symposium, Vol 73B) by H.W. Mollmann (Editor), B. May (Editor) (1996); ISBN: 0792387082; http://www.amazon.com/exec/obidos/ASIN/0792387082/icongroupinterna

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Health Journeys: A Meditation to Help with Irritable Bowel Syndrome & Inflammatory Bowel Disease by Belleruth Naparstek, Steven M. Kohn; ISBN: 1881405508; http://www.amazon.com/exec/obidos/ASIN/1881405508/icongroupinterna

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If This is a Test, Have I Passed Yet?: Living with Inflammatory Bowel Disease by Ferne Sherkin-Langer, K. N. Jeejeebhoy (Preface) (1994); ISBN: 0771590466; http://www.amazon.com/exec/obidos/ASIN/0771590466/icongroupinterna

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Immunosuppression in Inflammatory Bowel Diseases: Standards, New Developments, Future Trends by K. Fellermann (Editor), et al; ISBN: 0792387678; http://www.amazon.com/exec/obidos/ASIN/0792387678/icongroupinterna

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Inflammatory Bowel Disease (Medical Pocketbooks) by Michael A. Kamm MD FRCP FRACP; ISBN: 185317341X; http://www.amazon.com/exec/obidos/ASIN/185317341X/icongroupinterna

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Inflammatory Bowel Disease (Special Issue: Digestive Diseases 2003, 2) by J. Scholmerich (Editor) (2003); ISBN: 3805576471; http://www.amazon.com/exec/obidos/ASIN/3805576471/icongroupinterna

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Inflammatory Bowel Disease and Coeliac Disease in Children by B. Herzog, et al (1990); ISBN: 0746201257; http://www.amazon.com/exec/obidos/ASIN/0746201257/icongroupinterna

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Inflammatory Bowel Disease in Children and Adolescents (Monographs in Clinical Pediatrics) by Jeremiah J. Levine (Editor), Michael J. Pettei (Editor); ISBN: 3718656566; http://www.amazon.com/exec/obidos/ASIN/3718656566/icongroupinterna

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Inflammatory Bowel Disease, Volume II by Hugh J. Freeman (Editor), et al; ISBN: 0849355230; http://www.amazon.com/exec/obidos/ASIN/0849355230/icongroupinterna

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Inflammatory Bowel Disease: A Clinical Approach by Henry D. Janowitz, Henry D. Janowtiz; ISBN: 0195078306; http://www.amazon.com/exec/obidos/ASIN/0195078306/icongroupinterna

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Inflammatory Bowel Disease: A Clinical Case Approach to Pathophysiology, Diagnosis, and Treatment (Falk Symposium, 122) by Italy)/ Fiocchi, C. Falk Symposium 2001 Bologna (Editor), et al (2002); ISBN: 0792387724; http://www.amazon.com/exec/obidos/ASIN/0792387724/icongroupinterna

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Inflammatory Bowel Disease: A Clinicians' Guide by Alastair, Bsc, Md, Frcp Forbes, Alastair Forbes; ISBN: 034080727X; http://www.amazon.com/exec/obidos/ASIN/034080727X/icongroupinterna

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Inflammatory Bowel Disease: A Guide for Patients and Their Families by Stanley H. Stein (Editor), et al; ISBN: 0397517718; http://www.amazon.com/exec/obidos/ASIN/0397517718/icongroupinterna

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Inflammatory Bowel Disease: A Personal View by Henry D. Janowitz; ISBN: 0931729017; http://www.amazon.com/exec/obidos/ASIN/0931729017/icongroupinterna

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Inflammatory Bowel Disease: Basic Research and Clinical Implications (Falk Symposium, No 46) by H. Goebell, et al (1989); ISBN: 0746200676; http://www.amazon.com/exec/obidos/ASIN/0746200676/icongroupinterna

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Inflammatory Bowel Disease: Clinical Diagnosis and Management by David Rampton (Editor); ISBN: 1853177342; http://www.amazon.com/exec/obidos/ASIN/1853177342/icongroupinterna

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Inflammatory Bowel Disease: Current Status and Future Approach: Proceedings (International Congress Series, No 775) by Richard P. MacDermott (Editor); ISBN: 0444810013; http://www.amazon.com/exec/obidos/ASIN/0444810013/icongroupinterna

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Inflammatory Bowel Disease: Diagnosis and Treatment by Gary Gitnick (Editor) (1991); ISBN: 0896401782; http://www.amazon.com/exec/obidos/ASIN/0896401782/icongroupinterna

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Inflammatory Bowel Disease: Experience and Controversy by Burton Korelitz (Editor); ISBN: 0808916939; http://www.amazon.com/exec/obidos/ASIN/0808916939/icongroupinterna

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Inflammatory Bowel Disease: Experience and Controversy by Teaching Seminar on Inflammatory Bowel Disease; ISBN: 0884163105; http://www.amazon.com/exec/obidos/ASIN/0884163105/icongroupinterna

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Inflammatory Bowel Disease: Fast Facts Series by Health Press, et al; ISBN: 1899541497; http://www.amazon.com/exec/obidos/ASIN/1899541497/icongroupinterna

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Inflammatory Bowel Disease: From Bench to Bedside by Stephan R. Targan (Editor), et al (2003); ISBN: 1402007132; http://www.amazon.com/exec/obidos/ASIN/1402007132/icongroupinterna

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Inflammatory Bowel Disease: Methods and Protocols by Subrata Ghosh (Editor) (2004); ISBN: 1588290484; http://www.amazon.com/exec/obidos/ASIN/1588290484/icongroupinterna

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Inflammatory Bowel Disease: Proceedings (Japan Medical Research Foundation Publication, No 22) by International Symposium on Etiopathogenesis and Treatment of Inflammat, et al; ISBN: 0860083640; http://www.amazon.com/exec/obidos/ASIN/0860083640/icongroupinterna

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Inflammatory Bowel Disease: Progress in Basic Research and Clinical Implications (Falk Symposium, Vol 60) by H. Goebell (Editor) (1991); ISBN: 0792389565; http://www.amazon.com/exec/obidos/ASIN/0792389565/icongroupinterna

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Inflammatory Bowel Disease: Tenth International Berzelius Symposium Sponsored by the Swedish Society of Medicine by Gunnar Jarnerot (Editor) (1987); ISBN: 0881673188; http://www.amazon.com/exec/obidos/ASIN/0881673188/icongroupinterna

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Inflammatory Bowel Disease by S. Schreiber (1999); ISBN: 3540148167; http://www.amazon.com/exec/obidos/ASIN/3540148167/icongroupinterna

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Inflammatory Bowel Disease by R. N. Allan (Editor) (1997); ISBN: 0443050678; http://www.amazon.com/exec/obidos/ASIN/0443050678/icongroupinterna

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Inflammatory Bowel Disease by F. T. De Dombal (Editor) (1994); ISBN: 0192613545; http://www.amazon.com/exec/obidos/ASIN/0192613545/icongroupinterna

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Inflammatory Bowel Disease by Miles C. Allison, et al; ISBN: 0723418888; http://www.amazon.com/exec/obidos/ASIN/0723418888/icongroupinterna

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Inflammatory Bowel Disease by Richard P. MacDermott, William Stenson (Editor); ISBN: 0838540694; http://www.amazon.com/exec/obidos/ASIN/0838540694/icongroupinterna

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Inflammatory Bowel Disease by Joseph B. Kirsner (Editor); ISBN: 0721676162; http://www.amazon.com/exec/obidos/ASIN/0721676162/icongroupinterna

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Inflammatory Bowel Disease by Russell D. Cohen (Editor); ISBN: 0896039099; http://www.amazon.com/exec/obidos/ASIN/0896039099/icongroupinterna

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Inflammatory Bowel Disease by Marshall Sparberg; ISBN: 0874885582; http://www.amazon.com/exec/obidos/ASIN/0874885582/icongroupinterna

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Inflammatory Bowel Diseases (Falk Symposium, Vol 85) by Guido N.J. Tytgat (Editor), et al (1996); ISBN: 0792388941; http://www.amazon.com/exec/obidos/ASIN/0792388941/icongroupinterna

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Inflammatory Bowel Diseases (Nestle Nutrition Workshop Series. Clinical & Performance Programme, V. 2) by Bruce R. Bistrian (Editor), John A. Walker-Smith (Editor) (1999); ISBN: 3805568851; http://www.amazon.com/exec/obidos/ASIN/3805568851/icongroupinterna

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Inflammatory Bowel Diseases : New Insights Into Mechanisms of Inflammation & Challenges. by Portugal)/ Veloso, F. Tavarela Falk Symposium 1994 Estoril (Editor), Estela Monteiro; ISBN: 0792388844; http://www.amazon.com/exec/obidos/ASIN/0792388844/icongroupinterna

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Inflammatory Bowel Diseases 1986 by Daniel Rachmilewitz (Editor) (1986); ISBN: 0898387965; http://www.amazon.com/exec/obidos/ASIN/0898387965/icongroupinterna

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Inflammatory Bowel Diseases 1986 (1986); ISBN: 9024726123; http://www.amazon.com/exec/obidos/ASIN/9024726123/icongroupinterna

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Inflammatory Bowel Diseases and Chronic Recurrent Abdominal_pain by F. Hadziselimovic (Editor), B. Herzog (Editor); ISBN: 0792387228; http://www.amazon.com/exec/obidos/ASIN/0792387228/icongroupinterna

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Inflammatory Bowel Diseases, from Bench to Bedside (Falk Symposium , Vol 96) by T. Andus (Editor), et al (1997); ISBN: 0792387287; http://www.amazon.com/exec/obidos/ASIN/0792387287/icongroupinterna

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Inflammatory Bowel Diseases: New Developments and Standards: Proceedings of the Falk Symposium No. 82, Held in Halle/Saale, Germany, November 18-19, 1994 (Falk Symposium, Vol 82) by W. E. Fleig (Editor) (1995); ISBN: 0792388909; http://www.amazon.com/exec/obidos/ASIN/0792388909/icongroupinterna

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Inflammatory Bowel Diseases: Pathophysiology As Basis of Treatment: Proceedings of the 67th Falk Symposium Held in Regensburg, Germany June 25-27, (Falk Symposium, Vol 67) by J. Scholmrich, et al (1993); ISBN: 0792389964; http://www.amazon.com/exec/obidos/ASIN/0792389964/icongroupinterna

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Inflammatory Bowel Diseases by Jack Satsangi, et al (2003); ISBN: 0443071217; http://www.amazon.com/exec/obidos/ASIN/0443071217/icongroupinterna

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Inflammatory Bowel Diseases by R.N. Allan, et al (1990); ISBN: 0443038198; http://www.amazon.com/exec/obidos/ASIN/0443038198/icongroupinterna

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Inflammatory Bowel Diseases-1994: Proceedings of the 72nd Falk Symposium Held in Strasbourg, France, September 6-8, 1993 (Falk Symposium, Vol 72) by D. Rachmitewitz (Editor), Daniel Rachmilewitz (1994); ISBN: 0792388453; http://www.amazon.com/exec/obidos/ASIN/0792388453/icongroupinterna

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Innovative Concepts in Inflammatory Bowel Disease (Falk Symposium, Vol 105) by J. Emmrich (Editor), et al (1999); ISBN: 079238749X; http://www.amazon.com/exec/obidos/ASIN/079238749X/icongroupinterna

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Kirsner's Inflammatory Bowel Disease by R. Balfour Sartor, William Sandborn (2003); ISBN: 0721600018; http://www.amazon.com/exec/obidos/ASIN/0721600018/icongroupinterna

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Management of Inflammatory Bowel Disease by Burton I. Korelitz, Norman Sohn (1992); ISBN: 0801664934; http://www.amazon.com/exec/obidos/ASIN/0801664934/icongroupinterna

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Operative Strategies in Inflammatory Bowel Disease by Fabrizio Michelassi (Editor), Jeffrey W. Milsom (Editor) (1999); ISBN: 0387949666; http://www.amazon.com/exec/obidos/ASIN/0387949666/icongroupinterna

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Origins and Directions of Inflammatory Bowel Disease: Early Studies of the Nonspecific Inflammatory Bowel Diseases by Joseph B. Kirsner (Editor), Ulrich Klotz; ISBN: 0792387775; http://www.amazon.com/exec/obidos/ASIN/0792387775/icongroupinterna

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People Not Patients: A Source Book for Living With Inflammatory Bowel Disease by Penny Steiner, et al; ISBN: 0961549505; http://www.amazon.com/exec/obidos/ASIN/0961549505/icongroupinterna

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Radiology in Inflammatory Bowel Disease (Diagnostic Radiology Series, V. 2) by Clive I. Bartram, et al (1983); ISBN: 0824718046; http://www.amazon.com/exec/obidos/ASIN/0824718046/icongroupinterna

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Strategic Perspectives: Inflammatory Bowel Disease - The Rise of Remicade [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B00008R3YX; http://www.amazon.com/exec/obidos/ASIN/B00008R3YX/icongroupinterna

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Targets of Treatment in Chronic Inflammatory Bowel Diseases (Falk Symposium) by H. Herfarth (Editor), et al (2003); ISBN: 0792387848; http://www.amazon.com/exec/obidos/ASIN/0792387848/icongroupinterna

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The Clinicians Guide to Inflammatory Bowel Disease by Gary R, MD Lichtenstein (Editor), et al (2003); ISBN: 1556425546; http://www.amazon.com/exec/obidos/ASIN/1556425546/icongroupinterna

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The Inflammatory Bowel Disease Yearbook 2003 by Charles Bernstein (Editor) (2003); ISBN: 1901346579; http://www.amazon.com/exec/obidos/ASIN/1901346579/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 New People: Not Patients: A Source Book for Living With Inflammatory Bowel Disease by Penny Steiner-Grossman (1997); ISBN: 0787242829; http://www.amazon.com/exec/obidos/ASIN/0787242829/icongroupinterna

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Therapy of Inflammatory Bowel Disease: New Medical and Surgical Approaches (Inflammatory Disease and Therapy, Series 2) by Mark A. Peppercorn (Editor); ISBN: 0824781694; http://www.amazon.com/exec/obidos/ASIN/0824781694/icongroupinterna

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Treating Ibd: A Patient's Guide to the Medical and Surgical Management of Inflammatory Bowel Disease by Lawrence J. Brandt (Editor), et al; ISBN: 0881675326; http://www.amazon.com/exec/obidos/ASIN/0881675326/icongroupinterna

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Trends in Inflammatory Bowel Disease Therapy 1996 by Robin S. McLeod (Editor), et al (1997); ISBN: 079238718X; http://www.amazon.com/exec/obidos/ASIN/079238718X/icongroupinterna

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Trends in Inflammatory Bowel Disease Therapy 1999 by C. Noel Williams (Editor), et al; ISBN: 0792387627; http://www.amazon.com/exec/obidos/ASIN/0792387627/icongroupinterna

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Trends in Inflammatory Bowel Disease Therapy: Proceedings of the 56th Falk Symposium Held at Halifax, Nova Scotia, Canada Jund 6-9, 1990 (Falk Symposium, Vol 56) by C.N. Williams (Editor) (1991); ISBN: 0792389522; http://www.amazon.com/exec/obidos/ASIN/0792389522/icongroupinterna

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Trends in Inflammatory Bowel Disease Therapy: Proceedings of the 66th Falk Symposium Held in Quebec City, Canada, May 20-23, 1992 (Falk Symposium, V) by C.N. Williams, F. Martin (1993); ISBN: 0792388275; http://www.amazon.com/exec/obidos/ASIN/0792388275/icongroupinterna

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V International Symposium on Inflammatory Bowel Diseases by D. Rachmilewitz (Editor); ISBN: 0792387430; http://www.amazon.com/exec/obidos/ASIN/0792387430/icongroupinterna

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VI International Symposium on Inflammatory Bowel Diseases: Proceedings of Falk Symposium 123 Held in Istanbul, Turkey, September 3-5, 2001 (Falk Symposium, 123) by D. Rachmilewitz (Editor), et al (2002); ISBN: 0792387732; http://www.amazon.com/exec/obidos/ASIN/0792387732/icongroupinterna

Chapters on Inflammatory Bowel Disease In order to find chapters that specifically relate to inflammatory bowel disease, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and inflammatory bowel disease 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 “inflammatory bowel disease” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on inflammatory bowel disease: ·

Steroid Unresponsiveness in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 133-137. 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: Although systemic glucocorticoid treatment is associated with a large number and sometimes severe side effects, this is still the first and most useful therapeutic tool in treating patients with both acute ulcerative colitis (UC) and Crohn's disease (CD). In these clinical situations, glucocorticoids are both rapidly acting, within 48 hours, and effective, with a response rate of about 80 percent. Unresponsiveness to steroid treatment leads to the need for therapeutic decisions including surgical resection or the use of immunosuppressive drugs. This chapter on steroid unresponsiveness is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with CD and UC, together known as inflammatory

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bowel disease (IBD). When a patient presents with steroid resistance, it is important to rule out false causes of refractoriness, such as bile-salt malabsorption, bacterial overgrowth, and coexistent irritable bowel syndrome. It also is important to detect the existence of viral or bacterial gastrointestinal infections that may enhance the synthesis of inflammatory mediators perpetuating the disease process. The molecular basis of genuine steroid resistance is unclear but an understanding will allow earlier diagnosis and treatment. Therapeutic alternatives to steroids should be individualized; the author outlines a personal schematic approach in a patient care algorithm. 2 figures. 12 references. ·

Epidemiology of Inflammatory Bowel Disease Source: in Lichtenstein, G.R. The Clinician's Guide to Inflammatory Bowel Disease. Thorofare, NJ: SLACK Incorporated. 2003. p. 1-8. Contact: Available from SLACK Incorporated. 6900 Grove Road, Thorofare, NJ 080869447. (856) 848-1000. Fax (856) 853-5991. Website: www.slackbooks.com. PRICE: $44.95; plus shipping and handling. ISBN: 556425546. Order number: 75546. Summary: Although the term inflammatory bowel disease (IBD) describes a wide range of inflammatory states, it generally refers to ulcerative colitis (UC) and Crohn's disease. This chapter on epidemiology of IBD is from a handbook that presents an up to date guide on selected topics in IBD, focusing on those clinically important areas that have undergone recent changes or discoveries. In this chapter, the authors note that methodologically rigorous studies, which evaluate the epidemiology of these disorders, are relatively rare. Furthermore, much of the available literature is limited by referral bias and inadequate case definition. The latter issue is particularly relevant since the current concept that Crohn's disease and ulcerative colitis are unique entities has been challenged by recent genetic discoveries. Nonetheless, the current phenotypic-based classification is clinically useful and provides a valuable framework for research. The authors cover incidence and prevalence rates, morbidity and mortality, and environmental risk factors, including cigarette smoking, oral contraceptives, geography, diet, nonsteroidal antiinflammatory drugs (NSAIDs), mycobacteria, measles virus, and appendectomy. The authors also briefly consider genetic risk factors, covering familial aggregation, race and ethnicity, and gene identification. 19 references.

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Inflammatory Bowel Diseases Source: in Bonci, L. American Dietetic Association Guide to Better Digestion. Hoboken, NJ: John Wiley and Sons, Inc. 2003. p. 74-98. Contact: Available from John Wiley and Sons, Inc. Customer Care Department, One Wiley Drive, Somerset, NJ 08875. (800) 762-2974 or (317) 572-3993. Fax (317) 572-4002. Website: www.wiley.com. PRICE: $14.95 plus shipping and handling. ISBN: 0471442232. Summary: Coping with a gastrointestinal disorder, whether it is irritable bowel syndrome (IBS), gas (flatulence), constipation, heartburn, or another condition, can be embarrassing and debilitating. While medical treatments and prescriptions can offer relief, one of the most important ways patients can help themselves is in their dietary choices. This chapter on inflammatory bowel disease (IBD) is from a book that describes how patients can self-manage their digestive disorders through dietary choices. IBD includes Crohn's disease and ulcerative colitis, both of which result in inflammation of different parts of the digestive tract. In this chapter, the author defines IBD and its possible causes, then discusses the symptoms of the condition, the diagnostic tests that are used to confirm IBD, treatment options, surgical options,

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medications that are commonly used for symptom management, the use of nutritional supplements, the impact of diet on IBD symptoms, foods and supplements that may be bothersome, and specific eating recommendations for ulcerative colitis and for Crohn's disease. A final section discusses short bowel syndrome (when the small bowel cannot function because of disease, or when it has been surgically removed). 9 figures. ·

Life-Style Issues and Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 531-533. 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: Inflammatory bowel diseases (IBDs), ulcerative colitis(UC), and Crohn's disease (CD) are chronic diseases that can afflict patients at various times of their lives. This chapter on lifestyle issues is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with CD and Ulcerative Colitis (UC). The author of this chapter, a practicing gastroenterologist specializing in IBD, and an IBD patient for almost 30 years, shares his experiences so other practitioners will be able to gain insight into living and functioning with IBD and how treating physicians, can become more effective practitioners for this unique group of patients. As with any chronic illness, treating only the symptoms and complications of these diseases may not meet all of the needs of the individual patient. The success or failure of a particular treatment plan also may be dependent on the ability of the family, or support system, to understand the situation and become the surrogate nurse for these patients. The author stresses that the lifestyle issues that need to be addressed in the individual patient are dependent upon the stage of that patient in life. Each of four stages are then discussed: children and adolescents, young adulthood, adulthood, and elderly patients. The author challenges physicians to take on the role of patient advocate, to learn about and use potential referral sources, and to address their own prejudices against patients with chronic diseases. Accessing support from organizations such as the CCFA (Crohn's and Colitis Foundation of America) is also encouraged. 4 references.

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Inflammatory Bowel Disease Nurse Advocate Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 535-537. 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: Many patients with Crohn's disease (CD) or ulcerative colitis (UC) report frequent encounters with health care providers who know little about inflammatory bowel disease (IBD) and how to manage it. The position of the Inflammatory Bowel Disease Nurse Advocate at the Johns Hopkins Hospital is designed to address this problem. This chapter describing the IBD nurse advocate 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 primary goal of this position is to responsibly address the

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multidisciplinary needs of this unique patient population. The author describes the essential and complementary skills needed for this position, primary responsibilities, measuring role impact, the use of telecommunication, and community outreach. Patients ranked effective communication of health-related information second to clinical skill as the most crucial element of outpatient care. Responding to patient perception, the 'advocate' model prioritizes the essentials of improved communication, patient education, and accessibility to the health care system. Using a collaborative approach, the IBD Nurse Advocate functions as a 'physician extender.' This approach to practice promotes productivity and effective use of personnel, and has a positive impact on patient outcomes. One figure reprints a customized intake form for patients with IBD. 1 figure. 3 references. ·

Nonsteroidal Anti-Inflammatory Drugs, Enterocolonic Ulceration, and Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 625-629. 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: Nonsteroidal antiinflammatory drugs (NSAIDs) cause damage through the gastrointestinal tract. This chapter on NSAIDS, enterocolonic (small bowel) ulceration and inflammatory bowel disease (IBD) 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 IBD. The authors outline an approach to treatment of the damage of NSAIDs to the small bowel and the management of patients with IBD who require NSAIDs. The authors caution that the use of NSAIDs in patients with IBD is challenging because the drugs may cause relapse of disease. Specific issues addressed include iron deficiency anemia, hypoalbuminemia (reduced levels of protein in the blood), strictures (narrowing of the intestine), NSAID induced colon damage, and the use of NSAIDs in patients with IBD. Rarely, NSAIDs actually cause colitis, but their use is associated with an enhanced risk of appendicitis in the elderly and diverticular complications (fistulae and abscesses). 6 references.

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Adherence Issues in Management of Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 9-11. 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 adherence issues 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 and CD are chronic, recurring conditions requiring life-long management. Most often, patients take their medicines when they are sick, but nonadherence is a common phenomenon with disease in remission. Many clinicians incorrectly assume that their patients follow prescribed therapeutic recommendations. The degree of adherence that patients are able to achieve early in the course of disease

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may decrease markedly after 1 to 2 years. Once remission has been established, patients often enter a 'honeymoon' phase of maintenance therapy. After a period of time, they may tire of taking their medications. Thus, during the transition from therapeutic to maintenance therapy, education regarding the importance of continued adherence to prevent relapse of disease or complications is vital. Failure to comply with recommended maintenance regimens increases the risk of recurrent active disease, possible hospitalization, or steroid exposure and the consequences of prolonged steroid use. It is worth considering that nonadherence also is associated with the risk of extraintestinal manifestations of IBD that parallel gastrointestinal disease activity, and may also be an important factor regarding long term cancer risks. Furthermore, the issue of compliance is not limited to medicines but includes lifestyle modifications (smoking cessation, dietary restrictions) and other follow-up care (surveillance colonoscopies and monitoring blood tests for certain medications). Patterns of nonadherence include under or overconsuming medication, taking doses at inappropriate intervals, or administering medication incorrectly (as in enema therapy). Factors that influence long-term adherence include those related to the health care provider, the patient, and also the medication itself. The author concludes that physicians cannot support patient compliance alone; a team approach using the strengths, knowledge, and experience of nurses, social workers, and pharmacists, and the patients themselves, will ultimately lead to the best medical care. 1 table. 7 references. ·

Arthritis Associated with Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 279-282. 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 arthritis associated with inflammatory bowel disease (IBD) 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 IBD. Arthritis is a relatively common complication of UC and CD, affecting 10 to 20 percent of patients. Arthritis may predate the bowel disease and may be severe enough to warrant treatment in its own right, perhaps with nonsteroidal anti-inflammatory drugs (NSAIDs). This may, itself, exacerbate the underlying bowel disease. In this chapter, the different forms of arthritis associated with IBD are identified and their management discussed in terms of their prognosis, possible modes of treatment, and when expert help should be sought. With the exception of ankylosing spondylitis (AS, fusion of the vertebral facet joints), the IBD associated joint disease is largely non deforming and non progressive, and so can be managed symptomatically, although the use of NSAIDs should be avoided. Management involves judicious use of physical treatments (rest, range of movement exercises, and physiotherapy) in addition to pharmacological treatments. Patients with AS or persistent or erosive peripheral joint disease should be referred to a rheumatologist. 2 tables. 6 references.

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Cancer Prevention Strategies in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 257-261.

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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 cancer prevention strategies in inflammatory bowel disease (IBD) 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 inflamatory bowel disease (IBD). Ulcerative colitis is associated with an increased risk of developing colorectal cancer (CRC). The risk of CRC is approximately 7 to 14 percent at 25 years of disease. Crohn's disease has a similar ageadjusted increased risk of developing CRC. The risks of developing CRC inUC correlate with increased disease duration and increased disease extent. Neoplasia (new tissue, which can include dysplasia, polyps, or cancer) usually is first evident after approximately 8 years of disease and is more likely to occur among patients with pancolitis than those with left-sided colitis. When cancer occurs in UC, it is more commonly found in the rectosigmoid. For CD, the increased risk is associated with disease duration and extent of 'at risk mucosa' as well. Patients with limited cecal disease are at limited risk for developing CRC and isolated ileal disease does not appear to increase the risk of CRC. The author reviews the pitfalls and benefits of dysplasia surveillance and offers suggestions for the clinical approach to patient counseling, surveillance timing, biopsy site and number, adenoma like masses, and the presence of pseudopolyps. Preventing or removing CRC at an early stage in UC patients is as advantageous as diagnosing early CRC in the general population. 2 figures. 12 references. ·

Cholangiocarcinoma in the Inflammatory Bowel Disease Patient Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 311-315. 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 cholangiocarcinoma (biliary tract cancer) 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). Cholangiocarcinoma (CC) is a dreaded complication of PSC due to its poor prognosis (median survival of 5 months) and limited treatment options. In the general population, CCs are rare tumors but occur in 5 to 15 percent of patients with primary sclerosing cholangitis (PSC). The major risk factor for CC development is chronicity of PSC. This duration of disease is somewhat difficult to prove as the precise onset of PSC is often uncertain. Most CC patients have already developed cirrhosis and have longstanding Ulcerative Colitis (UC). Its detection in the setting of PSC necessitates a high index of clinical suspicion in addition to serial assessments of serum biliary biochemistry and possible imaging with CT scan of the abdomen and ERCP with tissue sampling of dominant strictures. Early detection of potentially curable CC remains the challenge, and no proven technique exists. Serum IL-6 concentration and PET scanning may prove to be helpful in this regard. The only definitive treatment is surgical resection as the prognosis following liver transplantation remains unacceptably poor. Neoadjuvant therapy with chemoradiation may offer some benefit in reducing tumor bulk and increasing the proportion of patients suitable for

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curative resection. Palliative therapy aims to relieve the symptoms of biliary obstruction and optimize quality of life. Endoscopic stricture dilation and biliary stent placement is possible in the majority of patients and highly successful in effecting biliary decompression. A multidisciplinary approach optimizes the treatment strategy in the management of patients with CC. ·

Cutaneous Manifestations of Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 271-274. 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 cutaneous (skin) manifestations of inflammatory bowel disease (IBD) 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 IBD. Pyoderma gangrenosum is an idiopathic inflammatory skin disease manifested clinically by painful ulceration with characteristic purple borders. These ulcers most commonly present in an otherwise healthy patient as a single self-limited lesion of the lower extremities. Although a significant number of pyoderma gangrenosum lesions may resolve spontaneously after many months, the debility from pain and the potential of a superimposed local and systemic infection in such a necrotic wound prompts the institution of early therapeutic intervention (based on immunosuppressive therapy). Another condition, erythema nodosum (EN) is a reactive septal panniculitis (a chronic inflammation of subcutaneous fat) characterized by extremely painful, nonulcerating erythematous (reddened) nodules on pretibial (shin) areas. The vast majority of cases affect young women, and the triggering or underlying disease remains unknown. When a cause is identified, a preceding streptococcal infection is a common association. Other infections, sarcoidosis, drugs, rheumatologic disease, and IBD also can be associated with erythema nodosum. In contrast to pyoderma gangrenosum, the activity of erythema nodosum tends to reflect that of the associated intestinal disease. Erythema nodosum usually resolves spontaneously, and while waiting for resolution most cases will respond to nonsteroidal antiinflammatory drugs. Cutaneous CD is an unusual but potentially very debilitating complication of IBD. The most common presentation of cutaneous CD is perineal involvement secondary to enterocutaneous fistulae, and the clinical features of this presentation are draining sinuses, ulcerations, plaques, and nodules. The activity of the perineal disease tends to closely parallel that of the intestinal disease. Treatment involves combination immunosuppressive and antiinflammatory therapy. The author also discusses vasculitis, dermatosis arthritis syndrome, Sweet's syndrome, necrolytic migratory erythema, and other IBD associated mucous membrane disorders. 31 references.

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Fertility and Pregnancy in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 607-611. 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.

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Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on fertility and pregnancy in inflammatory bowel disease (IBD) 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 IBD. The peak incidence of the development of IBD occurs during the reproductive years and, therefore, is a common concern for the practicing obstetrician. Often, the first issue discussed when consulting a new patient with Crohn's disease or ulcerative colitis is their reproductive future. The ultimate concern is whether the outcome of a pregnancy will be successful and whether they can give birth to a healthy baby. This chapter focuses on gynecologic and obstetric issues in these challenging patients. The author outlines first, second, and third trimester considerations from the point of view of the obstetrician; an additional chapter addresses pregnancy in IBD from the perspective of a gastroenterologist. Women who have Crohn's disease and ulcerative colitis usually are able to live normal reproductive lives. In many cases, this is attributable to both medical and surgical advances. Integrating these advances into the care of the patient with IBD has enabled many who have been unable to get pregnant, either by choice or professional recommendation, to conceive, have healthy pregnancies, and deliver healthy babies. Obstetricians and gastroenterologists need to recognize this and relay it to patients in an encouraging manner. 14 references. ·

Gallstone Management in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 317-320. 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 gallstone (cholelithiasis) management in inflammatory bowel disease (IBD) 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 IBD. The association between IBD and hepatobiliary (liver, gallstone, bile ducts) disorders has been well established. Both CD and chronic Ulcerative Colitis (UC) can affect the liver and biliary system. Indeed, hepatobiliary involvement in patients with IBD varies from the asymptomatic state to the development of symptomatic complications related to chronic liver injury. Gallstones represent one of the most frequently encountered clinical hepatobiliary problems in patients with IBD especially those with Crohn's disease. In this chapter, the authors present an overview of the management of gallbladder stones and biliary sludge in patients with IBD. A summary of the epidemiology and pathogenesis of gallstones and biliary sludge in these patients is provided to guide therapeutic decisionmaking, which should aim not only to address symptomatic stones but also to prevent their development. Precipitating factors or conditions including prolonged fasting, total parenteral nutrition (TPN), and use of the drugs ceftriazone or octreotide must be avoided. Patients with symptomatic sludge or complications should have cholecystectomy (removal of the gallbladder). In poor surgical candidates, alternative interventions include oral agents for bile acid dissolution and percutaneous cholecystostomy. 1 figure. 1 table. 8 references.

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Growth and Nutritional Problems in Pediatric Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 245-249. 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 growth and development in pediatric inflammatory bowel disease (IBD) 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 inflamatory bowel disease (IBD). IBD is recognized increasingly as a common diagnosis in the pediatric age group, accounting for approximately 25 percent of all patients with IBD, with CD outnumbering UC by approximately 4 to 1. A small but notable fraction of IBD cases are being diagnosed during infancy. As in adults, a wide variety of gastrointestinal manifestations and extraintestinal complications are commonly encountered in children and adolescents with CD. In view of the added metabolic requirements for growth, children are more likely to suffer from malnutrition and micronutrient deficiencies than adults. Further-more, growth failure is a complication unique to the pediatric age group, which occurs in up to half of the cases of CD and in about 10 percent of those with UC. Although medications often achieve symptomatic relief, malnutrition and growth failure commonly persist, particularly in pediatric CD. The goal of completely suppressing disease activity and minimizing daily steroid use is detailed in another chapter on therapy of CD in children and adolescents. Growth failure may be the presenting complaint, at times in the absence of gastrointestinal symptoms. The combination of short stature and delayed puberty is often more disturbing to the patient than all other symptoms. Thus, nutritional therapy represents a very important adjunctive to effective medical or surgical management strategies for many children, particularly when their disease is accompanied by growth failure. In this chapter, the extent of nutritional problems in pediatric IBD is reviewed, along with an evidence-based review of the role of nutritional therapy in IBD. 2 figures. 17 references.

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Hematologic Problems in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 325-327. 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 hematologic (blood) problems in inflammatory bowel disease (IBD) 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 IBD. The hematologic abnormalities encountered in the management of inflammatory bowel disease (IBD) are varied and range from overt (obvious) and occult (hidden) gastrointestinal bleeding to an increased risk for thromboembolic (blood clotting) complications. Blood disorders are prevalent: anemia is present in more than 50 percent of patients, and a decreased serum iron level is found in over one-third of patients. Iron loss, defective iron transport, insufficient erythropoietin production, and even inhibition of marrow colony formation all have

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been described. Much of the pathophysiology associated with these abnormalities now is seen as either a direct or derivative consequence of the inflammatory cell responses that characterize the inflammatory bowel disorders. Effective clinical management arises from recognizing these relationships and adapting the overall advances in inflammation and immune modulation to these specific clinical settings. ·

Infectious Agents as Aggravating Factors in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 95-98. 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 infectious agents as aggravating factors 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 diarrhea, one of the first questions is whether it is an infection or an attack of IBD. Initial symptoms may be very similar, including diarrhea (with or without blood), abdominal pain or cramps, fever, and even arthralgias (pain in the joints). Clinical features that favor infection are acute onset of diarrhea (often greater than 10 bowel movements per day) and fever early in the course. Conversely, IBD usually has a more insidious onset, fewer than 6 bowel movements daily, and early fever is uncommon. Colonoscopic features can suggest infection or UC, but are rarely diagnostic. Mucosal biopsy, however, can be useful in distinguishing acute self-limited colitis or infectious-type colitis from IBD. However, to further complicate matters, infections sometimes can precipitate IBD, and intercurrent (happening at the same time) infections can mimic or induce flares of IBD. This chapter considers infections that mimic IBD, including amebic colitis and chronic infectious colitides (including Entamoeba histolytica and Yersinia); and infections that aggravate IBD, including Campylobacter jejuni, Salmonella, Shigella, Escherichia coli, Clostricium difficile, Cytomegalovirus, Herpes simplex virus, parasites, and mycobacterium. 1 table. 22 references.

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Insurance and Disability Advocacy Issues in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 555-559. 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 insurance and disability advocacy issues 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 physicians can be good advocates for their patients with IBD. The key to being a good advocate is to be knowledgeable about the issues and to be able to offer facts and guidance to patients with their many insurance and disability related issues. The author discusses the vulnerable age peak for obtaining insurance; changing employment; benefits programs including Medicare, Medicaid, high risk insurance pools, and Family and Medical

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Leave; and disability programs, including Social Security disability benefits, the Americans with Disabilities Act (ADA), and education issues for children with IBD. The chapter offers a list of tips for patients. Do not let current health insurance coverage lapse. If the patient does not have health insurance, look into the options available to obtain it. Have regular visits with the doctor, as insurers look favorably on patients who have regular visits, and this will also help the patient to stay well. Take medication as prescribed, because the condition likely will not improve on its own, even if the use of medication temporarily disallows eligibility to an insurance plan. If possible, choose a job with group insurance and portable benefits. For parents of children with IBD, anticipate their need for modified coverage prior to their eighteenth birthday. Determine with the insurance agent or benefits representative what the best options are for the teenager prior to turning 18 so that no lapse in coverage occurs. ·

Lymphoma in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 645-648. 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 lymphoma (a tumor of the lymphoid tissue, usually malignant) in inflammatory bowel disease (IBD) 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 IBD. Lymphoma may either mimic or complicate ulcerative colitis UC and CD, and the understanding of this relationship is of importance to physicians. There is significant overlap between the symptoms, signs, and the radiologic and endoscopic appearance of intestinal lymphoma and IBD. Small intestinal lymphoma may mimic CD and colonic lymphoma may mimic both colitis and colonicadnocarcinoma (cancer). The authors conclude that intestinal lymphomas are uncommon but both intestinal and extraintestinal lymphomas appear to be of increased incidence in chronic inflammatory bowel disease states, including IBD. The relationship between immune modifying therapy used in IBD and the development of lymphoma remains controversial. The differential diagnosis between IBD and lymphoma, either complicating IBD or occurring independently, is difficult. Most intestinal lymphomas diagnosed in the setting of IBD have been unanticipated and were found incidentally at the time of surgery performed for IBD indications or only subsequently in the histopathology of the resected specimen. Intestinal lymphoma also may complicate IBD; therefore, awareness of its association, clues to its presence, and knowledge of appropriate diagnostic investigations (and their shortcomings) are critical to patient management. 10 references.

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Managing Inflammatory Bowel Disease in the Managed Care Era Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 13-18. 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.

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Summary: This chapter on managed care issues 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 clinician is besieged daily by restraints set by managed care organizations (MCO) regarding utilizing diagnostic and therapeutic modalities for the IBD patient. These restraints often require lengthy and often unproductive precertification phone calls, written waivers, or outright rejection of what the physician perceives to be the correct care. The authors review the present vexing problems facing the clinician in this new 'paradigm' of care, that is, the MCO, and attempt to offer some insight into recent legal and legislative inroads with MCO policy. The authors provide the clinician with a user-friendly and hands-on, practical approach to dealing with the problems and obstacles of operating in such a paradigm. Specific strategies are offered in the areas of medical necessity decisions, inappropriate use of clinical guidelines, unionization, what to do when payment is denied, 'late' payment, and for recovery of payments due. The authors conclude that physicians will never be chastised for interceding on behalf of the patient and will win more times than expected. In addition, an organized and sustain response will often achieve success. The chapter concludes with two sample letters to send to MCOs and a summary of the process of dealing with MCO Denial of Services or Care. 8 references. ·

Ocular Manifestations of Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 275-277. 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 ocular (eye) manifestations of inflammatory bowel disease (IBD) 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 IBD. Historically, IBD related ocular inflammation could result in blindness, although blindness is less likely today due to better treatments. Ocular inflammation in patients with IBD has a reported range of frequency from as low as 1.9 percent to as high as 13 percent of patients. Ulcerative colitis appears to be less likely to have associated ocular inflammation than does Crohn's disease. Although a large number of inflammatory conditions have been reported with IBD, including uveitis, episcleritis, scleritis, keratitis, conjunctivitis, retinitis, retinal vasculitis, choroiditis, optic neuritis, orbital myositis, and orbital pseudotumor, lesions that appear to be more clearly associated with IBD include anterior uveitis, scleritis, keratitis, and retinal vasculitis and/or posterior uveitis. Of these, anterior uveitis is the most common and the primary focus of this chapter. Most patients with the serious ocular manifestations of IBD will be symptomatic, although the symptoms may need to be elicited. Any ocular symptoms should be evaluated by an ophthalmologist, as there are no symptoms that are specific for IBD related eye disease, and the symptoms of several problems are similar. Acute problems often are manifested by pain, redness, photophobia (sensitivity to light), and sometimes blurred vision, whereas chronic problems may present with blurred vision. Typical treatment involves topical prednisolone acetate 1 percent every hour while awake, and once inflammation is controlled, the frequency of administration is slowly tapered off. 8 references.

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Options in Managing Enteral Fistulae in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 401-404. 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 options in managing enteral fistula 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). Fistulae usually result from penetration of the inflammatory process from a segment of CD into adjacent tissue. Excluding postoperative complications, the most common cause of enteral fistulae in the Western world is CD. Intestinal fistulae are classified as internal, external, or mixed. Internal fistulae (in which an abnormal passageway develops between two segments of the intestinal tract) are relatively uncommon compared with external fistulae, in which a direct communication exists between the intestine and the skin of the abdominal wall or the vagina. Barium contrast radiography is the main diagnostic tool for fistula detection. Fistulae rarely close spontaneously and do not respond to sulfasalazine or steroids. Surgery often is required. Control of the associated inflammatory component by medical therapy (drugs) and bowel rest may allow for a smaller resection and fewer postoperative complications. It also is important to control any underlying infection and to optimize nutrition prior to surgery. However, the role of total parenteral (outside the gastrointestinal system) nutrition (TPN) is controversial. Medical management of fistulae in CD includes the use of antibiotics; immunomodulating agents including azathioprine, 6 mercaptopurine (6 MP), and cyclosporine; and anti tumor necrosis factor (TNF) alpha antibody (Remicade). The authors describe the use of each of these drugs and conclude with a brief discussion of rectovaginal fistulae, gastrocolic and duodenocolic fistulae, and enterovesicular fistulae; for each of the latter, the reader is referred to a separate chapter in the text. 1 table. 12 references.

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Pancreatitis in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 329-332. 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 pancreatitis 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). There is a higher incidence and prevalence of pancreatitis in patients with inflammatory bowel disease (IBD) than in the general population. The pancreatitis can be acute or chronic, or subclinical or overt, and has many causes. The most common cause is medications used to treat IBD, especially azathioprine and 6 mercaptopurine. Other causes of pancreatitis include duodenal involvement from Crohn's disease (CD), gallstones (cholelithiasis), and primary sclerosing cholangitis (PSC). Pancreatitis also can be caused by high serum concentrations of triglycerides during total parenteral nutritional (TPN) therapy for CD, and may also be a primary extra-intestinal

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manifestation of IBD. Treatment is different for each cause. For drug-induced pancreatitis, discontinuation of the drug should improvethe pancreatitis. For TPNinduced pancreatitis, oral medium-chain triglycerides should be substituted for the lipid emulsion. For pancreatitis that has developed from gallstones, the usual treatment is laparoscopic cholecystectomy (removal of the gallbladder). Idiopathic (of unknown cause) pancreatitis is often successfully treated by treating the underlying IBD. 1 table. 10 references. ·

Pregnancy and Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 613-618. 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 pregnancy in inflammatory bowel disease (IBD) 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 IBD. This chapter focuses on drug therapy and side effects issues in these challenging patients from the point of view of the gastroenterologist; an additional chapter addresses pregnancy in IBD from the perspective of an obstetrician. The author discusses inheritance, fertility, the influence of UC and CD on pregnancy, the activity of disease and the influence on pregnancy, and the assessment of disease activity in pregnant patients. The author then summarizes the use of medications in pregnancy, including nonspecific symptomatic agents, sulfasalazine, mesalamine, antibiotics, steroids, immunomodulatory drugs, methotrexate and cyclosporine, and infliximab. The author stresses the importance of physicians communicating clearly to their female patients desiring to get pregnant that their disease should be in remission before attempting to conceive and that medications that are keeping them in remission should not be discontinued either prior to conception or during the first trimester. 12 references.

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Pseudo-Intractability of Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 77-80. 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 pseudointractability of inflammatory bowel disease (IBD) 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 IBD. Inability to produce or sustain a clinical remission or to prevent frequent relapses should not lead physicians to make too early a presumption that the disease is truly intractable (resistant to treatment). Once the intractability label has been assigned, it connotes a more serious form of IBD, one that will require more time, more attention, more patient-family-physician distress, the likely inclusion of 'big gun' pharmacotherapy (drugs), and even the consideration of surgical intervention. Before embarking on a course of management, whether medical or surgical, for assumed intractability, it is reasonable to consider the alternative: that factors other than the IBD

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itself may account for recurrent, poorly or incompletely responsive, or even intractable symptomatology. It is easy to diagnose active inflammation but not always as easy to attribute the convincing and supportive objective features to a wide range of associated subjective complaints and objective findings. Because of this, pseudo-intractability or pseudo-relapse must always be considered a possible explanation for disagreement between subjective and objective symptoms. Factors possibly responsible for aggravating or mimicking disease activity should be sought, modified, or eliminated whenever possible. The author concludes that initiating, prolonging, or modifying therapies that have the potential for both short-term and long-term complications is serious business and any decision to do so should be considered carefully when managing what is thought to represent intractability or the inability to maintain disease remission. 1 table. 11 references. ·

Psychiatric Complications of Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 573-576. 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 psychiatric complications 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). About one-half of patients with active Crohn's disease have a diagnosable psychiatric disorder, a proportion that is significantly increased compared with that among patients suffering from other chronic medical illnesses. About one-quarter of patients suffering from ulcerative colitis likewise have a diagnosable psychiatric disorder. However, this proportion is not significantly greater than the proportion of patients with psychiatric disorder with other chronic medical illnesses. The common psychiatric disorders found in association with IBD include delirium, depression, anxiety, and personality disorders. The author discusses each of these disorders, emphasizing current concepts in management. The role of the psychiatrist in IBD is to assist the gastroenterologist in the recognition, diagnosis, and treatment of these conditions. 6 references.

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Coexistence of Inflammatory Bowel Disease and Irritable Bowel Syndrome Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 87-90. 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 coexistence of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) 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 IBD. Irritable bowel syndrome (IBS) is a chronic abdominal symptom complex for which no structural underlying abnormality can be demonstrated. It is a common disorder that affects all age groups with an increased frequency in females. Few if any of the clinical features of

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IBS can confidently distinguish it from IBD. The multiplicity and chronicity of symptoms and their relationship to altered bowel habit can be helpful hints. A psychoneurotic disposition, evidence of anxiety or depression, and a tendency to somatize symptoms referable not only to the gut but other organ systems are pointers in favor of IBS. However, when IBS occurs in a patient with established IBD, this can be a difficult diagnosis. Since IBS is a very common disorder, it is not unexpected to find patients with both IBS and IBD. The author considers whether there is a special relationship between these two disorders. There is good scientific evidence that inflammation of the gut alters its physiologic performance, and this may persist after resolution of the inflammation. The author concludes that IBS occurs with greater frequency in certain patients in remission from IBD, and this is more easily seen in UC than in CD. Symptoms of IBS in the context of IBD are no different from those typical for that condition. An awareness of this relationship is of key importance in making a confident diagnosis, as is a good knowledge of the patients' history and the characteristic behavior of their IBD. In some complicated IBD patients, extensive investigation by colonoscopy with or without small bowel radiography may be required. For most patients, treatment of IBS should follow the usual guidelines with notable exceptions in the case of patients with histories of obstruction. 1 figure. 17 references. ·

Consultations and the Patient with Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 23-24. 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 consultative process 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). Effective medical care of the patient with IBD not only requires concern for the patient's medical and psychosocial problems but also necessitates an understanding of the gastroenterologist-referring physician interface. The chronic nature of these disorders should prompt managed care organizations (MCOs) to recognize the importance of promoting a coordinated approach. Most primary care physicians are uncomfortable with assuming significant responsibility for the overall supervision of IBD patients, yet they usually do not wish to be excluded from the decision-making process. The chapter offers some personal views of the IBD consultative process, observations of the generalist-gastroenterologist interface as it relates to IBD, and several clinical suggestions regarding IBD patient management. Topics include parents and the IBD consultation, information seeking, hereditary concerns, communications with the referring physician, multiple visits, and surgical referral. The author concludes that the IBD consultation requires evaluation of the impact of IBD on the patient's ability to function as well as other clinical factors. The referring physician may either wish to delegate ongoing IBD care to the consultant or may intermittently refer the patient for reevaluation. In either case, close attention to letters after each visit and efforts to keep the referring physician involved in the management process are essential. 5 references.

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Azthioprine Metabolism in Inflammatory Bowel Disease: Correlation with Efficacy and Toxicity Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 377-381. 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 metabolism of azathioprine in patients with Crohn's disease (CD) is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with CD and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). In active CD, when combined with corticosteroids, azathioprine (AZA) induces remission faster, more frequently, and with a lower cumulative steroid dose than prednisone alone. Furthermore, AZA and 6MP (6 mercaptopurine, a subcompound of AZA) have been shown to eliminate the need for corticosteroids in about 75 percent of patients, with a median response time of 12 to 16 weeks, and these drugs have proven efficacy in maintaining long-term remission. Several well-controlled clinical trials in patients with CD has affirmed that the clinical response to azathioprine therapy largely is dependent on the duration of therapy. Indeed, patients who were weaned from prednisone before azathioprine could achieve its effect did not have a favorable clinical response to therapy. In most patients, treatment required at least 4 months of combination therapy. However, 30 percent of patients do not respond favorably to the usually administered doses (1 to 2 milligrams per kilogram). Most physicians measure drug efficacy either by an improvement in clinical symptoms and quality of life or by the ability to maintain remission while weaning off corticosteroid therapy. Practitioners tend to rely on their clinical judgment and experience in determining the dose of azathioprine to be used in treating patients with inflammatory bowel disease (IBD). Some start with 50 or 75 milligrams per day regardless of weight and then increase by 25 milligram increments. The wide dose range of azathioprine currently used in clinical practice would suggest that a safe and established therapeutic dose has not yet been established. As a consequence, clinicians must always remain aware of potential adverse effects, including allergic reactions, hepatitis (inflamed liver), pancreatitis, bone marrow suppression, and lymphoma (tumors of the lymphoid tissue), while attempting to achieve a therapeutic response. 1 figure. 18 references.

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Surgical Treatment of Inflammatory Bowel Disease Source: in Textbook of Gastroenterology. 4th ed. [2-volume set]. Hagerstown, MD: Lippincott Williams and Wilkins. 2003. p. 1760-1790. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-6423. Fax: (301) 223-2400. Website: www.lww.com. PRICE: $289.00. ISBN: 781728614. Summary: This chapter on the surgical treatment of inflammatory bowel disease (IBD) is from a comprehensive gastroenterology textbook that provides an encyclopedic discussion of virtually all the disease states encountered in a gastroenterology practice. This chapter covers Crohn's disease, ulcerative colitis, and indeterminate colitis. The authors note that although as many of half of the patients who have IBD require at least one surgical procedure during their lifetime, the decision to operate is rarely an easy one. Factors to take into consideration are the age and the general condition of the

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patient; the extent of the disease; the duration of the disease and the treatment offered to that point; and the specific complication in regard to the available treatment options. The authors consider surgical options and their anticipated results in view of the different indications for surgical treatment of IBD. The authors emphasize new options offered by advances in laparoscopic surgery. The chapter is illustrated with black-andwhite reproductions of imaging studies and drawings. 22 figures. 2 tables. 250 references. ·

Computer Database for Patients with Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 29-33. 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 a computer database 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). While physicians are seeing more and more patients with IBD, it remains a relatively rare entity, characterized by varied symptoms and possibly etiologies (causes). Progress in understanding and treating this heterogeneity will require the creation of large national and international cross-sectional IBD data resources. The goal of such a database would be to characterize a large number of currently followed IBD patients according to validated clinical classification systems. Use of a database system is now indispensable both at the individual (gastroenterologist) and collective (referral centers, national and international organizations) levels. The computer will allow the gastroenterologist to easily retrieve the history of each patient and to monitor other course in the context of other patients. The chapter describes a computer software program that was created on the Microsoft Access(r) DataBase Manager, with the oriented object language V.B.A. (Visual Basic for Application) concept, allowing a great level of interactivity. The two main bodies of the software are data management and data processing. Data management comprises four main parts: Patient identification record, which deals with administrative data; one or more patient evolution records, which describe the patient's history, clinical characteristics, and treatment; synthesis, which are summary files containing selected medical data; and tools to facilitate a patient's record search. The author notes that the data processing portion of the software is not in its final version. Numerous illustrations depict the screens of the software program. The author concludes by briefly describing the possibilities of putting the IBD database on the Internet. 6 figures. 8 references.

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Appropriate Use of Corticosteroids in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 363-366. 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 corticosteroids in managing inflammatory bowel disease (IBD) is from the second edition of a book devoted to the details of medical,

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surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as IBD. Glucocorticoids are a mainstay for the treatment of severe IBD. The efficacy of corticosteroids to induce remission in both CD and Ulcerative Colitis (UC) has been well established in large randomized controlled trials. At times, a focus on adverse events has diminished the recognition of the usefulness of corticosteroids. The authors suggest approaches for the appropriate use of corticosteroids, including corticosteroid-sparing strategies, in patients with IBD. Corticosteroids used in the treatment of IBD are prednisone, prednisolone, methylprednisolone, and budesonide. Prednisone and prednisolone have comparable glucocorticoid potency, whereas methylprednisolone is slightly more potent. In IBD, their use should be restricted to severe, active disease, with the aim of inducing remission. Simple dosing considerations can decrease the possibility of serious side effects. For example, steroids should be given as a single morning dose to coincide with the natural circadian rhythm of endogenous (naturally occurring in the body) corticosteroids. Corticosteroid sparing strategies incorporate the use of nutrition, budesonide, aminosalicylates, antibiotics, azathioprine and 6 mercaptopurine (immunomodulators), methotrexate, cyclosporine, and anti-tumor necrosis factor alpha. 13 references. ·

Systemic Corticosteroids in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 127-131. 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 systemic corticosteroids in the treatment 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). Any therapy in UC must be considered with respect to its use in acute relapse, maintenance, and with chronic continuous (chronic active colitis) or frequently relapsing colitis. Corticosteroid therapy in UC may be initiated topically or systemically, and systemic treatment may be given orally or parenterally (outside the gastrointestinal tract, e.g., intravenous or intramuscular). Systemic administration may be combined with local therapy; systemic corticosteroids may be combined with 5-ASA preparations, again either topically, orally, or both, and occasionally with immunosuppression. Different systemic corticosteroid preparations are available, with similar anti-inflammatory effects, but with some differences in potency and tendency to cause side effects. Despite the relative homogeneity of patients in UC as a clinical group (at least in comparison with Crohn's disease), there are different scenarios of disease onset, activity, severity, and distribution. With this substantial number of variables, despite a number of clinical trials performed since those that initially established the value of corticosteroids, there remain extensive areas in which there is no firm evidence to guide management. This chapter briefly surveys those corticosteroids available for systemic use before considering practicalities of use in patients with various categories of UC. 10 references.

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Methotrexate in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 383-386.

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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 the antiinflammatory drug methotrexate in treating inflammatory bowel disease (IBD) 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 IBD. The majority of patients who are treated with a course of conventional glucocorticoid therapy become either steroid dependent (36 percent) or steroid resistant (20 percent). Patients who require chronic steroid therapy are appropriate candidates for immunosuppressive drug therapy. The purine antimetabolites, 6-mercaptopurine (6-MP) and azathioprine, are effective in the majority of, but not all, patients both for induction of remission and for maintenance therapy in CD. Approximately 30 percent of patients are unresponsive to low-to-moderate doses of azathioprine. Although these agents are relatively well tolerated as chronic therapy, serious toxicity can occur; therefore, alternative medical treatments are desirable. Kozarek and colleagues (1989) pioneered the use of methotrexate for the treatment of IBD. In their studies, two-thirds of patients had improvement in symptoms and a steroid-sparing effect also was documented. Colonoscopic improvement was demonstrated in one-third of the patients with CD but not in the patients with Ulcerative Colitis (UC). Additional studies over the decade since Kozarek's work support the effectiveness of methotrexate both in active disease and for maintenance therapy in previously steroid dependent patients. Methotrexate given intramuscularly at a relatively high dose (25 milligrams per week) in conjunction with prednisone was an effective remission induction therapy. Fifteen milligrams of methotrexate intramuscularly was effective for maintenance therapy. Currently, no reliable data from controlled trials exist to support the use of methotrexate as a therapy for UC. The authors conclude with a brief discussion of the use of methotrexate in combination with other drugs, notably infliximab (a drug used to treat rheumatoid arthritis). 30 references. ·

Coexistent Irritable Bowel Syndrome and Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 91-94. 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 second chapter on the coexistence of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) 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 IBD. Irritable bowel syndrome (IBS) is a chronic abdominal symptom complex for which no structural underlying abnormality can be demonstrated. It is a common disorder that affects all age groups with an increased frequency in females. Few if any of the clinical features of IBS can confidently distinguish it from IBD. This chapter focuses on the prevalence of IBS, clinically relevant pathophysiology, and the importance of the patient-physician relationship. The author notes that there are several pathophysiologic alterations found in the small bowel and colon of patients with IBS that could be aggravated or brought to the level of clinical awareness by IBD or its treatment. These alterations include pain or

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diarrhea after ileo-right colon resection (removal); active proctosigmoiditis; ileal pouch procedures; and an exaggeration of the patient's response to secretagogues, including caffeine and problems with lactose intolerance. The author emphasizes the benefits of explaining to the patient with both IBS and IBD the fact that she or he has two different disorders and that each may cause its own symptoms. Explaining the pathophysiology seems to help the patient adjust medications and understand and accept symptoms caused by meals or by stress. 6 references. ·

Inflammatory Bowel Disease Genetics Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 523-526. 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: While both genetic and environmental factors have been implicated in the development of inflammatory bowel disease (IBD), within the environment of Western industrial countries, the greatest risk for developing IBD is genetic. This chapter on genetics 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 IBD. Overall, 15 to 20 percent of patients have a family history of IBD. That familial aggregation is primarily genetic rather than from a shared environmental etiology, such as an infectious agent, is suggested by a lack of increased risk to spouses, and the observed aggregation of IBD occurring among relative raised separately. The authors discuss how risk is defined in the offspring of patients with IBD, genetic implications for management, and potential gene markers. The authors note that there are also important nongenetic associations with disease type: younger age of onset is associated with stricturing (narrowing) disease and small bowel disease, and it is inversely associated with inflammatory disease. Jewish ethnicity, smoking, and use of nonsteroidal antiinflammatory drugs (NSAIDs) are important risk factors for fistulizing disease, again including perforating disease. 2 tables. 8 references.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to inflammatory bowel disease 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:11

11 You will need to limit your search to “Directory” and “inflammatory bowel disease” 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 “inflammatory bowel disease” (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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Digestive Diseases Centers Program of the National Institute of Diabetes and Digestive and Kidney Diseases Source: Bethesda, MD: National Institutes of Health. National Institute of Diabetes and Digestive and Kidney Diseases. 1991. 26 p. Contact: Available from Office of Health Research Reports. National Institutes of Health, NIDDK, 9000 Rockville Pike, Building 31, Room 9A04, Bethesda, MD 20892. (301) 4963583. PRICE: Single copy free. Summary: This document describes 12 digestive diseases centers, each funded by the National Institute of Diabetes and Digestive and Kidney Diseases grant program. A center grant is generally a large, multidisciplinary allocation intended to stimulate research in digestive diseases by pooling resources and attracting young investigators as well as seasoned researchers from other fields. This directory presents information about the programs, investigators, administrative structures, histories, research, and recent scientific advances for each of the 12 digestive diseases centers. Facilities included are: the Massachusetts General Hospital Center for the Study of Inflammatory Bowel Disease; the University of Chicago Digestive Diseases Research Center; the University of North Carolina Center for Gastrointestinal Biology and Disease; the Stanford University School of Medicine Digestive Disease Center; the Center for Ulcer Research and Education at the University of California, Los Angeles; the Yale Liver Research Center; the Liver Center at the University of California, San Francisco; the University of Colorado Hepatobiliary Research Center; the Albert Einstein Liver Research Center; the Harvard Digestive Diseases Center; the University of Michigan Gastrointestinal Peptide Research Center; and the Center for Gastrointestinal Research on Absorptive and Secretory Processes, Tufts University. (AA-M).

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CHAPTER 7. MULTIMEDIA ON INFLAMMATORY BOWEL DISEASE Overview In this chapter, we show you how to keep current on multimedia sources of information on inflammatory bowel disease. 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 inflammatory bowel disease is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “inflammatory bowel disease” 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 “inflammatory bowel disease” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on inflammatory bowel disease: ·

Update: Medical and Surgical Intervention in Inflammatory Bowel Disease Source: Secaucus, NJ: Network for Continuing Medical Education (NCME). 1992. Contact: Available from NCME. One Harmon Plaza, Secaucus, NJ 07094. (800) 223-0272 or, in New Jersey, (800) 624-2102, or (201) 867-3550. PRICE: $50 for 2-week rental or $75 for purchase. Available only to NCME subscribers; subscriber fees as of 1995 are $1,920 for VHS subscription, $2,120 for U-matic subscription. Summary: Evolving medical and surgical therapies may delay or eliminate the need for colostomy or ileostomy in patients with conditions such as Crohn's disease or ulcerative colitis. In this continuing education video program, the authors review available diagnostic modalities; explore the new classes of drugs that treat inflammatory bowel disease (IBD); and discuss the advantages and disadvantages of alternative surgical

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methods for this group of illnesses. The video program confers 2 hours of CME credit. (AA-M). ·

Managing Inflammatory Bowel Disease Source: Princton, NJ: Films for the Humanities and Sciences. 2001. (VHS; DVD). Contact: Available from Films for the Humanities and Sciences. PO Box 2053 Princeton, NJ 08543-2053. (800) 257-5126. Fax: (609) 275-3767. Website: www.films.com. PRICE: $129.95 for VHS; $154.95 for DVD; plus shipping and handling. Item number: BVL30009. Summary: For reasons that are not altogether certain, inflammatory bowel disease (IBD) is affecting more and more Americans every year. In this videotape program from The Doctor Is In, Dr. Scott Plevy, formerly of Mount Sinai School of Medicine, and Dr. Susan Edwards, of the Dartmouth-Hitchcock Medical Center, seek to understand the spreading incidence of IBD. The doctors consider both Crohn's disease and colitis, the two primary forms of IBD, while describing pharmaceutical and surgical treatment options. The program includes case studies of two young women with IBD that focus on how they manage their debilitating conditions.

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Inflammatory Bowel Disease: Coping with Crohn's and Colitis Source: Princton, NJ: Films for the Humanities and Sciences. 1998. (VHS; DVD). Contact: Available from Films for the Humanities and Sciences. PO Box 2053 Princeton, NJ 08543-2053. (800) 257-5126. Fax: (609) 275-3767. Website: www.films.com. PRICE: $129.95 for VHS; $154.95 for DVD; plus shipping and handling. Item number: BVL9193. Summary: Inflammatory bowel disease (IBD) accounts for 250,000 doctor visits, 20,000 hospitalizations, and the loss of more than 1 million workdays every year. This videotape program examines the two predominant types of IBD: Crohn's disease and ulcerative colitis. Health professionals and patients discuss various medications being used; surgical options, including the ileal pouch, anal anastomosis, and strictureplasty; and the importance of nutrition, education, and support groups in improving the quality of day to day life for patients and their families. The documentary also includes diagrams, X rays, and endoscopic imaging.

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CHAPTER 8. PERIODICALS AND NEWS ON INFLAMMATORY BOWEL DISEASE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover inflammatory bowel disease.

News Services and Press Releases One of the simplest ways of tracking press releases on inflammatory bowel disease 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 “inflammatory bowel disease” (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 inflammatory bowel disease. 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 “inflammatory bowel disease” (or synonyms). The following was recently listed in this archive for inflammatory bowel disease: ·

Inflammatory bowel disease raises risk of thrombosis Source: Reuters Medical News Date: March 15, 2004

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Depression may lead to relapse in patients with inflammatory bowel disease Source: Reuters Medical News Date: February 27, 2004

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5-ASA therapy for inflammatory bowel disease no bar to colon cancer Source: Reuters Medical News Date: January 28, 2004

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Refractory inflammatory bowel disease responds to pulse cyclophosphamide Source: Reuters Medical News Date: March 03, 2003

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6-mercaptopurine safe in childbearing women with inflammatory bowel disease Source: Reuters Medical News Date: February 04, 2003

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Prior appendicectomy associated with less severe inflammatory bowel disease Source: Reuters Medical News Date: November 14, 2002

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Fracture risk increased in patients with inflammatory bowel disease Source: Reuters Medical News Date: September 23, 2002

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Inflammatory bowel disease risk differentially affected by childhood factors Source: Reuters Medical News Date: June 14, 2002

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Maternal inflammatory bowel disease linked to adverse pregnancy outcomes Source: Reuters Medical News Date: April 23, 2002

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Enzyme mimetic protects colon in rodent model of inflammatory bowel disease Source: Reuters Medical News Date: December 19, 2001

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Left handedness linked to increased risk of inflammatory bowel disease Source: Reuters Medical News Date: July 11, 2001

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CMV linked with severe inflammatory bowel disease Source: Reuters Medical News Date: April 16, 2001

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Gene expression may be key to inflammatory bowel disease Source: Reuters Medical News Date: March 15, 2001

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Measles-containing vaccines do not increase risk of inflammatory bowel disease Source: Reuters Medical News Date: March 14, 2001

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Gene profiling key to inflammatory bowel disease Source: Reuters Health eLine Date: March 14, 2001

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Common cause of inflammatory bowel disease and colorectal cancer unlikely Source: Reuters Medical News Date: January 30, 2001

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Inflammatory bowel disease, colon cancer link examined Source: Reuters Health eLine Date: January 26, 2001

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Osteoporosis not associated with newly diagnosed inflammatory bowel disease Source: Reuters Medical News Date: November 13, 2000

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6-Mercaptopurine favored over azathioprine for inflammatory bowel disease Source: Reuters Medical News Date: October 30, 2000

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Engineered bacteria help to treat inflammatory bowel disease Source: Reuters Health eLine Date: August 24, 2000

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Fecal calprotectin predicts relapse in inflammatory bowel disease Source: Reuters Medical News Date: August 17, 2000

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Fecal calprotectin, intestinal permeability predict relapse in inflammatory bowel disease Source: Reuters Medical News Date: July 20, 2000

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Nutritional status deteriorates early in inflammatory bowel disease Source: Reuters Medical News Date: July 13, 2000

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Early measles infection linked to inflammatory bowel disease Source: Reuters Medical News Date: June 21, 2000

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Intestinal flora, TNF polymorphisms linked to inflammatory bowel disease Source: Reuters Medical News Date: November 26, 1999

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Matrix metalloproteinase levels elevated in patients with inflammatory bowel disease Source: Reuters Medical News Date: October 25, 1999

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Diabetes drug troglitazone inhibits inflammatory bowel disease in mice Source: Reuters Medical News Date: August 13, 1999

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Diabetes drug may help inflammatory bowel disease Source: Reuters Health eLine Date: August 12, 1999

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Inflammatory bowel disease suppository recalled Source: Reuters Health eLine Date: June 23, 1999

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Maternal inflammatory bowel disease associated with adverse birth outcomes Source: Reuters Medical News Date: May 27, 1999

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High prevalence of inflammatory bowel disease validated in Manitoba Source: Reuters Medical News Date: May 21, 1999

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Low sensitivity limits widespread use of serologic tests for inflammatory bowel disease in children Source: Reuters Medical News Date: May 04, 1999

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 “inflammatory bowel disease” (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 “inflammatory bowel disease” (or synonyms). If you know the name of a company that is relevant to inflammatory bowel disease, 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 “inflammatory bowel disease” (or synonyms).


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Newsletters on Inflammatory Bowel Disease Find newsletters on inflammatory bowel disease using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “inflammatory bowel disease.” 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 “inflammatory bowel disease” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: ·

Role of Radiology in Evaluation of Inflammatory Bowel Disease Source: Pediatric Crohn's and Colitis Association Newsletter. p. 1, 3. May 1994. Contact: Available from Pediatric Crohn's and Colitis Association, Inc. P.O. Box 188, Newton, MA 02168. (617) 244-6678. Summary: This newsletter article considers the role of radiology in the evaluation of inflammatory bowel disease (IBD). The author stresses that, while new diagnostic modalities are useful in many cases, the main tools for evaluation of IBD continue to be barium contrast studies of the gastrointestinal (GI) tract. The author explores the use of both the upper GI series and the barium enema. For each test, the author reviews the advantages and drawbacks and provides recommendations. The final section of the article summarizes the indications for newer modalities in evaluating IBD. Options reviewed include computerized tomography (CT scan), ultrasound, and nuclear medicine techniques. The author concludes that the pediatrician working together in consultation with the radiologist can decide the best test for the quickest and most accurate evaluation of IBD with the least morbidity.

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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.

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

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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 “inflammatory bowel disease” (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 inflammatory bowel disease: ·

Inflammatory Bowel Disease: Making Sense of a Mystery Ailment Source: Harvard Health Letter. 22(2): 4-6. December 1996. Contact: Available from Harvard Health Letter. P.O. Box 380, Boston, MA 02117. (617) 432-1485. Summary: This article introduces general readers to the symptoms and causes of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC). The authors discuss the differential diagnosis of IBD, including ruling out irritable bowel syndrome (IBS) and bacterial infections, and the diagnostic tests that are commonly used to confirm IBD. The authors note that IBD appears to run in families, and they report on current genetic research in this area as well as on research into a possible environmental stimulus that can trigger the disease in genetically susceptible people. The choice of therapy is largely determined by which part of the bowel is affected by IBD and whether the problem is Crohn's or UC. People can use topical therapy such as steroid suppositories or enemas to treat the inflammation directly if only the rectum or lower portion of the colon is affected. However, oral medication often becomes necessary. The first choice for drug therapy is sulfasalazine (Azulfidine). The authors conclude with a brief discussion of the surgical options available for people with IBD who don't respond to drug therapy. 1 table. (AA-M).

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Inflammatory Bowel Diseases: Misery Needn't be the Norm Source: Mayo Clinic Health Letter. 19(10): 1-3. October 2001. Contact: Available from Mayo Clinic Health Letter. Subscription Services, P.O. Box 53889, Boulder, CO 80322-3889. (800) 333-9037 or (303) 604-1465. Summary: This health education newsletter article familiarizes readers with inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis. The author describes the two types of IBD, and their incidence, symptoms, diagnosis, drug therapy, lifestyle treatments, and surgical options. The signs and symptoms of Crohn's disease and ulcerative colitis may develop gradually or suddenly and can be similar: chronic diarrhea, vomiting, abdominal cramping, blood in the stool, weight loss and fatigue, and fever in severe cases. In addition, people with Crohn's disease are more likely to develop open sores (ulcers) in their digestive tract. Blood tests and diagnostic imaging confirm the diagnoses of inflammatory bowel disease. Drug therapy is a key component of treating IBD. Although drugs do not offer a cure for IBD, they often help control the condition. Once the right drug or combination of drugs is determined, symptoms can often be reduced. Drugs can include anti-inflammatory drugs, immune modulators, and antibiotics. Lifestyle treatments include dietary management, adequate fluid intake, stress management (including the use of support groups), and avoidance of nonsteroidal anti-inflammatory drugs (NSAIDs). At least 70 percent of those patients with Crohn's disease will need at least one or more surgeries. One side bar reminds readers of the risk of colon cancer in people with IBD. 1 figure.


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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 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.

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Inflammatory Bowel Disease. Part II: Treatment Source: Intestinal Fortitude. 10(4): 1-3. 2000. Contact: Available from Intestinal Disease Foundation. 1323 Forbes Avenue, Suite 200, Pittsburgh, PA 15219. (412) 261-5888. Summary: This newsletter article, the second in a two part series on inflammatory bowel disease (IBD), reviews the treatment options for people with the disease. The goals of therapy for IBD include symptom control and remission; good nutrition, for healing and to avoid additional problems relating to nutritional deficiencies; and quality of life, a common goal for all of the therapies used, including medications, coping techniques, and surgeries. For ulcerative colitis (UC) patients, removal of the colon produces a cure. It is major surgery, however, and for that reason needs to be carefully considered. Surgery for Crohn's disease (CD) is usually done to treat obstructions (from strictures), infections (abscesses), or non healing fistulas. There is a 10 percent chance per year of recurrence of the CD following surgery, but use of medications, along with surgery, may help reduce the odds. The author reviews four traditional therapies for IBD: 5 aminosalicylates, antibiotics, corticosteroids, and immunomodulators. The authors also considers a new therapy, infliximab (Remicade), a medication that works on a cellular level to prevent inflammation and was recently approved by the FDA for treatment of CD. The future treatment of UC and CD will involve medications that better target the immune chemicals responsible for inflammation. For now, the treatment of IBD remains a multidisciplinary approach (medical, surgical, and nutritional) aimed at controlling symptoms and maintaining wellness.

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Academic Periodicals covering Inflammatory Bowel Disease Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to inflammatory bowel disease. In addition to these sources, you can search for articles covering inflammatory bowel disease 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 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 9. 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 inflammatory bowel disease. 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 DIÒ Advice for the PatientÒ 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 inflammatory bowel disease. 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,

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etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to inflammatory bowel disease: Infliximab ·

Systemic - U.S. Brands: Remicade http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203667.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

Sulfasalazine ·

Systemic - U.S. Brands: Azulfidine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202537.html

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 ConsultÔ Mosby’s Drug ConsultÔ 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,

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Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. 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 Institute12: ·

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/

12

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

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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.13 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:14 ·

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

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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

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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

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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

13 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). 14 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 NLM Gateway15 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.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “inflammatory bowel disease” (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 34062 210 1018 17 72 35379

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 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.19 Simply search by “inflammatory bowel disease” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

15

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

16

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). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

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 Biologists20 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.21 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.22 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 Inflammatory Bowel Disease In the following section, we will discuss databases and references which relate to the Genome Project and inflammatory bowel disease.

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).23 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. 20 Adapted from 21

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. 22 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. 23 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 “inflammatory bowel disease” (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 inflammatory bowel disease: ·

Inflammatory Bowel Disease 1 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=266600

·


·


·


·


·


·


·


·


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

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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, 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

·

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

·

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

·

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

·

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

·

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

·

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

·

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

·

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

·

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

·

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 “inflammatory bowel disease” (or synonyms) into the search box and click “Go.”

Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 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 Database25 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 24 Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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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 “inflammatory bowel disease” (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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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 inflammatory bowel disease 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 inflammatory bowel disease. 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 inflammatory bowel disease. 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 “inflammatory bowel disease”:

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·


Other guides Anal and Rectal Diseases http://www.nlm.nih.gov/medlineplus/analandrectaldiseases.html 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 Peptic Ulcer http://www.nlm.nih.gov/medlineplus/pepticulcer.html Ulcerative Colitis http://www.nlm.nih.gov/medlineplus/ulcerativecolitis.html

Within the health topic page dedicated to inflammatory bowel disease, the following was listed: ·

General/Overviews Crohn's Disease http://www.nlm.nih.gov/medlineplus/tutorials/crohnsdiseasloader.html Introduction to Crohn's Disease Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/research/info/aboutcd

·

Diagnosis/Symptoms Abdominal Pain, Long-Term Source: American Academy of Family Physicians http://familydoctor.org/528.xml Abdominal Pain, Short-Term Source: American Academy of Family Physicians http://familydoctor.org/527.xml 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 Lower GI Series Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/lowergi/index.htm Upper GI Series Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/uppergi/index.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 Surgery for Crohn's Disease Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/research/info/surgerycd Treatment Options in IBD Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/research/info/treatmentoptions Types of Medications for Inflammatory Bowel Disease Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/research/info/medications

·

Nutrition Diet and Nutrition Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/research/info/diet

·

Specific Conditions/Aspects Crohns Disease and Ulcerative Colitis: Understanding Colorectal Cancer http://www.ccfa.org/frameviewer/?url=/media/pdf/cancer.pdf Extraintestinal Complications of IBD: Arthritis Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/research/info/arthritis Extraintestinal Complications: Bone Loss Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/research/info/bone Extraintestinal Complications: Eye Disorders Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/research/info/eye Extraintestinal Complications: Kidney Disorders Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/research/info/kidney Extraintestinal Complications: Liver Disease Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/research/info/liver

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Extraintestinal Complications: Skin Disorders Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/research/info/skin Measles Vaccine and Inflammatory Bowel Disease (IBD) Source: National Immunization Program http://www.cdc.gov/nip/vacsafe/concerns/autism/ibd.htm Short Bowel Syndrome Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/shortbowel/index.htm ·

Children Treating IBD in Children and Adolescents Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/kidsmeds.html

·

From the National Institutes of Health Crohn's Disease Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/crohns/index.htm Crohn's Disease Source: National Institutes of Health http://www.nih.gov/news/WordonHealth/dec2001/story02.htm

·

Latest News Bacterial DNA Reduces Inflammation in Mice Source: 02/03/2004, National Institute of Allergy and Infectious Diseases http://www.nih.gov/news/pr/feb2004/niaid-03.htm

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Organizations American Gastroenterological Association http://www.gastro.org/ American Society of Colon and Rectal Surgeons http://ascrs.affiniscape.com/ Crohn's & Colitis Foundation of America http://www.ccfa.org/ National Institute of Diabetes and Digestive and Kidney Diseases http://www.niddk.nih.gov/

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Research Bacterial DNA Reduces Inflammation in Mice Source: National Institute of Allergy and Infectious Diseases http://www.nih.gov/news/pr/feb2004/niaid-03.htm Challenges in IBD Research: Updating the Scientific Agendas 2002 http://www.ccfa.org/frameviewer/?url=/media/pdf/laychallenges.pdf


Women Women's Issues http://www.ccfa.org/frameviewer/?url=/media/pdf/womens.pdf

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 inflammatory bowel disease. 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: ·

Facts About Inflammatory Bowel Disease Source: Toronto, Canada: Crohn's and Colitis Foundation of Canada. 1997. 12 p. Contact: Available from Crohn's and Colitis Foundation of Canada. 21 St. Clair Avenue East, Suite 30, Toronto, Ontario, Canada M4T 1L9. (800) 387-1479 or (416) 920-5035. Fax (416) 929-0364. E-mail: [email protected]. PRICE: Single copy free. Summary: This booklet describes inflammatory bowel disease (IBD), a term used to describe two similar, but distinct conditions: Crohn's disease and ulcerative colitis (UC). These diseases affect the digestive system and cause the intestines to become inflamed, form sores (ulcers), bleed easily, and scar. The booklet outlines the symptoms of IBD, the parts of the body involved, complications, and possible treatments (diet, medication, surgery). Potential complications of IBD include malnutrition and malabsorption. Nutritional therapy, which includes a combination of diet, nutritional supplements, and bowel rest is important in the treatment of IBD-related malnutrition and malabsorption. To control IBD, anti-inflammatory drugs, drugs to prevent or reduce symptoms, and drugs that treat complications are prescribed. People with Crohn's disease may need surgery to treat abscesses and fistulas, to remove an obstruction or blockage of the intestine, or to remove a piece of diseased intestine. Surgery is less common in UC than in Crohn's disease. This booklet also explains diagnostic tests, surgical procedures, and the role of the health care team. 1 figure.

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Nutrition, Diet and Inflammatory Bowel Disease Source: Toronto, Canada: Crohn's and Colitis Foundation of Canada. 1997. 8 p. Contact: Available from Crohn's and Colitis Foundation of Canada. 21 St. Clair Avenue East, Suite 30, Toronto, Ontario, Canada M4T 1L9. (800) 387-1479 or (416) 920-5035. Fax (416) 929-0364. E-mail: [email protected]. PRICE: Single copy free.

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Summary: This booklet describes the relationship between nutrition and inflammatory bowel disease (IBD), a term used to describe two similar, yet distinct conditions: Crohn's disease and ulcerative colitis (UC). These diseases affect the digestive system and cause the intestines to become inflamed, form sores (ulcers), bleed easily, scar, and lose the normal smoothness of their inner lining. Symptoms of IBD include abdominal pain, cramping, fatigue, and diarrhea. Malabsorption refers to the reduced ability of the digestive tract to absorb nutrients. Malabsorption may happen in IBD when nutrients are lost through bleeding and diarrhea, when medications interact adversely with nutrients, or when part of the intestine is surgically removed, leaving less absorptive tissue to process ingested nutrients. A healthy diet is a key component in the treatment of IBD. The booklet concludes with a nutrition checklist to help readers determine whether they ought to consult a physician or dietitian. 1 figure. 3 tables. ·

Medication for Inflammatory Bowel Disease Source: Toronto, Canada: Crohn's and Colitis Foundation of Canada. 1997. 12 p. Contact: Available from Crohn's and Colitis Foundation of Canada. 21 St. Clair Avenue East, Suite 30, Toronto, Ontario, Canada M4T 1L9. (800) 387-1479 or (416) 920-5035. Fax (416) 929-0364. E-mail: [email protected]. PRICE: Single copy free. Summary: This booklet describes the role of medications in the management of inflammatory bowel disease (IBD), a term used to describe two similar, but distinct conditions: Crohn's disease and ulcerative colitis (UC). These diseases affect the digestive system and cause the intestines to become inflamed, form sores (ulcers), bleed easily, and scar. People with Crohn's disease or UC may take prescription or over-thecounter medications to reduce inflammation in the gastrointestinal tract, to control diarrhea and cramps, and to treat complications. This booklet describes the most commonly prescribed medications: how they work, and common (or especially serious) side effects. The brochure also discusses the role of nicotine in UC and briefly mentions medications used to treat other symptoms and problems, including hemorrhoids and anal fissures, anal itching, vitamins and minerals, and pain killers. 1 figure.

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Sexuality, Fertility, Pregnancy and Inflammatory Bowel Disease Source: Toronto, Canada: Crohn's and Colitis Foundation of Canada. 1997. 8 p. Contact: Available from Crohn's and Colitis Foundation of Canada. 21 St. Clair Avenue East, Suite 30, Toronto, Ontario, Canada M4T 1L9. (800) 387-1479 or (416) 920-5035. Fax (416) 929-0364. E-mail: [email protected]. PRICE: Single copy free. Summary: This booklet discusses sexuality, fertility, pregnancy and inflammatory bowel disease (IBD), which is a term used to describe two similar, but distinct conditions: Crohn's disease and ulcerative colitis (UC). These diseases affect the digestive system and cause the intestines to become inflamed, form sores (ulcers), bleed easily, and scar. Abdominal cramps and diarrhea, which are common in IBD, may inhibit sexual activity. Malabsorption (which reduces the ability of the digestive tract to absorb the vitamins and minerals in food) may lead to undernourishment, weakness, or loss of energy, all of which may have an impact on the person's sexuality. Medications used to treat IBD do not particularly affect sexual desire or performance, although surgery, a common form of treatment for IBD, and postoperative recovery times do. IBD itself does not affect fertility, although the lack of proper nutrition can affect both men's and women's reproductive abilities. If IBD was controlled at the time of conception, the disease has little or no effect on the outcome of pregnancy. If the disease was active at conception, or becomes active during the pregnancy, there's a slightly increased risk of

Patient Resources 271 miscarriage or premature birth. Pregnancy does not increase the chance of recurrence of IBD. Good nutrition, important for all IBD patients, is especially crucial for a pregnant woman with IBD. Pregnant women should discuss with their physician the benefits and risks of taking IBD medications during pregnancy. 1 figure. ·

Physicians' Guide to Inflammatory Bowel Disease Source: New York, NY: Crohn's and Colitis Foundation of America. 1990. 26 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 booklet is aimed at increasing awareness of inflammatory bowel disease (IBD) among health care professionals, specialists, generalists, pharmacists, and nurses, by providing practical and specific information on diagnosing, treating, and managing IBD and its complications. Topics include a definition of IBD, diagnostic issues, treating the symptoms, treating the mucosal inflammation, surgical intervention, nutritional management in Crohn's disease, issues in infertility and pregnancy, and complications of IBD. Seven appendixes summarize the material presented. A quiz for continuing medical education credit is included.

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Inflammatory Bowel Diseases: Information for Patients and Their Families Source: Chicago, IL: Gastro-Intestinal Research Foundation. 1996. 17 p. Contact: Available from Gastro-Intestinal Research Foundation. 70 East Lake Street, Suite 1015, Chicago, IL 60601. (312) 332-1350. PRICE: Single copy free. Summary: This booklet was written to answer some of the questions patients often ask about inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis (UC). Topics include the normal digestive system, the nature of IBD, incidence, symptoms, diagnosis, treatment, and prognosis. Ulcerative colitis is an inflammation of the colon (large bowel). The inner lining of the colon is affected most severely, with vascular congestion, tiny ulcerations, and bleeding. Crohn's disease of the small intestine is an inflammation involving the entire thickness of the bowel wall. The most common area of the small intestine affected is the last segment entering the colon, known as the ileum. Diagnosis is aided by a description of the nature of the diarrhea, the type of abdominal pain, and characteristics of the rectal bleeding, in addition to a complete account of the health status and the life situation of the individual patient. The authors focus on the diagnosis of IBD as differentiated from irritable bowel syndrome (IBS). Since the causes of IBD are not known, treatment is directed at relieving the symptoms and improving and maintaining the general health of the patient physically, nutritionally, and emotionally. In most instances, IBD can be controlled and the majority of patients live a normal life, even though they may need to take medication and remain under medical supervision indefinitely. The authors hope that the booklet will reduce patient anxiety, increase understanding among patients and their families, aid in the effective implementation of treatment programs, and encourage interest in the support of the research necessary to identify the causes and subsequently the cures of these disorders. The brochure concludes with a discussion of the present basic research and clinical studies being undertaken in this area. 3 figures. (AA-M).

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Living with Inflammatory Bowel Disease: Your Illness and Its Treatment Source: San Bruno, CA: StayWell Company. 1998. 16 p.

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Contact: Available from StayWell Company. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 244-4512. PRICE: $1.60 plus shipping and handling; bulk copies available. Order number 11003. Summary: This brochure describes inflammatory bowel disease (IBD), characterized by inflammation (irritation and swelling) of the digestive tract. IBD has two subtypes: ulcerative colitis (UC) and Crohn's disease (CD). Ulcerative colitis occurs in the rectum and sometimes in the colon; Crohn's disease can occur anywhere from the mouth to the anus, but usually affects the last part of the small intestine. The brochure describes how the digestive tract works, how IBD affects the digestive tract, diagnosing and monitoring IBD, treating IBD with medication, managing daily life, managing nutrition, and surgery for IBD. The symptoms of Crohn's can include abdominal pain and bloating after meals, sores in the anal area, high fever and chills, loss of appetite (possible weight loss), bloody diarrhea, and nausea or vomiting. Diagnostic tests that may be used to confirm Crohn's disease include barium enema, upper GI series, and small bowel series, endoscopy, blood or stool tests, and CT scan. 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. Drug therapy for IBD can include antiinflammatory agents, corticosteroids, immunosuppressive agents, and antibiotics. Readers are advised to monitor their dietary habits and take note of which foods seem to be problematic. Surgical options described include limited bowel resection, ileoanal pouch, proctocolectomy with permanent ileostomy, continent ileostomy, strictureplasty, and anal fistula surgery; each technique is illustrated with a simple line drawing. The brochure also explains what patients can expect before and after surgery for IBD. The brochure encourages 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 numbers of the Crohn's and Colitis Foundation (800-9322423) and the United Ostomy Association (800-826-0826) are provided. The brochure is illustrated with full color drawings. 19 figures. ·

ABC's of Pediatric Inflammatory Bowel Disease Source: Newton, MA: Pediatric Crohn's and Colitis Association, Inc. 199x. 8 p. Contact: Available from Pediatric Crohn's and Colitis Association, Inc. Box 188, Newton, MA 02168. (617) 244-6678. PRICE: Single copy free. Summary: This brochure provides information for the parents of children newly diagnosed with inflammatory bowel disease (IBD), either in the form of Crohn's disease or ulcerative colitis. Written in a question-and-answer format, the brochure covers topics including a definition of IBD; the incidence and prevalence of IBD in children; the cause of IBD; medical tests that might be indicated; how the child's growth can be affected by IBD; treatment considerations; the emotional impact of IBD on a child; how IBD may affect the child at school; and how IBD affects family life. One chart summarizes the physical, social, emotional, and family issues that may exist for children with IBD and their families. The brochure concludes with a glossary of terms and a list of the scientific advisory board members of the association.

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Inflammatory Bowel Disease Source: Bethesda, MD: American Gastroenterological Association. 1996. 5 p.

Patient Resources 273 Contact: Available from GIDH-AGA Patient Education Center. P.O. Box 1274, West Caldwell, NJ 07007-9562. PRICE: 25 copies free to health care professionals for distribution to patients. Summary: This brochure provides patients with basic information about inflammatory bowel disease (IBD), a term that refers to both ulcerative colitis (UC) and Crohn's disease. Ulcerative colitis causes inflammation of the lining of the large intestine. Crohn's disease causes inflammation of the lining and wall of the large and or small intestine. When inflamed, the lining of the intestinal wall is red and swollen, becomes ulcerated, and bleeds. The brochure describes the normal function of the digestive system, the causes of IBD, the symptoms of UC, diagnostic tests used to confirm UC, the risk of colon cancer in people with UC, the symptoms of Crohn's disease, the complications associated with Crohn's disease (intestinal blockage, fistulas), treatment options for IBD, the role of nutrition and food choices, coping with IBD, and determining when surgery is needed. The goal of nutritional management for people with IBD is to modify the diet to decrease gastrointestinal symptoms while maintaining adequate nutrient intake. The author stresses that, although IBD is a chronic disease that has periods of remission and relapse, most people have a normal life span and a good quality of life. The brochure concludes with a glossary of terms. 4 figures. 3 references. (AA-M). ·

Medications for Inflammatory Bowel Disease Source: New York, NY: Crohn's and Colitis Foundation of America, Inc. (CCFA). 199x. 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 brochure reviews for health professionals the available information on both the standard drug therapy for inflammatory bowel disease (IBD) and the agents under investigation. Topics include 5-ASA agents, including sulfasalazine, topical and oral forms of aminosalicylates, slow-release agents (mesalamine), chemically linked agents (olsalazine), and the side effects of these drugs; corticosteroids in topical, oral, parenteral, and rapidly-metabolized forms; immunomodulators, including 6mercaptopurine and azathioprine, cyclosporin, and methotrexate; antibiotics, including metronidazole, ciproflaxin, and antituberculous agents; lipoxygenase inhibitors; nicotine; antidiarrheal agents, including loperamide, diphenoxylate with atropine, codeine, and deodorized tincture of opium; anticholinergic agents; psychotropic agents; miscellaneous agents that show potential benefit; and drugs that may exacerbate colitis. The brochure includes a section on the management of the pediatric patient, including the use of sulfasalazine, aminosalicylates, corticosteroids, immunomodulators, antibiotics, and antidiarrheal agents. It also addresses specific issues of adolescents.

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Inflammatory Bowel Disease: Clinical Features and Comparison to the Functional Bowel Disorders Source: Milwaukee, WI: International Foundation for Functional Gastrointestinal Disorders (IFFGD). 1996. 2 p. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217. (888) 964-2001 or (414) 964-

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1799. Fax (414) 964-7176. E-mail: [email protected]. Website: www.iffgd.org. PRICE: Single copy free; bulk copies available. Summary: This fact sheet summarizes the clinical features of inflammatory bowel disease (IBD) and compares IBD to the functional bowel disorders. The inflammatory bowel diseases cause the traditional gastrointestinal symptoms, but may also cause fever, chills, night sweats, weight loss, and inflammation within various organs of the body (oral cavity, eye, skin, liver, joints, ileum, and colon). The author describes the symptoms associated with ulcerative colitis (UC) and Crohn's disease and current treatment options. The fact sheet gives the toll free telephone number of the Crohn's and Colitis Foundation of America (800-932-2423). ·

Learning to Live with Inflammatory Bowel Disease Source: American Family Physician. 57(1): 71-72. January 1, 1998. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Also available at http://www.aafp.org/healthinfo. Summary: This patient education fact sheet provides a general overview of managing inflammatory bowel disease (IBD). IBD is a group of disorders that cause the intestines to become inflamed. Symptoms can include abdominal cramping and pain, diarrhea, weight loss, and bleeding from the intestines. The fact sheet describes Crohn's disease and ulcerative colitis, two types of IBD. The fact sheet also describes the causes of IBD, diagnostic considerations, treatment options, and where to obtain more information about IBD. Treatment relieves the inflammation through the use of anti-inflammatory medicines. A healthy diet and adequate rest can also be part of therapy for IBD. For severe symptoms, such as diarrhea, fever, or vomiting, patients may need to be hospitalized to be rehydrated and treated with intravenous medications. Also, because Crohn's disease and ulcerative colitis keep coming back and their symptoms cannot be predicted ahead of time, patients with these illnesses can become depressed. Sometimes antidepressant medications are prescribed. The fact sheet notes the contact information for the Crohn's and Colitis Foundation of America and the National Digestive Diseases Information Clearinghouse. The fact sheet is designed to be copied and distributed to patients by family care providers.

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: ·

Inflammatory Bowel Disease Summary: This online consumer health information fact sheet presents a general overview of different types of inflammatory bowel diseases; discusses symptoms, screening; diagnosis and treatment options; Source: American Gastroenterological Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5037


Inflammatory Bowel Disease (IBD) and Vaccines Summary: This article from the National Immunization Program was written in response to a news item that raised concerns about the measles, mumps rubella vaccine (MMR) being a cause of chronic inflammatory Source: National Immunization Program, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5038 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 inflammatory bowel disease. 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: ·

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/specific.htm

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

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Med Help International: http://www.medhelp.org/HealthTopics/A.html

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

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

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WebMDÒHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to inflammatory bowel disease. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with inflammatory bowel disease.

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 inflammatory bowel disease. For more

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information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.

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 “inflammatory bowel disease” (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 “inflammatory bowel disease”. 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 “inflammatory bowel disease” (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 “inflammatory bowel disease” (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.26

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

26

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)27: ·

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/

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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

27

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries 279

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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

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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

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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

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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

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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/

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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

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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

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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

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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

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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/

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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/

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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

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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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

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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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

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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/

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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).

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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INFLAMMATORY BOWEL DISEASE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-phosphate: A drug that halts cell suicide in human white blood cells. [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 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: A localized, circumscribed collection of pus. [NIH] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [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] 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] 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]

Acyl: Chemical signal used by bacteria to communicate. [NIH] Acylation: The addition of an organic acid radical into a molecule. [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

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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] Adenoma: A benign epithelial tumor with a glandular organization. [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] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] 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] 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] Adrenaline: A hormone. Also called epinephrine. [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] 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

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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] Age-Adjusted: Summary measures of rates of morbidity or mortality in a population using statistical procedures to remove the effect of age differences in populations that are being compared. Age is probably the most important and the most common variable in determining the risk of morbidity and mortality. [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 stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agranulocytosis: A decrease in the number of granulocytes (basophils, eosinophils, and neutrophils). [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Alagille Syndrome: Hypoplasia of the hepatic ducts, congenital pulmonary artery stenosis, facial abnormalities, and other congenital malformations, particularly skeletal. It is often presented as jaundice during the neonatal period. It is an autosomal recessive disease generally manifesting during childhood. "Arteriohepatic" refers to the pulmonary artery and the intrahepatic bile ducts, not to the hepatic artery. [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] 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]

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Alkaline: Having the reactions of an alkali. [EU] 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] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [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] 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 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] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [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] Amenorrhea: Absence of menstruation. [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

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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 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] Aminosalicylic Acids: A group of 2-hydroxybenzoic acids that can be substituted by amino groups at any of the 3-, 4-, 5-, or 6-positions. [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] 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] 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] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] 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] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [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] Anal Fissure: A small tear in the anus that may cause itching, pain, or bleeding. [NIH] Anal Fistula: A channel that develops between the anus and the skin. Most fistulas are the result of an abscess (infection) that spreads to the skin. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] 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]

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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] 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] Anemic: Hypoxia due to reduction of the oxygen-carrying capacity of the blood as a result of a decrease in the total hemoglobin or an alteration of the hemoglobin constituents. [NIH] Anergy: Absence of immune response to particular substances. [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] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [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] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix.

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[NIH]

Anode: Electrode held at a positive potential with respect to a cathode. [NIH] 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] Anovulation: Suspension or cessation of ovulation in animals and humans. [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] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] 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] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antidiabetic: An agent that prevents or alleviates diabetes. [EU] Antidiabetic Agent: A substance that helps a person with diabetes control the level of glucose (sugar) in the blood so that the body works as it should. [NIH] 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-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]

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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] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antitussive: An agent that relieves or prevents cough. [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] Apheresis: Components plateletpheresis. [NIH]

being

separated

out,

as

leukapheresis,

plasmapheresis,

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] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [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

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phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in 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] Arteriolar: Pertaining to or resembling arterioles. [EU] 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] Arthralgia: Pain in the joint. [NIH] Arthritis, Rheumatoid: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated. [NIH] Articular: Of or pertaining to a joint. [EU] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Asbestosis: A lung disorder caused by constant inhalation of asbestos particles. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] 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] 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 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]

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Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] 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] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] 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] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autonomic Pathways: Nerves and plexuses of the autonomic nervous system. The central nervous system structures which regulate the autonomic nervous system are not included. [NIH]

Avian: A plasmodial infection in birds. [NIH] Avidin: A specific protein in egg albumin that interacts with biotin to render it unavailable to mammals, thereby producing biotin deficiency. [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] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH]

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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] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [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 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] Belladonna: A species of very poisonous Solanaceous plants yielding atropine (hyoscyamine), scopolamine, and other belladonna alkaloids, used to block the muscarinic autonomic nervous system. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [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] 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

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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] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding agent: A substance that makes a loose mixture stick together. For example, binding agents can be used to make solid pills from loose powders. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] 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] 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] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Bladder: The organ that stores urine. [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] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH]

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Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [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 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 Fluids: Liquid components of living organisms. [NIH] Body Image: Individuals' personal concept of their bodies as objects in and bound by space, independently and apart from all other objects. [NIH] Body Regions: Anatomical areas of the body. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [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] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH]

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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] Brain Diseases: Pathologic conditions affecting the brain, which is composed of the intracranial components of the central nervous system. This includes (but is not limited to) the cerebral cortex; intracranial white matter; basal ganglia; thalamus; hypothalamus; brain stem; and cerebellum. [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] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Bronchoalveolar Lavage Fluid: Fluid obtained by washout of the alveolar compartment of the lung. It is used to assess biochemical and inflammatory changes in and effects of therapy on the interstitial lung tissue. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [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] Bullous: Pertaining to or characterized by bullae. [EU] 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

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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] 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] Canonical: A particular nucleotide sequence in which each position represents the base more often found when many actual sequences of a given class of genetic elements are compared. [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] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsular: Cataract which is initiated by an opacification at the surface of the lens. [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] 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]

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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] 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] 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] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] 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] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [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] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [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]

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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] 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 Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [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 motility: The ability of a cell to move. [NIH] Cell Physiology: Characteristics and physiological processes of cells from cell division to cell death. [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 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]

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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] 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] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] 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] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Cesarean Section: Extraction of the fetus by means of abdominal hysterotomy. [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] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] 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] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH]

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Chlorambucil: An anticancer drug that belongs to the family of drugs called alkylating agents. [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] Cholecystostomy: Establishment of an opening into the gallbladder either for drainage or surgical communication with another part of the digestive tract, usually the duodenum or jejunum. [NIH] Cholelithiasis: Presence or formation of gallstones. [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] 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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in cartilage. [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] Choroiditis: Inflammation of the choroid. [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] Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome. [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 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] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [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] 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]

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Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [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] 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] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [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 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] Clostridium: A genus of motile or nonmotile gram-positive bacteria of the family Bacillaceae. Many species have been identified with some being pathogenic. They occur in water, soil, and in the intestinal tract of humans and lower animals. [NIH] Clostridium difficile: A common inhabitant of the colon flora in human infants and sometimes in adults. It produces a toxin that causes pseudomembranous enterocolitis in patients receiving antibiotic therapy. [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]

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Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Coenzymes: Substances that are necessary for the action or enhancement of action of an enzyme. Many vitamins are coenzymes. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognitive restructuring: A method of identifying and replacing fear-promoting, irrational beliefs with more realistic and functional ones. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [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] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [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, 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] 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] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [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

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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 Neoplasms: Tumors or cancer of the either the colon or rectum or both. The most frequent malignant tumor in the United States. Etiological factors which increase the risk of colorectal cancer include chronic ulcerative colitis, familial polyposis of the colon, exposure to asbestos, irradiation of the cervix. [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] 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] Commensalism: A relationship between two kinds of living organism whereby one (the commensal) benefits and the other (the host) remains relatively or absolutely unaffected, and which is often obligatory for the commensal. [NIH] 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,

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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] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [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 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] Computerized 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 computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [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] 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] Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH]

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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] 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 the abdomen. [NIH] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [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] Contrast Sensitivity: The ability to detect sharp boundaries (stimuli) and to detect slight changes in luminance at regions without distinct contours. Psychophysical measurements of this visual function are used to evaluate visual acuity and to detect eye disease. [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] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [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 Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

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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 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] 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] 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] Counterimmunoelectrophoresis: Immunoelectrophoresis in which immunoprecipitation occurs when antigen at the cathode is caused to migrate in an electric field through a suitable medium of diffusion against a stream of antibody migrating from the anode as a result of endosmotic flow. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cross-Cultural Comparison: Comparison of various psychological, sociological, or cultural factors in order to assess the similarities or diversities occurring in two or more different cultures or societies. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [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] Curative: Tending to overcome disease and promote recovery. [EU] Custom-made: Any active implantable medical device specifically made in accordance with a medical specialist's written prescription which gives, under his responsibility, specific design characteristics and is intended to be used only for an individually named patient. [NIH]

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Cutaneous: Having to do with the skin. [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] Cyclin: Molecule that regulates the cell cycle. [NIH] 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] Cystathionine beta-Synthase: A multifunctional pyridoxal phosphate enzyme. In the second stage of cysteine biosynthesis it catalyzes the reaction of homocysteine with serine to form cystathionine with the elimination of water. Deficiency of this enzyme leads to hyperhomocysteinemia and homocystinuria. EC 4.2.1.22. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [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]

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] Cytopenia: A reduction in the number of blood cells. [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] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [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]

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Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Daclizumab: A monoclonal antibody that is being studied for treatment of adult T-cell leukemia. Also called dacliximab. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] 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] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Decompression Sickness: A condition occurring as a result of exposure to a rapid fall in ambient pressure. Gases, nitrogen in particular, come out of solution and form bubbles in body fluid and blood. These gas bubbles accumulate in joint spaces and the peripheral circulation impairing tissue oxygenation causing disorientation, severe pain, and potentially death. [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] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is

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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] 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] Depigmentation: Removal or loss of pigment, especially melanin. [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] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [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] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] 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] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic Imaging: Any visual display of structural or functional patterns of organs or tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses

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to physical and chemical stimuli, as well as ultramicroscopy. [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 Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]

Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [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] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilate: Relax; expand. [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] Diphenoxylate: A meperidine congener used as an antidiarrheal, usually in combination with atropine. At high doses, it acts like morphine. Its unesterified metabolite difenoxin has similar properties and is used similarly. It has little or no analgesic activity. [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] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU]

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Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissection: Cutting up of an organism for study. [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] 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] Diuresis: Increased excretion of urine. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] 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] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] 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

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dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [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] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] 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]

Ectoderm: The outer of the three germ layers of the embryo. [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] 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] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and 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]

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Electric Impedance: The resistance to the flow of either alternating or direct electrical current. [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]

Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] 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] 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] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endarterectomy:

Surgical

excision,

performed

under

general

anesthesia,

of

the

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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] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [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] 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] Enema: The injection of a liquid through the anus into the large bowel. [NIH] 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] Enhancer: Transcriptional element in the virus genome. [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

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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] 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 Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. [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] Enzyme Repression: The interference in synthesis of an enzyme due to the elevated level of an effector substance, usually a metabolite, whose presence would cause depression of the gene responsible for enzyme synthesis. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [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] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] 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

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lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] 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] Episiotomy: An incision of the posterior vaginal wall and a portion of the pudenda which enlarges the vaginal introitus to facilitate delivery and prevent lacerations. [NIH] Epistasis: The degree of dominance exerted by one gene on the expression of a non-allelic gene. [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] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Erysipeloid: An infection caused by Erysipelothrix rhusiopathiae that is almost wholly restricted to persons who in their occupation handle infected fish, shellfish, poultry, or meat. Three forms of this condition exist: a mild localized form manifested by local swelling and redness of the skin; a diffuse form that might present with fever; and a rare systemic form associated with endocarditis. [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] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Erythropoiesis: The production of erythrocytes. [EU] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [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]

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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] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [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 peripheral sense organ. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [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] Extender: Any of several colloidal substances of high molecular weight, used as a blood or plasma substitute in transfusion for increasing the volume of the circulating blood. [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] Extrapyramidal: Outside of the pyramidal tracts. [EU]

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Extravascular: Situated or occurring outside a vessel or the vessels. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Facial: Of or pertaining to the face. [EU] Faecal: Pertaining to or of the nature of feces. [EU] Familial polyposis: An inherited condition in which numerous polyps (tissue masses) develop on the inside walls of the colon and rectum. It increases the risk for colon cancer. [NIH]

Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fasciitis: Inflammation of the fascia. There are three major types: 1) Eosinophilic fasciitis, an inflammatory reaction with eosinophilia, producing hard thickened skin with an orangepeel configuration suggestive of scleroderma and considered by some a variant of scleroderma; 2) Necrotizing fasciitis, a serious fulminating infection (usually by a beta hemolytic Streptococcus) causing extensive necrosis of superficial fascia; 3) Nodular/Pseudosarcomatous/Proliferative fasciitis, characterized by a rapid growth of fibroblasts with mononuclear inflammatory cells and proliferating capillaries in soft tissue, often the forearm; it is not malignant but is sometimes mistaken for fibrosarcoma. [NIH] Fat: Total lipids including phospholipids. [NIH] Fathers: Male parents, human or animal. [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] Feasibility Studies: Studies to determine the advantages or disadvantages, practicability, or capability of accomplishing a projected plan, study, or project. [NIH] Febrile: Pertaining to or characterized by fever. [EU] 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] Femoral: Pertaining to the femur, or to the thigh. [EU] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fence: A hearing threshold level above which degrees of hearing handicap (or disability) are deemed to exist. [NIH] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [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 non-

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identical 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] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] 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] 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] Focal Adhesions: An anchoring junction of the cell to a non-cellular substrate. It is composed of a specialized area of the plasma membrane where bundles of microfilaments terminate and attach to the transmembrane linkers, integrins, which in turn attach through their extracellular domains to extracellular matrix proteins. [NIH]

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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] Forearm: The part between the elbow and the wrist. [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 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] Gallate: Antioxidant present in tea. [NIH] 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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gangliosides: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [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]

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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] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, 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 Neoplasms: Tumors or cancer of the gastrointestinal system. [NIH] Gastrointestinal tract: The stomach and intestines. [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] Gelsolin: A 90-kD protein produced by macrophages that severs actin filaments and forms a cap on the newly exposed filament end. Gelsolin is activated by calcium ions and participates in the assembly and disassembly of actin, thereby increasing the motility of some cells. [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] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Genes, mos: Retrovirus-associated DNA sequences (mos) originally isolated from the Moloney murine sarcoma virus (Mo-MSV). The proto-oncogene mos (c-mos) codes for a protein which is a member of the serine kinase family. There is no evidence as yet that human c-mos can become transformed or has a role in human cancer. However, in mice, activation can occur when the retrovirus-like intracisternal A-particle inserts itself near the c-mos sequence. The human c-mos gene is located at 8q22 on the long arm of chromosome 8. [NIH]

Genetic Code: The specifications for how information, stored in nucleic acid sequence (base

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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 Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [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] Germfree: Free from all living micro-organisms. [NIH] Germ-free: Free of bacteria, disease-causing viruses, and other organisms that can cause infection. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] 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] 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] 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] Glomerulosclerosis: Scarring of the glomeruli. It may result from diabetes mellitus (diabetic glomerulosclerosis) or from deposits in parts of the glomerulus (focal segmental glomerulosclerosis). The most common signs of glomerulosclerosis are proteinuria and kidney failure. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [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]

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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 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] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Gonads: The gamete-producing glands, ovary or testis. [NIH] Gout:

Hereditary

metabolic

disorder

characterized

by

recurrent

acute

arthritis,

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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] 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 recipient. [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] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Gram-Positive Bacteria: Bacteria which retain the crystal violet stain when treated by Gram's method. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granulomas: Small lumps in tissues caused by inflammation. [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] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [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] 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] Handedness: Preference for using right or left hand. [NIH] Handicap: A handicap occurs as a result of disability, but disability does not always

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constitute a handicap. A handicap may be said to exist when a disability causes a substantial and continuing reduction in a person's capacity to function socially and vocationally. [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] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [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] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Helicobacter: A genus of gram-negative, spiral-shaped bacteria that is pathogenic and has been isolated from the intestinal tract of mammals, including humans. [NIH] Helix-loop-helix: Regulatory protein of cell cycle. [NIH] Hematologic Diseases: Disorders of the blood and blood forming tissues. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [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] Hemoglobin C: A commonly occurring abnormal hemoglobin in which lysine replaces a glutamic acid residue at the sixth position of the beta chains. It results in reduced plasticity of erythrocytes. [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

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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]

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] Hepatic Artery: A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum. [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] Hepatitis C: A form of hepatitis, similar to type B post-transfusion hepatitis, but caused by a virus which is serologically distinct from the agents of hepatitis A, B, and E, and which may persist in the blood of chronic asymptomatic carriers. Hepatitis C is parenterally transmitted and associated with transfusions and drug abuse. [NIH] Hepatitis Viruses: Any of the viruses that cause inflammation of the liver. They include both DNA and RNA viruses as well viruses from humans and animals. [NIH] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Hepatocellular: Pertaining to or affecting liver cells. [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] Heterodimer: 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]

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Heterozygote: An individual having different alleles at one or more loci in homologous chromosome segments. [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] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Histocompatibility Antigens: A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Holidays: Days commemorating events. Holidays also include vacation periods. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [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] Homozygotes: An individual having a homozygous gene pair. [NIH] 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] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Humeral: 1. Of, relating to, or situated in the region of the humerus: brachial. 2. Of or belonging to the shoulder. 3. Of, relating to, or being any of several body parts that are analogous in structure, function, or location to the humerus or shoulder. [EU] 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

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hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [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 Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds. [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] Hydroxybenzoic Acids: Benzoic acid substituted by one or more hydroxy groups in any position on the benzene ring. [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] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hyperhomocysteinemia: An inborn error of methionone metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine betasynthase and is a risk factor for coronary vascular disease. [NIH] 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] 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] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately,

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convulsions and coma. [EU] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypotension: Abnormally low blood pressure. [NIH] 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] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hysterotomy: An incision in the uterus, performed through either the abdomen or the vagina. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [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] 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] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [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]

Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [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] 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] Immunologic Memory: The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus. [NIH] Immunology: The study of the body's immune system. [NIH] Immunomodulator: New type of drugs mainly using biotechnological methods. Treatment of cancer. [NIH] 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]

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Implant radiation: A procedure in which radioactive material sealed in needles, seeds, 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] 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] Induction therapy: Treatment designed to be used as a first step toward shrinking the cancer and in evaluating response to drugs and other agents. Induction therapy is followed by additional therapy to eliminate whatever cancer remains. [NIH] 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] Infantile: Pertaining to an infant or to infancy. [EU] 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]

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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] 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] Inhalation: The drawing of air or other substances into the lungs. [EU] 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] Inorganic: Pertaining to substances not of organic origin. [EU] 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] Insomnia: Difficulty in going to sleep or getting enough sleep. [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] Insurance Pools: An organization of insurers or reinsurers through which particular types of risk are shared or pooled. The risk of high loss by a particular insurance company is transferred to the group as a whole (the insurance pool) with premiums, losses, and expenses shared in agreed amounts. [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]

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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-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-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 Tlymphocytes. 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] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU]

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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] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intrahepatic: Within the liver. [NIH] Intrahepatic bile ducts: The bile ducts that pass through and drain bile from the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Intussusception: A rare disorder. A part of the intestines folds into another part of the intestines, causing blockage. Most common in infants. Can be treated with an operation. [NIH]

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 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] 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] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH]

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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] 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] Islet: Cell producing insulin in pancreas. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Joint Capsule: The sac enclosing a joint. It is composed of an outer fibrous articular capsule and an inner synovial membrane. [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] Keratitis: Inflammation of the cornea. [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] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lacerations: Torn, ragged, mangled wounds. [NIH] 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

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conditioned or may be acquired. [NIH] Lactulose: A mild laxative. [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] 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] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] 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] Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [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] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] 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]

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,

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and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [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] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [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] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [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] Ligation: Application of a ligature to tie a vessel or strangulate a part. [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] 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] Linoleic Acids: Eighteen-carbon essential fatty acids that contain two double bonds. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [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] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH]

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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] Lipoxygenase Inhibitors: Compounds or agents that combine with lipoxygenase and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of the eicosanoid products hydroxyeicosatetraenoic acid and various leukotrienes. [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] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [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] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] 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

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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] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [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] 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] 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 Activation: The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. [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

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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] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

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 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]

Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] 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] 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]

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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] 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] Melena: Black, tarry feces containing digested blood. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Microdomains: Detergent-insoluble cell membrane components. They are enriched in sphingolipids and cholesterol and clustered with glycosyl-phosphatidylinositol (GPI)-anchored proteins. [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] 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] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior

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producing either distress or impairment of function. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [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] Meperidine: 1-Methyl-4-phenyl-4-piperidinecarboxylic acid ethyl ester. A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration. [NIH] Mercaptopurine: An anticancer drug that belongs to the family of drugs called antimetabolites. [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] Metabolization: The chemical process by which matter is broken down into simpler substances, said especially of food processed by the human body. [EU] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [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] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [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

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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] Micronutrients: Essential dietary elements or organic compounds that are required in only small quantities for normal physiologic processes to occur. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms 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

Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [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] Minor Histocompatibility Antigens: Allelic alloantigens often responsible for weak graft rejection in cases when (major) histocompatibility has been established by standard tests. In the mouse they are coded by more than 500 genes at up to 30 minor histocompatibility loci. The most well-known minor histocompatibility antigen in mammals is the H-Y antigen. [NIH]

Minority Groups: A subgroup having special characteristics within a larger group, often bound together by special ties which distinguish it from the larger group. [NIH] Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the second trimester. [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] Mobility: Capability of movement, of being moved, or of flowing freely. [EU]

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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] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] 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] Monotherapy: A therapy which uses only one drug. [EU] 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]

Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [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] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH]

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Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] 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] 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] 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] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] 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] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts. [NIH]

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] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. [NIH]

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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] 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] Myositis: Inflammation of a voluntary muscle. [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 Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasal Polyps: Focal accumulations of edema fluid in the nasal mucosa accompanied by hyperplasia of the associated submucosal connective tissue. Polyps may be neoplasms, foci of inflammation, degenerative lesions, or malformations. [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 (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,

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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] 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] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] 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 Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neuritis: A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include pain; paresthesias; paresis; or hypesthesia. [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]

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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] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurotensin: A biologically active tridecapeptide isolated from the hypothalamus. It has been shown to induce hypotension in the rat, to stimulate contraction of guinea pig ileum and rat uterus, and to cause relaxation of rat duodenum. There is also evidence that it acts as both a peripheral and a central nervous system neurotransmitter. [NIH] Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis. [EU]

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] 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] Neutrophil: A type of white blood cell. [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

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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] Nonulcer Dyspepsia: Constant pain or discomfort in the upper GI tract. Symptoms include burning, nausea, and bloating, but no ulcer. Possibly caused by muscle spasms. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [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] 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 Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [NIH] 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] 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] Occult: Obscure; concealed from observation, difficult to understand. [EU] Octreotide: A potent, long-acting somatostatin octapeptide analog which has a wide range

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of physiological actions. It inhibits growth hormone secretion, is effective in the treatment of hormone-secreting tumors from various organs, and has beneficial effects in the management of many pathological states including diabetes mellitus, orthostatic hypertension, hyperinsulinism, hypergastrinemia, and small bowel fistula. [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] Oesophagitis: Inflammation of the esophagus. [EU] Oligomenorrhea: Abnormally infrequent menstruation. [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] Oncology: The study of cancer. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [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] Ophthalmologist: A medical doctor specializing in the diagnosis and medical or surgical treatment of visual disorders and eye disease. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [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 disc: The circular area (disc) where the optic nerve connects to the retina. [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

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the central nervous system. [NIH] Optic Neuritis: Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as multiple sclerosis, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis). [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] 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] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [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] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal 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] 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] 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]

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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 bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] 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] 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] Panniculitis: General term for inflammation of adipose tissue, usually of the skin, characterized by reddened subcutaneous nodules. [NIH]

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Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. [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] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [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] 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] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [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] 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]

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Pathophysiology: Altered functions in an individual or an organ due to disease. [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 Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pediatric Gastroenterologist: A doctor who treats children with digestive diseases. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Peer Group: Group composed of associates of same species, approximately the same age, and usually of similar rank or social status. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [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] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perennial: Lasting through the year of for several years. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] 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] Pericarditis: Inflammation of the pericardium. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels.

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[NIH]

Pericytes: Smooth muscle cell that wraps around normal blood 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]

Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [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] 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] Pernicious: Tending to a fatal issue. [EU] Pernicious anemia: A type of anemia (low red blood cell count) caused by the body's inability to absorb vitamin B12. [NIH] Personality Disorders: A major deviation from normal patterns of behavior. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [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] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [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] Pharmacology, Clinical: The branch of pharmacology that deals directly with the effectiveness and safety of drugs in humans. [NIH] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease

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appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharyngitis: Inflammation of the throat. [NIH] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [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] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [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] Phosphorylate: 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] Photophobia: Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [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]

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Pilot study: The initial study examining a new method or treatment. [NIH] Piperidines: A family of hexahydropyridines. Piperidine itself is found in the pepper plant as the alkaloid piperine. [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] 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 protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and 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] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [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.

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[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 veins. [EU] Pneumoconiosis: Condition characterized by permanent deposition of substantial amounts of particulate matter in the lungs, usually of occupational or environmental origin, and by the tissue reaction to its presence. [NIH] 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] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [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] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [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

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chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Population Control: Includes mechanisms or programs which control the numbers of individuals in a population of humans or animals. [NIH] Population Dynamics: The pattern of any process, or the interrelationship of phenomena, which affects growth or change within a population. [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] Postnatal: Occurring after birth, with reference to the newborn. [EU] 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-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [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] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [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 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] 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]

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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 Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] 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] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [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 coloproctectomy. [NIH]

the

colon and rectum. Also called

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] Progeny: The offspring produced in any generation. [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] 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] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prokinetic Drugs: Medicines that cause muscles in the GI tract to move food. An example is cisapride (SIS-uh-pryd) (Propulsid). [NIH]

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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] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [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] Propulsive: Tending or having power to propel; driving onward or forward; impelling to action or motion. [EU] 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). 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] 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 Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH]

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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 Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [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] 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] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [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] 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] 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] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Pseudogenes: Genes bearing close resemblance to known genes at different loci, but rendered non-functional by additions or deletions in structure that prevent normal transcription or translation. When lacking introns and containing a poly-A segment near the downstream end (as a result of reverse copying from processed nuclear RNA into doublestranded DNA), they are called processed genes. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a

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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] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] 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] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] 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 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] 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] 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] 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

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unknown. [NIH] 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] 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 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] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [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] Radiologist: A doctor who specializes in creating and interpreting pictures of areas inside the body. The pictures are produced with x-rays, sound waves, or other types of energy. [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] Radius: The lateral bone of the forearm. [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] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or

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other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Rarefaction: The reduction of the density of a substance; the attenuation of a gas. [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 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] 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, 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 Proteins: Proteins prepared by recombinant DNA technology. [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] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] 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] Rectal Prolapse: Protrusion of the rectal mucous membrane through the anus. There are various degrees: incomplete with no displacement of the anal sphincter muscle; complete with displacement of the anal sphincter muscle; complete with no displacement of the anal sphincter muscle but with herniation of the bowel; and internal complete with rectosigmoid or upper rectum intussusception into the lower rectum. [NIH] Rectovaginal Fistula: Abnormal communication between the rectum and the vagina. [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] 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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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]

Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] 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] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [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] Remission Induction: Therapeutic act or process that initiates a response to a complete or partial remission level. [NIH] Remission induction therapy: The initial chemotherapy a person receives to bring about a remission. [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

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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] Repressor Proteins: Proteins which are normally bound to the operator locus of an operon, thereby preventing transcription of the structural genes. In enzyme induction, the substrate of the inducible enzyme binds to the repressor protein, causing its release from the operator and freeing the structural genes for transcription. In enzyme repression, the end product of the enzyme sequence binds to the free repressor protein, the resulting complex then binds to the operator and prevents transcription of the structural genes. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resected: Surgical removal of part of an organ. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [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] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [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]

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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] Retrobulbar: Behind the pons. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [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] Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue structures which pertain to a variety of musculoskeletal disorders, such as arthritis. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhusiopathiae: Causal agent of the anthropozoonosis called erysipeloid. [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]

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Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rituximab: A type of monoclonal antibody used in cancer detection or therapy. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. [NIH] Rod: A reception for vision, located in the retina. [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] Rubella: An acute, usually benign, infectious disease caused by a togavirus and most often affecting children and nonimmune young adults, in which the virus enters the respiratory tract via droplet nuclei and spreads to the lymphatic system. It is characterized by a slight cold, sore throat, and fever, followed by enlargement of the postauricular, suboccipital, and cervical lymph nodes, and the appearances of a fine pink rash that begins on the head and spreads to become generalized. Called also German measles, roetln, röteln, and three-day measles, and rubeola in French and Spanish. [EU] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salicylic: A tuberculosis drug. [NIH] Salicylic Acids: Derivatives and salts of salicylic acid. [NIH] Saline: A solution of salt and water. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [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] Schematic: Representative or schematic eye computed from the average of a large number of human eye measurements by Allvar Gullstrand. [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

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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 fivesixths 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] 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] 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] 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] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains

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spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [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] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serologic Tests: Diagnostic procedures involving immunoglobulin reactions. [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] Serous: Having to do with serum, the clear liquid part of blood. [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 have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [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

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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] 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 Manifestations: Dermatologic disorders attendant upon non-dermatologic disease or injury. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sludge: A clump of agglutinated red blood cells. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Social Work: The use of community resources, individual case work, or group work to

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promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [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] 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] 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 spastic paralysis or in cerebral palsy. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] 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] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU]

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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] Spirochete: Lyme disease. [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] Spondylitis: Inflammation of the vertebrae. [EU] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [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] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stabilization: The creation of a stable state. [EU] 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] 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] 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]

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Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation. [NIH] Stilbenes: Organic compounds that contain 1,2-diphenylethylene as a functional group. [NIH]

Stillbirth: The birth of a dead fetus or baby. [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] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [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] Stress management: A set of techniques used to help an individual cope more effectively with difficult situations in order to feel better emotionally, improve behavioral skills, and often to enhance feelings of control. Stress management may include relaxation exercises, assertiveness training, cognitive restructuring, time management, and social support. It can be delivered either on a one-to-one basis or in a group format. [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] 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]

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Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a 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] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [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] 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] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [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] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] 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

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synapses; these are not included here but rather in gap junctions. [NIH] 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] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Fluid: The clear, viscous fluid secreted by the synovial membrane. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints. [NIH] 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] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

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] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] 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] Teichoic Acids: Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human

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somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Tendinitis: Inflammation of tendons and of tendon-muscle attachments. [EU] 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] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [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] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thioguanine: An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. [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

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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] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [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]

Thrombophilia: A disorder of hemostasis in which there is a tendency for the occurrence of thrombosis. [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 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] 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] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Time Management: Planning and control of time to improve efficiency and effectiveness. [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

Dictionary 383

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 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] Tissue Transplantation: Transference of tissue within an individual, between individuals of the same species, or between individuals of different species. [NIH] 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] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [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] Toxoplasma: A genus of protozoa parasitic to birds and mammals. T. gondii is one of the most common infectious pathogenic animal parasites of man. [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] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] 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

384


(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] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [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 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] Transport Vesicles: Vesicles that are involved in shuttling cargo from the interior of the cell to the cell surface, from the cell surface to the interior, across the cell or around the cell to various locations. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Triad: Trivalent. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trinitrobenzenesulfonic Acid: A reagent that is used to neutralize peptide terminal amino groups. [NIH] Troglitazone: A drug used in diabetes treatment that is being studied for its effect on reducing the risk of cancer cell growth in fat tissue. [NIH] Trophic: Of or pertaining to nutrition. [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for

Dictionary 385

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] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [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] 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] 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] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [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]

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] Uricosuric: 1. Pertaining to, characterized by, or promoting uricosuria (= the excretion of uric acid in the urine). 2. An agent that promotes uricosuria. [EU]

386


Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [NIH] Urinate: To release urine from the bladder to the outside. [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] 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] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] 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] Vagal: Pertaining to the vagus nerve. [EU] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU]

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Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] 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] Vertebral: Of or pertaining to a vertebra. [EU] 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] 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] Villous: Of a surface, covered with villi. [NIH] Villus: Cell found in the lining of the small intestine. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vincristine: 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 Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] 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] 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] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH]

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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] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [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] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [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]

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] 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] 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] 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]

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INDEX 1 1-phosphate, 201, 285 A Aberrant, 33, 49, 55, 73, 78, 89, 161, 176, 177, 184, 193, 285 Ablation, 73, 285 Abscess, 61, 285, 289, 374 Acantholysis, 285, 357 Acatalasia, 285, 300 Acceptor, 285, 340, 355, 384 Acetylcholine, 285, 303, 341, 352 Actin, 47, 81, 87, 285, 324, 346 Action Potentials, 164, 285 Acute leukemia, 285, 381 Acyl, 200, 285 Acylation, 200, 285 Adaptability, 285, 301 Adaptation, 22, 65, 105, 168, 285 Adenine, 286, 366 Adenocarcinoma, 36, 66, 286 Adenoma, 10, 53, 222, 286 Adenosine, 61, 286, 299, 359 Adhesions, 182, 286 Adipocytes, 286, 307, 339 Adipose Tissue, 169, 286, 355 Adjunctive Therapy, 4, 13, 286 Adjustment, 13, 22, 285, 286 Adolescence, 22, 120, 286, 357 Adoptive Transfer, 64, 87, 286 Adrenal Cortex, 286, 309, 363 Adrenal Glands, 286, 289 Adrenal Medulla, 286, 300, 319, 352 Adrenaline, 169, 286 Adrenergic, 286, 314, 319, 341, 379 Adverse Effect, 5, 9, 154, 233, 286, 375 Aerobic, 4, 286, 346, 348, 355 Aetiology, 179, 286 Afferent, 50, 72, 286, 339, 354 Affinity, 30, 65, 75, 174, 286, 287, 376 Agar, 287, 309, 360 Age Groups, 25, 231, 236, 287 Age of Onset, 81, 156, 237, 287 Age-Adjusted, 222, 287 Aged, 80 and Over, 287 Agonist, 75, 287, 314, 351 Agranulocytosis, 10, 287 Airway, 182, 185, 187, 195, 287 Alagille Syndrome, 195, 287

Albumin, 287, 294, 360, 380 Aldehydes, 172, 287 Alertness, 287, 299 Algorithms, 20, 27, 287, 296 Alkaline, 288, 289, 295, 299, 359, 381 Alkaloid, 288, 294, 299, 305, 347, 351, 356, 360 Alkylating Agents, 288, 303, 385 Alleles, 55, 68, 129, 195, 288, 330, 340 Allergen, 185, 288, 312, 374 Allergic Rhinitis, 184, 186, 288, 298 Allogeneic, 288, 327 Allograft, 44, 166, 288, 330 Allylamine, 288, 289 Alopecia, 86, 288, 310 Alpha Particles, 288, 367 Alternative medicine, 51, 103, 211, 244, 288 Alternative Splicing, 288, 365 Amebiasis, 128, 288, 345 Ameliorated, 37, 288 Ameliorating, 62, 191, 288 Amenorrhea, 288, 361 Amine, 175, 288, 330 Amino Acid Sequence, 43, 188, 289, 291, 320, 325, 363 Amino Acids, 168, 289, 319, 325, 351, 353, 357, 361, 365, 371, 374, 379, 384, 385 Aminosalicylic Acids, 9, 11, 289 Amino-terminal, 289, 363 Ammonia, 288, 289, 326 Amplification, 171, 289 Ampulla, 289, 317 Amyloidosis, 17, 67, 99, 289 Anabolic, 116, 289 Anaemia, 148, 289, 344 Anaerobic, 66, 289 Anaesthesia, 289, 334 Anal, 208, 240, 266, 270, 272, 289, 318, 322, 368 Anal Fissure, 270, 289 Anal Fistula, 272, 289 Analgesic, 75, 289, 305, 313, 345, 347, 353 Analog, 203, 289, 352 Analogous, 289, 314, 330, 361, 384 Anaphylactic, 290, 360 Anaphylatoxins, 290, 306 Anaphylaxis, 185, 290

390


Anastomosis, 208, 240, 290, 332 Anatomical, 66, 290, 297, 308, 313, 333, 373 Androgens, 73, 286, 290, 309 Anemia, 6, 14, 20, 53, 86, 165, 178, 192, 220, 225, 247, 261, 290, 323, 348, 358 Anemic, 53, 290 Anergy, 57, 290 Anesthesia, 287, 290, 316 Aneurysm, 290, 386 Angina, 192, 290 Angina Pectoris, 192, 290 Angiogenesis, 181, 290, 343 Angioplasty, 167, 290, 349 Animal model, 6, 34, 36, 40, 42, 44, 52, 55, 65, 75, 76, 162, 173, 290 Anionic, 201, 290 Anions, 287, 290, 337, 379 Annealing, 290, 361 Anode, 290, 291, 309 Anorexia, 192, 291, 324, 385 Anovulation, 291, 361 Antagonism, 291, 299 Antiallergic, 291, 309 Antibacterial, 291, 376 Antibiotic, 154, 171, 182, 183, 291, 304, 319, 376, 381 Antibody, 4, 20, 37, 39, 44, 61, 79, 93, 94, 98, 119, 156, 169, 171, 177, 178, 190, 196, 198, 201, 229, 287, 291, 297, 306, 309, 311, 328, 330, 333, 334, 336, 338, 343, 347, 367, 372, 374, 376, 388 Anticholinergic, 273, 291 Anticoagulant, 30, 291, 312, 365 Antidepressant, 274, 291 Antidiabetic, 57, 291 Antidiabetic Agent, 57, 291 Antigen-Antibody Complex, 291, 306 Antigen-presenting cell, 291, 312 Anti-inflammatory, 29, 33, 48, 51, 55, 57, 73, 85, 145, 154, 155, 167, 169, 173, 178, 182, 221, 235, 246, 269, 274, 291, 293, 309, 325, 363, 372, 373 Anti-Inflammatory Agents, 291, 293, 309 Antimetabolite, 291, 381 Antimicrobial, 188, 292, 303 Antimycotic, 292, 304 Antineoplastic, 288, 292, 309, 310, 381 Antioxidant, 31, 127, 292, 323, 355 Antiproliferative, 292, 336 Antipyretic, 292 Antispasmodic, 292, 353 Antitussive, 292, 353

Antiviral, 197, 292, 312, 333, 336, 357 Anus, 20, 178, 247, 272, 289, 292, 294, 295, 297, 317, 322, 332, 358, 368 Anxiety, 155, 192, 231, 232, 271, 292 Apheresis, 8, 292 Apoptosis, 49, 53, 56, 68, 73, 78, 82, 97, 181, 188, 200, 292 Appendectomy, 218, 292 Appendicitis, 220, 292 Applicability, 46, 292 Aqueous, 292, 295, 310, 316, 331, 339 Arachidonate 12-Lipoxygenase, 292, 341 Arachidonate 15-Lipoxygenase, 292, 341 Arachidonate Lipoxygenases, 292, 341 Arachidonic Acid, 42, 187, 292, 315, 340, 341, 364 Arginine, 290, 293, 352 Aromatic, 293, 359 Arterial, 288, 293, 331, 365, 380 Arteries, 293, 297, 308, 309, 345, 349, 382 Arteriolar, 40, 293, 298 Arterioles, 41, 167, 170, 191, 293, 297, 299, 346, 349 Arteriolosclerosis, 293 Arteriosclerosis, 170, 293 Arteriovenous, 293, 346 Arthralgia, 97, 196, 197, 293 Arthritis, Rheumatoid, 197, 198, 293 Articular, 19, 27, 29, 293, 338, 354 Asbestos, 182, 293, 306 Asbestosis, 293 Aseptic, 293, 377 Aspirin, 33, 293 Assay, 43, 173, 293, 333, 385 Asymptomatic, 116, 224, 285, 288, 293, 329, 355 Ataxia, 261, 293, 381 Atopic, 169, 170, 185, 190, 197, 198, 294 Atresia, 168, 294 Atrophy, 4, 261, 285, 293, 294, 319 Atropine, 273, 294, 295, 313 Attenuation, 66, 294, 368 Atypical, 169, 174, 294 Autoantibodies, 71, 174, 294, 312 Autoantigens, 294 Autodigestion, 294, 355 Autoimmune disease, 33, 37, 38, 55, 64, 82, 83, 86, 161, 175, 177, 185, 294, 348 Autoimmune Hepatitis, 174, 294 Autoimmunity, 7, 33, 37, 38, 51, 71, 83, 86, 87, 110, 177, 192, 194, 294 Autologous, 166, 167, 294

Index 391

Autologous bone marrow transplantation, 166, 167, 294 Autonomic, 72, 285, 294, 295, 352, 379 Autonomic Nervous System, 294, 295, 379 Autonomic Pathways, 72, 294 Avian, 161, 294 Avidin, 62, 294 B Bacterial Infections, 165, 200, 246, 294, 327, 370 Bacterial Physiology, 286, 294 Bactericidal, 175, 188, 294, 320 Bacteriophage, 295, 360, 383 Barbiturate, 295, 381 Barium, 103, 155, 162, 229, 245, 247, 272, 295 Barium enema, 155, 162, 245, 247, 272, 295 Basal Ganglia, 293, 295, 298, 323 Basal Ganglia Diseases, 293, 295 Base, 49, 81, 156, 173, 200, 286, 295, 299, 311, 312, 323, 324, 338, 358, 359, 381, 385 Base Sequence, 295, 323, 325 Basement Membrane, 41, 295, 320, 339 Basophils, 186, 287, 295, 327, 339, 360 Belladonna, 294, 295 Benign, 192, 200, 286, 293, 295, 323, 328, 350, 367, 372, 373 Benzoic Acid, 199, 295 Beta-Thromboglobulin, 295, 336 Bilateral, 295, 319, 361, 371 Bile, 91, 99, 218, 224, 295, 296, 303, 323, 329, 330, 337, 338, 341, 363, 377 Bile Acids, 91, 295, 296, 377 Bile Acids and Salts, 295, 296 Bile Ducts, 224, 296, 323, 337, 363 Bile Pigments, 296, 338 Biliary, 69, 91, 222, 224, 296, 299, 329, 355 Biliary Tract, 222, 296, 299, 355 Bilirubin, 287, 296, 323, 331 Binding agent, 176, 296 Bioavailability, 156, 296 Biochemical, 29, 48, 51, 60, 64, 65, 91, 99, 185, 288, 291, 296, 298, 326, 339, 354, 374 Biological response modifier, 296, 336 Biological therapy, 20, 296, 327 Biopsy, 5, 10, 102, 155, 184, 222, 226, 272, 296, 357 Biosynthesis, 91, 293, 296, 304, 310, 374 Biotechnology, 80, 92, 95, 146, 195, 244, 257, 259, 260, 261, 262, 296 Biotin, 150, 294, 296

Bladder, 197, 296, 334, 348, 350, 364, 385, 386 Blastocyst, 296, 307, 316, 360 Blister, 296, 357 Bloating, 272, 297, 334, 338, 343, 352 Blood Cell Count, 297, 358 Blood Coagulation, 199, 297, 299, 382 Blood Coagulation Factors, 297 Blood Glucose, 297, 328, 335 Blood Platelets, 297, 344, 360, 374, 382 Blood pressure, 297, 300, 331, 332, 347, 376 Blood transfusion, 30, 297 Blot, 51, 297, 333 Blotting, Western, 297, 333 Body Fluids, 297, 315, 322, 352, 376 Body Image, 210, 297 Body Regions, 297, 305 Bone Density, 17, 143, 297 Bone Marrow, 77, 84, 233, 285, 294, 297, 303, 310, 319, 327, 333, 336, 342, 344, 348, 376 Bone Marrow Transplantation, 297 Bone scan, 297, 372 Bowel Movement, 226, 272, 297, 313, 378 Brachial, 297, 330 Brachytherapy, 298, 336, 338, 367, 388 Bradykinin, 298, 352, 360 Brain Diseases, 163, 187, 298 Branch, 186, 281, 298, 329, 342, 351, 356, 358, 376, 379, 381 Breakdown, 63, 180, 298, 313, 323, 353 Breeding, 46, 298 Bronchi, 185, 298, 319, 383 Bronchial, 57, 185, 186, 298, 330 Bronchitis, 298, 303 Bronchoalveolar Lavage, 185, 298 Bronchoalveolar Lavage Fluid, 185, 298 Bronchoconstriction, 187, 298, 360 Bronchus, 298 Buccal, 298, 342 Budesonide, 7, 130, 235, 245, 298 Bulimia, 192, 298 Bullous, 298, 312 C Cachexia, 175, 192, 298 Cadherins, 167, 298 Caffeine, 237, 298, 366 Calcification, 293, 299 Calculi, 299, 327 Cannabidiol, 48, 299 Cannabinoids, 47, 75, 299 Cannabinol, 299

392


Canonical, 82, 299 Capillary, 298, 299, 387 Capsaicin, 51, 299 Capsular, 39, 299 Carbohydrate, 50, 196, 299, 309, 326, 361, 374 Carcinogen, 299, 345 Carcinogenesis, 10, 91, 97, 102, 205, 299, 302 Carcinogenic, 288, 299, 335, 353, 364, 377 Carcinoma, 131, 299 Cardiac, 180, 288, 299, 317, 319, 324, 349, 377 Cardiovascular, 46, 80, 183, 192, 300, 340, 374 Cardiovascular disease, 46, 80, 183, 192, 300 Carotene, 300, 370 Carrier Proteins, 300, 360 Carrier State, 288, 300 Case report, 12, 20, 126, 300, 304 Case series, 300, 304 Case-Control Studies, 74, 300, 318 Catabolism, 37, 300 Catalase, 175, 285, 300 Catalyse, 164, 300 Cataracts, 170, 300 Catecholamine, 300, 314, 359 Catheterization, 290, 300, 349 Cathode, 291, 300, 309, 316 Cations, 300, 337 Caudal, 300, 313, 332, 362 Causal, 26, 55, 301, 318, 371 Caveolae, 61, 301 Caveolins, 301 Cecum, 34, 301, 339 Celiac Disease, 38, 79, 81, 86, 105, 111, 116, 171, 193, 301 Cell, 8, 10, 15, 29, 31, 34, 35, 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 48, 50, 52, 53, 54, 55, 57, 58, 59, 61, 64, 67, 69, 70, 72, 73, 75, 77, 78, 79, 80, 81, 82, 83, 84, 86, 87, 88, 89, 91, 93, 125, 126, 133, 146, 161, 163, 164, 166, 167, 171, 172, 173, 175, 176, 177, 178, 184, 186, 188, 192, 193, 196, 198, 199, 200, 201, 202, 203, 204, 226, 260, 261, 285, 287, 290, 291, 292, 293, 294, 295, 296, 298, 300, 301, 303, 304, 306, 309, 310, 311, 312, 315, 316, 317, 320, 322, 323, 325, 327, 328, 331, 333, 335, 336, 337, 338, 339, 343, 344, 345, 346, 347, 349, 350, 353, 354, 355,

358, 359, 360, 361, 362, 364, 368, 370, 375, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388 Cell Adhesion, 166, 167, 178, 198, 199, 298, 301, 335 Cell Adhesion Molecules, 167, 301 Cell Count, 202, 301 Cell Cycle, 53, 301, 310, 328 Cell Death, 45, 48, 193, 292, 301, 325, 350 Cell Differentiation, 54, 55, 173, 192, 200, 202, 203, 301, 375 Cell Division, 53, 260, 294, 301, 327, 344, 346, 360, 364 Cell membrane, 164, 300, 301, 304, 312, 320, 323, 337, 344, 359 Cell Membrane Structures, 301 Cell motility, 81, 301 Cell Physiology, 81, 301 Cell proliferation, 10, 42, 59, 73, 171, 192, 200, 293, 301, 336, 375 Cell Respiration, 301, 346, 355, 370 Cell Survival, 78, 301, 327 Cellulose, 302, 360 Central Nervous System, 285, 294, 298, 299, 302, 323, 326, 328, 340, 341, 347, 348, 351, 354, 374 Ceramide, 200, 302 Cerebellar, 293, 302, 368 Cerebellum, 298, 302, 368 Cerebral, 101, 171, 293, 295, 298, 302, 308, 311, 319, 320, 356, 366, 376, 382 Cerebrospinal, 188, 302 Cerebrospinal fluid, 188, 302 Cerebrovascular, 295, 300, 302, 381 Cerebrum, 302, 385 Cervical, 302, 372 Cervix, 302, 306 Cesarean Section, 26, 302 Character, 290, 302, 311, 326 Chemokines, 39, 56, 73, 162, 163, 186, 196, 302 Chemoprevention, 131, 143, 205, 302 Chemopreventive, 73, 302 Chemotactic Factors, 186, 302, 306 Chemotaxis, 35, 302 Chemotherapy, 302, 369 Chest wall, 27, 302 Chimeras, 84, 302 Chlorambucil, 31, 303 Chlorophyll, 303, 317 Cholangitis, 17, 26, 102, 107, 138, 174, 222, 229, 303

Index 393

Cholecystectomy, 224, 230, 303 Cholecystostomy, 224, 303 Cholelithiasis, 26, 224, 229, 303 Cholera, 168, 303, 387 Cholesterol, 91, 295, 296, 301, 303, 309, 323, 341, 344, 377 Cholinergic, 303, 352 Chondroitin sulfate, 163, 303 Chorioretinitis, 303, 371 Choroid, 303, 370, 371, 386 Choroiditis, 228, 303 Chromatin, 292, 303 Chromosomal, 55, 289, 303, 360, 371 Chromosome, 16, 55, 74, 93, 112, 114, 115, 123, 194, 195, 303, 324, 328, 330, 340 Chromosome Mapping, 115, 303 Chronic, 3, 5, 6, 7, 10, 11, 13, 14, 16, 20, 22, 23, 26, 27, 29, 34, 35, 36, 43, 45, 46, 51, 52, 53, 59, 62, 66, 70, 74, 76, 82, 84, 85, 89, 90, 93, 102, 106, 112, 125, 133, 134, 136, 142, 143, 146, 160, 161, 162, 165, 167, 168, 172, 173, 174, 176, 178, 180, 182, 184, 185, 186, 188, 189, 190, 191, 192, 193, 195, 196, 197, 199, 203, 208, 209, 212, 215, 216, 219, 220, 223, 224, 226, 227, 228, 229, 231, 232, 235, 236, 246, 260, 273, 275, 288, 293, 298, 303, 305, 306, 312, 313, 317, 319, 329, 334, 338, 342, 355, 356, 357, 361, 363, 365, 366, 369, 373, 378, 380, 385 Chronic Disease, 6, 29, 53, 85, 165, 172, 186, 192, 219, 273, 298, 303, 305 Chronic myelogenous leukemia, 303, 342 Chronic Obstructive Pulmonary Disease, 180, 182, 186, 197, 303 Chronic renal, 303, 361, 385 Ciprofloxacin, 11, 303 Circadian, 235, 304 Circadian Rhythm, 235, 304 CIS, 82, 304, 370 Citrus, 22, 304 Clamp, 40, 41, 304 Clarithromycin, 11, 304 Clinical Medicine, 148, 169, 304, 362 Clinical study, 58, 304, 308 Clone, 58, 304 Cloning, 90, 94, 296, 304 Clostridium, 65, 209, 304 Clostridium difficile, 65, 209, 304 Clotrimazole, 154, 304 Coagulation, 118, 166, 297, 304, 329, 360, 382

Cod Liver Oil, 305, 316 Codeine, 273, 305, 353 Coenzymes, 305, 351 Cofactor, 305, 365, 382 Cognitive restructuring, 305, 378 Cohort Studies, 305, 318 Colchicine, 305, 385 Colectomy, 28, 30, 99, 154, 178, 209, 305 Colic, 110, 305 Collagen, 52, 55, 132, 293, 295, 305, 307, 320, 322, 324, 343, 360, 363, 364, 373 Collagen disease, 305, 373 Collagenous Colitis, 42, 105, 305 Collapse, 290, 298, 305 Colloidal, 287, 305, 316, 320, 358 Colonic flora, 45, 305 Colonoscopy, 5, 11, 27, 28, 92, 155, 162, 232, 247, 266, 305 Colorectal Cancer, 9, 28, 33, 106, 111, 116, 131, 132, 143, 183, 208, 222, 242, 267, 305, 306 Colorectal Neoplasms, 108, 306 Colostomy, 203, 239, 267, 306 Combination Therapy, 233, 306 Commensal, 39, 66, 69, 89, 93, 98, 191, 306 Commensalism, 135, 306 Complement, 39, 44, 90, 211, 290, 306, 335, 343, 347, 360, 374 Complement Activation, 44, 290, 306 Complementary and alternative medicine, 24, 103, 306 Complementary medicine, 24, 306 Complete remission, 24, 307, 369 Complete response, 307 Computational Biology, 257, 259, 307 Computed tomography, 297, 307, 372 Computerized axial tomography, 307, 372 Computerized tomography, 245, 307 Conception, 230, 270, 307, 308, 321, 363, 377 Cone, 307, 379 Congestion, 271, 307, 319 Conjugated, 177, 295, 296, 307, 310 Conjunctiva, 307, 373 Conjunctivitis, 166, 167, 170, 184, 186, 228, 307 Conjunctivitis, Allergic, 166, 167, 307 Connective Tissue, 119, 180, 297, 305, 307, 322, 323, 324, 342, 345, 349, 365, 371, 372, 380 Connective Tissue Cells, 307 Connective Tissue Diseases, 119, 307

394


Consciousness, 289, 307, 311, 312, 314 Constipation, 183, 218, 307, 338, 358 Constitutional, 25, 308, 348, 371 Constriction, 41, 308, 338, 386 Constriction, Pathologic, 308, 386 Consultation, 155, 210, 232, 245, 308 Consumption, 22, 148, 183, 308, 312, 324, 352, 370 Contact dermatitis, 169, 190, 308 Contamination, 308, 329 Continent Ileostomy, 272, 308 Contraception, 142, 308 Contraceptive, 103, 308, 344 Contraindications, ii, 308 Contrast Sensitivity, 308, 354 Controlled clinical trial, 14, 233, 308, 368 Controlled study, 153, 308 Conventional therapy, 11, 308 Conventional treatment, 308 Convulsions, 295, 308, 315, 332, 363 Coordination, 34, 302, 308, 348 Cornea, 195, 308, 326, 338, 373, 386 Coronary, 290, 300, 308, 309, 331, 345, 349 Coronary Arteriosclerosis, 308, 349 Coronary Circulation, 290, 308 Coronary heart disease, 300, 309 Coronary Thrombosis, 309, 345, 349 Corpus, 309, 363, 381 Corpus Luteum, 309, 363 Cortex, 293, 298, 309, 320, 368 Corticosteroid, 6, 9, 11, 24, 117, 144, 233, 235, 309, 362, 378 Cortisone, 309, 363 Counterimmunoelectrophoresis, 93, 309 Cranial, 302, 309, 328, 350, 353, 386 Cross-Cultural Comparison, 129, 309 Cross-Sectional Studies, 309, 318 Culture Media, 71, 287, 309 Curative, 203, 223, 309, 351, 371, 381 Custom-made, 64, 309 Cutaneous, 223, 308, 310, 341 Cyclic, 299, 310, 327, 352, 364 Cyclin, 53, 73, 310 Cyclophosphamide, 31, 242, 310 Cyclosporine, 8, 9, 26, 31, 178, 229, 230, 235, 245, 310 Cystathionine beta-Synthase, 310, 331 Cysteine, 118, 186, 302, 310, 379 Cystine, 310 Cytochrome, 200, 310, 370 Cytochrome b, 310, 370 Cytopenia, 192, 310

Cytoplasm, 174, 292, 295, 301, 310, 318, 327, 371, 380 Cytoskeletal Proteins, 79, 310 Cytoskeleton, 79, 81, 87, 310, 335 Cytotoxic, 31, 91, 299, 310, 333, 367, 375 Cytotoxicity, 59, 288, 311 D Daclizumab, 39, 311 Dairy Products, 183, 311 Databases, Bibliographic, 257, 311 De novo, 17, 72, 311 Decarboxylation, 311, 330 Decompression, 223, 311 Decompression Sickness, 311 Defecation, 40, 311 Defense Mechanisms, 45, 311, 335 Degenerative, 311, 329, 342, 347, 349, 354, 371 Dehydration, 12, 303, 311 Deletion, 36, 84, 194, 292, 311 Delirium, 192, 231, 311 Dementia, 163, 166, 167, 187, 192, 311 Denaturation, 38, 312, 361 Dendrites, 312, 351 Dendritic, 56, 57, 68, 78, 83, 88, 202, 312, 344 Dendritic cell, 56, 57, 68, 78, 83, 88, 202, 312 Density, 6, 19, 29, 89, 101, 109, 122, 138, 142, 147, 297, 312, 341, 353, 368, 376 Depigmentation, 312, 388 Depolarization, 41, 312, 375 Depressive Disorder, 90, 128, 312 Dermal, 166, 167, 312 Dermatitis, 164, 169, 170, 185, 190, 192, 197, 198, 312, 315 Dermatitis Herpetiformis, 164, 312 Dermatosis, 223, 312 Desensitization, 61, 312 Deuterium, 312, 331 Developed Countries, 55, 312 Dextran Sulfate, 44, 52, 56, 312 Diabetes Insipidus, 195, 312 Diabetes Mellitus, 65, 86, 312, 325, 326, 328, 353 Diagnostic Imaging, 246, 312 Diagnostic procedure, 159, 244, 313, 374 Diarrhoea, 183, 313, 324 Diastolic, 313, 331 Diencephalon, 313, 332, 381 Dietary Fats, 313, 340 Dietitian, 270, 313

Index 395

Diffusion, 309, 313, 335, 337, 351 Digestion, 130, 218, 287, 295, 296, 297, 313, 315, 334, 337, 340, 341, 357, 378, 386 Digestive system, 146, 157, 210, 269, 270, 271, 273, 313, 324, 348 Digestive tract, 7, 218, 246, 247, 270, 272, 303, 313, 375, 377 Dilatation, 167, 290, 313, 363, 386 Dilatation, Pathologic, 313, 386 Dilate, 10, 313 Dilation, 170, 191, 223, 298, 313, 386 Dimethyl, 313, 341 Diphenoxylate, 273, 313 Diploid, 313, 360 Disease Progression, 26, 313, 387 Disease Susceptibility, 16, 117, 133, 313 Disinfectant, 313, 320 Disorientation, 311, 313 Disposition, 232, 314 Dissection, 113, 314 Dissociation, 286, 314 Distal, 15, 25, 66, 144, 314, 365 Diuresis, 299, 314 Dizziness, 178, 314, 387 Dominance, 119, 314, 319 Dopamine, 119, 314, 359 Dorsal, 314, 350, 362 Drug Design, 75, 314 Drug Interactions, 250, 314 Drug Resistance, 111, 314 Drug Tolerance, 314, 383 Duct, 289, 300, 303, 315, 354, 372 Duodenal Ulcer, 197, 315 Duodenitis, 169, 190, 315 Duodenum, 51, 179, 295, 303, 315, 317, 324, 329, 338, 351, 357, 378 Dura mater, 315, 344, 355 Dyes, 295, 315 Dysentery, 288, 315 Dyskinesia, 315 Dyspepsia, 76, 315, 334 Dysphoric, 312, 315 Dysplasia, 10, 28, 107, 160, 208, 222, 261, 315 Dyspnea, 315, 366 Dystrophy, 195, 261, 315 E Eclampsia, 295, 315, 363 Ectoderm, 315, 350 Eczema, 169, 186, 190, 315 Edema, 47, 165, 190, 308, 315, 349, 350, 363, 385

Effector, 40, 55, 61, 64, 73, 78, 86, 87, 88, 173, 198, 285, 306, 315, 318, 351 Effector cell, 173, 315, 351 Efficacy, 4, 5, 8, 9, 20, 27, 84, 95, 105, 107, 127, 153, 233, 235, 314, 315 Eicosanoids, 33, 42, 56, 187, 315 Elasticity, 293, 308, 315 Elastin, 305, 307, 315, 320 Elective, 132, 315 Electric Impedance, 100, 316 Electrocoagulation, 304, 316 Electrolyte, 61, 309, 311, 316, 322, 346, 352, 362, 376, 385 Electrons, 292, 295, 300, 316, 337, 355, 367 Electrophoresis, 174, 316 Elementary Particles, 316, 351, 365 Embryo, 296, 301, 315, 316, 334, 361, 363, 377 Embryo Transfer, 316, 363 Emollient, 316, 326 Emphysema, 185, 303, 316 Empiric, 76, 316 Emulsion, 230, 316, 322 Encephalitis, 316 Encephalomyelitis, 55, 316 Encephalopathy, 166, 316 Endarterectomy, 290, 316 Endemic, 303, 317, 377 Endocarditis, 317, 319 Endocrine System, 317, 350 Endocytosis, 38, 81, 301, 317 Endoscope, 11, 317 Endoscopic, 10, 25, 26, 28, 70, 223, 227, 240, 305, 317, 375 Endoscopy, 5, 6, 10, 70, 76, 107, 121, 134, 135, 142, 209, 272, 317 Endothelial cell, 48, 109, 164, 166, 188, 202, 317, 322, 336, 382 Endothelium, 48, 161, 178, 196, 317, 352 Endothelium, Lymphatic, 317 Endothelium, Vascular, 317 Endothelium-derived, 317, 352 Endotoxic, 317, 340 Endotoxin, 46, 317, 385 End-stage renal, 303, 317, 361 Enema, 11, 154, 221, 317 Energy balance, 317, 339 Enhancer, 317, 370 Enteric bacteria, 59, 74, 317 Enteric Nervous System, 67, 318 Enteritis, 71, 164, 210, 318 Enterocolitis, 17, 52, 65, 101, 210, 304, 318

396


Environmental Exposure, 318, 353 Environmental Health, 55, 256, 258, 318 Enzymatic, 31, 41, 198, 299, 300, 306, 318, 330, 361, 370 Enzyme Induction, 318, 370 Enzyme Inhibitors, 318, 360 Enzyme Repression, 318, 370 Eosinophil, 187, 318 Eosinophilia, 318, 321 Eosinophilic, 41, 171, 193, 318, 321 Eosinophilic Gastroenteritis, 171, 193, 318 Epidemic, 318, 377 Epidemiologic Studies, 30, 318 Epidemiological, 16, 21, 27, 55, 193, 318 Epidermal, 4, 28, 42, 65, 318, 338, 344 Epidermal Growth Factor, 4, 28, 65, 318 Epidermis, 285, 296, 318, 338, 357, 366 Epidermoid carcinoma, 319, 377 Epinephrine, 286, 314, 319, 352, 385 Episcleritis, 228, 319, 373 Episiotomy, 26, 319 Epistasis, 93, 319 Epithelium, 41, 42, 45, 52, 61, 62, 69, 77, 89, 160, 179, 185, 209, 295, 317, 319, 324, 337 Epitopes, 61, 319 Erysipeloid, 67, 319, 371 Erythema, 67, 136, 223, 308, 319, 386 Erythema Nodosum, 136, 223, 319 Erythrocytes, 289, 290, 297, 319, 328, 355, 359, 368, 374 Erythromycin, 304, 319 Erythropoiesis, 6, 53, 319 Erythropoietin, 6, 225, 319 Esophagitis, 170, 171, 193, 319 Esophagitis, Peptic, 170, 319 Esophagus, 178, 179, 294, 313, 319, 320, 324, 328, 353, 357, 368, 378 Essential Tremor, 261, 320 Estrogen, 49, 320 Ethanol, 40, 72, 174, 320 Ethnic Groups, 23, 30, 68, 320 Eukaryotic Cells, 310, 320, 334, 354 Evacuation, 307, 320, 324, 339 Evoke, 320, 378 Excipient, 180, 320 Exocytosis, 68, 81, 320, 380 Exogenous, 49, 50, 182, 315, 320, 324, 364 Exon, 68, 288, 320 Extender, 220, 320 Extensor, 320, 366, 388

External-beam radiation, 320, 338, 367, 388 Extracellular, 62, 163, 167, 180, 307, 317, 320, 322, 335, 343, 376, 381 Extracellular Matrix, 163, 167, 180, 307, 320, 322, 335, 343 Extracellular Matrix Proteins, 320, 322, 343 Extracellular Space, 320 Extrapyramidal, 314, 320 Extravascular, 41, 321 Exudate, 303, 321, 353 F Facial, 287, 321, 356 Faecal, 110, 313, 321 Familial polyposis, 306, 321 Family Planning, 103, 257, 321 Fasciitis, 27, 321 Fat, 21, 181, 223, 286, 292, 296, 297, 300, 302, 309, 321, 339, 340, 348, 353, 362, 371, 376, 380, 384 Fathers, 139, 321 Fatigue, 117, 246, 247, 270, 321, 328 Fatty acids, 21, 28, 146, 245, 287, 315, 321, 326, 340, 341, 364 Feasibility Studies, 65, 321 Febrile, 321, 377 Feces, 307, 321, 344, 378 Femoral, 6, 321 Femur, 321 Fence, 61, 321 Ferritin, 6, 321 Fertilization in Vitro, 321, 363 Fetus, 26, 302, 319, 321, 360, 377, 378, 386 Fibrin, 166, 297, 321, 358, 382 Fibrinogen, 321, 360, 382 Fibroblast Growth Factor, 30, 163, 202, 203, 322 Fibroblasts, 57, 68, 131, 185, 188, 202, 307, 321, 322, 336 Fibronectin, 166, 322 Fibrosarcoma, 321, 322 Fibrosis, 52, 68, 128, 160, 261, 288, 322, 366, 372, 373 Fistula, 229, 322, 353 Fixation, 322, 374 Flatulence, 218, 322 Flatus, 322, 323 Fluid Therapy, 322, 352 Fluorescence, 43, 48, 71, 174, 322 Focal Adhesions, 79, 322 Folate, 143, 144, 323

Index 397

Fold, 55, 62, 323, 345 Folic Acid, 4, 11, 323 Forearm, 18, 297, 321, 323, 367 Frameshift, 74, 323, 385 Frameshift Mutation, 74, 323, 385 Fungi, 200, 292, 323, 327, 337, 345, 346, 388 Fungistatic, 295, 323 G Gallate, 52, 323 Gallbladder, 26, 224, 230, 285, 296, 303, 313, 323, 324, 329 Gallstones, 26, 224, 229, 296, 303, 323 Gamma Rays, 323, 367 Ganglia, 67, 285, 295, 318, 323, 350, 379 Ganglion, 323, 350, 353 Gangliosides, 201, 323 Gap Junctions, 323, 380 Gas, 218, 289, 311, 313, 322, 323, 331, 334, 338, 343, 352, 368 Gastric, 35, 50, 69, 79, 168, 294, 318, 319, 323, 324, 328, 330, 357 Gastric Emptying, 50, 324 Gastric Juices, 324, 357 Gastric Mucosa, 35, 324 Gastrin, 324, 330 Gastritis, 35, 169, 324 Gastroenteritis, 62, 168, 324 Gastroenterologist, 219, 224, 230, 231, 232, 234, 324 Gastrointestinal Neoplasms, 293, 324 Gelatin, 309, 324, 326, 379, 382 Gelsolin, 81, 324 Gene Expression, 35, 42, 53, 58, 60, 64, 65, 73, 77, 82, 83, 89, 121, 181, 262, 324 Gene Targeting, 37, 324 Genes, mos, 16, 324 Genetic Code, 324, 352 Genetic Markers, 23, 134, 325 Genetic testing, 325, 361 Genital, 69, 303, 325, 386 Genitourinary, 325, 386 Genotype, 66, 115, 133, 325, 359 Germfree, 66, 325 Germ-free, 39, 325 Gestation, 26, 325, 360, 377 Giant Cells, 325, 372 Giardiasis, 325, 345 Gland, 286, 309, 325, 342, 355, 356, 360, 364, 373, 378, 379, 382 Glomerular, 65, 325, 369 Glomeruli, 65, 325

Glomerulonephritis, 99, 165, 166, 168, 325, 342 Glomerulosclerosis, 86, 325 Glomerulus, 325, 350 Glucocorticoid, 4, 5, 115, 212, 217, 235, 236, 298, 325, 362, 363 Glucose, 50, 57, 65, 143, 261, 291, 297, 302, 312, 325, 326, 328, 331, 335, 372 Glucose Intolerance, 312, 326 Glucuronic Acid, 326, 329 Glutamate, 142, 326 Glutamic Acid, 323, 326, 328, 364 Glutamine, 11, 28, 147, 326 Glutathione Peroxidase, 326, 373 Gluten, 301, 326 Glycerol, 47, 326, 359 Glycerophospholipids, 326, 359 Glycine, 188, 295, 296, 326, 374 Glycoprotein, 132, 179, 319, 321, 322, 325, 326, 339, 348, 382, 385 Glycosaminoglycan, 162, 163, 303, 326 Glycosylation, 96, 163, 326 Goats, 311, 326 Goblet Cells, 68, 326 Gonadal, 326, 377 Gonadotropin, 65, 326 Gonads, 326, 332 Gout, 168, 305, 326 Governing Board, 327, 362 Graft, 177, 182, 197, 198, 327, 330, 333, 342, 346, 348, 349 Graft Rejection, 182, 327, 333, 342, 346 Graft-versus-host disease, 177, 327, 348 Gram-negative, 46, 89, 317, 327, 328, 387 Gram-Negative Bacteria, 89, 317, 327 Gram-positive, 89, 304, 327, 348, 378 Gram-Positive Bacteria, 304, 327 Granule, 35, 68, 188, 327, 371 Granulocytes, 174, 287, 327, 339, 348, 375, 388 Granulomas, 57, 327 Granulomatous Colitis, 59, 327 Granulomatous Disease, Chronic, 327, 370 Grasses, 323, 327 Gravis, 86, 126, 327 Growth factors, 41, 46, 52, 67, 72, 163, 192, 202, 327 Guanylate Cyclase, 327, 352 H Habitat, 327, 348, 351 Handedness, 242, 327 Handicap, 321, 327

398


Haploid, 328, 360 Haplotypes, 195, 328 Haptens, 287, 328 Headache, 299, 328, 331 Health Education, 246, 328 Health Status, 271, 328 Heart attack, 199, 300, 328 Heart failure, 85, 180, 192, 328, 366 Heartburn, 218, 328, 334 Helicobacter, 35, 60, 66, 69, 76, 93, 94, 109, 116, 165, 328 Helix-loop-helix, 67, 328 Hematologic Diseases, 34, 328 Heme, 296, 310, 328, 355 Hemoglobin, 6, 290, 297, 319, 328 Hemoglobin C, 290, 328 Hemoglobinuria, 261, 328 Hemolytic, 321, 328 Hemorrhage, 316, 328, 329, 349, 359, 366, 378 Hemorrhoids, 171, 193, 209, 270, 329 Hemostasis, 329, 335, 374, 382 Heparin, 8, 30, 329, 360 Hepatic, 34, 53, 116, 118, 287, 311, 329 Hepatic Artery, 287, 329 Hepatitis, 26, 32, 76, 91, 166, 168, 174, 233, 329, 387 Hepatitis A, 26, 91, 166, 329 Hepatitis C, 77, 166, 329 Hepatitis Viruses, 166, 329 Hepatobiliary, 19, 25, 26, 77, 116, 224, 238, 329 Hepatocellular, 76, 166, 329 Hepatocytes, 329 Hepatovirus, 329 Hereditary, 232, 307, 326, 329, 347, 371 Heredity, 324, 325, 329 Heterodimer, 59, 329 Heterogeneity, 12, 21, 117, 234, 287, 329 Heterogenic, 329 Heterogenous, 174, 329 Heterotrophic, 323, 329 Heterozygote, 68, 330 Histamine, 165, 186, 290, 330, 341 Histidine, 188, 330 Histocompatibility, 114, 173, 330, 346 Histocompatibility Antigens, 173, 330 Histology, 70, 72, 330 Holidays, 209, 330 Homeostasis, 6, 43, 53, 57, 60, 77, 81, 88, 181, 194, 203, 209, 330 Homodimer, 59, 330, 384

Homogeneous, 111, 174, 293, 330 Homologous, 46, 195, 288, 324, 330, 374, 380 Homozygotes, 314, 330 Hormonal, 6, 294, 309, 330, 388 Human growth hormone, 4, 330, 376 Humeral, 177, 330 Humoral, 37, 71, 327, 330 Humour, 330 Hybrid, 43, 304, 330, 331 Hybridization, 92, 330 Hybridomas, 331, 336 Hydrogen Bonding, 331, 352 Hydrogen Peroxide, 300, 326, 331, 340, 379 Hydrolysis, 331, 337, 359, 361, 365 Hydroxybenzoic Acids, 289, 331 Hydroxylysine, 305, 331 Hydroxyproline, 305, 331 Hyperaemia, 307, 331 Hyperalgesia, 72, 331 Hyperbilirubinemia, 331, 338 Hyperhomocysteinemia, 113, 310, 331 Hyperplasia, 331, 349 Hypersensitivity, 75, 166, 167, 170, 182, 288, 290, 307, 312, 318, 331, 340, 371, 374 Hypertension, 41, 80, 85, 192, 293, 300, 328, 331, 353, 363, 383, 385 Hypertrophy, 181, 192, 331 Hyperuricemia, 145, 327, 331 Hypnotic, 295, 331, 381 Hypoglycaemia, 311, 331 Hypogonadism, 86, 332 Hypotension, 192, 308, 332, 351, 360 Hypothalamic, 84, 119, 135, 332 Hypothalamus, 84, 294, 298, 313, 332, 351, 360, 376, 381 Hypothyroidism, 86, 332 Hypoxia, 290, 311, 332, 381 Hysterotomy, 302, 332 I Id, 149, 260, 275, 280, 282, 332 Idiopathic, 8, 40, 51, 55, 74, 89, 106, 133, 185, 190, 193, 209, 223, 230, 332, 366, 372 Ileal, 5, 10, 99, 154, 207, 222, 237, 240, 332 Ileitis, 120, 154, 164, 178, 194, 216, 332 Ileoanal Pull-Through, 209, 332 Ileostomy, 100, 211, 239, 267, 272, 332, 350 Ileum, 39, 189, 203, 204, 271, 274, 301, 332, 338, 351 Imidazole, 164, 296, 304, 330, 332 Immune function, 29, 36, 332, 333, 384

Index 399

Immune response, 8, 22, 32, 34, 36, 37, 48, 54, 55, 57, 58, 59, 60, 63, 70, 83, 85, 168, 171, 172, 176, 177, 181, 184, 186, 193, 290, 291, 294, 309, 327, 328, 332, 333, 343, 347, 373, 374, 379, 386, 387 Immune Sera, 332 Immunity, 36, 57, 68, 74, 78, 94, 119, 144, 177, 191, 332, 333, 336, 342, 353, 384 Immunization, 165, 268, 275, 286, 332, 333, 374 Immunoassay, 104, 333 Immunoblotting, 174, 333 Immunocompromised, 173, 210, 333 Immunodeficiency, 64, 87, 192, 197, 260, 333 Immunofluorescence, 174, 333 Immunogenic, 162, 183, 333, 340 Immunoglobulin, 143, 291, 333, 347, 374 Immunohistochemistry, 41, 92, 333 Immunologic, 23, 29, 63, 70, 168, 190, 193, 286, 302, 332, 333, 342, 367 Immunologic Memory, 70, 333 Immunology, 29, 33, 36, 44, 64, 69, 71, 89, 95, 98, 105, 110, 145, 179, 185, 287, 333 Immunomodulator, 70, 333 Immunosuppressive Agents, 9, 32, 51, 272, 333, 373 Immunosuppressive therapy, 7, 223, 333 Immunotherapy, 286, 296, 312, 333 Immunotoxins, 177, 333, 367 Impairment, 45, 293, 311, 315, 333, 345 Implant radiation, 334, 336, 338, 367, 388 Implantation, 307, 334 In situ, 42, 71, 92, 334 In Situ Hybridization, 42, 71, 334 In vitro, 34, 37, 40, 41, 42, 43, 45, 48, 51, 55, 57, 58, 59, 63, 67, 70, 73, 75, 78, 81, 83, 86, 92, 143, 195, 202, 316, 334, 361, 380 Incision, 305, 319, 332, 334, 337 Incontinence, 75, 334 Incubation, 334, 339 Incubation period, 334, 339 Indicative, 62, 211, 334, 356, 386 Indigestion, 334, 338 Induction, 8, 42, 52, 60, 63, 66, 78, 84, 88, 89, 91, 173, 200, 209, 236, 290, 334 Induction therapy, 334 Infancy, 225, 334, 371 Infant, Newborn, 287, 334 Infantile, 110, 334 Infarction, 334, 369 Infertility, 46, 171, 271, 334

Infiltration, 86, 196, 325, 335 Infusion, 20, 51, 335, 349, 384 Ingestion, 71, 183, 335, 361, 381 Inhalation, 293, 335, 361 Initiation, 31, 66, 78, 88, 92, 161, 173, 186, 335, 364, 383 Initiator, 335, 336 Inlay, 335, 370 Inorganic, 164, 335, 348 Inotropic, 314, 335 Insight, 30, 37, 53, 56, 64, 75, 86, 219, 228, 335 Insomnia, 195, 335 Insulator, 335, 348 Insulin, 39, 52, 143, 335, 338, 372 Insulin-dependent diabetes mellitus, 335 Insulin-like, 52, 335 Insurance Pools, 226, 335 Integrins, 20, 35, 167, 196, 199, 322, 335 Interferon, 4, 55, 73, 173, 179, 336, 342 Interferon-alpha, 336 Interferon-beta, 55, 336 Interleukin-1, 46, 51, 57, 85, 135, 145, 170, 175, 336 Interleukin-10, 52, 85, 145, 336 Interleukin-11, 170, 336 Interleukin-12, 135, 336 Interleukin-2, 70, 169, 336 Interleukin-6, 46, 104, 175, 336 Interleukin-8, 35, 175, 336 Interleukins, 8, 333, 336, 342 Intermittent, 162, 322, 336 Internal radiation, 336, 338, 367, 388 Interstitial, 38, 185, 298, 320, 336, 338, 350, 369, 388 Intestinal Flora, 39, 337 Intoxication, 311, 337, 388 Intracellular, 38, 40, 63, 66, 81, 145, 192, 201, 299, 334, 335, 337, 344, 352, 362, 364, 368, 373, 375 Intraepithelial, 34, 39, 77, 179, 337 Intrahepatic, 287, 337 Intrahepatic bile ducts, 287, 337 Intramuscular, 235, 337, 356 Intravascular, 166, 337 Intravenous, 24, 143, 235, 274, 335, 337, 356 Intrinsic, 25, 60, 176, 287, 295, 337 Introns, 337, 365 Intussusception, 337, 368 Invasive, 36, 71, 76, 126, 178, 203, 332, 337, 342

400


Involuntary, 295, 320, 337, 349 Ion Channels, 41, 164, 337, 351, 380 Ion Transport, 81, 337, 346 Ionizing, 288, 318, 337, 367 Ions, 51, 164, 295, 314, 316, 324, 331, 337, 347, 365 Iris, 308, 337, 366, 386 Irradiation, 87, 306, 338, 388 Irritable Bowel Syndrome, 72, 75, 102, 113, 121, 138, 183, 197, 211, 212, 218, 231, 236, 246, 247, 271, 338 Ischemia, 33, 294, 323, 338, 349, 369 Ischemic Colitis, 17, 338 Islet, 39, 338 J Jaundice, 26, 166, 287, 331, 338 Jejunum, 303, 338 Joint, 14, 19, 28, 88, 139, 221, 272, 293, 303, 311, 338, 354, 379, 380 Joint Capsule, 338, 380 K Kb, 55, 256, 338 Keratinocyte growth factor, 4, 338 Keratinocytes, 336, 338 Keratitis, 228, 338 Kidney Disease, 153, 155, 157, 238, 256, 261, 268, 338, 369 Kinetics, 61, 338 L Labile, 306, 338 Lacerations, 319, 338 Lactose Intolerance, 5, 237, 338 Lactulose, 105, 339 Lag, 14, 70, 339 Laminin, 132, 295, 320, 339 Larynx, 339, 383, 386 Latent, 339, 362 Lavage, 185, 339 Laxative, 287, 339 Least-Squares Analysis, 339, 369 Lectin, 82, 339, 344 Lens, 299, 300, 339 Lentivirus, 64, 339 Leptin, 83, 168, 339 Lesion, 10, 179, 223, 339, 341, 385 Lethal, 87, 294, 339 Lethargy, 332, 339 Leucocyte, 318, 339, 342 Leukapheresis, 155, 292, 339 Leukemia, 260, 303, 311, 339

Leukocytes, 35, 48, 88, 161, 164, 165, 167, 170, 177, 178, 179, 188, 196, 295, 297, 302, 327, 336, 339, 340, 355, 385 Leukopenia, 32, 178, 340 Leukotrienes, 41, 187, 292, 293, 315, 340, 341 Libido, 290, 340 Library Services, 280, 340 Life cycle, 323, 340 Life Expectancy, 23, 340 Ligament, 340, 364 Ligands, 57, 67, 80, 81, 91, 163, 166, 178, 192, 194, 195, 196, 301, 335, 340 Ligation, 64, 340 Likelihood Functions, 340, 369 Linear Models, 340, 369 Linkage, 16, 21, 25, 49, 55, 74, 87, 123, 325, 340, 357 Linkage Disequilibrium, 50, 74, 340 Linoleic Acids, 28, 340 Lipase, 81, 340 Lipid, 21, 33, 86, 142, 145, 181, 200, 230, 293, 301, 326, 335, 340, 341, 348, 355 Lipid A, 33, 340 Lipid Peroxidation, 340, 355 Lipopolysaccharide, 63, 89, 188, 327, 340 Lipoprotein, 327, 341 Lipoxygenase, 187, 245, 273, 292, 340, 341 Lipoxygenase Inhibitors, 273, 341 Liver scan, 341, 372 Liver Transplantation, 17, 26, 102, 107, 222, 341 Lobe, 330, 341 Local therapy, 235, 341 Localization, 38, 45, 49, 79, 110, 179, 333, 341 Localized, 67, 170, 173, 190, 285, 289, 319, 322, 334, 339, 341, 360, 373, 385, 386 Locomotion, 341, 360 Logistic Models, 341, 369 Loop, 66, 332, 341 Loperamide, 273, 341 Lucida, 339, 341 Lumbar, 6, 341 Lumen, 50, 61, 317, 341 Lupus, 33, 38, 65, 86, 162, 165, 166, 341, 342, 380 Lupus Nephritis, 38, 65, 342 Lymph, 133, 196, 302, 317, 330, 342, 372, 379 Lymph node, 133, 196, 302, 342, 372

Index 401

Lymphatic, 129, 317, 334, 342, 345, 361, 372, 376, 377, 382 Lymphatic system, 342, 372, 376, 377, 382 Lymphoblasts, 196, 342 Lymphocyte, 36, 37, 64, 71, 72, 133, 161, 162, 177, 196, 291, 342, 343 Lymphocyte Subsets, 37, 162, 342 Lymphocyte Transformation, 71, 342 Lymphocytic, 65, 209, 342 Lymphoid, 39, 58, 63, 64, 77, 196, 227, 233, 291, 339, 342 Lymphokines, 175, 342 Lymphoma, 9, 15, 17, 106, 108, 210, 227, 233, 260, 342 Lysine, 328, 331, 342, 363 Lytic, 342, 374 M Macrophage, 4, 46, 56, 57, 63, 78, 86, 179, 336, 342 Macrophage Activation, 86, 342 Macula, 342 Macula Lutea, 342 Macular Degeneration, 180, 342 Magnetic Resonance Imaging, 134, 342, 372 Maintenance therapy, 123, 221, 236, 343 Major Histocompatibility Complex, 16, 328, 330, 343 Malabsorption, 18, 218, 261, 269, 270, 301, 343, 375 Malabsorption syndrome, 343, 375 Malaise, 32, 343 Malformation, 10, 343 Malignancy, 8, 10, 32, 343 Malignant tumor, 200, 306, 343, 348 Malnutrition, 4, 12, 27, 146, 225, 269, 287, 294, 298, 343, 348 Mania, 343 Manic, 192, 343 Manifest, 172, 343 Matrix metalloproteinase, 109, 180, 243, 343 Measles Virus, 13, 218, 343 Meat, 313, 319, 343 Medial, 293, 343, 353 Mediate, 42, 52, 53, 66, 89, 169, 192, 199, 301, 314, 343 Mediator, 33, 35, 52, 53, 82, 192, 336, 343, 360, 374 Medical Records, 14, 344, 371 Medicament, 344, 379 MEDLINE, 257, 259, 261, 344

Medroxyprogesterone, 171, 193, 344 Medroxyprogesterone Acetate, 171, 193, 344 Megacolon, 67, 344 Megakaryocytes, 336, 344 Megaloblastic, 323, 344 Meiosis, 344, 380 Melanin, 312, 337, 344, 359, 385 Melanocytes, 344 Melanoma, 260, 344 Melena, 165, 344 Membrane Microdomains, 61, 344 Membrane Proteins, 301, 344 Memory, 55, 291, 311, 312, 344 Meninges, 302, 315, 344 Meningitis, 166, 167, 170, 344, 359 Menopause, 344, 362, 363 Menstrual Cycle, 344, 363 Mental Disorders, 158, 344, 359, 366 Mental Retardation, 192, 262, 345 Mentors, 37, 345 Meperidine, 313, 345 Mesenchymal, 293, 318, 345 Mesenteric, 124, 133, 181, 196, 345 Mesentery, 345, 358 Meta-Analysis, 55, 345 Metabolic disorder, 312, 326, 345 Metabolite, 31, 32, 313, 318, 345, 363 Metabolization, 199, 345 Metaplasia, 133, 345 Metastasis, 43, 81, 163, 166, 167, 187, 301, 343, 345 Methionine, 313, 345, 379 Metronidazole, 9, 11, 26, 250, 273, 345 MI, 180, 208, 283, 345 Microbe, 69, 93, 98, 345, 383 Microbiology, 29, 33, 70, 71, 102, 133, 146, 182, 286, 294, 345 Microcirculation, 41, 346 Microfilaments, 322, 346 Micronutrients, 148, 346 Microorganism, 305, 346, 356, 388 Micro-organism, 183, 325, 346 Microscopy, 41, 62, 65, 174, 295, 346 Microspheres, 99, 346 Migration, 20, 35, 42, 48, 61, 62, 67, 79, 131, 161, 163, 167, 170, 186, 187, 191, 196, 342, 346 Milligram, 233, 346 Milliliter, 297, 346 Mineralocorticoids, 286, 309, 346

402


Minor Histocompatibility Antigens, 330, 346 Minority Groups, 12, 346 Miscarriage, 271, 346 Mitochondria, 188, 200, 346, 349, 354 Mitochondrial Swelling, 346, 350 Mitosis, 292, 346 Mobility, 48, 346 Modeling, 314, 347 Modification, 58, 347, 367 Modulator, 73, 347 Molecular Structure, 347, 384 Monitor, 234, 272, 347, 352 Monoclonal, 3, 15, 20, 39, 61, 64, 78, 82, 156, 311, 331, 333, 338, 347, 367, 372, 388 Monoclonal antibodies, 3, 15, 61, 82, 311, 333, 347, 372 Monocyte, 86, 161, 188, 347 Monokines, 166, 175, 347 Mononuclear, 34, 58, 86, 143, 175, 186, 196, 321, 347, 385 Monotherapy, 5, 347 Morbillivirus, 343, 347 Morphine, 305, 313, 345, 347, 353 Morphological, 10, 62, 316, 344, 347 Morphology, 36, 342, 347 Motility, 40, 67, 81, 324, 347, 374 Motion Sickness, 347, 349 Movement Disorders, 347, 381 Mucins, 68, 326, 347 Mucolytic, 298, 348 Mucosal Ulceration, 43, 348 Mucositis, 170, 348 Mucus, 68, 187, 315, 347, 348, 385 Multiple Myeloma, 74, 166, 348 Multiple Organ Failure, 169, 190, 348 Muscle Fibers, 348 Muscular Atrophy, 261, 348 Muscular Dystrophies, 315, 348 Mutagenesis, 75, 348 Mutagens, 323, 348 Myalgia, 67, 348 Myasthenia, 86, 126, 348 Mycobacterium, 71, 94, 226, 348, 356, 385 Mycophenolate mofetil, 134, 348 Mydriatic, 313, 348 Myelin, 348 Myeloid Cells, 174, 348 Myelosuppression, 192, 348 Myocardial infarction, 171, 192, 295, 309, 345, 349 Myocardial Ischemia, 163, 187, 290, 349

Myocardial Reperfusion, 349, 370 Myocardial Reperfusion Injury, 349, 370 Myocarditis, 166, 167, 349 Myocardium, 290, 345, 349 Myositis, 228, 349 Myotonic Dystrophy, 261, 349 N Naive, 40, 55, 349 Nasal Mucosa, 349 Nasal Polyps, 182, 349 Natural killer cells, 336, 349 Nausea, 20, 32, 178, 272, 324, 334, 349, 352, 385 NCI, 1, 157, 255, 304, 349 Necrosis, 4, 43, 88, 166, 176, 179, 292, 321, 334, 345, 349, 350, 369, 372 Necrotizing Enterocolitis, 168, 170, 350 Neonatal, 77, 287, 350 Neonatal period, 287, 350 Neoplasia, 5, 54, 170, 222, 260, 350 Neoplasm, 350, 372, 385 Neoplastic, 10, 31, 42, 53, 68, 81, 124, 331, 342, 350 Nephritis, 39, 44, 161, 166, 167, 350 Nephropathy, 65, 161, 338, 350 Nephrosis, 350 Nephrotic, 99, 350 Nephrotic Syndrome, 99, 350 Nephrotoxic, 44, 350 Nervous System, 261, 286, 294, 302, 343, 350, 351, 376, 379, 380 Networks, 13, 350 Neural, 67, 72, 286, 330, 350 Neural Crest, 67, 350 Neuritis, 350, 354 Neuroendocrine, 72, 125, 350 Neurogenic, 350, 386 Neuronal, 65, 67, 72, 84, 188, 351 Neurons, 67, 72, 84, 312, 323, 351, 352, 379, 380 Neuropathy, 196, 197, 351 Neuropeptide, 65, 185, 351 Neuropharmacology, 72, 351 Neurophysiology, 312, 351 Neuroretinitis, 351, 371 Neurosis, 351 Neurotensin, 65, 351 Neurotic, 197, 351 Neurotransmitters, 351 Neutralization, 82, 88, 351 Neutrons, 288, 338, 351, 367 Neutropenia, 192, 351, 360

Index 403

Neutrophil, 33, 35, 56, 61, 97, 118, 125, 160, 176, 351 Neutrophil Infiltration, 35, 160, 351 Niacin, 4, 351, 385 Niche, 44, 351 Nicotine, 7, 8, 107, 147, 270, 273, 351 Nitric Oxide, 6, 72, 96, 100, 205, 352 Nitrogen, 288, 290, 310, 311, 320, 322, 326, 352, 385 Nonulcer Dyspepsia, 76, 352 Nonverbal Communication, 352, 366 Norepinephrine, 119, 286, 314, 352 Nuclear, 56, 57, 73, 80, 91, 120, 147, 174, 181, 245, 295, 316, 320, 323, 350, 352, 365, 381 Nuclear Medicine, 120, 147, 245, 352 Nuclei, 84, 288, 316, 337, 343, 346, 351, 352, 353, 365, 372 Nucleic acid, 31, 94, 191, 194, 195, 202, 295, 324, 330, 334, 348, 352, 366 Nucleic Acid Hybridization, 94, 330, 352 Nucleus, 47, 53, 292, 294, 295, 303, 310, 312, 316, 320, 323, 344, 347, 351, 352, 364, 365, 378, 381 Nursing Care, 352, 357 Nutritional Status, 28, 142, 352 Nutritional Support, 9, 208, 352 O Occult, 225, 352 Octreotide, 224, 352 Ocular, 19, 126, 170, 228, 353 Odds Ratio, 353, 369 Oesophagitis, 169, 353 Oligomenorrhea, 353, 361 Omega-3 fatty acid, 33, 353 Oncogene, 49, 260, 324, 353 Oncogenic, 74, 335, 339, 353 Oncology, 205, 353 Opacity, 300, 312, 353 Open Reading Frames, 339, 353 Operon, 353, 364, 370 Ophthalmologist, 228, 353 Opium, 273, 347, 353, 356 Opsin, 353, 370 Optic Chiasm, 332, 353 Optic disc, 353, 354 Optic Nerve, 351, 353, 354, 355, 370, 371, 373 Optic Neuritis, 228, 354 Orbit, 354 Orbital, 228, 354 Organ Transplantation, 9, 166, 167, 354

Organelles, 310, 344, 354 Orthostatic, 353, 354 Osmosis, 354 Osmotic, 81, 287, 346, 354 Ossification, 354, 371 Osteoarthritis, 162, 171, 188, 192, 354 Osteoporosis, 4, 6, 17, 18, 19, 25, 28, 127, 144, 171, 180, 192, 203, 243, 354 Ostomy, 209, 272, 354 Otitis, 186, 354 Otitis Media, 186, 354 Outpatient, 18, 220, 354 Ovaries, 354, 361, 374 Ovary, 309, 326, 354, 361 Overexpress, 86, 354 Ovum, 309, 325, 340, 354, 363, 388 Oxidants, 45, 47, 355 Oxidation, 187, 285, 292, 310, 326, 340, 355 Oxidation-Reduction, 355 Oxidative metabolism, 340, 355 Oxidative Stress, 31, 47, 85, 355 Oxygenase, 97, 355 P Pachymeningitis, 344, 355 Paediatric, 101, 121, 130, 355 Palliative, 19, 223, 355, 381 Pancreas, 285, 296, 313, 324, 329, 335, 338, 340, 355, 376 Pancreatic, 65, 67, 260, 355 Pancreatic cancer, 260, 355 Pancreatitis, 32, 161, 171, 229, 233, 355 Pancytopenia, 10, 355 Panniculitis, 223, 355 Papaverine, 353, 356 Parasite, 39, 177, 356, 384 Parasitic, 315, 356, 383 Parathyroid, 138, 356, 371, 381 Parathyroid Glands, 356, 371 Parathyroid hormone, 138, 356 Paratuberculosis, 71, 94, 356 Parenteral, 4, 7, 14, 28, 39, 118, 168, 184, 209, 224, 229, 273, 356 Parenteral Nutrition, 4, 7, 14, 28, 118, 168, 209, 224, 229, 356 Parotid, 356, 372 Paroxysmal, 261, 290, 356 Partial remission, 24, 356, 369 Partial response, 356 Particle, 84, 324, 356, 376, 383 Patch, 40, 41, 356 Pathogen, 39, 57, 64, 68, 171, 334, 356

404


Pathologic, 46, 53, 86, 87, 179, 184, 292, 296, 298, 308, 331, 356, 362, 366 Pathologic Processes, 292, 356 Pathologies, 166, 167, 176, 356 Pathophysiology, 7, 29, 47, 51, 54, 65, 81, 93, 102, 144, 213, 215, 226, 236, 357 Patient Care Management, 27, 209, 357 Patient Compliance, 221, 357 Patient Education, 31, 220, 269, 273, 274, 278, 280, 283, 357 Patient Selection, 14, 357 Pediatric Gastroenterologist, 48, 357 Pediatrics, 14, 42, 52, 60, 69, 77, 108, 210, 213, 357 Peer Group, 22, 357 Pelvic, 357, 364 Pemphigus, 38, 285, 357 Pepsin, 357 Peptic, 68, 80, 169, 171, 266, 357 Peptic Ulcer, 68, 80, 169, 171, 266, 357 Peptide, 4, 33, 34, 39, 53, 62, 65, 167, 238, 304, 322, 339, 357, 361, 363, 364, 365, 382, 384 Peptide Chain Elongation, 304, 357 Peptide T, 357, 384 Perception, 220, 307, 357, 373 Percutaneous, 224, 357 Perennial, 186, 357 Perforation, 357, 388 Perfusion, 51, 332, 357, 383 Pericarditis, 67, 357 Pericardium, 357, 380 Pericytes, 137, 358 Perineal, 223, 358 Perineum, 358 Periodontal disease, 46, 180, 358 Periodontitis, 170, 358 Perioperative, 4, 13, 358 Peripheral blood, 34, 71, 143, 336, 358 Peripheral stem cells, 327, 358 Peritoneal, 68, 73, 358 Peritoneum, 345, 358 Peritonitis, 67, 358, 388 Pernicious, 86, 344, 358 Pernicious anemia, 86, 358 Personality Disorders, 231, 358 Petrolatum, 316, 358 PH, 123, 297, 358 Phagocyte, 355, 358 Phagocytosis, 46, 70, 358 Pharmacists, 221, 271, 358 Pharmacokinetic, 156, 358

Pharmacologic, 290, 358, 383, 386 Pharmacology, Clinical, 211, 358 Pharmacotherapy, 146, 230, 358 Pharyngitis, 170, 359 Phenolphthalein, 316, 359 Phenotype, 36, 38, 64, 67, 70, 98, 115, 359 Phenyl, 199, 345, 359 Phenylalanine, 35, 359, 385 Phospholipases, 359, 375 Phospholipids, 201, 321, 341, 359 Phosphorus, 299, 356, 359 Phosphorylate, 74, 359 Phosphorylation, 35, 58, 74, 79, 192, 200, 359 Photocoagulation, 304, 359 Photophobia, 228, 359 Physical Examination, 155, 359 Physical Therapy, 27, 28, 359 Physiologic, 35, 64, 232, 287, 296, 312, 344, 346, 359, 364, 368 Physiology, 37, 41, 46, 52, 79, 81, 91, 101, 134, 144, 324, 351, 359 Phytohemagglutinins, 342, 359 Pigment, 296, 312, 344, 359 Pilot study, 80, 116, 155, 360 Piperidines, 186, 187, 360 Pituitary Gland, 72, 309, 322, 360 Placenta, 360, 363 Plant Diseases, 317, 360 Plants, 200, 288, 294, 295, 298, 304, 325, 339, 347, 352, 360, 361, 362, 372, 383 Plaque, 46, 290, 360 Plasma cells, 291, 348, 360 Plasma protein, 170, 191, 287, 317, 360, 365 Plasmapheresis, 292, 360 Plasmid, 43, 360, 386 Platelet Activating Factor, 167, 360 Platelet Activation, 360, 375 Platelet Aggregation, 290, 352, 360, 382 Platelet Factor 4, 336, 360 Plateletpheresis, 292, 361 Platelets, 96, 292, 295, 348, 352, 355, 360, 361, 382 Platinum, 341, 361 Plexus, 67, 361 Pneumoconiosis, 182, 361 Poisoning, 186, 311, 324, 337, 349, 361, 374 Pollen, 70, 361 Polycystic, 65, 261, 361 Polycystic Ovary Syndrome, 65, 361 Polymerase, 104, 361, 364, 370 Polymerase Chain Reaction, 104, 361

Index 405

Polymers, 99, 163, 361, 365 Polymorphism, 34, 122, 124, 131, 136, 361 Polypeptide, 163, 192, 289, 305, 318, 322, 331, 361, 363, 365, 376, 388 Polyposis, 42, 306, 361 Polysaccharide, 39, 151, 291, 302, 326, 361, 365 Polyunsaturated fat, 21, 33, 57, 362, 382 Population Control, 22, 362 Population Dynamics, 183, 362 Posterior, 228, 289, 293, 302, 303, 314, 319, 337, 354, 355, 362, 373 Postmenopausal, 354, 362 Postnatal, 362, 377 Postoperative, 9, 13, 103, 207, 229, 270, 345, 348, 362 Postoperative Complications, 229, 362 Postsynaptic, 362, 375, 379, 380 Post-translational, 43, 58, 68, 362 Potassium, 143, 164, 346, 362 Potentiate, 336, 362 Potentiation, 144, 362, 375 Practicability, 321, 362 Practice Guidelines, 258, 362 Precancerous, 302, 362 Precursor, 10, 77, 293, 310, 314, 315, 318, 352, 359, 362, 363, 365, 384, 385, 388 Predisposition, 16, 362 Prednisolone, 5, 17, 228, 235, 362, 363 Prednisone, 233, 235, 236, 363 Preeclampsia, 26, 171, 363 Pregnancy Outcome, 242, 363 Premenopausal, 101, 122, 363 Presynaptic, 363, 379, 380 Primary Biliary Cirrhosis, 119, 363 Probe, 16, 64, 68, 363 Procollagen, 137, 363 Proctocolectomy, 27, 124, 272, 363 Proctocolitis, 190, 363 Proctosigmoiditis, 26, 162, 210, 237, 363 Proctosigmoidoscopy, 155, 363 Prodrug, 5, 200, 363 Progeny, 78, 363 Progesterone, 171, 193, 363, 377 Progression, 4, 53, 66, 73, 161, 198, 290, 363 Progressive disease, 178, 363 Projection, 311, 352, 353, 363, 368 Prokinetic Drugs, 67, 363 Proline, 305, 331, 363, 364 Promoter, 42, 78, 83, 90, 364 Promotor, 364, 370

Prone, 7, 82, 364 Prophase, 364, 380 Prophylaxis, 9, 160, 183, 189, 364, 386 Proportional, 49, 364 Propulsive, 67, 364 Prostaglandin, 57, 176, 188, 364, 382 Prostaglandins A, 364 Prostate, 73, 80, 260, 364 Protease, 184, 185, 188, 306, 364 Protein Binding, 62, 364, 383 Protein C, 36, 62, 65, 186, 287, 289, 295, 321, 341, 365 Protein Conformation, 289, 365 Protein Isoforms, 163, 288, 365 Protein S, 31, 58, 192, 261, 262, 296, 304, 319, 325, 330, 365, 371, 381 Proteinuria, 325, 348, 350, 363, 365 Proteoglycan, 163, 360, 365 Proteolytic, 306, 322, 365 Prothrombin, 110, 365, 382 Protocol, 93, 154, 365 Protons, 51, 288, 331, 337, 365, 367 Protozoa, 315, 346, 365, 383 Proximal, 19, 60, 79, 179, 314, 363, 365, 374 Pruritic, 312, 315, 365 Pruritus, 186, 365, 385 Pseudogenes, 98, 365 Psychiatric, 7, 90, 210, 231, 344, 366 Psychiatry, 7, 322, 366 Psychogenic, 366, 386 Psychomotor, 311, 366 Psychopathology, 90, 366 Psychotherapy, 90, 366 Psychotropic, 48, 273, 366 Puberty, 6, 14, 104, 225, 366 Public Policy, 257, 366 Publishing, 12, 23, 25, 92, 366 Pulmonary Artery, 287, 297, 366, 387 Pulmonary Fibrosis, 161, 166, 182, 185, 366 Pulse, 242, 347, 366 Pupil, 308, 313, 348, 354, 366 Purines, 295, 366, 374 Purpura, 164, 366 Purulent, 366 Pyoderma, 95, 223, 366 Pyoderma Gangrenosum, 95, 223, 366 Q Quiescent, 117, 367, 388 R Race, 218, 346, 367

406


Radiation, 17, 78, 82, 210, 290, 316, 318, 320, 322, 323, 336, 337, 338, 345, 367, 372, 388 Radiation therapy, 320, 336, 338, 367, 388 Radioactive, 297, 331, 333, 334, 336, 338, 341, 347, 352, 353, 367, 372, 388 Radiography, 6, 209, 229, 232, 367 Radioimmunotherapy, 367 Radiolabeled, 130, 297, 338, 367, 388 Radiological, 27, 357, 367 Radiologist, 245, 367 Radiology, 96, 216, 245, 352, 367 Radiotherapy, 183, 298, 338, 367, 388 Radius, 6, 367 Randomized, 20, 31, 39, 90, 153, 235, 315, 367 Randomized Controlled Trials, 235, 367 Rarefaction, 293, 368 Reactive Oxygen Species, 6, 171, 368 Reagent, 312, 368, 384 Receptors, Serotonin, 368, 374 Recombinant, 15, 44, 46, 56, 81, 82, 170, 192, 195, 198, 368, 386 Recombinant Proteins, 195, 368 Recombination, 324, 325, 368 Reconstitution, 58, 81, 368 Rectal, 14, 19, 30, 154, 162, 165, 178, 247, 250, 266, 268, 271, 272, 368 Rectal Prolapse, 165, 368 Rectovaginal Fistula, 229, 368 Recurrence, 9, 207, 247, 271, 302, 304, 368 Red blood cells, 199, 319, 328, 348, 355, 368, 372, 375 Red Nucleus, 293, 368 Refer, 1, 189, 232, 298, 306, 314, 322, 323, 341, 342, 349, 351, 367, 368 Reflux, 319, 368 Refraction, 368, 376 Refractory, 7, 20, 27, 30, 51, 242, 316, 369 Regeneration, 322, 368, 369 Regimen, 17, 143, 315, 357, 358, 369 Regional enteritis, 190, 369 Regression Analysis, 8, 22, 369 Regurgitation, 328, 369 Relapse, 7, 29, 72, 128, 132, 172, 220, 221, 231, 235, 242, 243, 273, 369 Relative risk, 15, 55, 369 Reliability, 130, 151, 369 Remission Induction, 236, 369 Remission induction therapy, 236, 369 Renal failure, 311, 329, 369 Renal Osteodystrophy, 203, 369

Reperfusion, 33, 170, 171, 349, 369 Reperfusion Injury, 33, 170, 171, 369 Repressor, 80, 353, 370 Repressor Proteins, 80, 370 Reproduction Techniques, 363, 370 Research Design, 90, 370 Resected, 183, 227, 370 Resection, 5, 9, 122, 168, 217, 222, 229, 237, 272, 370, 375 Respiration, 347, 355, 370 Respiratory Burst, 35, 370 Response Elements, 73, 370 Response rate, 217, 370 Restitution, 42, 79, 81, 370 Restoration, 50, 349, 359, 368, 369, 370, 388 Retina, 303, 339, 342, 351, 353, 370, 371, 372, 386 Retinal, 228, 307, 353, 370, 387 Retinitis, 166, 167, 170, 228, 371 Retinoblastoma, 260, 371 Retinol, 370, 371 Retrobulbar, 354, 371 Retrospective, 8, 15, 17, 106, 371 Retrospective study, 17, 371 Retrovirus, 324, 371 Reversion, 371, 385 Rheumatic Diseases, 34, 96, 99, 132, 170, 371 Rheumatism, 167, 371 Rheumatology, 39, 112, 371 Rhinitis, 166, 167, 168, 171, 186, 371 Rhusiopathiae, 319, 371 Ribose, 286, 371 Ribosome, 371, 384 Rickets, 203, 371, 388 Rigidity, 360, 371 Risk factor, 13, 19, 21, 25, 30, 49, 111, 123, 162, 218, 222, 237, 318, 331, 341, 369, 371 Risk patient, 28, 372 Rituximab, 39, 372 Rod, 304, 372 Rosiglitazone, 153, 372 Rubella, 275, 372 S Salicylate, 372 Salicylic, 23, 372 Salicylic Acids, 372 Saline, 298, 372 Salivary, 313, 355, 372, 379 Salivary glands, 313, 372 Saponins, 372, 377 Sarcoidosis, 57, 71, 177, 185, 223, 372

Index 407

Sarcoma, 322, 324, 372 Scans, 55, 372 Schematic, 218, 372 Schizoid, 372, 388 Schizophrenia, 192, 372, 373, 388 Schizotypal Personality Disorder, 373, 388 Sclera, 303, 307, 319, 373, 386 Scleritis, 164, 228, 373 Scleroderma, 164, 293, 321, 373 Sclerosis, 38, 48, 55, 72, 86, 161, 163, 166, 167, 171, 173, 177, 180, 182, 185, 186, 187, 197, 198, 199, 205, 261, 293, 305, 348, 354, 373 Screening, 28, 43, 49, 116, 121, 155, 164, 173, 274, 304, 373 Secondary tumor, 345, 373 Secretory, 43, 50, 61, 125, 238, 373, 379, 380 Sedative, 155, 295, 305, 373 Segmental, 325, 373 Seizures, 311, 356, 373 Selenium, 134, 373 Sella, 360, 373 Semen, 364, 373 Semisynthetic, 304, 333, 374 Senile, 354, 374 Sensibility, 289, 331, 374 Sensitization, 72, 75, 374 Septal, 223, 374 Septic, 46, 166, 167, 169, 190, 192, 293, 374 Septicemia, 46, 374 Sequence Analysis, 63, 66, 374 Sequence Homology, 81, 357, 374 Sequencing, 55, 173, 361, 374 Serine, 74, 185, 188, 192, 310, 324, 374 Serologic, 25, 244, 333, 374 Serologic Tests, 244, 374 Serotonin, 165, 359, 368, 374, 385 Serous, 317, 374 Serrated, 138, 374 Sex Characteristics, 286, 290, 366, 374 Sex Determination, 261, 374 Shock, 45, 46, 71, 85, 169, 190, 192, 290, 374, 384 Short Bowel Syndrome, 168, 219, 268, 375 Sigmoid, 363, 375 Sigmoid Colon, 363, 375 Sigmoidoscope, 363, 375 Sigmoidoscopy, 153, 154, 162, 247, 375 Signal Transduction, 35, 40, 42, 59, 62, 65, 68, 81, 92, 163, 192, 301, 375 Signs and Symptoms, 4, 127, 246, 369, 375, 385

Skeletal, 19, 29, 287, 290, 304, 348, 375 Skeleton, 285, 321, 338, 364, 375 Skin Manifestations, 67, 375 Skull, 354, 375, 381 Sludge, 224, 375 Small intestine, 14, 38, 42, 77, 168, 178, 184, 189, 204, 210, 247, 271, 272, 273, 296, 301, 308, 315, 318, 325, 330, 332, 337, 338, 369, 375, 387 Smooth muscle, 50, 137, 200, 201, 288, 290, 299, 307, 330, 347, 356, 358, 375, 379 Social Environment, 367, 375 Social Support, 13, 375, 378 Social Work, 221, 375 Sodium, 11, 44, 50, 52, 56, 65, 199, 327, 346, 376 Soft tissue, 297, 321, 322, 375, 376 Solid tumor, 290, 376 Solvent, 320, 326, 354, 376 Somatic, 286, 330, 344, 346, 376, 381, 386 Somatostatin, 352, 376 Sound wave, 367, 376 Soybean Oil, 362, 376 Spastic, 338, 376 Spatial disorientation, 314, 376 Specialist, 276, 309, 313, 376 Specificity, 15, 37, 77, 174, 287, 292, 298, 376, 383 Spectrum, 11, 27, 30, 35, 190, 304, 376 Sperm, 290, 303, 361, 376, 385 Sphincter, 339, 368, 376 Spinal cord, 177, 297, 302, 303, 315, 316, 318, 323, 344, 350, 351, 355, 377, 379 Spirochete, 377, 380 Spleen, 289, 342, 372, 377 Spondylitis, 19, 28, 29, 221, 377 Spontaneous Abortion, 26, 363, 377 Sporadic, 10, 42, 91, 111, 208, 371, 377 Sprue, 63, 377 Squamous, 73, 319, 377 Squamous cell carcinoma, 73, 319, 377 Squamous cells, 377 Stabilization, 47, 377 Staging, 6, 372, 377 Standard therapy, 55, 377 Steel, 304, 377 Stem Cells, 77, 319, 358, 377 Stent, 223, 354, 377 Sterile, 293, 356, 377 Sterility, 13, 310, 334, 377

408


Steroid, 7, 9, 20, 25, 30, 32, 34, 73, 154, 217, 221, 225, 233, 236, 245, 246, 296, 309, 372, 377, 378 Steroid therapy, 32, 236, 378 Stilbenes, 182, 378 Stillbirth, 363, 378 Stimulant, 299, 330, 378 Stimulus, 35, 164, 171, 246, 314, 315, 333, 336, 337, 339, 378, 382 Stoma, 354, 378 Stool, 155, 246, 272, 308, 332, 334, 338, 339, 378, 381 Stool test, 272, 378 Strand, 164, 361, 378 Streptococcal, 223, 378 Streptococcus, 183, 321, 378 Stress management, 210, 246, 378 Stricture, 19, 26, 223, 378 Stroke, 158, 166, 167, 197, 199, 256, 300, 378 Structure-Activity Relationship, 73, 75, 378 Subacute, 334, 378 Subarachnoid, 328, 359, 378 Subclinical, 229, 334, 373, 378 Subcutaneous, 223, 286, 315, 355, 356, 378 Submaxillary, 318, 379 Subspecies, 376, 379 Substance P, 319, 345, 368, 373, 379 Substrate, 81, 318, 322, 341, 370, 379 Sulfur, 167, 312, 320, 345, 379 Superoxide, 105, 370, 379 Superoxide Dismutase, 105, 379 Supplementation, 6, 9, 11, 21, 379 Support group, 121, 240, 246, 272, 379 Suppositories, 26, 246, 324, 379 Suppression, 20, 34, 40, 76, 78, 167, 233, 309, 379 Suppressive, 45, 173, 379 Sympathetic Nervous System, 135, 294, 379 Sympathomimetic, 314, 319, 352, 379 Symphysis, 364, 379 Symptomatic, 20, 26, 28, 224, 225, 228, 230, 355, 379 Symptomatology, 231, 379 Synapses, 67, 351, 379, 380 Synapsis, 380 Synaptic, 164, 352, 375, 379, 380 Synaptic Transmission, 164, 352, 380 Synaptic Vesicles, 379, 380 Synergistic, 52, 380

Synovial, 68, 177, 202, 293, 338, 380 Synovial Fluid, 380 Synovial Membrane, 202, 293, 338, 380 Syphilis, 182, 380 Systemic disease, 5, 293, 374, 380 Systemic lupus erythematosus, 38, 86, 170, 182, 305, 342, 380 Systemic therapy, 73, 380 Systolic, 331, 380 T Tacrolimus, 8, 17, 119, 380 Teichoic Acids, 327, 380 Telangiectasia, 261, 380 Telomerase, 133, 380 Temporal, 33, 342, 381 Tendinitis, 27, 381 Tenesmus, 19, 315, 381 Testicular, 192, 381 Testis, 326, 381 Tetany, 356, 381 Tetracycline, 81, 381 Tetrahydrocannabinol, 299, 381 Thalamic, 293, 381 Thalamic Diseases, 293, 381 Thalamus, 298, 313, 381 Thalidomide, 8, 381 Thermal, 293, 314, 351, 361, 381 Thigh, 321, 381 Thioguanine, 108, 127, 136, 381 Third Ventricle, 332, 381 Thorax, 285, 341, 382, 386 Threonine, 192, 357, 374, 382 Threshold, 32, 321, 331, 382 Thrombin, 321, 360, 365, 382 Thrombocytes, 361, 382 Thrombocytopenia, 32, 360, 382 Thromboembolism, 137, 382 Thrombomodulin, 365, 382 Thrombophilia, 118, 131, 382 Thrombosis, 123, 124, 144, 166, 241, 295, 335, 365, 378, 382 Thromboxanes, 293, 315, 382 Thrombus, 309, 334, 349, 360, 382, 387 Thymus, 77, 78, 333, 342, 382 Thyroid, 65, 86, 332, 356, 382, 385 Thyroid Gland, 356, 382 Thyrotropin, 332, 382 Thyroxine, 287, 359, 382 Time Management, 378, 382 Tinnitus, 354, 382 Tissue Distribution, 298, 383 Tissue Transplantation, 163, 187, 383

Index 409

Tolerance, 34, 60, 63, 88, 127, 204, 285, 326, 383 Tomography, 383 Tooth Preparation, 285, 383 Topical, 23, 88, 144, 154, 170, 184, 228, 246, 273, 320, 331, 358, 383 Toxaemia, 363, 383 Toxic, iv, 31, 79, 166, 167, 177, 288, 294, 311, 316, 318, 327, 332, 333, 350, 351, 373, 383 Toxicity, 31, 134, 168, 174, 211, 233, 236, 314, 383 Toxicology, 258, 383 Toxins, 170, 182, 291, 316, 326, 333, 334, 347, 367, 374, 383 Toxoplasma, 39, 383 Trachea, 185, 298, 339, 382, 383 Traction, 304, 383 Transcriptase, 371, 380, 383 Transcription Factors, 42, 56, 73, 181, 370, 383 Transduction, 40, 42, 51, 60, 84, 192, 375, 383 Transfection, 42, 47, 296, 384 Transfer Factor, 333, 384 Transferases, 326, 384 Transforming Growth Factor beta, 63, 384 Transfusion, 320, 329, 384 Transgenes, 84, 384 Translation, 36, 82, 129, 130, 319, 365, 384 Translational, 33, 69, 70, 89, 104, 384 Translocation, 47, 73, 304, 319, 384 Transmitter, 285, 314, 337, 343, 352, 379, 380, 384 Transplantation, 17, 26, 65, 102, 177, 303, 316, 330, 333, 343, 384 Transport Vesicles, 43, 384 Trauma, 170, 190, 295, 311, 319, 328, 350, 355, 381, 383, 384 Triad, 188, 384 Trichomoniasis, 345, 384 Tricyclic, 72, 205, 384 Trinitrobenzenesulfonic Acid, 72, 384 Troglitazone, 243, 384 Trophic, 28, 67, 384 Tryptophan, 305, 374, 384 Tuberculosis, 71, 182, 308, 341, 372, 385 Tuberous Sclerosis, 261, 385 Tubulin, 47, 385 Tumor Necrosis Factor, 3, 42, 46, 113, 131, 173, 175, 188, 194, 229, 235, 381, 385 Tumour, 43, 323, 385

Typhimurium, 62, 188, 385 Tyrosine, 35, 314, 385 U Ulcer, 179, 238, 315, 352, 385 Ulceration, 168, 190, 210, 220, 223, 348, 357, 385 Ultrasonography, 102, 134, 385 Unconscious, 311, 332, 385 Uracil, 180, 385 Uraemia, 355, 385 Urethra, 364, 385, 386 Uric, 327, 331, 366, 385 Uricosuric, 145, 385 Urinary, 75, 136, 192, 197, 299, 303, 325, 334, 386 Urinary Retention, 192, 386 Urinate, 386 Urine, 6, 296, 312, 314, 318, 328, 334, 365, 385, 386 Urogenital, 19, 325, 386 Urticaria, 68, 171, 186, 290, 386 Uterus, 302, 309, 332, 351, 354, 363, 386 Uvea, 386 Uveitis, 136, 170, 177, 184, 228, 386 V Vaccination, 12, 13, 66, 162, 386 Vaccine, 13, 66, 83, 165, 268, 275, 365, 386 Vacuoles, 317, 354, 386 Vagal, 51, 386 Vagina, 229, 302, 332, 368, 386 Vaginal, 26, 319, 386 Vagus Nerve, 386 Vasculitis, 17, 31, 67, 167, 223, 228, 355, 386 Vasoconstriction, 41, 319, 386 Vasodilation, 96, 356, 386 Vasodilator, 298, 314, 330, 349, 356, 386 Vector, 64, 84, 383, 386 Vein, 83, 124, 155, 290, 293, 337, 352, 356, 386, 387 Venereal, 380, 386 Venous, 101, 137, 293, 295, 297, 329, 365, 386, 387 Venous Thrombosis, 101, 295, 387 Ventricle, 366, 380, 382, 387 Ventricular, 93, 349, 387 Venules, 167, 170, 191, 196, 297, 299, 317, 346, 387 Vertebrae, 377, 387 Vertebral, 221, 387 Vertigo, 354, 387 Vesicular, 312, 387

410


Veterinary Medicine, 257, 387 Vibrio, 303, 387 Vibrio cholerae, 303, 387 Villous, 138, 301, 387 Villus, 81, 387 Vinblastine, 385, 387 Vincristine, 385, 387 Viral, 58, 64, 84, 165, 166, 167, 176, 184, 188, 192, 218, 316, 325, 353, 371, 383, 387 Viral Hepatitis, 165, 166, 387 Viral Load, 58, 387 Viral vector, 84, 387 Virulence, 62, 76, 383, 387 Virus, 13, 64, 84, 108, 166, 197, 226, 295, 317, 324, 325, 329, 336, 360, 372, 383, 387 Visceral, 72, 75, 294, 358, 386, 387 Visual Acuity, 308, 373, 387 Vitamin D, 138, 203, 371, 388 Vitiligo, 38, 86, 388 Vivo, 37, 40, 42, 43, 44, 45, 48, 50, 52, 56, 57, 58, 59, 63, 66, 72, 75, 77, 78, 81, 86,

90, 143, 177, 179, 202, 329, 334, 342, 355, 380, 382, 388 Volvulus, 168, 388 W Wakefulness, 311, 388 White blood cell, 154, 285, 291, 303, 318, 339, 340, 342, 347, 348, 349, 351, 360, 388 Windpipe, 298, 382, 388 Withdrawal, 73, 75, 311, 345, 388 Wound Healing, 42, 162, 199, 301, 322, 335, 343, 388 X Xenograft, 290, 388 X-ray, 6, 29, 70, 155, 295, 297, 300, 307, 322, 323, 338, 352, 367, 372, 388 X-ray therapy, 338, 388 Y Yeasts, 323, 337, 359, 388 Z Zygote, 307, 388 Zymogen, 365, 388

Index 411

412


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Irritable Bowel Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Canavan Disease: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Parkinson's Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Degenerative Joint Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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End-Stage Renal Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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Tay-Sachs Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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Raynaud's Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Wilson's Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Chronic Obstructive Pulmonary Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Addison's Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

Graves' Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Inflammatory Bowel Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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Irritable Bowel Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Canavan Disease: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Parkinson's Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Degenerative Joint Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hirschsprung's Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Peyronie's Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

Alzheimer's Disease: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Gastroesophageal Reflux Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

End-Stage Renal Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Batten Disease: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Tay-Sachs Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Cushing's Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

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

Huntington's Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

Creutzfeldt-Jakob Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

Degenerative Disc Disease: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Raynaud's Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Wilson's Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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Addison's Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

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