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

BILIARY CIRRHOSIS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

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 2004 by ICON Group International, Inc. Copyright 2004 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., 1960Biliary Cirrhosis: 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: 0-497-00136-5 1. Biliary Cirrhosis-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 biliary cirrhosis. 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 BILIARY CIRRHOSIS ................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Biliary Cirrhosis............................................................................ 8 E-Journals: PubMed Central ....................................................................................................... 20 The National Library of Medicine: PubMed ................................................................................ 20 CHAPTER 2. NUTRITION AND BILIARY CIRRHOSIS ......................................................................... 67 Overview...................................................................................................................................... 67 Finding Nutrition Studies on Biliary Cirrhosis .......................................................................... 67 Federal Resources on Nutrition ................................................................................................... 69 Additional Web Resources ........................................................................................................... 69 CHAPTER 3. ALTERNATIVE MEDICINE AND BILIARY CIRRHOSIS ................................................... 71 Overview...................................................................................................................................... 71 National Center for Complementary and Alternative Medicine.................................................. 71 Additional Web Resources ........................................................................................................... 77 General References ....................................................................................................................... 77 CHAPTER 4. DISSERTATIONS ON BILIARY CIRRHOSIS ..................................................................... 79 Overview...................................................................................................................................... 79 Dissertations on Biliary Cirrhosis ............................................................................................... 79 Keeping Current .......................................................................................................................... 79 CHAPTER 5. BOOKS ON BILIARY CIRRHOSIS ................................................................................... 81 Overview...................................................................................................................................... 81 Book Summaries: Federal Agencies.............................................................................................. 81 Book Summaries: Online Booksellers........................................................................................... 82 Chapters on Biliary Cirrhosis ...................................................................................................... 82 CHAPTER 6. PERIODICALS AND NEWS ON BILIARY CIRRHOSIS ..................................................... 85 Overview...................................................................................................................................... 85 News Services and Press Releases................................................................................................ 85 Newsletter Articles ...................................................................................................................... 87 Academic Periodicals covering Biliary Cirrhosis ......................................................................... 87 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................... 89 Overview...................................................................................................................................... 89 U.S. Pharmacopeia....................................................................................................................... 89 Commercial Databases ................................................................................................................. 90 Researching Orphan Drugs ......................................................................................................... 90 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 95 Overview...................................................................................................................................... 95 NIH Guidelines............................................................................................................................ 95 NIH Databases............................................................................................................................. 97 Other Commercial Databases....................................................................................................... 99 APPENDIX B. PATIENT RESOURCES ............................................................................................... 101 Overview.................................................................................................................................... 101 Patient Guideline Sources.......................................................................................................... 101 Associations and Biliary Cirrhosis............................................................................................. 106 Finding Associations.................................................................................................................. 106 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 109 Overview.................................................................................................................................... 109 Preparation................................................................................................................................. 109 Finding a Local Medical Library................................................................................................ 109 Medical Libraries in the U.S. and Canada ................................................................................. 109

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ONLINE GLOSSARIES................................................................................................................ 115 Online Dictionary Directories ................................................................................................... 115 BILIARY CIRRHOSIS DICTIONARY ...................................................................................... 117 INDEX .............................................................................................................................................. 161

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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 biliary cirrhosis 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 biliary cirrhosis, 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 biliary cirrhosis, 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 biliary cirrhosis. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to biliary cirrhosis, 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 biliary cirrhosis. 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 BILIARY CIRRHOSIS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on biliary cirrhosis.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and biliary cirrhosis, 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 “biliary cirrhosis” (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: •

Risk Factors for Primary Biliary Cirrhosis in a Cohort of Patients from the United States Source: Hepatology. 33(1): 16-21. January 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Although the etiology (cause) of primary biliary cirrhosis (PBC) remains unknown, environmental factors may act to trigger the disease in genetically susceptible hosts. This article reports on a study undertaken to assess specific risk factors. In the study, the authors conducted a survey using standardized NHANES questions to 241 PBC patients in the United States, 261 of their siblings, and 141 friends without PBC. The overall response rate was 199 of 241 (83 percent) among PBC cases, 171 of 261 (67

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percent) among siblings, and 141 of 225 (62.7 percent) among friend controls. The female to male ratio among cases in this sample was approximately 10 to 1, the mean age was 53 years, and 97 percent were Caucasian. Other autoimmune diseases reported most frequently by PBC cases included Sjogren's syndrome (17.4 percent) and Raynaud's syndrome (12.5 percent). Approximately 6 percent of cases reported at least one family member with PBC. Adjusted odds ratios (OR) were elevated for cases compared with friends for other autoimmune diseases, smoking, tonsillectomy, and vaginal or urinary tract infection (UTI) in females only. Similarly elevated ORs were observed for these risk factors when cases were compared with their siblings. The higher rate of UTI among cases is particularly interesting in light of previous data, and raises the possibility of an infectious etiology for PBC and of molecular mimicry as an etiologic mechanism. The significance of smoking supports the findings of previous studies and raises the issue of the influence of smoking on the immune system. 5 tables. 34 references. •

Management of Primary Biliary Cirrhosis Source: Hepatology. 31(4): 1005-1013. April 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Primary biliary cirrhosis (PBC) is a presumed autoimmune disease of the liver, which predominantly affects women once over the age of 20 years. Most cases are diagnosed when asymptomatic (60 percent). This article offers guidelines to assist physicians in the recognition, diagnosis, and management of patients with PBC. The antimitochondrial antibody is present in serum (blood) in most, but not all, patients with PBC. The disease generally progresses slowly, but survival is less than an age and gender matched general population. The symptomatic patients may have fatigue, generalized pruritis (itching), portal hypertension (high blood pressure), osteoporosis, skin xanthomata (yellowish nodules), fat soluble vitamin deficiencies, and or recurrent asymptomatic urinary tract infections (UTI). Many non liver autoimmune diseases are found in association with PBC and may prompt initial presentation. To date, immunosuppressive therapy has not been shown to prolong survival in PBC. The use of urodeoxycholic acid (UDCA) can delay the time to liver transplantation or death (typically given in a dose of 13 to 15 mg per kg daily). This therapy also causes a significant improvement of all the biochemical markers of cholestasis but has no beneficial effects on any of the symptoms or associated disorders. Treatment with UDCA does not obviate the need for liver transplantation. Therapies to prevent complications arising from malabsorption, portal hypertension, and or osteoporosis are required as well. Good control of pruritus can be achieved in most patients. PBC is diagnosed with increasing frequency, but the agent(s) responsible for this slowly progressive destruction of the bile ducts remains elusive and hence a specific therapy remains unavailable. 3 figures. 1 table. 105 references.

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Primary Biliary Cirrhosis, Sclerosing Cholangitis and Cholangitis Source: Current Opinion in Gastroenterology. 6(3): 358-364. June 1990. Summary: This article discusses the etiology, clinical presentation, diagnosis, prognosis, and treatment of primary biliary cirrhosis, sclerosing cholangitis, and cholangitis. Primary biliary cirrhosis (PBC) is a disease of unknown cause in which the intrahepatic bile ducts are progressively destroyed. Primary sclerosing cholangitis is marked by inflammation and obliterative fibrosis, and segmental dilatation of the intra-and extrahepatic bile ducts. Other forms of sclerosing cholangitis are related to

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immunosuppression, infections, and interference with the hepatic arterial supply to the bile ducts. 2 figures. 49 annotated references. •

High Prevalence of Celiac Sprue Among Patients with Primary Biliary Cirrhosis Source: Journal of Clinical Gastroenterology. 25(1): 328-329. July 1997. Contact: Available from Lippincott-Raven Publishers. P.O. Box 1550, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Summary: This article explores the high prevalence of celiac sprue among patients with primary biliary cirrhosis (PBC). The authors note that, although coexisting PBC and celiac sprue have been described, celiac is sufficiently common in western Europe for chance to explain isolated cases. The authors screened their patients with PBC for celiac sprue by serum testing, with confirmation by duodenal biopsy. Of 57 patients, 6 (11 percent) tested positive. Four of these agreed to have a biopsy taken, and all had villous atrophy, yielding a minimum prevalence of 1 in 14 (7 percent). Apart from anemia in one patient, none of the four had symptoms or routine laboratory abnormalities suggestive of celiac sprue. None had improvement in liver biochemical tests after 12 to 24 months on gluten-free diets, despite the disappearance of the immune marker. The authors conclude that celiac sprue is common among patients with PBC and they should be routinely screened for this condition. Symptoms wrongly attributed to PBC may respond to gluten exclusion, and both conditions are potent risk factors for osteoporosis. 20 references. (AA-M).

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Update on Primary Biliary Cirrhosis Source: Canadian Journal of Gastroenterology. 14(1): 43-48. January 2000. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail: [email protected]. Summary: This article offers an update on primary biliary cirrhosis (PBC), a chronic inflammatory condition of the liver characterized by generalized pruritis (itching), enlargement and hardening of the liver, fatigue, weight loss, and diarrhea with pale, bulky stools. The diagnosis of PBC is most often made in the asymptomatic phase, sometimes before the development of abnormal liver biochemistry. The antimitochondrial antibody remains the predominant hallmark. The etiology (cause) of PBC remains elusive; studies suggest that the interlobular bile duct destruction is immune based, and associated autoimmune diseases are common. There are no markers that predict outcome in asymptomatic patients, whose chance of survival is less than that of age and sex matched populations, but much better than the median survival of eight years in patients with symptomatic PBC. Symptoms common in this disease include fatigue, pruritis, and xanthelasma (soft yellow spots or plaque occurring on the eyelids), as well as complications of portal hypertension (high blood pressure) and osteoporosis. Treatment includes symptomatic and preventive measures, as well as specific therapeutic measures. Immunosuppressive therapy has yielded disappointing results in the long term management of PBC, and the only therapy shown to improve survival in the hydrophobic dihydroxy bile acid, urosdeoxycholic acid. Treatment at a dose of 13 to 15 milligrams per kilogram of body weight per day is optimal, given in separate doses or as a single dose at least 4 hours from giving the oral anion exchange resin cholestyramine, which may be used to control pruritis. However, liver transplantation remains the only cure for this disease. Recurrence after transplantation takes place but is rarely symptomatic and does not deter from the benefits of transplantation. 55 references.

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Therapy for Primary Biliary Cirrhosis: A Personal View Source: Contemporary Gastroenterology. 5(5): 16, 21. June-July 1992. Summary: This article presents one physician's opinion of current treatment methods, notably drug therapy, for primary biliary cirrhosis (PBC). The author reports on work at the Mayo Clinic to devise a diagnostic formula based on bilirubin level, albumin level, age, prothrombin time in seconds, and signs of fluid retention. These parameters are obtained at each patient encounter and scores calculated with a computer. By using this diagnostic formula, clinicians can offer their patients relatively-untried drug therapies while still monitoring the progress of their cirrhosis. The author then reviews the various drug therapies that are currently in use, and concludes that ursodiol and methotrexate are two useful drugs for treatment of PBC.

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Caring for the Patient with Primary Biliary Cirrhosis Source: IM. Internal Medicine. 17(5): 64-66, 68, 73-76. May 1996. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Summary: This article provides an overview to the diagnosis and management of primary biliary cirrhosis (PBC). Topics include the pathogenesis of PBC; how to recognize and diagnose PBC; symptoms and signs; disease progression and prognosis; treatment options, including symptomatic, preventive, and specific therapies; patient issues, including pregnancy, hypercholesterolemia, recurrent urinary tract infections, and alcohol consumption; and followup ambulatory care. 2 figures. 4 tables. 29 references.

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Primary Biliary Cirrhosis: Don't Be Deceived by a 'Tanned' Glow Source: AJN. American Journal of Nursing. 99(12): 38-39. December 1999. Contact: Available from Lippincott Williams and Wilkins. AJN, P.O. Box 50480, Boulder, CO 80322-0480. (800) 627-0484 or (303) 604-1464. Summary: This article provides nurses with an overview of primary biliary cirrhosis (PBC), a slowly progressive chronic liver disease that causes inflammatory destruction of the bile ducts, bile acid buildup, cirrhosis, and ultimately liver failure. The etiology of PBC is unknown, but it is suspected to be an autoimmune disorder. Many patients with PBC are asymptomatic; intense pruritis (itching) is commonly the presenting symptom. Patients may also report painful joints or bones, indigestion or nausea, persistent abdominal ache in the upper right quadrant, and fluid retention. Dark urine, pale stools, easy bruising or bleeding, esophageal varices, increased skin pigmentation, and jaundice mark late stage disease. Diagnosis is confirmed by liver biopsy. Treatment with ursodeoxycholic acid may slow progression of the disease; other interventions focus on increasing quality of life and delaying the need for liver transplant. The author concludes by reviewing patient education strategies for patients with PBC. 1 figure.

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Clinical Significance of Serum Bilirubin Levels Under Ursodeoxycholic Acid Therapy in Patients with Primary Biliary Cirrhosis Source: Hepatology. 29(1): 39-43. January 1999. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000.

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Summary: This article reports on a study undertaken to determine whether the normalization of serum bilirubin level (SBL) induced by ursodeoxycholic acid (UDCA) therapy was associated with an improved clinical outcome in patients with primary biliary cirrhosis (PBC). The authors estimated the prognostic values of SBL measured after 6 months of UDCA treatment for survival free of orthotopic liver transplantation (OLT). The authors used a database of 548 patients with PBC followed in three trials of UDCA. Survival free of OLT was significantly longer in patients who had normalized SBL. Survival free of OLT was not significantly different between UDCA patients with normalized SBL and placebo patients with a normal baseline SBL. The authors conclude that normalization of SBL during therapy is associated with improved clinical outcome. SBL under UDCA therapy is a prognostic factor in PBC. Because the biological response can be measured early in the course of therapy, it can help identify nonresponders to UDCA therapy. In addition, the association between a given value of SBL and the risk of OLT or death is the same in patients treated with UDCA as in original placebo patients. From a clinical standpoint, this means that in UDCA treated patients with PBC, SBL should be interpreted as it is for untreated patients. 3 figures. 2 tables. 28 references. •

Treatment of Primary Biliary Cirrhosis: Review Source: Journal of Gastroenterology and Hepatology. 11(7): 605-609. July 1996. Summary: This review article covers the treatment of primary biliary cirrhosis (PBC), a slowly progressive chronic cholestatic disease of the liver thought to be caused by immune destruction of the interlobular bile ducts. Therapeutic regimens should aim to control symptoms, prevent complications, and control disease progression. Preventative therapy includes regular screening for thyroid dysfunction and replacement therapy when necessary, and administration of the fat soluble vitamins A, D, and K for hyperbilirubinemia. Esophageal varices may develop early in the course of PBC; nonselective beta blocker therapy should be used as prophylaxis against variceal hemorrhage. The only specific therapy shown to benefit patients with PBC is ursodeoxycholic acid (UDCA). Treatment with UDCA delays disease progression, but does not result in a cure. Currently, liver transplantation is the only definitive treatment available for end stage disease. 29 references. (AA-M).

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Ursodeoxycholic Acid in Primary Biliary Cirrhosis: A Review Source: Practical Gastroenterology. 19(2): 23, 24, 26. February 1995. Summary: This review article explores the use of ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis (PBC). The author reviews the experimental evidence that points to several possible mechanisms for the beneficial action of this agent, including displacement of more toxic endogenous bile acids, immunomodulation, and induction of choleresis producing increased excretion of toxic compounds. The author notes that several biochemical markers have been evaluated for their potential usefulness in assessing prognosis and response to therapy, but none has yet been shown to be clearly reliable. Trial results suggest that UDCA is not effective in late-stage disease and may even induce hepatic decompensation; therefore, early diagnosis and intervention are crucial. 13 references. (AA-M).

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Cost-Effectiveness of Ursodeoxycholic Acid Therapy in Primary Biliary Cirrhosis Source: Hepatology. 29(1): 21-26. January 1999. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000.

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Summary: Ursodeoxycholic acid (UDCA) is a safe, effective treatment for patients with primary biliary cirrhosis (PBC), but the cost of the drug has raised cost effectiveness concerns. This article reports on a study undertaken to determine the cost effectiveness of UDCA in PBC. The authors compared the costs and outcomes of managing PBC in patients with and without UDCA. From two previously published trials, the effectiveness of UDCA was determined by comparing the annual reduction in the development of ascites, varices, variceal bleeding, encephalopathy, liver transplantation, and death between the treatment groups. Average annual costs for each of these events were estimated from the literature and from institutional data. Approximately twice as many major events occurred in the placebo group as in the UDCA group. The relative risk of liver transplantation and of development of esophageal varices was significantly higher in the placebo group than in the UDCA group. There were no significant increases in the of ascites, variceal bleeding, encephalopathy, or death between the two groups. On the basis of the estimated annual cost of managing these events and the annual cost of UDCA ($2,500), there was an annual cost savings per patient of $1,372. Compared with the placebo group, patients receiving UDCA had a lower incidence of major complications and lower medical care costs. 6 figures. 5 tables. 21 references. (AAM).

Federally Funded Research on Biliary Cirrhosis The U.S. Government supports a variety of research studies relating to biliary cirrhosis. 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 biliary cirrhosis. 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 biliary cirrhosis. The following is typical of the type of information found when searching the CRISP database for biliary cirrhosis: •

Project Title: AUTOANTIGEN ARRAYS TO SELECT VACCINES FOR MODEL OF PBC Principal Investigator & Institution: Utz, Paul J.; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 23-SEP-2002; Project End 31-MAY-2004 Summary: (provided by applicant): The broad, long-term objective of this proposal is to use autoantibody profiling to guide the selection of DNA tolerizing vaccines for the treatment of an animal model of primary biliary cirrhosis (PBC) called experimental autoimmune cholangitis (EAC). We will test the hypothesis that large-scale, parallel

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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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detection of autoantibody profiles can be used to explore epitope spreading, the role played by a subset of inflammatory cytokines in the initiation and propagation of autoimmunity, and ultimately in selection of antigen-specific tolerizing therapies. We will use biochemical, immunological, and molecular biological techniques to validate and extend our ongoing protein array platform in exploring three specific aims in this proposal: (i.) to construct a PBC autoantigen microarray suitable for the identification of human and murine autoantibodies. This array will be used to identify dominant B cell epitopes in the EAC model, and to determine the precise ordering of epitope spreading in EAC. (ii.) to determine whether interleukin-4 (IL-4) and interferon-gamma (IFNy) are required for the development of EAC. An imbalance between Thl and Th2 lymphocytes is thought to play an important role in some autoimmune diseases, and IL-4 and IFN3' represent critical cytokines in the pathogenesis of autoimmunity. (iii.) to employ DNA vaccination to prevent and treat EAC using cDNAs encoding autoantigens identified using protein microarrays developed in the first aim. The results of this proposal will determine the long-term usefulness of the newly described EAC animal model of PBC. Successful treatment of EAC using plasmids encoding prominent autoantigens may herald an era of customized, antigen- or tissue- specific tolerizing therapy in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AUTOIMMUNITY CENTERS OF EXCELLENCE Principal Investigator & Institution: Chess, Leonard; Professor; Medicine; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 28-SEP-1999; Project End 31-MAR-2008 Summary: (provided by applicant): The overall goals of this ACE renewal application will be to further develop our interdisciplinary basic and clinical research program at Columbia primarily focused on the evaluation of novel therapeutic approaches to human autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid and psoriatic arthritis (RA), multiple sclerosis (MS), type I diabetes mellitus (TIDM), biliary cirrhosis and scleroderma. In each of these diseases, there are ongoing basic and clinical research programs involving pathophysiologic and/or clinical immunotherapeutic studies. We hypothesize that there are four principal events involved in the immunopathogenesis of these diseases: (1) predisposing genes establish a T-cell repertoire capable of recognizing self peptides intrinsic to the autoimmune process; (2) previously tolerant autoreactive T-cell clones are activated, expand to change the T cell repertoire to reflect autoreactive effector T cells and migrate to sites of inflammation; (3) regulatory mechanisms, including cytokines and CD4+ and CD8+ regulatory T cells fail and (4) pathogenic autoantibodies and T cells effect tissue injury. We predict that reducing the clonal expansion and migration of relevant autoreactive T cells by blockade of TCR signaling with agents like anti-CD3 or interruption of the signaling and migration of autoreactive memory T cells with agents like anti-VLA-1 could down-modulate disease activity. We propose to test these hypotheses during the natural history of disease and during specific immune intervention. In this ACE renewal, we plan to continue ongoing studies of anti-CD3 therapy of TIDM, initiate trials of biliary cirrhosis employing Mycophenolate Mofetil and continue pre-clinical assessment of the VLA-1 pathway as a prelude to clinical trials with anti-VLA-1 moAbs anticipated to begin in 2004. During these studies, we will: (1) identify by PCR based CDR3 length techniques and TCR sequencing, autoantigen-driven expansions in the CD4 and CD8 cz_ TCR repertoire; (2) Identify changes in the T cell functional response to autoantigens and (3) directly study the regulatory interactions of TH1, TH2 as well as CD4+ and CD8+ T cells in controlling the TCR repertoire. In select patients, we will

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Biliary Cirrhosis

directly study cells at the site of inflammation (CNS, skin, kidney, joints) using HVS immortalization techniques as well as by laser capture technology for repertoire and microarray analysis of activated genes. In addition, we plan new basic studies of the control of the autoreactive T cell repertoire in autoimmune disease by analysis of EAE in the mouse and studies of human regulatory cells in TIDM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF URSODEOXYCHOLIC ACID PLUS METHOTREXATE VS UDCA Principal Investigator & Institution: Bonancini, Mauizio; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPIDEMIOLOGY OF PRIMARY BILIARY CIRRHOSIS Principal Investigator & Institution: Gershwin, Merrill E.; The Jack and Donald Chia Professor; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 956165200 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: Primary biliary cirrhosis (PBC) is an enigmatic autoimmune disease characterized by female predominance, high titer anti- mitochondrial antibodies (AMA), small bile duct destruction, and liver failure. Our group was the first to clone and identify the mitochondrial antigens, a family of phylogenetically conserved 2- oxo acid dehydrogenase proteins recognized by T and B cells in PBC. In addition, recent data has provided us with the basis for the following working hypotheses. We submit that PBC is most likely the result of an inappropriate or malcontrolled response to an environmental (either chemical or biological) insult. The initiating insult in PBC could be either a urinary tract infection (UTI) or an exposure to halogen containing chemicals. In the case of UTI's, there are high degrees of homology between the mitochondrial proteins present in micro-organisms that characteristically cause UTI's and their eukaryotic (i.e. human) analogs. Alternatively, the liver-based metabolism of halogenated hydrocarbons as xenobiotics generates activated halogen containing intermediates that react to form halogen modified proteins. In both, UTIs and halogenated chemical exposures, the introduction of these foreign proteins may initiate an immunological response that results in the immune system inappropriately targeting self proteins. These insults, which appear to be necessary but are not sufficient to elicit an autoimune response, given their widespread occurrence, needs to occur in conjunction with other disease associated contributory factors (i.e. genetic background) to produce PBC. We propose to take advantage of our strengths, including a nationwide network of PBC researchers, to accomplish this goal. We will collect and analyze data on demographics (race/ethnicity, socio-economic status, place of birth), medical history, reproductive history (parity, birth outcomes/complications, fertility problems, oral contraceptive use), menstrual history (age at menarche, age at menopause, average cycle length, cycle regularity) and lifestyle factors (smoking, physical activity, occupation and occupational exposures) using a questionnaire that we have tested in a preliminary study of 201 patients and 171 unaffected siblings. The project data will be collected from a sample of 2000 cases from 17 medical centers around the country and an equal number of matched (on age, gender and residence) random-digit dialed controls. The proposed study would be the first

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comprehensive epidemiologic study of PBC to be conducted in the United States, and directed at testing our thesis in the hope of improving our understanding of this serious disease and potentially identifying preventive measures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FELLOWSHIPS FOR STUDENTS WITH DISABILITIES Principal Investigator & Institution: Foreman, Angela L.; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 956165200 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2007 Summary: (provided by applicant): PBC is an autoimmune liver disease characterized by obstruction of intrahepatic bile ducts and high titer antimitochondrial autoantibodies (AMA). The predominant autoantigen is PDC-E2. It has been demonstrated that a single dominant epitope within the mitochondrial autoantigens is engaged by both autoantibodies and autoreactive CD4+ helper T cells. In addition, precursors to autoreactive T cells to PDC-E2 are found at 100-150 fold higher frequency in target tissues (liver) than in PBMC. While there are likely multiple pathways of destruction of biliary ductules, this application will focus on the role of CD8+ T cells in PBC. Considerable advances have been made on the identification of the epitopes and fragments of the major autoantigens of PBC that are the target of humoral responses and CD4+ T cells, however, relatively little is known with regard to CD8+ responses. This takes on additional significance as PBC is characterized by extensive CD8+ infiltrates, the mitochondrial autoantigens are intracellularly localized, and the lysis of BECs in situ. Moreover, recent pilot data shows a marked increase in the frequency of PDC-E2 spectflc CD8+ T cells in the PBMC of patients with PBC as determined by an ICC assay and pCTL frequency analysis. Thus, our hypothests is that CD8+ T cells play a role in the pathogenesis of PBC. To more cleady define this role, we propose that i) identification of the autoantigen-specific epitopes recognized by MHC class I restricted CD8+ T cells in PBC; ii) determination of the precursor frequency of PDC-E2-specific CD8+ CTL in patients with PBC compared to controls, and using MHC class I tetramers, examining whether these frequencies change with stage of disease; and iii) the definition of differential responses of T cells to altered peptide ligands to identify disease-specific immune therapeutic reagents will accomplish this goal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC MODIFIERS OF CF LIVER DISEASE Principal Investigator & Institution: Knowles, Michael R.; Professor; Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 28-FEB-2009 Summary: (provided by applicant): The clinical heterogeneity in cystic fibrosis (CF) is only partly explained by mutations in the CFTR gene. Most CF patients have evidence of liver dysfunction and focal biliary cirrhosis (fibrosis), and a subset of these patients (5-7%) progresses to severe liver disease (CFLD), as defined by portal hypertension and multilobular cirrhosis. The development of CFLD has no relationship to specific CFTR mutations or other biomarkers, and there is currently no way to identify which CF infants will develop severe liver disease. The central hypothesis of this proposal is that the development of CFLD reflects the influence of non-CFTR "modifier" alleles (genes). This project is designed to identify associations between non-CFTR genes and CFLD, and test the biological effect of selected alleles on hepatic fibrosis in transgenic murine

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Biliary Cirrhosis

models. We hypothesize that polymorphisms in multiple genes, each with a conceptual or mechanistic link to liver disease, increase the risk for developing end-stage CF liver disease, and that interactions among these risk factors will define the pathophysiology of this disorder. To achieve our goals, we will study 400 CF patients with welldocumented severe liver disease and portal hypertension, and 400 gender and genotype-matched CF patients > age 15 years who have no evidence of CFLD. We propose to identify heritable risk factors for the development of CFLD by evaluation of functional sequence variants within, and single nucleotide polymorphisms associated with, multiple genes associated with CFLD pathogenesis. To test ("validate") the biological effects (impact) of selected genetic alleles on liver fibrosis, we will develop transgenic mice homozygous for deltaF508, who are also expressing an additional candidate gene modifier allele. Better definition of the complex genotypes that increase risk for severe liver disease in CF will allow early identification of CF infants predisposed to develop end-stage liver disease, and thereby allow testing of currently available therapies. Better understanding of the pathobiology of hepatic fibrosis in CF will identify novel targets to prevent (or reduce) the development of CFLD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERLEUKIN PROLIFERATION

6

AND

HUMAN

BILIARY

EPITHELIAL

Principal Investigator & Institution: Demetris, Anthony J.; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-MAR-1996; Project End 28-FEB-2007 Summary: Cirrhosis, which is the 9th leading cause of death in the United States. It develops over a period of years to decades because chronic necro-inflammatory activity gradually transforms the normal architecture into nodules. This proposal is focused on the ductular reaction, which is important predictor of the development of cirrhosis and refers to the preferential growth of biliary epithelial cells over hepatocytes, recognized at the interface zone of diseased livers. By either favoring biliary epithelial cell or inhibiting hepatocyte proliferation some cytokines and growth factors hasten the development of cirrhosis, whereas others that stimulate hepatocytes (IL-6/gp130, HGF) and inhibiting biliary epithelial cell proliferation prevent architectural distortion and liver failure. In this proposal we plan to: a. Characterize the effect of IL-6/gp130/STAT3 signaling, extracellular matrix and immunosuppressive drugs on biliary epithelial cell mitogenesis, apoptosis and maintenance of intercellular junctions, in vitro. b. Further characterize an experimental animal model of decompensated biliary cirrhosis in IL-6/- mice after bile duct ligation using gene chip expression array analysis. Determine the role of p21 in hepatocyte proliferation and apoptosis during the development of cirrhosis and whether administration or exogenous recombinant growth factors, or transient transfection of vectors containing growth factors can influence the ductular reaction. c. Determine in humans, whether cytokine polymorphisms influence the susceptibility or the rate of progression of various chronic inflammatory liver diseases. The ultimate goal is to understand molecular mechanisms of differential biliary epithelial cell and hepatocyte growth control in diseased livers, which will serve as a rational basis for therapeutic intervention with cytokines and growth factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MEDIATORS OF PULMONARY VASODILATATION IN LIVER DISEASE Principal Investigator & Institution: Fallon, Michael B.; Associate Professor; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: Endothelial dysfunction underlies the vascular abnormalities of chronic liver disease and is characterized by changes in the levels and activity of endothelial nitric oxide synthase. How these changes occur and why there is variability in the vascular beds involved is incompletely characterized. The hepatopulmonary syndrome is one important vascular complication of liver disease where 15-20 percent of patients with cirrhosis develop pulmonary microvascular dilatation leading to hypoxemia. No effective medical therapies are available. Experimental biliary cirrhosis reproduces the pulmonary vascular and gas exchange abnormalities of human hepatopulmonary syndrome in association with an increase in pulmonary microvascular endothelial nitric oxide levels and activity. Pre-hepatic portal hypertension alone does not cause pulmonary vascular or endothelial nitric oxide synthase alterations, implying that mediators released during hepatic injury may trigger endothelial alterations in the lung. Hepatic and plasma endothelin-1 levels rise and correlate directly with the degree of intrapulmonary vasodilatation in experimental biliary cirrhosis and preliminary studies reveal that chronic low level endothelin-1 infusion in pre-hepatic portal hypertensive animals results in selective pulmonary microvascular dilatation. Although classically recognized as a vasoconstrictor, circulating endothelin-1 stimulates endothelial cell endothelial nitric oxide synthase activity and can cause vasodilatation. Our hypothesis is that endothelin-1, released into the circulation during liver injury, preferentially activates pulmonary vascular endothelial nitric oxide synthase and triggers pulmonary microvascular dilatation. To test this hypothesis our specific aims will 1) define the effects of chronic endothelin-1 infusion on the development of intrapulmonary vasodilatation and endothelial nitric oxide synthase expression and activity in normal, pre- hepatic portal hypertensive and biliary cirrhotic animals in vivo 2) assess the effects of exogenous emdothelin-1 on endothelial nitric oxide synthase expression and activity in isolated pulmonary vascular segments and endothelial cells from normal, pre-hepatic portal hypertensive and biliary cirrhotic animals and 3) directly measure the effects of exogenous endothelin-1 on pulmonary microvascular reactivity in normal, pre-hepatic portal hypertensive and biliary cirrhotic animals. Our long-term goal is to use an understanding of endothelial dysfunction in hepatopulmonary syndrome to develop specific medical therapies and as a paradigm for understanding the pathogenesis of other vascular complications of liver disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR RESPONSE OF BILE DUCT CELL TO BILE DUCT INJURY Principal Investigator & Institution: Holterman, Ai-Xuan L.; Surgery; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2006 Summary: (provided by applicant) The applicant's long term goal is to develop effective strategies to prevent or attenuate the damage of biliary cirrhosis from chronic biliary obstruction based on an understanding of the genes and cellular mechanisms regulating the bile duct epithelia (BDE) function and response to biliary injury. The departments of Molecular Genetics and Surgery at the University of Illinois at Chicago are fully

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Biliary Cirrhosis

committed to support this endeavor by providing the candidate with protected time, core facilities usage, laboratory space and continuing research educational opportunities. The mentor is a major contributor to the field of tissue specific gene regulation and has identified several hepatocyte transcription factors essential for liver gene expression and function, including hepatocyte nuclear factor HNF-6 which is important to the performance of this project. The goal of this project is to understand the transcriptional mechanisms regulating BDE gene expression and function during the BDE proliferative response to biliary obstruction, and the role of the early BDE proliferation in the pathogenesis of liver fibrosis using the animal model of common bile duct division. HNF-6 regulates important liver specific gene expression for hepatocyte function. Since HNF-6 is abundant in the BDE and its expression is diminished in the proliferating BDE following bile duct ligation, HNF-6 may regulate the expression of differentiated genes essential to BDE function. We will overexpress HNF-6 or inhibit HNF-6 function in BDE cell lines with an adenovirus expressing a dominant negative HNF-6 protein and use differential hybridization of gene array blots of mock infected or transduced cells to identify differentiated BDE genes. We will use an adenovirus HNF-6 expression vector to transduce the BDE and restore in vivo BDE expression of HNF-6 with the aim to inhibit BDE proliferation during mouse bile duct ligation. This in vivo intervention is anticipated to impede BDE dedifferentiation and proliferation. Bile duct specific target gene mRNA and protein expression will be assessed and the effect on the development of biliary fibrosis will be determined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PRIMARY TREATMENT PROTOCOL

BILIARY

CIRRHOSIS--UDCA-METHOTREXATE

Principal Investigator & Institution: Boyer, Thomas D.; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002 Summary: This is a clinical trial of UDCA and MTX in the treatment of patients with PBC. UDCA appears to protect against the cytotoxic effects of endogenous bile acids that accumulate as a result of bile duct destruction. BMT is being shown to improve liver tests, symptoms and liver histology in a small number of pre-cirrhotic patients with PBC. The mechanism of action is unknown but is felt to be related to anti-inflammatory immunosuppressive effects of MTX. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RETROVIRAL ETIOLOGY OF PRIMARY BILIARY CIRRHOSIS Principal Investigator & Institution: Mason, Andrew L.; Associate Professor; Ochsner Clinic Foundation New Orleans, La 70121 Timing: Fiscal Year 2002; Project Start 30-SEP-1997; Project End 31-JUL-2002 Summary: Primary biliary cirrhosis (PBC) is an idiopathic multisystem autoimmune disorder that primarily effects women. Patients with PBC have a pluriglandular syndrome resulting in cirrhosis and sicca syndrome, and a demonstrable autoimmune response to specific mitochondrial oxo-acid dehydrogenase E2 proteins. PBC patients are also prone to develop other autoimmune diseases such as Sjogren's syndrome, thyroiditis, and systemic lupus erythematosus. These autoimmune disorders have all been linked to rettroviral infection as by Western blot studies 30 to 35 percent of patients have indeterminate serum reactivity to HIV proteins and 85 to 05 percent have serum reactivity to human intracisternal A type particle (HIAP-I) which was isolated from

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salivary glands of patients with Sjogren's syndrome and also visualized by electron microscopy. Likewise, 15 percent of PBC patients have been reported to have false positive HIV ELISA reactivity and in preliminary studies, retrovirus particles have been observed by electron microscopy in the biliary epithelial cells of PBC patients but not controls. Using representational difference analysis, we have isolated and cloned novel retroviral nucleic acid sequences from the liver of a PBC patients. These clones have been used to screen a cDNA library made from bilary epithelium cells isolated from three transplant recipients with PBC. We have now identified more than ten qunique cDNA clones with sequence homology to HIV, SIV, HTLV-1, and IAP as well as the E2 mitochondrial autoantigens. To date, our RTPCR studies have revealed that all the RDA and 3 of 3 novel clones tested to data are not unique to PBC patients, suggesting that they may be derived from endogenous retroviruses. Also, we have conducted Western blot studies which reveal that approximately 74 percent of PBC patients sera have indeterminate reactivity to HIAP proteins and 35 percent of patients react to HIV p24 gag, compared to less than 5 percent of liver disease controls. This suggests that the putative PBC retrovirus shares antigenic determinants with HIV-I and HIAP-I but is a separate virus. In order to further characterize the agent associated with PBC, we plan to identify specific retroviral proteins and nucleic sequences with the ultimate goal of investigating the role this virus plays in the eitology of PBC. Our specific aims are to (1) Clone full length PBC retrovirus from hepatic tissue and PBC cDNA libraries; (2) Isolate the PBC retrovirus in lymphoblastoid and hepatic cell lines by co-culture with infected hepatic tissue; (3) Assess the prevalence of retroviral infection in PBC patients and controls by nucleic acid hybridization techniques and western blot experiments of recombinant or purified viral proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF APOPTOTIC CHOLANGIOCYTES IN PBC Principal Investigator & Institution: Odin, Joseph A.; Medicine; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (adapted from the application) My academic and clinical experience of the past fourteen years have laid the foundation for success in studying the pathogenesis of PBC. The combination of a Ph.D. and M.D. allows one to more easily take insights from the bedside to the research bench and back again. Working within a newly established PBC research center at Mount Sinai Medical Center will give me the intellectual and technical support necessary for the transition to an independent investigative career. Initially, I will focus on the role of apoptotic cholangiocytes in the pathogenesis of PBC. Later, I plan to use these findings to develop an animal model of PBC in which potential treatment strategies can be tested. Additionally, I intend to investigate in greater detail the role of protein sulfhydryl oxidation in apoptotic signaling pathways. My clinical and teaching activities will increase over time, but I will remain focused on a translational research career. Our preliminary results suggest that in patients with PBC, apoptotic cholangiocytes are the source of immunogenic PDC-E2, the major PBC autoantigen, that is responsible for the activation of autoreactive B cells. Autoantibodies recognize only the reduced sulfhydryl form of PDC-E2, yet persistence of PDC-E2, in a reduced state occurs only in select cell types, such as cholangiocytes, following apoptosis. Whether or not presentation by antigen presenting cells of novel peptides derived from reduced PDC-E2 in apoptotic cholangiocytes is similarly responsible for the activation of autoreactive T cells is unknown. This issue is important since autoreactive T cells are thought to be pathogenic in PBC and not simple secondary to cholangiocyte damage. To

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Biliary Cirrhosis

account for this paradox, we have developed a model of PBC pathogenesis in which an initial subclinical episode of biliary inflammation leads to self sustaining biliary inflammation following activation of PDC-E2 specific T cells in susceptible individuals. The crux of this model is whether or not healthy cholangiocytes engulf apoptotic cholangiocytes and present novel peptides derived from this exogenous source of reduced PDC-E2. In this proposal, we aim to determine the following: 1) whether autoreactive T cells from patients with PBC preferentially respond to peptides derived from reduced, rather than oxidized, PDC-E2;2) the antigen presenting cell that most effectively activates autoreactive T cells following incubation with exogenous sources of reduced PDC-E2; and 3) whether PBC patient cholangiocytes engulf apoptotic cells in vivo. Together, these studies will help determine whether autoreactive T cells in patients with PBC are truly pathogenic or simply secondary to idiopathic cholangiocyte destruction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF CD40-CD40 LIGAND IN PRIMARY BILIARY CIRRHOSIS Principal Investigator & Institution: Mayo, Marlyn J.; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 15-MAY-2000; Project End 31-MAR-2003 Summary: (adapted from the application) Primary biliary cirrhosis is a chronic autoimmune liver disease characterized by inflammatory destruction of small and medium sized intrahepatic bile ducts, leading to cholestasis, then fibrosis, cirrhosis, and its complications. Although the etiology is unknown, T cells that surround the bile ductules are the likely mediators of bile duct destruction. Other cell types within the portal infiltrate, including macrophages and B cells, probably contribute to this autoimmune process. However, the manner in which these cells communicate and collaborate to cause bile duct lesions is not understood. The hypothesis of this proposed project is that T cells orchestrate the immune attack on cholangiocytes via signaling to other cells in the liver through CD40 ligand. Specifically, expression of CD40 ligand by activated T cells in the liver stimulates B cells to increase production of immunoglobulins; activates macrophages to produce IL-12, which leads to a shift of T helper cells to the Th1 phenotype and subsequent IL-2 and IFN-gamma production; and induces cholangiocytes to undergo apoptosis at an increased rate. This hypothesis will be tested by a correlative analysis of the level of expression of CD40 ligand in the liver of PBC patients with the potential consequences of CD40-CD40 ligand interaction; such as upregulation of immunoglobulin and cytokine production, and apoptosis of cholangiocytes. Expression of CD40 and CD40 ligand will be localized in the liver with immunohistochernistry. These patient-oriented studies will be supplemented by in vitro experiments designed to study CD40-ligand induced apoptosis in cholangiocytes. These studies will provide insight into the role of T cells in the pathogenesis of PBC and provide information useful in developing new treatment modalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STUDY OF T CELL CHARACTERISTICS AND ADHESION MOLECULES Principal Investigator & Institution: Bergasa, Nora V.; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008

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Summary: Primary biliary cirrhosis (PBC) is chronic liver disease of unknown etiology. Histologically, PBC is characterized by a progressive immunologically mediated inflammation known as chronic nonsuppurative destructive cholangitis (CNSDC) that leads to bile duct destruction, ductopenia and biliary cirrhosis. At present there is no cure for PBC. The most common symptoms associated with PBC are fatigue and pruritus. More than 90% of patients with PBC are women. The average age of diagnosis is about 50 years. Asymptomatic patients have a four-fold increase in mortality when compared to the U.S.A. population matched for age and the median survival from the onset of symptoms is 7.5 to 9 years. PBC is considered a model autoimmune disease; it is associated with hypergammaglobulinemia, autoantibodies, defects of immune regulation, and an increased incidence of other autoimmune conditions (thyroiditis, Sjogren's syndrome, scleroderma). The liver injury is characterized by a rich inflammatory infiltrate composed of CD4+ and CD8+ cells, cytokines, adhesion molecules and other immunologic mediators. The consequence of CNSDC is biliary cirrhosis and liver failure. The only treatment approved to treat PBC is ursodeoxycholic acid (UDCA), which appears to delay the time to liver transplantation but does not cure for the disease. Thus, the need for the provision of effective and safe treatments for PBC is clear. Patients with PBC may benefit from treatment with an appropriate immunosuppressive drug. Mycophenolate mofetil meets the criteria of a superior immunosuppressive agent. In this proposal we are going to explore immune mediators of PBC including T cells and adhesion molecules in patients with PBC and the effect of treatment with MMF in combination with UDCA on these factors in patients who are participants in a clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: T PNEUMONITIS

CELL

ADHESION

MOLECULES

IN

MURINE

LUPUS

Principal Investigator & Institution: Curtis, Jeffrey L.; Professor of Internal Medicine; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-DEC-1998; Project End 30-NOV-2002 Summary: Pulmonary involvement in systemic lupus erythematosus (SLE) is common, often incapacitating, and occasionally lethal. Current therapies are less effective for pulmonary involvement than for other organ systems. To define the molecular pathogenesis of SLE, we have developed a murine model system that depends on adoptive transfer of syngeneic activated CD4+ T cells treated with DNA methyltransferase (DNA MTase) inhibitors such as procainamide (Pca). Normal AKR mice receiving cells of the cloned T cell line D10 that have been treated with Pca (D10Pca) develop high-titer anti-DNA autoantibodies, nephritis, liver disease resembling biliary cirrhosis, and lymphoid interstitial pneumonitis (LIP). Splenectomy abrogates disease activity in all organs except the lungs, indicating that pathology in this organ does not depend of autoantibody production. Treatment with DNA MTase inhibitors increases expression of the Beta2 integrin LFA-1 (CD11a/CD18). T cells transfected with CD18 are also autoreactive and induce lupus on transfer to syngeneic mice. Lymphocyte DNA hypo-methylation and LFA-1 over-expression is also seen in patients with active lupus. These findings imply that T cell overexpression of LFA-1 is sufficient to initiate SLE, and that the T cell-dependent lung lesion may be the earliest stage in the process. This proposal will examine the molecular mechanisms involved in lung pathology in this model system, utilizing a variety of techniques and lessons learned from the study of other models of lung lymphocyte trafficking. Central

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Biliary Cirrhosis

Hypothesis: Increased LFA-1 expression by autoreactive T cells mediates adhesion both to lung endothelial cells and to lung antigen-presenting cells (APCs), especially macrophages (Mphis) (resulting in apoptosis and release of autoantigens). These interactions initiate recruitment of other activated T cells to the lung via VLA-4/VCAM and selectin-dependent interactions, inducing LIP. Specific Aim 1: To verify the lung localization of D10Pca is required to induce drug-induced murine LIP. Specific Aim 2: To determine the adhesive interactions mediating lung localization of D10Pca and other lung lymphocytes during development of LIP. Specific Aim 3: To determine whether inhibiting pulmonary retention of D10Pca via monoclonal antibody (mAb) treatment prevents development of LIP. Our long-term goal is to develop effective therapies to treat established SLE based on anti-adhesive strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRIAL OF LOW DOSE ORAL PULSE METHOTREXATE VS COLCHICINE Principal Investigator & Institution: Kaplan, Marshall; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: URSODEOXYCHOLATE AND METHOTREXATE FOR BILIARY CIRRHOSIS Principal Investigator & Institution: Bass, Nathan M.; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: URSODEOXYCHOLATE(UDCA) VS UDCA AND METHOTREXATE Principal Investigator & Institution: Larson, Anne; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002 Summary: The purpose of this phase 3 study is to compare the efficacy and safety of chronic ursodeoxycholic acid (UDCA) therapy vs. the combination of UDCA and methotrexate (MTX) therapy in patients with primary biliary cirrhosis (PBC). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: URSODEOXYCHOLIC ACID AND METHOTREXATE FOR PRIMARY BILIARY CIRRHOSIS Principal Investigator & Institution: Luketic, Velimer A.; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: URSODEOXYCHOLIC ACID--METHOTREXATE FOR PRIMARY BILIARY CIRRHOSIS Principal Investigator & Institution: Boyer, James L.; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: URSODIOL-METHOTREXATE FOR PRIMARY BILIARY CIRRHOSIS Principal Investigator & Institution: Combes, Burton; Professor of Internal Medicine; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-APR-1993; Project End 31-MAR-2004 Summary: The major thrust of this randomized, double-blinded clinical trial is to determine whether treatment of patients with Primary Biliary Cirrhosis (PBC) with Ursodiol (Ursodeoxycholic Acid-UDCA) plus methotrexate (MTX) is more effective than treatment with UDCA alone. PBC is a chronic cholestatic liver disease, predominantly of women, in which interlobular and septal bile ducts undergo inflammation and destruction. Once initiated, the disease persists and progresses at varying rates. Neither the initiating nor perpetuating mechanisms are well understood. Current concepts of pathogenesis include (1) destruction of bile ducts is maintained and perhaps initiated by autoimmune mechanisms; (2) hydrophobic bile acids which accumulate in serum and liver cause functional and cytotoxic liver injury; (3) cytokines and lymphokines released at sites of inflammation may contribute to cell damage and fibrosis. A considerable body of evidence indicates that UDCA when fed orally leads to improvement in liver tests, in pruritus and in liver histology. There exist differences in opinion as to whether development of complications of liver disease, liver transplantation or transplant-free survival is affected. UDCA a relatively non-toxic bile acid, when administered orally, alters the composition of the bile acid pool in factor of its enrichment with UDCA and appears to protect against the cytotoxic effects of endogenous bile acids that accumulate as a result of bile duct destruction. MTX is being shown to improve liver tests, symptoms and liver histology in a small number of precirrhotic patients with PBC. The mechanism of action is unknown but felt to be related to antiinflammatoryimmunosuppressive effects of MTX. The current trial explores whether MTX improves the therapeutic effects of UDCA in PBC. Patients with PBC whose serum bilirubin is less than 3 mg percent, who have been on UDCA for at least 6 months, and who satisfy a series of inclusion and exclusion criteria are stratified into 2 groups on the basis of liver histologic stage (Ludwig classification), i.e. early (Stages I or II) versus late (Stages III or IV). They are then randomized to receive either methotrexate or its placebo as a second drug while continuing to receive UDCA. The relative value of the two treatment arms is assessed by comparing their effects on symptoms, results of laboratory tests, development of complications of liver disease, histologic changes in liver, liver transplantation, and on transplant-free survival. The safety of each therapeutic regimen is also being determined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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 “biliary cirrhosis” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for biliary cirrhosis in the PubMed Central database: •

Bcl-2 --dependent oxidation of pyruvate dehydrogenase-E2, a primary biliary cirrhosis autoantigen, during apoptosis. by Odin JA, Huebert RC, Casciola-Rosen L, LaRusso NF, Rosen A.; 2001 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=203018

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In vitro cell-mediated cytotoxicity in primary biliary cirrhosis and chronic hepatitis. Dysfunction of spontaneous cell-mediated cytotoxicity in primary biliary cirrhosis. by Vierling JM, Nelson DL, Strober W, Bundy DM, Jones EA.; 1977 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372464

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Primary biliary cirrhosis and autoimmune cholangitis are not associated with coeliac disease in Crete. by Chatzicostas C, Roussomoustakaki M, Drygiannakis D, Niniraki M, Tzardi M, Koulentaki M, Dimoulios P, Mouzas I, Kouroumalis E.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102761

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Reactivity of primary biliary cirrhosis sera with Escherichia coli dihydrolipoamide acetyltransferase (E2p): characterization of the main immunogenic region. by Fussey SP, Ali ST, Guest JR, James OF, Bassendine MF, Yeaman SJ.; 1990 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=54029

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The 210-kD nuclear envelope polypeptide recognized by human autoantibodies in primary biliary cirrhosis is the major glycoprotein of the nuclear pore. by Courvalin JC, Lassoued K, Bartnik E, Blobel G, Wozniak RW.; 1990 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296718

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

3 4

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

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

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

A case of advanced primary biliary cirrhosis treated with granulocyte and monocyte apheresis. Author(s): Takegoshi K, Tohyama T, Okada E. Source: Therap Apher Dial. 2003 August; 7(4): 468-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12887733

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A case of well-differentiated hepatocellular carcinoma arising in primary biliary cirrhosis. Author(s): Yano Y, Yoon S, Seo Y, Ninomiya T, Nagano H, Nakaji M, Hayashi Y, Kasuga M. Source: The Kobe Journal of Medical Sciences. 2003; 49(1-2): 39-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12796567

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A patient with E. coli-induced pyelonephritis and sepsis who transiently exhibited symptoms associated with primary biliary cirrhosis. Author(s): Ohno N, Ota Y, Hatakeyama S, Yanagimoto S, Morisawa Y, Tsukada K, Koike K, Kimura S. Source: Intern Med. 2003 November; 42(11): 1144-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14686759

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A patient with primary biliary cirrhosis complicated with slowly progressive insulindependent diabetes mellitus. Author(s): Nakasone H, Kinjo K, Yamashiro M, Kamiyama T, Kamiyama S, Miyazato H, Matsushita T, Arakawa Y, Ohshiro T, Toma S, Chinen K, Yamashiro M, Miyagi M, Makishi T, Hokama A, Sakugawa H, Kinjo F, Saito A. Source: Intern Med. 2003 June; 42(6): 496-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12857047

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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A patient with Takayasu's arteritis treated with corticosteroids who developed primary biliary cirrhosis. Author(s): Ito S, Ohkoshi S, Aoyagi T, Suzuki K, Takahashi T, Nomoto M, Nakano M, Arakawa M, Asakura H, Gejyo F. Source: Intern Med. 2003 May; 42(5): 443-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12793718

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A randomized controlled trial of colchicine plus ursodiol versus methotrexate plus ursodiol in primary biliary cirrhosis: ten-year results. Author(s): Kaplan MM, Cheng S, Price LL, Bonis PA. Source: Hepatology (Baltimore, Md.). 2004 April; 39(4): 915-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15057894

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Addison's other disease: primary biliary cirrhosis as a model autoimmune disease. Author(s): Jones DE. Source: Clinical Medicine (London, England). 2003 July-August; 3(4): 351-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12938751

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Alendronate is more effective than etidronate for increasing bone mass in osteopenic patients with primary biliary cirrhosis. Author(s): Guanabens N, Pares A, Ros I, Alvarez L, Pons F, Caballeria L, Monegal A, Martinez de Osaba MJ, Roca M, Peris P, Rodes J. Source: The American Journal of Gastroenterology. 2003 October; 98(10): 2268-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14572578

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An autopsy case of primary biliary cirrhosis with severe interstitial pneumonia. Author(s): Hiraoka A, Kojima N, Yamauchi Y, Ninomiya T, Masumoto T, Michitaka K, Horiike N, Onji M. Source: Intern Med. 2001 November; 40(11): 1104-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11757764

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Analysis of major histocompatibility complex and CTLA-4 alleles in Brazilian patients with primary biliary cirrhosis. Author(s): Bittencourt PL, Palacios SA, Farias AQ, Abrantes-Lemos CP, Cancado EL, Carrilho FJ, Laudanna AA, Kalil J, Goldberg AC. Source: Journal of Gastroenterology and Hepatology. 2003 September; 18(9): 1061-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911663

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Antibodies against homologous microbial caseinolytic proteases P characterise primary biliary cirrhosis. Author(s): Bogdanos DP, Baum H, Sharma UC, Grasso A, Ma Y, Burroughs AK, Vergani D. Source: Journal of Hepatology. 2002 January; 36(1): 14-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11804659

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Antibodies and primary biliary cirrhosis - piecing together the jigsaw. Author(s): Neuberger J. Source: Journal of Hepatology. 2002 January; 36(1): 126-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11804675

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Antimitochondrial antibodies in primary biliary cirrhosis: the role of xenobiotics. Author(s): Long SA, Van de Water J, Gershwin ME. Source: Autoimmunity Reviews. 2002 February; 1(1-2): 37-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12849056

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Antinuclear antibodies specific for primary biliary cirrhosis. Author(s): Worman HJ, Courvalin JC. Source: Autoimmunity Reviews. 2003 June; 2(4): 211-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848948

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Apolipoprotein E polymorphism, a marker of disease severity in primary biliary cirrhosis? Author(s): Corpechot C, Benlian P, Barbu V, Chazouilleres O, Poupon RE, Poupon R. Source: Journal of Hepatology. 2001 September; 35(3): 324-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11592592

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Are esophagogastric varices a late manifestation in primary biliary cirrhosis? Author(s): Nakanuma Y. Source: Journal of Gastroenterology. 2003; 38(11): 1110-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673735

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Assessing quality of life in primary biliary cirrhosis. Author(s): Rannard A, Buck D, Jones DE, James OF, Jacoby A. Source: Clin Gastroenterol Hepatol. 2004 February; 2(2): 164-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017622

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Association between the primary biliary cirrhosis specific anti-sp100 antibodies and recurrent urinary tract infection. Author(s): Bogdanos DP, Baum H, Butler P, Rigopoulou EI, Davies ET, Ma Y, Burroughs AK, Vergani D. Source: Dig Liver Dis. 2003 November; 35(11): 801-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674671

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Autoimmunity and environmental factors in the pathogenesis of primary biliary cirrhosis. Author(s): Kita H, He XS, Gershwin ME. Source: Annals of Medicine. 2004; 36(1): 72-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15000349

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Autoreactivity to lipoate and a conjugated form of lipoate in primary biliary cirrhosis. Author(s): Bruggraber SF, Leung PS, Amano K, Quan C, Kurth MJ, Nantz MH, Benson GD, Van de Water J, Luketic V, Roche TE, Ansari AA, Coppel RL, Gershwin ME. Source: Gastroenterology. 2003 December; 125(6): 1705-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724823

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B7-2 positive cells around interlobular bile ducts in primary biliary cirrhosis and chronic hepatitis C. Author(s): Kaji K, Tsuneyama K, Nakanuma Y, Harada K, Sasaki M, Kaneko S, Kobayashi K. Source: Journal of Gastroenterology and Hepatology. 1997 July; 12(7): 507-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9257241

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Bcl-2-dependent oxidation of pyruvate dehydrogenase-E2, a primary biliary cirrhosis autoantigen, during apoptosis. Author(s): Odin JA, Huebert RC, Casciola-Rosen L, LaRusso NF, Rosen A. Source: The Journal of Clinical Investigation. 2001 July; 108(2): 223-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11457875

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Beneficial hepatic effect of troglitazone in a patient with antimitochondrial antibodynegative primary biliary cirrhosis. Author(s): Okai T, Mouri H, Yamaguchi Y, Nakanuma Y, Sawabu N. Source: The American Journal of Gastroenterology. 2002 January; 97(1): 209-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11808957

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Benefit of transplantation in primary biliary cirrhosis between 1985-1997. Author(s): Tinmouth J, Tomlinson G, Heathcote EJ, Lilly L. Source: Transplantation. 2002 January 27; 73(2): 224-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11821734

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Bezafibrate in the treatment of primary biliary cirrhosis: comparison with ursodeoxycholic acid. Author(s): Kurihara T, Niimi A, Maeda A, Shigemoto M, Yamashita K. Source: The American Journal of Gastroenterology. 2000 October; 95(10): 2990-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11051391

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Bile duct cell apoptosis is a rare event in primary biliary cirrhosis. Author(s): Ballardini G, Guidi M, Susca M, Ghetti S, Grassi A, Lari F, Fusconi M, Zauli D, Bianchi FB. Source: Dig Liver Dis. 2001 March; 33(2): 151-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11346144

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Bile duct cell apoptosis: a rare event in primary biliary cirrhosis? Author(s): Ishibashi H, Kamihira T, Shimoda S. Source: Dig Liver Dis. 2001 March; 33(2): 122-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11346138

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Bile duct cells in primary biliary cirrhosis are 'primed' for apoptosis. Author(s): Graham AM, Dollinger MM, Howie SE, Harrison DJ. Source: European Journal of Gastroenterology & Hepatology. 1998 July; 10(7): 553-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9855077

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Bile duct epithelia as target cells in primary biliary cirrhosis and primary sclerosing cholangitis. Author(s): Dienes HP, Lohse AW, Gerken G, Schirmacher P, Gallati H, Lohr HF, Meyer zum Buschenfelde KH. Source: Virchows Archiv : an International Journal of Pathology. 1997 August; 431(2): 119-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9293893

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Biliary bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid. Author(s): Combes B, Carithers RL Jr, Maddrey WC, Munoz S, Garcia-Tsao G, Bonner GF, Boyer JL, Luketic VA, Shiffman ML, Peters MG, White H, Zetterman RK, Risser R, Rossi SS, Hofmann AF. Source: Hepatology (Baltimore, Md.). 1999 June; 29(6): 1649-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10347103

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Biliary cirrhosis induces type IIx/b fiber atrophy in rat diaphragm and skeletal muscle, and decreases IGF-I mRNA in the liver but not in muscle. Author(s): Gayan-Ramirez G, van de Casteele M, Rollier H, Fevery J, Vanderhoydonc F, Verhoeven G, Decramer M. Source: Journal of Hepatology. 1998 August; 29(2): 241-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9722205

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Biliary Cirrhosis

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Biliary secretion of endotoxin and pathogenesis of primary biliary cirrhosis. Author(s): Sakisaka S, Koga H, Sasatomi K, Mimura Y, Kawaguchi T, Tanikawa K. Source: Yale J Biol Med. 1997 July-August; 70(4): 403-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9626760

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Biliary tract inflammatory disorders: primary sclerosing cholangitis and primary biliary cirrhosis. Author(s): Franco J, Saeian K. Source: Current Gastroenterology Reports. 1999 April; 1(2): 95-101. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10980934

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Biochemistry and autoimmune response to the 2-oxoacid dehydrogenase complexes in primary biliary cirrhosis. Author(s): Bassendine MF, Jones DE, Yeaman SJ. Source: Seminars in Liver Disease. 1997 February; 17(1): 49-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9089910

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Blood fetal microchimerism in primary biliary cirrhosis. Author(s): Invernizzi P, De Andreis C, Sirchia SM, Battezzati PM, Zuin M, Rossella F, Perego F, Bignotto M, Simoni G, Podda M. Source: Clinical and Experimental Immunology. 2000 December; 122(3): 418-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11122249

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Bone disease in primary biliary cirrhosis: independent indicators and rate of progression. Author(s): Menon KV, Angulo P, Weston S, Dickson ER, Lindor KD. Source: Journal of Hepatology. 2001 September; 35(3): 316-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11592591

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Bone loss in primary biliary cirrhosis: absence of association with severity of liver disease. Author(s): Le Gars L, Grandpierre C, Chazouilleres O, Berenbaum F, Poupon R. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 March; 69(2): 195-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12027312

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Breakdown of tolerance to pyruvate dehydrogenase complex in experimental autoimmune cholangitis: a mouse model of primary biliary cirrhosis. Author(s): Jones DE, Palmer JM, Yeaman SJ, Kirby JA, Bassendine MF. Source: Hepatology (Baltimore, Md.). 1999 July; 30(1): 65-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10385640

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Bronchiolitis obliterans organising pneumonia and primary biliary cirrhosis-like lung involvement in a patient with primary biliary cirrhosis. Author(s): Strobel ES, Bonnet RB, Werner P, Schaefer HE, Peter HH. Source: Clinical Rheumatology. 1998; 17(3): 246-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9694063

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BSEP and MDR3 haplotype structure in healthy Caucasians, primary biliary cirrhosis and primary sclerosing cholangitis. Author(s): Pauli-Magnus C, Kerb R, Fattinger K, Lang T, Anwald B, Kullak-Ublick GA, Beuers U, Meier PJ. Source: Hepatology (Baltimore, Md.). 2004 March; 39(3): 779-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14999697

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Caspase induction by IgA antimitochondrial antibody: IgA-mediated biliary injury in primary biliary cirrhosis. Author(s): Matsumura S, Van De Water J, Leung P, Odin JA, Yamamoto K, Gores GJ, Mostov K, Ansari AA, Coppel RL, Shiratori Y, Gershwin ME. Source: Hepatology (Baltimore, Md.). 2004 May; 39(5): 1415-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15122771

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Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis. Author(s): Muratori P, Muratori L, Ferrari R, Cassani F, Bianchi G, Lenzi M, Rodrigo L, Linares A, Fuentes D, Bianchi FB. Source: The American Journal of Gastroenterology. 2003 February; 98(2): 431-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12591064

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Cholangiocytes and primary biliary cirrhosis: prediction and predication. Author(s): Gershwin ME, Van de Water J. Source: The Journal of Clinical Investigation. 2001 July; 108(2): 187-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11457871

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Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration. Author(s): Del Puppo M, Galli Kienle M, Crosignani A, Petroni ML, Amati B, Zuin M, Podda M. Source: Journal of Lipid Research. 2001 March; 42(3): 437-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11254756

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Clinical and biochemical features and therapy responses in primary biliary cirrhosis and primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Author(s): Gunsar F, Akarca US, Ersoz G, Karasu Z, Yuce G, Batur Y. Source: Hepatogastroenterology. 2002 September-October; 49(47): 1195-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12239904

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Clinical denouement and mutation analysis of patients with cystic fibrosis undergoing liver transplantation for biliary cirrhosis. Author(s): Mack DR, Traystman MD, Colombo JL, Sammut PH, Kaufman SS, Vanderhoof JA, Antonson DL, Markin RS, Shaw BW Jr, Langnas AN. Source: The Journal of Pediatrics. 1995 December; 127(6): 881-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8523183

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Clinical features of forty patients with primary biliary cirrhosis. Author(s): Zhang F, Jia J, Cui R, Wang B, Wang H. Source: Chinese Medical Journal. 2002 June; 115(6): 904-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12123563

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Clonal analysis of liver-derived T cells of patients with primary biliary cirrhosis. Author(s): Hoffmann RM, Pape GR, Spengler U, Rieber EP, Eisenburg J, Dohrmann J, Paumgartner G, Riethmuller G. Source: Clinical and Experimental Immunology. 1989 May; 76(2): 210-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2788045

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Cloning the human betaretrovirus proviral genome from patients with primary biliary cirrhosis. Author(s): Xu L, Sakalian M, Shen Z, Loss G, Neuberger J, Mason A. Source: Hepatology (Baltimore, Md.). 2004 January; 39(1): 151-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752833

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Colchicine in primary biliary cirrhosis. Author(s): Mollengarden GA. Source: Gastroenterology. 1989 June; 96(6): 1628-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2714590

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Combined analysis of the effect of treatment with ursodeoxycholic acid on histologic progression in primary biliary cirrhosis. Author(s): Poupon RE, Lindor KD, Pares A, Chazouilleres O, Poupon R, Heathcote EJ. Source: Journal of Hepatology. 2003 July; 39(1): 12-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821038

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Combined endoscopic variceal ligation and sclerotherapy for bleeding rectal varices associated with primary biliary cirrhosis: a case showing a long-lasting favorable response. Author(s): Shudo R, Yazaki Y, Sakurai S, Uenishi H, Yamada H, Sugawara K, Kohgo Y. Source: Gastrointestinal Endoscopy. 2001 May; 53(6): 661-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11323601

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Common variants of the matrix metalloproteinase-3 (stromelysin) gene promoter in primary biliary cirrhosis. Author(s): Selmi C, Zuin M, Meda F, Podda M, Biondi ML, Cecchini F. Source: Gastroenterology. 2002 January; 122(1): 247-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11806373

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Comprehensive mapping of HLA-A0201-restricted CD8 T-cell epitopes on PDC-E2 in primary biliary cirrhosis. Author(s): Matsumura S, Kita H, He XS, Ansari AA, Lian ZX, Van De Water J, Yamamoto K, Tsuji T, Coppel RL, Kaplan M, Gershwin ME. Source: Hepatology (Baltimore, Md.). 2002 November; 36(5): 1125-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12395322

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Concurrent de novo autoimmune hepatitis and recurrence of primary biliary cirrhosis post-liver transplantation. Author(s): Tan CK, Sian Ho JM. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2001 May; 7(5): 461-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11349269

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Consecutive occurrence of primary biliary cirrhosis and autoimmune hepatitis: a case report and review of the literature. Author(s): Weyman RL, Voigt M. Source: The American Journal of Gastroenterology. 2001 February; 96(2): 585-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11232713

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Construction and expression of a humanized M2 autoantigen trimer and its application in the diagnosis of primary biliary cirrhosis. Author(s): Jiang XH, Zhong RQ, Yu SQ, Hu Y, Li WW, Kong XT. Source: World Journal of Gastroenterology : Wjg. 2003 June; 9(6): 1352-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12800255

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Correlation between histopathological findings of the liver and IgA class antibodies to 2-oxo-acid dehydrogenase complex in primary biliary cirrhosis. Author(s): Masuda J, Omagari K, Ohba K, Hazama H, Kadokawa Y, Kinoshita H, Hayashida K, Hayashida K, Ishibashi H, Nakanuma Y, Kohno S. Source: Digestive Diseases and Sciences. 2003 May; 48(5): 932-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12772793

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Current management of primary biliary cirrhosis and primary sclerosing cholangitis. Author(s): Levy C, Lindor KD. Source: Journal of Hepatology. 2003; 38 Suppl 1: S24-37. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12591184

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Cutaneous T cell lymphoma in a patient with primary biliary cirrhosis and secondary Sjogren's syndrome. Author(s): Stroehmann A, Dorner T, Lukowsky A, Feist E, Hiepe F, Burmester GR. Source: The Journal of Rheumatology. 2002 June; 29(6): 1326-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12064854

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Damaged interlobular bile ducts in primary biliary cirrhosis show reduced expression of glutathione-S-transferase-pi and aberrant expression of 4hydroxynonenal. Author(s): Tsuneyama K, Harada K, Kono N, Sasaki M, Saito T, Gershwin ME, Ikemoto M, Arai H, Nakanuma Y. Source: Journal of Hepatology. 2002 August; 37(2): 176-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12127421

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Defective regulation of cholangiocyte Cl-/HCO3(-) and Na+/H+ exchanger activities in primary biliary cirrhosis. Author(s): Melero S, Spirli C, Zsembery A, Medina JF, Joplin RE, Duner E, Zuin M, Neuberger JM, Prieto J, Strazzabosco M. Source: Hepatology (Baltimore, Md.). 2002 June; 35(6): 1513-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12029638

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Defenses gone awry. Primary biliary cirrhosis. Author(s): Brettler S. Source: Rn. 2003 September; 66(9): 38-3; Quiz 44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14533509

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Delayed opioid withdrawal-like reaction in primary biliary cirrhosis following naloxone therapy. Author(s): Shawcross DL, Jalan R. Source: Gastroenterology. 2001 September; 121(3): 743-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11547785

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Demonstration of peptide-specific and cross-reactive epitopes in proteins reacting with antimitochondrial antibodies of primary biliary cirrhosis. Author(s): Fusconi M, Baum H, Caselli A, Cassani F, Ballardini G, Lenzi M, Volta U, Zauli D, Bianchi FB. Source: Journal of Hepatology. 1992 May; 15(1-2): 162-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1380527

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Destruction of canals of Hering in primary biliary cirrhosis. Author(s): Saxena R, Hytiroglou P, Thung SN, Theise ND. Source: Human Pathology. 2002 October; 33(10): 983-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12395370

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Detection of antimitochondrial autoantibodies in immunofluorescent AMA-negative patients with primary biliary cirrhosis using recombinant autoantigens. Author(s): Miyakawa H, Tanaka A, Kikuchi K, Matsushita M, Kitazawa E, Kawaguchi N, Fujikawa H, Gershwin ME. Source: Hepatology (Baltimore, Md.). 2001 August; 34(2): 243-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11481607

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Detection of autoantibodies to recombinant mitochondrial proteins in patients with primary biliary cirrhosis. Author(s): Van de Water J, Cooper A, Surh CD, Coppel R, Danner D, Ansari A, Dickson R, Gershwin ME. Source: The New England Journal of Medicine. 1989 May 25; 320(21): 1377-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2716784

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Detection of male DNA in the liver of female patients with primary biliary cirrhosis. Author(s): Fanning PA, Jonsson JR, Clouston AD, Edwards-Smith C, Balderson GA, Macdonald GA, Crawford DH, Kerlin P, Powell LW, Powell EE. Source: Journal of Hepatology. 2000 November; 33(5): 690-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11097474

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Detection of serum nitrite and nitrate in primary biliary cirrhosis: possible role of nitric oxide in bile duct injury. Author(s): Hokari A, Zeniya M, Esumi H, Kawabe T, Gershwin ME, Toda G. Source: Journal of Gastroenterology and Hepatology. 2002 March; 17(3): 308-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11982702

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Development of an enzyme immune assay for detecting M2 autoantibodies specific for primary biliary cirrhosis. Author(s): Jiang XH, Fang XY, Zhong RQ, Wang XP, Hu Y, Kong XT. Source: Hepatobiliary Pancreat Dis Int. 2003 May; 2(2): 290-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599987

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Development of autoimmune hepatitis in the setting of long-standing primary biliary cirrhosis. Author(s): Angulo P, El-Amin O, Carpenter HA, Lindor KD. Source: The American Journal of Gastroenterology. 2001 October; 96(10): 3021-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11693344

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Diagnosis and treatment of primary biliary cirrhosis. Author(s): Nishio A, Keeffe EB, Ishibashi H, Gershwin EM. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2000 January-February; 6(1): 181-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11208308

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Differences in the efficacy of ursodeoxycholic acid and bile acid metabolism between viral liver diseases and primary biliary cirrhosis. Author(s): Nakashima T, Yoh T, Sumida Y, Kakisaka Y, Mitsuyoshi H. Source: Journal of Gastroenterology and Hepatology. 2001 May; 16(5): 541-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11350551

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Different apheresis methods in the treatment of hypercholesterolemia in primary biliary cirrhosis: a case report. Author(s): Kojima S, Toyota Y, Shiba M, Tsushima M, Matsuoka H, Yamamoto A. Source: Artificial Organs. 1995 September; 19(9): 938-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8687302

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Differential expression of intestinal trefoil factor in biliary epithelial cells of primary biliary cirrhosis. Author(s): Kimura Y, Leung PS, Kenny TP, Van De Water J, Nishioka M, Giraud AS, Neuberger J, Benson G, Kaul R, Ansari AA, Coppel RL, Gershwin ME. Source: Hepatology (Baltimore, Md.). 2002 November; 36(5): 1227-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12395334

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Discussion on the true impact of fatigue in primary biliary cirrhosis: a population study. Author(s): Kingham JG. Source: Gastroenterology. 2003 February; 124(2): 582; Author Reply 582. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12557171

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Disease recurrence after living liver transplantation for primary biliary cirrhosis: a clinical and histological follow-up study. Author(s): Hashimoto E, Shimada M, Noguchi S, Taniai M, Tokushige K, Hayashi N, Takasaki K, Fuchinoue S, Ludwig J. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2001 July; 7(7): 588-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11460225

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Distinct costimulation dependent and independent autoreactive T-cell clones in primary biliary cirrhosis. Author(s): Kamihira T, Shimoda S, Harada K, Kawano A, Handa M, Baba E, Tsuneyama K, Nakamura M, Ishibashi H, Nakanuma Y, Gershwin ME, Harada M. Source: Gastroenterology. 2003 November; 125(5): 1379-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14598254

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Does a betaretrovirus infection trigger primary biliary cirrhosis? Author(s): Xu L, Shen Z, Guo L, Fodera B, Keogh A, Joplin R, O'Donnell B, Aitken J, Carman W, Neuberger J, Mason A. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 July 8; 100(14): 8454-9. Epub 2003 June 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12832623

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Early diagnosis of primary biliary cirrhosis in type 1 diabetes: the possible role of eosinophilia. Author(s): Gazzaruso C, Giordanetti S, De Cata P, Poggi G, Fratino P. Source: Diabetes Care. 2003 October; 26(10): 2963-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14514618

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Effect of bezafibrate in primary biliary cirrhosis: a pilot study. Author(s): Ohmoto K, Mitsui Y, Yamamoto S. Source: Liver. 2001 June; 21(3): 223-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11422787

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Effects of chenodeoxycholic and ursodeoxycholic acids on interferon-gamma production by peripheral blood mononuclear cells from patients with primary biliary cirrhosis. Author(s): Saeki R, Ogino H, Kaneko S, Unoura M, Kobayashi K. Source: Journal of Gastroenterology. 1995 December; 30(6): 739-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8963391

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Efficacy of colchicine in patients with primary biliary cirrhosis poorly responsive to ursodiol and methotrexate. Author(s): Lee YM, Kaplan MM. Source: The American Journal of Gastroenterology. 2003 January; 98(1): 205-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12526960

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Efficiency of liver transplantation in patients with primary biliary cirrhosis. Author(s): Markus BH, Dickson ER, Grambsch PM, Fleming TR, Mazzaferro V, Klintmalm GB, Wiesner RH, Van Thiel DH, Starzl TE. Source: The New England Journal of Medicine. 1989 June 29; 320(26): 1709-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2659986

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Elevated expression of tyrosine kinase DDR2 in primary biliary cirrhosis. Author(s): Mao TK, Kimura Y, Kenny TP, Branchi A, Gishi RG, Van de Water J, Kung HJ, Friedman SL, Gershwin ME. Source: Autoimmunity. 2002 December; 35(8): 521-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12765478

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Endoscopic ligation of oesophageal varices compared with injection sclerotherapy in primary biliary cirrhosis. Author(s): Tsugawa K, Hashizume M, Migou S, Kishihara F, Kawanaka H, Tomikawa M, Tanoue K, Sugimachi K. Source: European Journal of Gastroenterology & Hepatology. 2000 October; 12(10): 11115. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11057456

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Enhanced expression of Bcl-2 in lymphocytes infiltrating into the liver of patients with primary biliary cirrhosis. Author(s): Deguchi A, Arima K, Masaki T, Yachida M, Nakai S, Ito T, Kita Y, Kurokohchi K, Watanabe S, Kuriyama S. Source: International Journal of Molecular Medicine. 2002 June; 9(6): 571-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12011972

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Enhanced hepatic lipid peroxidation in patients with primary biliary cirrhosis. Author(s): Kawamura K, Kobayashi Y, Kageyama F, Kawasaki T, Nagasawa M, Toyokuni S, Uchida K, Nakamura H. Source: The American Journal of Gastroenterology. 2000 December; 95(12): 3596-601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11151898

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Enhanced intrahepatic inducible nitric oxide synthase expression and nitrotyrosine accumulation in primary biliary cirrhosis and autoimmune hepatitis. Author(s): Sanz-Cameno P, Medina J, Garcia-Buey L, Garcia-Sanchez A, Borque MJ, Martin-Vilchez S, Gamallo C, Jones EA, Moreno-Otero R. Source: Journal of Hepatology. 2002 December; 37(6): 723-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12445411

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Epidemiology and pathogenesis of primary biliary cirrhosis. Author(s): Selmi C, Invernizzi P, Keefe EB, Coppel RL, Podda M, Rossaro L, Ansari AA, Gershwin ME. Source: Journal of Clinical Gastroenterology. 2004 March; 38(3): 264-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15128074

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Epitope mapping on E1alpha subunit of pyruvate dehydrogenase complex with autoantibodies of patients with primary biliary cirrhosis. Author(s): Mori T, Ono K, Hakozaki M, Kochi H. Source: Liver International : Official Journal of the International Association for the Study of the Liver. 2003 October; 23(5): 355-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14708897

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Esophagogastric varices as a prognostic factor for the determination of clinical stage in patients with primary biliary cirrhosis. Author(s): Takeshita E, Kumagi T, Matsui H, Abe M, Furukawa S, Ikeda Y, Matsuura B, Michitaka K, Horiike N, Onji M. Source: Journal of Gastroenterology. 2003; 38(11): 1060-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673723

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Etidronate for osteoporosis in primary biliary cirrhosis: a randomized trial. Author(s): Lindor KD, Jorgensen RA, Tiegs RD, Khosla S, Dickson ER. Source: Journal of Hepatology. 2000 December; 33(6): 878-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11131448

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Evaluation of a new scoring system for primary biliary cirrhosis and its related variant forms. Author(s): Imura J, Fujimori T. Source: Journal of Gastroenterology. 2003; 38(1): 106-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12560933

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Evaluation of newly developed ELISA using "MESACUP-2 test mitochondrial M2" kit for the diagnosis of primary biliary cirrhosis. Author(s): Kadokawa Y, Omagari K, Hazama H, Ohba K, Masuda J, Kinoshita H, Hayashida K, Isomoto H, Mizuta Y, Murase K, Murata I, Kohno S. Source: Clinical Biochemistry. 2003 May; 36(3): 203-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12726929

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Evidence of an increased nitric oxide production in primary biliary cirrhosis. Author(s): Battista S, Bar F, Mengozzi G, Pollet C, Torchio M, Cavalli G, Rosina F, David E, Cutrin JC, Cavalieri B, Poli G, Molino G. Source: The American Journal of Gastroenterology. 2001 March; 96(3): 869-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11280567

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Expression and DNA-binding activity of signal transducer and activator of transcription 3 in alcoholic cirrhosis compared to normal liver and primary biliary cirrhosis in humans. Author(s): Starkel P, Bishop K, Horsmans Y, Strain AJ. Source: American Journal of Pathology. 2003 February; 162(2): 587-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12547716

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Expression of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 protein and messenger RNA in primary biliary cirrhosis. Author(s): Yokomori H, Oda M, Yoshimura K, Nomura M, Ogi M, Wakabayashi G, Kitajima M, Ishii H. Source: Intern Med. 2003 October; 42(10): 947-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14606706

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Expression of uncoupling protein-2 in biliary epithelial cells in primary biliary cirrhosis. Author(s): Taniguchi E, Harada M, Kawaguchi T, Koga H, Kumemura H, Hanada S, Shishido S, Baba S, Kumashiro R, Ueno T, Sakisaka S, Sata M. Source: Liver. 2002 December; 22(6): 451-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12445169

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Familial intrahepatic cholestatic cirrhosis with positive antimitochondrial antibody: familial primary biliary cirrhosis. Author(s): Ramakrishna B, Eapen CE, Kang G, Kurian G, Chandy GM. Source: Journal of Clinical Gastroenterology. 2000 April; 30(3): 255-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10777183

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Familial primary biliary cirrhosis and autoimmune cholangitis. Author(s): Agarwal K, Jones DE, Watt FE, Burt AD, Floreani A, Bassendine MF. Source: Dig Liver Dis. 2002 January; 34(1): 50-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11930900

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Familial primary biliary cirrhosis in Hiroshima. Author(s): Tsuji K, Watanabe Y, Van De Water J, Nakanishi T, Kajiyama G, Parikh-Patel A, Coppel R, Gershwin ME. Source: Journal of Autoimmunity. 1999 August; 13(1): 171-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10441183

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Familial primary biliary cirrhosis reassessed: a geographically-based population study. Author(s): Jones DE, Watt FE, Metcalf JV, Bassendine MF, James OF. Source: Journal of Hepatology. 1999 March; 30(3): 402-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10190721

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Fas ligand expressing mononuclear cells around intrahepatic bile ducts co-express CD68 in primary biliary cirrhosis. Author(s): Iwata M, Harada K, Hiramatsu K, Tsuneyama K, Kaneko S, Kobayashi K, Nakanuma Y. Source: Liver. 2000 April; 20(2): 129-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10847481

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Fatal scleroderma renal crisis caused by gastrointestinal bleeding in a patient with scleroderma, Sjogren's syndrome and primary biliary cirrhosis overlap. Author(s): Szigeti N, Fabian G, Czirjak L. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2002 May; 16(3): 276-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12195572

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Fatigue and primary biliary cirrhosis: association of globus pallidus magnetisation transfer ratio measurements with fatigue severity and blood manganese levels. Author(s): Forton DM, Patel N, Prince M, Oatridge A, Hamilton G, Goldblatt J, Allsop JM, Hajnal JV, Thomas HC, Bassendine M, Jones DE, Taylor-Robinson SD. Source: Gut. 2004 April; 53(4): 587-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15016756

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Fatigue in primary biliary cirrhosis. Author(s): Cauch-Dudek K, Abbey S, Stewart DE, Heathcote EJ. Source: Gut. 1998 November; 43(5): 705-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9824355

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Fat-soluble vitamin levels in patients with primary biliary cirrhosis. Author(s): Phillips JR, Angulo P, Petterson T, Lindor KD. Source: The American Journal of Gastroenterology. 2001 September; 96(9): 2745-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11569705

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Fenofibrate for patients with asymptomatic primary biliary cirrhosis. Author(s): Dohmen K, Mizuta T, Nakamuta M, Shimohashi N, Ishibashi H, Yamamoto K. Source: World Journal of Gastroenterology : Wjg. 2004 March 15; 10(6): 894-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15040040

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Fenofibrate treatment in patients with primary biliary cirrhosis. Author(s): Ohira H, Sato Y, Ueno T, Sata M. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 2147-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12190200

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Fetal microchimerism alone does not contribute to the induction of primary biliary cirrhosis. Author(s): Tanaka A, Lindor K, Gish R, Batts K, Shiratori Y, Omata M, Nelson JL, Ansari A, Coppel R, Newsome M, Gershwin ME. Source: Hepatology (Baltimore, Md.). 1999 October; 30(4): 833-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10498630

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Fetal microchimerism in primary biliary cirrhosis. Author(s): Corpechot C, Barbu V, Chazouilleres O, Poupon R. Source: Journal of Hepatology. 2000 November; 33(5): 696-700. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11097475

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Fetal microchimerism: an aetiological factor in primary biliary cirrhosis? Author(s): Jones DE. Source: Journal of Hepatology. 2000 November; 33(5): 834-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11097494

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Fine specificity of T cells reactive to human PDC-E2 163-176 peptide, the immunodominant autoantigen in primary biliary cirrhosis: implications for molecular mimicry and cross-recognition among mitochondrial autoantigens. Author(s): Shigematsu H, Shimoda S, Nakamura M, Matsushita S, Nishimura Y, Sakamoto N, Ichiki Y, Niho Y, Gershwin ME, Ishibashi H. Source: Hepatology (Baltimore, Md.). 2000 November; 32(5): 901-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11050037

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First report of association of chronic pancreatitis, primary biliary cirrhosis, and systemic sclerosis. Author(s): Hastier P, Buckley MJ, Le Gall P, Bellon S, Dumas R, Delmont J. Source: Digestive Diseases and Sciences. 1998 November; 43(11): 2426-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9824129

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FISH for Y chromosome in women with primary biliary cirrhosis: lack of evidence for leukocyte microchimerism. Author(s): Rubbia-Brandt L, Philippeaux MM, Chavez S, Mentha G, Borisch B, Hadengue A. Source: Hepatology (Baltimore, Md.). 1999 September; 30(3): 821-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10490375

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Flow cytometric analysis of IL-6 receptors on peripheral lymphocytes in patients with primary biliary cirrhosis. Author(s): Yamashiki M, Kosaka Y, Nishioka J, Tameda Y, Takase K, Watanabe S, Kaito M, Nishimura A, Suzuki H, Nomoto M. Source: Journal of Clinical Laboratory Analysis. 1998; 12(2): 83-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9524291

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Frequency of monosomy X in women with primary biliary cirrhosis. Author(s): Invernizzi P, Miozzo M, Battezzati PM, Bianchi I, Grati FR, Simoni G, Selmi C, Watnik M, Gershwin ME, Podda M. Source: Lancet. 2004 February 14; 363(9408): 533-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14975617

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Functional status of patients with primary biliary cirrhosis. Author(s): Parik-Patel A, Gold EB, Utts J, Worman H, Krivy KE, Gershwin ME. Source: The American Journal of Gastroenterology. 2002 November; 97(11): 2871-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12425562

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Gastroduodenal and intestinal permeability in primary biliary cirrhosis. Author(s): Di Leo V, Venturi C, Baragiotta A, Martines D, Floreani A. Source: European Journal of Gastroenterology & Hepatology. 2003 September; 15(9): 967-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12923368

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Generalized morphoea and primary biliary cirrhosis: a rare association and improvement with oxypentifylline. Author(s): Wong SS, Holt PJ. Source: Clinical and Experimental Dermatology. 1992 September; 17(5): 371-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1458651

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Genes within the HLA class II region confer both predisposition and resistance to primary biliary cirrhosis. Author(s): Begovich AB, Klitz W, Moonsamy PV, Van de Water J, Peltz G, Gershwin ME. Source: Tissue Antigens. 1994 February; 43(2): 71-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8016844

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Genetic and familial considerations of primary biliary cirrhosis. Author(s): Tanaka A, Borchers AT, Ishibashi H, Ansari AA, Keen CL, Gershwin ME. Source: The American Journal of Gastroenterology. 2001 January; 96(1): 8-15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11197292

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Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis and autoimmune hepatitis. Author(s): Vogel A, Strassburg CP, Manns MP. Source: Hepatology (Baltimore, Md.). 2002 January; 35(1): 126-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11786968

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Genetic factors in primary biliary cirrhosis. Author(s): Gregory WL, Bassendine MF. Source: Journal of Hepatology. 1994 June; 20(6): 689-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7930465

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Genetic factors in the pathogenesis of primary biliary cirrhosis. Author(s): Jones DE, Donaldson PT. Source: Clinics in Liver Disease. 2003 November; 7(4): 841-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594133

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Genetic susceptibility to primary biliary cirrhosis. Author(s): Agarwal K, Jones DE, Bassendine MF. Source: European Journal of Gastroenterology & Hepatology. 1999 June; 11(6): 603-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10418930

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Genetic variants of endothelial nitric oxide synthase in patients with primary biliary cirrhosis: association with disease severity. Author(s): Selmi C, Zuin M, Biondi ML, Invernizzi P, Battezzati PM, Bernini M, Meda F, Gershwin ME, Podda M. Source: Journal of Gastroenterology and Hepatology. 2003 October; 18(10): 1150-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12974901

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Genomic analysis of differentially expressed genes in liver and biliary epithelial cells of patients with primary biliary cirrhosis. Author(s): Tanaka A, Leung PS, Kenny TP, Au-Young J, Prindiville T, Coppel RL, Ansari AA, Gershwin ME. Source: Journal of Autoimmunity. 2001 August; 17(1): 89-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11488641

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Glibenclamide induced chronic cholestasis simulating primary biliary cirrhosis: a case report. Author(s): Ramanathan M, Wahinuddin S, Kew ST. Source: Med J Malaysia. 1996 March; 51(1): 140-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10967995

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Glucocorticoid treatment of primary biliary cirrhosis in a pregnant woman. Author(s): Ji H, Haring P, Kirkinen P, Saarikoski S. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1995 September; 74(8): 654-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7660778

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Glutathione S-transferase expression in primary biliary cirrhosis supports concept of "ductular metaplasia" of hepatocytes. Author(s): Hiley CG, Strange RC, Davies MH, Elias E, Hubscher SG. Source: Journal of Clinical Pathology. 1993 April; 46(4): 381. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8496402

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Gluten sensitivity in patients with primary biliary cirrhosis. Author(s): Niveloni S, Dezi R, Pedreira S, Podesta A, Cabanne A, Vazquez H, Sugai E, Smecuol E, Doldan I, Valero J, Kogan Z, Boerr L, Maurino E, Terg R, Bai JC. Source: The American Journal of Gastroenterology. 1998 March; 93(3): 404-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9580141

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Goodpasture's syndrome associated with primary biliary cirrhosis. Author(s): Komatsu T, Utsunomiya K, Oyaizu T. Source: Intern Med. 1998 July; 37(7): 611-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9711889

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Granulomatous destruction of bile ducts after liver transplantation: primary biliary cirrhosis recurrence or hepatitis C virus infection? Author(s): Farges O, Bismuth H, Sebagh M, Reynes M. Source: Hepatology (Baltimore, Md.). 1995 June; 21(6): 1765-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7768528

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Granulomatous myositis, primary biliary cirrhosis, pancytopenia, and thymoma. Author(s): Herrmann DN, Blaivas M, Wald JJ, Feldman EL. Source: Muscle & Nerve. 2000 July; 23(7): 1133-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10883012

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Granulomatous uveitis, CREST syndrome, and primary biliary cirrhosis. Author(s): Santos PS, Oliveira L, Moraes MF, Da Graca JP, Monteiro E, Abecasis P, De Oliveira LN. Source: The British Journal of Ophthalmology. 2000 May; 84(5): 548-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10847709

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Grip strength and subjective fatigue in patients with primary biliary cirrhosis. Author(s): Goldblatt J, James OF, Jones DE. Source: Jama : the Journal of the American Medical Association. 2001 May 2; 285(17): 2196-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11325320

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GSTM1 null polymorphism at the glutathione S-transferase M1 locus: phenotype and genotype studies in patients with primary biliary cirrhosis. Author(s): Davies MH, Elias E, Acharya S, Cotton W, Faulder GC, Fryer AA, Strange RC. Source: Gut. 1993 April; 34(4): 549-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8491405

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Hand involvement in primary biliary cirrhosis in an 85-year-old woman. Author(s): Stone M, Inman RD, Salonen D. Source: The Journal of Rheumatology. 2003 July; 30(7): 1628-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12858471

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Hepatic lymph nodes as follow-up factor in primary biliary cirrhosis. An ultrasound study. Author(s): Lyttkens K, Prytz H, Forsberg L, Hagerstrand I. Source: Scandinavian Journal of Gastroenterology. 1995 October; 30(10): 1036-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8545610

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Hepatic Met-enkephalin immunoreactivity is enhanced in primary biliary cirrhosis. Author(s): Bergasa NV, Liau S, Homel P, Ghali V. Source: Liver. 2002 April; 22(2): 107-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12028403

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Hepatitis and liver dysfunction with rifampicin therapy for pruritus in primary biliary cirrhosis. Author(s): Prince MI, Burt AD, Jones DE. Source: Gut. 2002 March; 50(3): 436-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11839728

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Hepatitis C virus testing in primary biliary cirrhosis. Author(s): Bertolini E, Battezzati PM, Zermiani P, Bruno S, Moroni GA, Marelli F, Villa E, Manenti F, Zuin M, Crosignani A, et al. Source: Journal of Hepatology. 1992 May; 15(1-2): 207-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1324271

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Hepatocellular carcinoma and survival in patients with primary biliary cirrhosis. Author(s): Shibuya A, Tanaka K, Miyakawa H, Shibata M, Takatori M, Sekiyama K, Hashimoto N, Amaki S, Komatsu T, Morizane T. Source: Hepatology (Baltimore, Md.). 2002 May; 35(5): 1172-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11981767

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Hepatocellular carcinoma complicating biliary cirrhosis caused by biliary atresia: report of a case. Author(s): Kohno M, Kitatani H, Wada H, Kajimoto T, Matuno H, Tanino M, Nakagawa T, Takarada A. Source: Journal of Pediatric Surgery. 1995 December; 30(12): 1713-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8749933

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Hepatocellular carcinoma in a patient with primary biliary cirrhosis and seronegativity for markers of hepatitis B virus and hepatitis C virus: report of a case. Author(s): Sunagawa H, Takayama H, Yamashiro T, Sasaki H, Sashida Y, Matsuura K, Kayou M. Source: Surgery Today. 2003; 33(3): 219-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12658391

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Hepatocellular carcinoma in primary biliary cirrhosis: case reports and review of the literature. Author(s): Sato K, Takagi H, Fukusato T, Kanda D, Mori M. Source: Histopathology. 2002 May; 40(5): 490-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12010375

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Hepatocellular carcinoma in primary biliary cirrhosis: similar incidence to that in hepatitis C virus-related cirrhosis. Author(s): Caballeria L, Pares A, Castells A, Gines A, Bru C, Rodes J. Source: The American Journal of Gastroenterology. 2001 April; 96(4): 1160-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11316164

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Hereditary haemorrhagic telangiectasia and secondary biliary cirrhosis. Author(s): Mendoza A, Oliff S, Elias E. Source: European Journal of Gastroenterology & Hepatology. 1995 October; 7(10): 9991002. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8590149

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High prevalence of antibodies to recombinant CENP-B in primary biliary cirrhosis: nuclear immunofluorescence patterns and ELISA reactivities. Author(s): Parveen S, Morshed SA, Nishioka M. Source: Journal of Gastroenterology and Hepatology. 1995 July-August; 10(4): 438-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8527711

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High sensitivity of a novel ELISA for anti-M2 in primary biliary cirrhosis. Author(s): Miyakawa H, Kikuchi K, Jong-Hon K, Kawaguchi N, Yajima R, Ito Y, Maekubo H. Source: Journal of Gastroenterology. 2001; 36(1): 33-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11211208

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High serum osteoprotegerin and low RANKL in primary biliary cirrhosis. Author(s): Szalay F, Hegedus D, Lakatos PL, Tornai I, Bajnok E, Dunkel K, Lakatos P. Source: Journal of Hepatology. 2003 April; 38(4): 395-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12663228

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HLA class II markers and clinical heterogeneity in Swedish patients with primary biliary cirrhosis. Author(s): Wassmuth R, Depner F, Danielsson A, Hultcrantz R, Loof L, Olson R, Prytz H, Sandberg-Gertzen H, Wallerstedt S, Lindgren S. Source: Tissue Antigens. 2002 May; 59(5): 381-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12144621

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HLA-DRB1 and DQB1 genes in anticentromere antibody positive patients with SSc and primary biliary cirrhosis. Author(s): Akimoto S, Abe M, Ishikawa O, Takagi H, Mori M. Source: Annals of the Rheumatic Diseases. 2001 June; 60(6): 639-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11386258

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Human leukocyte antigen Class II associations in serum antimitochondrial antibodies (AMA)-positive and AMA-negative primary biliary cirrhosis. Author(s): Stone J, Wade JA, Cauch-Dudek K, Ng C, Lindor KD, Heathcote EJ. Source: Journal of Hepatology. 2002 January; 36(1): 8-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11804658

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Hyperbilirubinemia induced by endoscopic variceal ligation for esophageal varices in a patient with primary biliary cirrhosis: a case report. Author(s): Akahoshi T, Hashizume M, Tanoue K, Morita M, Tomikawa M, Sugimachi K. Source: Hepatogastroenterology. 2001 November-December; 48(42): 1659-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11813595

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Hypercholesterolemia and atherosclerosis in primary biliary cirrhosis: what is the risk? Author(s): Crippin JS, Lindor KD, Jorgensen R, Kottke BA, Harrison JM, Murtaugh PA, Dickson ER. Source: Hepatology (Baltimore, Md.). 1992 May; 15(5): 858-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1568727

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Hyperlipidaemic state and cardiovascular risk in primary biliary cirrhosis. Author(s): Longo M, Crosignani A, Battezzati PM, Squarcia Giussani C, Invernizzi P, Zuin M, Podda M. Source: Gut. 2002 August; 51(2): 265-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12117892

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Identification and characterization of four M2 mitochondrial autoantigens in primary biliary cirrhosis. Author(s): Bassendine MF, Fussey SP, Mutimer DJ, James OF, Yeaman SJ. Source: Seminars in Liver Disease. 1989 May; 9(2): 124-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2471276

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Identification of beta-subunit of bacterial RNA-polymerase--a non-species-specific bacterial protein--as target of antibodies in primary biliary cirrhosis. Author(s): Roesler KW, Schmider W, Kist M, Batsford S, Schiltz E, Oelke M, Tuczek A, Dettenborn T, Behringer D, Kreisel W. Source: Digestive Diseases and Sciences. 2003 March; 48(3): 561-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12757171

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Identification of HLA-A2-restricted CD8(+) cytotoxic T cell responses in primary biliary cirrhosis: T cell activation is augmented by immune complexes crosspresented by dendritic cells. Author(s): Kita H, Lian ZX, Van de Water J, He XS, Matsumura S, Kaplan M, Luketic V, Coppel RL, Ansari AA, Gershwin ME. Source: The Journal of Experimental Medicine. 2002 January 7; 195(1): 113-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11781370

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Identification of novel molecules and pathogenic pathways in primary biliary cirrhosis: cDNA array analysis of intrahepatic differential gene expression. Author(s): Shackel NA, McGuinness PH, Abbott CA, Gorrell MD, McCaughan GW. Source: Gut. 2001 October; 49(4): 565-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11559656

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Idiopathic myelofibrosis associated with primary biliary cirrhosis. Author(s): Hernandez-Boluda JC, Jimenez M, Rosinol L, Cervantes F. Source: Leukemia & Lymphoma. 2002 March; 43(3): 673-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12002780

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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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Immunohistochemical differences in the portal tract and acinar infiltrates between primary biliary cirrhosis and autoimmune cholangitis. Author(s): O'Donohue J, Wong T, Portmann B, Williams R. Source: European Journal of Gastroenterology & Hepatology. 2002 October; 14(10): 114350. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12362106

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Immunopathogenesis of primary biliary cirrhosis. Author(s): Nishio A, Keeffe EB, Gershwin ME. Source: Seminars in Liver Disease. 2002 August; 22(3): 291-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12360422

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Immunoreactivity of organic mimeotopes of the E2 component of pyruvate dehydrogenase: connecting xenobiotics with primary biliary cirrhosis. Author(s): Long SA, Quan C, Van de Water J, Nantz MH, Kurth MJ, Barsky D, Colvin ME, Lam KS, Coppel RL, Ansari A, Gershwin ME. Source: Journal of Immunology (Baltimore, Md. : 1950). 2001 September 1; 167(5): 295663. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11509645

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Impaired sulfoxidation in patients with primary biliary cirrhosis. Author(s): Scharschmidt BF, Lake JR. Source: Hepatology (Baltimore, Md.). 1989 April; 9(4): 654-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2925168

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Improved liver tests and greater biliary enrichment with high dose ursodeoxycholic acid in early stage primary biliary cirrhosis. Author(s): Roda E, Azzaroli F, Nigro G, Piazza F, Jaboli F, Ferrara F, Liva S, Giovanelli S, Miracolo A, Colecchia A, Festi D, Mazzeo C, Bacchi L, Roda A, Mazzella G. Source: Dig Liver Dis. 2002 July; 34(7): 523-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12236487

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Incomplete response to ursodeoxycholic acid in primary biliary cirrhosis: is a double dosage worthwhile? Author(s): Angulo P, Jorgensen RA, Lindor KD. Source: The American Journal of Gastroenterology. 2001 November; 96(11): 3152-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11721764

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Increased expression of WAF1 in intrahepatic bile ducts in primary biliary cirrhosis relates to apoptosis. Author(s): Harada K, Furubo S, Ozaki S, Hiramatsu K, Sudo Y, Nakanuma Y. Source: Journal of Hepatology. 2001 April; 34(4): 500-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11394648

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Increased incidence of fungal infections in advanced primary biliary cirrhosis. Author(s): Samonakis DN, Chatzicostas C, Vardas E, Roussomoustakaki M, Kouroumalis EA. Source: Journal of Clinical Gastroenterology. 2003 April; 36(4): 369. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12642749

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Intestinal absorption of the bile acid analogue 75Se-homocholic acid-taurine is increased in primary biliary cirrhosis, and reverts to normal during ursodeoxycholic acid administration. Author(s): Lanzini A, De Tavonatti MG, Panarotto B, Scalia S, Mora A, Benini F, Baisini O, Lanzarotto F. Source: Gut. 2003 September; 52(9): 1371-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12912872

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Investigation into the efficacy of bezafibrate against primary biliary cirrhosis, with histological references from cases receiving long term monotherapy. Author(s): Kurihara T, Maeda A, Shigemoto M, Yamashita K, Hashimoto E. Source: The American Journal of Gastroenterology. 2002 January; 97(1): 212-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11808959

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Irregular regeneration of hepatocytes and development of hepatocellular carcinoma in primary biliary cirrhosis. Author(s): Miyakawa H, Fujikawa H, Kikuchi K, Kitazawa E, Kawashima Y. Source: The American Journal of Gastroenterology. 2002 February; 97(2): 488. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11866295

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Is bezafibrate histologically effective for primary biliary cirrhosis? Author(s): Yano K, Kato H, Morita S, Takahara O, Ishibashi H, Furukawa R. Source: The American Journal of Gastroenterology. 2002 April; 97(4): 1075-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12003404

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Is continued enthusiasm for ursodeoxycholic acid therapy for the treatment of primary biliary cirrhosis warranted? Author(s): Wiesner RH. Source: Hepatology (Baltimore, Md.). 1992 May; 15(5): 971-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1568740

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Isoursodeoxycholic acid: metabolism and therapeutic effects in primary biliary cirrhosis. Author(s): Marschall HU, Broome U, Einarsson C, Alvelius G, Thomas HG, Matern S. Source: Journal of Lipid Research. 2001 May; 42(5): 735-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11352980

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Jaundice in non-cirrhotic primary biliary cirrhosis: the premature ductopenic variant. Author(s): Vleggaar FP, van Buuren HR, Zondervan PE, ten Kate FJ, Hop WC; Dutch Multicentre PBC study group. Source: Gut. 2001 August; 49(2): 276-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11454806

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Kinetics of anti-M2 antibodies after liver transplantation for primary biliary cirrhosis. Author(s): Dubel L, Farges O, Bismuth H, Sebagh M, Homberg JC, Johanet C. Source: Journal of Hepatology. 1995 December; 23(6): 674-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8750166

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Lack of evidence for involvement of fetal microchimerism in pathogenesis of primary biliary cirrhosis. Author(s): Schoniger-Hekele M, Muller C, Ackermann J, Drach J, Wrba F, Penner E, Ferenci P. Source: Digestive Diseases and Sciences. 2002 September; 47(9): 1909-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12353828

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Laparoscopic features of primary biliary cirrhosis in AMA-positive and AMAnegative patients. Author(s): Fujioka S, Yamamoto K, Okamoto R, Miyake M, Ujike K, Shimada N, Terada R, Miyake Y, Nakajima H, Piao CY, Iwasaki Y, Tanimizu M, Tsuji T. Source: Endoscopy. 2002 April; 34(4): 318-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11932789

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Levels of BAFF in serum in primary biliary cirrhosis and autoimmune diabetes. Author(s): Mackay IR, Groom J, Mackay CR. Source: Autoimmunity. 2002 December; 35(8): 551-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12765482

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Liver transplantation for primary biliary cirrhosis. Author(s): MacQuillan GC, Neuberger J. Source: Clinics in Liver Disease. 2003 November; 7(4): 941-56, Ix. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594139

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Liver transplantation for primary biliary cirrhosis. Author(s): Neuberger J. Source: Autoimmunity Reviews. 2003 January; 2(1): 1-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848968

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Liver transplantation for primary biliary cirrhosis. Author(s): Tzakis AG, Carcassonne C, Todo S, Makowka L, Starzl TE. Source: Seminars in Liver Disease. 1989 May; 9(2): 144-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2658105

•

Liver transplantation for primary biliary cirrhosis: a long-term pathologic study. Author(s): Khettry U, Anand N, Faul PN, Lewis WD, Pomfret EA, Pomposelli J, Jenkins RL, Gordon FD. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 January; 9(1): 87-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12514778

•

Liver transplantation for primary biliary cirrhosis: indications and risk of recurrence. Author(s): Neuberger J. Source: Journal of Hepatology. 2003 August; 39(2): 142-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873808

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Biliary Cirrhosis

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Liver transplantation in primary biliary cirrhosis: risk assessment and 11-year followup. Author(s): Rust C, Rau H, Gerbes AL, Pape GR, Haller M, Kramling H, Schildberg FW, Paumgartner G, Beuers U. Source: Digestion. 2000; 62(1): 38-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10899724

•

Liver transplantation restores low serum levels of very low density and high density lipoproteins in end-stage primary biliary cirrhosis. Author(s): Nikkila K. Source: Annals of Medicine. 1992 April; 24(2): 129-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1610540

•

Living-related liver transplantation for patients with primary biliary cirrhosis. Author(s): Hirata M, Harihara Y, Hisatomi S, Miura Y, Yoshino H, Mizuta K, Ito M, Sano K, Taniai N, Kusaka K, Kita Y, Kawarasaki H, Kubota K, Takayama T, Hashizume K, Makuuchi M. Source: Transplantation Proceedings. 2000 November; 32(7): 2208-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11120135

•

Living-related liver transplantation for primary biliary cirrhosis. Author(s): Sugawara Y, Makuuchi M, Takayama T, Imamura H. Source: Transplantation. 2001 September 27; 72(6): 1087-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11579305

•

Local antigen-driven oligoclonal expansion of B cells in the liver portal areas of patients with primary biliary cirrhosis. Author(s): Sugimura T, Shiokawa S, Haraoka S, Fujimoto K, Ohshima K, Nakamuta M, Nishimura J. Source: Liver International : Official Journal of the International Association for the Study of the Liver. 2003 October; 23(5): 323-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14708892

•

Localized morphoea, xanthomatosis and primary biliary cirrhosis. Author(s): Reed JR, De Luca N, McIntyre AS, Wilkinson JD. Source: The British Journal of Dermatology. 2000 September; 143(3): 652-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10971351

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Longitudinal bone loss in postmenopausal women with primary biliary cirrhosis and well-preserved liver function. Author(s): Ormarsdottir S, Ljunggren O, Mallmin H, Olsson R, Prytz H, Loof L. Source: Journal of Internal Medicine. 2002 December; 252(6): 537-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12472915

Studies

51

•

Long-term efficacy of sertraline as a treatment for cholestatic pruritus in patients with primary biliary cirrhosis. Author(s): Browning J, Combes B, Mayo MJ. Source: The American Journal of Gastroenterology. 2003 December; 98(12): 2736-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14687826

•

Lymphadenopathy in primary biliary cirrhosis: CT observations. Author(s): Outwater E, Kaplan MM, Bankoff MS. Source: Radiology. 1989 June; 171(3): 731-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2717743

•

Lymphocyte subsets in peripheral blood and bronchoalveolar lavage in patients with primary biliary cirrhosis. Author(s): Musialik J, Petelenz M, Jastrzebski D, Ziora D, Kondera-Anasz Z, Mertas A, Oklek K, Gonciarz Z. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2001 May; 7 Suppl 1: 311-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12211744

•

Mallory body formation in primary biliary cirrhosis is associated with increased amounts and abnormal phosphorylation and ubiquitination of cytokeratins. Author(s): Fickert P, Trauner M, Fuchsbichler A, Stumptner C, Zatloukal K, Denk H. Source: Journal of Hepatology. 2003 April; 38(4): 387-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12663227

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Management of osteoporosis, fat-soluble vitamin deficiencies, and hyperlipidemia in primary biliary cirrhosis. Author(s): Levy C, Lindor KD. Source: Clinics in Liver Disease. 2003 November; 7(4): 901-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594136

•

Markov models in primary biliary cirrhosis. Author(s): Talwalkar JA. Source: Gastroenterology. 2002 November; 123(5): 1750-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12404263

•

Medical treatment of primary biliary cirrhosis and primary sclerosing cholangitis. Author(s): Holtmeier J, Leuschner U. Source: Digestion. 2001; 64(3): 137-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11786661

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Biliary Cirrhosis

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Methotrexate therapy for primary biliary cirrhosis. Author(s): Bach N, Bodian C, Bodenheimer H, Croen E, Berk PD, Thung SN, Lindor KD, Therneau T, Schaffner F. Source: The American Journal of Gastroenterology. 2003 January; 98(1): 187-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12526956

•

Microscopic polyangiitis associated with primary biliary cirrhosis. Author(s): Iannone F, Falappone P, Pannarale G, Gentile A, Grattagliano V, Covelli M, Lapadula G. Source: The Journal of Rheumatology. 2003 December; 30(12): 2710-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14719218

•

Molecular mimicry of mitochondrial and nuclear autoantigens in primary biliary cirrhosis. Author(s): Shimoda S, Nakamura M, Ishibashi H, Kawano A, Kamihira T, Sakamoto N, Matsushita S, Tanaka A, Worman HJ, Gershwin ME, Harada M. Source: Gastroenterology. 2003 June; 124(7): 1915-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12806624

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Morphologic capillary changes and manifestations of connective tissue diseases in patients with primary biliary cirrhosis. Author(s): Fonollosa V, Simeon CP, Castells L, Garcia F, Castro A, Solans R, Lima J, Vargas V, Guardia J, Vilardell M. Source: Lupus. 2001; 10(9): 628-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11678451

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Mycophenolate mofetil in primary biliary cirrhosis. Author(s): Castedal M, Olsson R. Source: Hepatology (Baltimore, Md.). 2002 November; 36(5): 1297. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12395345

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Myeloperoxidase-positive inflammatory cells participate in bile duct damage in primary biliary cirrhosis through nitric oxide-mediated reactions. Author(s): Wu CT, Eiserich JP, Ansari AA, Coppel RL, Balasubramanian S, Bowlus CL, Gershwin ME, Van De Water J. Source: Hepatology (Baltimore, Md.). 2003 October; 38(4): 1018-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14512889

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Natural history of primary biliary cirrhosis. Author(s): Pares A, Rodes J. Source: Clinics in Liver Disease. 2003 November; 7(4): 779-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594131

Studies

53

•

Natural history of pruritus in primary biliary cirrhosis. Author(s): Talwalkar JA, Souto E, Jorgensen RA, Lindor KD. Source: Clin Gastroenterol Hepatol. 2003 July; 1(4): 297-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017671

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Nature of the mitochondrial antigens of primary biliary cirrhosis and their possible relationships to the etiology of the disease. Author(s): Baum H. Source: Seminars in Liver Disease. 1989 May; 9(2): 117-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2658103

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Negative conversion of antimitochondrial antibody in primary biliary cirrhosis: a case of autoimmune cholangitis. Author(s): Cho YJ, Han DS, Kim TY, Jang SJ, Jeon YC, Sohn JH, Lee IH, Park KN. Source: Journal of Korean Medical Science. 1999 February; 14(1): 102-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10102534

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New knowledge in primary biliary cirrhosis. Author(s): Gershwin ME, Mackay IR. Source: Hosp Pract (Off Ed). 1995 August 15; 30(8): 29-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7543484

•

New weapon for primary biliary cirrhosis from Japan. Author(s): Zeniya M. Source: Journal of Gastroenterology. 2003; 38(6): 619-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12858848

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Non-Hodgkin's lymphoma & primary biliary cirrhosis with Sjogren's syndrome. Author(s): Hahn JS, Kim C, Min YH, Ko YW, Suh CO, Park YY. Source: Yonsei Medical Journal. 2001 April; 42(2): 258-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11371117

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Non-invasive assessment of bone density in primary biliary cirrhosis. Author(s): Pereira SP, Bray GP, Pitt PI, Li F, Moniz C, Williams R. Source: European Journal of Gastroenterology & Hepatology. 1999 March; 11(3): 323-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10333207

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Novel therapeutic approach to primary biliary cirrhosis patients: anti-eosinophil strategy. Author(s): Miyaguchi S, Oda M, Saito H, Ishii H. Source: Hepatogastroenterology. 1998 September-October; 45(23): 1457-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9840083

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Nucleotide variations amongst V(H)Genes of AMA-producing B cell clones in primary biliary cirrhosis. Author(s): Fukushima N, Ikematsu H, Nakamura M, Matsui M, Shimoda S, Hayashida K, Niho Y, Koike K, Gershwin ME, Ishibashi H. Source: Journal of Autoimmunity. 2000 May; 14(3): 247-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10756087

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Open-label pilot study of tetracycline in the treatment of primary biliary cirrhosis. Author(s): Maddala YK, Jorgensen RA, Angulo P, Lindor KD. Source: The American Journal of Gastroenterology. 2004 March; 99(3): 566-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15056105

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Oral tolerance and pyruvate dehydrogenase in patients with primary biliary cirrhosis. Author(s): Suzuki A, Van de Water J, Gershwin ME, Jorgensen R, Angulo P, Lindor K. Source: Developmental Immunology. 2002 June; 9(2): 55-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12739782

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Orbital myositis in a patient with primary biliary cirrhosis: successful treatment with methotrexate and corticosteroids. Author(s): Magrini L, Rotiroti G, Conti F, Viganego F, Alessandri C, Picardo V, Valesini G. Source: Isr Med Assoc J. 2003 November; 5(11): 825-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14650113

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Osteopontin is involved in the formation of epithelioid granuloma and bile duct injury in primary biliary cirrhosis. Author(s): Harada K, Ozaki S, Sudo Y, Tsuneyama K, Ohta H, Nakanuma Y. Source: Pathology International. 2003 January; 53(1): 8-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12558864

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Osteoporosis in primary biliary cirrhosis. Author(s): Newton J, Jones D. Source: Panminerva Medica. 2002 December; 44(4): 335-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12434115

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Osteoporosis: still a typical complication of primary biliary cirrhosis? Author(s): Solerio E, Isaia G, Innarella R, Di Stefano M, Farina M, Borghesio E, Framarin L, Rizzetto M, Rosina F. Source: Dig Liver Dis. 2003 May; 35(5): 339-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12846406

Studies

55

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Overlap collagen vascular disease as a marker for development of primary biliary cirrhosis. Author(s): Smith KJ, Skelton H. Source: International Journal of Dermatology. 2002 July; 41(7): 390-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12121549

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Overlap syndrome between autoimmune hepatitis and primary biliary cirrhosis complicated by hepatocellular carcinoma. Author(s): Gheorghe L, Iacob S, Bolog N, Stoicescu A, Parvulescu I, Popescu I. Source: Rom J Gastroenterol. 2004 March; 13(1): 33-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15054524

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Oxidant stress is a significant feature of primary biliary cirrhosis. Author(s): Aboutwerat A, Pemberton PW, Smith A, Burrows PC, McMahon RF, Jain SK, Warnes TW. Source: Biochimica Et Biophysica Acta. 2003 March 20; 1637(2): 142-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12633902

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Peripheral blood T, B lymphocytes and NK cells in primary biliary cirrhosis. Author(s): Panasiuk A, Prokopowicz D, Zak J. Source: Rocz Akad Med Bialymst. 2001; 46: 231-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11780567

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Portal tract eosinophils and hepatocyte cytokeratin 7 immunoreactivity helps distinguish early-stage, mildly active primary biliary cirrhosis and autoimmune hepatitis. Author(s): Goldstein NS, Soman A, Gordon SC. Source: American Journal of Clinical Pathology. 2001 December; 116(6): 846-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11764073

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Primary biliary cirrhosis and CREST syndrome. Author(s): Marin Gabriel JC, Solis Herruzo JA. Source: Rev Esp Enferm Dig. 2004 March; 96(3): 219-20. English, Spanish. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15053737

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Primary biliary cirrhosis associated with ulcerative colitis. Author(s): Nakayama M, Tsuji H, Shimono J, Azuma K, Ogata H, Matsumoto T, Aoyagi K, Fujishima M, Iida M. Source: Fukuoka Igaku Zasshi. 2001 October; 92(10): 354-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11729641

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Primary biliary cirrhosis complicated with sigmoid colonic varices: the usefulness of computed tomographic angiography. Author(s): Kakizaki S, Ishikawa T, Koyama Y, Yamada H, Kobayashi R, Sohara N, Otsuka T, Takagi H, Mori M. Source: Abdominal Imaging. 2003 November-December; 28(6): 831-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14753600

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Primary biliary cirrhosis: for want of an X chromosome? Author(s): Kaplan MM, Bianchi DW. Source: Lancet. 2004 February 14; 363(9408): 505-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14975609

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Primary biliary cirrhosis: modalities of injury and death in biliary epithelium. Author(s): Marucci L, Ugili L, Macarri G, Feliciangeli G, Bendia E, Jezequel AM, Orlandi F, Benedetti A. Source: Dig Liver Dis. 2001 October; 33(7): 576-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11816547

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Primary biliary cirrhosis: new thoughts on pathophysiology and treatment. Author(s): Mason A, Nair S. Source: Current Gastroenterology Reports. 2002 February; 4(1): 45-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11825541

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Prolonged follow-up of patients in the U.S. multicenter trial of ursodeoxycholic acid for primary biliary cirrhosis. Author(s): Combes B, Luketic VA, Peters MG, Zetterman RK, Garcia-Tsao G, Munoz SJ, Lin D, Flye N, Carithers RL Jr. Source: The American Journal of Gastroenterology. 2004 February; 99(2): 264-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15046215

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Promoter polymorphism of the CD14 endotoxin receptor gene and primary biliary cirrhosis. Author(s): Corpechot C, Poupon R. Source: Hepatology (Baltimore, Md.). 2002 January; 35(1): 242-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11786986

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Qualitative and quantitative differences between bile ducts in chronic hepatitis and in primary biliary cirrhosis. Author(s): Rubio CA. Source: Journal of Clinical Pathology. 2000 October; 53(10): 765-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11064670

Studies

57

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Quality of life before and after liver transplantation: experiences with 7 patients with primary biliary cirrhosis in a 2-year follow-up. Author(s): Lahteenmaki A, Hockerstedt K, Kajaste S, Huttunen M. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1992; 5 Suppl 1: S705-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14621915

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Quality of life, major medical complications and hospital service utilization in patients with primary biliary cirrhosis after liver transplantation. Author(s): Navasa M, Forns X, Sanchez V, Andreu H, Marcos V, Borras JM, Rimola A, Grande L, Garcia-Valdecasas JC, Granados A, Rodes J. Source: Journal of Hepatology. 1996 August; 25(2): 129-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8878772

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Quantitation and phenotypic analysis of natural killer T cells in primary biliary cirrhosis using a human CD1d tetramer. Author(s): Kita H, Naidenko OV, Kronenberg M, Ansari AA, Rogers P, He XS, Koning F, Mikayama T, Van De Water J, Coppel RL, Kaplan M, Gershwin ME. Source: Gastroenterology. 2002 October; 123(4): 1031-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12360465

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Quantitative analysis of intrahepatic bile duct component in normal adult human liver and in primary biliary cirrhosis. Author(s): Casali AM, Siringo S, Sofia S, Bolondi L, Di Febo G, Cavalli G. Source: Pathology, Research and Practice. 1994 February; 190(2): 201-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8058574

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Quantitative analysis of macrophages and perisinusoidal cells in primary biliary cirrhosis. Author(s): Mathew J, Hines JE, Toole K, Johnson SJ, James OF, Burt AD. Source: Histopathology. 1994 July; 25(1): 65-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7959647

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Quantitative and functional analysis of PDC-E2-specific autoreactive cytotoxic T lymphocytes in primary biliary cirrhosis. Author(s): Kita H, Matsumura S, He XS, Ansari AA, Lian ZX, Van de Water J, Coppel RL, Kaplan MM, Gershwin ME. Source: The Journal of Clinical Investigation. 2002 May; 109(9): 1231-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11994412

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Quantitative measurement of autoantibodies to recombinant mitochondrial antigens in patients with primary biliary cirrhosis: relationship of levels of autoantibodies to disease progression. Author(s): Van Norstrand MD, Malinchoc M, Lindor KD, Therneau TM, Gershwin ME, Leung PS, Dickson ER, Homburger HA. Source: Hepatology (Baltimore, Md.). 1997 January; 25(1): 6-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8985257

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Quantitative testing of liver function compared to prognostic scores in patients with primary biliary cirrhosis. Author(s): Herold C, Ganslmayer M, Deynet C, Hahn EG, Schuppan D. Source: Liver. 2002 April; 22(2): 159-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12028411

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Randomized pilot trial of vitamin K2 for bone loss in patients with primary biliary cirrhosis. Author(s): Nishiguchi S, Shimoi S, Kurooka H, Tamori A, Habu D, Takeda T, Kubo S. Source: Journal of Hepatology. 2001 October; 35(4): 543-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11682046

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Recurrence of primary biliary cirrhosis after liver transplantation. Author(s): Salguero O, Moreno JM, Seijas MC, Rubio E, Salas C, Laporta R, CuervasMons V. Source: Transplantation Proceedings. 2003 March; 35(2): 721-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644111

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Recurrence of primary biliary cirrhosis after liver transplantation: Histologic estimate of incidence and natural history. Author(s): Sylvestre PB, Batts KP, Burgart LJ, Poterucha JJ, Wiesner RH. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 October; 9(10): 1086-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14526404

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Recurrence of primary biliary cirrhosis after orthotopic liver transplantation. Author(s): Kurdow R, Marks HG, Kraemer-Hansen H, Luttges J, Kremer B, HenneBruns D. Source: Hepatogastroenterology. 2003 March-April; 50(50): 322-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12749212

Studies

59

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Recurrent primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis after transplantation. Author(s): Faust TW. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2001 November; 7(11 Suppl 1): S99-108. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11689782

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Recurrent primary biliary cirrhosis. Author(s): Neuberger J. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 June; 9(6): 539-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12783392

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Reduction of CD45RA isoform expression and decrease in CD4 and CD8 receptor density in lymphocytes of patients with primary biliary cirrhosis. Author(s): Musialik J, Michalkiewicz J, Petelenz M, Mazurek U, Mazur W, Madalinski K, Gonciarz Z. Source: Scandinavian Journal of Gastroenterology. 2003 April; 38(4): 421-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12739715

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Retrovirus infection as a trigger for primary biliary cirrhosis? Author(s): Poupon R, Poupon RE. Source: Lancet. 2004 January 24; 363(9405): 260-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14751695

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Rheumatic disorders and primary biliary cirrhosis: an appraisal of 170 Italian patients. Author(s): Marasini B, Gagetta M, Rossi V, Ferrari P. Source: Annals of the Rheumatic Diseases. 2001 November; 60(11): 1046-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11602476

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Role of apoptosis in development of primary biliary cirrhosis. Author(s): Marzioni M, Glaser SS, Alpini G, LeSage GD. Source: Dig Liver Dis. 2001 October; 33(7): 531-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11816539

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Safety and efficacy of estrogen therapy in preventing bone loss in primary biliary cirrhosis. Author(s): Menon KV, Angulo P, Boe GM, Lindor KD. Source: The American Journal of Gastroenterology. 2003 April; 98(4): 889-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738473

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Serum hepatocyte growth factor levels in primary biliary cirrhosis. Author(s): Rudi J, Waldherr R, Raedsch R, Stremmel W. Source: European Journal of Gastroenterology & Hepatology. 1995 November; 7(11): 1081-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8680908

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Sex hormone profile and endometrial cancer risk in primary biliary cirrhosis: a casecontrol study. Author(s): Floreani A, Paternoster D, Mega A, Farinati F, Plebani M, Baldo V, Grella P. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2002 July 10; 103(2): 154-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12069739

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Short-term outcomes of living-related liver transplantation for primary biliary cirrhosis and its recurrence: report of five cases. Author(s): Takeishi T, Sato Y, Ichida T, Yamamoto S, Kobayashi T, Hatakeyama K. Source: Transplantation Proceedings. 2003 February; 35(1): 372. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12591445

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Similarity between hepatic graft-versus-host disease and primary biliary cirrhosis. Author(s): Wakae T, Takatsuka H, Seto Y, Iwata N, Mori A, Okada M, Fujimori Y, Okamoto T, Kakishita E, Hara H. Source: Hematology (Amsterdam, Netherlands). 2002 October; 7(5): 305-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12850818

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Simvastatin in primary biliary cirrhosis: effects on serum lipids and distinct disease markers. Author(s): Ritzel U, Leonhardt U, Nather M, Schafer G, Armstrong VW, Ramadori G. Source: Journal of Hepatology. 2002 April; 36(4): 454-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11943414

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Single nucleotide polymorphisms of the mannose-binding lectin are associated with susceptibility to primary biliary cirrhosis. Author(s): Matsushita M, Miyakawa H, Tanaka A, Hijikata M, Kikuchi K, Fujikawa H, Arai J, Sainokami S, Hino K, Terai I, Mishiro S, Gershwin ME. Source: Journal of Autoimmunity. 2001 November; 17(3): 251-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11712863

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Steroid withdrawal under tacrolimus for primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis after liver transplantation and long-term survival. Author(s): Jain A, Pokharna R, Eghtesad B, Potdar S, Kashyap R, Kingery L, Fung J. Source: Transplantation Proceedings. 2002 August; 34(5): 1524-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12176467

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Structural and oxidative modifications of erythrocyte ghosts in patients with primary biliary cirrhosis: relation with the disease stage and effect of bile acid treatment. Author(s): Grattagliano I, Giudetti AM, Grattagliano V, Palmieri VO, Gnoni GV, Lapadula G, Palasciano G, Vendemiale G. Source: European Journal of Clinical Investigation. 2003 October; 33(10): 868-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14511358

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Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis: follow-up for up to 28 years. Author(s): Prince M, Chetwynd A, Newman W, Metcalf JV, James OF. Source: Gastroenterology. 2002 October; 123(4): 1044-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12360466

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Tamoxifen in treatment of primary biliary cirrhosis. Author(s): Invernizzi P, Alvaro D, Crosignani A, Gaudio E, Podda M. Source: Hepatology (Baltimore, Md.). 2004 April; 39(4): 1175-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15057925

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T-cell receptor polymorphism in primary biliary cirrhosis. Author(s): Selmi C, Invernizzi P, Tripputi P, Battezzati PM, Bignotto M, Zuin M, Crosignani A, Podda M. Source: Ann Ital Med Int. 2003 July-September; 18(3): 149-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14621425

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The changing clinical presentation of recurrent primary biliary cirrhosis after liver transplantation. Author(s): Sanchez EQ, Levy MF, Goldstein RM, Fasola CG, Tillery GW, Netto GJ, Watkins DL, Weinstein JS, Murray NG, Byers D, Christensen LL, Klintmalm GB. Source: Transplantation. 2003 December 15; 76(11): 1583-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14702528

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The epidemiology of primary biliary cirrhosis. Author(s): Prince MI, James OF. Source: Clinics in Liver Disease. 2003 November; 7(4): 795-819. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594132

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The geographical distribution of primary biliary cirrhosis in a well-defined cohort. Author(s): Prince MI, Chetwynd A, Diggle P, Jarner M, Metcalf JV, James OF. Source: Hepatology (Baltimore, Md.). 2001 December; 34(6): 1083-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11731995

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The natural history of primary biliary cirrhosis: of genes and cooperation. Author(s): Gershwin ME. Source: Journal of Hepatology. 2001 September; 35(3): 412-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11592604

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The use of ursodeoxycholic acid in patients with primary biliary cirrhosis: sense or nonsense. Author(s): Van Den Bogaert E, Francque S, Pelckmans P, Michielsen P. Source: Acta Gastroenterol Belg. 2003 October-December; 66(4): 283-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14989050

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Treatment of primary biliary cirrhosis. Author(s): Szalay F. Source: Journal of Physiology, Paris. 2001 January-December; 95(1-6): 407-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11595467

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Treatment with ursodeoxycholic acid is associated with weight gain in patients with primary biliary cirrhosis. Author(s): Siegel JL, Jorgensen R, Angulo P, Lindor KD. Source: Journal of Clinical Gastroenterology. 2003 August; 37(2): 183-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869893

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Trials in primary biliary cirrhosis: need for the right drugs at the right time. Author(s): Poupon R. Source: Hepatology (Baltimore, Md.). 2004 April; 39(4): 900-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15057890

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Ultrastructural and cytochemical changes in the liver of primary biliary cirrhosis patients. Author(s): Jorge AD, Gutierrez LS, Jorge O, Burgos MH. Source: Biocell. 2002 August; 26(2): 253-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12240560

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Unusual suspects in primary biliary cirrhosis. Author(s): Vergani D, Bogdanos DP, Baum H. Source: Hepatology (Baltimore, Md.). 2004 January; 39(1): 38-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752820

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Up-regulation of CD11a (LFA-1) expression on peripheral CD4+ T cells in primary biliary cirrhosis. Author(s): Shiina M, Kobayashi K, Mano Y, Ueno Y, Ishii M, Shimosegawa T. Source: Digestive Diseases and Sciences. 2002 June; 47(6): 1209-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12064793

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Ursodeoxycholic acid and long-term survival in primary biliary cirrhosis. Author(s): Levy C, Angulo P. Source: The American Journal of Gastroenterology. 2004 February; 99(2): 269-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15046216

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Ursodeoxycholic acid and primary biliary cirrhosis with features of autoimmune hepatitis. Author(s): Chazouilleres O, Poupon R. Source: Hepatology (Baltimore, Md.). 2002 October; 36(4 Pt 1): 1026-7; Author Reply 1027. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12297861

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Ursodeoxycholic acid enhances fractional calcium absorption in primary biliary cirrhosis. Author(s): Verma A, Maxwell JD, Ang L, Davis T, Hodges S, Northfield TC, Zaidi M, Pazianas M. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 August; 13(8): 677-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12181628

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Ursodeoxycholic acid for primary biliary cirrhosis: final results of a 12-year, prospective, randomized, controlled trial. Author(s): Papatheodoridis GV, Hadziyannis ES, Deutsch M, Hadziyannis SJ. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 2063-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12190178

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Ursodeoxycholic acid for primary biliary cirrhosis: treat early to slow progression. Author(s): Paumgartner G. Source: Journal of Hepatology. 2003 July; 39(1): 112-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821052

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Ursodeoxycholic acid therapy and the risk of colorectal adenoma in patients with primary biliary cirrhosis: an observational study. Author(s): Serfaty L, De Leusse A, Rosmorduc O, Desaint B, Flejou JF, Chazouilleres O, Poupon RE, Poupon R. Source: Hepatology (Baltimore, Md.). 2003 July; 38(1): 203-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12830003

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Ursodeoxycholic acid therapy attenuated expression of adhesion molecule in primary biliary cirrhosis. Author(s): Yokomori H, Oda M, Wakabayashi G, Kitajima M, Ishii H. Source: Intern Med. 2003 December; 42(12): 1259-61. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14714971

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Vaginal variceal hemorrhage in a patient with primary biliary cirrhosis: a case successfully treated by balloon-occluded retrograde transvenous obliteration. Author(s): Hoshida Y, Saitoh S, Murashima N, Ogawa A, Arase Y, Kobayashi M, Suzuki Y, Tsubota A, Chayama K, Ikeda K, Kumada H. Source: The American Journal of Gastroenterology. 1999 October; 94(10): 3081-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10520888

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Validation of a fatigue impact score in primary biliary cirrhosis: towards a standard for clinical and trial use. Author(s): Prince MI, James OF, Holland NP, Jones DE. Source: Journal of Hepatology. 2000 March; 32(3): 368-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10735604

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Variceal bleeding is associated with reduced risk of severe cholestasis in primary biliary cirrhosis. Author(s): Thornton JR, Triger DR, Losowsky MS. Source: The Quarterly Journal of Medicine. 1989 May; 71(265): 467-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2602544

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Vascular impairment in patients with primary biliary cirrhosis. Author(s): Marasini B, Pipia C, DeValle G, Crosignani A, Petroni L, Cugno M, Zeni S, Bruno S, Bassani C. Source: Int J Microcirc Clin Exp. 1995 March-April; 15(2): 75-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8655255

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Vasculitis in primary biliary cirrhosis--response to prednisolone. Author(s): Mutimer DJ, Bassendine MF, Crook P, James OF. Source: The Quarterly Journal of Medicine. 1990 May; 75(277): 509-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2388998

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Visual field changes following hepatic transplantation in a patient with primary biliary cirrhosis. Author(s): Grey RH. Source: The British Journal of Ophthalmology. 1991 June; 75(6): 377-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2043586

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Vitamin D receptor gene analysis in primary biliary cirrhosis. Author(s): Resnick RH, Chopra S. Source: Gastroenterology. 2000 December; 119(6): 1805. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11187436

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Vitamin D receptor, oestrogen receptor-alpha gene and interleukin-1 receptor antagonist gene polymorphisms in Hungarian patients with primary biliary cirrhosis. Author(s): Lakatos LP, Bajnok E, Hegedus D, Toth T, Lakatos P, Szalay F. Source: European Journal of Gastroenterology & Hepatology. 2002 July; 14(7): 733-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12169981

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Vitamin D-receptor genotypes as independent genetic predictors of decreased bone mineral density in primary biliary cirrhosis. Author(s): Springer JE, Cole DE, Rubin LA, Cauch-Dudek K, Harewood L, Evrovski J, Peltekova VD, Heathcote EJ. Source: Gastroenterology. 2000 January; 118(1): 145-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10611163

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Vitamin E deficiency and psychomotor dysfunction in adults with primary biliary cirrhosis. Author(s): Arria AM, Tarter RE, Warty V, Van Thiel DH. Source: The American Journal of Clinical Nutrition. 1990 August; 52(2): 383-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1973868

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When is liver biopsy needed in the diagnosis of primary biliary cirrhosis? Author(s): Zein CO, Angulo P, Lindor KD. Source: Clin Gastroenterol Hepatol. 2003 March; 1(2): 89-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017500

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Yes, hepatocellular cancer does occur in primary biliary cirrhosis. Author(s): Gores GJ. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 June; 8(6): 570-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12037792

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CHAPTER 2. NUTRITION AND BILIARY CIRRHOSIS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and biliary cirrhosis.

Finding Nutrition Studies on Biliary Cirrhosis 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 “biliary cirrhosis” (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 information is typical of that found when using the “Full IBIDS Database” to search for “biliary cirrhosis” (or a synonym): •

A female with asymptomatic primary biliary cirrhosis associated with pernicious anemia. Author(s): Third Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan. [email protected] Source: Takahashi, T Honma, T Ishizuka, K Fuse, I Asakura, H J-Gastroenterol-Hepatol. 2001 December; 16(12): 1420-4 0815-9319

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A rare association of primary biliary cirrhosis and pernicious anemia. Author(s): First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. Source: Aoyama, H Sakugawa, H Nakasone, H Nakayoshi, T Kinjo, A Tamayose, M Higa, H Uema, E Chinen, T Tomiyama, R Uchima, N Kugai, Y Kinjo, F Saito, A Kinjo, M J-Gastroenterol. 2002; 37(7): 560-3 0944-1174

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Autoimmune hemolysis associated with primary biliary cirrhosis responding to ursodeoxycholic acid as sole treatment. Author(s): Sydney University Department of Medicine, Nepean Hospital, Penrith, New South Wales, Australia. [email protected] Source: Fuller, S J KuMarch, P Weltman, M Wiley, J S Am-J-Hematol. 2003 January; 72(1): 31-3 0361-8609

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Detection of anti-branched chain 2-oxo acid dehydrogenase complex (BCOADC)-E2 antibody in primary biliary cirrhosis by ELISA using recombinant fusion protein. Author(s): Fourth Department of Internal Medicine, Teikyo University School of Medicine, Kanagawa, Japan. Source: Miyakawa, H Abe, K Kitazawa, E Kikuchi, K Fujikawa, H Matsushita, M Kawaguchi, N Kako, M Autoimmunity. 1999; 30(1): 11-20 0891-6934

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Immune dysfunction in primary biliary cirrhosis (PBC): I. Increased sensitivity of PHA stimulated lymphocyte cultures to indomethacin. Source: Licastro, F Lenzi, M Chiricolo, M Davis, L J Cassani, F Bianchi, F Franceschi, C JClin-Lab-Immunol. 1987 May; 23(1): 19-23 0141-2760

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Immunoreactivity of porcine heart dihydrolipoamide acetyl- and succinyltransferases (PDC-E2, OGDC-E2) with primary biliary cirrhosis sera: characterization of the autoantigenic region and effects of enzymatic delipoylation and relipoylation. Author(s): Department of Pathological Biochemistry, Atomic Disease Institute, Nagasaki University School of Medicine, Japan. Source: Koike, K Ishibashi, H Koike, M Hepatology. 1998 June; 27(6): 1467-74 0270-9139

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Primary biliary cirrhosis associated with type A gastritis and chronic thyroiditis. Author(s): Department of Gastroenterology, Saiseikai Kanazawa Hospital, Kanazawa, Japan. Source: Wakabayashi, T Ohno, H Hayakawa, Y Kawashima, A Sawabu, N JGastroenterol. 1999 June; 34(3): 415-9 0944-1174

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The influence of sulindac on patients with primary biliary cirrhosis that responds incompletely to ursodeoxycholic acid: a pilot study. Author(s): Medical Clinic II, Johann Wolfgang Goethe Universitat, Frankfurt am Main, Germany. Source: Leuschner, M Holtmeier, J Ackermann, H Leuschner, U Eur-J-GastroenterolHepatol. 2002 December; 14(12): 1369-76 0954-691X

Nutrition

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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The following is a specific Web list relating to biliary cirrhosis; 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: •

Minerals Calcium Source: Healthnotes, Inc.; www.healthnotes.com Calcium: Which Form Is Best? Source: Healthnotes, Inc.; www.healthnotes.com

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Food and Diet Chocolate Source: Healthnotes, Inc.; www.healthnotes.com

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

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

Accelerated nonproteolytic cleavage of C3 in plasma from patients with primary biliary cirrhosis. Author(s): Lindgren S. Source: The Journal of Laboratory and Clinical Medicine. 1989 December; 114(6): 655-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2531785

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Adjuvant cholylsarcosine during ursodeoxycholic acid treatment of primary biliary cirrhosis. Author(s): Ricci P, Hofmann AF, Hagey LR, Jorgensen RA, Rolland Dickson E, Lindor KD. Source: Digestive Diseases and Sciences. 1998 June; 43(6): 1292-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9635620

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Antifibrotic effect of silymarin in rat secondary biliary fibrosis is mediated by downregulation of procollagen alpha1(I) and TIMP-1. Author(s): Jia JD, Bauer M, Cho JJ, Ruehl M, Milani S, Boigk G, Riecken EO, Schuppan D. Source: Journal of Hepatology. 2001 September; 35(3): 392-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11592601

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C1 dissociation in serum: estimation of free C1q by electroimmunoassay. Author(s): Sjoholm AG, Martensson U, Laurell AB. Source: Acta Pathol Microbiol Immunol Scand [c]. 1985 August; 93(4): 161-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3876685

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Characterization of autoantibodies against uridine-diphosphate glucuronosyltransferase in patients with inflammatory liver diseases. Author(s): Bachrich T, Thalhammer T, Jager W, Haslmayer P, Alihodzic B, Bakos S, Hitchman E, Senderowicz AM, Penner E. Source: Hepatology (Baltimore, Md.). 2001 May; 33(5): 1053-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343231

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Clinical studies with silymarin: fibrosis progression is the end point. Author(s): Schuppan D, Hahn EG. Source: Hepatology (Baltimore, Md.). 2001 February; 33(2): 483-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11172360

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Complement activation in primary biliary cirrhosis: an in vitro model. Author(s): Lindgren S, Johnson U. Source: The Journal of Laboratory and Clinical Medicine. 1985 April; 105(4): 432-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3872338

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Complement components and activation in primary biliary cirrhosis. Author(s): Lindgren S, Laurell AB, Eriksson S. Source: Hepatology (Baltimore, Md.). 1984 January-February; 4(1): 9-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6420306

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Drug-induced cholestasis. Author(s): Chitturi S, Farrell GC. Source: Semin Gastrointest Dis. 2001 April; 12(2): 113-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11352118

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Effect of a medium dose of ursodeoxycholic acid with or without taurine supplementation on the nutritional status of patients with cystic fibrosis: a randomized, placebo-controlled, crossover trial.

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Author(s): Merli M, Bertasi S, Servi R, Diamanti S, Martino F, De Santis A, Goffredo F, Quattrucci S, Antonelli M, Angelico M. Source: Journal of Pediatric Gastroenterology and Nutrition. 1994 August; 19(2): 198-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7815243 •

Effect of dietary fiber on serum bile acids in patients with chronic cholestatic liver disease under ursodeoxycholic acid therapy. Author(s): Sauter G, Beuers U, Paumgartner G. Source: Digestion. 1995; 56(6): 523-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8536824

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Effects of selenium supplementation on blood and urine selenium levels and liver function in patients with primary biliary cirrhosis. Author(s): Valimaki M, Alfthan G, Vuoristo M, Ylikahri R. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1991 January 31; 196(1): 7-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2022060

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Grapefruit juice for the pruritus of cholestatic liver disease. Author(s): Cadranel JF, Di Martino V, Devergie B. Source: Annals of Internal Medicine. 1997 June 1; 126(11): 920-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9163307

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High cholestanol and low campesterol-to-sitosterol ratio in serum of patients with primary biliary cirrhosis before liver transplantation. Author(s): Nikkila K, Hockerstedt K, Miettinen TA. Source: Hepatology (Baltimore, Md.). 1991 April; 13(4): 663-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2010161

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High serum cholestanol and low campesterol/sitosterol ratio indicate severe liver damage and liver transplantation in primary biliary cirrhosis. Author(s): Nikkila K, Hockerstedt K, Miettinen TA. Source: Transplantation Proceedings. 1992 February; 24(1): 383-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1539326

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Is oriental folk use of bear bile vindicated (yet)? Author(s): Achord JL. Source: Gastroenterology. 1990 April; 98(4): 1090-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2311865

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Isolation of circulating immune complexes by conglutinin and separation of antigen from dissociated complexes by immobilized protein A. Author(s): Gupta RC, Tan EM.

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Source: Clinical and Experimental Immunology. 1981 October; 46(1): 9-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7337970 •

Langerhans' cell histiocytosis presenting with hepatic dysfunction. Author(s): Squires RH Jr, Weinberg AG, Zwiener RJ, Winick N. Source: Journal of Pediatric Gastroenterology and Nutrition. 1993 February; 16(2): 190-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8450389

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Lipoprotein binding to cultured human hepatoma cells. Author(s): Krempler F, Kostner GM, Friedl W, Paulweber B, Bauer H, Sandhofer F. Source: The Journal of Clinical Investigation. 1987 August; 80(2): 401-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3038957

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Liver copper content in patients with inflammatory bowel disease and associated liver disorders. Author(s): Ritland S, Elgjo K, Johansen O, Steinnes E. Source: Scandinavian Journal of Gastroenterology. 1979; 14(6): 711-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=531503

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Liver transplantation modifies serum cholestanol, cholesterol precursor and plant sterol levels. Author(s): Nikkila K, Hockerstedt K, Miettinen TA. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1992 June 30; 208(3): 205-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1499139

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Nucleotide pyrophosphatase and phosphodiesterase I. Demonstration of activity in normal serum, and an increase in cholestatic liver disease. Author(s): Haugen HF, Skrede S. Source: Scandinavian Journal of Gastroenterology. 1976; 11(2): 121-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4880

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Oral antioxidant supplementation for fatigue associated with primary biliary cirrhosis: results of a multicentre, randomized, placebo-controlled, cross-over trial. Author(s): Prince MI, Mitchison HC, Ashley D, Burke DA, Edwards N, Bramble MG, James OF, Jones DE. Source: Alimentary Pharmacology & Therapeutics. 2003 January; 17(1): 137-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12492743

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Peritoneo-venous shunting for ascites. Author(s): Leveen HH, Christoudias G, Ip M, Luft R, Falk G, Grosberg S.

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Source: Annals of Surgery. 1974 October; 180(4): 580-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4415019 •

Precursor of 27-nor-5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 24,25-pentol in man. Author(s): Karlaganis G, Bremmelgaard A, Karlaganis V, Sjovall J. Source: J Steroid Biochem. 1983 June; 18(6): 725-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6865414

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Prescribing habits in primary biliary cirrhosis: a national survey. Author(s): Verma A, Jazrawi RP, Ahmed HA, Northfield TC. Source: European Journal of Gastroenterology & Hepatology. 1999 August; 11(8): 817-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10514110

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Regulation of the hepatic endothelin system in advanced biliary fibrosis in rats. Author(s): Rothermund L, Leggewie S, Schwarz A, Thone-Reinecke C, Cho JJ, Bauer C, Paul M, Neumayer HH, Schuppan D, Hocher B. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2000 June; 38(6): 507-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10987198

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Serum 27-hydroxycholesterol in patients with primary biliary cirrhosis suggests alteration of cholesterol catabolism to bile acids via the acidic pathway. Author(s): Del Puppo M, Kienle MG, Petroni ML, Crosignani A, Podda M. Source: Journal of Lipid Research. 1998 December; 39(12): 2477-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9831637

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Serum cholestanol, cholesterol precursors, and plant sterols during placebocontrolled treatment of primary biliary cirrhosis with ursodeoxycholic acid or colchicine. Author(s): Miettinen TA, Farkkila M, Vuoristo M, Karvonen AL, Leino R, Lehtola J, Friman C, Seppala K, Tuominen J. Source: Hepatology (Baltimore, Md.). 1995 May; 21(5): 1261-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7737632

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Serum cholesterol precursors, cholestanol, and plant sterols in primary biliary cirrhosis. Author(s): Nikkila K, Miettinen TA. Source: Scandinavian Journal of Gastroenterology. 1988 October; 23(8): 967-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3201135

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Silymarin in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid. Author(s): Angulo P, Patel T, Jorgensen RA, Therneau TM, Lindor KD.

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Source: Hepatology (Baltimore, Md.). 2000 November; 32(5): 897-900. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11050036 •

Special issue dedicated in memory of Dr. Edward H. Ahrens, Jr. Author(s): Ahrens EH Jr. Source: Cardiovasc Drug Rev. 2002 Winter; 20(4): 237-343. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12481196

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Suppression of proliferative cholangitis in a rat model by local delivery of paclitaxel. Author(s): Park SM, Choi JW, Kim ST, Cho MC, Sung RH, Jang LC, Park JW, Lee SP, Park YH. Source: Journal of Hepato-Biliary-Pancreatic Surgery. 2003; 10(2): 176-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14505153

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The flavonoid quercetin ameliorates liver damage in rats with biliary obstruction. Author(s): Peres W, Tunon MJ, Collado PS, Herrmann S, Marroni N, Gonzalez-Gallego J. Source: Journal of Hepatology. 2000 November; 33(5): 742-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11097482

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The metabolism of cholestanol in primary biliary cirrhosis. Author(s): Gylling H, Vuoristo M, Farkkila M, Miettinen TA. Source: Journal of Hepatology. 1996 April; 24(4): 444-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8738731

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The pathobiology of biliary epithelia. Author(s): Alpini G, McGill JM, Larusso NF. Source: Hepatology (Baltimore, Md.). 2002 May; 35(5): 1256-68. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11981776

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The relief of pruritus in primary biliary cirrhosis by hydroxyethylrutosides. Author(s): Hishon S, Rose JD, Hunter JO. Source: The British Journal of Dermatology. 1981 October; 105(4): 457-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7295558

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The UDCA dosage deficit: a fate shared with CDCA. Author(s): Roda E, Liva S, Ferrara F, Azzaroli F, Giovanelli S, Nigro G, Festi D, Mazzella G. Source: European Journal of Gastroenterology & Hepatology. 2002 March; 14(3): 213-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11953683

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Treatment of progressive familial intrahepatic cholestasis: liver transplantation or partial external biliary diversion.

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Author(s): Ismail H, Kalicinski P, Markiewicz M, Jankowska I, Pawlowska J, Kluge P, Eliadou E, Kaminski A, Szymczak M, Drewniak T, Revillon Y. Source: Pediatric Transplantation. 1999 August; 3(3): 219-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10487283

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

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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

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

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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

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

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

General Overview Liver Cirrhosis Source: Healthnotes, Inc.; www.healthnotes.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html.

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This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON BILIARY CIRRHOSIS Overview In this chapter, we will give you a bibliography on recent dissertations relating to biliary cirrhosis. 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 “biliary cirrhosis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on biliary cirrhosis, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Biliary Cirrhosis 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 biliary cirrhosis. 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: •

Predicting outcomes post liver transplantation in patients with primary biliary cirrhosis and primary sclerosing cholangitis by Zapatochny Rufo, Rebecca Jo; DNSc from Rush University, College of Nursing, 2003, 95 pages http://wwwlib.umi.com/dissertations/fullcit/3108984

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. BOOKS ON BILIARY CIRRHOSIS Overview This chapter provides bibliographic book references relating to biliary cirrhosis. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on biliary cirrhosis 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 “biliary cirrhosis” (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 biliary cirrhosis: •

Primary Biliary Cirrhosis: From Pathogenesis to Clinical Treatment Source: Boston, MA: Kluwer Academic Publishers. 1998. 176 p. Contact: Available from Kluwer Academic Publishers. Customer Service Deparment, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. Summary: This monograph reprints papers from a conference held in November 1997 in Chicago, Illinois, on the clinical features (symptoms), pathogenesis, and treatment of primary biliary cirrhosis (PBC). PBC is generally considered to be an autoimmune disease and one that occurs in patients who are genetically predisposed to the disease. The part played by mitochondrial antibodies (AMA) in pathogenesis of PBC remains controversial. Alternatively, the disease may have an infectious etiology (cause). Therapy can be directed against any of these injurious processes. Drug therapy, notably

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combinations of drugs, can be used. Fibrosis (scarring) of the bile ducts occurs in PBC and is responsible for the end picture of cirrhosis (liver scarring). Complications such as ascites (fluid accumulation) and portal hypertension (high blood pressure) need to be treated; other complications can include bone thinning and pruritus (itching). Liver (hepatic) transplantation performed before the terminal stages of PBC offers a five year survival exceeding 85 percent. There is evidence of recurrence in the graft. The monograph includes 20 chapters covering the natural history and demography of PBC, the immune basis for PBC, isolation and cloning of antimitochondrial antibodies, determining pathogenesis, molecular considerations of PBC, animal models of PBC, fibrogenesis in PBC, natural history models, portal hypertension in patients with PBC, osteoporosis, managing fatigue in the patients with PBC, pruritus associated with cholestasis (suppression of the flow of bile), immunosuppressant agents, methotrexate and colchicine in the treatment of PBC, corticosteroids in PBC, ursodeoxycholic acid treatment of PBC, ursodiol and combination therapy, transplantation, and new clinical trials in PBC. Each chapter concludes with references and a subject index concludes the monograph.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “biliary cirrhosis” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “biliary cirrhosis” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “biliary cirrhosis” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Primary Biliary Cirrhosis - From Pathogenesis to Clinical Treatment by Keith D. Lindor (Editor), et al; ISBN: 0792387406; http://www.amazon.com/exec/obidos/ASIN/0792387406/icongroupinterna

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

Primary Biliary Cirrhosis: Diagnosis and Treatment Source: in McDonald, J.W.D.; Burroughs, A.K.; Feagan, B.G., eds. Evidence Based Gastroenterology and Hepatology. London, UK: BMJ Publishing Group. 1999. p. 345359.

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Contact: Available from BMJ Publishing Group. BMA Books, BMA House, Tavistock Square, London WCIH 9JR. Fax 44 (0)20 7383 6402. E-mail: [email protected]. Website: www.bmjbooks.com. PRICE: Contact publisher for price. Summary: Primary biliary cirrhosis (PBC) is an inflammatory disease of the interlobular and septal bile ducts of the liver; the disease is thought to be immune-mediated. Granulomatous destruction of these bile ducts leads to duct deficiency and hence, persistent cholestasis (stoppage of the flow of bile). Progressive fibrosis and eventual cirrhosis develop and liver failure is a terminal event unless intervention with a liver transplant occurs. This chapter on the diagnosis and treatment of PBC is from a book that emphasizes the approaches of evidence based medicine in gastroenterology (the study of the gastrointestinal tract and gastrointestinal diseases) and hepatology (the study of the liver and liver diseases). The author of this chapter notes that PBC may be diagnosed in several situations. Most commonly (60 percent of the time), PBC is diagnosed in a patient without symptoms, but with anicteric cholestatic biochemical tests, with a positive serological test for AMA (antimitochondrial antibodies), and with a diagnostic or confirmatory biopsy. Symptoms typical of PBC, such as fatigue, do not correlate with the severity of disease. However, the degree of hyperbilirubinemia has been shown to correlate extremely well with survival. Treatment with ursodeoxycholic acid (UDCA) is not curative. It may delay the progression of disease in some patients, but the evidence for this benefit is not clear. Several small trials of UDCA in combination with methotrexate, colchicine, and prednisolone have been conducted, but no study has been large enough to adequately assess the effectiveness of these drugs. Prognostic research indicates that liver transplantation leads to a marked survival benefit in patients with PBC. Currently, transplantation remains the only curative therapy for this disease. 1 table. 91 references.

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CHAPTER 6. PERIODICALS AND NEWS ON BILIARY CIRRHOSIS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover biliary cirrhosis.

News Services and Press Releases One of the simplest ways of tracking press releases on biliary cirrhosis 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 “biliary cirrhosis” (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 biliary cirrhosis. 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 “biliary cirrhosis” (or synonyms). The following was recently listed in this archive for biliary cirrhosis: •

Prevalence of primary biliary cirrhosis in US exceeds rates in Europe Source: Reuters Medical News Date: December 20, 2000

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•

Case of primary biliary cirrhosis after erythromycin therapy documented Source: Reuters Medical News Date: July 17, 2000

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Use of ursodeoxycholic acid by patients with biliary cirrhosis questioned Source: Reuters Medical News Date: September 24, 1999

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High risk of primary biliary cirrhosis identified in patients with celiac disease Source: Reuters Medical News Date: May 19, 1999

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Risk factors for progression of asymptomatic primary biliary cirrhosis remain elusive Source: Reuters Medical News Date: February 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 “biliary cirrhosis” (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 “biliary cirrhosis” (or synonyms). If you know the name of a company that is relevant to biliary cirrhosis, you can go to any stock trading Web site (such as http://www.etrade.com/)

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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 “biliary cirrhosis” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “biliary cirrhosis” (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 biliary cirrhosis: •

Sjogren's Syndrome and the Gastrointestinal Tract Source: Moisture Seekers Newsletter. 17(2): 1, 4-5. March 1999. Contact: Available from Sjogren's Syndrome Foundation, Inc. 8120 Woodmont Avenue, Suite 530, Bethesda, MD 20814-1437. (301) 718-0300 or (800) 475-6473. Fax (301) 718-0322. Website: www.sjogrens.org. Summary: This article on Sjogren's syndrome (SS) and the gastrointestinal tract is from a patient education newsletter for people with SS. The author outlines the areas where the gastroenterologist may play a role in caring for the person with SS, such as dealing with swallowing difficulties, dyspepsia (indigestion), diarrhea, and jaundice (usually due to primary biliary cirrhosis, or scarring). Difficulty in swallowing is usually due to the lack of saliva associated with SS, but occasionally it may be due to a blockage (postcricoid web) or a weakness of the muscle contractions involved in swallowing. In addition, those patients with SS are vulnerable to acid reflux, which causes heartburn symptoms. Children with SS are prone to achalasia, a type of muscle problem involving the lower esophageal sphincter. Dyspepsia (indigestion) is relatively common in patients with SS, as is inflammation of the stomach (gastritis). The author briefly discusses the role of the bacterium Helicobacter pylori in gastritis. There are at least two diseases associated with SS and diarrhea: chronic pancreatitis and celiac disease (gluten intolerance). The author notes that the link between SS and gastroenterological conditions is often via abnormal autoantibodies.

Academic Periodicals covering Biliary Cirrhosis Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to biliary cirrhosis. In addition to these sources, you can search for articles covering biliary cirrhosis that have been

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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 7. 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 biliary cirrhosis. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP).

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Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to biliary cirrhosis by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “biliary cirrhosis” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for

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marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for biliary cirrhosis: •

Ursodiol (trade name: URSO) http://www.rarediseases.org/nord/search/nodd_full?code=256

•

Ursodiol (trade name: Actigall) http://www.rarediseases.org/nord/search/nodd_full?code=262

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 Institute8: •

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/

8

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.9 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:10 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

9

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). 10 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 Gateway11 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.12 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “biliary cirrhosis” (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 6818 22 912 6 38 7796

HSTAT13 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.14 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.15 Simply search by “biliary cirrhosis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

11

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

12

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). 13 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 14 15

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 Biologists16 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.17 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.18 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/.

16 Adapted 17

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 18 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.

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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 biliary cirrhosis 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 biliary cirrhosis. 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 biliary cirrhosis. 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 “biliary cirrhosis”:

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Bile Duct Diseases http://www.nlm.nih.gov/medlineplus/bileductdiseases.html Cirrhosis http://www.nlm.nih.gov/medlineplus/cirrhosis.html Gallbladder Diseases http://www.nlm.nih.gov/medlineplus/gallbladderdiseases.html Liver Diseases http://www.nlm.nih.gov/medlineplus/liverdiseases.html Liver Transplantation http://www.nlm.nih.gov/medlineplus/livertransplantation.html

Within the health topic page dedicated to biliary cirrhosis, the following was listed: •

General/Overviews What Is Bile Duct Cancer? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_Is_bile_duct_ca ncer_69.asp?sitearea=

•

Diagnosis/Symptoms Abdominal Pain, Long-Term Source: American Academy of Family Physicians http://familydoctor.org/528.xml ERCP (Endoscopic Retrograde Cholangiopancreatography) Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/ercp/index.htm GGT (Gamma-Glutamyl Transferase) Test Source: American Association for Clinical Chemistry http://labtestsonline.org/understanding/analytes/ggt/test.html How Is Bile Duct Cancer Diagnosed? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_bile_duct_ca ncer_diagnosed_69.asp?rnav=cri How Is Bile Duct Cancer Staged? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_bile_duct_ca ncer_staged_69.asp?rnav=cri Ultrasound-Abdomen Source: American College of Radiology, Radiological Society of North America http://www.radiologyinfo.org/content/ultrasound-abdomen.htm What Is a HIDA (Hepatobiliary Iminodiacetic Acid) Scan (Cholescintigraphy)? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00424

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Treatment Common Bile Duct Exploration Source: Cleveland Clinic Foundation http://www.clevelandclinic.org/health/healthinfo/docs/1700/1718.asp?index=6901 Radiation Therapy for Bile Duct Cancer Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_4X_Radiation_Therapy_69 .asp?rnav=cri Surgery for Bile Duct Cancer Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_4X_Surgery_69.asp?rnav= cri

•

Specific Conditions/Aspects Bile Reflux Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00259 Do We Know What Causes Bile Duct Cancer? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_Do_we_know_what_c auses_bile_duct_cancer_69.asp?sitearea= Primary Biliary Cirrhosis Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/primarybiliarycirrhosis/index.ht m Primary Sclerosing Cholangitis Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/primarysclerosingcholangitis/ind ex.htm What Are the Risk Factors for Bile Duct Cancer? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_What_are_the_risk_fa ctors_for_bile_duct_cancer_69.asp?rnav=cri What Is Primary Biliary Cirrhosis (PBC)? Source: American Liver Foundation http://www.liverfoundation.org/cgibin/dbs/articles.cgi?db=articles&uid=default&ID=1014&view_records=1 What Is Primary Sclerosing Cholangitis? Source: American Liver Foundation http://www.liverfoundation.org/cgibin/dbs/articles.cgi?db=articles&uid=default&ID=1015&view_records=1

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Children Biliary Atresia Source: Children's Liver Association for Support Services http://www.classkids.org/library/biliaryatresia.htm Choledochal Cysts Source: Children's Hospital Boston http://www.childrenshospital.org/cfapps/A2ZtopicDisplay.cfm?Topic=Choledoca l%2520Cysts What is Alagille Syndrome? Source: American Liver Foundation http://www.liverfoundation.org/cgibin/dbs/articles.cgi?db=articles&uid=default&ID=1010&view_records=1 What Is Biliary Atresia? Source: American Liver Foundation http://www.liverfoundation.org/cgibin/dbs/articles.cgi?db=articles&uid=default&ID=1012&view_records=1

•

From the National Institutes of Health Extrahepatic Bile Duct Cancer (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/bileduct/patient/

•

Organizations American Gastroenterological Association http://www.gastro.org/ American Liver Foundation http://www.liverfoundation.org/ National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ National Institute of Diabetes and Digestive and Kidney Diseases http://www.niddk.nih.gov/

•

Research Noninvasive Diagnosis of Biliary Disease Source: American College of Physicians http://www.annals.org/cgi/content/full/139/7/I-32 What's New in Bile Duct Cancer Research and Treatment? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_6X_Whats_new_in_bile_d uct_cancer_research_and_treatment_69.asp?rnav=cri

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Statistics What Are the Key Statistics for Bile Duct Cancer? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_sta tistics_for_bile_duct_cancer_69.asp?rnav=cri

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 biliary cirrhosis. 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: •

Primary Biliary Cirrhosis Source: Toronto, Ontario: Canadian Liver Foundation. 2001. 2 p. Contact: Available from Canadian Liver Foundation. Suite 1500, 2235 Sheppard Avenue East, Toronto Ontario, M2J 5B5. (416) 491-3353 or (800) 563-5483. Fax (416) 491-4952. Email: [email protected]. Website: [email protected]. PRICE: Contact organization for print copies. Summary: This brochure describes primary biliary cirrhosis (PBC), a chronic liver disease. The brochure reviews the causes of PBC, its symptoms, diagnostic tests used to confirm the condition, prognosis, and treatment options. It is believed that PBC results from an abnormal reaction of the body's immune system. The immune system of PBC patients attacks the liver causing slow, progressive damage to the bile ducts, resulting in the accumulation in the liver of bile and other substances. These retained toxic substances and inflammation can cause further damage. While there is no known specific treatment for PBC, there are various treatments that can help patients cope with the symptoms. Liver transplantation is now a common treatment option for people with advanced PBC. The brochure concludes with a brief description of the goals and activities of the Canadian Liver Foundation (www.liver.ca). 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 biliary cirrhosis. 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

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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

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

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

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

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

•

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

•

WebMDHealth: http://my.webmd.com/health_topics

Associations and Biliary Cirrhosis The following is a list of associations that provide information on and resources relating to biliary cirrhosis: •

Primary Biliary Cirrhosis Support Group Telephone: (281) 997-1516 Fax: (281) 412-9161 Email: [email protected] Web Site: http://www.pbcers.org Background: The PBCers Organization is a source of support and education for those who suffer from primary biliary cirrhosis and other autoimmune liver diseases. Family members and friends are also encouraged to join and learn more about PBC. The organization offers various types of support and education such as the e-mail PBC daily digest, quarterly newsletter and annual PBC conference. Members discuss medical information, pain management, medications, and research; ask questions; and vent anger and fears. The PBCers was formed in 1996. Current membership is more than 2,400 worldwide.

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to biliary cirrhosis. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with biliary cirrhosis.

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107

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 biliary cirrhosis. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. 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 “biliary cirrhosis” (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 “biliary cirrhosis”. 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 “biliary cirrhosis” (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 “biliary cirrhosis” (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.19

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

19

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)20: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

20

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

111

•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

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

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

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

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

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

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

115

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

117

BILIARY CIRRHOSIS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] Abscess: A localized, circumscribed collection of pus. [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] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [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] Adverse Effect: An unwanted side effect of treatment. [NIH] 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]

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] 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,

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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] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] 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] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [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] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [NIH]

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] Ampulla: A sac-like enlargement of a canal or duct. [NIH] 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] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans.

Dictionary 119

Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] 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-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] 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] 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] Antipruritic: Relieving or preventing itching. [EU] Anus: The opening of the rectum to the outside of the body. [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] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH]

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Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [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] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autopsy: Postmortem examination of the body. [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] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [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] 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]

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Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta blocker: A drug used to slow the heart rate and reduce pressure inside blood vessels. It also can regulate heart rhythm. [NIH] Bezafibrate: Antilipemic agent that lowers cholesterol and triglycerides. It decreases low density lipoproteins and increases high density lipoproteins. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [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 Atresia: Atresia of the biliary tract, most commonly of the extrahepatic bile ducts. [NIH]

Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] 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] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [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

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technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] 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 Glucose: Glucose in blood. [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 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]

Body Fluids: Liquid components of living organisms. [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] 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] 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] Breast Feeding: The nursing of an infant at the mother's breast. [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] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] 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

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many enzymatic processes. [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] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] 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] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [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 Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [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] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [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] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. [NIH]

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Cholangitis: Inflammation of a bile duct. [NIH] Choleretic: A choleretic agent. [EU] Cholestanol: A cholesterol derivative found in human feces, gallstones, eggs, and other biological matter. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [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] Cholestyramine: Strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium as Cl(-) anion. It exchanges chloride ions with bile salts, thus decreasing their concentration and that of cholesterol. It is used as a hypocholesteremic in diarrhea and biliary obstruction and as an antipruritic. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [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] 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] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] 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] 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] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and

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leaves the body through the anus. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Common Bile Duct: The largest biliary duct. It is formed by the junction of the cystic duct and the hepatic duct. [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] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] 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] Concentric: Having a common center of curvature or symmetry. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective

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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] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] 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 medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] 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] Corpus: The body of the uterus. [NIH] Corpus Striatum: Striped gray and white matter consisting of the neostriatum and paleostriatum (globus pallidus). It is located in front of and lateral to the thalamus in each cerebral hemisphere. The gray substance is made up of the caudate nucleus and the lentiform nucleus (the latter consisting of the globus pallidus and putamen). The white matter is the internal capsule. [NIH] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cost Savings: Reductions in all or any portion of the costs of providing goods or services. Savings may be incurred by the provider or the consumer. [NIH] Coumarins: Synthetic or naturally occurring substances related to coumarin, the deltalactone of coumarinic acid. Coumarin itself occurs in the tonka bean. The various coumarins have a wide range of proposed actions and uses including as anticoagulants, pharmaceutical aids, indicators and reagents, photoreactive substances, and antineoplastic agents. [NIH]

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Curative: Tending to overcome disease and promote recovery. [EU] 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] Cystic Duct: The tube that carries bile from the gallbladder into the common bile duct and the small intestine. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B 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] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [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] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Demography: Statistical interpretation and description of a population with reference to distribution, composition, or structure. [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]

Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Dietary Fiber: The remnants of plant cell walls that are resistant to digestion by the alimentary enzymes of man. It comprises various polysaccharides and lignins. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH]

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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] Dihydroxy: AMPA/Kainate antagonist. [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] 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] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dyspnea: Difficult or labored breathing. [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] 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] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion

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applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Electrolytes: Substances that break up into ions (electrically charged particles) when they are dissolved in body fluids or water. Some examples are sodium, potassium, chloride, and calcium. Electrolytes are primarily responsible for the movement of nutrients into cells, and the movement of wastes out of cells. [NIH] 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] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endogenous Retroviruses: Retroviruses that have integrated into the germline (Proviruses) that have lost infectious capability but retained the capability to transpose. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometrium: The layer of tissue that lines the uterus. [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] 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-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Enterohepatic: Of or involving the intestine and liver. [EU] Enterohepatic Circulation: Recycling through liver by excretion in bile, reabsorption from intestines into portal circulation, passage back into liver, and re-excretion in bile. [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] 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]

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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] Epidemiological: Relating to, or involving epidemiology. [EU] 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] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

ERCP: Endoscopic retrograde cholangiopancreatography (en-do-SKAH-pik RET-ro-grade ko-LAN-jee-o-PAN-kree-a-TAW-gra-fee). A procedure to x-ray the bile and pancreatic ducts. In this procedure, a thin, lighted tube (endoscope) is passed through the mouth and down into the first part of the small intestine (duodenum). A smaller tube (catheter) is then inserted through the endoscope into the bile and pancreatic ducts. A dye is injected through the catheter into the ducts, and an x-ray is taken. [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] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Varices: Stretched veins in the esophagus that occur when the liver is not working properly. If the veins burst, the bleeding can cause death. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH] Etidronate: A drug that belongs to the family of drugs called bisphosphonates. Bisphosphonates are used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] 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,

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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] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] 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] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Flatus: Gas passed through the rectum. [NIH] Foam Cells: Lipid-laden macrophages originating from monocytes or from smooth muscle cells. [NIH] Foetoplacental: Pertaining to the fetus and placenta. [EU] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma-interferon: Interferon produced by T-lymphocytes in response to various mitogens and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [NIH]

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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] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] Gastroenterologist: A doctor who specializes in diagnosing and treating disorders of the digestive system. [NIH] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] 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 Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [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] Globus Pallidus: The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus. [NIH] Glomeruli: Plural of glomerulus. [NIH]

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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] 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] 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] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] 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-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Gravidity: Pregnancy; the condition of being pregnant, without regard to the outcome. [EU] 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] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to

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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] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hepatology: The field of medicine concerned with the functions and disorders of the liver. [NIH]

Hepatoma: A liver tumor. [NIH] Hepatopulmonary Syndrome: A syndrome consisting of the triad of liver dysfunction, pulmonary vascular dilatation, and abnormal arterial oxygenation in the absence of detectable intrinsic disease of the lung and heart. [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]

Histiocytosis: General term for the abnormal appearance of histiocytes in the blood. Based on the pathological features of the cells involved rather than on clinical findings, the histiocytic diseases are subdivided into three groups: Langerhans cell histiocytosis, nonLangerhans cell histiocytosis, and malignant histiocytic disorders. [NIH] Histology: The study of tissues and cells under a microscope. [NIH]

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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] 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] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] 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] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] 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] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperlipidemia: An excess of lipids in the blood. [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] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic

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chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxemia: Deficient oxygenation of the blood; hypoxia. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Idiopathic: Describes a disease of unknown cause. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [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 factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [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] Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [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] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [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] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU]

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In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] 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] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] 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]

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] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] 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] 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,

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genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intercellular Adhesion Molecule-1: A cell-surface ligand with a role in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue. [NIH] Intercellular Junctions: Strictly, and so far as it can be distinguished, the amorphous isotropic layer between adjacent primary walls of cells. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] 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-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] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intrahepatic: Within the liver. [NIH] Intrahepatic bile ducts: The bile ducts that pass through and drain bile from the liver. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

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] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile

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pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [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] Keratoconjunctivitis: Simultaneous inflammation of the cornea and conjunctiva. [NIH] Keratoconjunctivitis Sicca: Drying and inflammation of the conjunctiva as a result of insufficient lacrimal secretion. When found in association with xerostomia and polyarthritis, it is called Sjogren's syndrome. [NIH] Lacrimal: Pertaining to the tears. [EU] Lactation: The period of the secretion of milk. [EU] 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] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [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] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [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] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [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 Transplantation: The transference of a part of or an entire liver from one human or animal to another. [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] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a

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person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [NIH] Lymphocyte Function-Associated Antigen-1: A heterodimer molecule widely expressed on cells of hematopoietic origin. CD11a antigen comprises the alpha chain and the CD18 antigen the beta chain. LFA-1 is a major receptor of T-cells, B-cells, and granulocytes. It mediates the leukocyte adhesion reactions underlying cytolytic conjugate formation, helper T-cell interactions, and antibody-dependent killing by natural killer cells and granulocytes. Intracellular adhesion molecule-1 (ICAM-1) has been defined as a ligand for LFA-1. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [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] 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] 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] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and

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spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [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] Menarche: The establishment or beginning of the menstrual function. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] 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] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Methyltransferase: A drug-metabolizing enzyme. [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] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH]

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Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milk Thistle: The plant Silybum marianum in the family Asteraceae containing the bioflavonoid complex silymarin. For centuries this has been used traditionally to treat liver disease. [NIH] 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] 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] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] 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] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] 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] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [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 Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin

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filaments slide inward among the myosin filaments. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelofibrosis: A disorder in which the bone marrow is replaced by fibrous tissue. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myositis: Inflammation of a voluntary muscle. [EU] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [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, 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] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neutrophil: A type of white blood cell. [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]

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 Envelope: The membrane system of the cell nucleus that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (nuclear pore). [NIH]

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Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [NIH] 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] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation. [NIH] 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] Oestrogen: A generic term for oestrus-producing steroid compounds; the female sex hormones. In humans, oestrogen is formed in the ovary, possibly the adrenal cortex, the testis, and the foetoplacental unit; it has various functions in both sexes. It is responsible for the development of the female secondary sex characteristics, and during the menstrual cycle it acts on the female genitalia to produce an environment suitable for the fertilization, implantation, and nutrition of the early embryo. Oestrogen is used in oral contraceptives and as a palliative in cancer of the breast after menopause and cancer of the prostate; other uses include the relief of the discomforts of menopause, inhibition of lactation, and treatment of osteoporosis, threatened abortion, and various functional ovarian disorders. [EU]

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] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] 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

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by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [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] 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]

Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] 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 Ducts: Ducts that collect pancreatic juice from the pancreas and supply it to the duodenum. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Pancytopenia: Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. [NIH] Parity: The number of offspring a female has borne. It is contrasted with gravidity, which refers to the number of pregnancies, regardless of outcome. [NIH] Particle: A tiny mass of material. [EU] Pathogen: Any disease-producing microorganism. [EU] 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] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

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PDQ: Physician Data Query. PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information is available on the CancerNet Web site, and more specific information about PDQ can be found at http://cancernet.nci.nih.gov/pdq.html. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [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] Peptic Ulcer Hemorrhage: Bleeding from a peptic ulcer. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [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] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] 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] 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] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] 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

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teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [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] 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] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Plant sterols: Plant-based compounds that can compete with dietary cholesterol to be absorbed by the intestines. This results in lower blood cholesterol levels. They may have some effect in cancer prevention. Also known as phytosterols. [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] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [NIH] 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] 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] Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and

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molds. Also called "farmer's disease". [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] Polyarthritis: An inflammation of several joints together. [EU] 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] 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] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] 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] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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] 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] 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]

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Primary Sclerosing Cholangitis: Irritation, scarring, and narrowing of the bile ducts inside and outside the liver. Bile builds up in the liver and may damage its cells. Many people with this condition also have ulcerative colitis. [NIH] Procainamide: A derivative of procaine with less CNS action. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] 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 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 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] 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]

Prothrombin Time: Measurement of clotting time of plasma recalcified in the presence of excess tissue thromboplastin. Factors measured are fibrinogen, prothrombin, and factors V,

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VII, and X. It is used for monitoring anticoagulant therapy with coumarins. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial infection. [EU] Pyruvate Dehydrogenase Complex: An organized assembly of three kinds of enzymes; catalyzes the oxidative decarboxylation of pyruvate. [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] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [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]

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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] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [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] 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] Reductase: Enzyme converting testosterone to dihydrotestosterone. [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] 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] 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] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Reproductive History: An important aggregate factor in epidemiological studies of women's health. The concept usually includes the number and timing of pregnancies and their outcomes, the incidence of breast feeding, and may include age of menarche and menopause, regularity of menstruation, fertility, gynecological or obstetric problems, or contraceptive usage. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [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] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] 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] Rheumatoid: Resembling rheumatism. [EU] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood,

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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] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]

Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] 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] Sclerotherapy: Treatment of varicose veins, hemorrhoids, gastric and esophageal varices, and peptic ulcer hemorrhage by injection or infusion of chemical agents which cause localized thrombosis and eventual fibrosis and obliteration of the vessels. [NIH] Screening: Checking for disease when there are no symptoms. [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] 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]

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Segmentation: The process by which muscles in the intestines move food and wastes through the body. [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] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [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] 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] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [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] Sicca: Failure of lacrimal secretion, keratoconjunctivitis sicca, failure of secretion of the salivary glands and mucous glands of the upper respiratory tract and polyarthritis. [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] Silymarin: A mixture of flavonoids extracted from seeds of the milk thistle, Silybum marianum. It consists primarily of three isomers: silicristin, silidianin, and silybin, its major component. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent. [NIH] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH]

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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 Pigmentation: Coloration of the skin. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Sprue: A non febrile tropical disease of uncertain origin. [NIH] 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] 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] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [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] Subacute: Somewhat acute; between acute and chronic. [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] 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]

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Sulindac: A sulfinylindene derivative whose sulfinyl moiety is converted in vivo to an active anti-inflammatory analgesic that undergoes enterohepatic circulation to maintain constant blood levels without causing gastrointestinal side effects. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] 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] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] 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] 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] Thoracic: Having to do with the chest. [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] Thromboplastin: Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thymoma: A tumor of the thymus, an organ that is part of the lymphatic system and is located in the chest, behind the breastbone. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and

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multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [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] Tonicity: The normal state of muscular tension. [NIH] 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] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [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] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [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] 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]

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Translocation: The movement of material in solution inside the body of the plant. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Triad: Trivalent. [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] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] 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] 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] 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]

Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. [NIH] 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]

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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] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

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] Varices: Stretched veins such as those that form in the esophagus from cirrhosis. [NIH] Varicose: The common ulcer in the lower third of the leg or near the ankle. [NIH] Varicose vein: An abnormal swelling and tortuosity especially of the superficial veins of the legs. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilators: Any nerve or agent which induces dilatation of the 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] Venous: Of or pertaining to the veins. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Proteins: Proteins found in any species of virus. [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] 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]

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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] 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] Xanthomatosis: A condition of morphologic change in which there is accumulation of lipids in the large foam cells of tissues. It is the cutaneous manifestation of lipidosis in which plasma fatty acids and lipoproteins are quantitatively changed. The xanthomatous eruptions have several different distinct morphologies dependent upon the specific form taken by the disease. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [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] 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]

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INDEX A Abdomen, 102, 117, 122, 139, 146, 154 Abdominal, 6, 56, 102, 117, 127, 145, 146, 157 Abdominal Pain, 102, 117, 157 Aberrant, 30, 117 Abscess, 117, 153 Acceptor, 117, 139, 145, 156 Acetylcholine, 117, 143 Actin, 117, 142, 143 Adenocarcinoma, 117, 134 Adenoma, 64, 117 Adenovirus, 14, 117 Adoptive Transfer, 17, 117 Adrenal Cortex, 117, 126, 144 Adverse Effect, 117, 153 Agar, 117, 147 Agonist, 117, 143 Albumin, 6, 117, 147 Algorithms, 118, 122 Alimentary, 74, 118, 127, 138 Alkaline, 118, 122 Alkaloid, 118, 124 Alleles, 11, 22, 118 Alternative medicine, 86, 118 Ambulatory Care, 6, 118 Amino Acid Sequence, 118, 119, 132 Amino Acids, 118, 130, 132, 146, 148, 149, 156, 157 Ampulla, 118, 124, 129 Anaesthesia, 118, 137 Analgesic, 118, 155 Analogous, 118, 148, 156 Analytes, 102, 118 Anatomical, 118, 136, 152 Anemia, 5, 118, 146 Angiography, 56, 118 Animal model, 8, 12, 14, 15, 82, 118 Anions, 117, 119, 138 Antibiotic, 119, 130, 155 Antibodies, 10, 23, 24, 27, 30, 31, 44, 45, 48, 81, 83, 119, 120, 134, 136, 147 Antibody, 4, 5, 18, 24, 27, 36, 44, 46, 53, 68, 119, 125, 130, 135, 136, 137, 140, 142, 154 Anticoagulant, 119, 149, 150 Antigen, 9, 15, 18, 44, 50, 73, 119, 125, 127, 135, 136, 137, 140 Antigen-presenting cell, 18, 119, 127

Anti-inflammatory, 14, 119, 126, 133, 137, 155 Antimetabolite, 119, 141 Antineoplastic, 119, 126, 131, 141, 145 Antioxidant, 74, 119, 153 Antipruritic, 119, 124 Anus, 119, 125, 138, 151 Apheresis, 21, 32, 119 Apoptosis, 12, 15, 16, 18, 20, 24, 25, 47, 59, 119 Arginine, 119, 143 Arterial, 5, 120, 134, 135, 149, 155 Arteries, 120, 122 Arterioles, 120, 122, 123 Arteritis, 22, 120 Artery, 120 Ascites, 8, 74, 82, 120 Assay, 11, 32, 120 Asymptomatic, 4, 5, 6, 17, 38, 68, 86, 120, 145 Atrophy, 5, 25, 120 Attenuated, 64, 120, 158 Autacoids, 120, 137 Autoantibodies, 9, 11, 15, 17, 20, 31, 32, 35, 58, 72, 87, 120 Autoantigens, 9, 11, 15, 18, 31, 38, 45, 52, 120 Autodigestion, 120, 145 Autoimmune disease, 4, 5, 9, 10, 14, 17, 22, 81, 120, 142 Autoimmune Hepatitis, 28, 29, 32, 35, 40, 55, 59, 61, 63, 120 Autoimmunity, 9, 23, 24, 34, 37, 41, 49, 54, 60, 68, 120 Autopsy, 22, 120 B Bacteria, 119, 120, 121, 129, 131, 134, 141, 152, 153, 156, 157, 158 Bacteriostatic, 120, 130 Bacterium, 87, 120 Base, 120, 132, 139, 157 Basement Membrane, 120, 130 Basophils, 121, 133 Benign, 117, 121, 143 Beta blocker, 7, 121 Bezafibrate, 25, 33, 47, 48, 121 Bile Acids, 7, 14, 19, 25, 73, 75, 121, 154, 155

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Bile Acids and Salts, 121 Bile Pigments, 121, 139 Biliary Atresia, 43, 104, 121 Biliary Tract, 121, 145 Bilirubin, 6, 7, 19, 117, 121, 135 Biochemical, 4, 5, 7, 9, 28, 83, 118, 119, 121, 139, 153 Biological response modifier, 121, 138 Biological therapy, 121, 133 Biomarkers, 11, 121 Biopsy, 5, 6, 65, 83, 121 Biosynthesis, 121, 139, 153 Biotechnology, 20, 86, 97, 121 Bladder, 122, 142, 149, 157 Bloating, 122, 137 Blood Cell Count, 122, 146 Blood Coagulation, 122, 155 Blood Glucose, 122, 134, 137 Blood pressure, 4, 5, 82, 122, 135, 142, 148 Blood vessel, 118, 121, 122, 123, 129, 133, 138, 140, 150, 155, 158 Blot, 14, 122 Body Fluids, 121, 122, 128, 129, 157 Bone Density, 53, 122 Bone Marrow, 122, 132, 133, 136, 140, 143 Bowel, 122, 128, 137, 157 Bradykinin, 122, 143, 147 Breast Feeding, 122, 151 Bronchoalveolar Lavage, 51, 122 Buccal, 122, 140 C Calcium, 63, 70, 122, 125, 129, 130, 135, 141, 149, 158 Capillary, 52, 122, 123, 152, 158 Carbon Dioxide, 123, 127, 132 Carcinogenic, 123, 137, 149, 154 Carcinogens, 123, 144, 159 Carcinoma, 123 Cardiac, 123, 127, 130, 154 Cardiovascular, 45, 123, 153 Case report, 29, 32, 41, 43, 45, 123 Catabolism, 75, 123 Catheter, 123, 130 Causal, 123, 134 Cause of Death, 12, 123 Celiac Disease, 86, 87, 123 Cell Death, 119, 123, 143 Cell Division, 120, 123, 133, 142, 147 Cell motility, 123, 134 Cell proliferation, 12, 123 Cell Survival, 123, 133

Central Nervous System, 117, 123, 142, 153 Character, 123, 127, 133 Chenodeoxycholic Acid, 123, 157 Cholangitis, 4, 8, 17, 20, 26, 37, 46, 53, 76, 124 Choleretic, 123, 124, 157 Cholestanol, 73, 74, 75, 76, 124 Cholestasis, 4, 16, 41, 64, 72, 76, 82, 83, 124 Cholesterol, 27, 74, 75, 121, 124, 135, 139, 147, 153, 154 Cholestyramine, 5, 124 Chromatin, 119, 124, 140 Chromosomal, 124, 151 Chromosome, 39, 56, 124, 142 Clinical Medicine, 22, 71, 72, 124, 148 Clinical trial, 8, 9, 14, 17, 19, 82, 97, 124, 128, 146, 150 Cloning, 28, 82, 121, 124 Coenzyme, 124, 139, 153 Cofactor, 124, 149, 155 Colchicine, 22, 28, 34, 75, 82, 83, 124 Colitis, 124 Collagen, 55, 120, 124, 126, 131, 141, 147, 149 Colloidal, 117, 124 Colon, 124, 125, 137, 139, 153, 157 Colorectal, 64, 125 Combination Therapy, 82, 125 Common Bile Duct, 14, 103, 125, 127 Complement, 72, 125, 132, 140, 147 Complementary and alternative medicine, 71, 77, 125 Complementary medicine, 71, 125 Computational Biology, 97, 125 Concentric, 125, 143 Conception, 125, 126 Conjugated, 24, 121, 123, 125, 144 Connective Tissue, 46, 52, 122, 124, 125, 126, 131, 140, 155 Connective Tissue Cells, 126 Connective Tissue Diseases, 46, 52, 126 Consciousness, 118, 126, 128, 150 Contamination, 126, 134 Contraceptive, 10, 126, 151 Contraindications, ii, 126 Contrast medium, 118, 126 Coordination, 126, 142 Cornea, 126, 139, 152, 158 Corpus, 126, 132 Corpus Striatum, 126, 132 Corticosteroid, 126, 148

163

Cortisol, 118, 126 Cost Savings, 8, 126 Coumarins, 126, 150 Curative, 83, 127, 152, 155 Cutaneous, 30, 127, 140, 159 Cyclic, 127, 133, 143, 146 Cystic Duct, 125, 127 Cytokine, 12, 16, 127 Cytoplasm, 119, 121, 127, 129, 140, 143 Cytotoxic, 14, 19, 45, 57, 127, 136 Cytotoxicity, 20, 127 D De novo, 29, 127 Decarboxylation, 127, 150 Decompensation, 7, 127 Degenerative, 127, 134 Deletion, 119, 127 Demography, 82, 127 Dendrites, 127 Dendritic, 45, 127 Dendritic cell, 45, 127 Desensitization, 127, 136 Diabetes Mellitus, 9, 127, 133, 134 Diagnostic procedure, 86, 127 Diaphragm, 25, 127 Diarrhea, 5, 87, 124, 127 Diastolic, 127, 135 Dietary Fiber, 73, 127 Digestion, 50, 51, 73, 118, 121, 122, 127, 128, 137, 139, 146, 154 Digestive system, 128, 132 Dihydroxy, 5, 128, 152 Diploid, 128, 142, 147 Direct, iii, 124, 128, 151 Disease Progression, 6, 7, 58, 128 Dissociation, 72, 128 Dissociative Disorders, 128 Double-blind, 19, 128 Double-blinded, 19, 128 Drug Interactions, 90, 128 Drug Tolerance, 128, 156 Duct, 5, 10, 12, 13, 14, 16, 17, 19, 25, 31, 52, 54, 57, 83, 102, 103, 104, 105, 118, 121, 124, 125, 128, 140, 152 Duodenum, 121, 128, 129, 130, 145, 146, 154 Dyspepsia, 87, 128, 137 Dyspnea, 127, 128 E Edema, 127, 128, 157 Effector, 9, 117, 125, 128, 146 Efficacy, 18, 32, 34, 47, 51, 59, 128

Elastic, 128, 133 Elastin, 124, 126, 129, 131 Electrolytes, 121, 129 Electrons, 119, 120, 129, 138, 145, 150 Embryo, 129, 137, 144, 148 Encephalopathy, 8, 129 Endogenous, 7, 14, 15, 19, 120, 129, 156 Endogenous Retroviruses, 15, 129 Endometrial, 60, 129 Endometrium, 129, 141 Endoscope, 129, 130 Endoscopic, 29, 34, 45, 102, 129, 130 Endothelial cell, 13, 18, 129 Endothelium, 129, 143 Endothelium-derived, 129, 143 Endotoxin, 26, 56, 129 Enkephalin, 42, 129 Enterohepatic, 129, 155 Enterohepatic Circulation, 129, 155 Environmental Health, 96, 98, 129 Enzymatic, 68, 123, 125, 129 Eosinophil, 53, 129 Eosinophilia, 33, 129 Eosinophilic, 129, 130 Epidemiological, 130, 151 Epinephrine, 130, 157 Epithelial, 12, 15, 32, 36, 41, 117, 130, 134 Epithelial Cells, 12, 15, 32, 36, 41, 130, 134 Epithelium, 15, 56, 120, 129, 130 Epitope, 9, 11, 35, 130 ERCP, 102, 130 Erythrocytes, 118, 122, 130, 134, 145 Erythromycin, 86, 130 Esophageal, 6, 7, 8, 45, 130, 152 Esophageal Varices, 6, 8, 45, 130, 152 Esophagus, 128, 130, 132, 133, 139, 146, 151, 154, 158 Estrogen, 59, 130 Etidronate, 22, 35, 130 Exogenous, 12, 13, 16, 129, 130 Extracellular, 12, 126, 130, 131, 141 Extracellular Matrix, 12, 126, 130, 141 Extracellular Matrix Proteins, 130, 141 Extracellular Space, 130, 131 Eye Infections, 117, 131 F Family Planning, 97, 131 Fat, 4, 7, 38, 51, 121, 122, 126, 131, 139, 142, 157 Fatigue, 4, 5, 17, 32, 37, 42, 64, 74, 82, 83, 131 Fatty acids, 117, 131, 149, 159

164

Biliary Cirrhosis

Febrile, 131, 154 Feces, 124, 131 Fibrinogen, 131, 147, 149, 155 Fibrosis, 4, 11, 14, 16, 19, 28, 72, 75, 82, 83, 131, 152 Flatus, 131, 132 Foam Cells, 131, 159 Foetoplacental, 131, 144 Fold, 11, 17, 131 Forearm, 122, 131 Free Radicals, 119, 128, 131 G Gallbladder, 102, 117, 121, 127, 128, 131, 132 Gamma-interferon, 131, 138 Gas, 13, 123, 131, 132, 135, 137, 143 Gas exchange, 13, 132 Gastric, 120, 132, 133, 146, 152 Gastrin, 132, 135 Gastritis, 68, 87, 132 Gastroenterologist, 87, 132 Gastrointestinal, 29, 37, 83, 87, 122, 130, 132, 153, 154, 155, 157 Gastrointestinal tract, 83, 87, 132, 153, 157 Gene, 11, 12, 14, 29, 46, 56, 65, 117, 118, 122, 132, 144 Gene Expression, 14, 46, 132 Gene Therapy, 117, 132 Genetic Code, 132, 144 Genetic Engineering, 121, 124, 132 Genetics, 13, 132, 146 Genotype, 12, 42, 132, 146 Gland, 117, 126, 132, 140, 145, 149, 152, 156 Globus Pallidus, 37, 126, 132 Glomeruli, 132, 150 Glomerulus, 132, 133, 143 Glucocorticoid, 41, 133, 148 Glucose, 122, 127, 133, 137 Glucose Intolerance, 127, 133 Glutathione Peroxidase, 133, 153 Gluten, 5, 41, 87, 123, 133 Glycoprotein, 20, 131, 133, 142 Gout, 124, 133 Governing Board, 133, 148 Grade, 130, 133 Graft, 60, 82, 133, 136 Graft-versus-host disease, 60, 133 Granulocyte, 21, 133 Granuloma, 54, 133 Gravidity, 133, 145 Growth factors, 12, 133

Guanylate Cyclase, 133, 143 H Heartburn, 87, 133, 137 Hemoglobin, 118, 122, 130, 133 Hemolysis, 68, 134 Hemorrhage, 7, 64, 134 Hemorrhoids, 134, 152 Hepatic, 4, 7, 11, 13, 15, 24, 34, 42, 60, 65, 74, 75, 82, 118, 125, 134, 153 Hepatitis, 20, 24, 41, 43, 56, 134 Hepatitis A, 56, 134 Hepatocellular, 21, 43, 48, 55, 65, 134 Hepatocellular carcinoma, 21, 43, 48, 55, 134 Hepatocyte, 12, 14, 55, 60, 124, 134 Hepatocyte Growth Factor, 60, 134 Hepatoma, 74, 134 Hepatopulmonary Syndrome, 13, 134 Hepatovirus, 134 Hereditary, 44, 126, 133, 134, 147 Heredity, 132, 134 Heterodimer, 134, 140 Heterogeneity, 11, 44, 134 Histiocytosis, 74, 134 Histology, 14, 19, 134 Homologous, 23, 118, 132, 135 Hormonal, 120, 126, 135, 158 Hormone, 60, 126, 130, 132, 135, 137, 153, 156, 158 Humoral, 11, 135 Humour, 135 Hybrid, 135 Hybridization, 14, 135 Hydrogen, 117, 120, 131, 133, 135, 139, 142, 144, 145, 146 Hydrogen Bonding, 135, 144 Hydrogen Peroxide, 133, 135, 139 Hydrolysis, 135, 148 Hydrophobic, 5, 19, 135 Hydroxylysine, 124, 135 Hydroxyproline, 124, 135 Hyperbilirubinemia, 7, 45, 83, 135, 138 Hypercalcemia, 130, 135 Hypercholesterolemia, 6, 32, 45, 135 Hyperlipidemia, 51, 135 Hypersensitivity, 127, 129, 135 Hypertension, 4, 12, 82, 135, 148, 157 Hypothalamus, 129, 135 Hypoxemia, 13, 136 Hypoxia, 136 I Idiopathic, 14, 16, 46, 136

165

Immune response, 119, 120, 126, 136, 140, 154, 158 Immune system, 4, 10, 105, 119, 120, 121, 136, 140, 142, 159 Immunity, 136, 140 Immunization, 117, 136 Immunofluorescence, 44, 136 Immunogenic, 15, 20, 136 Immunoglobulins, 16, 136, 147 Immunologic, 17, 117, 136 Immunosuppressant, 82, 136, 141 Immunosuppression, 5, 136, 140 Immunosuppressive, 4, 5, 12, 14, 17, 19, 133, 136, 155 Immunosuppressive Agents, 136 Immunosuppressive therapy, 4, 5, 136 Immunotherapy, 117, 121, 127, 136 Impairment, 64, 124, 131, 136 Implantation, 125, 136, 144 In situ, 11, 137 In vitro, 12, 16, 20, 72, 132, 137, 155 In vivo, 13, 14, 16, 132, 137, 140, 155 Incision, 137, 138 Incubation, 16, 137 Indigestion, 6, 87, 137 Indomethacin, 68, 137 Induction, 7, 27, 38, 137, 153 Infection, 14, 33, 41, 59, 121, 131, 133, 137, 140, 150, 154, 159 Inflammatory bowel disease, 46, 74, 137 Infusion, 13, 137, 152 Initiation, 9, 137, 156 Insecticides, 137, 159 Insight, 16, 137 Insulator, 137, 142 Insulin, 21, 137 Insulin-dependent diabetes mellitus, 21, 137 Intercellular Adhesion Molecule-1, 36, 138 Intercellular Junctions, 12, 138 Interferon, 9, 33, 131, 138 Interferon-alpha, 138 Interleukin-1, 65, 138 Interleukin-2, 138 Internal Medicine, 6, 10, 11, 16, 17, 19, 50, 68, 73, 132, 138 Interstitial, 17, 22, 131, 138, 143 Intestinal, 32, 39, 47, 123, 138, 140, 158 Intestinal Mucosa, 123, 138 Intestines, 117, 129, 131, 132, 138, 147, 153 Intoxication, 138, 159 Intracellular, 137, 138, 140, 143, 152, 153

Intrahepatic, 4, 11, 16, 35, 36, 37, 46, 47, 57, 76, 138 Intrahepatic bile ducts, 4, 11, 16, 37, 47, 138 Intravenous, 137, 138 Intrinsic, 9, 120, 134, 138 Invasive, 53, 136, 138 Ions, 120, 124, 128, 129, 135, 138, 149 Ischemia, 120, 138 J Jaundice, 6, 48, 87, 135, 138 K Kb, 96, 139 Keratoconjunctivitis, 139, 153 Keratoconjunctivitis Sicca, 139, 153 L Lacrimal, 139, 153 Lactation, 139, 144 Large Intestine, 128, 138, 139, 151, 154 Latent, 139, 148 Lectin, 60, 139 Lesion, 17, 133, 139 Lethal, 17, 139 Leucocyte, 129, 139 Leukapheresis, 119, 139 Ligands, 11, 139 Ligation, 12, 14, 29, 34, 45, 139 Lipid, 27, 34, 48, 75, 131, 137, 139, 142 Lipid Peroxidation, 34, 139 Localization, 18, 139 Localized, 11, 16, 50, 117, 137, 139, 147, 152 Lovastatin, 139, 153 Lower Esophageal Sphincter, 87, 139 Lupus, 17, 52, 140, 155 Lymph, 42, 51, 129, 135, 140 Lymph node, 42, 140 Lymphatic, 129, 137, 140, 155 Lymphatic system, 140, 155 Lymphocyte Depletion, 136, 140 Lymphocyte Function-Associated Antigen-1, 36, 140 Lymphocytes, 9, 18, 34, 39, 55, 57, 59, 119, 127, 131, 136, 138, 139, 140, 143, 155, 159 Lymphoid, 17, 119, 139, 140 Lymphokines, 19, 140 Lymphoma, 30, 46, 53, 140 M Macrophage, 138, 140 Major Histocompatibility Complex, 22, 140 Malabsorption, 4, 123, 140

166

Biliary Cirrhosis

Malignant, 117, 119, 134, 140, 143 Malnutrition, 118, 120, 141 Matrix metalloproteinase, 29, 141 Medial, 132, 141 Medical Staff, 128, 141 MEDLINE, 97, 141 Melanin, 141, 146, 157 Membrane, 125, 141, 142, 143, 145, 146, 151, 153, 156 Memory, 9, 76, 141 Menarche, 10, 141, 151 Menopause, 10, 141, 144, 148, 151 Menstrual Cycle, 141, 144 Menstruation, 141, 151 Mental, iv, 8, 96, 98, 128, 131, 141, 150, 152, 157 Mental Processes, 128, 141, 150 Metaplasia, 41, 141 Metastasis, 141, 143 Methotrexate, 6, 18, 19, 22, 34, 52, 54, 82, 83, 141 Methyltransferase, 17, 141 Microorganism, 124, 141, 145, 159 Micro-organism, 10, 141 Microscopy, 15, 120, 141 Microtubules, 141, 145 Migration, 9, 138, 142 Milk Thistle, 142, 153 Milliliter, 122, 142 Mitosis, 119, 142 Modification, 132, 142, 150 Molecular, 4, 9, 12, 13, 17, 34, 38, 52, 82, 97, 99, 121, 125, 131, 142, 156 Molecule, 64, 119, 120, 124, 125, 128, 129, 130, 135, 139, 140, 142, 144, 145, 151, 156, 158 Monitor, 32, 51, 142, 143 Monoclonal, 18, 142 Monocyte, 21, 142 Mononuclear, 33, 37, 133, 142 Monosomy, 39, 142 Monotherapy, 47, 142 Motility, 137, 142, 153 Motion Sickness, 142, 143 Mucins, 142, 152 Mucolytic, 122, 142 Mucosa, 140, 142 Mucus, 142, 157 Multiple sclerosis, 9, 142 Muscle Contraction, 87, 142 Myelin, 142, 143 Myelofibrosis, 46, 143

Myosin, 143 Myositis, 42, 54, 143 N Naloxone, 30, 143 Natural killer cells, 140, 143 Nausea, 6, 137, 143, 157 NCI, 1, 95, 143, 146 Necrosis, 119, 143 Neoplasms, 117, 119, 123, 143 Nephritis, 17, 143 Neural, 135, 143 Neutrophil, 138, 143 Nitric Oxide, 13, 31, 35, 36, 40, 52, 143 Nuclear, 14, 20, 44, 52, 129, 143, 144 Nuclear Envelope, 20, 143, 144 Nuclear Pore, 20, 143, 144 Nuclear Proteins, 144 Nucleic acid, 15, 132, 135, 144 Nucleic Acid Hybridization, 15, 135, 144 Nucleus, 119, 121, 124, 126, 127, 132, 140, 142, 143, 144, 154 Nutritional Status, 72, 144 O Observational study, 64, 144 Occupational Exposure, 10, 144 Odds Ratio, 4, 144, 151 Oestrogen, 65, 144 Oncogene, 134, 144 Opiate, 129, 143, 144 Osmotic, 117, 144 Osteoporosis, 4, 5, 35, 51, 54, 63, 82, 144, 145 Ovary, 144, 145, 148 Overexpress, 14, 145 Oxidation, 15, 20, 24, 117, 119, 133, 139, 145 Oxygenation, 134, 136, 145 P Paclitaxel, 76, 145 Palliative, 144, 145, 155 Pancreas, 117, 121, 128, 132, 137, 145, 157 Pancreatic, 76, 130, 145 Pancreatic Ducts, 130, 145 Pancreatitis, 39, 87, 145 Pancytopenia, 42, 145 Parity, 10, 145 Particle, 14, 145 Pathogen, 137, 145 Pathologic, 49, 119, 121, 135, 145 Pathologic Processes, 119, 145 Pathophysiology, 12, 56, 145

167

Patient Education, 6, 87, 105, 110, 112, 115, 145 PDQ, 104, 146 Pelvis, 117, 146, 150, 157 Peptic, 146, 152 Peptic Ulcer, 146, 152 Peptic Ulcer Hemorrhage, 146, 152 Peptide, 11, 31, 38, 146, 148, 149 Pericardium, 146, 155 Peripheral blood, 33, 51, 55, 138, 146 Peripheral stem cells, 133, 146 Peritoneal, 120, 146 Peritoneal Cavity, 120, 146 Pernicious, 68, 146 Pernicious anemia, 68, 146 PH, 28, 46, 122, 146 Pharmacologic, 120, 146, 156 Phenotype, 16, 42, 146 Phenylalanine, 146, 157 Phosphodiesterase, 74, 146 Phospholipids, 131, 146 Phosphorus, 122, 146, 147 Phosphorylation, 51, 147 Physiologic, 117, 121, 141, 147, 151 Physiology, 62, 132, 147 Pigment, 121, 147 Pilot study, 33, 54, 68, 147 Plant sterols, 75, 147 Plants, 118, 123, 133, 139, 147, 148, 152, 156 Plaque, 5, 147 Plasma, 13, 71, 117, 119, 131, 133, 134, 139, 147, 149, 159 Plasma cells, 119, 147 Plasma protein, 117, 147, 149 Plasmapheresis, 119, 147 Plasmids, 9, 147 Platelet Aggregation, 143, 147 Plateletpheresis, 119, 147 Platelets, 143, 145, 147, 153 Pneumonia, 22, 27, 126, 147 Pneumonitis, 17, 147 Poisoning, 138, 143, 148 Pollen, 148, 150 Polyarthritis, 139, 148, 153 Polymerase, 45, 148 Polymorphism, 23, 42, 56, 61, 148 Polypeptide, 20, 118, 124, 131, 135, 148 Polysaccharide, 119, 148 Portal Hypertension, 4, 5, 11, 13, 82, 148 Portal Vein, 148 Postmenopausal, 50, 145, 148

Potentiates, 138, 148 Practice Guidelines, 98, 148 Precursor, 11, 74, 75, 128, 129, 146, 148, 149, 157, 158 Predisposition, 40, 148 Prednisolone, 64, 83, 148 Prevalence, 5, 15, 44, 46, 85, 144, 148 Primary Sclerosing Cholangitis, 25, 26, 27, 30, 51, 59, 61, 79, 103, 149 Procainamide, 17, 149 Procaine, 149 Prognostic factor, 7, 35, 149 Progression, 6, 7, 12, 26, 28, 61, 63, 72, 83, 86, 119, 149 Progressive, 4, 6, 7, 17, 21, 76, 83, 105, 124, 128, 143, 149 Proline, 124, 135, 149 Promoter, 29, 56, 149 Prone, 14, 87, 149 Prophylaxis, 7, 149, 158 Prostaglandins, 137, 149 Prostaglandins A, 137, 149 Prostate, 121, 144, 149, 157 Protease, 125, 149 Protein C, 117, 118, 149 Protein S, 15, 122, 130, 132, 149, 155 Prothrombin, 6, 149, 155 Prothrombin Time, 6, 149 Proto-Oncogene Proteins, 145, 150 Proto-Oncogene Proteins c-mos, 145, 150 Protozoa, 141, 150, 158 Proximal, 150, 153 Pruritus, 4, 17, 19, 43, 51, 53, 73, 76, 82, 150, 157 Psychoactive, 150, 159 Psychology, 128, 150 Public Policy, 97, 150 Publishing, 20, 82, 83, 150 Pulmonary, 13, 17, 122, 130, 134, 150 Pulmonary Artery, 122, 150 Pyelonephritis, 21, 150 Pyruvate Dehydrogenase Complex, 26, 35, 150 Q Quality of Life, 6, 23, 150, 155 Quercetin, 76, 150 R Race, 10, 142, 150 Radiation, 103, 131, 136, 150, 159 Radioactive, 135, 136, 143, 150 Randomized, 19, 22, 35, 58, 63, 72, 74, 128, 150

168

Biliary Cirrhosis

Receptor, 40, 56, 59, 61, 65, 119, 134, 140, 151, 153 Recombinant, 12, 15, 31, 44, 58, 68, 151, 158 Rectal, 29, 151 Rectum, 119, 124, 125, 128, 131, 132, 137, 139, 149, 151, 153 Recurrence, 5, 29, 33, 41, 49, 58, 60, 82, 151 Reductase, 139, 141, 151, 153 Refer, 1, 122, 125, 139, 151, 156 Reflux, 87, 103, 151 Regeneration, 48, 151 Regimen, 19, 128, 151 Regurgitation, 133, 151 Relative risk, 8, 151 Remission, 151 Reproductive History, 10, 151 Response rate, 3, 151 Retina, 151, 152, 158 Retrograde, 64, 102, 130, 151 Retrovirus, 15, 59, 151 Rheumatoid, 9, 151 Rickets, 151, 158 Rickettsiae, 152, 158 Risk factor, 3, 5, 12, 86, 151, 152 Rod, 120, 152 Rutin, 150, 152 S Saline, 122, 152 Saliva, 87, 152 Salivary, 15, 128, 152, 153 Salivary glands, 15, 128, 152, 153 Schizoid, 152, 159 Schizophrenia, 152, 159 Schizotypal Personality Disorder, 152, 159 Sclera, 152, 158 Scleroderma, 9, 17, 37, 152 Sclerosis, 39, 142, 152 Sclerotherapy, 29, 34, 152 Screening, 7, 124, 146, 152 Secretion, 26, 126, 135, 137, 139, 142, 152, 153 Segmental, 4, 152 Segmentation, 152, 153 Selenium, 73, 153 Senile, 145, 153 Sepsis, 21, 153 Septal, 19, 83, 153 Sequence Homology, 15, 153 Sequencing, 9, 153 Serotonin, 153, 157 Sertraline, 51, 153

Serum, 4, 5, 6, 7, 14, 19, 31, 44, 49, 50, 60, 72, 73, 74, 75, 117, 125, 140, 153 Sex Characteristics, 144, 153 Sicca, 14, 153 Side effect, 89, 91, 117, 121, 153, 155, 156 Sigmoid, 56, 153 Sigmoid Colon, 56, 153 Silymarin, 72, 75, 142, 153 Simvastatin, 27, 60, 153 Skeletal, 25, 153 Skeleton, 117, 153, 154 Skin Pigmentation, 6, 154 Small intestine, 123, 127, 128, 130, 135, 138, 154, 158 Social Environment, 150, 154 Somatic, 135, 142, 154 Specialist, 107, 154 Species, 45, 124, 130, 135, 142, 147, 150, 153, 154, 157, 158, 159 Specificity, 38, 154 Sperm, 124, 148, 154 Spinal cord, 123, 124, 154 Sprue, 5, 154 Steroid, 61, 75, 121, 126, 144, 153, 154 Stomach, 87, 117, 120, 128, 130, 132, 135, 138, 139, 143, 146, 151, 154 Strand, 148, 154 Stress, 55, 126, 143, 148, 154 Subacute, 137, 154 Subclinical, 16, 137, 154 Subspecies, 154 Substance P, 130, 152, 154 Sulindac, 68, 155 Supplementation, 72, 73, 74, 155 Supportive care, 146, 155 Suppression, 76, 82, 126, 155 Symptomatic, 4, 5, 6, 145, 155 Systemic, 9, 14, 17, 39, 122, 130, 137, 148, 152, 155 Systemic lupus erythematosus, 9, 14, 17, 155 Systolic, 135, 155 T Tacrolimus, 61, 155 Taurine, 47, 72, 121, 123, 155 Telangiectasia, 44, 155 Testis, 144, 155 Tetracycline, 54, 155 Therapeutics, 74, 90, 155 Thermal, 128, 155 Thoracic, 127, 140, 155, 159 Threshold, 135, 155

169

Thrombin, 131, 147, 149, 155 Thromboplastin, 149, 155 Thrombosis, 149, 152, 155 Thymoma, 42, 155 Thymus, 136, 140, 155 Thyroid, 7, 156, 157 Thyroid Gland, 156 Thyroiditis, 14, 17, 68, 156 Thyroxine, 118, 146, 156 Tolerance, 26, 54, 133, 156 Tomography, 122, 156 Tonicity, 134, 156 Toxic, iv, 7, 19, 105, 127, 136, 153, 156 Toxicity, 128, 156 Toxicology, 98, 156 Toxin, 129, 156 Trachea, 156 Transcriptase, 151, 156 Transcription Factors, 14, 156 Transfection, 12, 121, 132, 156 Transferases, 68, 156 Translation, 130, 156 Translational, 15, 156 Translocation, 130, 157 Trauma, 143, 145, 157 Triad, 134, 157 Troglitazone, 24, 157 Tryptophan, 124, 153, 157 Tuberculosis, 140, 157 Tumor marker, 121, 157 Tyrosine, 34, 157 U Ulcerative colitis, 55, 137, 149, 157 Uraemia, 145, 157 Ureters, 157 Urethra, 149, 157 Urinary, 4, 6, 10, 24, 157 Urinary tract, 4, 6, 10, 24, 157 Urinary tract infection, 4, 6, 10, 24, 157 Urine, 6, 73, 122, 157 Uterus, 126, 129, 141, 157, 158 Uvea, 158

Uveitis, 42, 158 V Vaccination, 9, 158 Vaccines, 8, 158 Vagina, 141, 158 Vaginal, 4, 64, 158 Varices, 7, 8, 23, 29, 34, 35, 56, 158 Varicose, 152, 158 Varicose vein, 152, 158 Vascular, 13, 55, 64, 129, 134, 137, 143, 156, 158 Vasculitis, 64, 145, 158 Vasodilatation, 13, 158 Vasodilators, 143, 158 Vector, 14, 158 Vein, 138, 143, 148, 158 Venous, 74, 122, 127, 134, 149, 158 Venules, 122, 123, 158 Veterinary Medicine, 97, 158 Villi, 158 Villous, 5, 123, 158 Viral, 15, 32, 151, 158 Viral Proteins, 15, 158 Virulence, 120, 156, 158 Virus, 15, 41, 43, 132, 138, 147, 158 Vitamin D, 4, 51, 65, 152, 158 Vitro, 159 Vivo, 14, 140, 159 W White blood cell, 119, 133, 140, 142, 143, 147, 159 Windpipe, 156, 159 Withdrawal, 30, 61, 159 Wound Healing, 141, 159 X Xanthomatosis, 50, 159 Xenobiotics, 10, 23, 46, 159 Xenograft, 119, 159 X-ray, 122, 126, 130, 143, 159 Y Yeasts, 146, 159

170

Biliary Cirrhosis

171

172

Biliary Cirrhosis