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

LIVER

TRANSPLANT 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., 1960Liver Transplant: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84484-4 1. Liver Transplant-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 liver transplant. 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 LIVER TRANSPLANT .................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Liver Transplant ......................................................................... 15 E-Journals: PubMed Central ....................................................................................................... 62 The National Library of Medicine: PubMed ................................................................................ 66 CHAPTER 2. NUTRITION AND LIVER TRANSPLANT ...................................................................... 115 Overview.................................................................................................................................... 115 Finding Nutrition Studies on Liver Transplant ........................................................................ 115 Federal Resources on Nutrition ................................................................................................. 121 Additional Web Resources ......................................................................................................... 122 CHAPTER 3. DISSERTATIONS ON LIVER TRANSPLANT ................................................................. 123 Overview.................................................................................................................................... 123 Dissertations on Liver Transplant ............................................................................................. 123 Keeping Current ........................................................................................................................ 124 CHAPTER 4. CLINICAL TRIALS AND LIVER TRANSPLANT ............................................................ 125 Overview.................................................................................................................................... 125 Recent Trials on Liver Transplant ............................................................................................. 125 Keeping Current on Clinical Trials ........................................................................................... 129 CHAPTER 5. PATENTS ON LIVER TRANSPLANT ............................................................................ 131 Overview.................................................................................................................................... 131 Patents on Liver Transplant ...................................................................................................... 131 Patent Applications on Liver Transplant .................................................................................. 135 Keeping Current ........................................................................................................................ 136 CHAPTER 6. BOOKS ON LIVER TRANSPLANT ................................................................................ 137 Overview.................................................................................................................................... 137 Book Summaries: Federal Agencies............................................................................................ 137 Book Summaries: Online Booksellers......................................................................................... 139 Chapters on Liver Transplant .................................................................................................... 140 CHAPTER 7. MULTIMEDIA ON LIVER TRANSPLANT ..................................................................... 145 Overview.................................................................................................................................... 145 Video Recordings ....................................................................................................................... 145 CHAPTER 8. PERIODICALS AND NEWS ON LIVER TRANSPLANT .................................................. 147 Overview.................................................................................................................................... 147 News Services and Press Releases.............................................................................................. 147 Newsletters on Liver Transplant ............................................................................................... 151 Newsletter Articles .................................................................................................................... 151 Academic Periodicals covering Liver Transplant....................................................................... 152 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 153 Overview.................................................................................................................................... 153 U.S. Pharmacopeia..................................................................................................................... 153 Commercial Databases ............................................................................................................... 154 Researching Orphan Drugs ....................................................................................................... 154 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 159 Overview.................................................................................................................................... 159 NIH Guidelines.......................................................................................................................... 159 NIH Databases........................................................................................................................... 161 Other Commercial Databases..................................................................................................... 163 APPENDIX B. PATIENT RESOURCES ............................................................................................... 165 Overview.................................................................................................................................... 165

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Patient Guideline Sources.......................................................................................................... 165 Finding Associations.................................................................................................................. 176 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 179 Overview.................................................................................................................................... 179 Preparation................................................................................................................................. 179 Finding a Local Medical Library................................................................................................ 179 Medical Libraries in the U.S. and Canada ................................................................................. 179 ONLINE GLOSSARIES................................................................................................................ 185 Online Dictionary Directories ................................................................................................... 186 LIVER TRANSPLANT DICTIONARY...................................................................................... 187 INDEX .............................................................................................................................................. 253

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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 liver transplant 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 liver transplant, 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 liver transplant, 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 liver transplant. 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 liver transplant, 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 liver transplant. 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 LIVER TRANSPLANT Overview In this chapter, we will show you how to locate peer-reviewed references and studies on liver transplant.

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

Pilot Study of Interferon Alfa and Ribavirin Combination in Liver Transplant Recipients with Recurrent Hepatitis C Source: Hepatology. 36(5): 1253-1258. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Although interferon alfa (IFNa) and ribavirin are widely used in the treatment of hepatitis C, their role in the transplant recipient is unclear. This article reports on a pilot study conducted to determine the efficacy and safety of this therapy in transplant recipients with recurrent hepatitis C. Patients at least 6 months posttransplantation were treated with IFNa and ribavirin for 48 weeks followed by ribavirin monotherapy for 24 weeks. The primary end point was sustained virologic

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response, and secondary end points included biochemical, virologic, and histologic responses at the end of combination treatment. Thirty-eight patients initiated therapy, but 16 withdrew due to adverse effects, including 2 with myocardial infarction (heart attack). Median age was 50 years, 74 percent were men, and 91 percent had genotype 1 hepatitis C. On an intention-to-treat basis, 7 patients (18 percent) had a biochemical and 5 patients (13 percent) had a virological response at the end of combination treatment. Inflammatory activity did not change, but fibrosis worsened in virologic nonresponders. Ribavirin maintenance caused a further decrease in serum alanine aminotransferase levels, but hepatitis C virus (HCV) RNA levels increased. Only 2 of the 38 patients (5 percent) had a sustained virologic response. Several patients required treatment with erythropoietin for anemia. The authors conclude that IFN alfa and ribavirin are effective in a small proportion of liver allograft recipients with recurrent hepatitis C. 1 figure. 4 tables. 16 references. •

Medical Problems Occurring After Orthotopic Liver Transplantation Source: Digestive Diseases and Sciences. 42(8): 1666-1674. August 1997. Summary: Common medical problems such as hypertension, hypercholesterolemia, and obesity are seen in long term clinical follow up after liver transplantation. In addition to these problems, specific areas of post transplant dysfunction include: diabetes mellitus, malignancy, bone disease, sexual dysfunction, neurological disease, and recurrence of the primary liver disease. In this article, the authors review these medical problems and discuss the most common etiologies. The incidence of diabetes mellitus ranges from 4 to 20 percent following solid organ transplantation. Immunosuppressive agents contribute to glucose intolerance, hyperlipidemia, and hypertension. These combined comorbidities increase cardiovascular risk. Patients with primary sclerosing cholangitis (PSC) and ulcerative colitis experience up to a 13 percent incidence of colon cancer after transplantation. Lymphomas occur in 1 to 3 percent of patients after transplantation and account for 57 percent of malignancies occurring in adult patients. Atraumatic bone fracture occurs in 22 to 38 percent of patients and neurological complications, including seizures, headache, and neuropathy occur in 19 to 47 percent of patients following liver transplantation. Patients undergoing liver transplantation may experience recurrent of their primary liver disease. In patients not receiving immunoprophylaxis after transplantation for chronic hepatitis B, recurrent hepatitis B is seen in up to 90 percent of patients. Recurrent hepatitis C is seen in the majority of patients; current treatment modalities are inadequate. Recurrence of primary biliary cirrhosis or PSC in the allograft is infrequent. The authors also discuss psychiatric issues, quality of life, and rehabilitation. 3 tables. 36 references. (AA-M).

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Long-Term Follow-Up of the Orthotopic Liver Transplantation Patient Source: Seminars in Liver Disease. 15(2): 173-180. May 1995. Contact: Available from Thieme Medical Publishers, Inc. 381 Park Avenue South, New York, NY 10016. (800) 782-3488. Summary: In this article, the authors highlight aspects of both routine and special needs of patients following liver transplantation. Topics covered include immunosuppression medications; hypertension medications; anti-infective agents; medications for other medical disorders; specialized medications; vaccines; monitoring of immunosuppression; laboratory studies for clinical monitoring; specialized studies; routine physician visits, including a recommended schedule; specialized followup studies; the role of good communication between patient, primary care provider, and

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the transplant center; the needs of daily living, including nutrition, the use of ethanol (alcohol), exercise, return to work, sexual activity, pregnancy, and travel; complications, including headache, hypertension, renal dysfunction, allograft rejection, biliary disorders, opportunistic infection, recurrent disease, and bone disease; and the need for retransplantation. 3 tables. 54 references. (AA-M). •

Hepatitis C and Liver Transplantation Source: Journal of Gastroenterology and Hepatology. 10(4): 471-480. July-August 1995. Summary: In this article, the authors review the interrelationship between hepatitis C virus (HCV) and liver transplantation. HCV is important to the liver transplant recipient for several reasons: chronic HCV infection is a frequent cause of end-stage liver disease; recurrence of HCV after liver transplantation is almost universal; HCV infection in the organ donor or in blood transfusions make acquisition of HCV possible; and liver transplantation for chronic HCV infection represents a major financial burden. The authors discuss the prevalence of hepatitis C in patients undergoing liver transplantation; the natural history of HCV infection following liver transplantation; pathology and pathogenesis; and treatment options. They note that factors that determine why some patients are more susceptible to liver damage than others are currently under study. 4 figures. 1 table. 61 references. (AA-M).

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New Aspects of Heterotopic Liver Transplantation Source: Transplant International. 5(1): 43-50. 1992. Summary: In this article, the history and clinical results of heterotopic liver transplantation (HLT) are reviewed and some special aspects of current research on HLT are highlighted. After a brief review of the history of HLT, the authors discuss aspects of HLT, including the absence of intraoperative fibrinolysis, the stability of hemodynamic parameters during the HLT procedure, the effect of HLT on portal pressure and hypersplenism, the interaction between the two livers in situ, the role of portal blood flow in HLT, the temporary support given by the heterotopic graft in acute liver failure, and the possible role of HLT in inborn errors of hepatic metabolism. 4 figures. 3 tables. 67 references.

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Pediatric Liver Transplantation: Part II: Managing the Long-Term Complications Source: Gastroenterology Nursing. 13(1): 44-53. Summer 1990. Summary: Increasing numbers of children are receiving liver transplants at major centers and returning to their home hospitals for long-term follow-up. This article summarizes the recognition and management of long-term complications in pediatric liver transplant recipients. Emphasis is placed on an understanding of the practical aspects of the pharmacokinetics and toxicity of cyclosporine, the major immunosuppressive drug used in these patients. Common infectious problems, particularly serious viral infections, are reviewed with their unique clinical presentations in this immunocompromised population. Therapeutic alternatives for episodes of acute rejection are offered to facilitate communication with the transplant center and familiarize the local pediatric gastroenterologist and his or her staff with the management issues facing those who take care of these complex patients. 55 references. (AA-M).

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Disease Recurrence After Liver Transplantation: Need We Worry? (editorial) Source: Journal of Gastroenterology and Hepatology. 17(7): 733-736. July 2002. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: It has long been recognized that in patients transplanted for hepatitis B or C related liver disease, recurrence of hepatitis infection in the graft is common and that this may result in serious and progressive liver injury. There are now varying levels of evidence to suggest that most other forms of chronic liver disease also have the potential to recur in the graft. This editorial stresses that it is important for those involved in the care of liver transplant recipients to recognize the possibility of disease recurrence, so that patients may be adequately counseled, liver biochemistry, radiology and histology correctly interpreted, and to ensure that appropriate therapy is instituted. The authors briefly report on recent studies in this area. The authors conclude that is it likely that as the overall results of liver transplantation continue to improve, recurrence of diseases such as primary sclerosing cholangitis, autoimmune hepatitis, and hepatitis C disease will become increasingly recognized as a major cause of late morbidity and mortality. In contrast, the problems of recurrence of hepatitis B and hepatocellular cancer have now largely been overcome, resulting in an increased demand for transplantation for these indications, at a time when overall organ donor rates are falling. This has major implications for both patient selection and donor organ allocation.

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Prophylactic Use of OKT3 in Liver Transplantation: A Review Source: Digestive Diseases and Sciences. 36(10): 1427-1430. October 1991. Summary: Liver rejection in the era of cyclosporine-based immunosuppression is approximately 60-70 percent. About 15-25 percent of liver transplant patients will require hemodialysis following transplantation. These facts argue for a potent, less nephrotoxic immunosuppressive regimen. This review article examines the potential benefits and pitfalls of a prophylactic regimen of OKT3 (orthoclone) as a means to decrease the need for hemodialysis while maintaining potent immunosuppression. The authors stress that a lack of documentation of long-term patient and graft survival, the potential susceptibility to infectious complications, development of sensitization, and cost factors must be weighed against the decreased need for hemodialysis and the control of early rejection episodes. 22 references. (AA).

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Review: Hepatitis B and Liver Transplantation Source: Journal of Gastroenterology and Hepatology. 13(3): 217-223. March 1997. Contact: Available from Blackwell Science Pty Ltd. P.O. Box 378, Carlton, Victoria 3053, Australia. Phone: 61 3 9347 0300; Fax: 61 3 9347 5001; Web site: http://www.blacksci.co.uk. Summary: Liver transplantation in hepatitis B virus (HBV) infected patients is very commonly followed by recurrence of infection in the transplanted liver. This review article focuses on new strategies for the prevention and treatment of disease recurrence after transplantation. Most recipients with HBV recurrence will develop chronic hepatitis that follows a more aggressive course than is seen in nonimmunocompromised subjects; this frequently results in graft failure. The presence of hepatitis B e antigen or significant levels of HBV-DNA in the serum is highly predictive of recurrence and this has led to the view that patients, whose serum is positive for these conventional markers

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of replication, should be excluded from transplantation. The key to improving the results of transplantation in patients with HBV infection lies in the development of effective strategies to prevent reinfection. High dose anti-HBs immunoglobulin is effective in patients who are coinfected with hepatitis D, those transplanted for fulminant hepatitis, and cirrhotic patients who have very low levels of viral replication prior to transplantation. Unfortunately, immunoprophylaxis does not seem to influence the outcome in those patients with higher levels of replication. There are several new orally active nucleoside analogues that are potent inhibitors of hepatitis B replication that may be effective for both the prevention and treatment of recurrent disease. The most promising are lamivudine and famciclovir. Both agents have been extensively evaluated in animal models of HBV and have been shown to rapidly suppress viral replication. The author concludes that the initial experience with these agents in liver transplant recipients has been promising and a number of studies are currently under way to determine whether these drugs, used alone or in combination with immunoprophylaxis, are able to prevent recurrence in those patients at highest risk of posttransplant HBV recurrence. 1 table. 59 references. (AA-M). •

Resource Utilization in Liver Transplantation: Effects of Patient Characteristics and Clinical Practice Source: JAMA. Journal of the American Medical Association. 281(15): 1381-1386. April 21, 1999. Summary: Liver transplantation is among the most costly of medical services, yet few studies have addressed the relationship between the resources used for this procedure and specific patient characteristics and clinical practices. This article reports on a study to assess the relationship between pretransplant patient characteristics and clinical practices on the one hand and hospital resource utilization on the other. The prospective cohort included 711 patients who received single organ liver transplants, were at least 16 years old, and had nonfulminant liver disease. The main outcome measure was a standardized resource utilization derived from a database created by matching all services to a single price list. Higher adjusted resource utilization was associated with a donor age of 60 or older; a recipient age of 60 or older; alcoholic liver disease; ChildPugh class C; care in the intensive care unit at time of transplant; death in the hospital; and multiple liver transplants during the index hospitalization. Adjusted length of stay and resource utilization also differed significantly among transplant centers. The authors conclude that clinical, economic, and ethical dilemmas in liver transplantation are highlighted by these findings. Recipients who were older, had alcoholic liver disease, or were severely ill were the most expensive to treat; this suggests that organ allocation criteria may affect transplant costs. Clinical practices and resource utilization varied considerably among transplant centers. The authors note that methods to reduce variation in practice patterns, such as clinical guidelines, might lower costs while maintaining quality of care. 1 figure. 2 tables. 29 references.

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Liver Transplantation for Viral Hepatitis: Current Status Source: American Journal of Gastroenterology. 87(4): 409-418. April 1992. Summary: Liver transplantation is now considered a definitive therapy for end-stage liver disease and has been playing an increasingly important role in the management of fulminant hepatic failure. This article reviews the current status of liver transplantation used for this indication. The authors note that, with the advent of effective immunosuppression and improved surgical techniques, high survival rates can be expected for most transplanted patients. It has become apparent, however, that

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transplantation for patients with viral hepatitis is associated with some unique problems because of the propensity for viral reinfection of the grafted liver. Patients with actively replicating hepatitis B viral infection before transplantation appear to be the most likely to experience clinically significant recurrent hepatitis after transplantation. Recurrent hepatitis D (delta) and hepatitis C appear to be relatively less serious in the transplanted liver. Interventions to prevent or treat this graft reinfection have thus far met with limited success. The authors call for further studies to define more precisely which patients with viral hepatitis are likely to do poorly after liver transplantation, and to develop strategies to treating recurring hepatitis in transplant recipients. 3 tables. 57 references. (AA-M). •

Liver Transplantation: What the Non-Hepatologist Should Know Source: Practical Gastroenterology. 25(4): 42, 47-48, 50, 52, 54, 56-58, 60, 62, 64, 66. April 2001. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: Over the last two decades, liver transplantation (LT) has been transformed from an experimental procedure with uncertain outcome to a safe and reliable treatment for hepatic failure that has dramatically changed the natural history of liver diseases. This article familiarizes health care providers (who are not liver specialists) with the present indications for liver transplantation and care of patients undergoing this procedure. More than 3,000 LTs are performed each year in the United States; the number is limited only by the shortage of donor organs. The 5 year survival rate after LT is up to 80 percent in the most successful centers and LT is the only reasonable option for individuals with end stage liver disease. However, because of the reduced number of available organs and the long waiting times on transplant lists, the selection and timing of patient referral to a transplant center is crucial. Equally important is the long term medical followup of individuals with liver transplants. The goals should be to prevent and to recognize at the earliest opportunity any complications that can be managed appropriately. For all this to occur, all the medical personnel involved in the care of an individual with liver disease must be familiar with the option of LT as well as with the pathophysiology of liver failure, its clinical recognition and management. The authors conclude with a discussion of the side effects of immunosuppression, noting that these adverse drug events are common medical problems in allograft recipients. These complications include hypertension (high blood pressure), diabetes mellitus, renal dysfunction (kidney failure), infection (usually by an opportunistic organism), and new onset neoplasia, including cancer. 2 figures. 10 tables. 30 references.

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Nutrition Support for Liver Transplant Patients Source: Nutrition and the M.D. 17(3): 3-4. March 1991. Summary: Patients facing liver transplantation are often in a poor nutritional state. Hepatic failure causes fluid and sodium retention, may be associated with protein intolerance, and usually causes poor appetite. This article reports on a recent study that investigated the effects of nutrition support for at least a week after liver transplantation in 28 hypoalbuminemic cirrhotic patients. The patients were randomly assigned to one of three postoperative regimens: no nutritional support, other than isotonic intravenous glucose solutions; a standard total parenteral nutrition (TPN) formula; or an isocaloric, isonitrogenous TPN formula enriched with branched-chain amino acids. Both TPN groups were weaned from respirators more rapidly, and thus left the intensive care unit

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earlier. The researchers concluded that specialized branched-chain formula may not be necessary to achieve benefits from TPN in liver transplant patients. •

Features of Recurrent Primary Sclerosing Cholangitis in Two Consecutive Liver Allografts After Liver Transplantation Source: Journal of Clinical Gastroenterology. 32(2): 151-154. February 2001. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: Primary sclerosing cholangitis (PSC) is a disease of unknown etiology (cause) that is characterized by inflammation and fibrosis (scarring) of the biliary tree, which results in stricture formation and, eventually, in liver failure. Recurrence of PSC after liver transplantation is very uncommon. The true incidence of recurrence is unknown, mainly because of the difficulty in differentiating ischemic strictures from that of recurrent disease. PSC and ischemic strictures have identical histopathologic and cholangiographic (a type of diagnostic test) features. In this article, the authors report the case of a young man who had recurrence of PSC in two allografts (transplants) and also report their experience with 32 patients who had liver transplantation for PSC. Six patients (18 percent) had evidence of non anastomotic strictures and, of these, only one patient (reported here) had unequivocal evidence of true recurrence. The strictures in the other five patients happened because of ischemia (lack of blood flow to the organ involved). The authors conclude that the recurrence of the disease in two allografts in an immunosuppressed patient (taking drugs to avoid rejection of the transplant), in the absence of ischemia, chronic rejection, or any known pathogen, raises the question of the role of an unidentified infectious agent in the cause of PSC. 2 figures. 2 tables. 14 references.

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Should Alcoholics Compete Equally for Liver Transplantation? Source: JAMA. Journal of the American Medical Association. 265(10): 1295-1298. March 13, 1991. Summary: The circumstances of liver transplantation are unique among organ transplantation because of the scarcity of donor livers and the predominance of one disease, alcohol-related end-stage liver disease, as the principal cause of liver failure. The authors of this article propose that patients who develop end-stage liver disease through no fault of their own should have higher priority for receiving a liver transplant than those whose end-stage liver disease results from failure to obtain treatment for alcoholism. This proposal is based on considerations of fairness, and on whether public support for liver transplantation can be maintained if patients with alcohol-related end-stage liver disease receive more than half the available donor livers. The authors conclude that since not all can live, priorities must be established for the use of scarce health care resources. 43 references. (AA).

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NIDDK Liver Transplantation Database Source: Liver Transplantation and Surgery. 3(1): 10-22. January 1997. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Liver Transplantation Database was established to prospectively investigate questions related to the experience of patients evaluated for and undergoing liver

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transplantation. This article presents the study design, methods, and quality of data collection, along with some of the overall results. An initial 4 year planning phase was used to develop data collection instruments and quality control procedures for assessing transplantation, liver donors, and the recipients course before and after surgery. During the 1990-1995 implementation phase, three clinical centers refined the data collection instruments and enrolled and followed consecutive liver transplant candidates who agreed to be included in the protocol. The database contains more than 49,000 data forms from 1,563 candidates, 1,002 donors, and 916 transplant recipients followed up to 5 years after transplantation. Overall, 95 percent of protocol forms were completed. The database includes uniformly defined histology results of liver biopsies performed per protocol or for complications throughout followup. In addition, the database maintains an inventory of available sera for the serum bank. All test results of studies performed on the sera are added to the database. Of the 1,563 patients evaluated, 59 percent were deemed eligible for liver transplantation. Of the others who were too well or had contraindications, 15 percent became eligible later. Characteristics of patients in this study were generally comparable to those of patients nationally. The authors conclude that the NIDDK Liver Transplantation Database has yielded comprehensive, high quality data and is a rich resource for extensive analysis about many important clinical aspects of liver transplantation. 5 figures. 2 tables. 10 references. (AA). •

Survey of Liver Transplantation from Living Adult Donors in the United States Source: New England Journal of Medicine. NEJM. 348(9): 818-825. February 27, 2003. Summary: The transplantation of the right lobe of a liver from a living adult donor into an adult recipient has been performed increasingly frequently in the United States. Although the use of grafts from living donors is standard practice in transplantation in children, their use in adults remains controversial. This article reports on a study that used a 24 item questionnaire, sent to all liver transplantation programs in the U.S., to collect data on the indications, evaluation, and outcomes of the use of liver transplantation from a living donor. Questionnaires were returned by 84 of the 122 programs (69 percent) describing the results of 449 adult-to-adult transplantations of partial livers from living donors that were performed in 42 centers. A total of 45 percent of potential donors who were evaluated eventually donated a lobe of their liver; 99 percent of these donors were genetically or emotionally related to the recipient. Complications in the donor were more frequent in the centers performing the fewest transplantations from living donors in adults and included biliary complications requiring intervention (6.0 percent), reoperation (4.5 percent), and death (in one donor). Among the recipients, 1.6 percent did not meet criteria for receipt of a cadaveric transplant; cancer, retransplantation, and acute liver failure were uncommon indications for transplantation from a living donor. Biliary complications occurred in 22.0 percent of recipient, and vascular complications occurred in 9.8 percent. The authors conclude that adult-to-adult liver transplantation from a living donor is increasingly performed in the United States but is concentrated in a few large-volume centers. Mortality among donors is low, but complications in the donor are relatively common. 2 figures. 3 tables. 26 references.

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Oral Management of the Patient with End-Stage Liver Disease and the Liver Transplant Patient Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 86(1): 55-64. July 1998.

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Contact: Available from Mosby, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-3318. (800) 453-4351 or (314) 453-4351. Summary: This article addresses the oral management of the patient with end stage liver disease and the liver transplant patient. The authors emphasize that the patient with end stage liver disease, who is in need of a liver transplant, should have a pretransplant dental evaluation. Such a patient faces lifelong immunosuppression with an increased risk of infection. The article discusses both the need for control of oral diseases before liver transplantation and guidelines for oral care in the immediately postoperative and long term transplant patient. Specific indications for antibiotic prophylaxis and antibiotic regimens are presented; in addition, the adverse reactions and side effects of immunosuppressant drugs are discussed. The authors review pertinent drug interactions related to the dental management of patients with end stage liver disease, and present specific management recommendations. Specific drugs covered include cyclosporine, FK 506, prednisone, monoclonal antibody (OKT3), azathioprine, antilymphocyte globulin (ATG), morphine, codeine, nonsteroidal antiinflammatory drugs (NSAIDs), sedatives and anxiolytic drugs, local anesthetics, barbiturates, and propofol. 5 tables. 95 references. (AA-M). •

Dialysis in Liver Failure and Liver Transplantation Source: Transplantation Proceedings. 25(2): 1740. April 1993. Summary: This article briefly reports on a study designed to define the long-term survival of liver transplant candidates and recipients who also require dialysis and to determine the factors important in predicting outcome. From May 1988 to June 1989, 141 patients with liver failure or liver transplant recipients required hemodialysis at the University of Pittsburgh. Eighty-eight patients received liver transplants; of these, 3 were dialyzed before transplantation, 7 were receiving dialysis at the time of transplantation, and 78 were dialyzed after transplantation. Actuarial patient survival was 51 percent after 18 months in the transplanted group. The authors summarize that acute renal failure after liver transplantation typically occurs in the setting of multiorgan failure and is associated with high mortality rates. They note that the leading cause of renal failure was ischemic acute tubular necrosis and not hepatorenal syndrome or nephrotoxic immunosuppressants. 5 references.

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Dental Treatment of a Prospective Recipient of a Liver Transplant: A Case Report Source: Journal of Clinical Pediatric Dentistry. 23(1): 75-78. 1998. Contact: Available from Journal of Clinical Pediatric Dentistry. P.O. Box 830259, Birmingham, AL 35283-0259. (800) 633-4931 or (205) 991-1177. Fax (205) 995-1588. Website: www.pediatricdentistry.com. Summary: This article describes a protocol to treat a carious (dental cavities) condition in a young girl scheduled to receive a liver transplantation. The child's teeth with serious caries were filled with amalgam. Those teeth with pulp exposure were extracted. To stop bleeding, sutures and a surgical splint with a periodontal pack were used. All procedures were performed as rapidly as possible to minimize stress. Antibiotics were used sparingly. The major goal of dental intervention, before and after liver transplantation, is the prevention of bacteremia from an oral source that could lead to systemic infection. The authors conclude that by improving the oral health of transplant recipients, the chances that the transplanted liver will become infected are much reduced, increasing the likelihood of a successful surgical outcome for the transplant. The child described in the case received her liver transplant more than two years ago,

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maintained effective oral hygiene procedures, and is still alive and well. 5 figures. 14 references. •

Hepatitis B Infection and Liver Transplantation Source: Canadian Journal of Gastroenterology. 11(5): 462-468. July-August 1997. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Summary: This article discusses liver transplantation in patients with hepatitis B. Patients with chronic hepatitis B virus (HBV) infection have historically high rates of allograft reinfection from extrahepatic (outside the liver) reservoirs of HBV, with worse long term outcome compared with that of transplant recipients without HBV infection. As a result, chronic HBV infection has been considered a contraindication for transplantation. However, prophylaxis against HBV recurrence, in the form of passive immunization with high dose hepatitis B hyperimmunoglobulin and the antiviral agent lamivudine, has recently been demonstrated to decrease the risk of reinfection. The author summarizes past experience and current status of HBV infection and transplantation, with emphasis on the issues surrounding prophylaxis. The author concludes that with appropriate prophylaxis, liver transplantation can be a viable proposition for patients with HBV infection. The main obstacles to high dose HBIG prophylaxis are the continued availability of the product, practicality of administration, and the cost and long term duration of treatment. 2 tables. 60 references. (AA-M).

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Dental Treatment of the Liver Transplant Patient Source: Oral Surgery, Oral Medicine, Oral Pathology. 73(4): 419-426. April 1992. Summary: This article first reviews the history and current status of human liver transplantation. The authors present the complications and side effects of the agents used for immunosuppression. The dental treatment of patients before and after liver transplantation is discussed in detail. 8 tables. 22 references. (AA-M).

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Review of Liver Transplantation for the Dentist and Guidelines for Dental Management Source: SCD. Special Care in Dentistry. 13(2): 74-80. March-April 1993. Summary: This article provides a review of liver transplantation for the dentist. The authors present information on the indications for liver transplant, the selection process, the surgery itself, and the mechanism and implications of immunosuppression. In addition, the authors discuss dental considerations and present protocols for the dental management of patients pre-and posttransplantation. They note that the major goal of dental intervention, before and after liver transplantation, is the prevention of bacteremia from an oral source that could lead to systemic infection. In addition, pretransplant medical conditions of concern to the dentist include poor drug metabolism, bleeding disorders, poor wound healing, and an inability to metabolize swallowed blood. Post-transplant dental treatment must take into consideration immunosuppressive drugs and the potential for infections. 6 tables. 39 references. (AAM).

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Outcomes Following Liver Transplantation for Patients with Alcohol-Versus Nonalcohol-Induced Liver Disease Source: Canadian Journal of Gastroenterology. 14(10): 851-855. November 2000.

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Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail: [email protected]. Summary: This article reports on a study undertaken to document and compare the outcomes of adult patients who received liver transplants for alcohol and nonalcohol induced liver diseases. These patients also attended a liver transplantation followup clinic in an urban, nontransplantation center at a time when no formal alcohol abuse program for transplant candidates or recipients was offered. The study population included 10 alcoholic patients and 48 nonalcoholic patients followed for an average of 41 months (range 5 to 79 months) and 46 months (range 2 to 116 months), respectively. Primary outcome variables included rates of recidivism (going back to drinking), duration of abstinence after transplantation, and compliance with posttransplant medical followup visits. Secondary outcome variables included time to discharge after transplantation, episodes of graft rejection, liver and renal biochemical abnormalities, diabetes, hypertension, sepsis, strictures, complications unrelated to transplantation, and changes in psychosocial status. Significant differences were found with respect to a higher incidence of recidivism (50 percent for alcoholic patients compared with 2 percent for nonalcoholic patients), a shorter period of abstinence after transplantation (mean of 14.7 months for alcoholic patients compared with a mean of 26.3 months for nonalcoholic patients), and more missed office visits (2.7 for alcoholic patients compared with 1.0 for nonalcoholic patients) in the alcoholic group. The alcoholic group also had a lower incidence of rejection episodes, but higher rates of posttransplantation diabetes, more nontrasplantation related complications, and higher serum creatinine but lower bilirubin and cyclosporine A levels. Marital separations were also more common in the alcoholic group. The authors conclude that, in the absence of formal alcohol abuse programs, the posttransplantation outcome in alcoholic patients generally does not compare well with that of patients who undergo transplantation for nonalcoholic related liver diseases. 3 tables. 13 references. •

Current Concepts in Pediatric Liver Transplant Source: Seminars in Liver Disease. 18(3): 295-307. 1998. Contact: Available from Thieme Medical Publishers, Inc. 333 Seventh Avenue, New York, NY 10001. (212) 760-0888. Fax (212) 947-1112. Website: www.thieme.com. Summary: This article reviews orthotopic liver transplantation, a procedure that has significantly improved the survival rate of children with end stage liver disease. Efforts to correct abnormalities existing prior to transplantation, coupled with improved surgical techniques and immunosuppression have led to better quality of life and 1 year survival rates approaching 90 percent in many centers. Despite this success, the expanding waiting list has driven the development of surgical techniques to expand the donor pool. Building on the success of reduced size transplantation, split liver and living donor transplantation are now suitable alternatives, especially when used in candidates with satisfactory clinical stability. In the postoperative period, infectious complications represent an important cause of morbidity and mortality. Although antimicrobial regimens are effective in the immediate postoperative phase, acquisition of viral infections represents a major concern, particularly in the young liver recipient. Early detection and development of new antiviral agents are likely to decrease occurrence of posttransplant proliferative disorders and optimize long term outcomes. 4 figures. 6 tables. 70 references. (AA).

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Liver Transplantation: Current Status and Novel Approaches to Liver Replacement Source: Gastroenterology. 120(3): 749-762. February 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: This article reviews the current status and novel approaches to liver replacement. The author contends that the major challenge currently facing liver transplantation is the performance of a greater number of liver transplants, which has been fueled by the large and growing disparity between the increasing number of qualified patients listed for transplantation and the relatively static number of available cadaver donor organs. In the past 2 years, approximately 4,500 liver transplants have been performed annually, with 1 year survival rates in the 85 to 90 percent range, while the waiting list has expanded as of November 2000 to more than 16,000 patients, resulting in an increasing death rate among listed patients. In the short term, there will continue to be a major focus on more effective use of available cadaver donor organs to balance the competing principles of justice (patients with most urgent need for transplant and lower probability of posttransplant survival) and medical utility (patients with less urgent need for transplant and higher odds of postoperative survival). Over the long term, there will be an increasing application of novel approaches to liver replacement including cadaver split liver transplantation and adult living donor liver transplantation and possibly, in the more distant future, xenotransplantation (using organs from other mammals) and hepatocyte transplantation. The treatment, and ideally the prevention, of recurrent disease after liver transplantation, notably chronic hepatitis C, is a major priority to optimize the use of liver grafts. Finally, improved immunosuppressive strategies, including movement toward minimal immunosuppression and steroid withdrawal and the development of safer and more effective drugs, is another important factor that has the potential to increase the success of liver transplantation. 2 figures. 11 tables. 104 references.

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Nutrition Considerations in Liver Transplantation Source: Topics in Clinical Nutrition. 7(3): 24-33. June 1992. Summary: This article reviews the nutritional considerations in liver transplantation. Topics include the types of liver disease that may require transplantation as a therapeutic option; nutrition assessment of the orthotopic liver transplant (OLT) patient; short-term posttransplant nutrition problems and requirements; and long-term nutrition treatment, problems, and needs. The article concludes with a detailed case study of a patient that illustrates the difficult nutrition needs of an OLT patient and an unusual complication (Stevens-Johnson syndrome).

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Alcoholics and Liver Transplantation Source: JAMA. Journal of the American Medical Association. 265(10): 1299-1301. March 13, 1991. Summary: Two arguments underlie a widespread unwillingness to consider patients with alcoholic cirrhosis of the liver as candidates for transplantation. First, alcoholics are considered by some to be morally blameworthy and their condition is believed to be the result of their own misconduct; this disqualifies alcoholics in unavoidable competition for organs with others who are equally sick but blameless. Second, because of their habits, it is believed that alcoholics will not exhibit satisfactory rates of survival after transplantation; good stewardship of a scarce lifesaving resource therefore requires that

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alcoholics not be considered for liver transplantation. This article carefully analyzes these arguments and proves them to be defective. The authors conclude that there is not good moral or medical reason for categorically precluding alcoholics as candidates for liver transplantation. 19 references. (AA-M).

Federally Funded Research on Liver Transplant The U.S. Government supports a variety of research studies relating to liver transplant. 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 liver transplant. 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 liver transplant. The following is typical of the type of information found when searching the CRISP database for liver transplant: •

Project Title: A GENERALIZED MODEL FOR POST-TRANSPLANT SURVIVAL Principal Investigator & Institution: Chang, Chung-Chou H.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant) The applicant's long-term career goal is to become an independent investigator in analytical methodologies for clinical and health services research. She will dedicate her career to conducting quantitative studies and promoting the proper use of analytical methodologies in these research areas. This career development award will provide her with initial support for achieving her career goals. There are three goals for her career development over the next five years. First, she will develop a general survival regression model that is more encompassing than any of the semi-parametric regression models currently used in the analysis of liver transplantation data. The proposed research will result in less restrictive assumptions and provide a systematic way of constructing survival models in liver transplantation studies. The products of the research include a new model that can be used to provide estimates on post-transplant survival, which in turn can be used to estimate the optimal timing for liver transplantation. Her second objective is to develop expertise in clinical applications of survival analysis for patient-oriented research. The third goal is to become an educator to clinical researchers in analytical methodologies. While many other questions are also important in the area of transplantation (such as which organ allocation method is optimal and what is the appropriate time to list a patient for transplant), many of the clinically related questions require accurate and clinically relevant predictions of survival. The proposed research will focus on: Aim 1:

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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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Development of a general survival regression model. Aim 2: Development of diagnostic procedures for the general survival regression model. Aim 3: Assessment of the impact of different survival models on the prognosis in liver transplantation. The proposed general survival model that reduces to both the additive and multiplicative model as special cases. Moreover, the covariate effect on hazard in this model can be either constant or time-varying. Estimation of the model parameters will through the penalized log-partial likelihood with double penalty terms. Inference on the effect of any given covariate will also be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ACCESS OF BLACK PATIENTS TO LIVER TRANSPLANTATION Principal Investigator & Institution: Reid, Andrea E.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 29-SEP-2005 Summary: (adapted from the application) Orthotopic liver transplantation is the treatment of choice for selected patients with end-stage liver disease (ESLD). Unfortunately, liver allografts are a scarce resource. The disparity between the supply and demand for donor livers creates a potential for bias in the selection of organ recipients and the allocation of available organs. There is evidence that liver transplants are less available to blacks that to whites, despite a higher burden of ESLD, and higher rates of death from ESLD among blacks. Several small studies have suggested that barriers do exist for black patients with ESLD, but these barriers have not been defined. The overall goal of this grant is to determine what and where the barriers to transplantation are for black patients with ESLD. We will examine two components of the pre-transplant process in this study. We will focus on the referral process from the physician to the transplant center, and on patient perceptions of liver transplantation and the transplantation process. The specific aims of our study are: 1) To compare the referral rates for liver transplant evaluation and the overall clinical outcome in black and white patients with ESLD who were treated at three urban hospitals in Boston between 1994 and 1998, and 2) To determine if there are racial differences in knowledge and preferences about liver transplantation among patients with chronic liver disease. We will perform a retrospective cohort study of black and white patients with ESLD to determine if there are different rates of referral for liver transplant based on race. We will examine the clinical, financial, social, socioeconomic, and demographic factors that influence the rates of referral for liver transplant evaluation for these populations. We will also test the hypothesis that patient knowledge, attitudes and preferences about liver transplantation vary according to race and may influence the willingness of patients with ESLD to accept a liver transplant. To accomplish this, we will conduct a survey of a racially diverse group of patients with chronic liver disease. We will develop an appropriate instrument during the course of this grant, validate and pre-test it, then administer it to our study cohort. Advanced-level coursework in clinical epidemiology, biostatistics, survey development, and outcomes will also be a critical element of this project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ADLDT: AN OPPORTUNITY TO EXPAND THE NATIONAL DONOR POOL Principal Investigator & Institution: Busuttil, Ronald W.; Surgery; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024

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Timing: Fiscal Year 2002; Project Start 17-SEP-2002; Project End 31-AUG-2009 Summary: (provided by applicant):The overall objective of this proposal is to establish a Clinical Research Consortium to define the outcomes of ALDLT. We propose the following specific aims to fully evaluate the impact of ALDLT: 1. Core Study: Establish a Donor and Recipient Core Information Database for Adult LDLT and Non-ALDLT Patients Hypothesis: ALDLT short-term survival outcomes, but not complication rates, are equivalent to whole cadaveric and SLT transplantation. We and others, achieved excellent short-tem survival outcomes of ALDLT, despite a high rate of recipient complications, in non-urgent patients. To fully evaluate the benefits of ALDLT, the technique will be applied to both urgent and non-urgent recipients, and compare its outcomes to three sets of patient cohorts that include: a) whole organ recipients, b) cadaveric SLT recipients, and c) candidates who ultimately do not receive a transplant. The living donor section will compare living donors and potential donors who do not undergo donation. Primary endpoints define survival outcomes and complication rates in donors and recipients at 1, 2 and 3 years posttransplantation. This will elucidate the efficacy of ALDLT as compared to whole cadaveric, SLT, and control (untransplanted) patients in the entire spectrum of recipients' status, and determine if ALDLT is justified when compared to the natural history of non-transplanted non-urgent controls. Secondary endpoints assess the impact of technical variations on postoperative recovery, liver regeneration postdonation, impact of living donation on the cadaveric donor pool, and defines donor exclusion criteria.2. Clinical Research Protocol for Recipient Outcome: Determine the impact of ALDLT on Posttransplant HCV Recurrence in Transplant Recipients Hypothesis: ALDLT may be accompanied by accelerated recurrence of HCV versus whole cadaveric liver transplantation. Rapid and severe HCV recurrence observed, at our center, in ALDLT recipients compared to whole organ transplant patients, may offset the benefits of early transplantation with living donors. This protocol compares the time to histological recurrence of HCV in ALDLT and whole organ graft recipients at 6 months, 1, 2, and 3 years posttransplantation. The effects on patient and graft survival and the correlation between the degree of histological disease and HCV RNA levels are investigated by our secondary endpoints.3. Clinical Research Protocol for Donor Outcome: Determine Health-Related Quality of Life Outcomes and Resource Utilization of Adult Living Donation Hypothesis: HRQL of living donors is impacted in the short-, but not, the long-term and the HRQL of ALDLT recipients may be enhanced following ALDLT. HRQL in both donors and recipients will be compared before ALDLT and at 6 and 12 months posttransplantation through generic and diseasespecific instruments. Additionally, health utility index assessments and evaluation of health care resource utilization will be conducted. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADULT LIVE DONOR LIVER TRANSPLANT-A COMPARATIVE ANALYSIS Principal Investigator & Institution: Abecassis, Michael; Associate Professor of Surgery; Surgery; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 17-SEP-2002; Project End 31-AUG-2009 Summary: (provided by applicant):The shortage of available cadaver organs has prompted the transplant community to consider living donor liver transplantation (LDLT) as an effective alternative to cadaveric liver transplantation (CLT). The potential limitations of LDLT consist primarily of 1) the potential risk to an otherwise healthy donor, and 2) the uncertainty regarding graft and patient outcomes for LDLT as compared to CLT. The core project of this proposal will compare outcomes for recipients

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of LDLT to those of CLT, while addressing the potential complications to living donors. In addition, we propose to analyze two separate issues. First, we will evaluate donor hepatic steatosis in both LDLT and CLT. We will compare novel non-invasive measurements of steatosis in living donors with the current gold standard, a liver biopsy. We will compare the results of transplanting steatotic livers from living and cadaveric donors, assessing graft and patient outcomes in both groups. We will also evaluate the role of hepatic steatosis on liver regeneration in both the living donor and recipient. We hypothesize that outcome of transplantation in steatotic livers of LDLT is superior to results obtained in steatotic CLT recipients. This first aim will help design a decision algorithm for the use of steatotic livers in both CLT and LDLT while validating non-invasive measurements of hepatic steatosis. Second, we propose to address the potential role for LDLT in the multimodal management of hepatocellular carcinoma (HCC). Given the lack of randomized trials and large case series, this issue has been recently addressed in studies utilizing decision-modeling analysis. This second aim will provide clinical data to validate these studies, and will compare CLT, with its inherent waiting times, to LDLT, a strategy that theoretically eliminates waiting times. We hypothesize that the outcome of transplantation of HCC in LDLT is superior to results obtained with CLT. In the aggregate, these studies will define the efficacy of LDLT in the US, while a focus on both a donor issue (hepatic steatosis) and a recipient issue (the special problem of HCC) will help delineate the potential advantages of LDLT over CLT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADULT TO ADULT LDLT COHORT STUDY Principal Investigator & Institution: Shaked, Abraham; Surgery; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 17-SEP-2002; Project End 31-AUG-2009 Summary: (provided by applicant):The aim of this proposal is to demonstrate that the group of physicians and scientists at the Liver Transplant Program of the University of Pennsylvania has the interest, infrastructure and resources to participate in the Living Donor Liver Transplantation (LDLT) Cohort Study among adults awaiting transplantation. Progress in the care of patients suffering from end stage liver disease has been hampered by the limited availability of donor organs for transplantation. Adult to adult LDLT is expected to significantly expand the donor pool and provide numerous organs to be transplanted into designated recipients. The initial results are encouraging, however, there are many questions related to donor and recipient outcomes and whether better management of these patients can improve these results.A prospective mutli-center study of LDLT in the adult setting is expected to: 1. Collect and analyze data that will assist in the establishment of reliable criteria for donor selection, examine operative techniques that are associated with the best short and long term outcomes, and recommend methods for long-term follow up of the donor's physical and psychosocial well being. 2. Determine recipient outcomes when compared to the cadaveric setting and study whether results are affected by preoperative selection and preparation, operative techniques, and the interrelationship between regeneration and immune response. 3. Study the effects of LDLT on clinical practice and socioeconomic issues in transplantation. Success in addressing these problems through a national collaborative network will depend on the scientific and operational performance of the centers involved in the consortium. The Penn Transplant center is committed to participate in these collaborative efforts, and contribute to the research efforts that are aimed at better understanding of medical and surgical issues of LDLT.Our proposal is

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divided into three sections. Section one: A description of the resources and participation of the team of physicians at Penn Transplant Center. Section two: A description and strategy for the development of a comprehensive database. Section three: Two research proposals describing a four year research effort to identify: a. the interrelationship between the regenerative process, graft function, alloimmune response. and b. the biopsychosocial impact of LDLT on donors and recipients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADULT TO ADULT LIVING DONOR LIVER TRANSPLANTATION Principal Investigator & Institution: Fisher, Robert A.; Surgery; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 17-SEP-2002; Project End 31-AUG-2009 Summary: (provided by applicant):Over the past decade a growing shortage of donated organs has greatly increased the number of patients who have developed complications of end-stage cirrhosis including hepatocellular carcinoma (HCC) and the mortality for patients awaiting liver transplantation (LT). Living donor liver transplantation (LDLT) was conceived as a way to increase the availability of donated organs and was initiated in infants and children more than a decade ago. Controlled trials demonstrated the safety and efficacy of this procedure. Recently, LDLT has been adapted for the adult. Since then patients, their families and the transplant community have embraced this procedure despite reports of donor morbidity, mortality and early reports that recipients may have increased post-operative complications and reduced survival compared to CADLT. The specific aims of the LDLT cohort study is to define the short and long term risks of morbidity and mortality for the adult donor and to determine the efficacy of this procedure for the adult recipient compared to patients undergoing LT with a cadaveric liver (CADLT). Individuals interested in becoming living donors will be asked to participate in this study. Those who are selected and undergo the surgical procedure will be followed at periodic intervals to define the long term morbidity and mortality of the procedure. Individuals not selected as living donors will be matched to the actual donors 2:1 by age, race and gender and also followed prospectively as a donor control group. Individuals being evaluated for LT will be asked if they would be interested in undergoing LDLT. Those patients who identify an acceptable donor and undergo LDLT will be followed prospectively at periodic intervals to define the short and long term morbidity and mortality associated with this procedure. Those patients who are unable to identify a living donor will be matched to an actual LDLT recipient 2:1 by age, race, gender, disease etiology and severity of liver disease (MELD score). These patients will act as the recipient control group and will and be followed prospectively before and after they undergo CADLT. Ancillary studies accompanying the main trial will specifically evaluate the ability of LDLT to improve the long term outcome of patients with HCC and to evaluate the effects of donation and LDLT on hepatic histology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ADULT TO ADULT LIVING DONOR LIVER TRANSPLANTATION COHOR* Principal Investigator & Institution: Emond, Jean C.; Surgery; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2009 Summary: (provided by applicant): Living donor liver transplantation (LDLT) has been widely accepted for the transplantation of children with excellent results in the recipient,

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and a track record of donor safety that approaches renal donation. In the face of a progressive scarcity of cadaver donors, LDLT has been extended to adults and proliferated rapidly over the last 4 years. This operation requires a more extensive hepatectomy and thus an increased risk to the donor which has not been adequately quantified. The combination of uncertain donor risk and unregulated proliferation has led to cries of alarm in both the scientific literature and the lay press. The current study will provide a structured response to these concerns and an opportunity to address fascinating biological questions inherent to this procedure. Our interest in LDLT spans nearly two decades across a broad range of surgical and medical issues. The liver transplant program in our center was constituted from the outset with the expectation that LDLT would be a significant proportion of our transplants because of the enormous waiting list in New York State. Currently LDLT accounts for nearly 1/3 of adult transplants in our center; we will perform 30 this year with continued anticipated growth in the next 5 years. Our team is broadly constituted and exceptionally capable of addressing a range of issues pertaining to structured health assessment of donor outcomes, medical indications and application of LDLT as well as surgical and biological questions. We have particular strength in epidemiology, virology, and immunology, in addition to transplant hepatology and surgery. While we recognize that a broad range of surgical questions will need to be addressed, we find two issues specific to LDLT related to the central theme of regeneration of the allograft most compelling; first, the pathophysiology and possible treatment of failure of regeneration in the recipient, ie. "small-for-size syndrome", and second, the risk of early and more severe recurrence of hepatitis C in a regenerating liver graft. The central theme of regeneration pervades LDLT, and likely hinges on inflammatory injury. Our collaborative partners, Charles Rice of the New York-Presbyterian Center for the Study of Hepatitis C and Manikkan Suthanthiran in the Transplantation Medicine program position us to test our hypotheses using novel techniques for the assessment of inflammatory cytokines and viral reinfection on the cellular level. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADULT TO ADULT LIVING DONOR LIVER TRANSPLANTATION COHORT Principal Investigator & Institution: Freise, Chris; Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2009 Summary: (provided by applicant): Cadaveric liver transplantation is recognized as the optimal therapy for end stage liver disease, with marked improvement in results over the last two decades. With the increasing success of this treatment, the demand for suitable donor organs has also risen, resulting in a large discrepancy between the number of transplantable organs and the number of patients waiting. This imbalance has led to the development of living donor liver transplantation (LDLT) as an additional method to increase organ supply. The exact indications for this procedure as well as long-term results and potential impact on the healthy donor are questions that remain unanswered. These issues form the basis for this research protocol, which proposes a longitudinal cohort study of live donor liver transplant recipients and their donors across eight transplant centers with an extended period of follow-up. The aims of this cohort study will be the formation of a core database containing information collected pre-transplant, intraoperatively and post-transplant. At least 250 living liver donor/recipient pairs and an equal or greater number of cadaveric recipients will be followed for a minimum of two years to provide critically needed information on the

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safety and efficacy of living donor liver transplantation, the potential impact on disease progression and recurrence, and ultimately to better define the specific role of living donor liver transplantation in the management of end stage liver disease.In addition to core data collection, this cohort study will offer an opportunity to address specific research questions unique to the setting of LDLT. The first project focuses on patients with hepatitis C, the most common indication for transplantation in the U.S. The kinetics of recurrent hepatitis C viral load post-transplantation will be compared in living donor and matched cadaveric recipients, and the effect of pre-transplant interferon treatment on the tempo and severity of recurrence evaluated. The second project focuses on optimization of pain control in living donors, comparing the use of preemptive thoracic epidural catheter analgesia delivery with patient controlled intravenous analgesia, and using pain scores and quality of life instruments to evaluate the impact of these treatments on long and short-term outcomes.We anticipate that the study will provide the necessary information to aid physicians in the counseling of patients regarding transplant options, and help prospective donors and recipients to better understand the risks and benefits of the procedure. Additionally, the information gained through this cohort study can be expected to impact the entire living donor transplantation procedure itself, by identifying factors that can be modified pre-transplantation, intraoperativiely, and post-transplantation to improve donor and recipient outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALCOHOL, INOS UPREGULATION, LEAKY GUT & LIVER DISEASE Principal Investigator & Institution: Keshavarzian, Ali; Professor of Pharmacology & Molecular Bi; Rush University Medical Center Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): Clinically significant alcoholic (A) liver damage (LD), secondary to a hepatic necroinflammatory cascade (HNIC), occurs only in a subset of alcoholics. Hence, factors other than ethanol (E) must be involved. Hypothesis: The key cofactor for ALD is a breakdown of gut barrier integrity ("leaky gut") due to chronic E use, which allows intestinal endotoxin to reach the liver & initiate a HNIC; this leakiness is due to cytoskeletal instability caused by oxidation of cytoskeletal proteins which is elicited by E-induced gut iNOS upregulation & nitric oxide (NO) overproduction. We found: 1} in man, gut leakiness in alcoholics with LD but not in those without LD or in nonalcoholics with LD; 2} in rats, E-induced leaky gut is associated with LD; reversal of gut leakiness attenuates LD; 3} in intestinal monolayers, E-induced iNOS upregulation causes cytoskeletal & barrier disruption. We will continue to use this successful translational approach (monolayers, rats & man) to test our current hypotheses. Aims: (1) To see if, in a larger sample, a leaky gut: a) occurs only in alcoholics with LD & precedes cirrhosis b) persists during abstinence & after liver transplant for ALD, c) correlates quantitatively with LD severity, d) is associated with NO overproduction & HNIC, e) is more pronounced in females. We predict that gut leakiness (excess urinary lactulose, mannitol & sucralose levels after oral sugar load): i) is seen only in alcoholics with LD, precedes cirrhosis; ii) correlates with severity of LD (clinical parameters, liver enzymes); iii) is associated with NO overproduction (gut mucosal NO), serum endotoxin & HNIC (high neopterin/cytokines). (2) To see if, in rats, prevention of E-induced leaky gut also prevents E-induced LD & if a hyperactive, NO pathway is involved. We predict that in E-fed rats with LD: i) leaky gut, endotoxemia, HNIC, upregulation of intestinal iNOS, NO overproduction & oxidation of actin & tubulin occurs; ii) preventing gut leakiness (by oats, iNOS inhibitors or Arginine) prevents LD. (3) To see, using monolayers of wild type ((inhibitors) &

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transfected cells, if E-induced iNOS upregulation & its consequences (assessed by cytoskeletal oxidation/disarray & barrier disruption) are mediated by NF-kappaB activation. We predict i) E activates NF-kappaB by degrading IkappaBalpha; ii) preventing NF-kappaB activation prevents E-induced iNOS upregulation & its consequences. Significance: Showing that ALD requires a leaky gut, & that NO & cytoskeletal pathways are involved, could 1) identify drinkers at risk for LD (sugar test); 2) lead to therapies to prevent LD in those drinkers unable to abstain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CANDIDATES

ALCOHOLISM

TREATMENT

IN

LIVER

TRANSPLANT

Principal Investigator & Institution: Weinrieb, Robert M.; Assistant Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 22-SEP-1999; Project End 31-AUG-2004 Summary: Alcoholism is the most common root cause of end stage liver disease in the United States. By the time cirrhosis with liver failure is diagnosed, there are often no viable alternatives to liver transplantation even for the then-abstinent alcoholic. Liver transplant surgery is costly and donor organs are scarce. Once selected for transplant, patients typically wait two years for an organ and must remain "medically and psychologically stable". Data from our studies indicate that 15 percent of listed alcoholic liver transplant candidates admit drinking - and we believe this may be an underestimate. Further, studies have shown that cirrhotic alcoholics who continue to drink have high rates of mortality. Once listed, alcoholic patients are typically referred off-site for alcohol treatment or to AA meetings. But, our research has shown that greater than 50 percent of alcoholic patients who received liver transplants never attended formal substance abuse treatment or AA. Based on the data from these pilot efforts and from the larger literature on promising therapies for alcohol dependence, we plan to test a modified and expanded version of Motivational Enhancement Therapy (MET) combined with case management techniques (STD-MET), for use in the treatment of alcoholics awaiting liver transplant. We will test this integrated alcohol treatment in a randomized controlled design comparing two samples of 100 listed alcoholic liver transplant patients, each receiving supplemental treatments for their alcoholism over a six month period while listed. Both groups will receive standard referral to AA and community treatment. One group will receive on-site, integrated STD-MET while the second group will receive an equal number of sessions, on-site, viewing alcohol educational videos (STD-VID). Hypotheses: 1.During the pre-transplant "wait list" period - patients receiving STD-MET will show better engagement into the liver transplant regimen, reduced drinking and better general function than patients assigned to (STD-VID). STD-MET group will show: a) greater compliance with appointments and medical regimen - measured by standard measures of attendance, medical status, recall and understanding of their medication regimen, b) more awareness and acceptance of alcohol, smoking and/or other drug problems - measured by the (SOCRATES) stage of change, c) more attendance at standard off-site alcohol treatment programs and AA meetings - measured by standard checks on treatment attendance as well as TSR from subjects and collaterals, d) greater and more lasting reductions in drinking, cigarette and other drug use - measured by urine screens, breathalyzer, self-report and collateral TLFB measures, e) lower levels of depression and anxiety - measured by the BDI, BAI and the ASI psychiatric scale every three months, f) less mortality and morbidity prior to organ transplant - than the STD-VID group. 2. For patients who ultimately receive a liver transplant - STD-MET patients will show better general recovery than patients assigned

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to the alcohol education video series STD-VID. The STD-MET will show: a) fewer complications during during hospitalization measured by standard surgical records, b) better general function at one- month post hospital discharge-measured by standard medical evaluation and ASI than the STD-VID group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: APOPTOSIS IN TRANSPLANTATION Principal Investigator & Institution: Krams, Sheri M.; Associate Professor; Surgery; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: (adapted from applicant's abstract): Apoptosis is a highly regulated program of cell death. Recent studies suggest that apoptosis is an important mechanism of tissue injury in allograft rejection. The hypothesis to be tested is that apoptosis has a dual role in the allograft, a deleterious role is a mechanism of graft cell damage and a beneficial role involving elimination of alloreactive cells. The overall goal of this project is to modulate apoptosis during organ transplantation so as to inhibit death of graft associated cells and to promote deletion of infiltrating host reactive cells. An integrated series of studies utilizing well defined animal models of orthotopic liver transplantation and small intestinal transplantation are proposed. In Specific Aim 1 the mechanisms responsible for apoptotic graft damage during allograft rejection will be defined. RNase protection assays, and competitive reverse transcriptase polymerase chain reaction will be utilized to determine the cellular and soluble initiators as well as the signaling pathways which culminate in irreversible cell damage and death. Further studies will utilize functional assays to examine the proteolytic cleavage of caspases during graft rejection. Specific peptide inhibitors of caspase activation will be administered to allograft recipients to disrupt the apoptotic pathway and graft damage. The investigators have previously determined that CD8+ cells are not essential for allograft rejection or graft cell apoptosis. The apoptotic pathways that function independent of CD8 cells will therefore be elucidated and modulated in Specific Aim 2. In Specific Aim 3 they will examine the role of apoptosis in inducing allograft tolerance. Recently, they have determined that depletion of the majority of host CD4+ T cells results in abundant apoptosis of graft infiltrating cells with minimal allograft damage and rejection. The cellular and biochemical mechanisms by which infiltrating lymphocytes are deleted will be examined using this model. Furthermore, the impact of conventional immunosuppressives and the deletion of alloreactive host lymphocytes will be studied. Definition and characterization of apoptotic pathways in organ transplantation will lead to novel therapeutics to enhance graft survival and eliminate alloreactive cells while preserving the host immune response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIORAD ASPERGILLOSIS

GALACTOMANNAN

EIA

FOR

DIAGNOSIS

OF

Principal Investigator & Institution: Marr, Kieren A.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 29-FEB-2008 Summary: (provided by applicant): The Bio-Rad galactomannan enzyme immunoassay (GM EIA) will soon be submitted to the FDA for approval as an aid to diagnose aspergillosis, a frequent cause of infectious death in immunosuppressed patients. Our preliminary studies suggest that the assay may also be used as a screening test to enable

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Liver Transplant

early diagnoses; however, the optimal cut-offs for positivity have not been determined. Defining cut-offs to optimize performance is critical for patients who have different manifestations of infection (endobronchial vs. invasive), such as in solid organ transplant recipients, and in children, who appear to have frequent false-positive results. The studies proposed in this project will define parameters to use the GM EIA in multiple different patient populations, using clinical samples obtained from a large ongoing FHCRC longitudinal protocol in adult allogeneic hematopoietic stem cell transplant (HSCT) recipients, and samples obtained from multicenter trials sponsored by the NIH. Aim 1 will define parameters for use of the GM EIA as an early diagnostic test for aspergillosis in adult allogeneic HSCT patients. Studies will be performed to determine the lower limit of GM detection, identify clinical factors that impact levels of circulating GM, and to determine the role of GM EIA applied to non-blood fluids (bronchoalveolar lavage fluid and urine). Aim 2 will define appropriate cut-offs for positivity and characterize performance of the GM EIA as a diagnostic assay for aspergillosis in high-risk solid organ transplant recipients. To do this, longitudinal sample collection will be performed in a protocol conducted as a companion to an ongoing CDC-sponsored multicenter surveillance study. Aim 3 will define parameters for use of the GM EIA as an early diagnostic test for aspergillosis in neutropenic children. To determine the appropriate cut-offs for positivity in children, GM EIAs will be performed on serial sera obtained from children at high risk for aspergillosis after treatment with induction chemotherapy for AML, and after cord blood transplant. Companion protocols will be performed to collect sera as part of ongoing multicenter studies performed by the Children' s Oncology Group and the NHLBI Cord Blood Transplantation Study. Studies will be performed to determine if false-positivity of the GM EIA in children corresponds with gut translocation of GM during periods of mucositis, by measuring surrogate markers for GI integrity in a case-control study. This project is enabled by the cooperative activities of FHCRC investigators, Bio-Rad Laboratories, and several multicenter networks supported by the CDC, NIAID, and NHLBI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BOUND SOLUTE DIALYSIS Principal Investigator & Institution: Patzer, John F.; Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-APR-2007 Summary: (provided by applicant): The American Liver Foundation estimates that one in ten people has some form of liver disease and that 26,000 people die each year from liver disease. In the year 2000, 18,137 people were listed for liver transplantation, only 4,934 cadaveric donor liver transplants were made, and 1,636 patients died while awaiting transplant. A medical need for a treatment modality that can "bridge" patients to transplant or slow or reverse the progression of liver disease clearly exists. Even better would be a new standard of care treatment that can be easily employed by any hospital at early stages (Parson's encephalopathy grade 1 and 2) of liver failure that would retard or prevent progression to acute liver failure that requires OLTx. Bound solute dialysis (BSD), practiced heuristically by the MARS and Biologic-DT approaches, offers the potential of a new standard of care treatment modality. Improvements in such heuristic practice require a theoretical approach that encompasses the underlying thermodynamics and transport phenomena. Such an analysis indicates that BSD is both more robust and more easily employed than expected from the heuristic approaches practiced here-to-fore. Experimental observations follow the theoretical predictions. The

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objective of this research proposal is to expend upon the preliminary studies in order to define what is necessary to bring BSD to the status of an easily employed standard of care treatment for liver disease that can be practiced with minimal requirements by any hospital or clinic. This will be accomplished by expanding the theoretical approach to encompass other forms of BSD, experimental validation of modeling predictions, development of an animal model of chronic liver failure, and preclinical evaluation of the various modes of BSD with the animal model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMPREHENSIVE FOLLOW-UP OF LIVING DONORS Principal Investigator & Institution: Matas, Arthur J.; Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: The aims of this project are to definitively determine the long-term risks associated with kidney donation and the short- and long-term risk of liver donation. These represent 2 separate situations: a) living kidney donation has been done for the last 4 decades and the short-term risks have been well-defined. But (previous retrospective) long-term studies have suffered from inability to contact all the donors. In some of these studies, it has been shown that some donors have hypertension, proteinuria, and renal dysfunction. And it is know that some donors have developed ESRD. Yet, because follow-up is incomplete, it is unclear whether the risk to the donor exceeds that of the general population. We plan a long-term study, in which we maintain regular contact with the kidney donors, to determine: the risk of developing hypertension, albuminuria, and renal dysfunction (and any progression should they develop). We will also determine the incidence of type 2 diabetes and study whether nephropathy occurs more rapidly in the uninephrectomized donor. And we will study the impact of postdonation proteinuria on cardiovascular risk. Living donor (especially right lobe) liver transplantation is a relatively new innovation. There are few short-term and no long-term follow-up studies. We plan a long-term study, in which we maintain regular contact with the donors to determine both short- and long-term term consequences of living donor liver transplantation. Both of these follow-up studies are necessary to be able to provide accurate information to prospective donors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--CLINICAL AND TRANSLATIONAL RESEARCH Principal Investigator & Institution: Peters, Marion G.; Professor; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAY-2007 Summary: (provided by the applicant) The Core Facility provides Liver Center investigators with biostatistical consultation, data analysis, interpretation, and assistance in writing up statistical methods and results; serum samples, peripheral blood mononuclear cells and liver specimens from patients with liver disease and limited clinical data from these patients. Investigation of liver disease transcends many disciplines from adult hepatology to pediatrics, from surgery to radiology to pathology, from basic immunology to clinical virology to epidemiology. Liver Center investigators have been studying questions related not only to liver transplantation and antiviral therapy but also to biliary disease, variceal bleeding, cost effectiveness and quality of life. The Core has been able to provide support for a broad range of investigations into hepatobiliary diseases and normal hepatic metabolism, and to serve as a regional and

26

Liver Transplant

national resource for clinical research in viral hepatitis and transplant. Finally, the Core has been instrumental in bringing together a group of investigators focused on liver cancer, who now have applied for expanded funding in this area, through the NCI SPORE mechanism. The Core provides comprehensive assistance to investigators at all stages of study development and execution, including assistance with study design, database construction, statistical analysis, and manuscript writing. By removing the inertial barriers to entering clinical research, it plays a major role in the productivity and career development of UCSF trainees and junior faculty while also assisting more senior investigators with established research programs. The extensive collection of serum and tissue samples has been made available to, and utilized extensively by, Liver Center members and, on a limited basis, by non-Center investigators at other academic institutions. The diversity and number of specimens available through the Core provides a scarce and unique human resource for those engaged in clinical and translational research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--HUMAN LIVER AND TISSUE BANKS Principal Investigator & Institution: Thummel, Kenneth E.; Professor; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 06-AUG-2003; Project End 31-JUL-2008 Summary: HUMAN LIVER AND INTESTINE BANKS: The PPG Core has been obtaining human tissue for use in research since 1986. This occurred initially through a collaboration with Dr. Craig Eddy, in the Department of Surgery at UWMC, and later through a collaboration with a past Core co-investigator, Dr. James Perkins, Director of Transplantation in the Division of Transplant Surgery. In addition, the procurement of tissue occurred with the assistance and consent of the regional Organ Procurement Agency, formerly the Northwest Organ Procurement Agency and now LifeCenter Northwest. Protocols for the acquisition and safe handling of human tissue have been approved by the University of Washington Human Subjects Review Committee. As of September 2002, a total of 71 human livers and 64 human intestines have been collected. Approximately half of the livers were rejected for transplantation, the other half were obtained either before the establishment of the liver transplant program (before 1991) or represent waste tissue from split liver transplants in a pediatric population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CYTOGAM TO PREVENT EBV INFECTION IN PED LIVER TRANSPLANT Principal Investigator & Institution: Burroughs, Margaret; Mount Sinai School of Medicine of Cuny New York, Ny 10029 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: CYTOKINES AND LIVER TRANSPLANTATION Principal Investigator & Institution: Martinez, Olivia M.; Associate Professor; Surgery; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-JUL-1993; Project End 30-NOV-2003

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Summary: The long term goal of this project is to understand the role of cytokines in the cellular and molecular mechanisms of liver allograft rejection. During the previous funding period the in situ cytokine profile during human liver allograft rejection was characterized for the first time. The findings indicate that human allograft rejection does not conform to the Th1/Th2 paradigm. Elucidation of the intragraft cytokine profile led to the identification of cellular effector pathways that are operative in human allografts. Furthermore, a novel T cell subset that expresses CD30 and is the primary source of IL-5 and IFN-gamma produced in response to alloantigen has been identified. The hypothesis to be tested is that CD30 expression identifies a population of alloreactive, cytokine-producing T cells that promote graft rejection. In the first specific aim the development, regulation, and function of alloreactive CD30+ T cells will be characterized. Alloactivated CD30+ T cells obtained by fluorescence activated cell sorting and single cell cloning will be utilized to define the cytokine profile of CD4+CD30+ and CD8+CD30+ cells. CD30+ T cells will be added to mixed leukocyte cultures to determine their ability to regulate allospecific proliferative responses, cytotoxic T cell development, and antibody production. Antibody blocking and transfection strategies will define the contribution of the co- stimulatory molecules B7-1 and B7-2 to the development of CD30 cells. The influence of immunosuppression and the form of alloantigen on the development of CD30 T cells will be determined. Aim 2 will characterize the function of the CD30 molecule. The hypothesis to be tested is that CD30 ligation engages the cytokine gene expression program in alloactivated T cells. CD30+ T cells will be stimulated with agonistic anti-CD30 mAbs and the effect on cytokine gene and protein expression will be determined. Transfection experiments will examine the link between CD30 signaling and cytokine gene promoter activity. Truncation mutants of the CD30 molecule will identify the intracellular regions necessary for induction of cytokine gene expression. Aim 3 will define the role of CD30+ T cells in allograft rejection utilizing a rat orthotopic liver transplant model. The development and function of alloreactive CD30 cells during graft rejection will be assessed by immunohistochemical staining and by isolation and characterization of CD30+ T cells from rejecting allografts. CD30+ T cells will be depleted by antibodybased approaches, including immunotoxins, and the impact on the cellular and molecular pathways of graft rejection will be assessed. The contribution of CD30+ T cells to graft rejection will be directly determined in an adoptive transfer model. We anticipate elucidation of the function of CD30+ cells and their role in liver allograft rejection. Identification and characterization of an alloreactive immunoregulatory subset with discrete phenotypic markers would enhance the development of therapeutic strategies to achieve specific immunosuppression in organ allograft recipients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETECTION AND CTL THERAPY OF PTLD AFTER LIVER TRANSPLANT Principal Investigator & Institution: Goss, John A.; Surgery; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 28-FEB-2005 Summary: (provided by applicant): Despite advances in medical and gene therapy, orthotopic liver transplantation remains the only definitive therapeutic option for children with end-stage liver disease and certain metabolic disorders. Recent advances in pre-, intra-and early post-transplant care have resulted in a dramatic improvement in survival of the pediatric liver transplant patient. The broad long-range goal of our research program is directed at enhancing the patients' long-term survival. Our primary

28

Liver Transplant

focus relates to obligate life-long immunosuppression, with its inherent complications including severe infection and development of cancer. These two complications come together in a single disease, Epstein-Barr Virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD). EBV, a latent human lymphotrophic herpes virus infects and immortalizes human B cells. Primary infection usually occurs via salivary exchange and results in a mild, self-limiting illness (infectious mononucleosis) followed by life-long EBV-specific T cell controlled EBV latency. T-cell based immunosuppression prevents allograft rejection, however, it also suppresses cytotoxic T lymphocyte (CTL) function generating an environment in which EBV-infected B cells can proliferate. Patients receiving life-long T cell based immunosuppression have an increased risk of developing PTLD due to their inability to produce normal immunoregulatory responses. Studies have suggested that EBV load and maintenance of host immunoregulation may be an important indicator of PTLD development. This disease is particularly devastating to the pediatric patient as its incidence is at least 4-fold greater than in the adult liver transplant-patient population. In fact, PTLD is the number one cause of death following pediatric liver transplantation. At this time, there is no definitive method of prospectively detecting, diagnosing, or treating PTLD, and current treatment protocols place the liver allograft and patient at risk. Therefore, a diagnostic tool that is both sensitive and specific, and a treatment strategy with low toxicity are greatly needed to decrease the morbidity and mortality suffered by the pediatric liver transplant patient with PTLD. The investigation proposed herein involves studies that will support our hypothesis that the combination of a persistently elevated EBV load in the setting of a diminished immune response to EBV will be an early risk indicator associated with PTLD development, and that pre-emptive treatment utilizing autologous adoptive EBV-specific CTL immunotherapy will provide a low toxicity treatment option. The specific experimental goals proposed include: Specific Aim 1: To identify pediatric liver transplant recipients with persistently high EBV levels who fail to mount an adequate immune response to EBV, and Specific Aim 2: To determine if infusions of autologous EBV-specific CTL lines are safe, increase immunity to EBV and reduce viral burden in pediatric liver transplant recipients. We plan to serially follow our pediatric liver transplant recipients monthly following transplantation with real time quantitative DNA analysis for EBV load and antiviral immunity via EBV-specific ELISPOT assays. In patients found to have persistently high loads of EBV and a diminished level of EBV-specific immunity, despite minimization of T-cell based immunosuppressive medications, EBV-specific CTLs will be generated and administered in a phase 1 dose escalation study. These studies represent a phase 1 trial to determine the relevance of EBV load and EBV-specific immune responses following liver transplantation. In addition, these studies will determine the safety and ability of autologous adoptive EBV-specific CTL immunotherapy to enhance EBV-specific immunocompetency. The data from our proposed study will provide the database for the development of future larger multi-centered trials to determine the utility of this adoptive immunotherapeutic regimen Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT OF A NOVEL BIOARTIFICIAL LIVER Principal Investigator & Institution: Rozga, Jacek; Arbios Technologies, Inc. 2331 Buckingham Ln Los Angeles, Ca 90077 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 30-NOV-2003 Summary: ARBIOS developed a novel hybrid bioartificial live r(HyBAL) to treat patients with liver failure of various etiologies. In the absence of any other alternative,

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29

such patients must receive a liver transplant or endure prolonged hospitalization. In treating acute liver failure it is critical to provide whole liver functions. It is believed that liver support at this level of complexity requires utilization of viable isolated liver cells. Our own argument, which dates back to the development of our first-generate bioartificial liver, is that a truly effective system should be a hybrid one, i.e., it should combine liver cell therapy and detoxification using sorbents (e.g., activated charcoal, exchange resin). The HYBAL is the first liver assist system in which these two functions are integrated in a single molecule. Depending on the cause of liver disease, severity of illness and deficiency of specific liver functions, these modes of therapy can be provided individually, simultaneously or sequentially. In addition, the HYBAL's basic commercially available kidney dialysis platform represents a major improvement in efficiency with a concomitant reduction in cost and complexity compared to other existing systems. The goal of this proposal is to validate the HyBAL concept. The prototype HyBAL devices will utilize matrix-anchored rat or pig hepatocytes and sorbents (charcoal and exchange resin particles). They will e perfused for 8 hours with plasma removed with pigs with surgically-induced fulminant hepatic failure(FHF). Changes in plasma levels of ammonia, urea, bilirubin and other liver-specific parameters will be monitored. In addition, the HyBAL will be challenged with exogenous ammonium chloride, galactose and lidocaine. In vivo, he ability of HyBAL to support pigs with FHF will be examined. In both experimental settings, HyBAL devices from which either cell therapy or sorbents have been omitted, will be tested to determine the respective role of cell and sorption therapy in the overall HyBAL performance. PROPOSED COMMERCIAL APPLICATIONS: The National Center for Health Statistics (NCHS) reported that in 1999, over 250,000 patients underwent 340,000 hospitalizations due to acute liver failure; 43,000 patients died (7th leading cause of death). Based on these data, NCHS estimates that more than 200,000 liver support treatments are needed annually in the U.S. lone to keep liver failure patients alive until an organ becomes available for transplantation or the native liver recovers from injury ($1.5-billion market). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DFMO PREVENTION STUDY (2B) IN ORGAN TRANSPLANT SUBJECTS Principal Investigator & Institution: Bailey, Howard H.; Assistant Professor of Medicine; Human Oncology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Skin cancer is the most common malignancy encountered in the US. While most occurrences of non-melanoma skin cancer can be successfully treated, the growing number of cases and the increased virulence of the malignancy in certain populations make it a significant societal risk. An example of a population at increased risk based on incidence and virulence is organ transplant recipients (OTR), a growing subset of our population due to increased graft survival and numbers of graft recipients. In most series, the incidence of skin cancers in OTR has been > 50% by 20 years post-graft. Initiators and promoters of skin epithelial tumor formation have long been observed to cause increased levels of polyamines and their rate-limiting biosynthetic enzyme ornithine decarboxylase (ODC). Conversely, compounds that decrease ODC activity inhibit skin tumor formation. Difluoromethylornithine (DFMO) is a specific inhibitor of ODC and has been observed to significantly reduce tumor formation secondary to many different initiators and promoters. Past and ongoing

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chemoprevention studies of DFMO at the UW and other institutions have revealed significant inhibition in ODC activity and polyamine levels in target tissues at relatively nontoxic doses. Due to concerns about chronic immunosuppressants, like cyclosporine, interfering with the ability to adequately measure promoter-induced ODC activity in skin samples and DFMO effects upon graft survival, an initial phase I pilot study of 0.5 and 1.0 g/day of DFMO in OTR was performed. It revealed that 28 days of 0.5 g/day of DFMO significantly inhibited TPA-induced ODC activity and decreased polyamine (putrescine) levels in skin samples of OTR without toxicity.Prior to pursuing a large phase III study of DFMO in OTR, we propose to perform a phase 2b randomized study of 0.5g/day of DFMO versus placebo for one year in OTR at high risk for skin cancer. The primary endpoint would be a greater than 50% reduction in TPA-induced ODC activity in skin samples for one year. Secondary endpoints will be a 50% decrease in skin putrescine and decreased development of skin lesions (actinic keratoses and carcinomas) for one year. Additional parameters include: toxicity assessment including audio grams for ototoxicity, graft status, compliance, and DFMO and immunosuppressant levels.The importance of assessing the biochemical and potential toxic effects of DFMO in OTR, a population at considerable risk of skin cancer, is magnified further by the increased incidence of multiple malignancies in OTR and the importance of ODC induction in many types of tissue carcinogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DRUG TREATMENT FOR TRANSPLANT CANDIDATES Principal Investigator & Institution: Haller, Deborah L.; Associate Professor; St. Luke'sRoosevelt Inst for Hlth Scis Health Sciences New York, Ny 10019 Timing: Fiscal Year 2003; Project Start 10-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): This application proposes a Stage I project targeting substance abusers with end-stage liver or renal disease who are seeking organ transplant. The proposed research is perfectly suited to a Stage I study because substance abuse: (1) causes/exacerbates both liver and renal disease; (2) has a negative impact on transplant outcomes; and (3) poses a barrier to obtaining life-prolonging surgery. At present, no empirically validated treatment exists for organ transplant candidates with co-occurring addiction; in addition, no RCT of any validated substance abuse intervention has been conducted in pre-transplant candidates. Lack of relevant substance abuse services for this population is further worsened because organ transplant patients have difficulty assimilating into community drug treatment programs. Together, these factors suggest the need for a "tailored" intervention. The proposed approach will allow us to develop and pilot test a homebased (telephone) intervention on a small number of pre-transplant patients to determine if it is sufficiently promising to warrant further evaluation in a Stage II clinical trial. It is hoped that the proposed treatment will result in increased: (1) readiness to change drug use behavior; (2) abstinence, both pre- and post-transplant; (3) treatment adherence; (4) behavioral health; and (4) psychological status/Quality of Life (QOL). Longer term medical outcomes of interest include: (1) being listed for transplant; (2) receiving a transplant; (3) morbidity (e.g., rejection episodes); and (4) mortality. The Transplant & Addiction Program (TAP) is a 12- session telephone intervention that uses motivational interviewing (MI) as its therapeutic platform, supplemented by CBT exercises, health education and contracting. TAP emphasizing abstinence, disease management, and adherence, while de-emphasizing confrontation, labeling, and telling the patient what to do. Because it is home-based, the intervention will be accessible to patients who live far away from their chosen transplant center or who are too ill to attend drug treatment in

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the community. Following the development and piloting of TAP and adherence/competence scales, 20 subjects will be randomized to TAP + TAU and 20 to TAU alone. For this study, TAU consists of medical management by a designated transplant team (internist, RN transplant coordinator, surgeon, and medical social worker) who will adhere to the research protocol. Subjects will be evaluated at baseline, upon completion of treatment (wk. 12) and at 3 and 6- month follow-up points. Hair analysis, BAL, urine (plasma for those no longer making urine) and collateral reports will serve as the dependent measures of substance use. The medical team will provide information regarding medical status and service utilization to the research team on a monthly basis until such time as the subject dies, is administratively discharged from the program, or the study ends. The focus during the extended follow-up period will be on secondary end-points (i.e., medical outcomes) as well as relapse. If the proposed behavioral intervention proves to be efficacious, we will next propose a Stage II study that will likely involve several transplant centers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: END-STAGE LIVER DISEASE/PREVALENCE & TREATMENT VARIATION Principal Investigator & Institution: Bryce, Cindy L.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: (adapted from the application) The primary purpose of this proposal is to provide the applicant with means and structure for achieving two goals. The immediate goal is to evaluate the effect of gender, race and income on access to liver transplant services. The long-term goal is to gain independence as a health services researcher by developing methodological expertise in decision sciences and multivariate statistical modeling and research expertise in organ transplantation and health policy evaluation. The applicant will obtain further instruction in computer simulation, geographic information systems, and advanced statistical analysis; in addition, she will receive clinical education to better understand the liver transplantation process and overall delivery of patient care. This training will be provided through formal coursework, directed readings, seminars and conferences, a clinical preceptorship, and research. Most activities will take place at the University of Pittsburgh's School of Medicine, Graduate School of Public Health, and Center for Research on Health Care. The applicant's research project evaluates the role of gender, race, and income in determining access to liver transplantation and explaining variation in liver transplant rates. To date, most studies on access to transplantation have focused on renal transplant services; few researchers have studied hepatic transplantation because of serious data limitations. Whereas the federal government maintains a comprehensive database of persons with renal disease from the time they receive dialysis, there is no centralized, population-based registry for persons with end-stage liver disease (ESLD). Most information on ESLD patients is collected on liver transplant candidates by the United Network for Organ Sharing. The hypothesis of this project is that demographic and economic factors significantly affect early access to transplant services, namely referral rates to transplant centers and listing rates by transplant centers. To address this issue, better information is needed. Therefore, the project will satisfy two aims: (1) develop and validate a population-based methodology for identifying and tracking a cohort of "transplant potential" patients with ESLD; and (2) estimate the effect of gender, race and income on movement through the transplantation process. This project will collect new information on patients with ESLD and combine it with existing data

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resources made available through The Optimal Timing of Liver Transplantation Project (AHCPR, R01 HS09694-02). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENGINEERING ASPECTS OF LIVER SUPPORT SYSTEMS Principal Investigator & Institution: Clemens, Mark G.; Professor and Chair; Biology; University of North Carolina Charlotte Office of Research Services Charlotte, Nc 282230001 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): In spite of many advances in liver transplant surgery, an increasing number of patients with terminal liver disease are dying while awaiting transplants. Consequently, further advances in the storage of donor livers, as well as alternative replacement options and mechanisms for supporting liver function while awaiting a donor liver are needed. A very promising area of research and development is in the development of engineered solutions to the problems of liver support for either natural donor organs or bioartificial livers. However, efforts undertaken within a single discipline are hampered by the complexity of both the engineering and biological aspects of such projects. This proposal constitutes a partnership between bioengineers, biologists and a liver transplant surgeon with the goal of combining their expertise to devise improved methods of liver support via bioartificial livers and improved preservation of donor livers via machine perfusion preservation (MPP). The partnership encompasses three inter-related projects. The first project focuses on delivery of oxygen and other nutrients to the cells in in vitro systems such as the bioartificial liver. The approach involves the modification of the support matrix to facilitate enhanced mass transport. The second project addresses the hypothesis that improved bioartificial liver function can be attained by providing a more physiological combination of cell types in the support device. Specifically, we will investigate the relationship between Kupffer cells and hepatocytes in maintaining prolonged hepatic-specific function in culture. The final project focuses on development of methods for optimization of microvascular perfusion in machine-perfused livers. This project uses a combination of intravital microscopy and mathematical modeling. In all of the projects, engineering and biological approaches, as well as clinical experience, are combined to address focused, clinically relevant problems. Moreover, the unique environment that supports the partnership will maximize the potential for success in this interdisciplinary approach and provide an avenue for potential clinical application of laboratory advances. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENERATION/EMERGENCE OF VARIANT IN HEPADNAVIRUS INFECTON Principal Investigator & Institution: Summers, Jesse; Professor; Cell Biology and Physiology; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: The objectives of the proposed research are to understand the mechanisms for the generation and emergence of variants during chronic infection with hepadnaviruses. Variants are thought to be important in the pathogenesis or persistence of HBV infections in humans, and are known to be responsible for the development of drug resistance during antiviral therapy and for infection in vaccinated individuals and

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liver transplant recipients. However, because chronic infection is due to persistent infection at the cellular level, and the liver is a relatively quiescent tissue, it is not clear how variants that are generated during a chronic infection emerge as the dominant species of virus. The research we propose is designed to clarify the mechanisms for emergence of virus strains. Understanding the processes that result in evolution of the virus population in a chronically infected liver requires gaining new fundamental information about the nature of chronic infections; i.e. about how the progeny of the infecting viruses and variants are distributed in the liver, how much viral and cellular turnover occurs during chronic infection, and how virus lineages are segregated in different populations of hepatocytes where selection of individual variants can occur. Because these questions cannot be addressed experimentally in human HBV infections, we will use the duck hepatitis B virus (DHBV) model. DHBV, a member of the hepadnavirus family, closely resembles HBV in virus structure, genome replication, persistence, and tissue tropism. DHBV is the only member of this family of viruses that can be genetically manipulated in vitro and tested conveniently in animal infections. The five specific aims are (1) to measure the spontaneous mutation frequency in a single round of transcription and reverse transcription of the DHBV genome, (2) to determine the nature of mixed infections of the liver at the cellular level, particularly the frequency of doubly and singly infected hepatocytes, cell-to-cell variation in covalently closed circular DNA (cccDNA) copy number, and the effects of liver growth and regeneration on these properties, (3) to measure the dynamic state of in vivo chronic infections, (4) to describe the process of replacement of a cytopathic strain by a noncytopathic reverant in vivo, and (5) to determine the spatial distribution of virus strains in mixed infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HCV QUASISPECIES DYNAMICS AND LIVER TRANSPLANT Principal Investigator & Institution: Vargas, Hugo E.; Associate Professor; Mayo Clinic Coll of Med, Mayo Clinic Az Sc Johnson Research Medical Building Scottsdale, Az 85259 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2005 Summary: (provided by applicant): HCV related cirrhosis is the leading cause of liver transplantation in this country and in Europe. A significant proportion of patients have a rapid recurrence of hepatitis that leads to graft loss and mortality. The dynamic nature of HCV populations could underlie its biology, including immune evasion and persistence. We propose to study the transmission and evolution of HCV quasispecies 65 liver transplantation recipients. Aim 1: Is there a selection of viral variants within quasispecies at the time of transmission? We hypothesize that not all viral variants present in infectious blood are able to establish infection in a susceptible host. Therefore, we will compare the composition of viral quasispecies in all 65 transplant recipients using single-strand conformation polymorphism (SSCP), cloning and sequencing to evaluate changes that correlate with the clinical course. This analysis will be conducted in the highly variable E2 and conserved 5' untranslated (5'UTR) regions. Aim 2: How does the HCV quasispecies distribution evolve over time in the natural course of infection and does it have a prognostic value with respect to outcome? We hypothesize that in OLT recipients infected with HCV, the quasispecies composition evolves in the E2 and 5'UTR regions and these changes correlate with the clinical outcome. Therefore, we will analyze quasispecies complexity, divergence and genetic drift longitudinally using SSCP and heteroduplex mobility assays in all 65 infected recipients. We will correlate quasispecies behavior with clinical outcome of the infection. Aim 3: What is the biological basis of selective transmission and evolution of quasispecies in the E2 and 5'UTR regions? We hypothesize that the selection and evolution of variants within the

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5'UTR quasispecies is related to differences in viral fitness associated to its competence to direct translation. We will clone representative 5'UTR fragments into bicistronic dual luciferase reporter plasmid and we will measure and compare their translation efficiency in vitro. We hypothesize that E2 region quasispecies variants bound by antibodies are less efficient in establishing infection in the graft. Furthermore, we postulate that new viral variants appearing during the infection represent mutants which escape immune detection. We will separate viral variants bound in immunocomplexes from "free" virus and compare the variants using SSCP, cloning and sequencing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEPATIC DIFFERENTIATION OF CO-CULTURED ES CELLS Principal Investigator & Institution: Fair, Jeffrey H.; Surgery; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 29-SEP-2005 Summary: (provided by applicant): Candidate: The overall objective of this K18 Career Enhancement Award application is to provide the resources for enhanced training for the principal investigator so that he will become an independently funded surgical scientist who will contribute at a national level in stem cell biology leading to new cell therapies for liver disease. The principal investigator has enlisted the ongoing stem cell expertise of the following mentors: Terry Magnuson, PhD, Oliver Smithies, PhD, and Larysa Pevny, PhD, who are experts in stem cell and developmental biology. Retraining is required due to the length of time in the last seven years spent in clinical practice and patient-based research. There is a clear need to retrain in current recombinant DNA practices, advanced PCR analysis, and basic molecular biology in order to make the transition from clinical to basic science research. Environment: UNC-CH has a strong academic tradition and a commitment to training clinical scientists. The School of Medicine has a strong core facility including the Lineberger Cancer Center, the UNC Genomics Lab, the Confocal Microscopy Lab, and the Mouse Histology Facility to support all aspects of the basic stem cell research. Dr. Terry Magnuson, the stem cell mentor for this project, has an extensive track record of scientific success and is committed to the mentoring process necessary to carry this research to its fruition. Research: In this proposal, we will define the characteristics of embryonic stem cells in vitro as they differentiate in the hepatic lineage and co-culture with either embryonic cardiac mesoderm or hepatic progenitors. Our hypothesis is that Hepatic Progenitor (HP) cells signal Embryonic Stem (ES) cells to undergo tissue-restricted differentiation towards hepatocyte lineage in vitro that are capable of organ specific function in vivo. We will then investigate the biologic fate of these cells in vivo using a cellular transplant model of 2/3 partial hepatectomy. Growth factor culture conditions have been used to derive hepatocyte-like cells from ES cultures, but the in vivo function of the cells is unknown, and may be capable of producing malignancy. In addition, experiments in other organ systems suggest that manipulation of cell culture conditions alone is insufficient, but that cell-cell interactions are required in order to reconstruct and restore organ function. Furthermore, MHC expression, essential in the alloimmune response to liver transplants and the induction of tolerance, is not understood in ES cell development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEPATITIS C: STUDIES OF IMMUNITY AND PATHOGENESIS Principal Investigator & Institution: Rice, Charles M.; Professor; Lab/Virology & Infect Diseases; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2002; Project Start 01-AUG-1996; Project End 30-JUN-2005 Summary: Hepatitis C virus (HCV) is an important cause of chronic liver disease, cirrhosis and hepatocellular carcinoma in most parts of the world. Its fastidious nature and limited host range have made it difficult to study. In this program, four separate groups of investigators join forces to attack the hepatitis C virus from a variety of different but interrelated vantage points. The four groups (PIs H. Greenberg, C. Rise, T. Wright, and M. Kay) have a well-documented history of collaborations in the general areas of hepatitis viruses and bring a pathogenesis and immunity and will range from clinically based investigation to fundamental analysis of the interaction of the HCV genome and the host. By combining resources, reagents and ideas, the program team hopes to advance the state of knowledge concerning HCV pathogenesis. The individual projects in this program are briefly outlined. Dr. Greenberg who is the overall program director, will carry out studies on the class I restricted CD8+ T cell response to HCV in patients with acute and chronic hepatitis and in patients undergoing liver transplant. He will take advantage of several new assay systems (tetramers and intracellular cytokines) to study responses in peripheral blood and the liver and will work closely with Drs. Wright and Kay to carry out these studies. Dr. Wright will continue her longitudinal analysis of two groups of patients: examine the contributions of virologic and immunologic variables to disease progression and will work collaboratively with Drs. Greenberg and Rice to study host immune responses and hepatocyte response to HCV infection. Dr. Kay will continue to develop his murine model for HCV replication. This model involves the engraftment of human hepatocytes on immunodeficient mice treated with antibody to c-met. Once established, Drs. Kay and Wright to study HCV strain variation phenotypes in the grafts. Finally, Dr. Rice will collaborate with Dr. Greenberg to study hepatocytes and other liver cell transcriptional responses to HCV using microarray techniques. These studies will involve cells in culture which express HCV proteins under the control of an inducible promoter, hepatocytes in vivo derived from chimpanzees and humans, and, when feasible, infected hepatocytes engrafted in our mouse model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEPATOTOXICITY CLINICAL RESEARCH NETWORK Principal Investigator & Institution: Davern, Timothy J.; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): Hepatotoxicity, or drug-induced liver inury (DILl), is currently the most common cause of fulminant hepatic failure in the United States and the main indication for market withdrawal of drugs and, thus, it is a problem of enormous medical, financial, legal and regulatory importance. Although a vast number of drugs, toxins and alternative medications have the potential to cause hepatotoxcity, severe DILl is a problem of sufficient rarity that a large group of dedicated investigators working in a coordinated effort will be required to better understand the pathogenesis of DILl and develop effective prevention and treatment strategies. This proposal brings together a unique, multi-disciplinary consortium of investigators and resources, concentrated within Northern California but also including sites across the country, with a plan for a participating Clinical Center in the Hepatotoxicity Clinical Research

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Network (HCRN). Our research plan describes, firstly, the establishment of a large multicomponent Clinical Center patient database that would contribute to the proposed multicenter HCRN. The proposed DILl patient informational database, serum, DNA and tissue bank will comprise a prospective cohort derived from several sources, each providing distinct epidemiological facets and research potential. These include the Liver Transplant Programs at UCSF, Stanford University and California Pacific Medical Center, the Tuberculosis Clinics at San Francisco General Hospital, Boston University, Emory University, University of Puerto Rico, and Louisiana Health Sciences Center, and the HIV Clinic at San Francisco General Hospital. At each site, we have developed strategies to identify well-defined cases of toxin-induced liver injury in a prospective manner that will permit careful collection of detailed epidemiological and clinical information, as well as serum, DNA and tissue samples for biochemical, pharmacological and genetic studies. We plan to initially identify patients with potential DILl based on proposed operational diagnostic criteria and then further evaluate cases using a validated causality assessment instrument. Patients classified as having "highly probable" DILl using this instrument will be followed prospectively in order to better define the natural history of DILl. Identification of such DILl-associated polymorphisms is an essential first step in the development of a rational gene-based prevention strategy. We anticipate that our Clinical Center will recruit approximately 120 cases and wellmatched controls from an ethnically and racially diverse patient population to the national HCRN network. We have a well-organized, multi-disciplinary group of physicians, scientists, and research nurses who are dedicated to the success of this Clinical Center and the overall National Hepatoxicity Clinical Research Network. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ICOS-B7H AUTOIMMUNITY

IN

ISLET

TRANSPLANT

REJECTION

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Principal Investigator & Institution: Shapiro, Andrew M.; University of Alberta Edmonton T6g 2E1, Canada Edmonton, Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Recent progress in clinical islet transplantation with the introduction of the 'Edmonton Protocol' has created enthusiasm for this approach as an effective therapy for highly selected patients with unstable forms of Type I diabetes. The therapy, however, is not suitable for patients in the earliest stages of Type I diabetes because of potential risks associated with anti-rejection therapies. While the risk of malignancy and life-threatening infection has been very low in recent clinical series, complications of severe mouth ulceration, elevated cholesterol, hypertension and the need for two or more organ donors to secure insulin independence emphasize the need for further improvements in the safety and efficacy profile of islet transplantation if it is to be more broadly applied in diabetes. Our Laboratory has focused intense efforts in exploring ways to induce minimal immunosuppression or tolerance in mouse models of islet transplantation. Recently, we have found that an antibody directed against the surface inducible co-stimulatory molecule ICOS (12A8) is highly effective in prolonging islet allograft survival beyond 100 days in approximately half of treated mice. The current proposal is designed to further explore blockade of the ICOS-B7h pathway in control of allograft rejection and autoimmune recurrence after islet transplantation in mice. We believe that this promising finding could be further enhanced by rational combination of anti-ICOS therapy with complimentary approaches that have potential for rapid clinical translatability. More specifically, anti-ICOS will be combined with either donor specific transfusion, CTLA4-1g, CD40 blockade, or with the drug FTY720 to

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evaluate its effect in preventing islet allograft rejection. The most promising of these approaches will be further tested in the primary and secondary prevention of spontaneous diabetes in NOD mice. We will explore the immunological mechanisms associated with tolerance phenotypes [mice treated with anti-ICOS based therapies] by donor and third party islet and skin graft rechallenge, by thymectomy, or by following the fate of donor-specific T cells in TCR-transgenic models. Furthermore, in vitro coculture assays and adoptive transfer studies, in addition to islet-kidney graft retransplantation experiments will be conducted to search for regulatory T cell activity. We will also study our clinical islet transplant patients by flow cytometry and TaqMan quantitative PCR for ICOS expression in peripheral blood and in graft biopsies. We will correlate clinical outcomes with ICOS expression to determine if ICOS monitoring might be a useful tool for prediction of clinical course. If these initial studies show promise, we would plan to further explore anti-ICOS therapies in primate models of islet transplantation within the context of an extended future proposal, with a view to ultimate testing in clinical islet transplant recipients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNE PATHOGENESIS OF HEPATITIS C VIRUS--HUMAN MODEL Principal Investigator & Institution: Wright, Teresa L.; Professor of Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002 Summary: This proposal is focused on the identification of predictors of disease progression in hepatitis C (HCV) infection. We will examine the influence of the immune response on the natural history in two cohorts; immune compromised liver transplant patients and immune competent patients with HCV. Our primary hypothesis is that fibrosis progression is accelerated by immune suppression. Our secondary hypothesis is that type of immune suppression and ethnicity contribute to fibrosis progression. We will use databases of patients who have undergone liver transplantation and immune competent patients who have undergone liver biopsy, databases which include clinical, demographic, biochemical and histological data as well as information regarding risk exposures and alcohol consumption. All liver biopsies have been graded and staged for the degree of inflammation and fibrosis respectively. Serum is available from the majority. Initial analysis of 284 liver transplant recipients showed that post-transplantation fibrosis progression was linear but variable, and was independently associated with year of transplantation, non-Caucasian ethnicity, number of steroid boluses and HCV RNA level at transplantation. Since the explanation of these associations was not apparent, we expanded the transplantation databases in order to identify precisely predictors of disease progression. We will also measure variables including ethnicity in fibrosis progression in immune competent patients. In most studies of natural history, the duration of HCV infection is estimated retrospectively from time of presumed first risk exposure. Through modeling timing of exposures, we will develop an approach to assign accurately time of initial infection. We will also investigate the association between genetic diversity in the envelope and NS3 genes and disease progression. Finally, we will collect lymphocytes from HCV- infected patients for future analysis of the association between genetic markers and disease progression. These cohorts will provide lymphocytes to Dr. Greenberg to measure HCVspecific CTL response and HCV variants to Dr. Kay to measure pathogenicity of HCV in an animal model. Elucidation of the mechanisms by which HCV causes disease is essential for the identification of those at risk for serious consequences.

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

Project Title: IMPROVING DRUG ABUSE TREATMENT PLANNING CRITERIA Principal Investigator & Institution: Gastfriend, David R.; Director; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 20-SEP-2000; Project End 30-JUN-2005 Summary: Improving Drug Abuse Treatment Planning Criteria: This K-24 Mid- Career Investigator Award will provide an intense phase of career development and mentoring in drug abuse health services research. The research goal is to develop criteria for determining treatment quality and appropriateness, parameters that become increasingly important as clinical management changes focus on cost reduction to costeffectiveness. The specific aims are to apply the ASAM PPC algorithms to 4 additional data sets that complement the ASAM Study sample, to extend our knowledge of the 1) concurrent validity and 2) predictive validity of the ASAM PPC and 3) to improve it. These cohorts include: non-treatment seekers, outpatient treatment seekers, hospitalized liver transplant candidates and opiate anesthesia detoxification candidates. This is an efficient opportunity to study all levels of care described by the ASAM Criteria, without the cost/effort of devising controlled, prospective trials. The hypotheses are that the ASAM PPC: H1) will show baseline between-group differences that are useful for disease staging, H2) will demonstrate predictive validity for clinical and utilization outcomes, and H3) will yield some dimensional constructs, decision rules and scoring thresholds that do not initially meet validity criteria but, with revision and iterative reanalysis, can achieve significance. The results will facilitate future controlled trials via RO1 applications. The Mentoring Plan will focus on Post-residency Fellows in Addiction Psychiatry (3 per year), and also incorporate post- doctoral trainees in health services research and dissertation students in health policy. Mentoring will occur through trainees' participation in the research projects that are planned in each of the four naturalistic convenience samples (for whom complete data are already gathered or are substantially underway). Validation work is required for each of the 6 ASAM PPC assessment dimensions, for each level of care, and within sub-populations. This range of research needs offers a rich matrix of opportunities for a group of trainees and junior investigators in patient-oriented research. Over the next five years, the candidate seeks to: a) move to full-time effort in research and research mentoring, b) increase the depth of his own skills in psychometrics, health economics and data analysis through specific trainings, c) increase his ability to incorporate advanced modeling approaches through collaborations with statistical and health economics experts, and to d) increase his efforts at dissemination, both through publication of results in the scientific literature and through a generation of junior investigators who will acquire the fascination and skills to advance this new area of patient- oriented research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LIVER EXPRESSED MHC ANTIGENS Principal Investigator & Institution: Stroynowski, Iwona T.; Associate Professor; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003 Summary: Mammalian liver has been long known to exhibit properties of immunologically privileged tissue: it expresses low levels of surface class I MHC antigens on parenchymal hepatocytes and induces donor-specific allotolerance in MHC mismatched transplant recipients. The suppressed display of surface class I MHC

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proteins is paradoxical in view of the high constitutive transcription of H-2K, D genes in mice and HLA-A, -B, -C in human, and in view of the liver s ability to clear intracellular hepatic pathogens via CTL-mediated, class I-restricted immune responses. This application seeks to define a full set of class I genes expressed in hepatocytes of normal, cytokine treated (IFNgamma, TNFalpha) and pathogen (Listeria monocytogens, recombinant adenovirus used for liver gene therapy) infected mice and to explore the role of class I antigen processing pathway in their expression. We will restrict our studies to C57BL/6 mice and its H-2Kb,Db-deficient mutant, which will serve to optimize the conditions for detection of rare class Ib products. The results of the proposed research will provide information about the heterogeneity of distince class Ib proteins expressed in parenchymal tissue of liver. Furthermore, the studies of the regulated expression of the components of class I antigen- processing machinery in liver cells will contribute to the understanding of the mechanisms involved in class Imediated responses against model hepatotrophic pathogens. This knowledge is relevant for clinical research addressing liver transplantation, opportunistic infections of liver and liver gene therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIVER REGENERATION AS A MODEL FOR ANGIOGENESIS Principal Investigator & Institution: Stolz, Donna B.; Assistant Professor; Cell Biology and Physiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2004; Project Start 15-AUG-1998; Project End 30-NOV-2008 Summary: (provided by applicant): Angiogenesis is the process whereby new blood vessels sprout from existing vessels and requires that the specialized resident cells lining the vasculature, the endothelial cells (ECs), proliferate, migrate and differentiate spatially and temporally in response to specific signals. Vasculogenesis, on the other hand, has only recently emerged as an alternative mechanism of blood vessel growth in adult tissues and is the result of homing and engraftment of circulating EC precursors (ECPs) of bone marrow origin to areas of neovascularization. Both events are known to occur within the liver vasculature under very different conditions of growth, injury and repair, but the extent of each and the mechanisms by which they proceed in each case is completely unknown. The overall goal of this proposal is to determine the specific growth factor signaling events that induce angiogenic versus vasculogenic blood vessel growth in the context of liver and determine the subsequent microenvironmental milieu that induces EPC recruitment and/or differentiation of the liver-specific sinusoidal endothelial cell (SEC) fenestrated morphotype. Two paradigms of clinically-relevant liver repair allow us to spatially and temporally detail the growth factor signaling events and evaluate sinusoidal ultrastructure and liver-specific SEC function in the rat. AIM I: Growth factor and microenvironmental interactions will be examined at the sinusoidal surface following 70% partial hepatectomy (PHx) since there is initially extensive hepatocyte proliferation in the absence of EC proliferation until 96 hr postPHx, resulting in avascular hepatic foci. Subsequent proliferation and infiltration of the SEC into these avascular parenchymal clusters and reestablishment of the normal hepatic architecture provides a well-timed model for evaluating physiological angiogenesis. AIM II: Angiogenic and vasculogenic events will be examined concurrently using an allogeneic liver transplant model (dual cross strain and female to male transplants, non-GFP to GFP rats) to ascertain the source of SEC (host vs. graft) and determine extent of recipient and donor involvement in SEC engraftment and/or proliferation. Prior to transplantation, livers are stored under cold, ischemic conditions

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for 18 h, and upon transplantation (warm reperfusion), a majority of the SEC slough off immediately from the sinusoidal surface. Remarkably, within 24 hr, the SEC lining has nearly completely repopulated at least partially from ECPs, but microvascular remodeling, morphological and functional modification occurs over subsequent days. Comparative analysis of these two systems will elucidate both similar and dissimilar growth factor signaling mechanisms and the role of the microenvironment that control these events and potentially lead to optimization of therapies that will reflect the specific requirements for injury based liver neovascularization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIVER TRANSPLANTATION: THE ROLE OF DENDRITIC CELLS Principal Investigator & Institution: Thomson, Angus W.; Professor; Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-MAY-1996; Project End 30-NOV-2005 Summary: (adapted from the applicant's abstract): The precise role of donor dendritic cells in the inherent tolerogenicity of hepatic allografts remains unresolved. We have shown, however, that poorly stimulatory, immature liver dendritic cells, or dendritic cells whose co-stimulatory function is blocked, can strikingly enhance activationinduced death in allogeneic T cells. Moreover, infusion of such immature donor dendritic cells plus co-stimulatory blockade augments apoptotic death of host immunoreactive T cells and markedly enhances graft survival. These data support our hypothesis that liver dendritic cells have potential to promote the development of tolerance in allogeneic recipients by mediating the apoptotic death of allospecific T cells. Aim 1 is to elucidate the role of apoptosis in the outcome of liver dendritic cellallogeneic T cells interactions and the factors that influence this activity. These studies will test whether myeloid and lymphoid dendritic cells exhibit functional differences in their interaction with T cells and whether they have equal potential to mediate apoptosis in activated T cells and whether Th1 and Th2 cells are equally susceptible. The role of critical co-stimulatory pathways and of IL-2 in the regulation of T cell death will be examined. Aim 2 will ascertain the death regulatory pathways that may determine T cell apoptosis by liver dendritic cells. Contribution of the Fas pathway and the role of TNF families, in particular TRAIL, will be examined. Cell survival factors and death resistance molecules will also be examined for the possible differential resistance of Th1/Th2 subsets to dendritic cell induced death. Aim 3 studies will examine the ability of liver dendritic cells to delete alloreactive cells in vivo and will examine factors that modulate this activity. These studies will involve quantitative assessment of proliferation and apoptosis of CD4 and CD8 T cells in vivo. The impact of blockade of specific co-stimulaory pathways and whether antigen specific T cells are deleted selectively will be ascertained. Finally, Aim 4 studies will assess and maximize the therapeutic potential of liver dendritic cell induced alloantigen-specific T cell apoptosis in organ transplant recipients. In these clinically-relevant studies, emphasis will be placed on targeting specific costimulatory pathways, including use of novel blocking agents. The results will provide new insight into how liver dendritic cells can modulate survival of alloreactive T cells, and determine the potential of donor dendritic cells to delete allospecific T cells to facilitate transplant tolerance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LIVER-INDUCED ACTIVATED T CELL DEATH Principal Investigator & Institution: Qian, Shiguang; Associate Professor; Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260

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Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): Hepatic tolerance was initially demonstrated by spontaneous acceptance of liver allografts in pigs, and subsequently in rats and mice. In humans, rejection of liver transplants is a common occurrence, which is, however, easy to control. There are well-documented cases in which liver grafts survive for years after discontinuation of immunosuppressive therapy. Vulnerability of livers to chronic infection (hepatitis and parasitic infection) and cancerous metastasis has also been attributed to the tolerogenic properties of the liver. The involved mechanisms are unclear. Accumulating data have demonstrated however, that hepatic tolerance is associated with activated T cell apoptosis probably via differentiation of T regulatory cells. These observations support our hypothesis that the liver has the potential to promote apoptotic death of activated antigen-specific T cells, and generate T regulatory activity. The overall goal of this proposal is to yield insights into the underlying mechanisms using T cell receptor (TCR) transgenic mice. There are four Specific Aims. In Specific Aim 1, we will characterize the responses of both CD4+ and CD8+ TCR transgenic T cells to the antigens that are exclusively expressed in the liver. The use of this system will also allow us to precisely test whether tolerance towards the antigen expressed in the liver is local or systemic, and whether it involves attenuation of affector or effector arms of the immune response (Specific Aim 1). The nature of antigen presenting cells (APC) in the liver is another area that has mostly been investigated in vitro, but little has virtually been explored in vivo or ex vivo, despite the suggested central role of these cells in regulating tolerance induction. Thus, we will characterize the behavior, antigen-presenting capacity of liver APC and interaction with T cells (Specific Aim 2). In Specific Aim 3 and 4, we will ascertain the mechanisms of two key events occurring in hepatic tolerance: activated T cell apoptosis and T regulatory cell differentiation, both of which are believed to be crucial in induction of peripheral immune tolerance. We will determine how the liver induces activated T cell death (Specific Aim 3), and the role of T regulatory activity in hepatic tolerance (Specific Aim 4). We believe that these focused relevant studies will provide better understanding of liver immunity and facilitate novel therapeutic strategies to combat chronic liver diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIVING DONOR LIVER TRANSPLANT DATA COORDINATING CENTER Principal Investigator & Institution: Merion, Robert M.; Surgery; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 21-AUG-2002; Project End 31-JUL-2009 Summary: (provided by applicant):We propose to develop and maintain a Data Coordinating Center (DCC) to support the Adult to Adult Living Donor Liver Transplantation (AALDLT) Cohort Study including a Specimen Core Facility. The proposed AALDLT DCC will be comprised of multidisciplinary expertise in liver transplantation, biostatistics, epidemiology, clinical trials, and data management. We will develop a secure, integrated Internet-based data entry and data management system to support data and specimen acquisition. The AALDLT DCC will coordinate the design and implementation of the AALDLT cohort study and clinical protocols and will provide support in the relevant content areas to the Steering Committee and the NIDDK in its effort to accomplish the primary goal of conducting a longitudinal study of the recipients and donor outcomes in AALDLT. The DCC will accomplish the foregoing goals through the implementation of the following specific aims: 1. Design,

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Liver Transplant

organize, implement and coordinate a secure electronic, centralized web-based distributed data entry system for the participating transplant centers (TCs) 2. Establish a secure data management and archival system for the AALDLT cohort study, clinical protocols and substudies 3. Develop comprehensive, valid data collection instruments4. Establish a high standard, quality-assured central repository for biological specimens acquired from AALDLT donors, recipients, and controls5. Perform methodologically rigorous analyses of AALDLT data 6. Facilitate the presentation, dissemination and publication of the results of the AALDLT study. 7. Organize, schedule and manage the meetings, conferencing and communication of the Steering Committees, subcommittees, the DSMB and the central laboratories involved in the AALDLT study. 8. Provide timely and effective communication among the NIDDK project officer and project scientists, DCC, and participating TCs regarding all aspects of the AALDLT study to ensure the fulfillment of the programs scientific goals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIVING DONOR LIVER TRANSPLANTATION COHORT STUDY Principal Investigator & Institution: Berg, Carl Lansing.; Associate Professor of Medicine; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 17-SEP-2002; Project End 31-AUG-2009 Summary: (provided by applicant):As the disparity between number of potential liver transplant recipients and available cadaveric organs has widened, novel approaches have been developed to permit the successful transplantation of the largest possible number of patients with end-stage liver disease. The most promising of these strategies has involved the application of adult to adult living donor liver transplantation (LDLT). More than fifteen U.S. transplant centers have now utilized LDLT as a standard method for liver replacement. Despite the increasingly widespread application of this approach, considerable heterogeneity exists between centers regarding donor and recipient evaluation as well as the surgical techniques employed. Moreover, information is lacking regarding outcomes of this procedure for both donor and recipient, no data available to identify donors or recipients who may benefit most (or least) from this procedure, and no data to determine whether using LDLT is a cost-effective strategy. In this setting, we propose to participate as a transplant center (TC) in the LDLT Clinical Research Consortium. In this role, we propose to participate in the development of a prospective comprehensive data base and information core that will permit the dissection of the factors which lead to favorable, or unfavorable, outcomes in LDLT as compared to standard cadaveric transplantation. The existing UVA STRANDS database will permit retrospective collection of data from LDLT and cadaveric transplants performed over the last 5 years. In addition, the TC proposes to build on its institutional strengths to lead two clinical research protocols. The first protocol will develop a Cost Utility Decision Analysis using the Adult to Adult Living Donor Liver Transplantation Cohort. This research will yield a valid decision analysis model that can be used in a general patient population to better define subpopulations that would benefit from LDLT as opposed to cadaveric liver transplant. Costs and utilities to the health care system and the patients involved will be clarified for use in patient counseling, medical decision-making, and policy formulation. The second clinical research proposal will examine the outcomes of LDLT in patients infected with hepatitis C and compare these outcomes to cadaveric controls. Mechanisms that contribute to rapid allograft infection and injury will be examined including hepatocyte infection, rates of viral replication and kinetics of serum viral clearance.

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

Project Title: LONG TERM FOLLOW UP OF THE NIDDK LTD Principal Investigator & Institution: Detre, Katherine M.; Professor; Epidemiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 31-AUG-2004 Summary: (Adapted from Investigator's abstract) The NIDDK Liver Transplantation Database (LTD) is a multicenter registry of more than 1500 consecutive candidates for liver transplantation (LT), recruited between 1990 and 1994, by three major liver transplant centers in the United States. As such, it is the only scientifically designed and implemented multicenter study from which the recent experience of a large cohort of LT candidates and recipients in this country can be rigorously analyzed. The effort to build this detailed and high quality resource was carried out under a 7-year NIDDK contract which ends in December 1997. Valuable information collected in this study includes clinical and laboratory data collected by protocol and at a time of events, and it is enriched with protocol biopsies from a high proportion of recipients, a bank of serial serum specimens, and a virtual tissue bank. Since the current contract only provided for follow-up of 3 years on average, the range of topics that could be investigated, using this comprehensive data base, is limited. The current plan is to continue the follow-up of the cohort of transplant recipients for another 5 years through the next phase of the posttransplantation period, when recurrence of the original disease and long-term adverse effects of immunosuppression and re-transplantation are most likely to occur. Thus, the Coordinating Center, with the support of the investigators of the three LTD clinical centers, will be able to obtain complete follow-up for an average of 10 years (8-12 years) to observe the information recorded in the study before, during an dafter transplantation. The proposed effort is expected to yield results of great scientific and clinical importance which could directly influence future transplant candidate selection and post-transplantation patient management. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISM(S) OF ALCOHOL-INDUCED LIVER GRAFT FAILURE Principal Investigator & Institution: Lemasters, John J.; Cell and Developmental Biology; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-AUG-1992; Project End 28-FEB-2006 Summary: (provided by applicant) Transplantation of fatty livers is a major problem since many of them fail when used as donor organs. Because the source of liver grafts is largely accident victims who use alcohol, the relationship between fatty liver and graft failure needs to be understood to expand the pool of donor organs. Therefore, the goals of this project are to elucidate mechanisms involved in the failure of fatty livers and to develop strategies to prevent graft failure. Studies with chemicals are often not specific making interpretation difficult therefore. we will use mice with specific genetic deletions to test unique hypotheses about the source of free radicals and the role of endotoxin and TNFa in mechanisms of liver graft failure. Our first goal to be achieved in Aim 1 will be to optimize liver transplantation in knockout mice using treatments and techniques which are routine in this laboratory for rats. Recently, we have established liver transplantation here in the mouse. Survival and non-survival conditions will be established in the mouse, validating it as a useful model for mechanistic studies. Next, we will use knockout mice to provide unequivocal evidence for or against the

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Liver Transplant

hypothesis that endotoxin and TNFa play a critical role in failure of fatty grafts. To test this hypothesis, CD-14 knockout and TNF receptor I (TNFRI) knockout mice and appropriate wild-type controls will be treated with ethanol in Aim 2. The time course of survival, transaminase release and bile production will be observed after transplantation. NFKB (a pivotal transcription factor), TNFa and ICAM-1 will be measured at appropriate times after transplantation. We expect that deletion of CD-14 and TNFRI will improve survival of marginal livers. In Aim 3, the source of free radicals will be identified. Mitochondria in hepatocytes and NADPH oxidase in Kupffer cells are two potential sources of free radicals. Accordingly, knockouts of p47Phox, a required subunit of NADPH oxidase, and transgenic mice over expressing mitochondrial MnSOD will be given ethanol and livers will be transplanted under non-survival conditions. We expect that NADPH oxidase deficiency will prevent free radical production and reduce ethanol-induced primary non-function after liver transplantation. Depending on the results of Aims 2 & 3, targeted therapies such as ebselen, an antioxidant and anti-inflammatory drug, soluble TNFa receptor, and a novel endotoxin antagonist, E5331, will be evaluated in Aim 4. Taken together, we expect that by using the knockout approach these studies will provide solid evidence supporting the roles of endotoxin, free radicals, NFKB and TNFa in primary graft non-function in fatty livers. This work will develop mechanism-based strategies to increase the use of marginal fatty livers for transplantation in the clinic and save lives. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF ISCHEMIA REPERFUSION INJURY IN THE LIVER Principal Investigator & Institution: Engelhardt, John F.; Associate Professor; Anatomy and Cell Biology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-MAY-1996; Project End 31-AUG-2005 Summary: Orthotopic liver transplantation is a common therapy for many acquired and inherited disorders. Liver damage caused by ischemia and reoxygenation (termed ischemia/reperfusion or I/R) has been proposed to substantially contribute to the initial poor function (IPF) of transplanted livers, acute rejection, and graft failure. Central mediators of I/R injury in the liver are reactive oxygen species (ROS) generated during reperfusion with oxygenated blood. Of the multiple forms of ROS potentially generated during reperfusion, O2-, H2O2, and OH will be addressed in the proposed studies. These ROS can cause direct damage to cellular proteins, lipids, and DNA, or they can act as intracellular second messengers to activate and/or inhibit signal transduction pathways that determine cell fates by altering the expression patterns of stress response genes. Central to the goals of this grant are to determine: 1) Which ROS are pathophysiologically important in I/R damage, 2) How do ROS lead to activation of AP1 and NFkB signal transduction pathways following liver I/R, 3) In which subcellular compartments (i.e., nucleus, mitochondria, endoplasmic reticulum, or cytoplasm) do these ROS act to alter the activity of AP-1 and NFkB signal transduction pathways, and 4) Is activation of AP-1 and NFkB beneficial or detrimental to the liver following I/R injury. Several model systems will be used to address these questions including: 1) Recombinant adenoviral vectors to modulate the cellular redox state and inhibit/activate specific signal transduction pathways, 2) transgenic knockout mice deficient in certain signal transduction components, 3) partial lobar, liver I/R mouse model, and 4) a syngeneic rat liver transplant model. Preliminary data has demonstrated that ectopic expression of MnSOD using reombinant adenovirus protects the liver from warm I/R injury and concordantly reduces AP-1 and NFkB activation.

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The mechanisms of NFkB activation appear to involve redox mediated tyrosine phosphorylation of 1kBalpha. The hypothesis that subcellular compartmentalized ROS are important in mechanisms of liver I/;R injury is supported by the fact that ectopic expression of Cu/ZnSOD does not protect the liver from I/R damage. Based on our findings that OH radicals and AP-1 activation are increased in Cu/ZnSOD but not MnSOD or LacZ expression livers, and inhibition of Rac1 pathways by expression of the dominant inhibitor N17Rac1 also activates AP-1, one novel focus of our mechanistic studies on AP-1 activating following I/R injury will involve Rac1/PI3-kinase /PKK/GSK modulation of c-Jun phosphorylation. Recombinant adenoviral mutants for the proteins in this signal transduction pathway will be used to dissect its importance. Using recombinant expressing dominant inhibitors and transgenic knockout mice to block either AP-1 and NFkB activation, we will attempt to determine the importance of each of these pathways in mediating both acute hepatic toxicity and subacute inflammatory responses following I/R injury. In the last phase of this proposal, studies will be aimed at determining the relevance of findings in our mouse partial lobar warm I/R model to the rat liver transplant model of cold ischemia. In summary, this proposal will provide experimental and mechanistic paradigms for linking ROS formation in the liver following I/R injury to both acute damage and subsequent inflammation. Moreover, these studies may provide clinically relevant gene therapy approaches for minimizing organ damage following transplantation, which may ultimately increase the graft survival in orthotopic liver transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MMP-9 MEDIATES CEREBRAL EDEMA IN FULMINANT LIVER FAILURE Principal Investigator & Institution: Nguyen, Justin H.; Mayo Clinic Coll of Med, Jacksonville Mayo Clinic Jacksonville Jacksonville, Fl 322243899 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Fulminant hepatic failure (FHF) is a life-threatening disease. The definitive treatment for FHF is a liver transplant. Unfortunately, 35% of all FHF patients and 62% of nonacetaminophen-induced FHF patients die within 48 hours after reaching stage 3 or 4 coma, while awaiting a transplant. Increasing this narrow therapeutic window would provide substantially more opportunities for these patients to be transplanted. One of the primary causes of death in these individuals is cerebral edema. The mechanisms responsible for cerebral edema in these FHF patients are poorly understood. Recent evidence from other laboratories has shown that matrix metalloproteinase-9 (MMP-9) may play a pivotal role in the development of cerebral edema in other disease states. For example, treatment with either MMP-9 synthetic inhibitors or anti-MMP-9 monoclonal antibodies has been shown to result in a significant reduction in the size of cerebral infarcts. Further, studies using MMP-9 knockout mice have shown a significant attenuation in cerebral edema following either cerebral ischemic or traumatic events. Based on these data we hypothesize that MMP-9 plays a critical role in the development of cerebral edema following FHF. Significant support for this hypothesis has come from two observations made in our laboratory. First, both proMMP-9 and MMP-9 are elevated in the sera of FHF patients and in rats with experimentally induced FHF. Second, in a pilot study, we have shown that treatment with an MMP-9 inhibitor (GM6001) results in an approximate 30% reduction in cerebral edema in rats with experimentally induced FHF. In this application, we specifically propose to: 1. To further determine if inhibition of MMP-9 by the MMP synthetic inhibitor GM6001 attenuates cerebral edema in rats with experimentally

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induced FHF. 2. To determine whether cerebral edema is attenuated in MMP-9 knockout mice following experimentally induced FHF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MODELS FOR OPTIMAL LIVER TRANSPLANT OUTCOMES Principal Investigator & Institution: Dickson, E R.; Mary Lowell Leary Professor of Medicine; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 15-JAN-1986; Project End 30-NOV-2006 Summary: Orthotopic liver transplantation (OLT) is now a well- established means of restoring health in patients with end stage liver disease. Our long-term objective is to provide evidence- based information to help optimize the outcome of OLT, which is relevant not only at the individual physician and patient level, but also at the health policy level. Building on our achievements from the previous program period and data collaboration from a network of academic transplant centers, we propose to study the three most important issues that face liver transplantation in the United States today. In specific aim 1, we will prospectively validate the Model for End-stage Liver Disease (MELD) in current OLT candidates. The MELD scale, a liver disease severity index developed by this program, has recently been adopted by the United Network for Organ Sharing (UNOS) as the national liver allocation system for OLT. Our central hypothesis is that the addition of further variables to the model will not materially improve the model, except in patients with hepatocellular carcinoma, in whom the risk of tumor progression needs to be considered in addition to the severity of underlying liver disease. In specific aim 2, we will identify determinants of the outcome of recurrent hepatitis C following OLT. OLT recipients with hepatitis C, the most common indication for the procedure today, have shorter survival and poorer quality of life. Our hypothesis is that pretransplant alcohol consumption and post-transplant obesity affect the rate of progression of recurrent hepatitis C and thus, the outcome. In specific aim 3, we will study the cardiovascular morbidity in long-term survivors following OLT. Based on the number of patients and length of follow-up available in our database, we will identify traditional (e.g., diabetes, hypertension, and hyperlipidemia) and transplant-specific (e.g., cytomegalovirus infection and liver disease diagnosis) risk factors that are associated with cardiovascular complications. The results of these studies will provide relevant information not only to clinicians in practice, but also transplantation policy makers. The feasibility of the proposed projects is supported by the extensive experience and track record of this program in creating and maintaining a large, multicenter, liver transplant database and strong statistical expertise. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOUSE MODEL FOR HCV INFECTION Principal Investigator & Institution: Kay, Mark A.; Professor; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002 Summary: The study of HCV infection, replication and development of new therapeutics has been hampered by the lack of a small animal model permissive to infection and replication. We have recently found a means to maintain human hepatocytes in mice for at least 5 months. We have demonstrated that these animals are susceptible to human hepatocytes in mice for at least 5 months We have demonstrated that these animals are susceptible to HBV/HDV infection/replication. We will now attempt to infect these mice with HCV. The goal of this proposal is two-fold. We plan to

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improve upon the human hepatocyte xenotransplant model by changing the transplantation strategies so that we can implant a larger number of cells. Moreover, we will characterize the implant by histological methods and gene expression profiles using microarray technologies to determine the similarity between the implanted cells and normal liver. We will then determine if this chimeric mouse is able to undergo HCV infection/replication. We will do this by implanting human hepatocytes isolated from HCV infected individuals, infection of normal hepatocytes ex vivo and in vivo with high titer HCV stocks, and infusion of an infectious RNA derived from a single clone. We will follow the animals for HCV infection by quantitating serum HCV RNA titers over time. Ultimately, we will combine the best transplant model with the best method for HCV infection to determine the highest possible HCV titer that can be achieved in mice. When we are successful, this animal model will be used for numerous studies. These include: gene therapy approaches to reduce or eliminate HCV infection, proliferation of quasispecies, viral pathogenicity, and the importance of the immune response in infection and pathogenicity. The development of a small animal model of HCV infection will be invaluable in our advancement for better knowledge and treatment of this devastating disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MYCOPHENOLATE TRANSPLANT RECIPIENTS

MOFETIL

IN

ORTHOTOPIC

LIVER

Principal Investigator & Institution: Dupuis, Robert; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MYCOPHENOLATEMOFETIL IN POST LIVER TRANSPLANT RENAL IMPAIRMENT Principal Investigator & Institution: Pinson, C Wright.; Professor & Vice-Chairman Surgery; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 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: NITRIC OXIDE IN PLASMA & RED CELLS--HEMODYNAMIC CHANGES IN LIVER TRANSPLANT Principal Investigator & Institution: Textor, S C.; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002 Summary: The overall hypothesis behind these studies is that reversal of the vasodilation of end-stage liver disease (ESLD) and the transition to vasoconstriction of post-transplant hypertension is closely related to alterations in endothelial generation of nitric oxide, which will be reflected by changes in levels and compartmental distribution of NO in plasma and red cells. To accomplish this objective, we wish to examine: Specific Aim No. 1. Changes in plasma and RBC NO during spontaneous variations in blood pressure and peripheral resistance during a 24-hour period in patients with ESLD and four months after liver transplantation. Our hypothesis is that plasma NO levels

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and partitioning between plasma and RBC will vary in parallel with circadian changes in wall stress induced by changes in arterial pressure. Specific Aim No. 2. Changes in plasma and RBC NO induced during infusion of excess substrate (L-arginine), which normally leads to systemic and renal vasodilation. Our hypothesis is that L-arginine excess will increase plasma NO levels in ESLD subjects, but will fail to do so in patients with impaired endothelial function, i.e. hypertension after liver transplantation. Specific aim No. 3: Changes in vasoconstrictor and vasodilator systems affecting blood flow and perfusion, specifically endothelin, prostacyclin and the renin-angiotensin system in relation to changes in plasma and RBC NO. Our hypothesis is that vasodilator effects of NO will be counterbalanced by greater activation of vasoconstrictor systems in ESLD as compared with post-transplant hypertensive patients with impaired endothelialdependent mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OLD AGE, LIFE EXTENSION, AND GERIATRICS Principal Investigator & Institution: Kaufman, Sharon R.; Professor; Institute for Health and Aging; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): The goal of this 4-year qualitative anthropological study is to investigate first, how physicians, patients age 70 and over and their families make decisions regarding the use of three groups of life-extending medical procedures (cardiac bypass, angioplasty and stent; kidney and liver transplant; and renal dialysis) and how they each respond to those procedures; and second, to identify socio-cultural issues of relevance to physicians and to society regarding the growing use of lifeextending medical procedures on elderly patients. This will be an empirical, ethnographic study based on the collection of data by in-depth interviews with physicians, patients and their families, and by participant-observation of support groups for cardiac and transplant patients and of physician-patient discussions where lifeextending procedures are discussed. There are 4 specific aims:1) to provide a descriptive account of physician, patient, and family understandings of relationships among changing conceptions of old age, health in late life and expectations about life-extending medical care; 2) to learn how physicians in different specialties are extending the lives of their elderly patients and the values underlying their decisions; 3) to learn the structural and cultural constraints on their choices for life-extending procedures; and 4) to describe patient and family choices, knowledge and values. Coding-based qualitative data analysis will be used: cross-sectional comparison, thematic analysis, case studies, and frequencies of response. The interpretive goal is to examine in detail the social, structural and medical practices and values brought to bear on the extension of life at progressively older ages. This will be the first research that comprehensively addresses medical and lay decision-making surrounding life-extending medical procedures for older persons, and the responses and experiences of physicians, patients and families to those procedures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ORAL HEALTH OUTCOMES IN PEDIATRIC TRANSPLANT RECIPIENTS Principal Investigator & Institution: Shiboski, Caroline H.; Assistant Professor; Stomatology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747

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Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2005 Summary: (provided by applicant): We propose to conduct a study to explore specific oral health outcomes in relation to new generation immunosuppressants in a population of pediatric renal transplant recipients (RTRs) and liver transplant recipients (LTRs) at UCSF. Oral health outcomes of interest include mucosal diseases (e.g., candidiasis, hairy leukoplakia, ulcers, warts, lip carcinoma, non-Hodgkin's lymphoma, and Kaposi's sarcoma (KS), gingival enlargement (GE), and dental needs. The principal investigator of the proposed study is a recipient of a K23 award that bears as its central theme the study of oral health outcomes among adult RTRs. Dr. Shiboski also received a small amount of pilot funds to study utilization of dental care among medically compromised children. As part of this pilot project she has been recruiting, and administering oral health questionnaires to pediatric RTRs and LTRs at UCSF. Taking advantage of this developing research infrastructure, the goal of the present application is to request funds to conduct a prospective study among pediatric RTRs and LTRs, exploring specific oral health outcomes by following these children at 6-months intervals over a 2year period. The Specific Aims of the proposed study among pediatric RTRs and LTRs are: a. To estimate the prevalence and incidence of oral mucosal diseases and GE in relation to new immunosuppressive drug regimens, type of transplant, and time since transplant surgery; b. To estimate the prevalence of unmet dental need in relation to socio-demographic variables and time since transplant surgery; c. To collect preliminary data on any potential association between unmet dental needs (e.g., advanced caries, chronic gingival inflammation associated with GE) and history of acute graft rejection episode(s). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ORGAN REPLACEMENT TECHNOLOGY ANALYSIS PROJECT (ORTAP) Principal Investigator & Institution: Stahl, James E.; Research Staff; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2007 Summary: There is a severe shortage of cadaveric organs for liver transplant. Critically ill patients compete with one another for the only therapy open to them. Only new supplies of organs or alternative therapies can address this need. The proposed research seeks to develop a model of the liver allocation system to evaluate the costs, effectivenesses and systemic implications of non-cadaveric organ replacement technologies (ORT). Using discrete event simulation (DES), the liver allocation system with and without ORTs will be modeled. DES is a modeling technique that explicitly captures the competition for limited resources, which is central to this problem. We will develop a model to estimate the health and economic effects of introducing new therapies such as tissue-engineered organs, xenotransplants, living-donor partial-liver transplants, and liver dialysis. Outcomes will include costs, quality-adjusted life-years and process measures such as waiting time and resource utilization. The model will also be used to identify performance characteristics required to make ORTs useful alternatives to cadaveric organs and help design future trials by identifying parameters which influence outcome and are not know with certainty. Finally, the model will help estimate the effects of gaming by patients and institutions and help predict the way ORTs will change the decision-making environment. Data from diverse sources such as the Optimal Timing of Liver Transplant project, UNOS and NIDDK and others will be used to derive parameter estimates for the models. Estimates of functionality, longevity, and time to production for ORTs will be derived from the literature and expert opinion.

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The candidate has previously developed and verified a model of the current liver allocation system. This model will be expanded and used to examine the following specific aims: 1) determine the role and cost-effectiveness of organ replacement therapies (ORT) that are functionally equivalent to cadaveric organs; 2) determine the role and cost-effectiveness of ORTs that are temporary or not as effective as cadaveric organ; 3) examine liver allocation policy with/without ORTs from the perspective of game theory and ethics. On completion, this project should contribute to the general knowledge of the liver allocation problem and help policy makers better understand which technologies are the best investments. The research will lay the groundwork for future R01 proposals by the candidate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OUTCOMES TRANSPLANTATION

OF

HEPATITIS

C

FOLLOWING

LIVER

Principal Investigator & Institution: Shakil, A. Obaid.; Associate Professor; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 07-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Hepatitis C is the leading indication for liver transplantation. Patients transplanted for hepatitis C virus (HCV) disease universally develop re-infection of the allograft. The resultant hepatitis has an accelerated course. With the continued shortage of donor organs, it is crucial to develop strategies to promote long-term graft survival. We hypothesize that in the immune suppressed transplant recipient, HCV genetic features play a dominant role in disease progression. The principal goal of this proposal is to determine the impact of HCV genomic variability on the outcome of recurrent hepatitis C in liver allograft recipients. We propose to examine clinical and viral data under three different scenarios to test the hypothesis that an association exists between levels of genetic diversity in HCV and the severity of recurrent hepatitis following transplantation. We will assess the levels of viral diversity prior to and following liver transplantation in a group of individuals from whom samples and clinical outcomes are available. Further, to gain a more clear understanding of changes in viral evolutionary dynamics associated with liver transplantation, we will track viral evolutionary changes at several time points leading to and immediately following transplantation in a small number of individuals. This study will test the presence of a relationship between viral diversity and transplantation outcome, as defined by the severity of hepatitis on allograft biopsy one year following transplantation. It will also reveal changes in viral evolutionary dynamics over a window encompassing liver transplantation. Much of the genetic analyses will be undertaken by Heteroduplex Mobility Assay (HMA). Selected samples that show interesting profiles in HMA will be sequenced and examined by phylogenetic analyses. Clinical evaluation will include recipient and donor demographics, details of immunosuppression and episodes of rejection, and graft and patient survival. Patients will be categorized to have mild or severe disease. The two groups will be compared for differences in clinical and laboratory variables including the HMA score. A statistical model will be created to predict severe disease. If validated such a model will greatly enhance our ability to optimize transplant outcomes. Completing the specific aim of this proposal may also provide valuable information about key aspects of host-viral interactions and the influence of such interactions on disease course. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHOGENESIS AND TREATMENT OF CHRONIC REJECTION Principal Investigator & Institution: Murase, Noriko; Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-JAN-1998; Project End 31-DEC-2003 Summary: (Adapted from the applicant's abstract): This investigation postulates that chronic rejection of allografts is caused by the elimination of donor antigen presenting cells residing in the graft, and that through retention of these cells, promotes low grade stimulation of the recipient s immune system leading to prevention of CR. An animal model as been developed to test this hypothesis. Animals are pretreated with donor bone marrow or a hepatic allograft in concert with Tacrolimus. Donor microchimerism persists for at least 100 days, and then, the animals are challenged with a heterotopic cardiac allograft (CCA). The PI has found that animals previously receiving a liver allograft do not experience CR while those that receive bone marrow do. The hypothesis is advanced that the liver provides the stromal elements for survival of donor hematopoietic stem cells which protect cardiac allografts from CR. In contrast, with animals receiving donor bone marrow, there is induction of a strong Th-1 type cell response due to a loss of microchimerism, which leads to CR. In this project, the PI proposes to study the mechanisms responsible for lymphocyte trafficking and cellular activation, the influence of persistent donor antigen presenting cells on the incidence and intensity of CR and whether maneuvers for augmentation of donor chimerism in human liver transplant patients lowers the severity of CR. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PH III: CELLCEPT IMPAIRMENT ON NEORAL

IN

LIVER

TRANSPLANT

W/

RENAL

Principal Investigator & Institution: Clavien, Pierre A.; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHARMACODYNAMIC THRESHOLDS OF IMMUNOSUPPRESSION Principal Investigator & Institution: Sindhi, Rakesh K.; Children's Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 15213

Hosp

Timing: Fiscal Year 2002; Project Start 04-SEP-2001; Project End 31-MAY-2005 Summary: (provided by applicant): Acute rejection or side effects occur in nearly half of all transplant patients receiving immunosuppression. During our studies with regimens of (SRL) sirolimus+cyclosporine/tacrolimus (CsA/TAC), cytokine and costimulatory cell surface proteins (biomarkers), have demonstrated sensitivity to clinically relevant immunosuppressive drug concentrations in mitogen-stimulated peripheral blood lymphocytes (PBL) from normal and transplanted human subjects. Effect: concentration (pharmacodynamic, PD) relationships between biomarkers and drug concentrations also indicate ability to measure single- and multiple-agent effects within combination regiments, and to predict the amount of drug needed to inhibit a certain amount of biomarker, both for patient populations and individuals. However, prior to use as measures of immunosuppressive effect, the amount of biomarker inhibition associated with clinical conditions representing insufficient, excessive and adequate immunosuppression must be known. This may define safe amounts of drugs for

52

Liver Transplant

children, who experience a higher incidence of life-threatening complications of immunosuppression such as post-transplant lymphoproliferative disorder. Therefore, the specific aim of this project is to measure biomarker expression during a planned pharmacokinetic (PK) evaluation of a SRL+TAC regimen in 40 children with liver transplants, relate it to amount of drug, and to determine whether the occurrence of acute rejection, side effects and stable post-transplant course can be related to threshold levels of biomarker inhibition or the amount of drug associated with such thresholds. During a sponsored clinical trial of SRL+TAC, our proposal will manage biomarker data as follows: 1. Measure mitogen-stimulated expression of the cytokines IL-2, TNF-alpha and IFN-gamma in T-cells, and of costimulatory proteins CD54 (intercellular adhesion molecule-1), CD86 (B7.2) and CD95 (Fas antigen) in B-cells, and the proliferative response of lymphocytes to donor antigen. This will be performed during PK studies planned in the clinical trial, and additionally, during rejection, side effects, and at 12, and 24 month after transplantiation. 2. PD modeling to predict biomarker thresholds or drug concentrations associated with them, which are related to the occurrence of acute rejection, side effects, and the stable post-transplant course. Potential benefits may include customized regimens in the future, and decreased complications in one-half of the nearly 40,000 new transplant recipients of solid organ and bone marrow grafts, each year. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHARMACOKINETICS OF ABBOTT CYCLOSPORINE FOLLOWING LIVER TRANSPLANT Principal Investigator & Institution: Pruett, Timothy L.; Professor of Surgery; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 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: PREDICTING OUTCOME--ALCOHOLIC LIVER TRANSPLANT PATIENTS Principal Investigator & Institution: Dimartini, Andrea F.; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-JUN-1998; Project End 31-MAY-2004 Summary: APPLICANT'S ABSTRACT: Alcoholic Cirrhosis is the most common reason for liver failure and the largest diagnostic category receiving liver transplantation. However, factors that shape policy, treatment choices, candidate selection, and public options are strongest against this group. Without guidance from rigorous research data, the future for alcohol cirrhotics pursuing transplantation is uncertain. To date, no studies of outcome in alcoholic cirrhotics have used alcohol research measures or models, as proposed herein. In the transplant literature there is a lack of consistency in relapse definitions, timing or methods of follow-up, or use of post-transplant factors to predict alcohol use. This proposed research will expand the primary aim of alcohol research which is to identify and explain the factors that shape alcohol use and its consequences in various populations. To investigate outcome in alcoholic cirrhotics undergoing liver transplantation, expertise in psychiatry, medicine, transplantation, and alcoholism is needed. The applicant, an M.D. board certified in psychiatry, has the basic requisite skills to embark on this line of research. Through five years of clinical work evaluating, treating, and following alcoholic cirrhotic patients pursuing transplantation

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the applicant has developed a high degree of clinical acumen as well as the necessary connections to one of the largest liver transplant teams in the U.S. This Mentored Clinical Scientist Development Award will allow the applicant the opportunity to consolidate clinical skills in conjunction with a structured educational program and mentored research. During the award period, the candidate will conduct a prospective longitudinal study of alcohol use following liver transplantation, while investigating pre-transplant and post-transplant factors hypothesized to influence return to drinking. This research experience will be complemented by career development activities supervised by pioneering researchers in addictions, transplantation, and psychiatric research. The proposed plan is designed to develop the candidate's expertise in: 1) longitudinal study design and analysis; 2) alcohol relapse identification and monitoring; 3) conceptual and analytic modeling of relapse factors; and 4) post-transplant alcohol use outcome, and will give her the necessary skills to become an independent academic researcher in addictions and transplantation research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEOMICS AND BIOMARKERS FOR HEPATOCELLULAR CANCER Principal Investigator & Institution: Afdhal, Nezam H.; Associate Professor of Medicine; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Hepatitis C (HCV) is the commonest cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) in the United States. HCC occurs primarily in patients with advanced fibrosis and cirrhosis from HCV. Current screening techniques involve the use of serum alfafetoprotein and liver imaging with ultrasound performed in high risk patients on a 3 to 6 monthly basis. Early detection can improve outcomes with liver transplantation and perhaps non-surgical therapies. However screening is not very effective and many patients present with large tumors or multifocal HCC with a median survival of only 6 months. There is a definite clinical need for better non-invasive biomarkers for HCC which can lead to early detection and treatment. The specific aims of this exploratory R21 proposal are to utilize a proteomic approach to identify novel biomarkers for HCC and then evaluate these biomarkers in a cohort of patients with HCV at high risk for HCC. The initial step will be identification of a matching group of patients with a high risk of HCC and those who have developed HCC during the prospective COPILOT study. The COPILOT study provides a large cohort of patients with HCV and cirrhosis who are randomized to treatment with either low dose PEGylated interferon alfa 2b or colchicine and are followed for 4 years with rigorous clinical screening for HCC. The study is in year 2 and the incidence of HCC is approximately 5%. Serum from these patients prior to and after the development of HCC is stored and will be utilized for proteomic studies. Tissue from normal liver and HCC is available from these patients who have undergone liver transplant. A control disease serum bank from patients with HCC unrelated to HCV is also available at BIDMC. The serum and tissue will be examined by proteomics for identification of novel biomarkers using SELDI-TOF mass spectrometry. Careful clinical characterization and matching will assist in the bioinformatic approach necessary to identify candidate biomarkers. Novel proteins and peptide biomarkers will be sequenced and identified and an ELISA will be developed for any promising candidate biomarkers. The candidate biomarker ELISA will then be validated in the large HCV serum bank at BIDMC of patients with all stages of HCV and those in the COPILOT

54

Liver Transplant

trial. These studies may lead to identification of more specific and sensitive biomarkers for HCC in HCV which can then be validated further in prospective clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: QUALITY TRANSPLANTATION

OF

LIFE

IN

CHILDREN

AFTER

LIVER

Principal Investigator & Institution: Alonso, Estella M.; Children's Memorial Hospital (Chicago) Chicago, Il 606143394 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 29-SEP-2004 Summary: The long-term goal of this study group is to improve outcome, quality of care, and promote cost-savings for pediatric liver transplant (LT) recipients. The primary objectives of the proposed study are to describe the health-related quality of life (HRQOL) of children who survive liver transplantation (LT) and to examine the impact of disease severity at transplant and the type of graft received (living-donor (LD) or cadaveric) on long-term HRQOL. The study will be conducted at five medical centers selected from the Studies of Pediatric Liver Disease (SPLIT) research network. SPLIT is a consortium of 38 centers in North America, established in 1995 to prospectively collect demographic and clinical outcome data from a large cohort of children receiving LT. Multi-center collaboration is needed to enroll a sufficient sample size to achieve the current study objectives. This is a cross-sectional study that will evaluate 150 children aged 2-18 years at the two-year anniversary of their transplant. Parents of these children will complete Child Health Questionnaire and the Family Assessment Device. These surveys are carefully validated multi-dimensional tools that have been used to test both normative and clinical samples. Data from these surveys will include measures of physical and mental health, role function, social limitations and family function. Patient demographic information and clinical data, both past and present, will be obtained from the SPLIT database and tested as predictors of these domains of HRQOL. Specifically, this project will test the hypothesis that children who have more advanced liver disease at the time of LT have lower HRQOL in long-term follow-up. It will also evaluate whether the LD LT process improves long-term HRQOL and family function as compared to cadaveric transplantation. Assessing the HRQOL of children following transplant is an important aspect of predicting their ongoing needs. HRQOL measures could be used to demonstrate to payers and policy makers the value of those interventions which may not affect traditional clinical outcomes but which may have great impact on patients? overall well being and ability to function in society. Selecting clinical options and interventions that maximize long-term HRQOL would help reduce the burden of care over time. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RECURRENT HEPATITIS B AFTER LIVER TRANSPLANTATION Principal Investigator & Institution: Lok, Anna S.; Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2008 Summary: Hepatitis B accounts for approximately 5000 deaths/yr in the United States. Early results with orthotopic liver transplantation (OLT) for hepatitis B were poor with recurrence rates of >80% and 2-year mortality rates of 50%. Recent studies found that continuous high dose IV hepatitis B immune globulin (HBIG) can decrease the rate of reinfection to <20%. However, high dose HBIG is very expensive ($30,000-$50,000/yr)

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and the efficacy is low in patients with replicative infection pre-OLT. Pilot studies showed that lamivudine (LAM, an oral nucleoside analog which costs $1,200-$1,500 per yr) can decrease the rate of recurrent hepatitis B to <30% during the first post-OLT year but the long-term efficacy is limited by drug resistant mutants. Three pilot studies reported that combination therapy of HBIG and LAM is more effective than either agent alone with recurrence rates <5%, but it is not clear how long HBIG needs to be administered. Given the high costs and the inconvenience of life-long HBIG therapy, there is a need for a prospective, randomized controlled trial to determine if prophylaxis with LAM and short-term HBIG is as effective as LAM and long-term HBIG in the prevention of recurrent hepatitis B post-OLT. The use of antiviral agents with potential activity against LAM resistant HBV mutants, such as adefovir dipivoxil, also needs to be evaluated. The specific aims of our study are: (1) To compare the safety, efficacy and cost-effectiveness of combination therapy with LAM and a 6-month course of HBIG with LAM and a 3-yr course of HBIG in the prevention of recurrent hepatitis B postOLT. (2) To identify the epidemiological, clinical and virological factors that are associated with recurrent hepatitis B post-OLT. (3) To determine the safety and efficacy of adefovir dipivoxil in the suppression of HBV replication in patients who have developed LAM resistant HBV mutants and to compare the rate of recurrent hepatitis B post-OLT in patients with and without LAM resistant mutants prior to transplant. This is a prospective, randomized, multi-center clinical trial involving 20 liver transplant centers in N. America, to be conducted under an investigator IND 59,167. 290 patients with hepatitis B who are listed for OLT as UNOS status 1 or 2 will be enrolled. Open label LAM will be administered to decrease virus load pre-OLT. Patients will be randomized after OLT to Group I: LAM and 3 yr-course of HBIG or Group II: LAM and 6-month course of HBIG. Patients who develop LAM resistant mutants pre- or postOLT will additionally receive adefovir dipivoxil. The primary end-point of this trial is the rate of recurrent hepatitis B during the first 3 yr post-OLT. This trial will provide definitive answers whether combination therapy with LAM and a 6-mon course of HBIG is as efficacious and more cost-effective than LAM and a 3-yr course of HBIG in the prevention of recurrent hepatitis B post-OLT. In addition, crucial data will be generated on the efficacy of pre-OLT LAM in virus clearance, incidence and outcome of silent allograft infection, clinical outcome of patients with LAM resistant HBV mutants, and management of patients with LAM resistant mutants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF CHOLANGIOCYTES BY INSP3 RECEPTOR ISOFORMS Principal Investigator & Institution: Ehrlich, Barbara E.; Professor; Pharmacology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Bile secretion is one of the principal functions of the liver. In order to maintain bile flow, not only must hepatocytes secrete bile, but this must then be modified and conditioned further by bile duct epithelial cells, or cholangiocytes. Abnormal cholangiocytes function results in cholestasis, which is a cardinal manifestation of liver disease. Cholestatic liver diseases are responsible for 20% of liver transplants in the US, and are the most common cause of liver disease among pediatric transplant patients. In addition, abnormal cholangiocyte function is responsible for the hepatic manifestations of cystic fibrosis, one of the most common inherited diseases. Bile secretion in cholangiocytes is regulated in part by cytosolic Ca2+. In general, cells are regulated both by the pattern of Ca2+ signals over time and by the

56

Liver Transplant

regions of the cells in which Ca2+ signals occur. However, little is known about temporal or spatial aspects of Ca2+ signaling in cholangiocytes, and nothing is known about how these Ca2+ signals are regulated. Inositol 1,4,5-trisphosphate receptors (InsP3R) mediate Ca2+ signaling in epithelia, and cholangiocytes express all three isoforms of this receptor. The hypothesis of this proposal is that Ca2+ signals in the cholangiocyte are regulated by the subcellular distribution of the InsP3R isoforms. This hypothesis will be investigated through the following specific aims: The function and regulation of the InsP3Rs will be compared at the single channel level. The contribution that each of the receptors plays to Ca2+ signaling in cholangiocytes will be examined in a bile duct cell line modified to express either one or a combination of these receptors. These findings will be related to the organization of Ca2+ signals and secretory function in native cholangiocytes, as determined in isolated microperfused bile duct segments. This work should not only identify the molecular mechanisms responsible for Ca2+ signaling in cholangiocytes, but serve as a model for how the molecular organization of signaling pathways is responsible for regulation of ductular secretion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TACROLIMUS

RIFAMPIN

ON

PHARMACOKINETIC

DISPOSITION

OF

Principal Investigator & Institution: Hebert, Mary; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002 Summary: Tacrolimus is an immunosuppressive agent, approved by the FDA in 1990 for the prevention of rejection following liver transplantation. Tacrolimus is known to be metabolized by cytochrome P450 3A4 in the liver and intestine. Since tacrolimus suppresses the immune system, it predisposes patients to reactivation and/or disseminatin of tuberculosis. Rifampin is one of the first line agents for treatment of tuberculosis and known to be an inducer of cytochrome P450 3A4. Rifampin has been shown to cause clinically significant interactions with agents which are also substrates for cytochrome P450 3A4 such as cyclosporine. There is one case report in the literature reporting decreased tacrolimus levels with the concomitant administration of rifampin. This pilot study will evaluate the effects of rifampin on the pharmacokinetic disposition of tacrolimus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RIGHT LOBE LIVING DONOR LIVER TRANSPLANTATION IN ADULTS Principal Investigator & Institution: Shrestha, Roshan; Associate Professor of Medicine; Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 17-SEP-2002; Project End 31-AUG-2009 Summary: (provided by applicant):The Liver Transplant Program at the University of North Carolina at Chapel Hill (UNC-CH) is a well-established and vitally important regional resource. This application proposes a multi-center cooperative core study in which a well-defined cohort from UNC-CH and other Transplant Centers (TC) will be followed prospectively to provide reliable, complete, and generalizable information on adult donor and recipient outcomes for both living donor and cadaveric liver transplants. A database structure and information core is proposed, and this application discusses the relevance of each proposed data element. This core study will be

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augmented by analysis of our historical cohort for which existing outcome data can be pooled across all the Transplant Centers (TC) participating in the Clinical Research Consortium. In addition to these studies, this application proposes two common protocols. The first will examine in-depth the short and long-term morbidity and quality of life of living donors. The second will examine differences in drug metabolism and immunosuppressive regimen between recipients of living donor and cadaveric liver transplants. UNC-CH is well qualified to be a Transplant Center (TC) within the Clinical Research Consortium having performed 13 LDLT in the last 18 months and 21 LDLT total. Projections for UNC-CH are 50-60 CADLT and 15-20 LDLT per year, thereby allowing accrual and followup of more than sufficient numbers of patients to contribute to the Consortium studies. Overall one-year patient and graft survival for both CADLT and LDLT are 90-95% and 77-85% respectively. The UNC-CH infrastructure includes 4 transplant surgeons, 5 hepatologists, and other relevant professionals in vascular surgery, anesthesiology, radiology and vascular/interventional radiology, immunology, infectious disease, pulmonary disease, pathology, pharmacy, nursing, blood bank, psychiatry or psychology and social services. All studies benefit from use of the Verne Caviness General Clinical Research Center (GCRC) as a primary site and collaboration with the Center for Gastrointestinal Biology and Disease (CGIBD). Particularly relevant to this application are the GCRC's Informatics Services and the epidemiologic services of the CGIBD.As a Transplant Center, UNC-CH is committed to close collaborations including membership on the Steering Committee. UNC-CH has participated in multiple multi-center trials and has a rich experiential base in working with data coordinating centers. Our application's strong institutional support for participation as a TC includes acceptance of per patient funding mechanisms for the common protocols. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF PRE TRANSPLANT CHEMOEMBOLIZATION FOR HEPATOMA Principal Investigator & Institution: Colquhoun, Steven D.; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 900481804 Timing: Fiscal Year 2002; Project Start 11-FEB-2000; Project End 31-JAN-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SAFETY, TOLERABILITY & PHARMACOKINETICS OF SDZ RAD IN DE NOVO LIVER TRANSPLANT Principal Investigator & Institution: Freeman, Richard; Associate Professor; 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: SOLID ORGAN TRANSPLANTATION IN HIV: MULTI-SITE STUDY Principal Investigator & Institution: Stock, Peter G.; Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JAN-2008

58

Liver Transplant

Summary: (provided by applicant): The primary aim of this study is to evaluate the safety and efficacy of solid organ transplantation in people with HIV disease by conducting a prospective, multi-center cohort of HIV-positive (+) patients who undergo kidney o liver transplantation. Our long-range goals are: (1) to provide patients and clinicians with information regarding the HIV-specific risks of transplantation, (2) to provide clinicians with information necessary to manage immunosuppressive and antiretroviral (ARV) medications together, and (3) to understand underlying basic science mechanisms that explain patient outcomes so that clinical management can be adjusted to maximize the outcomes. Patients with HIV infection are at significant risk for end stage organ disease. Prior to the advent of highly active antiretroviral therapy (HAART), such patients were often not considered as transplant candidates based on poor prognosis. However, with the use of HAART, HIV positive patients have experienced significant improvements in morbidity and mortality. Thus, increasing numbers of HIV+ patients with end stage kidney and liver disease are potential candidates for transplantation. Despite increasing referrals, patients and clinicians lack the necessary data to determine the safety and efficacy of transplantation and immunosuppression in this group. This lack of conclusive data has led to continued denial of care by many transplant centers and third party payers, resulting in frustration and confusion for both patients and their health care providers. Therefore, the primary clinical focus of this proposal is the design of a multi-center study that is powered to test the hypothesis that HIV+ liver and kidney transplant recipients will have patient and graft survival rates equivalent to other patient groups without HIV infection currently considered acceptable transplant candidates. In addition to providing the numbers required for a sufficiently powered study, the multicenter study provides access to 16 transplant centers for HIV+ patients facing end stage organ disease, facilitating regional access to avoid the logistic difficulties associated with limited access to distant sites. Of equal importance, the research plan establishes a prospective cohort that provides an ideal opportunity to explore mechanisms underlying disease progression in HIV+ transplant recipients and key issues in their medical management. The multi-center approach will capitalize on access to experts in the fields of virology and immunology. These investigators will explore the effects of immunosuppression (IS) on progression of HIV and viral co-pathogens known to be important in both transplant recipients and people with HIV infection. Progression of HIV and viral co-pathogens will be correlated with changes in the host immune response to HIV, viral co-pathogens, and allografts. These data will provide an essential contribution to an understanding of the factors that may be responsible for variations in graft and patient survival rates. This cohort will also provide the basis for describing the pharmacokinetic interactions between IS and the hepatically-metabolized ARVs, data that will greatly benefit health care workers managing HIV+ patients following transplantation, as maintaining appropriate levels of both of these classes of drugs will be essential for success. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STEROID WITHDRAWAL TRANSPLANTATION: RANDOMIZED

AFTER

SUCCESSFUL

LIVER

Principal Investigator & Institution: Seaman, David S.; 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: SYSTEMATIC INTEGRATION POR INTO CLINICAL PATHWAY OF HCC Principal Investigator & Institution: Schwartz, Myron E.; Surgery; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 31-JAN-2007 Summary: HCC Hepatocellular carcinoma (HCC) is an increasing pubic health problem in the United States. The Mount Sinai Hospital in New York has become a major referral center for this disease, with 231 new patients with HCC or suspected HCC first seen in 2000. Myron Schwartz, MD (the applicant) is Associate Professor of Surgery, Deputy Director of Liver Transplantation, and Chief of Hepatobiliary Surgery at Mount Sinai. Dr. Schwartz has proven record of patient-oriented research (POR), with 156 peerreviewed publications, and a long history of mentoring trainees who go on to successful careers in academic surgery, including 7 who are now directors of transplant programs. Dr.Schwartz's clinical and academic focus is on HCC, and he is an internationally recognized expert on HCC care. The central hypothesis of this proposal is that a program which seamlessly incorporates clinical care and POR will maximize quality of care, provide unparalleled research opportunities, and create an ideal setting for the training of clinician/researches. Dr.Schwartz's role is as director of the program, principal investigator for surgery-related projects, and mentor for trainees. The specific aims are to conduct projects exploring: 1. Etiology-" Gene Expression Profiles in HCC"; 2.Diagnosis-"Utility of AFP-L3% in Screening, Diagnosis, and Prognosis of HCC";3. Secondary prevention after resection- "Prevention of HCC Recurrence after Surgical Resection by Vaccination with Tumor-Derived Heat Shock Protein gp96 and Associated Peptides"; 4. Secondary prevention after transplantation- "Sirolimus vs Tacrolimus as the Primary Immunosuppressive Agent after Liver Transplantation for HCC"; and 5. "Treatment of unresectable HCC- "Cytokine Inhibition in HCC". Mount Sinai's commitment to furthering POR and education is reflected in the recent awarding by the NIH of a K30 institutional Clinical Research Curriculum Award, a T32 institutional Training Grant in Investigative Gastroenterology, and a K23 Mentored POR Career Development Award to a junior faculty member to study novel HCC therapies. This program provides a truly remarkable opportunity to make meaningful progress in understanding, preventing and treating HCC, while in the process providing fertile training ground for young physician-scientists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TACROLIMUS VS CYCLOSPORINE SIROLIMUS IN LIVER TRANSPLAN Principal Investigator & Institution: Fung, John J.; Professor of Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002 Summary: Compared with Imuran, cyclosporine (CSA) and tacrolimus have reduced acute rejection rates in orthotopic liver transplant (OLTx) recipients to <50% but have well known toxicities e.g. hypertension, nephrotoxicity and neurotoxicity. Sirolimus (SRL, Wyeth Ayerst Research. Radnor, PA) is a potent T-cell inhibitor without such toxicities inhibits the effects of IL-2 receptor stimulation and is synergistic with cyclosporine which inhibits IL-2 production. In controlled phase II trials in renal transplantation, SRL has decreased rejection rates to <10% when combined with cyclosporine. Multicenter phase III trials evaluating low and high dose SRL with

60

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cyclosporine have reduced rejection rates to between 11-19%. Eight OLTx recipients are currently on SRL without rejection at a mean followup of 6.5 months. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRAINING GRANT IN ACADEMIC GASTROENTEROLOGY Principal Investigator & Institution: Omary, M Bishr.; Professor of Medicine; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-JUL-1975; Project End 30-JUN-2006 Summary: (adapted from the application) The Stanford University GI training fellowship offers research opportunities that cover diverse investigative fields. In the GI division proper, active programs include: (a) the molecular determinants of pathogenesis and host immunity for viruses that infect the liver or GI tract (Glenn, Greenberg, Matsui), (b) the regulation of lipoproteins and lipids in the liver and intestine (Cooper, Levy-Wilson), (c) cellular oncogenesis and the role of c-src in intestinal cell differentiation/transformation (Cartwright), (d) function and disease association of digestive epithelial cytoskeletal proteins (Omary), (e) the molecular basis for intracellular vesicular sorting in the exocrine pancreas (Lowe), (f) controlled clinical trials of vaccines/antiviral therapy, and evaluation of liver transplantation outcomes (Garcia, Keeffe, Soetikno), (g) clinical and molecular studies of Barrett's esophagus (Omary, Triadafilopoulos), and (h) development and testing of novel endoscopic diapostic and therapeutic modalities (Van Dam, Soetikno). In addition to these research areas, fellows are encouraged to explore and take advantage of ongoing research in the programs of affiliated faculty including health policy, outcomes, microbiology, pathology, immunology and developmental biology. The trainees are individuals who have completed internal medicine or pediatric residencies and a year of clinical GI training in our own program and are interested in developing skills in bench and/or clinical research. Other trainees include physicians trained in other specialties, or postdoctoral Ph.D. trainees, who wish to pursue GI research. The training program has expanded in the past five years with the addition of a liver transplant program, the growth of existing programs and a recent NIH-funded Digestive Disease Center. We are also actively recruiting for additional faculty members to add to the recent appointment of two new faculty members (Van Dam with expertise in spectral endoscopy; Gerson with outcomes research training). At present, we have a program that includes a minimum of two years of research training (frequently 3 to 5 years) that enrolls two to four new trainees per year. We have several outstanding candidate trainees who can be enrolled. The training is provided by faculty whose laboratories are located within close proximity (5-15 minutes) to each other at Stanford University, the Palo Alto VA Hospital and the Palo Alto Research Foundation. All laboratories are well equipped, with over seven thousand square feet of state-of-the-art laboratory space currently occupied by the GI division. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSFUSION BIOLOGY AND MEDICINE Principal Investigator & Institution: Toy, Pearl T.; Professor; Laboratory Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-FEB-1996; Project End 31-DEC-2005 Summary: Transfusion support plays an increasingly prominent role in modern medical care. Blood transfusions are essential not only to save the lives of bleeding trauma victims, but also to the successful outcome of many complex treatments of cancer

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patients and patients undergoing transplant, cardiac or spine surgery. An estimated 12 million units of blood per year are collected in the United States for transfusion. Many questions remain regarding transfusion biology and medicine. The purpose of this SCOR program to continue to address some of these questions with a group of interrelated, collaborative projects. The areas of emphases in response to the RFA are cytokines, red blood cell transfusion, and immunomodulatory aspects of transfusion. In the area of cytokines, Project 2 proposes to use a novel mouse model developed in the previous grant to study molecular mechanisms of cytokine signaling in megacryocytopoiesis and Project 3 proposes to use gene-knockout mice to study src tyrosine kinases in cytokine signaling in hematopoiesis, In the area of red blood cell transfusions, Project 4 proposes to use the acute isovolemic hemodilution model developed in the previous grant to study the effects of acute anemia on the nervous system, heart and subcutaneous tissue in normal humans. These data will provide a scientific base to determine the indications for red blood cell transfusion. In the area of immunomodulatory aspects of transfusion, Project 6 proposes to study the persistence of donor cells in transfusion recipients and in liver transplant recipients, and Project 7 proposes to study B cells in autoimmunity and in tolerance to platelet alloimmunization. Project 5 was deleted in the last competitive review and Project 1 is being discontinued. The remaining five projects are supported by Administrative Core A and Biostatistics Core B. To grapple with these questions in Transfusion Medicine, we brought together a new multi-disciplinary team in the previous grant. The team has made novel findings and has developed novel experimental systems. In the renewal, we propose to use these novel systems to further study how blood is made and how blood affects different organs in health and disease. The ultimate goals of this program are to make optimal use of blood products, to evaluate and possibly modify the immune effects and understand and possibly stimulate blood production so as to reduce transfusion needs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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,

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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

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

Atlantic Canada's liver transplant program may be relaunched. by Moulton D.; 2003 Mar 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154945

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Calpain is a mediator of preservation-reperfusion injury in rat liver transplantation. by Kohli V, Gao W, Camargo CA Jr, Clavien PA.; 1997 Aug 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23191

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CMV infection of liver transplant recipients: comparison of antigenemia and molecular biology assays. by Amorim ML, Cabeda JM, Seca R, Mendes AC, Castro AP, Amorim JM.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=32208

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Comparison of Specific Serological Assays for Diagnosing Human Herpesvirus 6 Infection after Liver Transplantation. by Yoshikawa T, Black JB, Ihira M, Suzuki K, Suga S, Iida K, Saito Y, Asonuma K, Tanaka K, Asano Y.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96028

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.

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Concentrations in plasma and tissue penetration of ceftriaxone and ornidazole during liver transplantation. by Steib A, Jacoberger B, Von Bandel M, Beck F, Beller JP, Boudjema K, Koffel JC, Otteni JC.; 1993 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188085

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Detection of cytomegalovirus DNA in sera of liver transplant recipients. by Patel R, Smith TF, Espy M, Wiesner RH, Krom RA, Portela D, Paya CV.; 1994 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=264014

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Diagnostic Implications of Human Cytomegalovirus Immediate Early-1 and pp67 mRNA Detection in Whole-Blood Samples from Liver Transplant Patients Using Nucleic Acid Sequence-Based Amplification. by Blok MJ, Lautenschlager I, Goossens VJ, Middeldorp JM, Vink C, Hockerstedt K, Bruggeman CA.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87625

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Diagnostic Value of Anti-Hepatitis C Virus (HCV) Core Immunoglobulin M in Recurrence of HCV Infection after Orthotopic Liver Transplantation. by Casino C, Lilli D, Rivanera D, Comanducci A, Rossi M, Casciaro G, Pecorella I, Alfani D, Mancini C.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85330

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Disseminated Toxoplasmosis, Resulting from Infection of Allograft, after Orthotopic Liver Transplantation: Usefulness of Quantitative PCR. by Botterel F, Ichai P, Feray C, Bouree P, Saliba F, Tur Raspa R, Samuel D, Romand S.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130685

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Dynamic behavior of hepatitis C virus quasispecies in patients undergoing orthotopic liver transplantation. by Martell M, Esteban JI, Quer J, Vargas V, Esteban R, Guardia J, Gomez J.; 1994 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=236838

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Evaluation of PCR Primers for Early Diagnosis of Cytomegalovirus Infection following Liver Transplantation. by Mendez JC, Espy MJ, Smith TF, Wilson JA, Paya CV.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104571

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Evaluation of Quantitative PCR and Branched-Chain DNA Assay for Detection of Hepatitis B Virus DNA in Sera from Hepatocellular Carcinoma and Liver Transplant Patients. by Chen T, Luk JM, Cheung ST, Yu WC, Fan ST.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86641

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Evaluation of the COBAS AMPLICOR CMV MONITOR Test for Detection of Viral DNA in Specimens Taken from Patients after Liver Transplantation. by Sia IG, Wilson JA, Espy MJ, Paya CV, Smith TF.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86156

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External validation of a modified model of Acute Physiology and Chronic Health Evaluation (APACHE) II for orthotopic liver transplant patients. by Arabi Y, Abbasi A, Goraj R, Al-Abdulkareem A, Shimemeri AA, Kalayoglu M, Wood K.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125314

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Ganciclovir prophylaxis decreases frequency and severity of cytomegalovirus disease in seropositive liver transplant recipients treated with OKT3 monoclonal antibodies.

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by Lumbreras C, Otero JR, Herrero JA, Gomez R, Lizasoain M, Aguado JM, Colina F, Garcia I, Moreno E, Noriega AR.; 1993 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=192416 •

Genetic Clustering of Hepatitis C Virus Strains and Severity of Recurrent Hepatitis after Liver Transplantation. by Gigou M, Roque-Afonso AM, Falissard B, Penin F, Dussaix E, Feray C.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114714

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Haemophilus parainfluenzae Liver Abscess after Successful Liver Transplantation. by Friedl J, Stift A, Berlakovich GA, Taucher S, Gnant M, Steininger R, Muhlbacher F.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104634

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Impaired clearance of ceftizoxime and cefotaxime after orthotopic liver transplantation. by Burckart GJ, Ptachcinski RJ, Jones DH, Howrie DL, Venkataramanan R, Starzl TE.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=174715

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Kidney and liver transplants from a donor infected with Naegleria fowleri. by Kramer MH, Lerner CJ, Visvesvara GS.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229732

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Long-term results of pediatric liver transplantation in a combined pediatric and adult transplant program. by Atkison PR, Ross BC, Williams S, Howard J, Sommerauer J, Quan D, Wall W.; 2002 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116152

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Low predictive value of polymerase chain reaction for diagnosis of cytomegalovirus disease in liver transplant recipients. by Delgado R, Lumbreras C, Alba C, Pedraza MA, Otero JR, Gomez R, Moreno E, Noriega AR, Paya CV.; 1992 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265398

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Microbiological efficacy and pharmacokinetics of prophylactic antibiotics in liver transplant patients. by Arnow PM, Furmaga K, Flaherty JP, George D.; 1992 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245466

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Monitoring levels of human cytomegalovirus DNA in blood after liver transplantation. by Drouet E, Colimon R, Michelson S, Fourcade N, Niveleau A, Ducerf C, Boibieux A, Chevallier M, Denoyel G.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227954

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Monitoring of Viral Load by Quantitative Plasma PCR during Active Cytomegalovirus Infection of Individual Liver Transplant Patients. by Piiparinen H, Hockerstedt K, Lappalainen M, Suni J, Lautenschlager I.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120691

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Multigene Tracking of Hepatitis C Virus Quasispecies after Liver Transplantation: Correlation of Genetic Diversification in the Envelope Region with Asymptomatic or Mild Disease Patterns. by Sullivan DG, Wilson JJ, Carithers RL Jr, Perkins JD, Gretch DR.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110527

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Mycobacterium triplex Infection in a Liver Transplant Patient. by Hoff E, Sholtis M, Procop G, Sabella C, Goldfarb J, Wyllie R, Cunningham R, Stockman L, Hall G.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88079

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Ochrobactrum intermedium Infection after Liver Transplantation. by Moller LV, Arends JP, Harmsen HJ, Talens A, Terpstra P, Slooff MJ.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84223

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Parvovirus B19 in anemic liver transplant recipients. by Ndimbie OK, Frezza E, Jordan JA, Koch W, van Thiel DH.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170443

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Recovery of vancomycin-resistant gram-positive cocci from pediatric liver transplant recipients. by Green M, Barbadora K, Michaels M.; 1991 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=270362

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The first clinical isolate of Legionella parisiensis, from a liver transplant patient with pneumonia. by Lo Presti F, Riffard S, Vandenesch F, Reyrolle M, Ronco E, Ichai P, Etienne J.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229826

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Tracking hepatitis C virus quasispecies major and minor variants in symptomatic and asymptomatic liver transplant recipients. by Gretch DR, Polyak SJ, Wilson JJ, Carithers RL Jr, Perkins JD, Corey L.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190831

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Valganciclovir Results in Improved Oral Absorption of Ganciclovir in Liver Transplant Recipients. by Pescovitz MD, Rabkin J, Merion RM, Paya CV, Pirsch J, Freeman RB, O'Grady J, Robinson C, To Z, Wren K, Banken L, Buhles W, Brown F.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90155

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Voriconazole Inhibition of the Metabolism of Tacrolimus in a Liver Transplant Recipient and in Human Liver Microsomes. by Venkataramanan R, Zang S, Gayowski T, Singh N.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127452

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Water warming garment versus forced air warming system in prevention of intraoperative hypothermia during liver transplantation: a randomized controlled trial [ISRCTN32154832]. by Janicki PK, Stoica C, Chapman WC, Wright JK, Walker G, Pai R, Walia A, Pretorius M, Pinson CW.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137608

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

A case of electrical storm in a liver transplant patient. Author(s): Schmidt TD, Muir AJ. Source: Transplantation Proceedings. 2003 June; 35(4): 1437-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12826183

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A comparison of actual cost, DRG-based cost, and hospital reimbursement for liver transplant patients. Author(s): Skeie B, Mishra V, Vaaler S, Amlie E. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 2002 October; 15(9-10): 439-45. Epub 2002 September 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12389074

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A pilot study of interferon alfa and ribavirin combination in liver transplant recipients with recurrent hepatitis C. Author(s): Shakil AO, McGuire B, Crippin J, Teperman L, Demetris AJ, Conjeevaram H, Gish R, Kwo P, Balan V, Wright TL, Brass C, Rakela J. Source: Hepatology (Baltimore, Md.). 2002 November; 36(5): 1253-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12395337

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A retrospective review of sirolimus (Rapamune) therapy in orthotopic liver transplant recipients diagnosed with chronic rejection. Author(s): Neff GW, Montalbano M, Slapak-Green G, Berney T, Bejarano PA, Joshi A, Icardi M, Nery J, Seigo N, Levi D, Weppler D, Pappas P, Ruiz J, Schiff ER, Tzakis AG. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 May; 9(5): 477-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740790

6

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

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ABO-incompatible liver transplant: is it justifiable? Author(s): Stegall M. 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): 31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12514770

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Absorption of cyclosporine (Neoral) from a microemulsion formulation in a living donor liver transplant recipient. Author(s): Maeda Y, Kuzuya T, Ota S, Yamada K, Kobayashi T, Hayashi S, Yokoyama I, Nakao A, Nabeshima T. Source: Transplantation Proceedings. 2002 November; 34(7): 2784-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12431611

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Adult living donor liver transplantation: perspectives from 100 liver transplant surgeons. Author(s): Cotler SJ, Cotler S, Gambera M, Benedetti E, Jensen DM, Testa G. 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): 637-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12783411

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Adult-to-adult living donor liver transplant: UK experience. Author(s): Williams RS, Alisa AA, Karani JB, Muiesan P, Rela SM, Heaton ND. Source: European Journal of Gastroenterology & Hepatology. 2003 January; 15(1): 7-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12544688

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Air embolism as a complication of venovenous bypass during liver transplant for diffuse hemangiomatosis. Author(s): Viana JS, Furtado E, Romero A, Furtado AL. Source: Transplantation Proceedings. 2003 May; 35(3): 1128-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12947886

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An empirical comparison of EQ-5D and SF-6D in liver transplant patients. Author(s): Longworth L, Bryan S. Source: Health Economics. 2003 December; 12(12): 1061-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673814

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An open-label study of the safety and tolerability of converting stable liver transplant recipients to neoral. Author(s): Pasha TM, Wiesner RH, Dahlke LM, Porayko MK, Krom RA. Source: Liver Transplantation and Surgery : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 1998 September; 4(5): 410-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9724479

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An unusual oral chronic graft-versus-host disease-like syndrome following a liver transplant. Author(s): Bunetel L, Le Gall F, Delaval Y, Sixou JL, Dabadie A, Bonnaure-Mallet M. Source: J Periodontol. 2003 April; 74(4): 552-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12747462

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Analysis of gene polymorphisms in the regulatory region of MCP-1, RANTES, and CCR5 in liver transplant recipients. Author(s): Schroppel B, Fischereder M, Lin M, Marder B, Schiano T, Kramer BK, Murphy B. Source: Journal of Clinical Immunology. 2002 November; 22(6): 381-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12462338

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Analysis of intragraft gene and protein expression of the costimulatory molecules, CD80, CD86 and CD154, in orthotopic liver transplant recipients. Author(s): Bartlett AS, McCall JL, Ameratunga R, Yeong ML, Gane E, Munn SR. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2003 November; 3(11): 1363-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14525596

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Angioedema in pediatric liver transplant recipients under tacrolimus immunosuppression. Author(s): Lykavieris P, Frauger E, Habes D, Bernard O, Debray D. Source: Transplantation. 2003 January 15; 75(1): 152-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12544888

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Angiotensin-converting enzyme inhibitor-induced isolated visceral angioedema in a liver transplant recipient. Author(s): Rosenberg EI, Mishra G, Abdelmalek MF. Source: Transplantation. 2003 March 15; 75(5): 730-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12640318

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Antienvelope antibodies are protective against GBV-C reinfection: evidence from the liver transplant model. Author(s): Hassoba HM, Pessoa MG, Terrault NA, Lewis NJ, Hayden M, Hunt JC, Qiu X, Lou SC, Wright TL. Source: Journal of Medical Virology. 1998 November; 56(3): 253-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9783694

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Assessing the quality of the data in a transplant registry: the European Liver Transplant Registry. Author(s): van der Meulen JH, Jacob M, Copley L. Source: Transplantation. 2003 June 27; 75(12): 2164-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12829938

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Asymmetric cardiac hypertrophy at autopsy in patients who received FK506 (tacrolimus) or cyclosporine A after liver transplant. Author(s): Roberts CA, Stern DL, Radio SJ. Source: Transplantation. 2002 September 27; 74(6): 817-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12364862

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Atypical abdominal pain in a liver transplant recipient. Author(s): Handschin AE, Kadry Z, Selzner M, Mullhaupt B, Renner E, Weber M, Clavien PA. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 April; 9(4): 444-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12682900

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Backgrounds of early intragraft immune activation and rejection in liver transplant recipients. Impact of graft reperfusion quality. Author(s): Kiuchi T, Schlitt HJ, Oldhafer KJ, Nashan B, Ringe B, Kitai T, Tanaka A, Wonigeit K, Yamaoka Y, Pichlmayr R. Source: Transplantation. 1995 July 15; 60(1): 49-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7624942

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Beneficial effects of converting liver transplant recipients from cyclosporine to tacrolimus on blood pressure, serum lipids, and weight. Author(s): Neal DA, Gimson AE, Gibbs P, Alexander GJ. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2001 June; 7(6): 533-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11443583

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Benefits of cyclosporine microemulsion (Neoral) C(2) monitoring are sustained at 1 year in de novo liver transplant recipients. Author(s): Lake JR; Neo-INT-06 Study Group. Source: Transplantation Proceedings. 2001 November-December; 33(7-8): 3092-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750328

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Bile-independent absorption of cyclosporine from a microemulsion formulation in liver transplant patients. Author(s): Mueller EA, Kallay Z, Kovarik JM, Richard F, Wiesinger O, Schmidt K, Scheele J. Source: Transplantation. 1995 September 15; 60(5): 515-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7676504

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Biliary bacteria in living related liver transplant recipients: microbiology and rapid detection system using flow cytometry. Author(s): Saito T, Senda K, Takakura S, Fujihara N, Kudo T, Iinuma Y, Kiuchi T, Tanimoto M, Ichiyama S. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2003 February; 41(2): 159-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12667001

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Biliary complications after T-tube placement in liver transplant patients. Author(s): Kizilisik TA, al-Sebayel M, Hammad A, al-Traif I, Ramirez CG. Source: Transplantation Proceedings. 1997 November; 29(7): 2849-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9365588

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Biliary complications secondary to late hepatic artery thrombosis in adult liver transplant patients. Author(s): Margarit C, Hidalgo E, Lazaro JL, Murio E, Charco R, Balsells J. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1998; 11 Suppl 1: S251-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9664990

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Biliary endothelin levels in liver transplant recipients do not correlate with total bile acid concentration. Author(s): Kraus T, Sauer P, Mehrabi A, Bredt M, Golling M, Schonfuss T, Otto G, Stiehl A, Herfarth C, Klar E. Source: Transplantation Proceedings. 1998 May; 30(3): 836-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9595119

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Biliary tract complications of side-to-side without T tube versus end-to-end with or without T tube choledochocholedochostomy in liver transplant recipients. Author(s): Rabkin JM, Orloff SL, Reed MH, Wheeler LJ, Corless CL, Benner KG, Flora KD, Rosen HR, Olyaei AJ. Source: Transplantation. 1998 January 27; 65(2): 193-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9458013

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Biologic monitoring of the efficacy of immunosuppression in liver transplant patients. Author(s): Farges O, Buffello D, Swercz B, deGroote D, Bismuth H. Source: Transplantation Proceedings. 1995 August; 27(4): 2516-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7652911

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Blindness after liver transplant. Author(s): Dawson DG, Trobe JD. Source: Survey of Ophthalmology. 2002 July-August; 47(4): 387-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12161214

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Blood levels of TGFbeta1 in liver transplant recipients receiving either tacrolimus or micro-emulsified cyclosporine. Author(s): Hughes JR, Hughes VF, Trull AK, Metcalfe SM. Source: Transplantation. 1999 August 27; 68(4): 583-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10480422

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Blood pressure, endothelial function and circulating endothelin concentrations in liver transplant recipients. Author(s): Cifkova R, Pit'ha J, Trunecka P, Lanska V, Jindra A, Plaskova M, Peterkova L, Hrncarkova H, Horky K. Source: Journal of Hypertension. 2001 August; 19(8): 1359-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11518843

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Bloodstream infections in liver transplant recipients receiving tacrolimus. Author(s): Singh N, Gayowski T, Wagener MM, Marino IR. Source: Clinical Transplantation. 1997 August; 11(4): 275-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9267715

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Bone mass and mineral metabolism in liver transplant patients treated with FK506 or cyclosporine A. Author(s): Monegal A, Navasa M, Guanabens N, Peris P, Pons F, Martinez de Osaba MJ, Rimola A, Rodes J, Munoz-Gomez J. Source: Calcified Tissue International. 2001 February; 68(2): 83-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11310351

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Bradycardia associated with intravenous administration of tacrolimus in a liver transplant recipient. Author(s): Cox TH, Baillie GM, Baliga P. Source: Pharmacotherapy. 1997 November-December; 17(6): 1328-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9399620

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Brainstem auditory evoked potentials in liver transplant candidates. Author(s): Ellingson RJ, Wszolek ZK, Kendall JD, Donovan JP, Schafer DF. Source: Nebr Med J. 1995 July; 80(7): 167-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7651553

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Bronchiolitis obliterans organizing pneumonia associated with Pneumocystis carinii infection in a liver transplant patient receiving tacrolimus. Author(s): Kleindienst R, Fend F, Prior C, Margreiter R, Vogel W. Source: Clinical Transplantation. 1999 February; 13(1 Pt 1): 65-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10081638

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Bronchiolitis obliterans organizing pneumonia in an orthotopic liver transplant patient. Author(s): DeAngelo AJ, Ouellette D. Source: Transplantation. 2002 February 27; 73(4): 544-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11889426

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Budd-Chiari syndrome in pregnancy treated by caesarean section and liver transplant. Author(s): Salha O, Campbell DJ, Pollard S. Source: British Journal of Obstetrics and Gynaecology. 1996 December; 103(12): 1254-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8968247

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Cardiac hypertrophy in liver transplant recipients: tacrolimus, cyclosporine or both? Author(s): Therapondos G, Plevris JN, Dollinger MM, Hayes PC, Flapan AD. Source: Transplantation. 2003 July 27; 76(2): 446-7; Author Reply 447-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12883220

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Changes in portal blood flow following acute exercise in liver transplant recipients. Author(s): Ersoz G, Ersoz S. Source: Transplantation Proceedings. 2003 June; 35(4): 1456-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12826190

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Changes in the spectrum and risk factors for invasive candidiasis in liver transplant recipients: prospective, multicenter, case-controlled study. Author(s): Husain S, Tollemar J, Dominguez EA, Baumgarten K, Humar A, Paterson DL, Wagener MM, Kusne S, Singh N. Source: Transplantation. 2003 June 27; 75(12): 2023-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12829905

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Changing epidemiology and predictors of mortality in patients with spontaneous bacterial peritonitis at a liver transplant unit. Author(s): Singh N, Wagener MM, Gayowski T. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 June; 9(6): 531-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848729

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Characteristics and management of splenic artery aneurysm in liver transplant candidates and recipients. Author(s): Heestand G, Sher L, Lightfoote J, Palmer S, Mateo R, Singh G, Moser J, Selby R, Genyk Y, Jabbour N. Source: The American Surgeon. 2003 November; 69(11): 933-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627251

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Characterization of hepatitis B virus surface antigen and polymerase mutations in liver transplant recipients pre- and post-transplant. Author(s): Germer JJ, Charlton MR, Ishitani MB, Forehand CD, Patel R. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2003 June; 3(6): 743-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12780567

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Cholestasis and kidney dysfunction in liver transplant patients reduces cyclosporine metabolite excretion. Author(s): Totterman A, Lalla M, Salmela K, Hockerstedt K. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1992; 5 Suppl 1: S190-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14621772

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Cholesterol levels long-term after liver transplant. Author(s): Atillasoy E, Gurkan A, Mor E, Altaca G, Sheiner P, Guy S, Schwartz M, Miller C, Berk P, Emre S. Source: Transplantation Proceedings. 1998 August; 30(5): 2049-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9723387

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Clostridium difficile colitis associated with inflammatory pseudotumor in a liver transplant recipient. Author(s): Lykavieris P, Fabre M, Pariente D, Lezeau YM, Debray D. Source: Pediatric Transplantation. 2003 February; 7(1): 76-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581333

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Cognitive deficits in patients with hepatic cirrhosis and in liver transplant recipients. Author(s): Pantiga C, Rodrigo LR, Cuesta M, Lopez L, Arias JL. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Winter; 15(1): 84-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12556577

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Combination hepatitis B immune globulin and lamivudine versus hepatitis B immune globulin monotherapy in preventing recurrent hepatitis B virus infection in liver transplant recipients. Author(s): Ben-Ari Z, Mor E, Bar-Nathan N, Shaharabani E, Shapira Z, Tur-Kaspa R. Source: Transplantation Proceedings. 2003 March; 35(2): 609-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644066

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Comment: delayed wound healing with sirolimus after liver transplant. Author(s): Mathis AS. Source: The Annals of Pharmacotherapy. 2003 March; 37(3): 453. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12639183

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Comparison of RBCs and FFP with whole blood during liver transplant surgery. Author(s): Laine E, Steadman R, Calhoun L, Blackall D, Levin P, Braunfeld M, Nourmand H, Neelakanta G, Ting L, Gornbein J, Busuttil R, Petz L. Source: Transfusion. 2003 March; 43(3): 322-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12675716

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Cost analysis of four strategies for prevention of CMV infection in liver transplant recipients. Author(s): Post AB, Mulligan DC, Bush W. Source: Transplantation Proceedings. 1998 August; 30(5): 2102-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9723406

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Could spleen-size determine long-term thrombocytopenia following orthotopic liver transplant even after reversal of portal hypertension? Author(s): D'Arienzo A, Manguso F, Cimino L, Scaglione G, Celentano L, Vicinanza G, Parrilli G, Mattera D. Source: Ital J Gastroenterol Hepatol. 1998 August; 30(4): 441-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9789146

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Current concepts in pediatric liver transplant. Author(s): Alonso MH, Ryckman FC. Source: Seminars in Liver Disease. 1998; 18(3): 295-307. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9773429

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Cyclosporine A is associated with a shift of the Th1/Th2 balance in liver transplant patients. Author(s): van den Berg AP, Twilhaar WN, Corver K, Geerts AB, Mesander G, Klompmaker IJ, Slooff MJ, The TH, de Leij LH. Source: Transplantation Proceedings. 1998 August; 30(5): 2378-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9723510

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Cyclosporine A-induced achalasia-like esophageal motility disorder in a liver transplant recipient: successful conversion to tacrolimus. Author(s): Koch R, Zoller H, Graziadei I, Propst A, Vogel W. Source: Transplantation. 2003 August 27; 76(4): 744-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12973123

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Cytomegalovirus glycoprotein B sequence variation in Chinese liver transplant recipients. Author(s): Zheng SS, Zhou L, Qian J, Cai T, Fan J, Ma WH. Source: Hepatobiliary Pancreat Dis Int. 2002 February; 1(1): 26-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607617

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Cytomegalovirus infection in liver transplant recipients. Author(s): Fan J, Ma WH, Qian J, Chen Z, Huang DS, Wang WL, Zheng SS. Source: Hepatobiliary Pancreat Dis Int. 2002 February; 1(1): 30-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607618

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Delay of hepatitis C recurrence in liver transplant recipients: impact of mycophenolate mofetil on transplant recipients with severe acute rejection or with renal dysfunction. Author(s): Fasola CG, Netto GJ, Christensen LL, Molmenti EP, Sanchez EQ, Levy MF, Goldstein RM, Klintmalm GB. Source: Transplantation Proceedings. 2002 August; 34(5): 1561-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12176485

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Delayed domino liver transplantation: use of the remnant liver of a recipient of a temporary auxiliary orthotopic liver transplant as a liver graft for another patient. Author(s): Hashikura Y, Ikegami T, Nakazawa Y, Urata K, Ogino S, Terada M, Miyagawa S, Kawasaki S, Takei Y, Ikeda S. Source: Transplantation. 2004 January 27; 77(2): 324. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14743007

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Delayed wound healing with sirolimus after liver transplant. Author(s): Guilbeau JM. Source: The Annals of Pharmacotherapy. 2002 September; 36(9): 1391-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12196058

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Dendritic cell subset ratio in peripheral blood correlates with successful withdrawal of immunosuppression in liver transplant patients. Author(s): Mazariegos GV, Zahorchak AF, Reyes J, Ostrowski L, Flynn B, Zeevi A, Thomson AW. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2003 June; 3(6): 689-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12780560

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De-novo cholangiocarcinoma in the setting of recurrent primary sclerosing cholangitis following liver transplant. Author(s): Heneghan MA, Tuttle-Newhall JE, Suhocki PV, Muir AJ, Morse M, Bornstein JD, Sylvestre PB, Collins B, Kuo PC, Rockey DC. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2003 May; 3(5): 634-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12752322

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Detection of CMV-DNA in peripheral blood leukocytes of liver transplant patients after ganciclovir treatment. Author(s): Loginov R, Hockerstedt K, Lautenschlager I. Source: Archives of Virology. 2003 July; 148(7): 1269-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827460

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Detection of primary hepatic malignancy in liver transplant candidates: prospective comparison of CT, MR imaging, US, and PET. Author(s): Teefey SA, Hildeboldt CC, Dehdashti F, Siegel BA, Peters MG, Heiken JP, Brown JJ, McFarland EG, Middleton WD, Balfe DM, Ritter JH. Source: Radiology. 2003 February; 226(2): 533-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12563151

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Determinants of increased plasma homocysteine in 221 stable liver transplant patients. Author(s): Fernandez-Miranda C, Sanz M, de La Calle A, Loinaz C, Gomez P, DiazRubio P, de La Camara AG, Moreno E. Source: Clinical Chemistry. 2001 November; 47(11): 2037-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11673376

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Determination of risk factors for Epstein-Barr virus-associated posttransplant lymphoproliferative disorder in pediatric liver transplant recipients using objective case ascertainment. Author(s): Guthery SL, Heubi JE, Bucuvalas JC, Gross TG, Ryckman FC, Alonso MH, Balistreri WF, Hornung RW. Source: Transplantation. 2003 April 15; 75(7): 987-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698085

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Development of an adult liver transplant program in a public hospital in Argentina. Author(s): Imventarza O, Lendoire J, Bianco G, Saul J, Braslavsky G, Trigo P, Cueto G, Aziz H. Source: Transplantation Proceedings. 1998 September; 30(6): 2878-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9745608

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Diabetes mellitus after liver transplant new etiologic clues and cornerstones for understanding. Author(s): Tueche SG. Source: Transplantation Proceedings. 2003 June; 35(4): 1466-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12826194

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Diabetic ketoacidosis in a child on FK506 immunosuppression after a liver transplant. Author(s): Keshavarz R, Mousavi MA, Hassani C. Source: Pediatric Emergency Care. 2002 February; 18(1): 22-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11862133

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Diagnosis and monitoring of hepatitis virus infection in liver transplant patients. Author(s): Maina AM, Ciccorossi P, Oliveri F, Filipponi F, Brunetto MR. Source: Transplantation Proceedings. 2003 May; 35(3): 1025-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12947845

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Diagnosis and treatment of arterial steal syndromes in liver transplant recipients. Author(s): Nussler NC, Settmacher U, Haase R, Stange B, Heise M, Neuhaus P. 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): 596-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12783401

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Diagnosis and treatment of latent tuberculosis infection in liver transplant recipients in an endemic area. Author(s): Benito N, Sued O, Moreno A, Horcajada JP, Gonzalez J, Navasa M, Rimola A. Source: Transplantation. 2002 November 27; 74(10): 1381-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12451235

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Discordance between ALT values and fibrosis in liver transplant recipients treated with ribavirin for recurrent hepatitis C. Author(s): Saab S, Hu R, Ibrahim AB, Goldstein LI, Kunder G, Durazo F, Han S, Yersiz H, Ghobrial RM, Farmer DG, Busuttil RW, Lassman C. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2003 March; 3(3): 328-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12614290

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Do the results justify living donor and split liver transplant for children in Spain? Author(s): Lopez-Santamaria M, Gamez M, Murcia J, Leal N, Tovar J, Frauca E, Jara P, De Vicente E, Quijano Y, Nuno J. Source: Transplantation Proceedings. 2002 February; 34(1): 239. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11959263

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Donor anti-Jk(a) causing hemolysis in a liver transplant recipient. Author(s): Hareuveni M, Merchav H, Austerlitz N, Rahimi-Levene N, Ben-Tal O, Rahimi-Leveen N. Source: Transfusion. 2002 March; 42(3): 363-7. Erratum In: Transfusion. 2003 January; 43(1): 122. Rahimi-Leveen Neomi [corrected to Rahimi-Levene Naomi]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11961243

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Dose-adjusted cyclosporine c2 in a patient with jejunoileal bypass as compared to seven other liver transplant recipients. Author(s): Chenhsu RY, Wu Y, Katz D, Rayhill S. Source: Therapeutic Drug Monitoring. 2003 December; 25(6): 665-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639052

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Dual Y-chromosome painting and immunofluorescence staining of archival human liver transplant biopsies. Author(s): Dundas SR, Boyle S, Bellamy CO, Hawkins W, Garden OJ, Ross JA, Bickmore W. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 2001 October; 49(10): 1321-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11561017

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Early differentiation between rejection and infection in liver transplant patients by serum and biliary cytokine patterns. Author(s): Warle MC, Metselaar HJ, Hop WC, Gyssens IC, Kap M, Kwekkeboom J, De Rave S, Zondervan PE, IJzermans JN, Tilanus HW, Bouma GJ. Source: Transplantation. 2003 January 15; 75(1): 146-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12544887

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Early enteral supply of lactobacillus and fiber versus selective bowel decontamination: a controlled trial in liver transplant recipients. Author(s): Rayes N, Seehofer D, Hansen S, Boucsein K, Muller AR, Serke S, Bengmark S, Neuhaus P. Source: Transplantation. 2002 July 15; 74(1): 123-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12134110

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Effects of ribavirin on hepatitis C-associated nephrotic syndrome in four liver transplant recipients. Author(s): Pham HP, Feray C, Samuel D, Gigou M, Azoulay D, Paradis V, Ducret F, Charpentier B, Debuire B, Lemoine A. Source: Kidney International. 1998 October; 54(4): 1311-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9767549

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Efficacy and pharmacokinetics of tacrolimus oral suspension in pediatric liver transplant recipients. Author(s): Reding R, Sokal E, Paul K, Janssen M, Evrard V, Wilmotte L, Chardot C, Otte JB, Wallemacq P. Source: Pediatric Transplantation. 2002 April; 6(2): 124-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12000467

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Efficacy and safety of immunization for pre- and post- liver transplant children. Author(s): Kano H, Mizuta K, Sakakihara Y, Kato H, Miki Y, Shibuya N, Saito M, Narita M, Kawarasaki H, Igarashi T, Hashizume K, Iwata T. Source: Transplantation. 2002 August 27; 74(4): 543-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12352917

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Efficacy of galactomannan antigen in the Platelia Aspergillus enzyme immunoassay for diagnosis of invasive aspergillosis in liver transplant recipients. Author(s): Kwak EJ, Husain S, Obman A, Meinke L, Stout J, Kusne S, Wagener MM, Singh N. Source: Journal of Clinical Microbiology. 2004 January; 42(1): 435-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14715799

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Elevated kallikrein activity in plasma from stable liver transplant recipients. Author(s): Hayashi J, Salomon DR, Hugli TE. Source: International Immunopharmacology. 2002 November; 2(12): 1667-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12469941

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Embryonal rhabdomyosarcoma of the orbit in a liver transplant recipient. Author(s): Cescon M, Grazi GL, Assietti R, Scanni A, Frigerio F, Sparacio F, Ercolani G, Cavallari A. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 2003 June; 16(6): 437-40. Epub 2003 March 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12819877

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Encephalitis caused by human herpesvirus-6 in a liver transplant recipient. Author(s): Montejo M, Ramon Fernandez J, Testillano M, Valdivieso A, Aguirrebengoa K, Varas C, Olaizola A, De Urbina JO. Source: European Neurology. 2002; 48(4): 234-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12422078

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Endoscopic surveillance and primary prophylaxis for upper gastrointestinal bleeding in liver transplant candidates. Author(s): Burroughs AK. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 March; 8(3): 308-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11910579

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Endothelial cell chimerism does not influence allograft tolerance in liver transplant patients after withdrawal of immunosuppression. Author(s): Pons JA, Yelamos J, Ramirez P, Oliver-Bonet M, Sanchez A, Rodriguez-Gago M, Navarro J, Bermejo J, Robles R, Parrilla P. Source: Transplantation. 2003 April 15; 75(7): 1045-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698096

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Epstein-Barr virus-related lymphoproliferation in children after liver transplant: role of immunity, diagnosis, and management. Author(s): Smets F, Sokal EM. Source: Pediatric Transplantation. 2002 August; 6(4): 280-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12234267

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Evaluation of estimated and measured creatinine clearances for predicting the pharmacokinetics of vancomycin in adult liver transplant recipients. Author(s): Taber DJ, Fann AL, Malat G, Dupuis RE. Source: Therapeutic Drug Monitoring. 2003 February; 25(1): 67-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548147

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Evaluation of pediatric liver transplant recipients using quantitative hepatobiliary scintigraphy. Author(s): Gencoglu E, Karakayali H, Moray G, Aktas A, Haberal M. Source: Transplantation Proceedings. 2002 September; 34(6): 2160-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12270352

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Evaluation of the new EMIT enzyme immunoassay for the determination of wholeblood tacrolimus concentrations in kidney, heart, and liver transplant recipients. Author(s): Hesse CJ, Baan CC, Balk AH, Metselaar HJ, Weimar W, van Gelder T. Source: Transplantation Proceedings. 2002 November; 34(7): 2988-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12431679

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Evaluation of the splanchnic circulation with indocyanine green pharmacokinetics in liver transplant patients. Author(s): Niemann CU, Yost CS, Mandell S, Henthorn TK. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 May; 8(5): 476-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12004348

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Evidence of oxidative imbalance in long-term liver transplant patients. Author(s): Trevisani F, Caraceni P, Simoncini M, Micati M, Domenicali M, Dazzani F, Zambruni A, Stefanelli C, Grazi G, Nardo B, Guarnieri C, Bernardi M. Source: Dig Liver Dis. 2002 April; 34(4): 279-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12038812

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Evolution of hepatitis B virus sequence from a liver transplant recipient with rapid breakthrough despite hepatitis B immune globulin prophylaxis and lamivudine therapy. Author(s): Kim KH, Lee KH, Chang HY, Ahn SH, Tong S, Yoon YJ, Seong BL, Kim SI, Han KH. Source: Journal of Medical Virology. 2003 November; 71(3): 367-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12966541

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Experience with tacrolimus as primary immunosuppressor in pediatric liver transplant. Author(s): Asensio M, Chavez R, Ortega J, Iglesias J, Charco R, Margarit C. Source: Transplantation Proceedings. 2002 February; 34(1): 105-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11959208

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External validation of a modified model of Acute Physiology and Chronic Health Evaluation (APACHE) II for orthotopic liver transplant patients. Author(s): Arabi Y, Abbasi A, Goraj R, Al-Abdulkareem A, Al Shimemeri A, Kalayoglu M, Wood K. Source: Critical Care (London, England). 2002 June; 6(3): 245-50. Epub 2002 April 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12133186

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Factor V inhibitor in a liver transplant patient associated with porcine xenoperfusion. Author(s): Smith JD, Sindhi R, Rogers R, Lazarchick J. Source: Ann Clin Lab Sci. 1998 September-October; 28(5): 280-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9784828

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Factors associated with the development of candidemia and candidemia-related death among liver transplant recipients. Author(s): Nieto-Rodriguez JA, Kusne S, Manez R, Irish W, Linden P, Magnone M, Wing EJ, Fung JJ, Starzl TE. Source: Annals of Surgery. 1996 January; 223(1): 70-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8554421

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Factors associated with the development of post-transplant lymphoproliferative disease (PTLD) in Epstein-Barr virus (EBV)-seronegative adult liver transplant recipients. Author(s): Manez R, Breinig MK, Linden P, Kusne S, Torre-Cisneros J, Wilson J, Starzl TE, Ho M. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1994; 7 Suppl 1: S235-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11271213

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Factors influencing waiting time and successful receipt of cadaveric liver transplant in the United States. 1990 to 1992. Author(s): Klassen AC, Klassen DK, Brookmeyer R, Frank RG, Marconi K. Source: Medical Care. 1998 March; 36(3): 281-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9520954

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Fatal complication from central venous cannulation in a paediatric liver transplant patient. Author(s): Lovell M, Baines D. Source: Paediatric Anaesthesia. 2000; 10(6): 661-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11119200

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Fatal disseminated toxoplasmosis in a toxoplasma seropositive liver transplant recipient. Author(s): Wendum D, Carbonell N, Svrcek M, Chazouilleres O, Flejou JF. Source: Journal of Clinical Pathology. 2002 August; 55(8): 637. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12147667

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Fatal hepatic veno-occlusive disease associated with terbinafine in a liver transplant recipient. Author(s): Walter RB, Lukaschek J, Renner EL, Mullhaupt B, Bachli EB. Source: Journal of Hepatology. 2003 March; 38(3): 373-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12586307

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Fever in liver transplant recipients in the intensive care unit. Author(s): Singh N, Chang FY, Gayowski T, Wagener M, Marino IR. Source: Clinical Transplantation. 1999 December; 13(6): 504-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10617241

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Fever in liver transplant recipients: changing spectrum of etiologic agents. Author(s): Chang FY, Singh N, Gayowski T, Wagener MM, Marino IR. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1998 January; 26(1): 59-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9455510

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Fibrinolysis during liver transplant and use of solvent/detergent virus-inactivated plasma (ESDEP/Octaplas). Author(s): Solheim BG, Bergan A, Brosstad F, Innes R, Svennevig JL. Source: Anesthesia and Analgesia. 2003 April; 96(4): 1230-1; Author Reply 1231-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12651690

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Fibrosing cholestatic hepatitis in a liver transplant recipient with hepatitis C virus infection: a case report. Author(s): Furuta K, Takahashi T, Aso K, Hoshino H, Sato K, Kakita A. Source: Transplantation Proceedings. 2003 February; 35(1): 389-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12591454

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Fitness testing of pediatric liver transplant recipients. Author(s): Unnithan VB, Veehof SH, Rosenthal P, Mudge C, O'Brien TH, Painter P. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2001 March; 7(3): 206-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11244161

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Five-year experience with the development of a liver transplant program in Hong Kong. Author(s): Lo CM, Fan ST, Liu CL, Lo RJ, Lai CL, Lau GK, Chan JK, Ng IO, Wong J. Source: Transplantation Proceedings. 1998 November; 30(7): 3247-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9838434

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FK506 (tacrolimus) and its immunoreactive metabolites in whole blood of liver transplant patients and subjects with mild hepatic dysfunction. Author(s): Tokunaga Y, Alak AM. Source: Pharmaceutical Research. 1996 January; 13(1): 137-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8668663

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Flow cytometric analysis of antidonor-specific antibodies in liver transplant. Author(s): Piazza A, Adorno D, Torlone N, Valeri M, Poggi E, Monaco PI, Pisani F, Tisone G, Casciani CU. Source: Transplantation Proceedings. 1997 November; 29(7): 2975-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9365635

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Follow-up experience in pediatric liver transplantation in an academic, nontransplant-based gastroenterology group. Author(s): Kessler B, Gold D, Weinstein T, Levine J, Pettei M. Source: Pediatric Transplantation. 1999 February; 3(1): 45-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10359031

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Follow-up of antiretroviral treatment in liver transplant recipients with primary and chronic HIV type 1 infection. Author(s): Nowak P, Schvarcz R, Ericzon BG, Flamholc L, Sonnerborg A. Source: Aids Research and Human Retroviruses. 2003 January 1; 19(1): 13-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581512

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Forum on critical care issues in liver transplantation: fluids, electrolytes, and renal disease in the perioperative liver transplant recipient. Author(s): Plevak DJ. Source: Liver Transplantation and Surgery : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 1996 January; 2(1): 69 Discussion 70-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9346631

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Frequency and clinical implications of increased pulmonary artery pressures in liver transplant patients. Author(s): Castro M, Krowka MJ, Schroeder DR, Beck KC, Plevak DJ, Rettke SR, Cortese DA, Wiesner RH. Source: Mayo Clinic Proceedings. 1996 June; 71(6): 543-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8642882

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Fulminant hepatic failure resulting from lamivudine-resistant hepatitis B virus in a renal transplant recipient: durable response after orthotopic liver transplantation on adefovir dipivoxil and hepatitis B immune globulin. Author(s): Peters MG, Singer G, Howard T, Jacobsmeyer S, Xiong X, Gibbs CS, Lamy P, Murray A. Source: Transplantation. 1999 December 27; 68(12): 1912-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10628774

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Gadolinium-enhanced magnetic resonance portography: application in pediatric liver transplant recipients. Author(s): Ng KK, Cheng YF, Wong HF, Lui KW, Tseng JH, Tan CF, Hung CF, Yeow CM, Wan YL. Source: Transplantation Proceedings. 2000 November; 32(7): 2099-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11120085

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Gamma glutamyl transferase as a marker of liver transplant rejection. Author(s): Hickman PE, Lynch SV, Potter JM, Walker NI, Strong RW, Clouston AD. Source: Transplantation. 1994 April 27; 57(8): 1278-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7909967

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Ganciclovir prophylaxis decreases frequency and severity of cytomegalovirus disease in seropositive liver transplant recipients treated with OKT3 monoclonal antibodies. Author(s): Lumbreras C, Otero JR, Herrero JA, Gomez R, Lizasoain M, Aguado JM, Colina F, Garcia I, Moreno E, Noriega AR. Source: Antimicrobial Agents and Chemotherapy. 1993 November; 37(11): 2490-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8285641

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Ganciclovir treatment of hepatitis B virus infection in liver transplant recipients. Author(s): Gish RG, Lau JY, Brooks L, Fang JW, Steady SL, Imperial JC, Garcia-Kennedy R, Esquivel CO, Keeffe EB. Source: Hepatology (Baltimore, Md.). 1996 January; 23(1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8550028

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Gas gangrene limited to the right lobe of the liver after orthotopic liver transplant: sonographic, plain film and CT findings. Author(s): Patrick LE, Atkinson GO, Dodson TF, Niemer P. Source: Pediatric Radiology. 1994; 24(5): 340-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7824369

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Gastrointestinal toxicity associated with FK 506 in liver transplant recipients. Author(s): Fisher A, Schwartz M, Mor E, Sheiner P, Emre S, Guy S, Miller C. Source: Transplantation Proceedings. 1994 December; 26(6): 3106-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7527947

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General guidelines for the use of tacrolimus in adult liver transplant patients. Author(s): Busuttil RW, Klintmalm GB, Lake JR, Miller CM, Porayko M. Source: Transplantation. 1996 March 15; 61(5): 845-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8607197

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Generalised mitochondrial cytopathy is an absolute contraindication to orthotopic liver transplant in childhood. Author(s): Thomson M, McKiernan P, Buckels J, Mayer D, Kelly D. Source: Journal of Pediatric Gastroenterology and Nutrition. 1998 April; 26(4): 478-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9552151

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Genogrouping and incidence of virulence factors of Enterococcus faecalis in liver transplant patients differ from blood culture and fecal isolates. Author(s): Waar K, Muscholl-Silberhorn AB, Willems RJ, Slooff MJ, Harmsen HJ, Degener JE. Source: The Journal of Infectious Diseases. 2002 April 15; 185(8): 1121-7. Epub 2002 Apr 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11930322

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Genotyping of hepatocellular carcinoma in liver transplant recipients adds predictive power for determining recurrence-free survival. Author(s): Marsh JW, Finkelstein SD, Demetris AJ, Swalsky PA, Sasatomi E, Bandos A, Subotin M, Dvorchik I. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 July; 9(7): 664-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827550

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Giant intrahepatic hematoma after liver biopsy in a liver transplant recipient. Author(s): Yu MC, Jeng LB, Lee WC, Hung CM, Hung CF, Chiu CT, Chen MF. Source: Transplantation Proceedings. 2000 November; 32(7): 2217-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11120139

Studies

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Glucose and lipid metabolism in liver transplant patients under long-term tacrolimus (FK 506) monotherapy. Author(s): Loss M, Winkler M, Schneider A, Oldhafer K, Manns MP, Pichlmayr R. Source: Transplantation Proceedings. 1996 April; 28(2): 1006-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8623210

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Glucose metabolism in liver transplant recipients treated with FK 506 or cyclosporin in the European multicentre study. Author(s): Ericzon B, Groth C, Bismuth H, Calne R, McMaster P, Neuhaus P, Otto G, Pichlmayr R, Williams R. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1994; 7 Suppl 1: S11-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11271178

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Glycogenosis type IV: liver transplant at 12 years. Author(s): Dhawan A, Tan KC, Portmann B, Mowat AP. Source: Archives of Disease in Childhood. 1994 November; 71(5): 450-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7826120

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Glycopeptide-resistant Enterococcus faecium infections in paediatric liver transplant recipients: safety and clinical efficacy of quinupristin/dalfopristin. Author(s): Verma A, Dhawan A, Philpott-Howard J, Rela M, Heaton N, Vergani GM, Wade J. Source: The Journal of Antimicrobial Chemotherapy. 2001 January; 47(1): 105-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11152440

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Good and impaired response to ganciclovir treatment of severe CMV infections in liver transplant recipients. Author(s): Lautenschlager I, Hockerstedt K, Salmela K. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1994; 7 Suppl 1: S232-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11271212

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Graft versus host disease in a liver transplant patient with hepatitis B and hepatocellular carcinoma. Author(s): Merhav HJ, Landau M, Gat A, Gazit E, Baratz M, Bialy-Golan A, Konikof F, Bril S, Nakache R. Source: Transplantation Proceedings. 1999 June; 31(4): 1890-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10371987

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Gram-negative pulmonary colonization in liver transplant patients. Author(s): Tetteroo GW, den Hoed D. Source: Critical Care Medicine. 1995 April; 23(4): 784-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7712773

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Group proposes a new system on liver transplant priorities. Author(s): Kolata G. Source: Ny Times (Print). 1997 June 27; : A23. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11647212

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Health-related quality of life in pediatric liver transplant recipients: A single-center study. Author(s): Bucuvalas JC, Britto M, Krug S, Ryckman FC, Atherton H, Alonso MP, Balistreri WF, Kotagal U. 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): 62-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12514775

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Helicobacter pylori-associated gastric MALT lymphoma in liver transplant recipients. Author(s): Shehab TM, Hsi ED, Poterucha JJ, Gunaratnam NT, Fontana RJ. Source: Transplantation. 2001 April 27; 71(8): 1172-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11374421

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Hepatitis a vaccine in liver transplant recipients. Author(s): Avery RK, Dumot J. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 June 1; 32(11): 1656-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11340543

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Hepatitis B and C in the liver transplant recipient. Author(s): Rosen HR, Martin P. Source: Seminars in Liver Disease. 2000; 20(4): 465-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11200416

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Hepatitis B and C in the liver transplant recipient: current understanding and treatment. Author(s): Rosen HR. 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): S87-98. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11689781

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Hepatitis B vaccination in liver transplant candidates. Author(s): Castells L, Esteban R. Source: European Journal of Gastroenterology & Hepatology. 2001 April; 13(4): 359-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11338062

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Hepatitis C in liver transplant patients. Author(s): Pons JA, Ramirez P, Miras M, Robles R, Bueno FS, Marin C, Alberca F, Torrella E, Parrilla P. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1994; 7 Suppl 1: S213-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11271205

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Hepatitis C in the liver transplant recipient: current understanding and treatment. Author(s): Rosen HR. Source: Microbes and Infection / Institut Pasteur. 2002 October; 4(12): 1253-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12467767

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Hepatobiliary scintigraphy in liver transplant patients: the “blind end sign” and its differentiation from bile leak. Author(s): Young SA, Sfakianakis GN, Pyrsopoulos N, Nishida S. Source: Clinical Nuclear Medicine. 2003 August; 28(8): 638-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12897647

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HFE haemochromatosis gene mutations in liver transplant patients. Author(s): Halme L, Helio T, Makinen J, Hockerstedt K, Farkkila M, Piippo K, Krusius T, Kontula K. Source: Scandinavian Journal of Gastroenterology. 2001 August; 36(8): 881-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11495086

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HHV-6 reactivation is often associated with CMV infection in liver transplant patients. Author(s): Lautenschlager I, Linnavuori K, Lappalainen M, Suni J, Hockerstedt K. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 2000; 13 Suppl 1: S351-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11112030

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High incidence of noninfectious esophagitis in orthotopic liver transplant (OLT) recipients. Author(s): Karasu Z, Hulagu S, Gurakar A, Jazzar A, Kerwin B, Taydas E, McMillon G, Sebastian A, Wright H, Nour B. Source: J Okla State Med Assoc. 2001 February; 94(2): 43-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11288461

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High-dose acyclovir prophylaxis reduces cytomegalovirus disease in liver transplant patients. Author(s): Barkholt L, Lewensohn-Fuchs I, Ericzon BG, Tyden G, Andersson J. Source: Transplant Infectious Disease : an Official Journal of the Transplantation Society. 1999 June; 1(2): 89-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11428976

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Histologic changes resembling acute rejection in a liver transplant patient treated with terbinafine. Author(s): Lovell MO, Speeg KV, Havranek RD, Sharkey FE. Source: Human Pathology. 2003 February; 34(2): 187-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12612888

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How patients manage life and health while waiting for a liver transplant. Author(s): Baker MS, McWillam CL. Source: Progress in Transplantation (Aliso Viejo, Calif.). 2003 March; 13(1): 47-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12688650

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Human herpesvirus-6 is associated with cytomegalovirus reactivation in liver transplant recipients. Author(s): Humar A, Malkan G, Moussa G, Greig P, Levy G, Mazzulli T. Source: The Journal of Infectious Diseases. 2000 April; 181(4): 1450-3. Epub 2000 April 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10762575

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Human T lymphotropic virus type I (HTLV-1) associated myelopathy acquired through a liver transplant. Author(s): Zarranz JJ, Rouco I, Gomez-Esteban JC, Corral J. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2001 December; 71(6): 818. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11762319

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Hyperbilirubinemia during quinupristin-dalfopristin therapy in liver transplant recipients: correlation with available liver biopsy results. Author(s): Linden PK, Bompart F, Gray S, Talbot GH. Source: Pharmacotherapy. 2001 June; 21(6): 661-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11401179

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Hyperhomocysteinemia in liver transplant recipients: prevalence and multivariate analysis of predisposing factors. Author(s): Herrero JI, Quiroga J, Sangro B, Beloqui O, Pardo F, Cienfuegos JA, Prieto J. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2000 September; 6(5): 614-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10980061

Studies

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Hypertension and renal dysfunction in long-term liver transplant recipients. Author(s): Gonwa TA. 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): S22-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11689773

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Ileosplenic fistula and splenic abscesses caused by migration of biliary stents in a liver transplant recipient. Author(s): Baccarani U, Risaliti A, Sainz-Barriga M, Adani GL, Donini A, Toniutto P, Bresadola F. Source: Gastrointestinal Endoscopy. 2003 November; 58(5): 811-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14997896

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Immediate tracheal extubation of the liver transplant recipients in the operating room. Author(s): Ulukaya S, Ayanoglu HO, Acar L, Tokat Y, Kilic M. Source: Transplantation Proceedings. 2002 December; 34(8): 3334-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12493465

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Impact of donor age on graft survival among liver transplant recipients: analysis of the United Network for Organ Sharing database. Author(s): Rustgi SD, Marino G, Halpern MT, Umana WO, Tolleris C, Rustgi VK. Source: Transplantation Proceedings. 2002 December; 34(8): 3295-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12493451

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Impact of evolving trends in recipient and donor characteristics on cytomegalovirus infection in liver transplant recipients. Author(s): Singh N, Wannstedt C, Keyes L, Wagener MM, de Vera M, Cacciarelli TV, Gayowski T. Source: Transplantation. 2004 January 15; 77(1): 106-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724443

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Implementation of screening and preventive strategies in liver transplant candidates. Author(s): Macedo G, Lopes S, Barroso S, Malheiro L, Ferreira A, Campos M, CostaMaia J, de Matos N. Source: Transplantation Proceedings. 2003 May; 35(3): 1115. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12947880

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Increasing serum levels of IgM anti-HCV are diagnostic of recurrent hepatitis C in liver transplant patients with ALT flares. Author(s): Ciccorossi P, Filipponi F, Oliveri F, Campani D, Colombatto P, Bonino F, Campa M, Maltinti G, Mosca F, Brunetto MR. Source: Journal of Viral Hepatitis. 2003 May; 10(3): 168-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12753334

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Independent risk factors and natural history of renal dysfunction in liver transplant recipients. Author(s): Pawarode A, Fine DM, Thuluvath PJ. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 July; 9(7): 741-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827563

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Infectious complications occurring in liver transplant recipients receiving mycophenolate mofetil. Author(s): Paterson DL, Singh N, Panebianco A, Wannstedt CF, Wagener MM, Gayowski T, Marino IR. Source: Transplantation. 1998 September 15; 66(5): 593-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9753337

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Influence of continuous venovenous haemodiafiltration on the pharmacokinetics of tacrolimus in liver transplant recipients with small-for-size grafts. Author(s): Kishino S, Takekuma Y, Sugawara M, Shimamura T, Furukawa H, Todo S, Miyazaki K. Source: Clinical Transplantation. 2003 October; 17(5): 412-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14703922

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Influence of ischemia and surgery times on development of primary dysfunction liver transplant in patients. Author(s): Fernandez-Merino J, Nuno-Garza J, Lopez-Hervas P, Lopez-Buenadicha A, Quijano-Collazo Y, Vicente-Lopez E. Source: Transplantation Proceedings. 2003 June; 35(4): 1439-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12826184

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Institutional resource needs and optimising timing of living donor liver transplant. Author(s): Williams R. Source: Transplantation Proceedings. 2003 May; 35(3): 922-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12947801

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93

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Intra-abdominal pressure monitoring in liver transplant recipients: a prospective study. Author(s): Biancofiore G, Bindi ML, Romanelli AM, Boldrini A, Consani G, Bisa M, Filipponi F, Vagelli A, Mosca F. Source: Intensive Care Medicine. 2003 January; 29(1): 30-6. Epub 2002 December 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12528019

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Intracranial tuberculoma in a liver transplant patient: first reported case and review of the literature. Author(s): Henderson C, Meyers B, Humayun Gultekin S, Liu B, Zhang DY. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2003 January; 3(1): 88-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12492718

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Intravenous acyclovir treatment for extensive herpetic keratitis in a liver transplant patient. Author(s): Oshry T, Lifshitz T. Source: International Ophthalmology. 1997-98; 21(5): 265-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9756434

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Invasive aspergillosis in liver transplant recipients: outcome comparison of therapy with amphotericin B lipid complex and a historical cohort treated with conventional amphotericin B. Author(s): Linden PK, Coley K, Fontes P, Fung JJ, Kusne S. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 July 1; 37(1): 17-25. Epub 2003 June 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12830404

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Is there a necessity to implement ex vivo isolated, extracorporeal perfusion techniques of hepatic grafts in liver transplant medicine? Author(s): Kukan M. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 February; 9(2): 202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548518

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Is there disparity between risk and incidence of cardiovascular disease after liver transplant? Author(s): Neal DA, Tom BD, Luan J, Wareham NJ, Gimson AE, Delriviere LD, Byrne CD, Alexander GJ. Source: Transplantation. 2004 January 15; 77(1): 93-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724441

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Kaposi's sarcoma in liver transplant recipients on FK506. Author(s): Kadry Z, Bronsther O, Fung JJ. Source: Transplantation. 1998 April 27; 65(8): 1140. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9583882

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Kaposi's sarcoma in liver transplant recipients on FK506: two case reports. Author(s): Rezeig MA, Fashir BM, Hainau B, Al Ashgar HI. Source: Transplantation. 1997 May 27; 63(10): 1520-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9175820

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Kaposi's sarcoma in liver transplant recipients: morphological and clinical description. Author(s): Aseni P, Vertemati M, Minola E, Arcieri K, Bonacina E, Camozzi M, Osio C, Forti D. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2001 September; 7(9): 816-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11552218

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Kaposi's sarcoma presenting as a protracted multisystem illness in an adolescent liver transplant recipient. Author(s): Yokois NU, Perlman EJ, Colombani P, Wise B, Schwarz KB. Source: Liver Transplantation and Surgery : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 1997 September; 3(5): 541-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9346799

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Kidney transplantation for end-stage renal failure in liver transplant recipients with hepatitis C viral infection. Author(s): Molmenti EP, Jain AB, Shapiro R, Scantlebury V, Lee R, Totsuka E, Flohr J, Rakela J, Fung JJ. Source: Transplantation. 2001 January 27; 71(2): 267-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11213072

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Lack of efficacy of mupirocin in the prevention of infections with Staphylococcus aureus in liver transplant recipients and candidates. Author(s): Paterson DL, Rihs JD, Squier C, Gayowski T, Sagnimeni A, Singh N. Source: Transplantation. 2003 January 27; 75(2): 194-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548122

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Levetiracetam monotherapy for liver transplant patients with seizures. Author(s): Chabolla DR, Harnois DM, Meschia JF. Source: Transplantation Proceedings. 2003 June; 35(4): 1480-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12826199

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Liver fatty acid-binding protein as a sensitive serum marker of acute hepatocellular damage in liver transplant recipients. Author(s): Pelsers MM, Morovat A, Alexander GJ, Hermens WT, Trull AK, Glatz JF. Source: Clinical Chemistry. 2002 November; 48(11): 2055-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12406996

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Liver transplant and familial amyloidotic polyneuropathy. Author(s): Lewis WD. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 November; 8(11): 1085-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12424728

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Liver transplant recipients' ability to cope during the first 12 months after transplantation--a prospective study. Author(s): Forsberg A, Backman L, Svensson E. Source: Scandinavian Journal of Caring Sciences. 2002 December; 16(4): 345-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12445103

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Liver transplant recipients are not at increased risk for nonlymphoid solid organ tumors. Author(s): Kelly DM, Emre S, Guy SR, Miller CM, Schwartz ME, Sheiner PA. Source: Cancer. 1998 September 15; 83(6): 1237-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9740091

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Liver transplant recipients older than 60 years have lower survival and higher incidence of malignancy. Author(s): Herrero JI, Lucena JF, Quiroga J, Sangro B, Pardo F, Rotellar F, AlvarezCienfuegos J, Prieto J. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2003 November; 3(11): 1407-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14525602

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Liver transplant-associated graft-versus-host disease. Author(s): Smith DM, Agura E, Netto G, Collins R, Levy M, Goldstein R, Christensen L, Baker J, Altrabulsi B, Osowski L, McCormack J, Fichtel L, Dawson DB, Domiati-Saad R, Stone M, Klintmalm G. Source: Transplantation. 2003 January 15; 75(1): 118-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12544883

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Liver transplantation at Dumont-UCLA Transplant Center: an experience with over 3,000 cases. Author(s): Anselmo DM, Baquerizo A, Geevarghese S, Ghobrial RM, Farmer DG, Busuttil RW. Source: Clin Transpl. 2001; : 179-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12211780

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Long-term outcomes for patients with post-liver transplant anastomotic biliary strictures treated by endoscopic stent placement. Author(s): Morelli J, Mulcahy HE, Willner IR, Cunningham JT, Draganov P. Source: Gastrointestinal Endoscopy. 2003 September; 58(3): 374-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14528211

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Management of a liver transplant in a patient with asymptomatic superior vena cava obstruction. Author(s): Feierman DE, Barlow JC, Fishbein TM. Source: Journal of Cardiothoracic and Vascular Anesthesia. 2002 June; 16(3): 347-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12073209

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Mild course of C hepatitis after long-term follow-up in hepatitis B and C coinfected liver transplant recipients. Author(s): Caccamo L, Maggi U, Rossi G, Damilano I, Reggiani P, Melada E, Ghidoni P, Paone G, Gatti S, Fassati LR. Source: Transplantation Proceedings. 1998 August; 30(5): 2073-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9723396

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Model for End-Stage Liver Disease score does not predict patient or graft survival in living donor liver transplant recipients. Author(s): Hayashi PH, Forman L, Steinberg T, Bak T, Wachs M, Kugelmas M, Everson GT, Kam I, Trotter JF. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 July; 9(7): 737-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827562

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Molecular epidemiology of Enterococcus faecalis in liver transplant patients at University Hospital Groningen. Author(s): Waar K, Willems RJ, Slooff MJ, Harmsen HJ, Degener JE. Source: The Journal of Hospital Infection. 2003 September; 55(1): 53-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14505610

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Monitoring of viral load by quantitative plasma PCR during active cytomegalovirus infection of individual liver transplant patients. Author(s): Piiparinen H, Hockerstedt K, Lappalainen M, Suni J, Lautenschlager I. Source: Journal of Clinical Microbiology. 2002 August; 40(8): 2945-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12149357

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My son's liver transplant to change my stance on organ donation. Author(s): Caredeo K. Source: Progress in Transplantation (Aliso Viejo, Calif.). 2003 March; 13(1): 6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12688641

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Mycophenolate mofetil in stable liver transplant patients with calcineurin inhibitorinduced renal impairment: single-center experience. Author(s): Garcia CE, Ribeiro HB, Garcia RL, Copstein JL, Padilla JM, Santos TE, Amaral DD, Silva AO, D'Albuquerque LA. Source: Transplantation Proceedings. 2003 May; 35(3): 1131-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12947887

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Mycophenolate mofetil monotherapy in stable liver transplant recipients with progressive renal failure. Author(s): Detry O, De Roover A, Honore P, Delwaide J, Jacquet N, Meurisse M. Source: Transplantation Proceedings. 2002 May; 34(3): 782-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12034182

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Mycophenolic acid and mycophenolic acid glucuronide pharmacokinetics in pediatric liver transplant recipients: effect of cyclosporine and tacrolimus comedication. Author(s): Brown NW, Aw MM, Mieli-Vergani G, Dhawan A, Tredger JM. Source: Therapeutic Drug Monitoring. 2002 October; 24(5): 598-606. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12352931

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Mycophenolic acid pharmacokinetics in pediatric liver transplant recipients. Author(s): Aw MM, Brown NW, Itsuka T, Gonde CE, Adams JE, Heaton ND, Tredger JM, Mieli-Vergani G, Dhawan A. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 April; 9(4): 383-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12682891

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Natural history of Epstein-Barr viral load in peripheral blood of pediatric liver transplant recipients during treatment for posttransplant lymphoproliferative disorder. Author(s): Cacciarelli TV, Reyes J, Mazariegos GV, Sigurdsson L, Rowe DT, Fung JJ, Green M. Source: Transplantation Proceedings. 1999 February-March; 31(1-2): 488-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10083204

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Need for liver transplant in HIV-positive patients: first results of a specific survey in Italy, Project HOST. Author(s): Costigliola P, Tumietto F, Zagnoli A, Chiodo F. Source: Aids (London, England). 2003 September 26; 17(14): 2119-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14502016

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Neoral use in the liver transplant recipient. Author(s): Levy GA. Source: Transplantation Proceedings. 2000 May; 32(3A Suppl): 2S-9S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10814745

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Neurocognitive outcome in pediatric liver transplant recipients. Author(s): Krull K, Fuchs C, Yurk H, Boone P, Alonso E. Source: Pediatric Transplantation. 2003 April; 7(2): 111-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12654051

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New liver transplant rules favor acutely ill. Author(s): Hensley S. Source: Modern Healthcare. 1996 December 2; 26(49): 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10162700

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New methods to detect donor-type DNA in HLA-DRB1-matched living-related liver transplant recipients. Author(s): Kita Y, Uchida S, Ogawa A, Tadokoro K, Hirata M, Tanaka H, Sakamoto Y, Harihara Y, Kawarasaki H, Takayama T, Kubota K, Hashizume K, Makuuchi M. Source: Transplantation Proceedings. 1998 November; 30(7): 3493-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9838532

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Normalised intrinsic mortality risk in liver transplantation: European Liver Transplant Registry study. Author(s): Adam R, Cailliez V, Majno P, Karam V, McMaster P, Caine RY, O'Grady J, Pichlmayr R, Neuhaus P, Otte JB, Hoeckerstedt K, Bismuth H. Source: Lancet. 2000 August 19; 356(9230): 621-7. Erratum In: Lancet 2001 April 21; 367(9264): 1296. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10968434

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Normalization of T2 signal abnormalities in hemispheric white matter with liver transplant. Author(s): Rovira A, Cordoba J, Sanpedro F, Grive E, Rovira-Gols A, Alonso J. Source: Neurology. 2002 August 13; 59(3): 335-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12177365

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Novel immunoassay for the detection of hepatitis B surface 'escape' mutants and its application in liver transplant recipients. Author(s): Ijaz S, Torre F, Tedder RS, Williams R, Naoumov NV. Source: Journal of Medical Virology. 2001 March; 63(3): 210-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11170059

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Nutrition of liver transplant patients. Author(s): Weimann A, Plauth M, Bischoff SC, Kuse ER. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2000 November; 14 Suppl D: 85D-88D. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11110618

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Obesity and the liver transplant recipient. Author(s): Pruett T. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 February; 8(2): 171-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11862597

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Options for induction immunosuppression in liver transplant recipients. Author(s): Moser MA. Source: Drugs. 2002; 62(7): 995-1011. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11985487

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Oral ganciclovir and pharmacokinetics of valganciclovir in liver transplant recipients. Author(s): Pescovitz MD. Source: Transplant Infectious Disease : an Official Journal of the Transplantation Society. 1999; 1 Suppl 1: 31-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11565585

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Oral health in liver transplant children administered cyclosporin A or tacrolimus. Author(s): Wondimu B, Nemeth A, Modeer T. Source: International Journal of Paediatric Dentistry / the British Paedodontic Society [and] the International Association of Dentistry for Children. 2001 November; 11(6): 4249. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11759102

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Orthotopic liver transplant patients require less postoperative morphine than do patients undergoing hepatic resection. Author(s): Moretti EW, Robertson KM, Tuttle-Newhall JE, Clavien PA, Gan TJ. Source: Journal of Clinical Anesthesia. 2002 September; 14(6): 416-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12393108

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Osteoporosis screening in an outpatient liver transplant clinic: impact of primary immunosuppression. Author(s): Smallwood GA, Wickman JM, Martinez E, Stieber AC, Heffron TG. Source: Transplantation Proceedings. 2002 August; 34(5): 1569-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12176489

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Outcome and hepatic hemodynamics in liver transplant patients with portal vein arterialization. Author(s): Charco R, Margarit C, Lopez-Talavera JC, Hidalgo E, Castells L, Allende H, Segarra A, Moreiras M, Bilbao I. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2001 July; 1(2): 146-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12099362

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Outcome and management of hepatitis C in liver transplant recipients. Author(s): Chan SE, Rosen HR. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 September 15; 37(6): 807-12. Epub 2003 August 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12955642

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Outcome of lamivudine resistant hepatitis B virus infection in liver transplant recipients in Singapore. Author(s): Wai CT, Lim SG, Tan KC. Source: Gut. 2001 April; 48(4): 581. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11288740

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101

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Outcome of lamivudine resistant hepatitis B virus infection in liver transplant recipients in Singapore. Author(s): Wai CT, Lim SG, Tan KC. Source: Gut. 2000 November; 47(5): 741. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11203313

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Pegylated interferon for recurrent hepatitis C in liver transplant recipients with renal failure: a prospective cohort study. Author(s): Mukherjee S, Gilroy RK, McCashland TM, Schafer DF. Source: Transplantation Proceedings. 2003 June; 35(4): 1478-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12826198

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Perioperative perfusion strategies for optimal fluid management in liver transplant recipients with renal insufficiency. Author(s): Blackwell MM, Chavin KD, Sistino JJ. Source: Perfusion. 2003 March; 18(1): 55-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12705651

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Post-liver transplant obesity and diabetes. Author(s): T D Correia MI, Rego LO, Lima AS. Source: Current Opinion in Clinical Nutrition and Metabolic Care. 2003 July; 6(4): 45760. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12806221

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Post-transplant changes of segment 4 after living related liver transplantation. Author(s): Cheng YF, Chen CL, Haung TL, Lee TY, Chen TY, Chen YS, Liu PP, Chiang YC, Eng HL, Wang CC, Cheung HK, Jawan B, Goto S. Source: Clinical Transplantation. 1998 October; 12(5): 476-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9787960

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Practical management of liver transplant recipients for hepatitis C. Author(s): Saab S, Busuttil RW. Source: Minerva Chir. 2003 August; 58(4): 479-89. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14603160

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Predominant factors associated with bone loss in liver transplant patients - after prolonged post-transplantation period. Author(s): Segal E, Baruch Y, Kramsky R, Raz B, Tamir A, Ish-Shalom S. Source: Clinical Transplantation. 2003 February; 17(1): 13-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12588316

102

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Pregnancy outcome in liver transplant recipients. Author(s): Nagy S, Bush MC, Berkowitz R, Fishbein TM, Gomez-Lobo V. Source: Obstetrics and Gynecology. 2003 July; 102(1): 121-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12850617

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Prevalence and clinical significance of human herpesviruses 6 and 7 active infection in pediatric liver transplant patients. Author(s): Feldstein AE, Razonable RR, Boyce TG, Freese DK, El-Youssef M, Perrault J, Paya CV, Ishitani MB. Source: Pediatric Transplantation. 2003 April; 7(2): 125-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12654053

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Prevalence, molecular epidemiology, and clinical significance of heterogeneous glycopeptide-intermediate Staphylococcus aureus in liver transplant recipients. Author(s): Bert F, Clarissou J, Durand F, Delefosse D, Chauvet C, Lefebvre P, Lambert N, Branger C. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 5147-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605151

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Prevention of invasive fungal infections in liver transplant recipients: the role of prophylaxis with lipid formulations of amphotericin B in high-risk patients. Author(s): Fortun J, Martin-Davila P, Moreno S, Barcena R, de Vicente E, Honrubia A, Garcia M, Nuno J, Candela A, Uriarte M, Pintado V. Source: The Journal of Antimicrobial Chemotherapy. 2003 November; 52(5): 813-9. Epub 2003 October 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14563893

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Qualitative and semiquantitative polymerase chain reaction testing for cytomegalovirus DNA in serum allows prediction of CMV related disease in liver transplant recipients. Author(s): Evans PC, Soin A, Wreghitt TG, Alexander GJ. Source: Journal of Clinical Pathology. 1998 December; 51(12): 914-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10070333

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Qualitative patterns of biliary bile acids affect cyclosporine intestinal absorption in liver transplant recipients. Author(s): Romagnoli J, Baiocchi L, Tisone G, Angelico M, Pisani F, Negrini S, Iaria G, Nistri A, Casciani CU. Source: Transplantation Proceedings. 1996 December; 28(6): 3129-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8962212

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103

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Quality of life and cognitive function of liver transplant patients: a prospective study. Author(s): Moore KA, McL Jones R, Burrows GD. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2000 September; 6(5): 633-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10980064

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Quality of life and functional status of liver transplant recipients with recurrent viral hepatitis C. Author(s): Gayowski T, Wagener MM, Marino IR, Singh N. Source: Transplantation Proceedings. 1999 February-March; 31(1-2): 1386-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10083613

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Quality of life instruments for liver transplant recipients: too many choices? Author(s): Kim WR. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2000 November; 6(6): 784-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11084069

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Quality of life, functional status, and depression in male liver transplant recipients with recurrent viral hepatitis C. Author(s): Singh N, Gayowski T, Wagener MM, Marino IR. Source: Transplantation. 1999 January 15; 67(1): 69-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9921798

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Quantification of serum HCV core antigen by a fluorescent enzyme immunoassay in liver transplant recipients with recurrent hepatitis C--clinical and virologic implications. Author(s): Dickson RC, Mizokami M, Orito E, Qian KP, Lau JY. Source: Transplantation. 1999 November 27; 68(10): 1512-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10589948

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Quantitation of cytomegalovirus in the blood of liver transplant recipients. Author(s): Mutimer D, Matyi-Toth A, Elias E, Shaw J, O'Donnell K, Kilgariff H, Neuberger J, Gunson B, McMaster P, Stalhandske P. Source: Liver Transplantation and Surgery : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 1995 November; 1(6): 395-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9346619

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Quantitation of Epstein-Barr virus DNA in the blood of adult liver transplant recipients. Author(s): Mutimer D, Kaur N, Tang H, Singhal S, Shaw J, Whitehead L, Rickinson A, Niedobitek G. Source: Transplantation. 2000 March 15; 69(5): 954-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10755556

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Quantitative assessment of serum beta-2-microglobulin in liver transplant recipients and relationship to liver graft rejection. Author(s): Vivarelli M, Smith HM, Naoumov NV, Williams R. Source: European Journal of Gastroenterology & Hepatology. 1995 December; 7(12): 1215-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8789315

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Radiofrequency ablation causes 'thermal fixation' of hepatocellular carcinoma: a postliver transplant histopathologic study. Author(s): Coad JE, Kosari K, Humar A, Sielaff TD. Source: Clinical Transplantation. 2003 August; 17(4): 377-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12868996

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Randomized controlled trial of sequential intravenous and oral ganciclovir versus prolonged intravenous ganciclovir for long-term prophylaxis of cytomegalovirus disease in high-risk cytomegalovirus-seronegative liver transplant recipients with cytomegalovirus-seropositive donors. Author(s): Winston DJ, Busuttil RW. Source: Transplantation. 2004 January 27; 77(2): 305-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742998

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Recurrence of HCV infection in liver transplant patients: evaluation of IgM anti-HCV and IgM anti-CMV. Author(s): Ceccherini-Nelli L, Giannotti A, Malizia T, Ciccorossi P, Olivieri F, Vanni M, Lico S, Campani D, Filipponi F, Brunetto M, Mosca F, Campa M. Source: Transplantation Proceedings. 2003 May; 35(3): 1030-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12947847

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Recurrent hepatitis C following liver transplant: diagnosis, natural history, and therapeutic options. Author(s): Saab S, Wang V. Source: Journal of Clinical Gastroenterology. 2003 August; 37(2): 155-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869888

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Regional filter heparinization for continuous veno-venous hemofiltration in liver transplant recipients. Author(s): Biancofiore G, Esposito M, Bindi L, Stefanini A, Bisa M, Boldrini A, Consani G, Filipponi F, Mosca F. Source: Minerva Anestesiol. 2003 June; 69(6): 527-34; 534-8. English, Italian. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14564251

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Relationship between postoperative erythromycin breath test and early morbidity in liver transplant recipients. Author(s): Schmidt LE, Rasmussen A, Kirkegaard P, Dalhoff K. Source: Transplantation. 2003 July 27; 76(2): 358-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12883193

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Renal function improves in liver transplant recipients when switched from a calcineurin inhibitor to sirolimus. Author(s): Fairbanks KD, Eustace JA, Fine D, Thuluvath PJ. 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): 1079-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14526403

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Reply to Role of Echocardiography in detecting portopulmonary hypertension in liver transplant candidates. Author(s): Debusk MG, Kang Y, Doria C, Navarro VJ, Marino IR, Doyle HR. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 September; 9(9): 1000-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942469

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Right lobe living-related liver transplant: experience at Niguarda Hospital. Author(s): De Carlis L, Giacomoni A, Sammartino C, Lauterio A, Slim AO, Forti D. Source: Transplantation Proceedings. 2003 May; 35(3): 1015-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12947840

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Risk of hearing impairment in pediatric liver transplant recipients: a single center study. Author(s): Bucuvalas JC, O'Connor A, Buschle K, Krug S, Ryckman FC, Atherton H, Alonso MP, Balistreri WF. Source: Pediatric Transplantation. 2003 August; 7(4): 265-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890003

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Secondary osteoporosis in liver transplant recipients: a longitudinal study in patients with and without cholestatic liver disease. Author(s): Bjoro K, Brandsaeter B, Wiencke K, Bjoro T, Godang K, Bollerslev J, Schrumpf E. Source: Scandinavian Journal of Gastroenterology. 2003 March; 38(3): 320-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12737449

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Significance of and contributing factors for a high resistive index on Doppler sonography of the hepatic artery immediately after surgery: prognostic implications for liver transplant recipients. Author(s): Garcia-Criado A, Gilabert R, Salmeron JM, Nicolau C, Vilana R, Bianchi L, Bunesch L, Garcia-Valdecasas JC, Rimola A, Bru C. Source: Ajr. American Journal of Roentgenology. 2003 September; 181(3): 831-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12933490

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Significance of hyperattenuating and contrast-enhancing hepatic nodules detected in the cirrhotic liver during arterial phase helical CT in pre-liver transplant patients: radiologic-histopathologic correlation of explanted livers. Author(s): Freeny PC, Grossholz M, Kaakaji K, Schmiedl UP. Source: Abdominal Imaging. 2003 May-June; 28(3): 333-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12719903

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Sirolimus monotherapy in nephrotoxicity due to calcineurin inhibitors in liver transplant recipients. Author(s): Nair S, Eason J, Loss G. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 February; 9(2): 126-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548505

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Societal reintegration after liver transplantation: findings in alcohol-related and nonalcohol-related transplant recipients. Author(s): Cowling T, Jennings LW, Goldstein RM, Sanchez EQ, Chinnakotla S, Klintmalm GB, Levy MF. Source: Annals of Surgery. 2004 January; 239(1): 93-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14685106

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Strategies for optimizing immunosuppression in adolescent transplant recipients: a focus on liver transplantation. Author(s): Kelly DA. Source: Paediatric Drugs. 2003; 5(3): 177-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12608882

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Successful treatment of graft-vs-host disease after a second liver transplant. Author(s): Aziz H, Trigo P, Lendoire J, Bianco G, Saul J, Braslavsky G, Kien M, Zylberman M, Cueto G, Imventarza O. Source: Transplantation Proceedings. 1998 September; 30(6): 2891-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9745613

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Successful treatment of immune thrombocytopenic purpura with anti-D antibody following a cadaveric liver transplant for hepatoblastoma. Author(s): Rosoff PM, Tuttle-Newhall E, Treem WR. Source: Medical and Pediatric Oncology. 2003 June; 40(6): 402-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12692815

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Successful treatment of Xylohypha bantiana brain abscess mimicking invasive cerebral aspergillosis in a liver transplant recipient. Author(s): Lee YM, Tambyah PA, Lee KH, Tan KC, Lim SG. Source: The Journal of Infection. 2003 November; 47(4): 348-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14556762

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Survival of human immunodeficiency virus-infected liver transplant recipients. Author(s): Ragni MV, Belle SH, Im K, Neff G, Roland M, Stock P, Heaton N, Humar A, Fung JF. Source: The Journal of Infectious Diseases. 2003 November 15; 188(10): 1412-20. Epub 2003 Nov 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14624365

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Tacrolimus (FK506)-induced mutism after liver transplant. Author(s): Sokol DK, Molleston JP, Filo RS, Van Valer J, Edwards-Brown M. Source: Pediatric Neurology. 2003 February; 28(2): 156-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12699871

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Ten years of international experience with liver transplantation for familial amyloidotic polyneuropathy: results from the Familial Amyloidotic Polyneuropathy World Transplant Registry. Author(s): Herlenius G, Wilczek HE, Larsson M, Ericzon BG; Familial Amyloidotic Polyneuropathy World Transplant Registry. Source: Transplantation. 2004 January 15; 77(1): 64-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724437

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Ten years of sirolimus therapy in orthotopic liver transplant recipients. Author(s): Neff GW, Montalbano M, Tzakis AG. Source: Transplantation Proceedings. 2003 May; 35(3 Suppl): 209S-216S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12742498

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The role of endoscopy in the management of liver transplant patients. Author(s): Macedo G, Lopes S, Barroso S, Ribeiro A, Costa-Maia J, de Matos N. Source: Transplantation Proceedings. 2003 May; 35(3): 1133. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12947888

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The use of mycophenolate mofetil in liver transplant recipients. Author(s): Detry O, de Roover A, Delwaide J, Meurisse M, Honore P. Source: Expert Opinion on Pharmacotherapy. 2003 November; 4(11): 1949-57. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14596648

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Thrombotic microangiopathy and cytomegalovirus in liver transplant recipients: a case-based review. Author(s): Ramasubbu K, Mullick T, Koo A, Hussein M, Henderson JM, Mullen KD, Avery RK. Source: Transplant Infectious Disease : an Official Journal of the Transplantation Society. 2003 June; 5(2): 98-103. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12974791

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Timed Pediatric Risk of Mortality Scores predict outcomes in pediatric liver transplant recipients. Author(s): Carroll CL, Goodman DM, Superina RA, Whitington PF, Alonso EM. Source: Pediatric Transplantation. 2003 August; 7(4): 289-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890007

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Total hepatectomy and liver transplant for hepatocellular adenomatosis and focal nodular hyperplasia. Author(s): Marino IR, Scantlebury VP, Bronsther O, Iwatsuki S, Starzl TE. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1992; 5 Suppl 1: S201-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14621777

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Treatment strategies for hepatitis C: intervention prior to liver transplant, preemptively or after established disease. Author(s): Berenguer M, Wright TL. Source: Clinics in Liver Disease. 2003 August; 7(3): 631-50, Vii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14509531

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Tuscany liver transplant program: key aspects of the organizational model. Author(s): Filipponi F, Urbani L, Catalano G, Biancofiore G, Campatelli A, Baldoni L, Vignali C, Mosca F. Source: Transplantation Proceedings. 2003 May; 35(3): 1013-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12947839

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Ultrasound of non-vascular complications in the post liver transplant patient. Author(s): Shaw AS, Ryan SM, Beese RC, Sidhu PS. Source: Clinical Radiology. 2003 September; 58(9): 672-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12943637

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UNOS records requested. Liver transplant programs of Chicago hospitals under probe. Author(s): Taylor M. Source: Modern Healthcare. 2002 April 8; 32(14): 12, 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11989341

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Ursodeoxycholic acid modulates cyclosporin A oral absorption in liver transplant recipients. Author(s): Caroli-Bosc FX, Iliadis A, Salmon L, Macheras P, Montet AM, Bourgeon A, Garraffo R, Delmont JP, Montet JC. Source: Fundamental & Clinical Pharmacology. 2000 November-December; 14(6): 601-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11206711

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Use of combination cytomegalovirus immune globulin plus ganciclovir for prophylaxis in CMV-seronegative liver transplant recipients of a CMV-seropositive donor organ: a multicenter, open-label study. Author(s): Snydman DR, Falagas ME, Avery R, Perlino C, Ruthazer R, Freeman R, Rohrer R, Fairchild R, O'Rourke E, Hibberd P, Werner BG. Source: Transplantation Proceedings. 2001 June; 33(4): 2571-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11406251

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Use of daclizumab as initial immunosuppression in liver transplant recipients with impaired renal function. Author(s): Emre S, Gondolesi G, Polat K, Ben-Haim M, Artis T, Fishbein TM, Sheiner PA, Kim-Schluger L, Schwartz ME, Miller CM. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2001 March; 7(3): 220-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11244163

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Use of intraoperative Doppler ultrasound to diagnose hepatic venous obstruction in a right lobe living donor liver transplant. Author(s): Shapiro RS, Fishbein T, Schwartz M, Miller CM. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2001 June; 7(6): 547-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11443586

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Use of microwave coagulation therapy in liver transplant candidates with hepatocellular carcinoma: a preliminary report. Author(s): Kato T, Tamura S, Tekin A, Yamashiki N, Seki T, Berho M, Weppler D, Izumi N, Levi D, Khan F, Pinna A, Nery J, Tzakis AG. Source: Transplantation Proceedings. 2001 February-March; 33(1-2): 1469. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11267377

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Use of mycophenolate mofetil in liver transplant recipients experiencing renal dysfunction on cyclosporine or tacrolimus-randomized, prospective, multicenter study results. Author(s): Hodge EE, Reich DJ, Clavien PA, Kim-Schluger L. Source: Transplantation Proceedings. 2002 August; 34(5): 1546-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12176477

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Usefulness of albumin scintigraphy in a pediatric liver transplant recipient with gastrointestinal posttransplant lymphoproliferative disorder. Author(s): Mita A, Hashikura Y, Momose M, Nakayama J, Sasaki E, Ikegami T, Nakazawa Y, Chisuwa H, Terada M, Kawasaki S. 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): 568-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12037791

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Utility of pulse oximetry in the detection of arterial hypoxemia in liver transplant candidates. Author(s): Abrams GA, Sanders MK, Fallon MB. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 April; 8(4): 391-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11965585

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Vaccination, screening for malignancy, and health maintenance of the liver transplant recipient. Author(s): Zeldin GA, Maygers J, Klein A, Thuluvath PJ. Source: Journal of Clinical Gastroenterology. 2001 February; 32(2): 148-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11205651

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Valganciclovir results in improved oral absorption of ganciclovir in liver transplant recipients. Author(s): Pescovitz MD, Rabkin J, Merion RM, Paya CV, Pirsch J, Freeman RB, O'Grady J, Robinson C, To Z, Wren K, Banken L, Buhles W, Brown F. Source: Antimicrobial Agents and Chemotherapy. 2000 October; 44(10): 2811-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10991864

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Varicella in pediatric liver transplant patients: a retrospective analysis of treatment and outcome. Author(s): Pacini-Edelstein SJ, Mehra M, Ament ME, Vargas JH, Martin MG, McDiarmid SV. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 August; 37(2): 183-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12883306

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Varicella infection following varicella vaccination in a liver transplant recipient. Author(s): Levitsky J, Te HS, Faust TW, Cohen SM. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2002 October; 2(9): 880-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12392296

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Ventilator failure after pediatric liver transplant. Author(s): de Ville de Goyet J, Clarke JR. Source: Transplantation. 2002 January 27; 73(2): 166-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11821725

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Vertebral morphometry by X-ray absorptiometry before and after liver transplant: a cross-sectional study. Author(s): Giannini S, Nobile M, Dalle Carbonare L, Ciuffreda M, Germoni V, Iemmolo RM, Gerunda GE, Sartori L, Crepaldi G. Source: European Journal of Gastroenterology & Hepatology. 2001 October; 13(10): 12017. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11711777

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Very early tracheal extubation without predetermined criteria in a liver transplant recipient population. Author(s): Biancofiore G, Romanelli AM, Bindi ML, Consani G, Boldrini A, Battistini M, Filipponi F, Mosca F, Vagelli A. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2001 September; 7(9): 777-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11552211

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Viral hepatitis in the liver transplant recipient. Author(s): Rosen HR, Martin P. Source: Infectious Disease Clinics of North America. 2000 September; 14(3): 761-84. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10987119

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Vitamin D deficiency in liver transplant patients in Israel. Author(s): Segal E, Baruch Y, Kramsky R, Raz B, Ish-Shalom S. Source: Transplantation Proceedings. 2001 September; 33(6): 2955-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11543808

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Voriconazole inhibition of the metabolism of tacrolimus in a liver transplant recipient and in human liver microsomes. Author(s): Venkataramanan R, Zang S, Gayowski T, Singh N. Source: Antimicrobial Agents and Chemotherapy. 2002 September; 46(9): 3091-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12183280

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Waiting for a liver transplant: the experience of patients with familial amyloidotic polyneuropathy. Author(s): Jonsen E, Athlin E, Suhr OB. Source: Journal of Clinical Nursing. 2000 January; 9(1): 63-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11022494

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Weaning of immunosuppression in liver transplant recipients. Author(s): Mazariegos GV, Reyes J, Marino IR, Demetris AJ, Flynn B, Irish W, McMichael J, Fung JJ, Starzl TE. Source: Transplantation. 1997 January 27; 63(2): 243-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9020325

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Weaning of immunosuppression in living donor liver transplant recipients. Author(s): Takatsuki M, Uemoto S, Inomata Y, Egawa H, Kiuchi T, Fujita S, Hayashi M, Kanematsu T, Tanaka K. Source: Transplantation. 2001 August 15; 72(3): 449-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11502975

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Weaning of immunosuppression in long-term liver transplant recipients. Author(s): Ramos HC, Reyes J, Abu-Elmagd K, Zeevi A, Reinsmoen N, Tzakis A, Demetris AJ, Fung JJ, Flynn B, McMichael J, et al. Source: Transplantation. 1995 January 27; 59(2): 212-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7839442

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Weight gain and lipid profile changes in liver transplant recipients: long-term results of the American FK506 Multicenter Study. Author(s): Mor E, Facklam D, Hasse J, Sheiner P, Emre S, Schwartz M, Miller C. Source: Transplantation Proceedings. 1995 February; 27(1): 1126. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7533363

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Wernicke-Korsakoff syndrome in a liver transplant recipient. Author(s): DiMartini A. Source: Psychosomatics. 1996 November-December; 37(6): 564-7. Erratum In: Psychosomatics 1997 May-June; 38(3): 302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8942207

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When is liver transplant indicated in cirrhosis with bleeding varices? Author(s): Orloff MJ, Orloff MS, Girard B, Orloff SL. Source: Transplantation Proceedings. 2001 February-March; 33(1-2): 1366. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11267330

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Who gets the liver transplant? Which one's the mother? When do you lie? Author(s): Dreifus C, Caplan A. Source: N Y Times Mag. 1996 December 15; : 41-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11647143

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Who needs a liver transplant? (new disease specific indications). Author(s): Baker A, Dhawan A, Heaton N. Source: Archives of Disease in Childhood. 1998 November; 79(5): 460-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10193265

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CHAPTER 2. NUTRITION AND LIVER TRANSPLANT Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and liver transplant.

Finding Nutrition Studies on Liver Transplant 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 “liver transplant” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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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 “liver transplant” (or a synonym): •

A prospective randomized study of preoperative nutritional supplementation in patients awaiting elective orthotopic liver transplantation. Author(s): Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, England. Source: Le Cornu, K A McKiernan, F J Kapadia, S A Neuberger, J M Transplantation. 2000 April 15; 69(7): 1364-9 0041-1337

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A randomized double-blind comparative study of mycophenolate mofetil and azathioprine in combination with cyclosporine and corticosteroids in primary liver transplant recipients. Author(s): Mayo Clinic, Rochester, MN 55905, USA. [email protected] Source: Wiesner, R Rabkin, J Klintmalm, G McDiarmid, S Langnas, A Punch, J McMaster, P Kalayoglu, M Levy, G Freeman, R Bismuth, H Neuhaus, P Mamelok, R Wang, W Liver-Transpl. 2001 May; 7(5): 442-50 1527-6465

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Adult liver transplantation and steroid-azathioprine withdrawal in cyclosporine (Sandimmun)-based immunosuppression - 5 year results of a prospective study. Author(s): Department of Digestive Surgery, Liver Transplant Program, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Avenue Hippocrate 10, 1200 Brussels, Belgium. [email protected] Source: Lerut, J P Ciccarelli, O Mauel, E Gheerardhyn, R Talpe, S Sempoux, C Laterre, P F Roggen, F M Van Leeuw, V Otte, J B Gianello, P Transpl-Int. 2001 December; 14(6): 420-8 0934-0874

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Alpha interferon plus thymopentine in treatment of HBV and/or HDV positive patients undergoing liver transplant. Author(s): Microbiology Institute, Medical School, University La Sapienza, Roma, Italy. Source: Gaeta, A Mancini, C Bachetoni, A Sallusto, F Lorino, G Marinucci, G Di Giacomo, C Favalli, C Alfani, D Filadoro, F J-Biol-Regul-Homeost-Agents. 1990 AprJune; 4(2): 51-6 0393-974X

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Analysis of alloreactivity and intragraft cytokine profiles in living donor liver transplant recipients with graft acceptance. Author(s): Department of Transplantation and Immunology, Kyoto Universirty, Japan. Source: Takatsuki, M Uemoto, S Inomata, Y Sakamoto, S Hayashi, M Ueda, M Kanematsu, T Tanaka, K Transpl-Immunol. 2001 February; 8(4): 279-86 0966-3274

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Association between nasal methicillin-resistant Staphylococcus aureus carriage and infection in liver transplant recipients. Author(s): Mayo Clinic, Rochester, MN 55905, USA. Source: Patel, R Liver-Transpl. 2001 August; 7(8): 752-3 1527-6465

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Bleeding complications precipitated by unrecognized Gingko biloba use after liver transplantation. Author(s): VA Pittsburgh Healthcare System, Infectious Disease Section, University Drive C, Pittsburgh, PA 15240, USA. Source: Hauser, D Gayowski, T Singh, N Transpl-Int. 2002 July; 15(7): 377-9 0934-0874

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Blockade of the L-arginine/NO synthase pathway worsens hepatic apoptosis and liver transplant preservation injury. Author(s): Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA. Source: Yagnik, G P Takahashi, Y Tsoulfas, G Reid, K Murase, N Geller, D A Hepatology. 2002 September; 36(3): 573-81 0270-9139

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Bone loss after liver transplantation is not prevented by cyclical etidronate, calcium and alphacalcidol. The Liver Transplant Group, Groningen. Author(s): Department of Gastroenterology and Hepatology, University Hospital, Groningen, The Netherlands. Source: Riemens, S C Oostdijk, A van Doormaal, J J Thijn, C J Drent, G Piers, D A Groen, E W Meerman, L Slooff, M J Haagsma, E B Osteoporos-Int. 1996; 6(3): 213-8 0937-941X

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Calcineurin-inhibitor related nephrotoxicity- reversibility in paediatric liver transplant recipients. Author(s): Paediatric Liver Service, King's College Hospital, London, United Kingdom. Source: Aw, M M Samaroo, B Baker, A J Verma, A Rela, M Heaton, N D Mieli Vergani, G Dhawan, A Transplantation. 2001 August 27; 72(4): 746-9 0041-1337

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Conversion of liver transplant recipients on cyclosporine with renal impairment to mycophenolate mofetil. Author(s): Liver Unit, Clinica Universitaria, University of Navarra, Pamplona, Spain. Source: Herrero, J I Quiroga, J Sangro, B Girala, M Gomez Manero, N Pardo, F Alvarez Cienfuegos, J Prieto, J Liver-Transpl-Surg. 1999 September; 5(5): 414-20 1074-3022

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Corticosteroid withdrawal after liver transplantation. Author(s): Department of Surgery, University of Michigan Medical School, Ann Arbor, USA. Source: Punch, J D Shieck, V L Campbell, D A Bromberg, J S Turcotte, J G Merion, R M Surgery. 1995 October; 118(4): 783-6; discussion 786-8 0039-6060

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Current research in the treatment of alcoholism in liver transplant recipients. Author(s): Treatment Research Center, University of Pennsylvania, Philadelphia 191046178, USA. Source: Weinrieb, R M O'Brien, C P Liver-Transpl-Surg. 1997 May; 3(3): 328-36 1074-3022

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Drinking behavior and motivation for treatment among alcohol-dependent liver transplant candidates. Author(s): Department of Psychiatry, The University of Pennsylvania School of Medicine and the Philadelphia Veterans Affairs Medical Center, USA. [email protected] Source: Weinrieb, R M Van Horn, D H McLellan, A T Volpicelli, J R Calarco, J S Lucey, M R J-Addict-Dis. 2001; 20(2): 105-19 1055-0887

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Early metabolic treatment after liver transplant: amino acid tolerance. Author(s): Istituto Anestesiologia e Rianimazione dell'Universita, IRCCS Ospedale Maggiore, Milano, Italy. Source: Iapichino, G Radrizzani, D Bonetti, G Codazzi, D Colombo, A Gridelli, B Langer, M Ronzoni, G Savioli, M Intensive-Care-Med. 1995 October; 21(10): 802-7 0342-4642

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Effect of treatment with prostaglandin E1 and N-acetylcysteine on pediatric liver transplant recipients: a single-center study. Author(s): Pediatric Liver Care Center, Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA. [email protected] Source: Bucuvalas, J C Ryckman, F C Krug, S Alonso, M H Balistreri, W F Kotagal, U Pediatr-Transplant. 2001 August; 5(4): 274-8 1397-3142

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Effect of t-tube clamping on the pharmacokinetics of mycophenolic acid in liver transplant patients on oral therapy of mycophenolate mofetil. Author(s): Thomas E. Starzl Transplantation Institute, School of Medicine, The University of Pittsburgh, Pittsburgh, PA, USA.

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Source: Jain, A B Hamad, I Zuckerman, S Zhang, S Warty, V S Fung, J J Venkataramanan, R Liver-Transpl-Surg. 1999 March; 5(2): 101-6 1074-3022 •

Epstein-Barr virus-negative precursor B cell lymphoblastic lymphoma after liver transplantation: a unique form of posttransplant lymphoproliferative disease. Author(s): Departments of Pediatrics and Pathology, Massachusetts General Hospital, Boston, MA 02114, USA. Source: Borges, Elizabeth Ferry, Judith A Friedmann, Alison M Transplantation. 2002 February 27; 73(4): 541-3 0041-1337

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Hepatic de novo lipogenesis after liver transplantation. Author(s): Institute of Physiology, Lausanne University School of Medicine, Switzerland. Source: Minehira, K Novel Chate, V Schwarz, J M Gillet, M Darioli, R Chiolero, R Tappy, L JPEN-J-Parenter-Enteral-Nutr. 2001 Sep-October; 25(5): 229-35; discussion 235-6 01486071

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Improvement of acute and chronic renal dysfunction in liver transplant patients after substitution of calcineurin inhibitors by mycophenolate mofetil. Author(s): Klinik fur Viszeral- und Transplantationschirurgie and Abteilung Gastroenterologie und Hepatologie, Medizinische Hochschule Hannover, Germany. Source: Barkmann, A Nashan, B Schmidt, H H Boker, K H Emmanouilidis, N Rosenau, J Bahr, M J Hoffmann, M W Manns, M P Klempnauer, J Schlitt, H J Transplantation. 2000 May 15; 69(9): 1886-90 0041-1337

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Improvement of growth after growth hormone treatment in children who undergo liver transplantation. Author(s): Kinderklinik, Medizinische Hochschule, Hannover, Germany. Source: Rodeck, B Kardorff, R Melter, M Ehrich, J H J-Pediatr-Gastroenterol-Nutr. 2000 September; 31(3): 286-90 0277-2116

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Induction with basiliximab reduces acute rejection in pediatric liver transplant patients treated with tacrolimus and steroids. Author(s): Liver Transplant Unit, Hospital Vall d'Hebron, Passeig Vall d'Hebron 119129, 08030 Barcelona, Spain. Source: Asensio, M Margarit, C Chavez, R Ortega, J Charco, R Iglesias, J TransplantProc. 2002 August; 34(5): 1970-1 0041-1345

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Influence of N-acetylcysteine on hepatic amino acid metabolism in patients undergoing orthotopic liver transplantation. Author(s): Department of General and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. Source: Taut, F J Breitkreutz, R Zapletal, C M Thies, J C Babylon, A Martin, E Droge, W Transpl-Int. 2001 September; 14(5): 329-33 0934-0874

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Leukemia after liver transplant. Author(s): Department of Medicine, Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029, USA. Source: Doti, C A Gondolesi, G E Sheiner, P A Emre, S Miller, C M Aledort, L M Transplantation. 2001 November 27; 72(10): 1643-6 0041-1337

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Liver transplantation for citrullinaemia improves intellectual function. Author(s): Department of Chemical Pathology, Women's and Children's Hospital, North Adelaide, Australia. [email protected] Source: Fletcher, J M Couper, R Moore, D Coxon, R Dorney, S J-Inherit-Metab-Dis. 1999 June; 22(5): 581-6 0141-8955

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Long-term management of the liver transplant patient: Diabetes, hyperlipidemia, and obesity. Author(s): Liver Service and Liver Transplant Program, Medical University of South Carolina, Charleston, SC. Source: Reuben, A Liver-Transpl. 2001 November; 7(11 Suppl 2): S13-21 1527-6465

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Occurrence of gammopathies and lymphoproliferative disorders in liver transplant recipients randomized to tacrolimus (FK506)or cyclosporine-based immunosuppression. Author(s): Department of Biochemistry, Paul Brousse Hospital and Faculty of Medicine, Villejuif, France. Source: Pham, H Lemoine, A Salvucci, M Azoulay, D Frenoy, N Samuel, D Reynes, M Bismuth, H Debuire, B Liver-Transpl-Surg. 1998 March; 4(2): 146-51 1074-3022

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Perioperative parenteral and enteral nutrition for patients undergoing orthotopic liver transplantation. Results of a questionnaire from 16 European transplant units. Author(s): Klinik fur Abdominal- und Transplantationschirurgie, Medizinische Hochschule Hannover, Germany. Source: Weimann, A Kuse, E R Bechstein, W O Neuberger, J M Plauth, M Pichlmayr, R Transpl-Int. 1998; 11 Suppl 1S289-91 0934-0874

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Pneumocystis carinii pneumonia prophylaxis with atovaquone in trimethoprimsulfamethoxazole-intolerant orthotopic liver transplant patients: a preliminary study. Author(s): Transplant Infectious Diseases, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6574, USA. [email protected] Source: Meyers, B Borrego, F Papanicolaou, G Liver-Transpl. 2001 August; 7(8): 750-1 1527-6465

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Poor outcome in patients with diabetes mellitus undergoing liver transplantation. Author(s): Liver Unit, The Queen Elizabeth Hospital, Edgbaston, Birmingham. Source: Shields, P L Tang, H Neuberger, J M Gunson, B K McMaster, P Pirenne, J Transplantation. 1999 August 27; 68(4): 530-5 0041-1337

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Primary induction with mycophenolate mofetil and corticosteroids in a liver transplant recipient with hepatorenal syndrome. Author(s): Vancouver Hospital and Health Sciences Centre, British Columbia, Canada. Source: Carr, R R Yoshida, E M Chung, S W Partovi, N Ann-Pharmacother. 1998 January; 32(1): 45-8 1060-0280

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Protective role of the L-arginine-nitric oxide synthase pathway on preservation injury after rat liver transplantation. Author(s): Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pennsylvania 15213, USA. [email protected] Source: Geller, D A Chia, S H Takahashi, Y Yagnik, G P Tsoulfas, G Murase, N JPEN-JParenter-Enteral-Nutr. 2001 May-June; 25(3): 142-7 0148-6071

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Pulmonary blastoma after liver transplant: a case report. Author(s): Department of Medical Oncology, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture (PZ), Italy. [email protected] Source: Tartarone, Alfredo Romano, Giampiero Galasso, Rocco Coccaro, Mariarosa Cammarota, Aldo Sgambato, Alessandro Bochicchio, Annamaria Tumori. 2002 MarApril; 88(2): 173-5 0300-8916

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Recurrence of hepatitis C in liver transplant recipients treated with mycophenolate mofetil. Author(s): Transplantation Services, Baylor University Medical Center, 3500 Gaston Avenue, Roberts 4th Floor, Dallas, TX 75246, USA. Source: Fasola, C G Netto, G J Jennings, L W Christensen, L L Molmenti, E P Sanchez, E Q Levy, M F Goldstein, R M Klintmalm, G B Transplant-Proc. 2002 August; 34(5): 1563-4 0041-1345

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Renal failure after liver transplantation: outcome after calcineurin inhibitor withdrawal. Author(s): Liver Transplantation Unit, Pellegrin Hospital, Bordeaux Cedex, France. [email protected] Source: Neau Cransac, M Morel, D Bernard, P H Merville, P Revel, P Potaux, L Saric, J Clin-Transplant. 2002 October; 16(5): 368-73 0902-0063

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Renal sparing effects of mycophenolate when used in long-term liver transplant recipients [correction of receipients]. Author(s): Department of Pharmacy, Emory University Hospital Pharmacy, 1364 Clifton Road NE, Atlanta, GA 30322, USA. Source: Smallwood, G Stieber, A Davis, L Martinez, E Heffron, T Transplant-Proc. 2002 August; 34(5): 1550 0041-1345

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Safety and efficacy of isoniazid chemoprophylaxis administered during liver transplant candidacy for the prevention of posttransplant tuberculosis. Author(s): Veterans Affairs Medical Center and University of Pittsburgh, Pittsburgh, PA 15240, USA. [email protected]. Source: Singh, N Wagener, M M Gayowski, T Transplantation. 2002 September 27; 74(6): 892-5 0041-1337

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Serum hepatocyte growth factor as an index of extensive catabolism of patients awaiting liver transplantation. Author(s): Department of Surgery II, Mie University Medical School, Tsu, Japan. Source: Miki, C Mayer, A D Buckels, J A Iriyama, K Suzuki, H McMaster, P Gut. 1999 June; 44(6): 862-6 0017-5749

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Severe CPT-11-induced diarrhea in presence of FK-506 following liver transplantation for hepatocellular carcinoma. Author(s): Service de Cancerologie, Hjpital Paul Brousse, AP-HP, Villejuif, France. Source: Gornet J, M Lokiec, F Duclos Vallee J, C Azoulay, D Goldwasser, F AnticancerRes. 2001 Nov-December; 21(6A): 4203-6 0250-7005

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Single-agent immunosuppression after liver transplantation: what is possible? Author(s): Liver Transplantation and Hepato-Biliary Medicine, Royal Free Hospital, Hampstead, London, UK. Source: Raimondo, M L Burroughs, A K Drugs. 2002; 62(11): 1587-97 0012-6667

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Steroid elimination 24 hours after liver transplantation using daclizumab, tacrolimus, and mycophenolate mofetil. Author(s): Division of Organ Transplantation, UT Health Science Center, 7703 Floyd Curl Dr., MC7858, San Antonio, TX 78229, USA. [email protected] Source: Washburn, K Speeg, K V Esterl, R Cigarroa, F Pollack, M Tourtellot, C Maxwell, P Halff, G Transplantation. 2001 November 27; 72(10): 1675-9 0041-1337

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Steroid-free regimen with daclizumab, mycophenolate mofetil, and tacrolimus in liver transplant recipients. Author(s): Department of Surgery, Hospital Bellvitge, Feixa Llarga, S/N Hospitalet de Llobregat, 08907 Barcelona, Spain. Source: Figueras, J Bernardos, A Prieto, M Gomez, M Rimola, A Ortiz de Urbina, J Cuervas Mons, V de la Mata, M Dominguez Granados, R Transplant-Proc. 2002 August; 34(5): 1511-3 0041-1345

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Successful reversal of primary graft non-function in a liver transplant patient treated with prostaglandin E1. Author(s): Australian National Liver Transplantation Unit, Royal Prince Alfred Hospital, Children's Hospital, Camperdown. Source: Isai, H Sheil, A G McCaughan, G Dolan, P Waugh, R Aust-N-Z-J-Surg. 1992 April; 62(4): 314-6 0004-8682

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The natural history of untreated focal allograft rejection in liver transplant recipients. Author(s): Department of Surgery, University of Washington, Seattle 98195, USA. Source: McVicar, J P Kowdley, K V Bacchi, C E Barr, D Marsh, C L Perkins, J D Carithers, R L Liver-Transpl-Surg. 1996 Mar; 2(2): 154-60 1074-3022

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The safety and efficacy of a two-dose daclizumab (zenapax) induction therapy in liver transplant recipients. Author(s): University of Alabama at Birmingham, Alabama 35294-0007, USA. [email protected] Source: Eckhoff, D E McGuire, B Sellers, M Contreras, J Frenette, L Young, C Hudson, S Bynon, J S Transplantation. 2000 May 15; 69(9): 1867-72 0041-1337

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The University of Toronto liver transplant program. Author(s): Toronto Hospital, Hospital for Sick Children, Ontario, Canada. Source: Hemming, A W Cattral, M S Greig, P D Philosophe, B Superina, R A Lilly, L B Levy, G Clin-Transpl. 1996; 177-85 0890-9016

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Tube jejunostomy in liver transplant recipients. Author(s): Department of Surgery, Indiana University, Indianapolis 46202, USA. Source: Pescovitz, M D Mehta, P L Leapman, S B Milgrom, M L Jindal, R M Filo, R S Surgery. 1995 June; 117(6): 642-7 0039-6060

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Unusual presentation of graft-versus-host disease in pediatric liver transplant recipients: evidence of late and recurrent disease. Author(s): Department of Surgery, University of Miami, Florida, USA. [email protected] Source: Pinna, A D Weppler, D Berho, M Masetti, M DeFaria, W Kato, T Thompson, J Ricordi, C Tzakis, A G Pediatr-Transplant. 1999 August; 3(3): 236-42 1397-3142

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to liver transplant; 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: •

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

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

Dissertations on Liver Transplant 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 liver transplant. 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: •

Allocating Life: the Selection of Liver Transplant Patients by Pike, Kenneth Charles, PhD from University of Washington, 1996, 203 pages http://wwwlib.umi.com/dissertations/fullcit/9716897

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Social Judgments in Medical Decision-making: The Case of Alcoholic Liver Transplantation by Hegedus, Andrea Mary, PhD from University of Pittsburgh, 1991, 256 pages http://wwwlib.umi.com/dissertations/fullcit/9218825

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The Impact of Pre-Transplant Nutrition on Growth and Development Children Awaiting Liver Transplant by Falkenstein, Kathleen P.; PhD from New York University, 2003, 151 pages http://wwwlib.umi.com/dissertations/fullcit/3086906

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The Personal Experiences of Liver Transplant and the Interactive Processes of SelfRedefinition by Chadha, Janice Hays, PhD from University of Illinois at UrbanaChampaign, 1995, 310 pages http://wwwlib.umi.com/dissertations/fullcit/9624304

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

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CHAPTER 4. CLINICAL TRIALS AND LIVER TRANSPLANT Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning liver transplant.

Recent Trials on Liver Transplant The following is a list of recent trials dedicated to liver transplant.8 Further information on a trial is available at the Web site indicated. •

Detection and Cytotoxic T Lymphocyte Therapy Lymphoproliferative Disorder After Liver Transplant

of

Post-Transplant

Condition(s): Liver Disease; Lymphoproliferative Disorders Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Despite advances in medical and gene therapy, orthotopic liver transplantation remains the only definitive therapeutic option for children with endstage liver disease. Recent advances in pre-, intra-, and early post-transplant care have resulted in a dramatic improvement in survival of the pediatric liver transplant patient. The broad long-range goal of our research program is directed at enhancing the patient's long-term survival. Our primary focus relates to obligate life-long immunosuppression, with its inherent complications including severe infection and development of cancer. These two complications come together in a single disease, Epstein-Barr Virus (EBV)associated post-transplant lymphoproliferative disorder (PTLD). EBV, a latent human lymphotrophic herpes virus infects and immortalizes B cells. Primary infection usually occurs via salivary exchange and results in a mild, self-limited illness followed by lifelong EBV-specific T cell controlled EBV latency. T cell-based immunosuppression prevents allograft rejection, however, it also suppresses cytotoxic T lymphocyte (CTL) function, generating an environment in which EBV-infected cells can proliferate. Patients receiving life-long T cell-based immunosuppression have an increased risk of developing PTLD due to their inability to produce normal immunoregulatory 8

These are listed at www.ClinicalTrials.gov.

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responses. This disease is particularly devastating to the pediatric patient as its incidence is at least 4-fold greater than in the adult liver transplant patient population. In fact, PTLD is the number one cause of death following pediatric liver transplantation. At this time, there is no definitive method of prospectively detecting, diagnosing, or treating PTLD, and current treatment protocols place the liver allograft and patient at risk. Therefore, a diagnostic tool that is both sensitive and specific, and a treatment strategy with low toxicity are greatly needed to decrease the morbidity and mortality suffered by the pediatric liver transplant patient with PTLD. Our proposed studies will support our hypothesis that the combination of a persistently elevated EBV load in the setting of a diminished immune response to EBV will be an early risk indicator associated with PTLD development, and that pre-emptive treatment utilizing autologous adoptive EBV-specific CTL immunotherapy will provide a low toxicity treatment option. Phase(s): Phase I Study Type: Interventional Contact(s): John A Goss, MD 713-798-8355 [email protected] Web Site: http://clinicaltrials.gov/ct/show/NCT00063648 •

Kidney and Liver Transplantation in People with HIV Condition(s): HIV Infections; Kidney Transplantation; Liver Transplantation Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: With improved anti-HIV drug therapy, HIV infected patients are now living longer. These patients are at risk for liver and kidney failure and may need organ transplants. However, little is know about the safety and effectiveness of organ transplants in patients with HIV. This study will evaluate organ transplantation in HIV infected patients undergoing liver and kidney transplants. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00074386

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Osteoporosis in children and adults following liver transplantation Condition(s): Osteoporosis; Liver Transplantation Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: This pilot project aims to 1) estimate the prevalence of osteoporosis in adults having undergone liver transplantation in childhood, and 2) identify risk factors for osteoporosis in this group. We aim to study 40 individuals. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00008788

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Prevention of Recurrent Hepatitis B after Liver Transplantation Condition(s): Hepatitis B; Cirrhosis; Acute Liver Failure; Hepatocellular Carcinoma

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Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Hepatitis B accounts for approximately 5000 deaths per year in the United States. Liver transplantation offers the only hope for patients who develop endstage liver disease. Early results of liver transplantation for hepatitis B were poor with recurrence rate of 80% and 1-year survival of only 50%. Recent studies found that preventive therapy using hepatitis B immune globulin (HBIG) or antiviral medications such as lamivudine can reduce the recurrence rate to roughly 30% with accompanying improvement in survival. However, HBIG when given as intravenous infusion in high doses is very expensive, while long-term use of lamivudine is associated with drug resistance. Some studies found that preventive therapy using both HBIG and lamivudine may decrease recurrence rate to less than 10% but the dose and duration of HBIG needed when used in combination with lamivudine is not clear. Adefovir, a new antiviral medication, is effective against lamivudine resistant hepatitis B but its role in liver transplantation is uncertain because of the risk of kidney damage. Many studies showed that the risk of recurrent hepatitis B is related to the viral load before transplant. Thus, it may be possible to tailor the preventive therapy according to the risk. The aim of this study is to establish the most cost-effective preventive therapy for recurrent hepatitis B after liver transplantation. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00059267 •

Comparison of Two Treatments to Prevent Invasive Fungal Infections in Patients Who Have Received Liver Transplants Condition(s): Candidiasis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to compare the safety and effectiveness of 2 treatments to prevent invasive fungal infections (IFI), which are infections caused by yeasts and molds that are common in patients with weak immune systems or transplant patients. AmBisome, a new treatment, will be compared to fluconazole, the traditional treatment for fungal infections caused by the yeast Candida. Treatment will only be given to liver transplant patients who are found to be at high risk for IFI. Liver transplant patients who are at low risk for IFI will be monitored but will receive no study medication. IFIs are found mainly in a high risk group of liver transplant patients, and are not common in those with low risk. If IFI preventive therapy is focused on the high risk group, there may be a lesser chance of Candida becoming resistant (able to grow despite the presence of drugs used to kill it). Treating only the high risk group will also save money. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001107

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Vancomycin Resistant Enterococci in Patients Awaiting Liver Transplantation at the University of Michigan: Prevalence, Risk Factors, Natural History and Outcome of Colonization Condition(s): Liver Diseases Study Status: This study is no longer recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: Enterococci, especially vancomycin resistant enterococci (VRE), are increasing in prevalence in many hospitals in the United States. Patients undergoing liver transplantation are at particular risk for developing infection due to VRE. The effect of prior colonization with VRE on the outcome of liver transplantation is unknown. This prospective study will ascertain the prevalence of gastrointestinal colonization with vancomycin resistant enterococci among patients awaiting liver transplantation at the University of Michigan Health System. Risk factors for acquisition of the organism, natural history of colonization and outcome in colonized patients will also be determined. All patients currently listed on a priority waiting list for liver transplantation at UMHS will be invited to participate. Patients will receive a standardized letter from their primary gastroenterologist describing the rationale for the study. Patients will be contacted by telephone by a member of the study team in order to arrange an appointment in the GCRC at the time of their regularly scheduled Transplant Clinic appointment in order discuss their potential participation in the study. Patients who give informed consent, will be interviewed using a standard interview questionnaire. Demographic and historical data relevant to the risk of VRE colonization will be collected during the interview. A sample will be obtained via rectal swab for culture. Rectal swabs for culture and collection of information on the standardized questionnaire will be repeated every six months while the patient is awaiting liver transplantation. When a patient undergoes liver transplantation, a culture will be obtained at the time of admission and weekly after post-operatively until discharge. All patients will be followed for 60 days after transplantation to assess several primary outcomes, including operative and post-operative complications, VRE infection and mortality. Rectal swabs will be the only procedure performed for the purposes of this study. Culture results will not be made available to the transplant team in order to avoid bias in clinical care. All data will be entered into an electronic database. GCRC statisticians will assist in the analysis of risk factors and outcome analysis. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005667

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Study of the Pharmacokinetics of Mycophenolate Mofetil in Patients Who Have Undergone Orthotopic Liver Transplantation Condition(s): Graft Versus Host Disease Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); University of North Carolina Purpose - Excerpt: Objectives: I. Determine the effects of bile externalization and antibiotic gut sterilization on the pharmacokinetics of mycophenolate mofetil in patients who have undergone orthotopic liver transplantation. II. Correlate serum concentrations of mycophenolic acid with inosine monophosphate dehydrogenase activity in these patients.

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00007059

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “liver transplant” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 5. PATENTS ON LIVER TRANSPLANT Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “liver transplant” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on liver transplant, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Liver Transplant By performing a patent search focusing on liver transplant, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on liver transplant: •

Determining hepatic status of a liver transplant recipient by measuring PI glutathione S-transferase Inventor(s): Doyle; John Martin (Deansgrange, IE), Kilty; Cormac Gerard (Sandycove, IE), Manning; Fiona Mary (Lusk, IE) Assignee(s): Biotrin Intellectual Properties, Ltd. (county Dublin, Ie) Patent Number: 6,183,977 Date filed: July 31, 1998 Abstract: Hepatic status of a subject is determined by measuring the level of pi glutathione S-transferase (.pi.GST) in a biological fluid such as bile or plasma from the subject by an immunoassay. An increased level of.pi.GST as compared to a normal range of.pi.GST indicates an abnormal condition of the liver. Measuring.pi.GST level has particular application for determining the hepatic status of a liver transplant recipient because it enables detecting liver transplant rejection at a very early stage after transplantation. The immunoassay is preferably an enzyme immunoassay, and the entire immunoassay can be completed in 2.5 hours. The biological fluid may be diluted with a diluent which contains an effective amount of a protein such as serum albumin to optimize antibody-antigen reaction. When plasma is the fluid, the plasma should be collected and stored prior to the determination in the presence of an anti-coagulant under conditions which permit substantially no haemolysis. The level of alpha glutathione S-transferase (.alpha.GST) may also be determined in biological fluid from the subject to facilitate differentiation between graft rejection and non-specific hepatocellular damage. Excerpt(s): This invention relates to a method of determining the hepatic status of a subject, including a liver transplant recipient and, thereby, deciding on appropriate therapy or corrective action, if required, dependent on said hepatic status. The ability to differentiate between the various types of hepatic injury is of great significance in the treatment of both transplant patients and also individuals who suffer from other hepatic diseases which may affect the biliary system. Glutathione S-transferases (GSTs) comprise a multigene family of proteins consisting mainly of alpha (.alpha.GST), mu (.mu.GST), pi (.pi.GST) and theta-class (.theta.GST) isoforms as defined by isoelectric point and are responsible for the detoxification of a range of xenobiotics, mainly via conjugation to glutathione (Beckett, G. J and Hayes, J. D., Advances in Clinical Chemistry (1993); 30, 281-380). Generally, the proteins are dimeric in nature consisting of two 25-27kDa subunits and may exist in homodimeric or heterodimeric forms. Pi Glutathione S-transferase (.pi.GST) is a homodimer, and is located in the cytoplasm of bile duct epithelial cells within the liver (Beckett G. J. and Hayes, J. D., (1993) supra).alpha.GST is known to be present in hepatocytes within the liver and exists in both homodimeric and heterodimeric states (Campbell, J. A. H., et. al., Cancer (Philadelphia) (1991) 67, 1608-1613; Howie, A. F., et. al., Clin. Chem. Acta., (1988) 177, 65-76). This heterogenous GST distribution of.alpha. and.pi.GST suggests that the different isoenzymes have unique in vivo functions in different hepatic regions (Campbell, J. A. H., et. al., (1991) supra). Web site: http://www.delphion.com/details?pn=US06183977__

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•

Liver transplant clamp Inventor(s): Klintmalm; Goran B. (Dallas, TX) Assignee(s): Pilling Company (fort Washington, Pa) Patent Number: 5,019,092 Date filed: October 4, 1989 Abstract: A vascular clamp particularly suitable for use in liver transplant surgery. The free ends of pivoted handles arch toward each other and connect to the middle of elongate curved jaws which lie in substantially parallel planes when the handles are in the normal clamping position. The curvature of the jaws, projected into the parallel planes, decreases toward the ends farthest from the handles, and coincides at the other end with an arc, the extension of which smoothly merges near the pivoted connection with the handles. A bridge member joining the jaws to the handles prevent sutures from entangling on the clamp and reduces bending of the jaws at the juncture with free ends of the handles. Excerpt(s): The present invention relates generally to surgical instruments for occluding blood vessels during a surgical procedure, and more particularly to a vascular clamp suitable for closing the suprahepatic portion of the inferior vena cava when transplanting a liver. Surgical instruments such as forceps, hemostats and clamps, for temporary occlusion of blood vessels, come in various sizes and configurations to meet the specific requirements. For example, the Satinsky clamp, manufactured by Pilling Company, Fort Washington, Pa., is among the more popular and versatile of cardiac clamps and is designed to provide a non-crushing grip on the vena cava. However, the configuration of this clamp and others of the prior art do not meet the special needs in transplanting livers. The problem normally encountered is that these clamps, when used to occlude the suprahepatic inferior vena cava during surgery, do not fully close near the tips due to the amount of tissue between the jaws. This can also cause the jaws to slip off the upper vena cava cuff and produce a potentially life-threatening situation. If by mischance the jaws should slip, their tips might dig into the superior border of the right hepatic lobe of the liver causing lacerations and sometimes difficult bleeding. A more serious consequence might be that the tips penetrate the right hepatic vein. Accordingly, it is an object of the present invention to provide a vascular clamp with jaws suitable for uniformly and securely closing a blood vessel across its entire compressed width. Web site: http://www.delphion.com/details?pn=US05019092__

•

Measurement of an enzyme marker as an aid to diagnosis of liver transplant rejection Inventor(s): Kilty; Cormac G. (Monkstown, IE), O'Byrne; Seamus (Monkstown, IE) Assignee(s): Syncor Limited (monkstown, Ie) Patent Number: 5,217,868 Date filed: May 1, 1992 Abstract: A method which assists in the early diagnosis of rejection in a liver transplant recipient comprises measuring an increase in plasma or serum alpha glutathione Stranferase (.alpha.-GST) from said recipient in the absence of or preceding any change in plasma or serum transaminase.alpha.-GST is most suitably measured by enzymeimmunoassay, using a solid phase antibody which is monospecific for.alpha.-

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GST. The monospecific antibody cross-reacts with the.alpha.-GST dimers B.sub.1 B.sub.1, B.sub.1 B.sub.2 and B.sub.2 B.sub.2. Excerpt(s): This invention relates to a method which assists in the early diagnosis of rejection in a liver transplant recipient. In liver transplant recipients the risk of allograft rejection is greatest in the first few weeks after transplantation, although it can occur as late as the 8th post-operative month. Rejection is most common, however, between the 4th and 10th post-operative days. Prompt diagnosis is crucial to limit damage by this allogeneic immune response. It is also vital that the diagnosis is correct, since administration of augmented immunosuppression in the absence of rejection has its own morbidity--particularly in delaying wound healing and in predisposing the patient to serious infection. The most reliable evidence of rejection is histological but may not always be possible due to severe impairment of clotting. In current practice, the suspected diagnosis of rejection usually rests on evidence of progressive deterioration of liver function in the absence of any other explanation for this functional derangement (Calne, Ry, (1987); Liver Transplantation (2nd Edition), Ed Calne Ry, Grune & Stratton, Inc., London, 301-303). Thus, significant rejection is not diagnosed unless the serum bilirubin and alkaline phosphatase levels are elevated. If the serum transaminases and prothrombin time are also rising, then rejection is assumed unless there is evidence of (a) portal vein/hepatic artery obstruction, (b) septicaemia or (c) drug toxicity. The duration of treatment of rejection by augmented immunosuppression will depend on the improvement in liver function tests (LFTs). Patients with persistently raised LFTs have a poor prognosis. The biochemical assessment of liver function usually includes measurement of plasma or serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) activity. These cytosolic enzymes are released into the circulation following hepatocellular damage. The measurement of these aminotransferases for monitoring liver function has been questioned, however, as activities may be normal in patients with chronic liver disease. The poor sensitivity of aminotransferases in detecting damage in certain types of liver pathology may partly lie in their distribution within the liver. The periportal hepatocytes contain the highest concentrations of the aminotransferases but the centrilobular hepatocytes, which are relatively deficient in aminotransferases, are more susceptible to damage from hypoxia and toxins such as alcohol and paracetamol. Web site: http://www.delphion.com/details?pn=US05217868__ •

Method of testing a donor liver for transplant Inventor(s): Rao; Prakash N. (Pittsburgh, PA) Assignee(s): University of Pittsburgh of the Commonwealth System of Higher Education (pittsburgh, Pa) Patent Number: 5,260,188 Date filed: May 19, 1992 Abstract: A method for determining the suitability of an organ for transplant by performing one or more tests on the endothelial cells lining the blood vessels in the organ prior to the transplant operation. Specifically hyaluronic acid is used as the measure to determine liver transplant effectiveness. Excerpt(s): The invention relates to a method of noninvasively testing a donor organ in preparation for transplant. More specifically, the invention is directed to a method for preoperatively testing for the suitability of an organ, such as a liver, and predicting

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postoperative transplant graft function. In recent years, the medical field has developed techniques for saving and prolonging life by transplanting an organ, such as a liver into a patient. The process of harvesting an organ from a donor, preserving the organ in transport, which involves keeping the organ cold, and subsequently transplanting the organ is associated with what is known as "preservation/reperfusion injury" In particular, in the preservation stage of handling an organ, such as a liver, the "injury" is localized in a specific region, mainly, in the cells which line the blood vessels. These cells are known as microvascular endothelial cells. This "injury" is the principal cause of nonfunction of the organ when transplanted into the patient. Web site: http://www.delphion.com/details?pn=US05260188__

Patent Applications on Liver Transplant As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to liver transplant: •

Methods for identifying a preferred liver transplant donor Inventor(s): Rosen, Hugo R.; (Tigard, OR) Correspondence: Campbell & Flores Llp; 4370 LA Jolla Village Drive; 7th Floor; San Diego; CA; 92122; US Patent Application Number: 20020119468 Date filed: September 12, 2001 Abstract: The present invention provides a method of identifying a preferred liver transplant donor. The method includes the step of determining in an individual the presence or absence of a preferred genotype at a polymorphic site, where the preferred genotype is associated with altered activity of a tumor necrosis factor, and wherein the presence of the preferred genotype indicates that the individual is a preferred liver transplant donor. A preferred genotype can be associated with lower activity of a tumor necrosis factor such as TNF-.alpha. and can be, for example, TNF308.1. The methods of the invention are useful for identifying a preferred donor liver for transplant into a HCV infected patient. The invention additionally provides a method for selecting a preferred liver for transplantation. The invention further provides a method for limiting the recurrence of HCV infection in a liver transplant recipient. Excerpt(s): The present invention relates generally to the field of molecular medicine and more specifically to methods of identifying a preferred liver transplant donor. Chronic hepatitis C virus (HCV) infection afflicts an estimated 4 to 4.5 million Americans. HCV infection contributes to the deaths of more than 12,000 Americans every year and is a principal cause of chronic liver disease, cirrhosis, and liver cancer. Liver failure due to hepatitis C infection is the leading cause of liver transplants in the U.S. Even though acute hepatitis C, at first, is largely asymptomatic, a flu-like illness is often mentioned by patients who are later diagnosed with the disease. About nine out of ten people who contract an acute infection of HCV will go on to develop chronic hepatitis, characterized by extreme fatigue, depression, fever, mood changes, and

10

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

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weakness. Of those who eventually develop chronic hepatitis C, a large number will develop cirrhosis, portal hypertension, and liver failure, some in as few as 10 years, and some will require a liver transplant. Hepatitis C is a silent killer because both the acute and chronic phases of the disease usually produce no specific symptoms. The acute phase is identified only if there is a definite recent risk factor such as a needle stick, surgery or a tattoo. Modes of transmission include body piercing, oral surgery, dialysis, acupuncture, vaccinations, and tainted blood products. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with liver transplant, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “liver transplant” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on liver transplant. You can also use this procedure to view pending patent applications concerning liver transplant. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON LIVER TRANSPLANT Overview This chapter provides bibliographic book references relating to liver transplant. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on liver transplant 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 “liver transplant” (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 liver transplant: •

Liver Transplantation: Practice and Management Source: London: BMJ Publishing Group. 1994. 400 p. Contact: Available from American College of Physicians. P.O. Box 7777, Philadelphia, PA 19175-1140. (800) 523-1546, ext. 2600 or (215) 351-2600. Fax (215) 351-2799. PRICE: $45 for ACP members; $59 for non-members (as of 1995). Order no. 0424. ISBN: 0727907875. Summary: This medical textbook provides an overview of the practice and management of liver transplantation. The book is intended primarily for experienced physicians who see patients both pre-and posttransplantation, but whose practice is not based in liver units; it is also appropriate for medical students and physicians in training. The book consists of 19 chapters that cover topics the development of liver transplantation; when to refer for transplantation; psychiatric evaluation of liver transplant candidates;

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specific indications for both adult and pediatric liver transplant; management of the end stage liver disease patient, pretransplant; management in the transplant unit, including donor organ retrieval, allocation, and logistics; survival after transplantation; immunological complications, notably late rejection; immunosuppressive drugs; surgical considerations after liver transplantation; medical complications, including infections, malignancy, and recurrent disease; rehabilitation and quality of life; incidental problems in the management of liver transplant recipients, including reproductive health, immunization, and drug therapy; management of children after liver transplantation; ethical issues; and the costs and benefits of liver transplantation. Each chapter includes black-and-white photographs as well as extensive references; a subject index concludes the volume. •

Guide to Liver Transplantation Source: New York, NY: Igaku-Shoin Medical Publishers, Inc. 1992. 353 p. Contact: Available from Igaku-Shoin Medical Publishers, Inc. One Madison Avenue, New York, NY 10010. (212) 779-0123. PIRCE: $98.50 plus shipping and handling. ISBN: 0896402118. Summary: This volume, reflecting the experience of a single transplant team, is designed to serve as a guide and introduction to the field of liver transplantation. The seventeen chapters, each written by members of the same transplant team, cover topics including legal and ethical issues; allocating scarce donor organs; the role of the physician in the donor process; transplant biology; selection of patients for referral for liver transplantation; preoperative medical evaluation of the prospective recipient; psychiatric and social evaluation of the liver transplant candidate; medical and surgical management of the recipient; operative techniques and strategies in liver transplantation; evaluation, complications, and therapy in the immediate postoperative period; immunosuppression and rejection; outpatient management; the transplant coordinator; pediatric liver transplantation; and the histopathology of liver transplantation. Four appendices cover social support for liver transplantation; computer database systems in liver transplant; transplantation of foreign nationals; and diet therapy for patients with end-stage liver disease. A subject index concludes the volume.

•

Medical Care of the Liver Transplant Patient Source: Oxford, England: Blackwell Science Ltd. 1997. 409 p. Contact: Available from Blackwell Science, Inc. 238 Main Street, Cambridge, MA 02142. (800) 215-1000 or (617) 876-7000. Fax (617) 492-5263. PRICE: $95.00. ISBN: 0865425248. Summary: Written for physicians, nurses, and other health professionals who care for liver transplant patients, this book answers practical questions about drugs and drug interactions, complications, and the special medical concerns and primary care needs of such patients. The book covers selection and referral of patients for transplantation and post-transplant management, as well as problems that occur frequently in the course of pre-and postoperative management. Special sections on psychiatric evaluation and social rehabilitation reinforce the theme of a comprehensive approach. The authors support the reintegration of the care of liver transplant patients into the communitybased practice of medicine. Chapters also cover the timing of transplantation, fulminant hepatic failure, management of portal hypertension and biliary disease prior to transplantation, patients with alcoholic liver disease, financial considerations, procurement and allocation of donor livers, rejection or infection, vascular aspects of

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liver transplantation, biliary complication post-transplantation, histopathology and research. Renal function, obesity and hyperlipidemia after liver transplantation, social rehabilitation, pharmacology of immunosuppressive drugs and drug interactions, and liver transplantation in children are covered as well. Each chapter concludes with references and a subject index concludes the volume.

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 “liver transplant” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “liver transplant” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “liver transplant” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Clinical Aspects of Immunosuppression in Liver Transplantation by I.J. Klompmaker; ISBN: 9023230388; http://www.amazon.com/exec/obidos/ASIN/9023230388/icongroupinterna

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I'm Glad You're Not Dead : A Liver Transplant Story, 2nd edition by Elizabeth Parr; ISBN: 0965472817; http://www.amazon.com/exec/obidos/ASIN/0965472817/icongroupinterna

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Immunological, Metabolic and Infectious Aspects of Liver Transplantation by D.A. Vuitton (Editor), et al; ISBN: 0861963334; http://www.amazon.com/exec/obidos/ASIN/0861963334/icongroupinterna

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Liver transplant : life renewed and abundant by JoAnn Cirillo; ISBN: 1556739303; http://www.amazon.com/exec/obidos/ASIN/1556739303/icongroupinterna

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Manual of Liver Transplant Medical Care by Abhinav Humar (Editor), et al; ISBN: 1577491157; http://www.amazon.com/exec/obidos/ASIN/1577491157/icongroupinterna

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Medical Care of the Liver Transplant Patient by Paul G. Killenberg (Editor), et al; ISBN: 0632045663; http://www.amazon.com/exec/obidos/ASIN/0632045663/icongroupinterna

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Surviving Liver Diseases - Life with a Liver Transplant by Moustafa Ahmed, G.M. Dusheiko; ISBN: 095360070X; http://www.amazon.com/exec/obidos/ASIN/095360070X/icongroupinterna

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The Diffusion of Heart and Liver Transplantation Across Europe by Michael Bos; ISBN: 0903060841; http://www.amazon.com/exec/obidos/ASIN/0903060841/icongroupinterna

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

Liver Transplants: A Miracle of Modern Medicine Source: in Everson, G.T.; Weinberg, H. Living with Hepatitis B: A Survivor's Guide. Long Island, NY: Hatherleigh Press. 2002. p.175-197. Contact: Available from Hatherleigh Press. 5-22 46th Avenue Suite 200, Long Island City, NY 11101. (800) 528-2550. E-mail: [email protected]. Website: http://store.yahoo.com/hatherleighpress/index.html. PRICE: $15.95 plus shipping and handling. ISBN: 1578260841. Summary: Chronic hepatitis B can lead to cirrhosis (liver scarring), liver cancer, and the need for liver transplantation. This chapter on liver transplants is from a book that helps readers diagnosed with hepatitis B virus (HBV) infection educate themselves about the disease and its treatment. The authors first offer a brief history of liver transplantation, then discuss the indications for transplantation, denial of transplants, paying for transplants, the transplant team, waiting for a liver, the evaluation process, the waiting list, transplant support groups, liver transplant surgery, donor livers, the living donor liver transplant, the surgical procedure, the hospital stay, living with a new liver, medications to prevent rejection, managing complications, psychological transformation, survival rates, and how organs are allocated. Throughout the chapter the authors include quotes from real people who have gone through this process. The authors also include resource organizations that may offer additional support and information for readers. 1 reference.

•

Liver Transplantation: Prevention and Treatment of Rejection 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. 491511. 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: Liver transplant recipients are a heterogeneous group of individuals, with different predisposing factors and cofactors for the development of rejection. This chapter on the prevention and treatment of rejection in liver transplantation 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 authors of this chapter note that the success of hepatic (liver) transplantation has resulted in its widespread use for endstage and fulminant liver disease. Current immunosuppressive agents lack specificity and there is still a need to maintain a balance between over-immunosuppression, with its potential

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risk of life threatening sepsis, and under-immunosuppression leading to graft loss from rejection. At present, the vast majority of liver transplant recipients need to take life long immunosuppressive therapy. The gold standard for diagnosis of graft rejection is histological; rejection is classified as acute (occurring between 5 and 30 days after liver transplantation) or chronic (after 60 days from transplantation). Chronic rejection usually develops after an unresolved episode of acute rejection, or after multiple episodes of acute rejection, or quietly during a period of months to years with few or no clinically apparent acute episodes of cellular rejection. The authors consider the prognostic factors for rejection, including the number of acute rejection episodes, severity, and timing. The authors also consider strategies for weaning patients off immunosuppression, including steroid withdrawal, total withdrawal, and the use of subtherapeutic doses of immunosuppression; and choice of immunosuppressive agents, including calcineurin inhibitors, microemulsified cyclosporin, mycophenolate mofetil, ursodeoxycholic acid (UDCA), and trials comparing mono and combination therapies. 7 tables. 88 references. •

Liver Transplantation: Patient Selection and Postoperative Management Source: in Brandt, L., et al., eds. Clinical Practice of Gastroenterology. Volume Two. Philadelphia, PA: Current Medicine. 1999. p. 1019-1028. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. Website: www.wbsaunders.com. PRICE: $235.00 plus shipping and handling. ISBN: 0443065209 (two volume set); 0443065217 (volume 1); 0443065225 (volume 2). Summary: Liver transplantation has become standard therapy for end stage liver disease (ESLD) during the past decade. Several factors have contributed to this, including a better understanding of liver disease, improved immunosuppression (particularly the introduction of cyclosporine), refinements and standardization in surgical techniques, better and prolonged organ preservation, earlier recipient referral, increased donor availability, improved donor management and selection, meticulous postoperative care, and the training of new liver transplant teams. This chapter on liver transplantation is from a lengthy textbook that brings practitioners up to date on the complexities of gastroenterology practice, focusing on the essentials of patient care. The authors discuss indications for liver transplantation, contraindications, evaluation, timing, approval and listing process, the transplant procedure, postoperative management, postoperative complications (including graft dysfunction, infection, and extrahepatic complications), survival, retransplantation, and quality of life. A patient with either chronic, progressive, or fulminant liver disease for which no other effective medical or surgical therapy exists may be a transplant candidate. HIV infection is considered as an absolute contraindication, as is active substance abuse, extrahepatic malignancy, advanced cardiovascular disease, and uncontrolled infection. The successful evaluation and transplant program requires a multidisciplinary approach. Immunosuppression is a key feature of the postoperative management of orthotopic liver transplant (OLT) patients. Liver transplantation is associated with significant postoperative morbidity. The best outcomes, of 1 and 5 year survival rates, are achieved by patients with either cholestatic or metabolic liver disease; the worst outcome is in patients transplanted for malignant disease. 2 figures. 12 tables. 16 references.

•

Kidney, Pancreas, and Liver Transplantation Source: in Pizer, H.F. Organ Transplants: A Patient's Guide. Cambridge, MA: Harvard University Press. 1991. p. 146-183.

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Contact: Available from Harvard University Press. Sales Department, 79 Garden Street, Cambridge, MA 02138. (617) 495-2606. PRICE: $24.95. ISBN 067464235X. Summary: This book, from a patient guide to organ transplants, discusses kidney, pancreas, and liver transplantation. Topics include causes of kidney transplantation; dialysis; the transplant option; donor organs; pretransplant conferences; the operation; postoperative care; transplanting the pancreas; transplanting the liver; history of liver transplantation; the liver transplant candidate; matching donor and recipient; recovery issues; and anticipated future developments. Throughout the chapter, detailed stories are told of patients undergoing each type of transplant. •

Renal Function in the Liver Transplant Patient Source: in Killenberg, P.G.; Clavien, P.A., eds. Medical Care of the Liver Transplant Patient. Malden, MA: Blackwell Science, Inc. 1997. p. 280-291. Contact: Available from Blackwell Science. Commerce Place, 350 Main Street, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. PRICE: $150.00. ISBN: 0865425248. Summary: This chapter on renal function is from a textbook on the medical care of the liver transplant patient. The author begins by reminding readers that approximately 25 percent of liver transplant recipients have some impairment of renal function prior to transplantation, and the majority have renal insufficiency at some time in the posttransplant period. However, measurement of the glomerular filtration rate (GFR) can be complicated in these patients. In the chapter, the author presents a general approach to the patient with renal insufficiency, then discusses the specific causes of renal dysfunction in the liver transplant patient. These causes include cyclosporine toxicity, tacrolimus (FK506) toxicity, renal disease (glomerulonephritis) associated with viral hepatitis, and renal disease associated with poor hepatic function (including the hepatorenal syndrome, characterized by reduced GFR and urine output with avid conservation of sodium by the kidneys and an unremarkable urine sediment). Improvement in renal function often occurs in the first 6 weeks after successful liver transplantation (except in patients with the hepatorenal syndrome, in whom about 10 percent develop end-stage renal disease). Dialysis therapy in the immediate postoperative period requires close attention to hemodynamics and coagulation parameters. Also, in the liver transplant patient with impaired hepatic clearance and renal failure, attention should be paid to the route of excretion of all pharmacologic agents given and doses should be adjusted accordingly. 3 figures. 1 table. 14 references.

•

Kidney, Pancreas, and Liver Transplantation: Transplanting the Pancreas Source: in Massachusetts General Hospital Organ Transplant Team and Pizer, H.F. Organ Transplants: A Patient's Guide. Cambridge, MA: Harvard University Press. 1991. p. 166-173. Contact: Available from Harvard University Press. Sales Department, 79 Garden Street, Cambridge, MA 02138. (617) 495-2577. PRICE: $24.95. Summary: This chapter, from a patient's guide to organ transplants, reviews kidney, pancreas, and liver transplantation. The section on pancreas transplantation covers reasons why people might need a pancreas transplant, potential long-term complications of even well-controlled diabetes, the history and current techniques of pancreas transplantation, donor and recipient selection, the operation itself, postoperative care and recovery, and the expected results of the procedure. The author uses

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the story of one woman's experience with a combined kidney and pancreas transplant to illustrate the topics discussed. A brief final section discusses the future of pancreas transplantation. •

Nutrition Management Following Liver Transplantation Source: in American Dietetic Association. Manual of Clinical Dietetics. Chicago, IL: American Dietetic Association. 1996. p. 593-598. Contact: Available from American Dietetic Association. 216 West Jackson Boulevard, Chicago, IL 60606. (800) 877-1600 or (312) 899-0040. Fax (312) 899-4899. PRICE: $59.95 for members, $70.00 for nonmembers. ISBN: 0880911530. Summary: This section on the nutrition management of patients who have undergone liver transplantation is from a manual that serves as a nutrition care guide for dietetics professionals, physicians, nurses, and other health professionals. The manual integrates current knowledge of nutrition, medical science, and food to set forth recommendations for healthy individuals and those for whom medical nutrition therapy (MNT) is indicated. Dietary modifications for the patient presenting for liver transplantation are designed to ameliorate the symptoms of end stage liver disease (ESLD) and to optimize preoperative nutritional status. Postoperatively, the diet is designed to provide appropriate nutrients to promote anabolism and wound healing, to prevent and treat postoperative complications, and to manage the nutritional side effects of immunosuppressive and other drugs. The text outlines the purpose, use, modifications, and adequacy of the diet. A brief sample menu for the postoperative liver transplant patient is included. 1 table. 22 references. (AA-M).

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CHAPTER 7. MULTIMEDIA ON LIVER TRANSPLANT Overview In this chapter, we show you how to keep current on multimedia sources of information on liver transplant. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on liver transplant is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “liver transplant” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “liver transplant” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on liver transplant: •

Cirrhosis of the Liver Source: Los Angeles, CA: National Health Video, Inc. 1998. (videocassette). Contact: Available from National Health Video, Inc. 12021 Wilshire Blvd., Suite 550, Los Angeles, CA 90025. (800) 543-6803. Fax (310) 477-8198. E-mail: [email protected]. PRICE: $89.00 plus shipping and handling. Summary: This health education videotape is designed to convince viewers of the liver damage caused by alcohol intake. Narrated by a registered dietitian, the program first briefly reviews the anatomy of the liver and then describes the liver's functions: making clotting factors, supporting the immune system, filtering out chemical and alcohol toxins (regardless of how they enter the body), maintaining glycogen (stored food energy), aiding digestion of fats, protein and carbohydrates, and making bile for digesting fats and accessing vitamins. The main factor in keeping the liver healthy is the avoidance of alcohol, but the program also discusses the importance of a healthy diet and regular exercise. The program then focuses on cirrhosis, a condition in which

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normal liver cells are replaced by scar tissue. The program offers mortality statistics and reviews the causes of cirrhosis, including hepatitis, genetic disease, drug effects, and alcohol (which causes 75 percent of cirrhosis cases). There are no adequate warning signs that become apparent before the liver has been damaged. The program discusses the consequences of cirrhosis, including malnutrition, hepatic encephalopathy (ammonia induced mental impairment), swollen abdomen (ascites), fatty liver (in which fat cells replace normal liver cells), and reduced ability to manage medications and toxins. A final section discusses liver failure and liver transplantation, emphasizing that there are never enough donor livers available and that people who have alcohol induced liver disease are often not acceptable transplant candidates. The program features interviews and scenes with patients and physicians. •

Your Liver Source: Bronx, NY: Latin Organization for Liver Awareness. 199x. (videocassette). Contact: Available from Latino Organization for Liver Awareness (LOLA). 1560 Mayflower Avenue, Bronx, New York, NY 10465. (718) 892-8697. Fax (718) 918-0527. (888) 367-LOLA. PRICE: $10.00; plus shipping and handling. Summary: This videotape program reviews the physiology of the liver, and describes different types of liver disease, focusing on hepatitis. Narrated by Debbie Delgado-Vega, a liver transplant recipient and advocate and educator in the field, the program first summarizes the functions of the liver. The liver stores vitamins and minerals, makes bsoleilwelile to help digestion, detoxifies chemicals, stores energy, removes poisons and pollutants that may be ingested from the air, makes clotting factors, and defends against germs that cause disease. The program then lists the types of liver disease, including liver disorders in children, alcohol related liver disease, liver cancer, cirrhosis (scarring), and viral hepatitis (inflammation of the liver due to viral infection). The program discusses hepatitis in depth, explaining the differences between acute disease (less than 6 months in duration) and chronic disease; the numbers of people in the United States with hepatitis B (1.2 million) and hepatitis C (4.8 million); the complications of chronic hepatitis that can lead to cirrhosis (inflammation, scarring and nodules); symptoms, notably fatigue; how hepatitis B and C are transmitted in blood and other body fluids; other risk factors, including the use of intranasal cocaine, intravenous drugs, tattoos or body piercing, pre 1992 blood transfusion, unprotected sex, and having served time in jail; treatment options, including interferons and ribavirin; and why it is important to get tested and treated, even if there are no apparent symptoms. The narrator stresses that more Latinos die from liver disease than any other minority group and chronic liver disease is the third leading cause of death among Latinos. The conclusion of the program shows clips and materials from educational programs and public health and advocacy activities conducted by LOLA (Latino Organization for Liver Awareness). The program is narrated in English, with some clips at the end in Spanish.

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CHAPTER 8. TRANSPLANT

PERIODICALS

AND

NEWS

ON

LIVER

Overview In this chapter, we suggest a number of news sources and present various periodicals that cover liver transplant.

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

New liver transplant allocation policy improves outcome in patients with cancer Source: Reuters Medical News Date: January 08, 2004

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•

Hepsera reduces lamivudine-resistant HBV levels in liver transplant patients Source: Reuters Industry Breifing Date: January 06, 2004

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HIV no bar to liver transplantation Source: Reuters Medical News Date: December 15, 2003

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Liver transplant extends survival in patients with liver cancer Source: Reuters Medical News Date: October 31, 2003

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Living donor liver transplants offer fewer complications than cadaveric organs Source: Reuters Medical News Date: October 13, 2003

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Nut allergy passed through liver transplant Source: Reuters Medical News Date: January 29, 2003

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New rules approved for live-donor liver transplants in New York Source: Reuters Medical News Date: December 20, 2002

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FDA grants Nabi HCV therapy orphan drug status for liver transplants Source: Reuters Medical News Date: December 05, 2002

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CMV co-infection predicts mortality in HCV-infected liver transplant recipients Source: Reuters Medical News Date: November 20, 2002

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In living-donor liver transplantation, left-lobe may be preferable to right-lobe grafts Source: Reuters Medical News Date: November 08, 2002

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New model identifies patients with best chance of surviving liver transplant Source: Reuters Medical News Date: October 04, 2002

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Risk factors for HBV breakthrough after liver transplantation identified Source: Reuters Medical News Date: October 02, 2002

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Split liver transplantation successful in children Source: Reuters Medical News Date: August 26, 2002

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GI decontamination fails to prevent infection in liver transplant recipients Source: Reuters Medical News Date: July 10, 2002

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Liver transplants at bargain prices Source: Reuters Health eLine Date: May 20, 2002

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Preemptive ganciclovir prevents CMV infection after liver transplant Source: Reuters Industry Breifing Date: May 02, 2002

Periodicals and News

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Liver transplants can be safely performed without steroids Source: Reuters Industry Breifing Date: May 01, 2002

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Tacrolimus seems to curb chronic rejection in pediatric liver transplants Source: Reuters Industry Breifing Date: April 30, 2002

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Liver transplant feasible for HIV-infected patients with HCV Source: Reuters Medical News Date: April 29, 2002

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Wyeth strengthens liver transplant contraindication on Rapamune label Source: Reuters Industry Breifing Date: April 26, 2002

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Colorectal disease common after liver transplant Source: Reuters Medical News Date: April 22, 2002

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Plasma amino acids abnormal after liver transplant Source: Reuters Medical News Date: March 27, 2002

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Italy to allow liver transplants in HIV patients Source: Reuters Health eLine Date: March 27, 2002

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Italy to allow HIV patients to receive liver transplants Source: Reuters Medical News Date: March 27, 2002

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Mount Sinai liver transplant death blamed on poor staffing Source: Reuters Medical News Date: March 13, 2002

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NYC liver transplant death blamed on poor staffing Source: Reuters Health eLine Date: March 12, 2002

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Lactate levels identify paracetamol overdose cases requiring liver transplant Source: Reuters Medical News Date: February 14, 2002

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Early referral important for successful pediatric liver transplantation Source: Reuters Medical News Date: February 04, 2002

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Race influences liver transplant survival in US Source: Reuters Health eLine Date: January 25, 2002

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Race seems to affect outcome after liver transplantation Source: Reuters Medical News Date: January 24, 2002

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After donor death, Mt Sinai in New York suspends living donor liver transplants Source: Reuters Medical News Date: January 16, 2002

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Liver transplant method could cut live donor need Source: Reuters Health eLine Date: January 10, 2002

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Hepatitis B lingers in lamivudine-treated liver transplant recipients Source: Reuters Industry Breifing Date: November 20, 2001

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Partial liver transplant allows for regeneration, immunosuppression withdrawal Source: Reuters Medical News Date: November 13, 2001

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New liver transplantation technique reduces time and transfusion requirements Source: Reuters Medical News Date: November 02, 2001

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Combined heart-lung-liver transplantation is feasible in certain patients Source: Reuters Medical News Date: September 10, 2001

•

HHS wins praise for expanding coverage of liver transplants Source: Reuters Industry Breifing Date: August 30, 2001 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 “liver transplant” (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.

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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 “liver transplant” (or synonyms). If you know the name of a company that is relevant to liver transplant, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “liver transplant” (or synonyms).

Newsletters on Liver Transplant Find newsletters on liver transplant using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “liver transplant.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “liver transplant” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •

Patient Selection for Heart or Liver Transplantation Source: Intramural Research Highlights. Number 20: [p.1-4]. February 1993. Contact: Available from Agency for Health Care Policy and Research. 2101 East Jefferson Street, Suite 501, Rockville, MD 20852. (800) 358-9295. Summary: This issue of Intramural Research Highlights discusses patient selection for heart or liver transplantation. The newsletter article is based on a chapter in Health Economics Worldwide, a book published in 1991. Topics include a general overview of heart and liver transplantation, focusing on organ availability and cost issues; characteristics of transplant recipients, including contraindications, age, and insurance coverage; hospital charges for transplant recipients; care and charges for nonrecipients; and the potential impact of the growing use of organ transplants on health care costs and insurance coverage. The article presents facts and figures from the Hospital Cost and Utilization Project database, which contains records of all discharges from a national sample of almost 500 hospitals and includes about 10 percent of U.S. transplants that occurred from 1984 to 1987. 2 figures.

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

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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 “liver transplant” (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 liver transplant: •

FK506: Tacrolimus for the Prevention of Rejection in Patients Receiving Liver Transplants Source: HMI's Prescription Plus. 5(1): 8-9. Fall-Winter 1994. Contact: Available from Homecare Management, Inc. 80 Air Park Drive, Ronkonkoma, NY 11779. Summary: This newsletter article addresses the recently-approved drug, tacrolimus (FK506, Prograf), indicated for the prevention of organ rejection in patients receiving liver transplants. The article describes clinical research prior to the approval of FK506; the natural origin of the drug; how FK506 is metabolized by the liver; adverse reactions and toxicities; and how tacrolimus will be used in treating transplant patients. The author concludes that, for patients who have received liver transplants and who are experiencing rejection not controlled by cyclosporine or are experiencing severe or intolerable side effects related to cyclosporine, switching to tacrolimus has been demonstrated to be an important option.

Academic Periodicals covering Liver Transplant Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to liver transplant. In addition to these sources, you can search for articles covering liver transplant that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 9. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for liver transplant. 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 nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with liver transplant. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to liver transplant: Ursodiol •

Systemic - U.S. Brands: Actigall http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202587.html

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

Mosby’s Drug 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 liver transplant 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 “liver transplant” (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

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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 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 liver transplant: •

Monoclonal antibody to hepatitis B virus (human) http://www.rarediseases.org/nord/search/nodd_full?code=151

•

Hepatitis B immune globulin, intravenous (trade name: H-BIGIV) http://www.rarediseases.org/nord/search/nodd_full?code=735

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 Institute11: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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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/

11

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

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

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

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

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

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

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

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

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

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

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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

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

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

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

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

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

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

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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.12 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:13 •

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/

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

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

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

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

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

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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

12

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). 13 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 Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “liver transplant” (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 23514 137 786 112 84 24633

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “liver transplant” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

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

15

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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

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 Biologists19 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.20 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.21 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/.

19 Adapted 20

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. 21 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 liver transplant 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 liver transplant. 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 liver transplant. 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 “liver transplant”:

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Blood Transfusion and Donation http://www.nlm.nih.gov/medlineplus/bloodtransfusionanddonation.html Hepatitis http://www.nlm.nih.gov/medlineplus/hepatitis.html Hepatitis B http://www.nlm.nih.gov/medlineplus/hepatitisb.html Hepatitis C http://www.nlm.nih.gov/medlineplus/hepatitisc.html Kidney Transplantation http://www.nlm.nih.gov/medlineplus/kidneytransplantation.html Liver Diseases http://www.nlm.nih.gov/medlineplus/liverdiseases.html Liver Transplantation http://www.nlm.nih.gov/medlineplus/livertransplantation.html Organ Transplantation http://www.nlm.nih.gov/medlineplus/organtransplantation.html Pancreas Transplantation http://www.nlm.nih.gov/medlineplus/pancreastransplantation.html

Within the health topic page dedicated to liver transplant, the following was listed: •

General/Overviews Getting a New Liver: Facts about Liver Transplants Source: American Society of Transplantation http://www.a-s-t.org/patient_education/english/PAT102691%2520Liver.pdf Liver Transplant Source: American Liver Foundation http://www.liverfoundation.org/cgibin/dbs/articles.cgi?db=articles&uid=default&ID=1016&view_records=1

•

Coping Organ Transplantation: Coping with Waiting Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01150

•

Specific Conditions/Aspects About Organ Allocation: Matching Organs Source: United Network for Organ Sharing http://www.transplantliving.org/beforethetransplant/allocation/matchingOrgans. aspx About Organ Allocation: Waiting for an Organ Source: United Network for Organ Sharing http://www.transplantliving.org/beforethetransplant/allocation/waitingForOrga n.aspx

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Financing a Transplant Source: United Network for Organ Sharing http://www.transplantliving.org/beforethetransplant/finance/finance.aspx Getting on the List Source: United Network for Organ Sharing http://www.transplantliving.org/beforethetransplant/list/list.aspx Living Donor Transplantation Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.org/livertransplant-rst/ Selecting a Hospital Source: United Network for Organ Sharing http://www.transplantliving.org/beforethetransplant/hospital/hospital.aspx Supressing the Immune System for Organ Transplants Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZROAD2NAC &sub_cat=396 U.S. Liver Transplant Programs Accept Patients With History of Alcoholism, Drug Addiction Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZSKPTMOJC &sub_cat=627 •

Children Liver Transplantation In Children Source: Children's Liver Association for Support Services http://www.classkids.org/library/childtx.htm Pediatric Liver and Transplant Questions Source: Children's Liver Association for Support Services http://www.classkids.org/library/classqa.htm When Will Your Child Need a Transplant? Source: Children's Liver Association for Support Services http://www.classkids.org/library/when.htm

•

From the National Institutes of Health What I Need to Know about Liver Transplantation Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/livertransplant_ez/index.htm

•

Latest News Brewing Hope for Transplants Source: 02/24/2004, New York Times Syndicate http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_16283 .html

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Law and Policy Liver Policy Outcomes Encouraging at Six Months; Some Adjustments Recommended Source: United Network for Organ Sharing http://www.unos.org/news/newsDetail.asp?id=227

•

Organizations American Liver Foundation http://www.liverfoundation.org/ Children's Liver Association for Support Services http://www.classkids.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/ Scientific Registry of Transplant Recipients http://www.ustransplant.org/index.html

•

Research Immune Tolerance: Improving Transplantation Success Source: National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/publications/discovery/immune.htm Pretreatment Increases Liver Transplant Survival in Rats Source: National Institute on Alcohol Abuse and Alcoholism http://www.nih.gov/news/pr/jun2003/niaaa-30.htm

•

Statistics About Transplants: Fast Facts Source: Scientific Registry of Transplant Recipients http://www.ustransplant.org/facts.html Organ Facts Source: United Network for Organ Sharing http://www.transplantliving.org/OrganFacts/default.aspx

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.

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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 liver transplant. 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: •

Liver Transplantation Source: Toronto, Ontario: Canadian Liver Foundation. 2000. 4 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: A liver transplant is a life-giving operation that replaces a diseased liver with either a whole or portion of a healthy, donated liver. Livers are donated, either from individuals who are brain dead or from a living donor such as a relative or close friend. This brochure describes liver transplantation. Written in a question and answer format, the brochure discusses the diseases that are most commonly treated by liver transplant, patient selection considerations (patients with liver cancer, patients with alcohol-related liver disease), at what stage transplantation becomes appropriate, risk factors, success rates, postoperative care, the side effects of the anti-rejection medications, rejection, living liver donation, lifestyle changes after a liver transplantation, and problems with recurrence of the original disease in the transplanted liver. The brochure concludes with the contact information for the Canadian Liver Foundation (www.liver.ca).

•

Facts on Liver Transplantation Source: Cedar Grove, NJ: American Liver Foundation. 2000. [4 p.]. Contact: Available from American Liver Foundation. Information and Distribution Center, 1425 Pompton Avenue, Suite 3, Cedar Grove, NJ 07009-1000. (800) GO-LIVER, ext. 234 or (888) HEP-ABC. Fax (973) 256-3214. E-mail: [email protected]. Website: www.liverfoundation.org. PRICE: $0.75 for single copy; bulk orders available; plus shipping and handling. Summary: Many diseases are capable of interfering with the liver's functions sufficiently to threaten the life of the patient; many of these diseases are potentially treatable by liver transplantation. This brochure answers 26 commonly asked questions about liver transplantation. Cirrhosis, the death of liver cells due to a variety of causes, is one of the most common reasons for liver transplantation in adults. In children, the disease most often treated by liver transplantation is biliary atresia, a failure of the bile ducts to develop normally to drain bile from the liver. Most cancers of the liver begin somewhere else in the body and spread to the liver; these are not curable with a liver transplant. Before surgery, the risks are mainly the development of some acute complication of the disease that might render the patient unacceptable for surgery. With transplantation, there are risks common to all forms of major surgery, as well as technical difficulties in removing the diseased liver and implanting the donor liver. Immediately after surgery, bleeding, poor function of the grafted liver, and infections are major risks. The brochure describes immediate postoperative and acute recovery, as well as long term recovery, including concerns regarding rejection of the transplanted organ. All the drugs used to

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prevent rejection increase the person's susceptibility to infections (and possibly to the development of tumors). Routine follow up consists of monthly blood tests, measuring blood pressure by a local physician, and annual or semi-annual checkups at the transplant center. Most patients are able to return to a normal or near normal existence 6 to 12 months after a successful liver transplant. The brochure includes a discussion of organ donation and costs. The brochure concludes with a description of the American Liver Foundation (ALF) and its activities and contact information. •

What I Need to Know About Liver Transplantation Source: Bethesda, MD: National Digestive Disease Information Clearinghouse (NDDIC), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health. 2003. 24 p. Contact: Available from National Digestive Diseases Information Clearinghouse (NDDIC). 2 Information Way, Bethesda, MD 20892-3570. (301) 654-3810. Fax (301) 9078906. E-mail: [email protected]. PRICE: Single copy free; bulk copies available. Summary: This booklet explains liver transplantation in clear, nontechnical language. Topics include the role of the liver, the signs of liver problems, a description of liver transplantation, the waiting period to get a new liver, where donated livers come from, what one can expect in the hospital before and after the transplant, rejection and how it can be treated, other problems that can damage the transplant, postoperative care, recovery time at home, and daily activities, including work, diet, exercise, and sexuality. The booklet includes simple line drawings to illustrate the concepts discussed. A glossary of terms is included, as is a list of three resource organizations that provide readers with additional information. The booklet concludes with a brief description of the National Digestive Diseases Information Clearinghouse (NDDIC), an informational services of the National Institutes of Health. 10 figures.

•

Liver Transplant Fund Source: Cedar Grove, NJ: American Liver Foundation. 199x. 2 p. Contact: Available from American Liver Foundation. 1425 Pompton Avenue, Cedar Grove, NJ 07009. (201) 256-2550 or (800) 223-0179. PRICE: $0.50. Summary: This brochure describes the Liver Transplant Fund, established by the American Liver Foundation to assist patients and families in obtaining the money for liver transplantation. The brochure discusses how the Fund makes it easier to raise money, how contributions are handled, allowable expenses for the funding, the procedures for paying bills or obtaining reimbursement, how shortfalls or surpluses of available money are handled by the Fund, and the fact that the Foundation doesn't assess any charge for handling the Fund. Contact information for the American Liver Foundation is included.

•

Biliary Atresia and Liver Transplant Network Source: Staten Island, NY: Biliary Atresia and Liver Transplant Network. 1995. 2 p. Contact: Available from Biliary Atresia and Liver Transplant Network. 3835 Richmond Avenue, Box 190, Staten Island, NY 10312. (718) 987-6200. Fax (718) 987-6200. E-mail [email protected]. PRICE: Single copy free. Summary: This brochure describes the Biliary Atresia and Liver Transplant (BALT) Network, a nonprofit organization that provides a support network for families of

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children born with biliary atresia. The brochure describes the origin of the organization; the activities of the group; BALT services, including parent matching, the BALT library, resources, support team, the Spanish division, an Internet connection, a baby formula network, the Tree House club, the twin registry, and Angels Above Us, a bereavement support group; the goals of the BALT organization; and funding considerations. The brochure encourages readers to support the BALT organization with financial contributions. •

Liver Transplant Source: in Kerestes-Smith, J.; Chua, G.; Sullivan, K. Guidelines for Nutritional Care. Ann Arbor, MI: Food and Nutrition Services, University of Michigan Medical Center. 1995. Chapter 30, p. 30.1-30.4. Contact: Available from Guidelines for Nutritional Care. Food and Nutrition Services, 2C227-0056, University of Michigan Hospitals, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0056. (313) 936-5199. Fax (313) 936-5195. PRICE: $79.00 including shipping and handling (as of 1996). ISBN: 0964799405. Summary: This chapter on dietary recommendations for individuals with liver transplants is from a manual that outlines the impact nutrition has on promoting health and preventing and treating disease. The chapter divides the nutritional care of individuals with liver transplants into three phases: pretransplant, immediate posttransplant, and long-term posttransplant. Included are sections detailing indications for use, contraindications, a description of the diet including a brief physiological and/or biochemical rationale, guidelines for nutritional management, nutrient adequacy, ordering procedures, and references for both the health care providers and the layperson. The National Guideline Clearinghouse™

The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “liver transplant” (or synonyms). The following was recently posted: •

(1) Targeted tuberculin testing and treatment of latent tuberculosis infection Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2000 June 9 (addendum released 2003 August 8); 54 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4004&nbr=3134&a mp;string=liver+AND+transplants

•

2002 national guideline on the management of the viral hepatitides A, B, and C Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3454&nbr=2680&a mp;string=liver+AND+transplant

•

ACC/AHA guideline update on perioperative cardiovascular evaluation for noncardiac surgery: a report of the American College of Cardiology/American Heart

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Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperati Source: American College of Cardiology Foundation - Medical Specialty Society; 1996 March 15 (revised 2002); 58 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3149&nbr=2375&a mp;string=liver+AND+transplant •

ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evalua Source: American College of Cardiology Foundation - Medical Specialty Society; 1995 November 1 (revised 2001 Dec); 56 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3114&nbr=2340&a mp;string=liver+AND+transplant

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American Gastroenterological Association medical position statement: parenteral nutrition Source: American Gastroenterological Association - Medical Specialty Society; 2001 May 18; 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3056&nbr=2282&a mp;string=liver+AND+transplant

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American Gastroenterological Association medical position statement: short bowel syndrome and intestinal transplantation Source: American Gastroenterological Association - Medical Specialty Society; 2003 April; 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3795&nbr=3021&a mp;string=liver+AND+transplant

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An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia Source: American Society of Hematology - Medical Specialty Society; 1999 September 1; 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2363&nbr=1589&a mp;string=hepatic+AND+transplant

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ASHP therapeutic guidelines on antimicrobial prophylaxis in surgery Source: American Society of Health-System Pharmacists - Professional Association; 1999 September 15; 50 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2182&nbr=1408&a mp;string=liver+AND+transplant

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Chemotherapy and biotherapy: guidelines and recommendations for practice Source: Oncology Nursing Society - Professional Association; 2001; 226 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3209&nbr=2435&a mp;string=liver+AND+transplant

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Chronic hepatitis B Source: American Association for the Study of Liver Diseases - Private Nonprofit Research Organization; 2001 December; 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3446&nbr=2672&a mp;string=liver+AND+transplant

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Diagnosis and treatment of autoimmune hepatitis Source: American Association for the Study of Liver Diseases - Private Nonprofit Research Organization; 2002 August; 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3447&nbr=2673&a mp;string=liver+AND+transplant

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General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP) Source: American Academy of Family Physicians - Medical Specialty Society; 2002 February 8; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3180&nbr=2406&a mp;string=liver+AND+transplant

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Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients Source: American Society for Blood and Marrow Transplantation - Professional Association; 2000 October 20; 126 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2573&nbr=1799&a mp;string=liver+AND+transplant

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Hepatitis C. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3243&nbr=2469&a mp;string=liver+AND+transplant

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Lipids Source: National Committee on Cardiac Care (Singapore) - National Government Agency [Non-U.S.]; 2001 July; 52 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3075&nbr=2301&a mp;string=liver+AND+transplant

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Liver transplantation Source: American Association for the Study of Liver Diseases - Private Nonprofit Research Organization; 2000 January; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3449&nbr=2675&a mp;string=liver+AND+transplant

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Management of chronic kidney disease and pre-ESRD in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 2000 November; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3099&nbr=2325&a mp;string=liver+AND+transplant

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Management of hepatitis C: 2002 Source: National Institutes of Health (NIH) Consensus Development Panel on Management of Hepatitis C - Independent Expert Panel; 1997 March (revised 2002 August 26); 44 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3416&nbr=2642&a mp;string=liver+AND+transplant

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Management of primary biliary cirrhosis Source: American Association for the Study of Liver Diseases - Private Nonprofit Research Organization; 2000 April; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3445&nbr=2671&a mp;string=liver+AND+transplant

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Management of type 2 diabetes mellitus Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 March (revised 2002 Sep); 77 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3499&nbr=2725&a mp;string=liver+AND+transplant

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Massachusetts guidelines for adult diabetes care Source: Massachusetts Department of Public Health, Bureau of Family and Community Health, Diabetes Control Program - State/Local Government Agency [U.S.]; 1999 June (revised 2001 Jun); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3429&nbr=2655&a mp;string=liver+AND+transplants

•

National High Blood Pressure Education Program: Working Group report on high blood pressure in pregnancy Source: National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]; 1990 (revised 2000 Jul); 39 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1478&nbr=704&am p;string=liver+AND+transplant

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Practice guidelines for diseases caused by Source: Infectious Diseases Society of America - Medical Specialty Society; 2000 April; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2667&nbr=1893&a mp;string=hepatic+AND+transplant

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Practice guidelines for the treatment of candidiasis Source: Infectious Diseases Society of America - Medical Specialty Society; 2000 April; 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2670&nbr=1896&a mp;string=liver+AND+transplant

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Prevention of Hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP) Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1999 October 1; 39 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2139&nbr=1365&a mp;string=liver+AND+transplants

•

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Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2001 August 24; 56 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2931&nbr=2157&a mp;string=liver+AND+transplant

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Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Liver Transplantation Summary: Basic consumer information facts about this medical procedure which becomes necessary usually when disease makes the liver stop working. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2699 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 liver transplant. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

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

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

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

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

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

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

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to liver transplant. By consulting all of associations

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listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with liver transplant. 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 liver transplant. 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 “liver transplant” (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 “liver transplant”. 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 “liver transplant” (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 “liver transplant” (or a synonym) into the search box, and click “Submit Query.”

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179

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.22

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

22

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)23: •

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

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

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

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

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

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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

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California: Gateway Health Library (Sutter Gould Medical Foundation)

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

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

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

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

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

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

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

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

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

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

•

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

23

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

Finding Medical Libraries 181 •

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

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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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•

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

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

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

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

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

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

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

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

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

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

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

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

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

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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

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

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

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

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

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

Finding Medical Libraries 183 •

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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

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

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

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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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

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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on liver transplant: •

Basic Guidelines for Liver Transplant Liver transplant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003006.htm

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Signs & Symptoms for Liver Transplant Diarrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003126.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Jaundice Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003243.htm Problems breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm

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Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm •

Surgery and Procedures for Liver Transplant Heart transplant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003003.htm Kidney transplant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003005.htm

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Background Topics for Liver Transplant Bile Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002237.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Clot Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001124.htm Hepatic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002378.htm Kidney disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000457.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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LIVER TRANSPLANT 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] Ablation: The removal of an organ by surgery. [NIH] 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] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [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] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Actin: Essential component of the cell skeleton. [NIH] Acute Disease: Disease having a short and relatively severe course. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenocarcinoma: A malignant 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] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adoptive Transfer: Form of passive immunization where previously sensitized

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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] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Albuminuria: More than normal amounts of a protein called albumin in the urine. Albuminuria may be a sign of kidney disease. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Allergen: An antigenic substance capable of producing immediate-type hypersensitivity

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(allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] 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] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Ammonium Chloride: An acidifying agent that is used as an expectorant and a diuretic. [NIH]

Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but

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shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anastomosis: A procedure to connect healthy sections of tubular structures in the body after the diseased portion has been surgically removed. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anemic: Hypoxia due to reduction of the oxygen-carrying capacity of the blood as a result of a decrease in the total hemoglobin or an alteration of the hemoglobin constituents. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthesiology: A specialty concerned with the study of anesthetics and anesthesia. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angioedema: A vascular reaction involving the deep dermis or subcutaneous or submucal tissues, representing localized edema caused by dilatation and increased permeability of the capillaries, and characterized by development of giant wheals. [EU] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anomalies: Birth defects; abnormalities. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of

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which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsants: Drugs used to prevent seizures or reduce their severity. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. [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] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Antiviral Agents: Agents used in the prophylaxis or therapy of virus diseases. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. [NIH] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU]

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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] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Archaea: One of the three domains of life (the others being bacteria and Eucarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: 1) the presence of characteristic tRNAs and ribosomal RNAs; 2) the absence of peptidoglycan cell walls; 3) the presence of ether-linked lipids built from branched-chain subunits; and 4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least three kingdoms: crenarchaeota, euryarchaeota, and korarchaeota. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]

Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Aspartate: A synthetic amino acid. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [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] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] 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]

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Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autopsy: Postmortem examination of the body. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [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] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] 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] Barbiturates: A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are medically important as sedatives and hypnotics (sedatives, barbiturate), as anesthetics, or as anticonvulsants. [NIH] 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] 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]

Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [NIH] Beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. EC 3.5.2.6. [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

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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] 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 Stricture: A narrowing of the biliary tract from scar tissue. The scar tissue may result from injury, disease, pancreatitis, infection, or gallstones. [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] 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] Biopterin: A natural product that has been considered as a growth factor for some insects. [NIH]

Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blast phase: The phase of chronic myelogenous leukemia in which the number of immature, abnormal white blood cells in the bone marrow and blood is extremely high. Also called blast crisis. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Viscosity: The internal resistance of the blood to shear forces. The in vitro measure of whole blood viscosity is of limited clinical utility because it bears little relationship to the actual viscosity within the circulation, but an increase in the viscosity of circulating blood

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can contribute to morbidity in patients suffering from disorders such as sickle cell anemia and polycythemia. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachiocephalic Veins: Large veins on either side of the root of the neck formed by the junction of the internal jugular and subclavian veins. They drain blood from the head, neck, and upper extremities, and unite to form the superior vena cava. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Bronchoalveolar Lavage Fluid: Fluid obtained by washout of the alveolar compartment of the lung. It is used to assess biochemical and inflammatory changes in and effects of therapy on the interstitial lung tissue. [NIH] Bupivacaine: A widely used local anesthetic agent. [NIH] Busulfan: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH]

Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cadaver: A dead body, usually a human body. [NIH] Caesarean section: A surgical incision through the abdominal and uterine walls in order to deliver a baby. [NIH] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of

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phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]

Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrates: The largest class of organic compounds, including starches, glycogens, cellulose, gums, and simple sugars. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. [NIH] 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] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [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] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the

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heart and lungs. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catalyse: To speed up a chemical reaction. [EU] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cefotaxime: Semisynthetic broad-spectrum cephalosporin. [NIH] Ceftizoxime: A semisynthetic cephalosporin antibiotic which can be administered intravenously or by suppository. The drug is highly resistant to a broad spectrum of betalactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative organisms. It has few side effects and is reported to be safe and effective in aged patients and in patients with hematologic disorders. [NIH] Ceftriaxone: Broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to usually inaccessible infections, including those involving the meninges, eyes, inner ears, and urinary tract. [NIH] Celiac Artery: The arterial trunk that arises from the abdominal aorta and after a short course divides into the left gastric, common hepatic and splenic arteries. [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

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metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell 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 Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemical Warfare Agents: Chemicals that are used to cause the disturbance, disease, or death of humans during war. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve

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gallstones. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Choleretic: A choleretic agent. [EU] 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] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Aberrations: Deviations from the normal number or structure of chromosomes, not necessarily associated with disease. [NIH] Chromosome Painting: A technique for visualizing chromosome aberrations using fluorescently labeled DNA probes which are hybridized to chromosomal DNA. Multiple fluorochromes may be attached to the probes. Upon hybridization, this produces a multicolored, or painted, effect with a unique color at each site of hybridization. This technique may also be used to identify cross-species homology by labeling probes from one species for hybridization with chromosomes from another species. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [NIH] Chronic myelogenous leukemia: CML. A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myeloid leukemia or chronic granulocytic leukemia. [NIH] Chronic phase: Refers to the early stages of chronic myelogenous leukemia or chronic lymphocytic leukemia. The number of mature and immature abnormal white blood cells in the bone marrow and blood is higher than normal, but lower than in the accelerated or blast phase. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

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Clinical Protocols: Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy. [NIH] Clinical series: A case series in which the patients receive treatment in a clinic or other medical facility. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] 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] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2.

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Abnormal falling in of the walls of any part of organ. [EU] 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 leaves the body through the anus. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [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] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [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] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a

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fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid

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leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] 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] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Creatinine clearance: A test that measures how efficiently the kidneys remove creatinine and other wastes from the blood. Low creatinine clearance indicates impaired kidney function. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] 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] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH]

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Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [NIH] Daclizumab: A monoclonal antibody that is being studied for treatment of adult T-cell leukemia. Also called dacliximab. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [NIH] 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] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in

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common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Dietetics: The study and regulation of the diet. [NIH] Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [NIH]

Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] 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] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissection: Cutting up of an organism for study. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] 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]

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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 Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] 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] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU]

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Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxemia: A condition characterized by the presence of endotoxins in the blood. If endotoxemia is the result of gram-negative rod-shaped bacteria, shock may occur. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enteral Nutrition: Nutritional support given via the alimentary canal or any route connected to the gastrointestinal system (i.e., the enteral route). This includes oral feeding, sip feeding, and tube feeding using nasogastric, gastrostomy, and jejunostomy tubes. [NIH] 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] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers:

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1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] 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] 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] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] 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] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excrete: To get rid of waste from the body. [NIH]

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Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expectorant: 1. Promoting the ejection, by spitting, of mucus or other fluids from the lungs and trachea. 2. An agent that promotes the ejection of mucus or exudate from the lungs, bronchi, and trachea; sometimes extended to all remedies that quiet cough (antitussives). [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, 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] Extracorporeal: Situated or occurring outside the body. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] 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] Fatty Liver: The buildup of fat in liver cells. The most common cause is alcoholism. Other causes include obesity, diabetes, and pregnancy. Also called steatosis. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolysis: The natural enzymatic dissolution of fibrin. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or

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between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [NIH] Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]

Forearm: The part between the elbow and the wrist. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [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

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of free radical damage is being actively investigated. [NIH] Fulminant Hepatic Failure: Liver failure that occurs suddenly in a previously healthy person. The most common causes of FHF are acute hepatitis, acetaminophen overdose, and liver damage from prescription drugs. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Game Theory: Theoretical construct used in applied mathematics to analyze certain situations in which there is an interplay between parties that may have similar, opposed, or mixed interests. In a typical game, decision-making "players," who each have their own goals, try to gain advantage over the other parties by anticipating each other's decisions; the game is finally resolved as a consequence of the players' decisions. [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] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

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] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional

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support or gastrointestinal compression. [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 Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] 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] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] 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

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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] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonadal: Pertaining to a gonad. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Gram-Positive Cocci: Coccus-shaped bacteria that retain the crystal violet stain when treated by Gram's method. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its

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earliest stage to maturity. [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] Haemolysis: Disruption of the integrity of the red cell membrane causing release of haemoglobin. Haemolysis may be caused by bacterial haemolysins, by antibodies that cause complement-dependent lysis, by placing red cells in a hyptonic solution, or by defects in the red cell membrane. [EU] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Policy: Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodilution: Reduction of blood viscosity usually by the addition of cell free solutions.

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Used clinically l) in states of impaired microcirculation, 2) for replacement of intraoperative blood loss without homologous blood transfusion, and 3) in cardiopulmonary bypass and hypothermia. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemofiltration: Extracorporeal ultrafiltration technique without hemodialysis for treatment of fluid overload and electrolyte disturbances affecting renal, cardiac, or pulmonary function. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [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] Hepatic: Refers to the liver. [NIH] Hepatic Artery: A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatic Veins: Veins which drain the liver. [NIH] Hepatic Veno-Occlusive Disease: Blockage of the small- or medium-sized hepatic veins due to nonthrombotic subendothelial edema which may progress to fibrosis. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatitis Viruses: Any of the viruses that cause inflammation of the liver. They include both DNA and RNA viruses as well viruses from humans and animals. [NIH] Hepatoblastoma: A type of liver tumor that occurs in infants and children. [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.

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[NIH]

Hepatomegaly: Enlargement of the liver. [NIH] Hepatorenal Syndrome: Renal failure in those with liver disease, usually liver cirrhosis or obstructive jaundice. Historically called Heyd disease, urohepatic syndrome, or bile nephrosis. [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] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

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] 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] Hospital Charges: The prices a hospital sets for its services. Hospital costs (the direct and indirect expenses incurred by the hospital in providing the services) are one factor in the determination of hospital charges. Other factors may include, for example, profits, competition, and the necessity of recouping the costs of uncompensated care. [NIH] Host: Any animal that receives a transplanted graft. [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] 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]

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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] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [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] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypersplenism: Condition characterized by splenomegaly, some reduction in the number of circulating blood cells in the presence of a normal or hyperactive bone marrow, and the potential for reversal by splenectomy. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertension, Renal: Hypertension due to renal diseases, especially chronic parenchymal disease. Hypertension as a result of compression or obstruction of the renal artery or its branches is hypertension, renovascular. [NIH] Hypertension, Renovascular: Hypertension due to compression or obstruction of the renal artery or its branches. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] 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] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Ileum: The lower end of the small intestine. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH]

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Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. [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] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Immunotoxins: Semisynthetic conjugates of various toxic molecules, including radioactive isotopes and bacterial or plant toxins, with specific immune substances such as immunoglobulins, monoclonal antibodies, and antigens. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect. [NIH]

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Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] 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] Incidental: 1. Small and relatively unimportant, minor; 2. Accompanying, but not a major part of something; 3. (To something) Liable to occur because of something or in connection with something (said of risks, responsibilities, .) [EU] Incision: A cut made in the body during surgery. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indocyanine Green: A tricarbocyanine dye that is used diagnostically in liver function tests and to determine blood volume and cardiac output. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Induction therapy: Treatment designed to be used as a first step toward shrinking the cancer and in evaluating response to drugs and other agents. Induction therapy is followed by additional therapy to eliminate whatever cancer remains. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infectious Mononucleosis: A common, acute infection usually caused by the Epstein-Barr virus (Human herpesvirus 4). There is an increase in mononuclear white blood cells and other atypical lymphocytes, generalized lymphadenopathy, splenomegaly, and occasionally hepatomegaly with hepatitis. [NIH] Inferior vena cava: A large vein that empties into the heart. It carries blood from the legs and feet, and from organs in the abdomen and pelvis. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] 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] Information Systems: Integrated set of files, procedures, and equipment for the storage, manipulation, and retrieval of information. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical

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and surgical treatment. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inosine Monophosphate: Inosine 5'-Monophosphate. A purine nucleotide which has hypoxanthine as the base and one phosphate group esterified to the sugar moiety. [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] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

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] 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] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU]

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Intracellular: Inside a cell. [NIH] Intrahepatic: Within the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

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] Islet: Cell producing insulin in pancreas. [NIH] Isoelectric: Separation of amphoteric substances, dissolved in water, based on their isoelectric behavior. The amphoteric substances are a mixture of proteins to be separated and of auxiliary "carrier ampholytes". [NIH] Isoelectric Point: The pH in solutions of proteins and related compounds at which the dipolar ions are at a maximum. [NIH] Isoenzymes: One of various structurally related forms of an enzyme, each having the same mechanism but with differing chemical, physical, or immunological characteristics. [NIH] Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [NIH] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [EU] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Jejunoileal Bypass: A surgical procedure consisting of the anastomosis of the proximal part of the jejunum to the distal portion of the ileum, so as to bypass the nutrient-absorptive segment of the small intestine, to treat morbid obesity. [NIH] Jejunostomy: Surgical formation of an opening through the abdominal wall into the jejunum, usually for enteral hyperalimentation. [NIH] Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] 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] Keratitis: Inflammation of the cornea. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH]

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Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lacerations: Torn, ragged, mangled wounds. [NIH] Lactobacillus: A genus of gram-positive, microaerophilic, rod-shaped bacteria occurring widely in nature. Its species are also part of the many normal flora of the mouth, intestinal tract, and vagina of many mammals, including humans. Pathogenicity from this genus is rare. [NIH] Lactulose: A mild laxative. [NIH] Lamivudine: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented

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and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Length of Stay: The period of confinement of a patient to a hospital or other health facility. [NIH]

Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukoplakia: A white patch that may develop on mucous membranes such as the cheek, gums, or tongue and may become cancerous. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [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 cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]

Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Regeneration: Repair or renewal of hepatic tissue. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Living Donors: Non-cadaveric providers of organs for transplant to related or non-related recipients. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability,

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requiring periodic, intermittent, or continuous care. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphadenopathy: Disease or swelling of the lymph nodes. [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] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] 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] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lymphoproliferative Disorders: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malabsorption syndrome: A group of symptoms such as gas, bloating, abdominal pain, and diarrhea resulting from the body's inability to properly absorb nutrients. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

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] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of

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the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical 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] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesoderm: The middle germ layer of the embryo. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] 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

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inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] 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] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH]

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Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Motility: The ability to move spontaneously. [EU] Mouth Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter Studies: Controlled studies which are planned and carried out by several cooperating institutions to assess certain variables and outcomes in specific patient populations, for example, a multicenter study of congenital anomalies in children. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Multigene Family: The progeny of a single open-pollinated parent or of a single cross between two individuals. [NIH] Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Mupirocin: A topically used antibiotic from a strain of Pseudomonas fluorescens. It has shown excellent activity against gram-positive staphylococci and streptococci. The antibiotic is used primarily for the treatment of primary and secondary skin disorders, nasal infections, and wound healing. [NIH] Mutism: Inability or refusal to speak. [EU] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration,

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sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]

Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [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] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasogastric: The process of passing a small, flexible plastic tube through the nose or mouth into the stomach or small intestine. [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] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neopterin: A pteridine derivative present in body fluids; elevated levels result from immune system activation, malignant disease, allograft rejection, and viral infections. (From Stedman, 26th ed) Neopterin also serves as a precursor in the biosynthesis of biopterin. [NIH] Neoral: Drug that prevents transplant rejections. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon,

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and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [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]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] 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] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutrition Assessment: Evaluation and measurement of nutritional variables in order to assess the level of nutrition or the nutritional status of the individual. Nutrition surveys may be used in making the assessment. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH]

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Omentum: A fold of the peritoneum (the thin tissue that lines the abdomen) that surrounds the stomach and other organs in the abdomen. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Organ Preservation: The process by which organs are kept viable outside of the organism from which they were removed (i.e., kept from decay by means of a chemical agent, cooling, or a fluid substitute that mimics the natural state within the organism). [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Ornidazole: A nitroimidazole antiprotozoal agent used in ameba and trichomonas infections. It is partially plasma-bound and also has radiation-sensitizing action. [NIH] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Ornithine Decarboxylase: A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated Sadenosylmethionine to form spermidine. EC 4.1.1.17. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] 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] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of

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what is normally used. [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]

Oximetry: The determination of oxygen-hemoglobin saturation of blood either by withdrawing a sample and passing it through a classical photoelectric oximeter or by electrodes attached to some translucent part of the body like finger, earlobe, or skin fold. It includes non-invasive oxygen monitoring by pulse oximetry. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreas Transplant: A surgical procedure that involves replacing the pancreas of a person who has diabetes with a healthy pancreas that can make insulin. The healthy pancreas comes from a donor who has just died or from a living relative. A person can donate half a pancreas and still live normally. [NIH] Pancreas Transplantation: The transference of a pancreas from one human or animal to another. [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] Paradoxical: Occurring at variance with the normal rule. [EU] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU]

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Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] 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]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pediatric Gastroenterologist: A doctor who treats children with digestive diseases. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Phallic: Pertaining to the phallus, or penis. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotypes: An organism as observed, i. e. as judged by its visually perceptible characters resulting from the interaction of its genotype with the environment. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH]

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Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] 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] Pilot study: The initial study examining a new method or treatment. [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] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] 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]

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Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] 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 Pressure: The venous pressure measured in the portal vein. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Portography: Examination of the portal circulation by the use of X-ray films after injection of radiopaque material. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery. [NIH] Postoperative Period: The period following a surgical operation. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis,

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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] Preceptorship: Practical experience in medical and health-related services that occurs as part of an educational program wherein the professionally-trained student works outside the academic environment under the supervision of an established professional in the particular field. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Preoperative: Preceding an operation. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] 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] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] 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] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH]

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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] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propofol: A widely used anesthetic. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein 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]

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Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Prothrombin Time: Measurement of clotting time of plasma recalcified in the presence of excess tissue thromboplastin. Factors measured are fibrinogen, prothrombin, and factors V, VII, and X. It is used for monitoring anticoagulant therapy with coumarins. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] 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] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] 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] Psychometrics: Assessment of psychological variables by the application of mathematical procedures. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [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] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of

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pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] 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] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH]

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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] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [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] Reinfection: A second infection by the same pathogenic agent, or a second infection of an organ such as the kidney by a different pathogenic agent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal Artery: A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. [NIH] Renal Dialysis: Removal of certain elements from the blood based on the difference in their rates of diffusion through a semipermeable membrane. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reoperation: A repeat operation for the same condition in the same patient. It includes reoperation for reexamination, reoperation for disease progression or recurrence, or reoperation following operative failure. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Respirators: These enable the wearer to breathe in atmospheres polluted by dust, poisonous vapors, smoke, etc., and are therefore used in certain industries or in warfare; they consist essentially of a mask, a metal frame with outlet and inlet valves, and a socket. [NIH]

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Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols. [NIH] Rhabdomyosarcoma: A malignant tumor of muscle tissue. [NIH] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] Ribonucleoside Diphosphate Reductase: An enzyme of the oxidoreductase class that catalyzes the formation of 2'-deoxyribonucleotides from the corresponding ribonucleotides using NADPH as the ultimate electron donor. The deoxyribonucleoside diphosphates are used in DNA synthesis. (From Dorland, 27th ed) EC 1.17.4.1. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Rod: A reception for vision, located in the retina. [NIH] 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] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid

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or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [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] Screening: Checking for disease when there are no symptoms. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedatives, Barbiturate: Those derivatives of barbituric or thiobarbituric acid that are used as hypnotics or sedatives. The structural class of all such derivatives, regardless of use, is barbiturates. [NIH] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septicaemia: A term originally used to denote a putrefactive process in the body, but now

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usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Short Bowel Syndrome: A malabsorption syndrome resulting from extensive operative resection of small bowel. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin graft: Skin that is moved from one part of the body to another. [NIH] Skin test: A test for an immune response to a compound by placing it on or under the skin. [NIH]

Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH]

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Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [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] Splanchnic Circulation: The circulation of blood through the vessels supplying the abdominal viscera. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH]

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Splenectomy: An operation to remove the spleen. [NIH] Splenic Artery: The largest branch of the celiac trunk with distribution to the spleen, pancreas, stomach and greater omentum. [NIH] Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Splint: A rigid appliance used for the immobilization of a part or for the correction of deformity. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Steatosis: Fatty degeneration. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Sterile: Unable to produce children. [NIH] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [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] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may

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be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Superior vena cava: Vein which returns blood from the head and neck, upper limbs, and thorax. It is formed by the union of the two brachiocephalic veins. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppository: A medicated mass adapted for introduction into the rectal, vaginal, or urethral orifice of the body, suppository bases are solid at room temperature but melt or dissolve at body temperature. Commonly used bases are cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, polyethylene glycols of various molecular weights, and fatty acid esters of polyethylene glycol. [EU] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Surgical Instruments: Hand-held tools or implements used by health professionals for the performance of surgical tasks. [NIH] Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or

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chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Teichoic Acids: Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] 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] Thorax: A part of the trunk between the neck and the abdomen; 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] Thrombocytopenia: A decrease in the number of blood platelets. [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] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] 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]

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Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonicity: The normal state of muscular tension. [NIH] Topical: On the surface of the body. [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] Toxoplasma: A genus of protozoa parasitic to birds and mammals. T. gondii is one of the most common infectious pathogenic animal parasites of man. [NIH] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]

Traction: The act of pulling. [NIH] Transaminase: Aminotransferase (= a subclass of enzymes of the transferase class that catalyse the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally 2-keto acid). Most of these enzymes are pyridoxal-phosphate-proteins. [EU]

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] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] 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] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] 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]

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Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trichomonas: A genus of parasitic flagellate protozoans distinguished by the presence of four anterior flagella, an undulating membrane, and a trailing flagellum. [NIH] Trichomonas Infections: Infections in birds and mammals produced by various species of Trichomonas. [NIH] Trimethoprim-sulfamethoxazole: An antibiotic drug used to treat infection and prevent pneumocystis carinii pneumonia. [NIH] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculin: A sterile liquid containing the growth products of, or specific substances extracted from, the tubercle bacillus; used in various forms in the diagnosis of tuberculosis. [NIH]

Tuberculin Test: One of several skin tests to determine past or present tuberculosis infection. A purified protein derivative of the tubercle bacilli, called tuberculin, is introduced into the skin by scratch, puncture, or interdermal injection. [NIH] Tuberculoma: A tumor-like mass resulting from the enlargement of a tuberculous lesion. [NIH]

Tuberculostatic: Inhibiting the growth of Mycobacterium tuberculosis. [EU] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [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

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condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultrafiltration: The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in dialysis separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as hemofiltration or hemodiafiltration (if combined with hemodialysis). [NIH] Uncompensated Care: Medical services for which no payment is received. Uncompensated care includes charity care and bad debts. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Unresectable: Unable to be surgically removed. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] 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] 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] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Valganciclovir: An antiviral agent that is being studied as a treatment for AIDS-related cytomegalovirus. It is converted in the body to ganciclovir. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Varicella: Chicken pox. [EU] Varices: Stretched veins such as those that form in the esophagus from cirrhosis. [NIH]

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Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Vena: A vessel conducting blood from the capillary bed to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] 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] Virus Diseases: A general term for diseases produced by viruses. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] 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]

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Vivo: Outside of or removed from the body of a living organism. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [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]

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] 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] Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chainterminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [NIH] Zygote: The fertilized ovum. [NIH]

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INDEX A Abdomen, 146, 187, 195, 208, 219, 220, 223, 230, 232, 243, 244, 246 Abdominal, 69, 93, 106, 119, 187, 195, 197, 221, 224, 231, 232, 239, 243, 249 Abdominal Pain, 69, 187, 224, 232, 249 Ablation, 104, 187 Abscess, 64, 107, 187, 241 Acceptor, 187, 231, 247 Acetaminophen, 187, 211 Acetylcholine, 187, 229 Acetylcysteine, 117, 118, 187 Acidosis, 187, 222 Actin, 21, 187, 228 Acyclovir, 90, 93, 187, 211 Adaptability, 187, 198 Adenocarcinoma, 187, 215 Adenovirus, 39, 44, 187 Adolescence, 187, 232 Adoptive Transfer, 27, 37, 187 Adverse Effect, 4, 43, 188, 206, 242 Aerobic, 188, 197, 226 Affinity, 188, 243 Age of Onset, 188, 248 Alanine, 4, 134, 188 Albumin, 110, 188, 233 Albuminuria, 25, 188 Algorithms, 38, 188, 194 Alimentary, 188, 207, 231 Alkaline, 134, 187, 188, 189, 196 Alkaline Phosphatase, 134, 188 Alkaloid, 188, 200, 227 Alkylating Agents, 188, 195 Allergen, 188, 241 Allogeneic, 24, 39, 40, 134, 172, 189, 213 Allogeneic bone marrow transplantation, 172, 189 Allograft, 4, 5, 8, 12, 20, 23, 27, 28, 36, 42, 50, 51, 55, 63, 80, 121, 125, 134, 189, 228 Alternative medicine, 150, 189 Amino Acid Sequence, 189, 190 Ammonia, 29, 146, 189, 249 Ammonium Chloride, 29, 189 Amphetamines, 189, 200 Ampulla, 189, 199, 207 Anaerobic, 189, 197 Anaesthesia, 82, 189, 219 Anal, 53, 189, 210, 223, 227

Analgesic, 187, 189, 200, 227, 230 Analog, 55, 187, 189, 211, 222 Analogous, 189, 247 Anaphylatoxins, 189, 201 Anastomosis, 190, 221 Anatomical, 190, 199, 202, 205, 219 Anemia, 4, 61, 190, 195 Anemic, 65, 190 Anesthesia, 38, 83, 96, 100, 190, 207, 235 Anesthesiology, 57, 190 Anesthetics, 11, 190, 193, 208 Aneurysm, 73, 190, 250 Angioedema, 68, 190 Angiogenesis, 39, 190, 224 Angioplasty, 48, 190, 227 Angiotensinogen, 190, 239 Animal model, 7, 23, 25, 37, 46, 51, 190 Anions, 188, 190, 221, 242 Annealing, 190, 234 Anomalies, 190, 227 Antibacterial, 190, 221, 243, 249 Antibiotic, 11, 128, 190, 195, 197, 208, 227, 240, 243, 248 Antibiotic Prophylaxis, 11, 190 Antibodies, 34, 69, 84, 190, 191, 214, 215, 217, 224, 226, 233 Anticoagulant, 191, 236, 237 Anticonvulsants, 191, 193 Antifungal, 191, 210, 242 Antigen, 6, 39, 40, 41, 51, 52, 73, 79, 103, 132, 188, 191, 201, 204, 216, 217, 218, 219, 225, 241 Antigen-Antibody Complex, 191, 201 Antigen-presenting cell, 191, 204 Anti-infective, 4, 191 Anti-Infective Agents, 4, 191 Anti-inflammatory, 44, 187, 191, 212, 235 Antimetabolite, 187, 191, 225, 240 Antimicrobial, 13, 85, 87, 102, 110, 112, 172, 191 Antineoplastic, 188, 191, 203, 211, 217, 225, 242 Antioxidant, 44, 191 Antiviral, 12, 13, 25, 28, 32, 55, 60, 127, 187, 191, 211, 218, 220, 240, 249 Antiviral Agents, 13, 55, 191 Anuria, 191, 222 Anus, 189, 191, 195, 201, 238

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Anxiety, 22, 191 Anxiolytic, 11, 191 Apoptosis, 23, 40, 41, 116, 192, 197 Approximate, 45, 192 Aqueous, 192, 193, 204, 206 Arachidonic Acid, 192, 236 Archaea, 192, 226 Arginine, 21, 48, 116, 119, 189, 192, 229, 230, 238 Arterial, 48, 77, 106, 110, 192, 197, 217, 236, 246 Arteries, 192, 194, 197, 202, 226, 227 Arteriolar, 192, 195, 239 Arterioles, 192, 194, 196, 226 Arteriosus, 192, 237 Artery, 190, 192, 196, 202, 207, 227, 237, 239 Aspartate, 134, 192 Aspergillosis, 23, 79, 93, 107, 192 Assay, 23, 35, 50, 63, 192, 218, 240 Asymptomatic, 65, 96, 135, 192, 231 Attenuation, 41, 45, 192 Atypical, 69, 192, 219 Auditory, 72, 192, 208 Autoimmune disease, 192, 193 Autoimmune Hepatitis, 6, 173, 192 Autoimmunity, 61, 193 Autologous, 28, 126, 193 Autopsy, 69, 193 B Bacillus, 193, 248 Bacteremia, 11, 12, 193 Bactericidal, 193, 208 Bacteriophage, 193, 233, 247 Bacteriostatic, 193, 208 Bacterium, 193, 201 Barbiturates, 11, 193, 241 Base, 42, 43, 57, 61, 193, 204, 220, 221, 222, 246 Basophils, 193, 213, 223 Benign, 193, 214, 228, 251 Bereavement, 171, 193 Beta-Lactamases, 193, 197 Bile Acids, 61, 102, 193, 244 Bile Acids and Salts, 193 Bile duct, 55, 61, 132, 169, 194, 199, 211, 235 Biliary, 5, 9, 10, 25, 70, 71, 78, 91, 96, 102, 120, 132, 138, 169, 170, 194, 199, 231 Biliary Atresia, 169, 170, 194 Biliary Stricture, 96, 194 Biliary Tract, 194, 231

Bilirubin, 13, 29, 62, 134, 188, 194, 211 Biochemical, 4, 13, 23, 30, 36, 37, 134, 171, 191, 194, 195, 210, 222 Biological response modifier, 194, 220 Biomarkers, 51, 53, 194 Biopsy, 18, 37, 50, 86, 90, 194 Biopterin, 194, 228 Biotechnology, 62, 66, 150, 161, 194 Bladder, 194, 201, 236, 249 Blast phase, 194, 199 Blood Coagulation, 194, 196, 240, 246 Blood Platelets, 194, 246 Blood pressure, 8, 47, 69, 71, 170, 175, 194, 197, 217, 226, 234, 243 Blood transfusion, 5, 60, 146, 194, 215 Blood Viscosity, 194, 214 Blood Volume, 195, 219 Body Fluids, 146, 194, 195, 206, 210, 228, 229, 243, 248 Bone Marrow, 39, 51, 52, 194, 195, 199, 203, 208, 212, 213, 217, 218, 224, 227, 243, 245 Bone Marrow Transplantation, 195 Bowel, 79, 189, 195, 205, 220, 223, 232, 242, 244, 249 Bowel Movement, 195, 205, 244 Brachiocephalic Veins, 195, 245 Bradykinin, 195, 229, 233 Branch, 183, 195, 215, 224, 232, 237, 239, 243, 244, 246 Breakdown, 21, 195, 205, 211 Broad-spectrum, 195, 197 Bronchoalveolar Lavage, 24, 195 Bronchoalveolar Lavage Fluid, 24, 195 Bupivacaine, 195, 223 Busulfan, 172, 195 Bypass, 48, 67, 195, 221, 227 C Cadaver, 14, 17, 20, 195 Caesarean section, 72, 195 Calcineurin, 97, 105, 106, 117, 118, 120, 141, 195 Calcium, 117, 195, 196, 201, 208, 217, 224, 228, 237, 242 Calmodulin, 195, 196 Candidiasis, 49, 73, 127, 175, 196, 210 Candidosis, 196 Capillary, 195, 196, 212, 250 Capsules, 196, 212 Carbohydrates, 145, 196, 198 Carbon Dioxide, 196, 204, 210 Carcinogenesis, 30, 196

Index 255

Carcinogenic, 188, 196, 236, 244 Carcinogens, 196, 230, 251 Carcinoma, 49, 63, 126, 196 Cardiac, 34, 48, 51, 61, 69, 72, 133, 174, 196, 207, 208, 215, 219, 223, 228, 244 Cardiac Output, 196, 219 Cardiopulmonary, 196, 215 Cardiopulmonary Bypass, 196, 215 Cardiovascular, 4, 25, 46, 93, 141, 171, 197 Cardiovascular disease, 93, 141, 197 Case report, 56, 83, 94, 119, 197, 200 Case series, 18, 197, 200 Caspase, 23, 197 Catabolism, 120, 197 Catalyse, 197, 247 Catheter, 21, 197, 207 Catheterization, 190, 197, 227 Causal, 197, 215, 242 Causality, 36, 197 Cause of Death, 28, 29, 126, 146, 197 Cefotaxime, 64, 197 Ceftizoxime, 64, 197 Ceftriaxone, 63, 197 Celiac Artery, 197, 215 Cell Death, 23, 40, 41, 192, 197 Cell Differentiation, 41, 60, 198, 242 Cell Division, 193, 198, 226, 233 Cell membrane, 198, 204, 214, 221, 233 Cell motility, 198, 215 Cell proliferation, 198, 220, 242 Cell Respiration, 198, 226 Cell Size, 198, 210 Cellulose, 196, 198, 211, 233 Central Nervous System, 187, 188, 189, 195, 198, 200, 208, 211, 214, 227 Central Nervous System Infections, 198, 214 Cerebral, 45, 107, 198, 208 Cerebrovascular, 197, 198 Cerebrum, 198 Chemical Warfare, 198, 204 Chemical Warfare Agents, 198, 204 Chemoprevention, 30, 198 Chemotactic Factors, 198, 201 Chemotherapy, 24, 85, 87, 102, 110, 112, 173, 198 Chenodeoxycholic Acid, 198, 249 Chin, 199, 225 Cholangitis, 9, 199 Choleretic, 198, 199, 249 Cholestasis, 55, 73, 199

Cholesterol, 36, 73, 193, 199, 202, 211, 217, 244 Chromatin, 192, 199, 207 Chromosomal, 199, 233 Chromosome, 78, 199, 201, 223 Chromosome Aberrations, 199 Chromosome Painting, 78, 199 Chronic Disease, 146, 199 Chronic lymphocytic leukemia, 199 Chronic myelogenous leukemia, 194, 199 Chronic phase, 136, 172, 199 Chronic renal, 118, 199 Circadian, 48, 199 Clamp, 133, 199 Clinical Medicine, 199, 235 Clinical Protocols, 41, 200 Clinical series, 36, 200 Clinical study, 200, 202 Clone, 34, 47, 200 Cloning, 27, 33, 194, 200 Coagulation, 110, 142, 194, 200, 233 Coca, 200 Cocaine, 146, 200 Codeine, 11, 200, 230 Cofactor, 21, 200, 236, 246 Colchicine, 53, 200, 248 Colitis, 74, 200 Collagen, 189, 200, 209, 224, 233 Collapse, 195, 200 Colloidal, 188, 201, 242 Colon, 4, 200, 201, 222, 248 Combination Therapy, 55, 201 Complement, 38, 189, 201, 212, 214, 233, 241 Compliance, 13, 22, 30, 201 Computational Biology, 161, 201 Computer Simulation, 31, 201 Concomitant, 29, 56, 201 Conjugated, 193, 198, 201, 203 Conjugation, 132, 201 Connective Tissue, 195, 200, 202, 204, 209, 211, 241 Consciousness, 189, 202, 215, 237 Constipation, 202, 232 Constriction, 202, 221, 250 Constriction, Pathologic, 202, 250 Consultation, 25, 202 Consumption, 37, 46, 202, 229 Contamination, 202, 215, 216 Contraindications, ii, 10, 141, 151, 171, 202 Control group, 19, 202, 235 Controlled clinical trial, 60, 202

256

Liver Transplant

Controlled study, 73, 202 Conus, 202, 237 Cornea, 202, 221 Coronary, 197, 202, 226, 227 Coronary heart disease, 197, 202 Coronary Thrombosis, 202, 226, 227 Cortex, 202, 203, 208, 235, 239 Cortical, 202, 241 Corticosteroids, 116, 119, 202, 212, 235 Cortisol, 188, 203 Cortisone, 203, 235 Coumarins, 203, 237 Cranial, 203, 214 Craniocerebral Trauma, 203, 214 Creatinine, 13, 80, 203, 222 Creatinine clearance, 80, 203 Critical Care, 82, 84, 88, 203 Curative, 203, 246 Cutaneous, 196, 203 Cyclic, 196, 203, 214, 229, 236 Cytochrome, 56, 203 Cytokine, 27, 39, 51, 59, 61, 78, 116, 203, 242 Cytomegalovirus, 46, 63, 64, 75, 85, 90, 91, 97, 102, 103, 104, 108, 109, 203, 204, 211, 249 Cytomegalovirus Infections, 204, 211 Cytoplasm, 44, 132, 192, 193, 198, 204, 207, 213, 227, 240 Cytotoxic, 27, 28, 61, 125, 204, 218, 242 D Daclizumab, 109, 120, 121, 204 Data Collection, 10, 21, 42, 204 De novo, 70, 118, 204 Deamination, 204, 249 Decarboxylation, 204, 230, 238 Decontamination, 79, 148, 204 Degenerative, 202, 204, 215 Deletion, 23, 44, 192, 204 Delivery of Health Care, 204, 214 Denaturation, 204, 234 Dendrites, 204, 229 Dendritic, 40, 76, 204, 225 Dendritic cell, 40, 76, 204 Density, 204, 210 Dental Care, 49, 204 Depolarization, 204, 242 Dermis, 190, 204 Detoxification, 29, 38, 132, 204 Developmental Biology, 34, 43, 60, 204 Diabetes Mellitus, 4, 8, 119, 204, 213, 215 Diagnostic procedure, 16, 131, 150, 205

Dialyzer, 205, 214 Diarrhea, 120, 185, 205, 224 Diastolic, 205, 217 Dietetics, 143, 205 Dietitian, 145, 205 Digestion, 145, 146, 188, 193, 194, 195, 205, 220, 223, 244 Digestive system, 130, 205, 211, 227 Dilatation, 190, 205, 235, 250 Dilatation, Pathologic, 205, 250 Dilation, 195, 205, 250 Direct, iii, 34, 44, 153, 199, 205, 216, 234, 239 Discrete, 27, 49, 205 Disease Progression, 21, 35, 37, 50, 58, 205, 239, 250 Disinfectant, 205, 208 Disparity, 14, 16, 42, 93, 205 Disposition, 56, 205 Dissection, 42, 205 Distal, 205, 221, 237 Dopamine, 200, 205, 229, 232 Double-blind, 61, 116, 205, 206 Double-blinded, 61, 206 Drug Interactions, 11, 138, 154, 206 Drug Resistance, 32, 127, 206 Drug Tolerance, 206, 246 Drug Toxicity, 134, 206 Duct, 56, 61, 189, 197, 206, 209, 240, 244 Duodenum, 193, 206, 207, 215, 221, 244 E Ectopic, 44, 206 Edema, 45, 190, 206, 215, 227, 228 Effector, 27, 41, 187, 201, 206 Efficacy, 3, 17, 18, 19, 21, 36, 55, 58, 64, 71, 79, 87, 94, 120, 121, 206 Elective, 116, 206 Electrocoagulation, 200, 206 Electrolyte, 206, 210, 215, 222, 229, 234, 243 Embolism, 67, 206 Embryo, 198, 206, 219, 225 Empirical, 48, 67, 206 Emulsion, 206, 210 Encephalopathy, 24, 207 Endarterectomy, 190, 207 Endemic, 77, 207 Endocarditis, 196, 207 Endogenous, 61, 205, 207 Endoscope, 207 Endoscopic, 60, 80, 96, 207 Endoscopy, 60, 91, 96, 108, 207

Index 257

Endothelial cell, 39, 80, 134, 135, 207 Endothelium, 207, 229 Endothelium-derived, 207, 229 Endotoxemia, 21, 207 Endotoxin, 21, 43, 207, 248 End-stage renal, 94, 142, 199, 207 Enteral Nutrition, 119, 207 Environmental Health, 160, 162, 207 Enzymatic, 189, 196, 201, 207, 209, 234, 240 Eosinophils, 207, 213, 223 Epidemiological, 36, 55, 207 Epidermal, 207, 225, 251 Epidermis, 204, 207, 238 Epidural, 21, 208 Epigastric, 208, 231 Epinephrine, 205, 208, 229, 248 Epithelial, 29, 55, 60, 132, 187, 208, 215 Epithelial Cells, 55, 132, 208, 215 Erythrocytes, 190, 195, 208, 215, 241 Erythromycin, 105, 208 Erythropoietin, 4, 208 Escalation, 28, 208 Esophageal, 75, 208 Esophagitis, 89, 208 Esophagus, 60, 205, 208, 211, 244, 249 Ethanol, 5, 21, 44, 208 Etidronate, 117, 208 Evoked Potentials, 72, 208 Excitation, 189, 208, 210, 229 Excrete, 191, 208, 222 Exocrine, 60, 209, 231 Exogenous, 29, 207, 209, 248 Expectorant, 189, 209 Extracellular, 202, 209, 224, 243 Extracellular Matrix, 202, 209, 224 Extracellular Matrix Proteins, 209, 224 Extracorporeal, 93, 209, 215 Extravasation, 209, 214 Eye Infections, 187, 209 F Family Planning, 161, 209 Fat, 146, 192, 194, 195, 202, 209, 222, 223, 243 Fatigue, 135, 146, 209, 214 Fatty acids, 188, 209, 236 Fatty Liver, 43, 146, 209 Fetus, 208, 209, 218 Fibrin, 194, 209, 232, 246 Fibrinogen, 209, 233, 237, 246 Fibrinolysis, 5, 83, 209 Fibrosis, 4, 9, 37, 53, 55, 61, 78, 209, 215 Fistula, 91, 209

Fixation, 104, 210, 241 Flow Cytometry, 37, 70, 210 Fluconazole, 127, 210 Fluid Therapy, 210, 229 Fluorescence, 27, 210 Fluorescent Dyes, 210 Fold, 28, 46, 126, 210, 225, 230, 231 Follow-Up Studies, 25, 210 Forearm, 194, 210 Fovea, 210 Free Radicals, 43, 191, 210, 228 Fulminant Hepatic Failure, 7, 29, 35, 138, 211 Fungi, 191, 192, 201, 209, 211, 226, 246, 251 Fungus, 196, 211 G Gallbladder, 187, 194, 205, 211, 215 Gallstones, 194, 199, 211, 249 Game Theory, 50, 211 Gamma-interferon, 211, 220 Ganciclovir, 63, 65, 76, 85, 87, 99, 104, 109, 110, 148, 211, 249 Ganglia, 187, 211, 228 Gangrene, 86, 211 Gas, 86, 189, 196, 211, 216, 224, 229 Gastric, 88, 197, 211 Gastrin, 211, 216 Gastroenterologist, 128, 211 Gastrointestinal, 57, 80, 86, 91, 96, 110, 128, 140, 195, 207, 208, 211, 212, 244, 245, 248 Gastrointestinal tract, 140, 208, 211, 244, 248 Gastrostomy, 207, 211 Gene, 27, 36, 39, 45, 47, 59, 61, 68, 89, 125, 187, 194, 212, 230 Gene Expression, 27, 47, 59, 212 Gene Therapy, 27, 39, 45, 47, 125, 187, 212 Genetic Engineering, 194, 200, 212 Genetic Markers, 37, 212 Genetic testing, 212, 234 Genetics, 201, 212 Genotype, 4, 135, 212, 232 Gland, 203, 212, 231, 236, 241, 244, 246 Glomerular, 142, 212, 221, 222, 239 Glomerular Filtration Rate, 142, 212, 222 Glomeruli, 212 Glomerulonephritis, 142, 212 Glomerulus, 212 Glucocorticoid, 212, 235 Glucose, 4, 8, 87, 198, 204, 212, 213, 215, 220, 241

258

Liver Transplant

Glucose Intolerance, 4, 204, 212 Glucose tolerance, 213 Glucose Tolerance Test, 213 Glycine, 189, 193, 198, 213, 229 Glycogen, 145, 213 Glycoprotein, 75, 208, 209, 213, 227, 248 Gonadal, 213, 244 Gout, 200, 213 Governing Board, 213, 235 Grade, 24, 51, 213 Graft Rejection, 13, 23, 27, 49, 104, 132, 141, 213, 218 Graft Survival, 6, 17, 23, 29, 40, 45, 50, 57, 58, 91, 96, 213 Graft-versus-host disease, 68, 96, 121, 213, 227 Gram-negative, 88, 197, 207, 213 Gram-positive, 65, 197, 213, 222, 227, 244 Gram-Positive Cocci, 65, 213 Granulocytes, 213, 242, 251 Guanylate Cyclase, 214, 229 H Haemolysis, 132, 214 Half-Life, 197, 214 Headache, 4, 5, 214 Headache Disorders, 214 Health Care Costs, 151, 214 Health Education, 30, 145, 214 Health Expenditures, 214 Health Policy, 31, 38, 46, 60, 214 Health Services, 15, 31, 38, 204, 214 Heart attack, 4, 197, 214 Heart failure, 172, 214 Hematoma, 86, 214 Hematopoiesis, 61, 214 Hematopoietic Stem Cells, 51, 214 Heme, 194, 203, 214 Hemodialysis, 6, 11, 205, 214, 215, 222, 249 Hemodilution, 61, 214 Hemodynamics, 100, 142, 215 Hemofiltration, 105, 215, 249 Hemoglobin, 190, 208, 214, 215, 231 Hemoglobinopathies, 212, 215 Hemolysis, 78, 215 Hemorrhage, 203, 206, 214, 215, 228, 238, 245 Hepatic Artery, 70, 106, 134, 215 Hepatic Encephalopathy, 146, 215 Hepatic Veins, 215 Hepatic Veno-Occlusive Disease, 83, 215 Hepatitis A, 8, 35, 41, 96, 175, 215 Hepatitis Viruses, 35, 215

Hepatoblastoma, 107, 215 Hepatocellular, 6, 18, 19, 35, 46, 53, 59, 63, 86, 87, 95, 104, 108, 110, 120, 126, 132, 134, 215 Hepatocellular carcinoma, 18, 19, 35, 46, 53, 59, 86, 87, 104, 110, 120, 215 Hepatocyte, 14, 34, 35, 39, 42, 47, 120, 199, 215 Hepatocyte Growth Factor, 120, 215 Hepatology, 3, 5, 6, 20, 25, 66, 67, 83, 85, 89, 104, 111, 116, 117, 140, 215 Hepatomegaly, 216, 219 Hepatorenal Syndrome, 11, 119, 142, 216 Hepatovirus, 215, 216 Heredity, 212, 216 Herpes, 28, 125, 187, 216 Herpes virus, 28, 125, 216 Herpes Zoster, 216 Heterogeneity, 39, 42, 188, 216 Heterogenic, 216 Heterogenous, 132, 216 Histology, 6, 10, 19, 34, 61, 216 Homodimer, 132, 216 Homologous, 212, 215, 216, 241, 246 Hormone, 118, 203, 208, 211, 216, 220, 235, 242, 246 Hospital Charges, 151, 216 Host, 23, 28, 33, 35, 39, 40, 50, 58, 60, 87, 107, 128, 193, 196, 213, 216, 218, 249, 250 Humoral, 213, 216 Hybrid, 28, 200, 216 Hybridization, 199, 216 Hydrogen, 187, 193, 196, 204, 209, 216, 226, 231, 251 Hydrolysis, 193, 217, 232, 237 Hydrophobic, 61, 217 Hydroxyproline, 189, 200, 217 Hydroxyurea, 172, 217 Hypercalcemia, 208, 217 Hypercholesterolemia, 4, 217 Hyperlipidemia, 4, 46, 119, 139, 217 Hyperplasia, 108, 217 Hypersensitivity, 188, 217, 241 Hypersplenism, 5, 217 Hypertension, 4, 8, 13, 25, 36, 46, 47, 59, 71, 91, 105, 197, 214, 217, 234 Hypertension, Renal, 5, 217 Hypertension, Renovascular, 217 Hypertrophy, 69, 72, 217 Hypothermia, 65, 215, 217 Hypoxanthine, 217, 220 Hypoxemia, 110, 217

Index 259

Hypoxia, 134, 190, 217 I Id, 122, 166, 168, 171, 172, 173, 174, 175, 176, 182, 184, 217 Ileum, 217, 221 Immune function, 217, 218 Immune response, 18, 23, 28, 35, 37, 39, 41, 47, 58, 126, 134, 191, 192, 203, 213, 217, 218, 241, 242, 245, 249, 250 Immune Sera, 217, 218 Immune system, 51, 56, 127, 145, 191, 192, 193, 217, 218, 224, 228, 249, 251 Immune Tolerance, 41, 168, 218 Immunity, 28, 35, 41, 60, 80, 188, 218, 224, 247 Immunization, 12, 79, 138, 173, 175, 187, 218, 241 Immunoassay, 23, 79, 81, 99, 103, 132, 218 Immunocompromised, 5, 218 Immunodeficiency, 107, 218 Immunofluorescence, 78, 218 Immunoglobulin, 7, 63, 190, 218, 226 Immunologic, 35, 188, 198, 218 Immunology, 20, 25, 57, 58, 60, 68, 116, 188, 210, 218 Immunophilin, 196, 218 Immunosuppressant, 11, 30, 188, 218, 225, 242 Immunosuppressive Agents, 140, 218 Immunosuppressive therapy, 41, 141, 218 Immunotherapy, 28, 126, 188, 218 Immunotoxins, 27, 218 Impairment, 97, 105, 117, 134, 142, 146, 199, 209, 219, 225 In situ, 5, 27, 219 In vitro, 32, 33, 34, 37, 41, 194, 212, 219, 234, 240, 246 In vivo, 29, 33, 34, 35, 40, 41, 47, 132, 212, 219, 246 Incidental, 138, 219 Incision, 195, 219, 221 Indicative, 139, 219, 232, 250 Indocyanine Green, 81, 219 Induction, 24, 27, 30, 34, 41, 51, 99, 118, 119, 121, 219 Induction therapy, 121, 219 Infarction, 219, 239 Infectious Mononucleosis, 28, 219 Inferior vena cava, 133, 219 Infiltration, 39, 212, 219, 235 Information Systems, 31, 219 Informed Consent, 128, 219

Infusion, 40, 47, 48, 127, 220, 228, 247 Inner ear, 197, 220, 249 Inosine Monophosphate, 128, 220 Insecticides, 220, 251 Insight, 40, 220 Insulin, 36, 213, 220, 221, 222, 231, 248 Insulin-dependent diabetes mellitus, 220 Intensive Care, 7, 8, 83, 93, 220 Intercellular Adhesion Molecule-1, 52, 220 Interferon, 3, 21, 53, 66, 101, 116, 172, 211, 220 Interferon-alpha, 220 Interleukins, 218, 220 Intermittent, 210, 220, 224 Internal Medicine, 42, 54, 60, 61, 211, 220 Interstitial, 195, 220, 239 Intestinal, 21, 23, 60, 102, 172, 198, 213, 220, 222, 224 Intestine, 56, 60, 193, 195, 220, 222, 244 Intoxication, 220, 251 Intracellular, 27, 35, 39, 44, 60, 219, 221, 229, 234, 236, 242 Intrahepatic, 86, 221 Intramuscular, 221, 231 Intravenous, 8, 21, 72, 93, 104, 127, 146, 155, 220, 221, 231 Intrinsic, 99, 188, 221 Inulin, 212, 221 Invasive, 18, 24, 53, 73, 79, 93, 102, 107, 127, 218, 221, 231 Ions, 193, 196, 206, 216, 221, 237 Ischemia, 9, 44, 92, 221, 227, 239 Islet, 36, 221 Isoelectric, 132, 221 Isoelectric Point, 132, 221 Isoenzymes, 132, 221 Isoniazid, 120, 221 Isotonic, 8, 221 J Jaundice, 185, 216, 221 Jejunoileal Bypass, 78, 221 Jejunostomy, 121, 207, 221 Jejunum, 221 K Kb, 160, 221 Keratitis, 93, 221 Keto, 221, 247 Ketoacidosis, 77, 222 Ketone Bodies, 222 Ketosis, 222 Kidney Disease, 9, 125, 127, 130, 160, 168, 170, 174, 176, 188, 222

260

Liver Transplant

Kidney Failure, 8, 126, 207, 222 Kidney Failure, Acute, 222 Kidney Failure, Chronic, 222 Kidney Transplantation, 126, 142, 166, 222 Kinetics, 21, 42, 222 L Labile, 201, 222 Lacerations, 133, 222 Lactobacillus, 79, 222 Lactulose, 21, 222 Lamivudine, 7, 12, 55, 74, 81, 85, 100, 101, 127, 148, 150, 222 Large Intestine, 205, 220, 222, 238, 242 Latency, 28, 125, 222 Latent, 28, 77, 125, 171, 223 Laxative, 198, 222, 223 Length of Stay, 7, 223 Leukemia, 118, 172, 199, 204, 212, 223 Leukocytes, 76, 193, 195, 198, 207, 213, 220, 223, 227, 248 Leukoplakia, 49, 223 Library Services, 182, 223 Lidocaine, 29, 223 Ligation, 27, 223 Linkage, 212, 223 Lip, 49, 223 Lipid, 87, 93, 102, 112, 220, 221, 223 Liver cancer, 26, 135, 140, 146, 148, 169, 223 Liver Cirrhosis, 216, 223 Liver Regeneration, 17, 18, 223 Living Donors, 10, 17, 18, 19, 21, 57, 223 Lobe, 10, 25, 86, 105, 109, 133, 148, 223 Localized, 135, 187, 190, 210, 214, 219, 223, 227, 233 Longitudinal study, 41, 53, 106, 223 Long-Term Care, 15, 223 Luciferase, 34, 224 Lymph, 207, 219, 224 Lymphadenopathy, 219, 224 Lymphatic, 207, 219, 224, 243, 246 Lymphatic system, 224, 243, 246 Lymphoblastic, 118, 224 Lymphocyte, 28, 51, 125, 191, 224, 225 Lymphoid, 40, 191, 202, 224 Lymphokines, 61, 224 Lymphoma, 49, 88, 118, 224 Lymphoproliferative, 28, 52, 77, 82, 98, 110, 118, 119, 125, 224 Lymphoproliferative Disorders, 119, 125, 224

M Malabsorption, 224, 242 Malabsorption syndrome, 224, 242 Malignancy, 4, 29, 34, 36, 76, 95, 110, 138, 141, 224 Malignant, 141, 187, 191, 223, 224, 228, 240, 241 Malignant tumor, 224, 240 Malnutrition, 146, 188, 224 Matrix metalloproteinase, 45, 224 Mediate, 40, 56, 205, 224 Mediator, 62, 224 Medical Staff, 206, 225 MEDLINE, 161, 225 Melanin, 225, 232, 248 Melanocytes, 225 Melanoma, 29, 225 Membrane, 198, 201, 204, 205, 209, 213, 214, 225, 230, 233, 239, 242, 248 Meninges, 197, 198, 203, 225 Meningitis, 210, 225 Mental, iv, 15, 54, 130, 146, 160, 162, 199, 205, 209, 225, 237, 241, 249 Mental Disorders, 130, 225, 237 Mental Health, iv, 15, 54, 130, 160, 162, 225, 237 Mental Processes, 225, 237 Mentors, 34, 225 Mercury, 210, 225 Mesenteric, 225, 234 Mesoderm, 34, 225 Metabolic disorder, 27, 213, 225 Metabolite, 73, 225 Metastasis, 41, 224, 225 Methotrexate, 61, 225 MI, 30, 101, 171, 186, 226 Microbe, 226, 247 Microbiology, 60, 70, 73, 79, 97, 102, 116, 192, 226 Microcirculation, 215, 223, 226 Microorganism, 200, 226, 231, 250 Micro-organism, 226, 242 Microscopy, 32, 34, 226 Migration, 91, 220, 226 Mitochondria, 44, 226, 228, 230 Mitosis, 192, 226 Mobility, 33, 50, 226 Modeling, 18, 25, 31, 32, 37, 38, 49, 52, 53, 226 Modification, 32, 40, 189, 212, 226, 238, 251

Index 261

Molecule, 27, 29, 36, 191, 193, 201, 206, 207, 208, 215, 217, 226, 231, 233, 238, 242, 247, 250 Monitor, 203, 226, 229 Monoclonal, 11, 45, 63, 85, 155, 204, 218, 226 Monoclonal antibodies, 45, 63, 85, 204, 218, 226 Monocytes, 223, 227 Mononuclear, 25, 219, 227, 248 Monotherapy, 3, 74, 87, 95, 97, 106, 227 Morphine, 11, 100, 200, 227, 228, 230 Morphological, 40, 94, 206, 211, 225, 227 Motility, 75, 227 Mouth Ulcer, 36, 227 Mucolytic, 187, 195, 227 Mucositis, 24, 227 Mucus, 209, 227, 249 Multicenter Studies, 24, 227 Multicenter study, 43, 58, 110, 227 Multigene Family, 132, 227 Multivariate Analysis, 90, 227 Mupirocin, 94, 227 Mutism, 107, 227 Mycophenolate mofetil, 75, 92, 97, 108, 110, 116, 117, 118, 119, 120, 121, 128, 141, 227 Myocardial infarction, 4, 202, 226, 227 Myocardial Reperfusion, 227, 239 Myocardial Reperfusion Injury, 227, 239 Myocardium, 226, 227, 228 Myosin, 196, 228 N Narcotic, 227, 228 Nasogastric, 207, 228 NCI, 1, 26, 129, 159, 228 Neoplasia, 8, 228 Neoplasm, 228, 241 Neoplastic, 224, 228 Neopterin, 21, 228 Neoral, 67, 68, 70, 98, 228 Nephropathy, 25, 222, 228 Nephrosis, 216, 228 Nephrotic, 79, 228 Nephrotic Syndrome, 79, 228 Nephrotoxic, 6, 11, 228 Nerve, 190, 199, 204, 225, 228, 234, 235, 244, 248 Nervous System, 61, 198, 225, 228, 229, 245 Networks, 24, 228 Neurons, 200, 204, 211, 228, 245

Neuropathy, 4, 229, 251 Neurotoxicity, 59, 229 Neurotransmitter, 187, 189, 195, 205, 213, 229, 242, 245 Neutrophil, 220, 229 Nitric Oxide, 21, 47, 119, 229 Nitrogen, 188, 209, 210, 222, 229 Nuclear, 89, 201, 229 Nuclei, 202, 212, 226, 229 Nucleic acid, 216, 217, 229, 240, 243, 251 Nucleus, 44, 192, 193, 199, 203, 204, 207, 227, 229, 244 Nutrition Assessment, 14, 229 Nutritional Status, 143, 229 Nutritional Support, 8, 212, 229 O Office Visits, 13, 229 Oliguria, 222, 229 Omentum, 215, 230, 244 Oncogene, 215, 230 Ophthalmology, 71, 93, 210, 230 Opiate, 38, 227, 230 Opium, 227, 230 Opportunistic Infections, 39, 173, 230 Oral Health, 11, 49, 230 Oral Hygiene, 12, 230 Orbit, 80, 230 Organ Preservation, 141, 230 Organ Transplantation, 4, 9, 23, 31, 58, 66, 70, 73, 80, 82, 87, 89, 108, 120, 126, 166, 230 Organelles, 204, 225, 227, 230 Ornidazole, 63, 230 Ornithine, 29, 230, 238 Ornithine Decarboxylase, 29, 230 Osmotic, 188, 230, 242 Osteoporosis, 100, 106, 126, 230 Outpatient, 38, 100, 138, 230 Overdose, 149, 211, 230 Oxidation, 21, 187, 191, 203, 231 Oximetry, 110, 231 Oxygenation, 217, 231 P Paediatric, 82, 87, 100, 106, 117, 231 Palliative, 231, 246 Pancreas, 60, 141, 142, 166, 187, 194, 205, 211, 215, 220, 221, 231, 244, 248 Pancreas Transplant, 142, 166, 231 Pancreas Transplantation, 142, 166, 231 Pancreatitis, 194, 231 Paradoxical, 39, 231 Parasite, 231

262

Liver Transplant

Parasitic, 41, 231, 247, 248 Parenteral, 8, 119, 172, 231 Parenteral Nutrition, 8, 172, 231 Patch, 202, 223, 231 Pathogen, 9, 39, 231 Pathogenesis, 5, 32, 35, 60, 61, 232 Pathologic, 187, 192, 194, 196, 202, 217, 232, 234 Pathologic Processes, 192, 232 Pathophysiology, 8, 20, 232 Patient Education, 169, 180, 182, 186, 232 Patient Selection, 6, 141, 151, 169, 232 Pediatric Gastroenterologist, 5, 232 Pediatrics, 25, 118, 232 Pelvis, 187, 219, 232 Peptide, 23, 53, 189, 232, 236, 237 Perfusion, 32, 48, 93, 101, 217, 232 Perioperative, 84, 101, 119, 171, 232 Peripheral blood, 25, 35, 37, 51, 76, 98, 220, 232 Peripheral stem cells, 213, 232 Peritoneum, 230, 232 Peritonitis, 73, 232 Phallic, 210, 232 Pharmacokinetic, 52, 56, 58, 232 Pharmacologic, 142, 190, 214, 232, 247 Phenotypes, 35, 37, 232 Phenylalanine, 232, 248 Phospholipases, 232, 242 Phospholipids, 209, 233 Phosphorus, 196, 233 Phosphorylation, 45, 233 Photocoagulation, 200, 233 Physiologic, 214, 221, 233, 236, 238 Physiology, 32, 39, 63, 82, 118, 146, 211, 233 Pilot study, 3, 30, 45, 56, 66, 233 Plants, 188, 196, 200, 212, 221, 233, 240, 247, 248 Plaque, 190, 233 Plasma cells, 191, 233 Plasma protein, 188, 233, 237, 242 Plasmid, 34, 233, 250 Platelet Activation, 233, 242 Platelet Aggregation, 189, 229, 233 Platelets, 229, 233 Pneumonia, 65, 72, 119, 202, 233, 248 Poisoning, 206, 220, 225, 234 Polymerase, 64, 73, 102, 191, 234 Polymerase Chain Reaction, 64, 102, 234 Polymorphic, 135, 234 Polymorphism, 33, 234

Polysaccharide, 191, 198, 234 Portal Hypertension, 74, 136, 138, 234 Portal Pressure, 5, 234 Portal Vein, 100, 134, 234 Portography, 85, 234 Posterior, 189, 192, 231, 234 Postmenopausal, 230, 234 Postnatal, 234, 244 Postoperative, 8, 11, 13, 14, 17, 100, 105, 135, 138, 141, 142, 143, 169, 170, 234 Postoperative Complications, 141, 143, 234 Postoperative Period, 13, 138, 142, 234 Postsynaptic, 234, 242 Potassium, 234 Potentiation, 234, 242 Practice Guidelines, 162, 171, 172, 234 Preceptorship, 31, 235 Precipitating Factors, 197, 214, 235 Preclinical, 25, 235 Precursor, 118, 190, 192, 205, 206, 207, 228, 232, 235, 237, 243, 248, 249 Prednisolone, 235 Prednisone, 11, 235 Preoperative, 18, 116, 138, 143, 235 Prevalence, 5, 49, 90, 102, 126, 128, 235 Primary Biliary Cirrhosis, 4, 61, 174, 235 Primary endpoint, 17, 30, 235 Primary Sclerosing Cholangitis, 4, 6, 9, 76, 235 Probe, 109, 235 Procaine, 223, 235 Progeny, 33, 201, 227, 235 Progesterone, 235, 244 Prognostic factor, 141, 236, 245 Progression, 24, 25, 37, 46, 58, 190, 236 Progressive, 6, 20, 97, 134, 141, 198, 199, 206, 208, 213, 222, 233, 236, 239 Promoter, 27, 30, 35, 236 Prophylaxis, 12, 55, 63, 80, 81, 85, 90, 102, 104, 109, 119, 172, 191, 236, 249 Propofol, 11, 236 Prospective study, 49, 93, 95, 103, 116, 128, 223, 236 Prostaglandin, 117, 121, 236 Prostaglandins A, 236 Prostate, 194, 236, 248 Protease, 201, 236 Protein C, 188, 189, 193, 236, 249 Protein S, 132, 191, 194, 208, 236, 240 Proteinuria, 25, 228, 237 Proteolytic, 23, 201, 209, 237

Index 263

Prothrombin, 134, 237, 246 Prothrombin Time, 134, 237 Protocol, 10, 11, 17, 20, 24, 31, 36, 42, 43, 237 Protozoa, 201, 226, 237, 247 Proximal, 205, 221, 237, 241 Pruritus, 61, 237 Psychiatric, 4, 22, 53, 137, 138, 225, 237 Psychiatry, 22, 38, 52, 57, 90, 117, 210, 237 Psychic, 225, 237, 241 Psychoactive, 237, 251 Psychology, 57, 237 Psychometrics, 38, 237 Public Health, 31, 146, 162, 175, 237 Public Policy, 161, 237 Pulmonary, 57, 85, 88, 119, 194, 195, 202, 215, 222, 237, 250 Pulmonary Artery, 85, 194, 237, 250 Pulmonary Edema, 222, 237 Pulse, 110, 226, 231, 237 Purpura, 107, 238 Putrefaction, 211, 238 Putrescine, 30, 230, 238, 243 Pyogenic, 238, 242 Pyridoxal, 230, 238, 247 Q Quality of Life, 4, 13, 17, 21, 25, 30, 46, 54, 57, 88, 138, 141, 238 Quiescent, 33, 238 R Race, 16, 19, 31, 149, 226, 238 Radiation, 210, 218, 230, 238, 251 Radioactive, 204, 214, 216, 218, 226, 229, 238 Radiology, 6, 10, 25, 57, 76, 86, 109, 238 Randomized, 18, 22, 30, 31, 53, 55, 61, 65, 104, 110, 116, 119, 206, 238 Reactivation, 56, 89, 90, 238 Reactive Oxygen Species, 44, 238 Reagent, 224, 238 Receptor, 41, 44, 56, 59, 191, 205, 208, 215, 238, 242 Recombinant, 34, 39, 44, 238, 250 Recombination, 201, 212, 238 Rectal, 128, 238, 245 Rectum, 191, 195, 201, 205, 211, 222, 236, 238 Recur, 6, 238 Reductase, 226, 239 Refer, 1, 137, 201, 210, 211, 216, 239, 247 Refraction, 239, 243 Regeneration, 18, 20, 33, 150, 239

Regimen, 6, 22, 28, 52, 57, 62, 121, 200, 206, 239, 240 Reinfection, 7, 8, 12, 20, 54, 69, 239 Relapse, 31, 52, 239 Remission, 239 Renal Artery, 217, 239 Renal Dialysis, 48, 239 Renal failure, 11, 97, 101, 120, 142, 216, 239 Renin, 48, 190, 239 Renin-Angiotensin System, 48, 239 Reoperation, 10, 239 Reperfusion, 40, 44, 62, 69, 135, 227, 239 Reperfusion Injury, 62, 135, 239 Resection, 59, 100, 239, 242 Respirators, 8, 239 Restoration, 227, 238, 239, 240, 251 Retinal, 205, 240 Retreatment, 168, 240 Retrospective, 16, 25, 42, 66, 111, 240 Retroviral vector, 212, 240 Reverse Transcriptase Polymerase Chain Reaction, 23, 240 Rhabdomyosarcoma, 80, 240 Ribavirin, 3, 66, 78, 79, 146, 240 Ribonucleoside Diphosphate Reductase, 217, 240 Ribosome, 240, 247 Risk factor, 46, 73, 77, 92, 126, 128, 136, 146, 148, 169, 197, 236, 240 Risk patient, 53, 102, 240 Ristocetin, 240, 249 Rod, 193, 199, 207, 222, 240 S Saliva, 240 Salivary, 28, 125, 203, 204, 205, 240 Salivary glands, 203, 204, 205, 240 Saponins, 240, 244 Sarcoma, 49, 94, 241 Schizoid, 241, 251 Schizophrenia, 241, 251 Schizotypal Personality Disorder, 241, 251 Screening, 23, 53, 59, 91, 100, 110, 200, 241 Secondary tumor, 225, 241 Secretion, 55, 220, 227, 241 Secretory, 56, 241 Sedative, 200, 241 Sedatives, Barbiturate, 193, 241 Sediment, 142, 241 Sedimentation, 241, 248 Seizures, 4, 95, 191, 241 Semisynthetic, 197, 218, 241 Senile, 230, 241

264

Liver Transplant

Sensitization, 6, 241 Sepsis, 13, 141, 241 Septal, 61, 241 Septicaemia, 134, 241 Sequencing, 33, 234, 242 Serologic, 218, 242 Serum Albumin, 132, 242 Shock, 59, 207, 242, 248 Short Bowel Syndrome, 172, 242 Side effect, 8, 11, 12, 51, 143, 152, 153, 155, 169, 188, 197, 242, 247, 251 Signal Transduction, 44, 196, 242 Signs and Symptoms, 239, 242 Sirolimus, 51, 59, 66, 74, 76, 105, 106, 107, 242 Skeletal, 199, 242 Skeleton, 187, 236, 242 Skin graft, 37, 242 Skin test, 242, 248 Skull, 203, 230, 242, 246 Small intestine, 198, 206, 216, 217, 220, 221, 228, 242 Smooth muscle, 189, 227, 239, 243, 245 Social Environment, 238, 243 Social Support, 138, 243 Social Work, 31, 243 Sodium, 8, 142, 213, 243 Soft tissue, 195, 242, 243 Solid tumor, 190, 243 Solvent, 83, 208, 230, 243 Specialist, 177, 205, 243 Specificity, 140, 188, 243 Spectrum, 17, 73, 83, 197, 243 Sperm, 199, 243, 248 Spermidine, 230, 243 Spinal cord, 198, 199, 208, 225, 228, 229, 243 Splanchnic Circulation, 81, 243 Spleen, 74, 203, 224, 243, 244 Splenectomy, 217, 244 Splenic Artery, 73, 244 Splenic Vein, 234, 244 Splenomegaly, 217, 219, 244 Splint, 11, 244 Staging, 38, 244 Standard therapy, 141, 244 Steatosis, 18, 209, 244 Steel, 199, 244 Stem Cells, 34, 189, 208, 232, 244 Stenosis, 244 Stent, 48, 96, 244 Sterile, 244, 248

Sterilization, 128, 244 Steroid, 14, 37, 116, 120, 121, 141, 193, 203, 240, 244 Stimulus, 208, 222, 244, 246 Stomach, 187, 205, 208, 211, 213, 215, 216, 222, 228, 230, 242, 243, 244 Stool, 201, 222, 244 Strand, 33, 234, 244 Streptococci, 227, 244 Stress, 6, 11, 44, 48, 203, 244 Stricture, 9, 244 Stroke, 130, 160, 196, 197, 244 Stromal, 51, 245 Subacute, 45, 219, 245 Subarachnoid, 214, 245 Subclinical, 219, 241, 245 Subcutaneous, 61, 190, 206, 231, 245 Subspecies, 243, 245 Substance P, 208, 225, 240, 241, 245 Substrate, 48, 245 Sulfur, 209, 222, 245 Superior vena cava, 96, 195, 245 Supplementation, 116, 245 Support group, 48, 140, 171, 245 Suppository, 197, 245 Suppression, 37, 55, 245 Surgical Instruments, 133, 245 Survival Analysis, 15, 245 Survival Rate, 7, 8, 13, 14, 58, 140, 141, 245 Symptomatic, 65, 231, 245 Synaptic, 229, 242, 245 Synergistic, 59, 246 Systemic, 11, 12, 41, 48, 49, 154, 194, 196, 208, 215, 219, 235, 246, 247 Systolic, 217, 246 T Tachycardia, 193, 246 Tachypnea, 193, 246 Teichoic Acids, 213, 246 Temporal, 56, 214, 246 Therapeutics, 23, 46, 154, 246 Thermal, 104, 234, 246 Thoracic, 21, 246 Thorax, 187, 245, 246 Threshold, 52, 217, 246 Thrombin, 209, 233, 236, 237, 246 Thrombocytopenia, 74, 246 Thromboplastin, 237, 246 Thrombosis, 70, 236, 245, 246 Thrush, 196, 246 Thymus, 218, 224, 246 Thyroid, 246, 248

Index 265

Thyroxine, 188, 232, 246 Tolerance, 23, 34, 36, 40, 41, 61, 80, 117, 187, 213, 246 Tone, 230, 247 Tonicity, 215, 221, 247 Topical, 208, 247 Toxic, iv, 30, 61, 188, 202, 218, 228, 229, 238, 247, 249, 251 Toxicity, 5, 28, 30, 45, 86, 126, 142, 206, 225, 240, 247 Toxicology, 162, 247 Toxin, 36, 207, 218, 246, 247 Toxoplasma, 83, 247 Toxoplasmosis, 63, 83, 247 Traction, 199, 247 Transaminase, 44, 133, 247 Transcriptase, 222, 247, 251 Transduction, 44, 242, 247 Transfection, 27, 194, 212, 247 Transfer Factor, 218, 247 Transferases, 132, 247 Transfusion, 36, 60, 74, 78, 150, 166, 247 Translation, 34, 189, 208, 247 Translational, 21, 26, 248 Translocation, 24, 208, 248 Transmitter, 187, 205, 225, 248 Trauma, 60, 208, 231, 248 Trichomonas, 230, 248 Trichomonas Infections, 230, 248 Trimethoprim-sulfamethoxazole, 119, 248 Tropism, 33, 248 Tubercle, 248 Tuberculin, 171, 248 Tuberculin Test, 171, 248 Tuberculoma, 93, 248 Tuberculostatic, 221, 248 Tubulin, 21, 248 Tumor marker, 194, 248 Tumor Necrosis Factor, 135, 248 Type 2 diabetes, 25, 174, 248 Tyrosine, 45, 61, 205, 248 U Ulcerative colitis, 4, 235, 248 Ultrafiltration, 215, 249 Uncompensated Care, 216, 249 Unconscious, 190, 217, 249 Unresectable, 59, 249 Urea, 29, 222, 230, 249 Uremia, 222, 239, 249 Urethra, 236, 249 Urinary, 21, 197, 229, 249 Urinary tract, 197, 249

Urine, 22, 24, 31, 142, 188, 191, 194, 203, 222, 229, 237, 249 Ursodeoxycholic Acid, 61, 141, 249 V Vaccination, 59, 89, 110, 111, 249 Vaccine, 88, 237, 249 Vagina, 196, 222, 249 Vaginitis, 196, 249 Valganciclovir, 65, 99, 110, 249 Valves, 239, 249 Vancomycin, 65, 80, 128, 249 Varicella, 111, 249 Varices, 113, 249 Vascular, 10, 57, 96, 109, 133, 138, 190, 204, 207, 214, 219, 223, 226, 229, 250 Vasoconstriction, 47, 208, 250 Vasodilation, 47, 250 Vasodilator, 48, 195, 205, 227, 250 Vector, 247, 250 Vein, 133, 190, 219, 221, 229, 234, 244, 245, 250 Vena, 133, 250 Venous, 82, 105, 109, 234, 236, 250 Ventricle, 237, 238, 246, 250 Venules, 194, 196, 226, 250 Vesicular, 60, 216, 250 Veterinary Medicine, 161, 250 Vinblastine, 248, 250 Vincristine, 248, 250 Viral Hepatitis, 7, 8, 26, 92, 103, 142, 146, 250 Viral Load, 21, 64, 97, 98, 127, 250 Virulence, 29, 86, 247, 250 Virus Diseases, 191, 250 Visceral, 68, 232, 250 Viscosity, 187, 194, 250 Vitro, 34, 250 Vivo, 33, 34, 40, 41, 47, 93, 251 W Warts, 49, 251 White blood cell, 191, 194, 199, 219, 223, 224, 227, 229, 233, 251 Withdrawal, 14, 35, 76, 80, 116, 117, 120, 141, 150, 251 Wound Healing, 12, 74, 76, 134, 143, 224, 227, 251 X Xenobiotics, 132, 251 Xenograft, 190, 251 X-ray, 111, 210, 229, 234, 238, 251 Y Yeasts, 127, 196, 211, 251

266

Liver Transplant

Z Zalcitabine, 222, 251

Zygote, 202, 251

Index 267

268

Liver Transplant