The Official Patient's Sourcebook on Transplantation

THE OFFICIAL PATIENT’S SOURCEBOOK

on

TRANSPLANTATION

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

ii

ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright Ó2002 by ICON Group International, Inc. Copyright Ó2002 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: Tiffany LaRochelle 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 as a substitute for consultation with your physician. All matters regarding your health require medical supervision. 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, in close consultation with a qualified physician. The reader is advised to always check product information (package inserts) for changes and new information regarding dose and contraindications before taking 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., 1960The Official Patient’s Sourcebook on Transplantation: A Revised and Updated Directory for the Internet Age/James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary and index. ISBN: 0-597-82995-0 1. Transplantation-Popular works. I. Title.

iii

Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem or as a substitute for consultation with licensed medical professionals. 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, or the authors are not responsible for the content of any Web pages nor publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this sourcebook for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications are copyrighted. 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 sourcebook.

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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 sourcebook which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which directly or indirectly are dedicated to transplantation. All of the Official Patient’s Sourcebooks 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 sourcebook. 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 LaRochelle 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 the Official Patient’s Sourcebook series published 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 the Official Patient’s Sourcebook series published by ICON Health Publications.

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About ICON Health Publications In addition to transplantation, Official Patient’s Sourcebooks are available for the following related topics: ·

The Official Patient's Sourcebook on Cochlear Implants

·

The Official Patient's Sourcebook on Heart Failure

·

The Official Patient's Sourcebook on Kidney Failure

·

The Official Patient's Sourcebook on Vasectomy

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

Contents vii

Table of Contents INTRODUCTION...................................................................................... 1

Overview............................................................................................................... 1 Organization......................................................................................................... 3 Scope ..................................................................................................................... 3 Moving Forward................................................................................................... 4

PART I: THE ESSENTIALS ................................................. 7 CHAPTER 1. THE ESSENTIALS ON TRANSPLANTATION: GUIDELINES .. 9

Overview............................................................................................................... 9 What Is Transplantation? .................................................................................. 10 Many Obstacles Confront Transplantation ....................................................... 11 The Overriding Problem Common to All Transplantation................................ 13 Biological Differences ......................................................................................... 15 A Longer and Better Life .................................................................................... 18 Future Directions ............................................................................................... 19 National Institutes of Health.............................................................................. 20 More Guideline Sources ..................................................................................... 25 Vocabulary Builder............................................................................................. 36

CHAPTER 2. SEEKING GUIDANCE ....................................................... 41

Overview............................................................................................................. 41 Associations and Transplantation ...................................................................... 41 Finding More Associations................................................................................. 46 Finding Doctors.................................................................................................. 47 Finding Specialists.............................................................................................. 49 Selecting Your Doctor ........................................................................................ 49 Working with Your Doctor ................................................................................ 50 Broader Health-Related Resources ..................................................................... 51 Vocabulary Builder............................................................................................. 52

CHAPTER 3. CLINICAL TRIALS AND TRANSPLANTATION .................. 55

Overview............................................................................................................. 55 Recent Trials on Transplantation....................................................................... 58 Benefits and Risks............................................................................................... 59 Keeping Current on Clinical Trials.................................................................... 62 General References.............................................................................................. 63 Vocabulary Builder............................................................................................. 64

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL.................................................. 69 CHAPTER 4. STUDIES ON TRANSPLANTATION .................................... 71

Overview............................................................................................................. 71 The Combined Health Information Database ..................................................... 71

viii Contents

Federally Funded Research on Transplantation................................................. 73 E-Journals: PubMed Central .............................................................................. 78 The National Library of Medicine: PubMed ...................................................... 82 Vocabulary Builder............................................................................................. 84

CHAPTER 5. PATENTS ON TRANSPLANTATION .................................. 95

Overview............................................................................................................. 95 Patents on Transplantation ................................................................................ 96 Patent Applications on Transplantation .......................................................... 107 Keeping Current ............................................................................................... 116 Vocabulary Builder........................................................................................... 116

CHAPTER 6. BOOKS ON TRANSPLANTATION .................................... 121

Overview........................................................................................................... 121 Book Summaries: Federal Agencies .................................................................. 121 Book Summaries: Online Booksellers ............................................................... 124 The National Library of Medicine Book Index ................................................. 126 Chapters on Transplantation............................................................................ 128 Directories......................................................................................................... 130 Vocabulary Builder........................................................................................... 131

CHAPTER 7. MULTIMEDIA ON TRANSPLANTATION ......................... 135

Overview........................................................................................................... 135 Video Recordings .............................................................................................. 135 Bibliography: Multimedia on Transplantation ................................................ 138 Vocabulary Builder........................................................................................... 138

CHAPTER 8. PERIODICALS AND NEWS ON TRANSPLANTATION ...... 141

Overview........................................................................................................... 141 News Services & Press Releases ....................................................................... 141 Newsletters on Transplantation ....................................................................... 148 Newsletter Articles ........................................................................................... 150 Academic Periodicals covering Transplantation .............................................. 152 Vocabulary Builder........................................................................................... 154

CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES ................... 155

Overview........................................................................................................... 155 NIH Guidelines................................................................................................. 155 NIH Databases.................................................................................................. 156 Other Commercial Databases ........................................................................... 165 Specialized References....................................................................................... 165 Vocabulary Builder........................................................................................... 166

CHAPTER 10. DISSERTATIONS ON TRANSPLANTATION.................... 167

Overview........................................................................................................... 167 Dissertations on Transplantation..................................................................... 167 Keeping Current ............................................................................................... 168

PART III. APPENDICES .................................................. 169

Contents

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APPENDIX A. RESEARCHING YOUR MEDICATIONS.......................... 171

Overview........................................................................................................... 171 Your Medications: The Basics .......................................................................... 172 Learning More about Your Medications .......................................................... 173 Commercial Databases...................................................................................... 176 Contraindications and Interactions (Hidden Dangers) ................................... 179 A Final Warning .............................................................................................. 180 General References............................................................................................ 180 Vocabulary Builder........................................................................................... 181

APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ................... 183

Overview........................................................................................................... 183 What Is CAM? ................................................................................................. 183 What Are the Domains of Alternative Medicine?............................................ 184 Can Alternatives Affect My Treatment? ......................................................... 187 Finding CAM References on Transplantation ................................................. 188 Additional Web Resources................................................................................ 189 General References............................................................................................ 207 Vocabulary Builder........................................................................................... 207

APPENDIX C. RESEARCHING NUTRITION ......................................... 209

Overview........................................................................................................... 209 Food and Nutrition: General Principles........................................................... 210 Finding Studies on Transplantation ................................................................ 214 Federal Resources on Nutrition........................................................................ 215 Additional Web Resources................................................................................ 216 Vocabulary Builder........................................................................................... 218

APPENDIX D. FINDING MEDICAL LIBRARIES.................................... 221

Overview........................................................................................................... 221 Preparation ....................................................................................................... 221 Finding a Local Medical Library ...................................................................... 222 Medical Libraries Open to the Public............................................................... 222

APPENDIX E. YOUR RIGHTS AND INSURANCE ................................. 229

Overview........................................................................................................... 229 Your Rights as a Patient................................................................................... 229 Patient Responsibilities .................................................................................... 233 Choosing an Insurance Plan............................................................................. 234 Medicare and Medicaid .................................................................................... 237 NORD’s Medication Assistance Programs ..................................................... 240 Additional Resources ........................................................................................ 240 Vocabulary Builder........................................................................................... 241

ONLINE GLOSSARIES.................................................... 243 Online Dictionary Directories.......................................................................... 246

TRANSPLANTATION GLOSSARY ............................. 247

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Contents

General Dictionaries and Glossaries ................................................................ 273

INDEX................................................................................... 275

Introduction

1

INTRODUCTION Overview Dr. C. Everett Koop, former U.S. Surgeon General, once said, “The best prescription is knowledge.”1 The Agency for Healthcare Research and Quality (AHRQ) of the National Institutes of Health (NIH) echoes this view and recommends that every patient incorporate education into the treatment process. According to the AHRQ: Finding out more about your condition is a good place to start. By contacting groups that support your condition, visiting your local library, and searching on the Internet, you can find good information to help guide your treatment decisions. Some information may be hard to find—especially if you don’t know where to look.2 As the AHRQ mentions, finding the right information is not an obvious task. Though many physicians and public officials had thought that the emergence of the Internet would do much to assist patients in obtaining reliable information, 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.3

Quotation from http://www.drkoop.com. The Agency for Healthcare Research and Quality (AHRQ): http://www.ahcpr.gov/consumer/diaginfo.htm. 3 From the NIH, National Cancer Institute (NCI): http://cancertrials.nci.nih.gov/beyond/evaluating.html. 1 2

2

Transplantation

Since the late 1990s, physicians have seen a general increase in patient Internet usage rates. Patients frequently enter their doctor’s offices with printed Web pages of home remedies in the guise of latest medical research. This scenario is so common that doctors often spend more time dispelling misleading information than guiding patients through sound therapies. The Official Patient’s Sourcebook on Transplantation has been created for patients who have decided to make education and research an integral part of the treatment process. The pages that follow will tell you where and how to look for information covering virtually all topics related to transplantation, from the essentials to the most advanced areas of research. The title of this book includes the word “official.” This reflects the fact that the sourcebook draws from public, academic, government, and peerreviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on transplantation. Given patients’ increasing sophistication in using the Internet, abundant references to reliable Internet-based resources are provided throughout this sourcebook. Where possible, guidance is provided on how to obtain free-ofcharge, primary research results as well as more detailed information via the Internet. E-book and electronic versions of this sourcebook are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). Hard copy users of this sourcebook can type cited Web addresses directly into their browsers to obtain access to the corresponding sites. Since we are working with ICON Health Publications, hard copy Sourcebooks are frequently updated and printed on demand to ensure that the information provided is current. In addition to extensive references accessible via the Internet, every chapter presents a “Vocabulary Builder.” Many health guides offer glossaries of technical or uncommon terms in an appendix. In editing this sourcebook, we have decided to place a smaller glossary within each chapter that covers terms used in that chapter. Given the technical nature of some chapters, you may need to revisit many sections. Building one’s vocabulary of medical terms in such a gradual manner has been shown to improve the learning process. We must emphasize that no sourcebook on transplantation should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your best option. This sourcebook is no exception. Each patient is unique. Deciding on appropriate

Introduction

3

options is always up to the patient in consultation with their physician and healthcare providers.

Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching transplantation (e.g. finding guidelines on transplantation), followed by a number of topics, including information on how to get in touch with organizations and associations that dedicate their work to transplantation. It also gives you sources of information that can help you find a doctor in your local area specializing in transplantation. Collectively, the material presented in Part I is a complete primer on basic research topics for patients having transplantation. Part II moves on to advanced research dedicated to transplantation. Part II is intended for those willing to invest many hours of hard work and study. It is here that we direct you to the latest scientific and applied research on transplantation. When possible, contact names, links via the Internet, and summaries are provided. It is in Part II where the vocabulary process becomes important as authors publishing advanced research frequently use highly specialized language. In general, every attempt is made to recommend “free-to-use” options. Part III provides appendices of useful background reading for all patients undergoing transplantation. The appendices are dedicated to more pragmatic issues faced by many patients having transplantation. Accessing materials via medical libraries may be the only option for some readers, so a guide is provided for finding local medical libraries which are open to the public. Part III, therefore, focuses on advice that goes beyond the biological and scientific issues facing patients having transplantation.

Scope While this sourcebook covers transplantation, your doctor, research publications, and specialists may refer to your treatment plan using a variety of terms. Therefore, you should understand that transplantation is often considered a synonym closely related to the following: ·

Transplant

·

Transplant Surgery

·

Transplantation

4

Transplantation

In addition to synonyms and related terminology, physicians may refer to transplantation using certain coding systems. The CPT (Current Procedural Terminology) coding system published by the American Medical Association (AMA) is the most commonly used system of classification for the world’s medical procedures and treatments. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for transplantation:4 ·

996.8 complications of transplanted organ

·

996.80 transplanted organ, unspecified

·

996.81 kidney

·

996.82 liver

·

996.83 heart

·

996.84 lung

·

996.85 bone marrow

·

996.86 pancreas

·

996.87 intestine

·

996.89 other specified transplanted organ

For the purposes of this sourcebook, we have attempted to be as inclusive as possible, looking for official information for all of the synonyms relevant to transplantation. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.

Moving Forward Since the 1980s, the world has seen a proliferation of healthcare guides. Some are written by patients or their family members. These generally take a layperson’s approach to understanding and coping with a medical procedure or treatment. They can be uplifting, encouraging, and highly supportive. Other guides are authored by physicians or other healthcare providers who have a more clinical outlook. Each of these two styles of guide has its purpose and can be quite useful. As editors, we have chosen a third route. We have chosen to expose you to as many sources of official and peer-reviewed information as practical, for the purpose of educating you about basic and advanced knowledge as

4

Adapted from the AMA, 2002 CPT system: www.ama-assn.org.

Introduction

5

recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian. Why “Internet age”? All too often, patients having transplantation will log on to the Internet, type words into a search engine, and receive several Web site listings which are mostly irrelevant or redundant. These patients are left to wonder where the relevant information is, and how to obtain it. Since only the smallest fraction of information dealing with transplantation is even indexed in search engines, a non-systematic approach often leads to frustration and disappointment. With this sourcebook, we hope to direct you to the information you need that you would not likely find using popular Web directories. Beyond Web listings, in many cases we will reproduce brief summaries or abstracts of available reference materials. These abstracts often contain distilled information on topics of discussion. While we focus on the more scientific aspects of transplantation, there is, of course, the emotional side to consider. Later in the sourcebook, we provide a chapter dedicated to helping you find peer groups and associations that can provide additional support beyond research produced by medical science. We hope that the choices we have made give you the most options available in moving forward with your decision process. In this way, we wish you the best in your efforts to incorporate this educational approach into your treatment plan. The Editors

7

PART I: THE ESSENTIALS

ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on transplantation. The essentials of a procedure typically include the definition or description of the procedure and a discussion of who requires it. Your doctor or healthcare provider may have already explained the essentials of transplantation to you or even given you a pamphlet or brochure describing transplantation. Now you are searching for more indepth information. As editors, we have decided, nevertheless, to include a discussion on where to find essential information that can complement what your doctor has already told you. In this section we recommend a process, not a particular Web site or reference book. The process ensures that, as you search the Web, you gain background information in such a way as to maximize your understanding.

Guidelines

9

CHAPTER 1. THE ESSENTIALS ON TRANSPLANTATION: GUIDELINES Overview Official agencies, as well as federally-funded institutions supported by national grants, frequently publish a variety of guidelines on transplantation. 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. The great advantage of guidelines over other sources is that they are often written with the patient in mind. Since new guidelines on transplantation 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.

The National Institutes of Health (NIH)5 The National Institutes of Health (NIH) is the first place to search for relatively current patient guidelines and fact sheets on transplantation. Originally founded in 1887, the NIH is one of the world’s foremost medical research centers and the federal focal point for medical research in the United States. At any given time, the NIH supports some 35,000 research grants at universities, medical schools, and other research and training institutions, both nationally and internationally. The rosters of those who have conducted research or who have received NIH support over the years include the world’s most illustrious scientists and physicians. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine.

5

Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.

10 Transplantation

There is no guarantee that any one Institute will have a guideline on a specific diagnostic or therapeutic procedure, though the National Institutes of Health collectively publish many guidelines for both common and lesserknown procedures. The best way to access NIH guidelines is via the Internet. Although the NIH is organized into many different Institutes and Offices, the following is a list of key Web sites where you are most likely to find NIH clinical guidelines and publications dealing with transplantation and associated procedures: ·

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

·

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

·

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

·

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

Among the above, the National Institute of Allergy and Infectious Diseases (NIAID) is particularly noteworthy. The mission of the NIAID is to provide support for scientists conducting research aimed at developing better ways to diagnose, treat, and prevent the many infectious, immunologic and allergic diseases that afflict people worldwide.6 The NIAID is composed of four extramural divisions: the Division of AIDS; the Division of Allergy, Immunology and Transplantation; the Division of Microbiology and Infectious Diseases; and the Division of Extramural Activities. In addition, NIAID scientists conduct intramural research in laboratories located in Bethesda, Rockville and Frederick, Maryland, and in Hamilton, Montana. The following patient guideline was recently published by the NIAID on Transplantation.

What Is Transplantation?7 Transplantation is a life-saving procedure for many patients and is often the only viable treatment available. Each year, hundreds of thousands of people This paragraph has been adapted from the NIAID: http://www.niaid.nih.gov/facts/overview.htm. “Adapted” signifies that a passage has been reproduced exactly or slightly edited for this book. 7 Adapted from The National Institute of Allergy and Infectious Diseases (NIAID): http://www.niaid.nih.gov/publications/transplant/contents.htm 6

Guidelines 11

are affected by diseases which result in the need for transplantation and tens of thousands of people receive transplants. Some notable facts about transplantation and the diseases this procedure is used to treat are: ·

More than 200,000 people in the United States suffer from kidney failure.

·

Treatment of kidney failure represents medical payments of more than $7 billion annually.

·

More than 60,000 Americans die each year from liver failure.

·

When bone marrow transplantation is successful, it is curative for leukemia, immumodeficiency, sickle cell anemia, and certain metabolic disorders.

·

In 1992, more than 32,000 organ transplants were performed worldwide and nearly half of those were done in the United States. These transplants, collectively, involved every major organ.

·

Success rates vary for the different types of organs transplanted and can be as high as 90% or as low as 50% for one year.

·

Immunologic rejection is a major barrier to successful transplantation.

Although there are still many problems confronting transplant physicians and scientists, transplantation has provided a unique opportunity to learn more about the human immune system and has improved our understanding and treatment of immunologic diseases.

Many Obstacles Confront Transplantation NIAID research takes a comprehensive approach to the biological obstacles confronting transplantation today. Obstacles ·

The number of people needing transplants is increasing, each year. (see Fig.1)

·

Rejection is the body’s natural reaction to transplanted organs and tissues. This threatens each patient with the loss of the new organ or even loss of life.

·

There are several underserved populations, receiving fewer transplants than expected from their numbers on waiting lists.

12 Transplantation

·

Moving scientific discoveries from the laboratory bench to the bedside requires special efforts and careful planning to translate science into improved medical practice.

Figure 1 - The number of patients awaiting transplantation continues to increase.

The NIAID Approach ·

Prevent the need for transplantation by identifying the biologic mechanisms of the diseases that lead to the need for transplantation and finding ways to prevent and treat these diseases.

·

Prevent graft rejection by learning the processes used by the body not only to recognize transplants as foreign but also to reject them.

·

Develop better ways to treat graft rejection: methods that are less toxic and more effective.

·

Identify and develop ways to overcome the biological barriers to transplantation that put certain groups of patients at a disadvantage.

·

Support clinical trials and studies that rapidly evaluate new therapies.

Guidelines 13

NIAID Makes a Difference ·

Because of NIAID support, scientists today can identify the immunologic barriers to transplantation better than ever before.

·

As a result of NIAID-funded research, scientists now know more about how anti-rejection drugs work and new therapies have been developed.

·

Through NIAID studies on transplantation, scientists know more about basic immunology and how the human immune system works.

The Overriding Problem Common to All Transplantation Except for transplants between identical twins, all transplant donors and recipients are immunologically incompatible. This biologic incompatibility is a barrier that causes the recipient to try to destroy or reject the new organ, tissue or cells. In graft-versus-host disease, rejection occurs when the transplanted donor cells try to destroy or reject recipient tissues. (see Fig. 2) ·

Rejection episodes may be mild or severe but, with time, will lead to graft failure or patient death.

·

As surgical methods to transplant grafts improve, rejection becomes the major cause of graft failure.

·

Of those awaiting organ transplantation, more than one-fourth of patients have already had at least one graft failure.

·

Immunosuppression - the current therapy to prevent and treat rejection increases the incidence of infection and cancer.

14 Transplantation

Figure 2 - Graft survival rates decline sharply over time.

NIAID Approaches to Prevent and Overcome Rejection ·

Develop better drugs for immunosuppression.

·

Design methods to prevent rejection that do not require generalized immunosuppression, that has adverse side effects. This is known as donor-specific tolerance.

·

Control recognition and rejection of transplanted tissues by identifying the mechanisms involved.

Recent Accomplishments of NIAID-Supported Investigators ·

Determined the mode of action of some of the most important immunosuppressive agents, such as cyclosporine.

·

Developed a detailed understanding of the targets of rejection.

·

Ongoing development and evaluation of several new immunosuppressive agents with the potential to be more effective while having fewer undesirable side effects.

·

Ongoing development and evaluation of new methods to induce donorspecific tolerance.

Guidelines 15

·

Demonstrated significant improvement in one-year graft survival in kidney transplant recipients treated with donor bone marrow to induce tolerance.

Biological Differences People are biologically different and those differences can have significant effects on the risk for certain diseases and the need for, access to, and outcome of transplantation. ·

Several autoimmune diseases, such as diabetes and systemic lupus erythematosus, can lead to end-stage organ failure. These diseases affect some groups of patients significantly more than others. o End-stage renal disease is four times greater in African-Americans than in whites, mainly because of higher rates of hypertension and autoimmune disease. o End-stage renal disease is increasing most rapidly among Native Americans because of a significant growth in the incidence of diabetes. o Autoimmune diseases are six times more common in women than in men.

·

Some groups of patients are transplanted less frequently than others (see Fig.3), in part, because of immunologic incompatibility. In kidney transplantation, women, African-Americans, and children are among these disadvantaged groups.

·

Graft survival is poorer in African-Americans, patients who have had a previous transplant, and children. (see Fig.4)

·

Donor-recipient matching is a significant factor in graft survival, but identification of the transplantation antigens, the factors used in matching of African-Americans, Native Americans and Hispanics lags behind that of whites.

16 Transplantation

Figure 3 - Some groups of patients are less likely to be transplanted than are others.

Figure 4 - Graft survival is poorer in some groups of patients than in others.

Guidelines 17

NIAID Approaches to Overcoming Biologic Differences ·

Identify the cellular and molecular processes in autoimmune diseases and develop ways to prevent and treat these diseases.

·

Determine the biologic differences among groups of patients that increase the likelihood of graft rejection.

·

Better define the transplantation antigens of various racial groups to improve matching capabilities.

·

Conduct clinical trials to define the optimal therapies for overcoming incompatibility between donors and recipients and ensuring graft survival in various groups of patients.

NIAID Contributions ·

NIAID is sponsoring the first national study to improve the identification of transplantation antigens in African-Americans, Native Americans, and Hispanics.

·

An NIAID-supported researcher has identified several key factors related to the development of autoimmune disease.

·

An NIAID-funded scientist has demonstrated that some kidney and heart transplant patients are able to produce substances that overcome incompatibility, resulting in better graft survival in these patients than in others. This investigator is examining if the production of these substances is affected by gender or race.

·

An NIAID-supported physician is performing bone marrow transplants before rather than after birth for children with congenital defects, to increase the likelihood of a successful transplant and a normal, healthy life.

NIAID Research Findings Move Rapidly into the Clinical Setting ·

An NIAID-supported, eight-site cooperative clinical trial is evaluating new and innovative approaches to regulating the immune response in order to improve the outcome of kidney transplants.

·

NIAID’s national study of transplantation antigens in African-Americans, Hispanics, and Native Americans will improve the ability to define the quality of match between donors and recipients in these population groups.

18 Transplantation

·

NIAID-supported testing of a newly developed immunosuppressive agent, T1OB9, which was found to reverse graft rejection more effectively, more rapidly, and at lower cost than standard therapy.

·

NIAID supports ongoing studies to modify bone marrow for the improved treatment of leukemia, sickle cell anemia, and immunodeficiency.

A Longer and Better Life NIAID Transplantation Research Extends and Improves the Quality of Life of Transplant Recipients ·

Graft and patient survival is increasing steadily.

·

More types of transplants are possible because of improvements in treatment protocols. The organs, tissues, and cells transplanted include: kidneys, hearts, lungs, pancreata, livers, and small bowel; bone marrow, corneas, bones, and skin; and cells of muscle, bone, and pancreas.

·

Successful transplantation leads to improved quality of life. Patients are no longer dependent on life-saving procedures such as dialysis and insulin injections.

NIAID Transplantation Research Benefits Many Areas of Science and Medicine ·

The agents and protocols developed by NIAID investigators to prevent and treat transplant rejection are also used routinely to treat patients with autoimmune diseases.

·

Characterization of transplantation antigens has improved our understanding of the role of these factors in regulating the immune response in other conditions such as infection, vaccination, and cancer.

·

NIAID studies of the mechanisms and processes of transplant rejection have contributed knowledge about the basic processes in the immune response. Protocols aimed at preventing a recipient from rejecting the transplant from a specific donor have provided a unique opportunity to study, in humans, how the immune system recognizes self and why the fetus is not rejected like a transplant.

Guidelines 19

·

NIAID-supported studies in bone marrow transplantation have led to the development of more effective treatment protocols for cancer patients.

Future Directions Transplantation experts no longer speak in terms of just organs and tissues. NIAID-supported research is leading the way to the transplantation of cells and genes to prevent and cure disease. In the future: ·

Cell transplantation will provide almost unlimited opportunities. Some of the areas currently being explored are: o muscle cell transplants to treat muscular dystrophy. o nerve cell transplants to treat spinal cord injuries. o nerve tissue transplants to reverse the effects of Parkinson’s disease. o liver cell transplants to cure life-threatening metabolic diseases such as Tay-Sachs disease and, for other diseases, to prevent the need for liver transplantation. o islet cell transplants to treat diabetes.

·

Cells will be altered to provide patient-tailored treatment. Among the possibilities: o remove a patient’s cells, correct a genetic defect, and return the repaired, healthy cells to the body. o re-educate cells from a cancer patient to make them more effective in fighting the cancer. o modify a transplant recipient’s cells so that they no longer see a transplant as foreign tissue.

·

As new types of cells are explored as treatments for a variety of diseases, scientists will confront and conquer new immunologic barriers.

·

Investigators will explore variability in the immune response among groups of patients and between individuals and use the information to improve transplantation protocols and to remedy various immunologic diseases, optimize vaccination protocols, and prevent or treat infections and cancer.

·

Understanding the immune response to different types of tissues will enable scientists to explore the possibility of developing banks of cells, tissues, and organs from a variety of sources with hopes of overcoming the drastic shortage of organs.

20 Transplantation

National Institutes of Health Transplantation Research Coordinating Committee In 1989, the Director of the National Institutes of Health established the Transplantation Research Coordinating Committee (TRCC) and designated the National Institute of Allergy and Infectious Diseases as the lead institute. The mission of the TRCC is to enhance coordination of transplantation research and, to this end, the Committee collects and disseminates information about transplant activities at NIH and receives advice and suggestions from professional societies, the public, and governmental and private sector organizations interested in transplantation. Additional information about the activities and composition of the TRCC may be obtained from either the committee’s chair, Dr. Robert A. Goldstein, or the committee’s coordinator, Dr. Andrea A. Zachary. Information about the programs sponsored and conducted by the various institutes and agencies participating in the TRCC may be obtained by contacting the representatives listed below. National Institute of Allergy and Infectious Diseases Committee Chair Robert A. Goldstein, M.D., Ph.D. Director, Division of Allergy, Immunology and Transplantation National Institute on Aging Health Stephen Snyder, Ph.D. Scientist Administrator Tel: 301-496-9350 Fax: 301-496-1494 National Institute of Arthritis and Musculoskeletal and Skin Diseases Steven J. Hausman, Ph.D Deputy Director Tel: 301-402-1691 Fax: 301-480-6069 National Cancer Institute Roy S. Wu, Ph.D. Tel: 301-496-8866 Fax: 301-496-9384 National Institute of Child Health and Human Development

Guidelines 21

Charles U. Lowe, M.D. Associate Director of Special Projects Tel: 301-496-2500 Fax: 301-496-4757 National Institute of Dental Research Phillip D. Smith, M.D. Senior Investigator Tel: 301-496-2491 Fax: 301-402-1064 National Institute of Diabetes and Digestive and Kidney Diseases Lawrence C. Agadoa, M.D. Director, End-Stage Renal Disease Program Tel: 301-594-7554 Fax: 301-594-7501 National Eye Institute Ellen S. Liberman, Ph.D. Program Director Tel: 301-496-0484 Fax: 301-402-0528 National Institute of General Medical Sciences Marion Zatz, Ph.D. Chief, Cellular and Molecular Basis of Disease Program Tel: 301-594-7738 Fax: 301-594-7726 National Heart, Lung and Blood Institute John Barrett, M.D. Head, Bone Marrow Transplant Unit Tel: 301-402-4170 Fax: 301-496-8396 Carol E. Vreim, Ph.D. Associate Director for Scientific Program Operations Tel: 301-594-7430 Fax: 301-594-7487 National Library of Medicine Harold Schoolman, M.D.

22 Transplantation

Deputy Director, Research and Education Tel: 301-496-4725 Fax: 301-496-4450 National Center for Medical Rehabilitation Research Danuta Krotoski, Ph.D. Chief, Basic Rehabilitation Medicine Research Branch Tel: 301-402-2242 Fax: 301-402-0832 National Institute of Mental Health Susan Blumenthal, M.D. Acting Chief, Basic Prevention and Behavioral Medicine Research Branch Tel: 301-443-4337 Fax 301-443-1719 National Institute of Neurologic Disorders and Stroke Mary Ellen Michel, Ph.D. Health Science Administrator Tel: 301-496-4226 Fax: 301-480-1080 National Institute for Nursing Research Hilary D. Sigmon, Ph.D., R.N. Health/Nurse Scientist Administrator Tel: 301-594-7397 Fax: 301-594-7603 Food and Drug Administration Phillip D. Noguchi, M.D. Acting Director, Division of Cell and Gene Therapy Tel: 301-496-4709 Fax: 301-496-4684 Ronald J. Lieberman, M.D. Medical Officer, Center for Drug Evaluation and Research Staff College Tel: 301-443-2200 Fax: 301-443-6905 Health Resources and Services Administration Judith Braslow Director, Division of Organ Transplantation Tel: 301-443-7577

Guidelines 23

Fax: 301-594-6095 Steve J. Niemcryk, Ph.D. Epidemiologist Tel: 301-443-6560 Fax: 301-443-9645 Office of the Assistant Secretary for Health Nancy Pearce Chief, Information Collection Management Branch Tel: 202-690-7100 fax: 202-690-5882 Health Care Financing Administration Paul Eggers, Ph.D. Chief, Program Evaluation Branch Tel: 410-966-6691 Fax: 410-966-6511 Department of Veterans Affairs Pamela Steele, M.D. Chief, Cardiovascular Diseases Tel: 202-535-7577 Fax: 202-535-7225 Agency for Health Care Policy and Research Thomas Holohan, M.D. Director, Office of Health Technology Assessment Tel: 301-594-4023 Fax: 301-594-4030 Transplantation Organizations American Association of Kidney Patients Erwin Hytner, Executive Director 800-749-2257 American Association of Tissue Banks Jeanne Mowe, Executive Director 703-827-9582

24 Transplantation

American Diabetes Association John H. Graham, IV, Executive Director 703-549-1500 ext.298 American Red Cross Tissue Service S. Randolph May, Ph.D., National Head 202-728-6501 American Society for Histocompatibility and Immunogenetics Debbie J. Elder, Executive Director 913-541-0009 American Society of Minority Health and Transplant Professionals Karen Smith, President 301-443-7577 American Society of Nephrology Judith Walker, Executive Director 202-857-1190 American Society of Transplant Physicians M. Suthanthiran, M.D., President 212-772 6700 American Society of Transplant Surgeons Clyde F. Barker, M.D., President 708-824-5700 American Thoracic Society Marilyn Hansen, Executive Director 212-315-8700 Association of Organ Procurement Organizations Al Yokie, Executive Director 703-573-AOPO Eye Bank Association of America Patricia Aiken-O’Neill, Esq., President and CEO 202-775-4999 International Society for Heart and Lung Transplantation James B. Gantenberg, Executive Director 312-664 0828

Guidelines 25

National Kidney and Urologic Diseases Advisory Board Ralph L. Bain, Ph.D., Executive Director 301-496-6045 National Kidney Foundation John Davis, Executive Director 800-622-9010 North American Transplant Coordinators Organization Diedre Panjeda, Executive Director 913-492-3600 South-Eastern Organ Procurement Foundation Thomas Armata, Executive Director 804-342-1414 The Partnership for Organ Donation Michael Evanisko, Executive Director 617-330-8650 Transplant Recipient International Organization Jonesy Maxson, Interim Manager 412-687-2210 United Network for Organ Sharing Gene A. Pierce, Executive Director 804-330-8500

More Guideline Sources The guideline above on transplantation is only one example of the kind of material that you can find online and free of charge. The remainder of this chapter will direct you to other sources which either publish or can help you find additional guidelines on topics related to transplantation. Many of the guidelines listed below address topics that may be of particular relevance to your specific situation or of special interest to only some patients having transplantation. 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.

26 Transplantation

Topic Pages: MEDLINEplus For patients wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and patientoriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages.” You can think of a health topic page as a guide to patient guides. 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 as being relevant to transplantation: ·

Guides On Transplantation Organ Transplantation http://www.nlm.nih.gov/medlineplus/organtransplantation.html Kidney Transplantation http://www.nlm.nih.gov/medlineplus/kidneytransplantation.html Bone Marrow Transplantation http://www.nlm.nih.gov/medlineplus/bonemarrowtransplantation. html Liver Transplantation http://www.nlm.nih.gov/medlineplus/livertransplantation.html Heart Transplantation http://www.nlm.nih.gov/medlineplus/hearttransplantation.html Lung Transplantation http://www.nlm.nih.gov/medlineplus/lungtransplantation.html Islet Cell Transplantation http://www.nlm.nih.gov/medlineplus/isletcelltransplantation.html Pancreas Transplantation http://www.nlm.nih.gov/medlineplus/pancreastransplantation.html

·

Other Guides Stem Cells/Stem Cell Transplantation http://www.nlm.nih.gov/medlineplus/stemcellsstemcelltransplanta tion.html

Within the health topic page dedicated to transplantation, the following was recently recommended to patients:

Guidelines 27

·

General/Overviews Transplant 101: Frequently Asked Questions Source: United Network for Organ Sharing http://www.patients.unos.org/101_faq.htm

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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 Financing Your Transplant Source: United Network for Organ Sharing http://www.patients.unos.org/101_finance.htm Financing Your Transplant: Insurance Source: United Network for Organ Sharing http://www.patients.unos.org/101_finance_insurance.htm Getting on the List: You Need a Transplant, What's Next? Source: United Network for Organ Sharing http://www.patients.unos.org/101_needtx_list.htm Organ Sharing: Understanding Differences in Waiting Times Source: United Network for Organ Sharing http://www.patients.unos.org/101_sharing_wttimedifferences.htm

·

From the National Institutes of Health Your Guide to Organ/Tissue Transplantation Source: National Institutes of Health, Clinical Center http://www.cc.nih.gov/ccc/patient_education/pepubs/transplant.pdf

·

Latest News Donor Heartbeat Not Required for Transplant Success Source: 07/24/2002, Reuters Health http://www.nlm.nih.gov/medlineplus/news/fullstory_8673.html Living Liver Donors Recuperate Well, No Regrets Source: 07/30/2002, Reuters Health http://www.nlm.nih.gov/medlineplus/news/fullstory_8725.html

28 Transplantation

More News on Organ Transplantation http://www.nlm.nih.gov/medlineplus/alphanews_o.html#OrganTr ansplantation ·

Law and Policy Expanded Medicare Coverage for Transplant Recipients Source: Health Resources and Services Administration http://www.organdonor.gov/expanded.htm Improving the Nation's Organ Transplantation System http://www.hrsa.gov/osp/dot/Fact%2520Sheet.pdf

·

Organizations Division of Transplantation Source: Health Resources and Services Administration http://www.hrsa.gov/osp/dot/dotmain.htm Organ Procurement and Transplantation Network http://www.optn.org/default.asp Scientific Registry of Transplant Recipients http://www.ustransplant.org/index.html TransWeb http://www.transweb.org/ United Network for Organ Sharing http://www.unos.org/

·

Research Immune Tolerance: Improving Transplantation Success Source: National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/publications/discovery/immune.htm Study Identifies Factors Associated With Families' Consent for Organ Transplantation Source: American Medical Association http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=Z ZZH3T0DKOC&sub_cat=627

·

Statistics About Transplants: Fast Facts Source: Scientific Registry of Transplant Recipients http://www.ustransplant.org/facts.html

Guidelines 29

Critical Data: U.S. Facts About Transplantation Source: United Network for Organ Sharing http://www.unos.org/Newsroom/critdata_main.htm Facts About Organ Donation and Transplantation Source: National Kidney Foundation http://www.kidney.org/general/news/25facts.cfm If you do not find topics of interest when browsing health topic pages, then you can choose to use the advanced search utility of MEDLINEplus at the following: http://www.nlm.nih.gov/medlineplus/advancedsearch.html. This utility is similar to the NIH Search Utility, with the exception that it only includes material linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search.

The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on transplantation. One of the advantages of CHID over other sources is that it 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: ·

Post Transplant Diet Source: Birmingham, AL: University of Alabama at Birmingham Hospital. 1998. 30 p. Contact: Available from University of Alabama at Birmingham Hospital. University Hospital. Department of Food and Nutrition Services, 619 South 19th Street, Birmingham, AL 35233. (205) 934-8055. Fax (205) 9342987. PRICE: $3.25 for single copy; $2.75 each for five or more copies, plus shipping and handling. Summary: This booklet describes a dietary program that is designed to help people with transplants avoid some of the problems associated with their post-transplant drug therapy. The most common side effects of immunosupressive drugs include weight gain, increased blood sugar, increased blood pressure, increased fats in the blood (cholesterol and

30 Transplantation

triglycerides), fluid and sodium gain, and weakened bones (osteoporosis). The booklet first reminds readers of the important role of diet therapy, and then outlines strategies to cut down on fats, sodium (salt), and starches and sweets. The booklet then reviews guidelines for fruits and vegetables, meat and meat substitutes, milk and milk products, and beverages. Other topics covered include reading labels, dining out, food preparation and recommended substitutions, bag lunches, herbs and spices to flavor foods, tips for weight control. The booklet then offers a chart of food groups, which summarizes the recommended foods, foods that are allowed in small amounts, and foods that are not recommended in each of the following groups: fats and oils; meat, poultry, and fish; dairy products; starches; fruits and vegetables; snacks and desserts; soups; and seasonings. A form for a sample meal pattern is provided; the dietitian can work with the patient to establish guidelines for each food group at each meal. The booklet concludes with nine pages of recipes, each of which has the nutrient analysis per serving noted. 3 tables. ·

Transplant Foundation Source: Richmond, VA: Transplant Foundation. 1994. 2 p. Contact: Transplant Foundation. 8002 Discovery Drive, Suite 310, Richmond, VA 23229. (804) 285-5115. PRICE: Single copy free. Summary: This brochure describes the Transplant Foundation, a not-forprofit national organization established to provide financial and education resources to transplant recipients in the United States. The Foundation helps transplant recipients in crisis and helps those unable to purchase the daily medications needed to prevent organ rejection (immunosuppressive agents). In addition, the Foundation works actively in the legislative arena by championing recipient advocacy issues and pushing for longterm solutions to today's health care problems. The cost of immunosuppressive medications for a transplant recipient often totals $12,000 per year. Many insurance companies and government programs do not offer the necessary support to obtain medication. The brochure explains how applications for financial assistance are reviewed and addressed. The brochure concludes with a section encouraging readers to contribute to the Foundation.

·

Organ Transplant Fund, Inc.: Reaching Out To Help Source: Memphis, TN: Organ Transplant Fund, Inc. 199x. 2 p. Contact: Available from Organ Transplant Fund, Inc. 1102 Brookfield, Suite 202, Memphis, TN 38119. (800) 489-3863 or (901) 684-1697. Fax (901)

Guidelines 31

684-1128. E-mail: [email protected]. Web site: http://www.otf.org. PRICE: Single copy free. Summary: This brochure describes the Organ Transplant Fund (OTF), a not-for-profit organization that provides transplant candidates with proven fundraising training and advice to help them raise money for the cost of a transplant and related expenses. The assistance provided by OTF ranges from helping to organize the volunteer fundraising efforts, to counseling on the use of various fundraising techniques and approaches, to acknowledging charitable donations to the campaigns. In assisting with patient campaigns, OTF also helps with publicity, negotiates bills, and processes payments to hospitals, physicians, pharmacies, and other providers of transplant-related services. The brochure describes three different types of campaigns offered by the OTF: 'Celebration of Life' campaigns, the medication grants program, and the emergency grants program. The brochure concludes by encouraging readers to contribute to the OTF. A blank organ donor card is included. The brochure is printed on light cardstock. ·

Finger in the Dike Or: How to Raise $140,000 for Organ Transplant Surgery in Less Than Four Weeks Source: Portland, OR: Oregon Donor Program. 199x. 23 p. Contact: Available from Oregon Donor Program. P.O. Box 532, Portland, OR 97207. (800) 452-1369, ext. 7888 or (503) 279-7888. Website: www.ordonorprogram.org. PRICE: Single copy free. Summary: This booklet was written by volunteers involved in successful community fundraising campaigns for individuals needing transplants. The booklet first explains how the changes in medical care and administration often leave families responsible for the costs of certain procedures, such as transplants. The booklet then offers ideas for raising lifesaving money by soliciting the public, focusing on describing how money was actually raised to finance medical procedures when no other means of financing existed. The booklet describes three fundraising efforts that each raised over $100,000 in less than a month. Each effort was coordinated, staffed, and managed by willing volunteers who were not professional fundraisers. Topics include determining the target amount, getting started, working with the media, picking a campaign leader, finding a campaign center, assembling a campaign staff, and getting money from organizations. The booklet concludes by offering suggestions to avoid getting discouraged and by reminding readers of the ongoing need for organ and blood donors.

32 Transplantation

·

Financing Transplantation: What Every Patient Needs to Know. 2nd edition Source: Richmond, VA: UNOS. 1996. 39 p. Contact: Available from UNOS. 1100 Boulders Parkway, Suite 500, P.O. Box 13770, Richmond, VA 23225-8770. (800) 24-DONOR. PRICE: Single copy free. Summary: This patient education booklet answers common questions that patients have about handling the costs associated with organ transplantation. Topics include social services available for transplant patients; the costs of transplantation; funding for transplantation; essential questions to ask any funding organization; and posttransplantation considerations. The second edition of this booklet presents updated cost information, an expanded list of organizations that offer financial assistance, the new Medicare coverage guidelines for immunosuppressant drugs, and information about the Federal Rehabilitation Act.

·

Live Donor Liver Transplant. [Transplante de Higado de Donante Viviente] Source: Bronx, NY: Latino Organization for Liver Awareness. 199x. [6 p.]. Contact: Available from Latino Organization for Liver Awareness. 1560 Mayflower Avenue, Bronx, NY 10461. (888) 367-5652. PRICE: Single copy free. Summary: This brochure describes living donor liver transplantation, which involves the removal of a portion of the donor's healthy liver for transplantation into the recipient with liver disease. This procedure is possible because the liver has the ability to regenerate. The brochure reviews the selection process for living donor liver transplantation, noting that potential donors are usually immediate family members (mothers, fathers, sisters, brothers, sons or daughters). Certain conditions prevent a person from being a donor, including: incompatible blood type, liver disease or hepatitis, significant pulmonary disease, active alcohol or substance abuse, HIV positive, morbid obesity, or pregnancy. The most common problems associated with living donor surgery include pain related to the surgery, bleeding, and infection; other risks include pneumonia, blood clots to the lung, deep vein thrombosis (clotting), side effects from general anesthesia, and infection. The risks of living donation to the recipient are similar to the risks of the conventional cadaveric (from a dead person) transplant; these include bleeding, infection, and rejection. Overall the success rates for living donor liver transplantation is similar to that of cadaveric liver transplantation. The brochure briefly

Guidelines 33

describes the surgical procedure and donor recovery after surgery, as well as how to handle the costs. The brochure notes that any patient listed for a liver transplant should consider living donor transplantation. The back half of the brochure offers the same information in Spanish. ·

Transplant Recipients' Bill of Rights and Responsibilities Source: New York, NY: National Kidney Foundation (NKF). 2001. 9 p. Contact: Available from National Kidney Foundation (NKF). 30 East 33rd Street, New York, NY 10016. (800) 622-9010. Website: www.kidney.org. PRICE: Single copy free. Summary: Although solid organ transplantation is a successful intervention that prolongs and improves the quality of life for recipients, transplantation is a treatment, not a cure. Recipients face a new set of challenges and responsibilities, such as the potentially serious side effects of immunosuppressant medications, and have a continuing need for specialized aftercare, both medical and psychosocial. This Transplant Recipients' Bill of Rights and Responsibilities was created to empower recipients to be proactive in obtaining the specialized health care they need. This document represents a nondiscriminatory, culturally sensitive framework for identifying and addressing the continuing needs of recipients. The rights are outlined and described and include quality care, respect and personal dignity, a voice in decision making, information, emotional support, and freedom from discrimination. Transplant recipients also have responsibilities: maintain long term health, provide information, display mutual respect, meet financial obligations, and recognize financial contingencies.

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 their site located at http://www.guideline.gov by using the keyword “transplantation” or synonyms. The following was recently posted: ·

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.; 1999 September 1; 20 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1589&sSearch_string=Transplantation

34 Transplantation

·

Guidelines for preventing opportunistic hematopoietic stem cell transplant recipients.

infections

among

Source: Centers for Disease Control and Prevention/Infectious Diseases Society of America/American Society for Blood and Marrow Transplantation.; 2000 October 20; 126 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1799&sSearch_string=Transplantation ·

Pancreas transplantation for patients with type 1 diabetes. Source: American Diabetes Association.; 1999 November (republished 2002 Jan); 1 page http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2367&sSearch_string=Transplantation

·

Peripheral blood stem cell transplantation: recommendations for nursing education and practice. Source: Oncology Nursing Society.; 1997; 44 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 0914&sSearch_string=Transplantation

·

U.S. Public Health Service guideline on infectious disease issues in xenotransplantation. Source: Centers for Disease Control and Prevention/Food and Drug Administration (U.S.)/Public Health Service (U.S.)/Health Resources and Services Administration/National Institutes of Health (U.S.)/Department of Health and Human Services (U.S.).; 2001 August 24; 56 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2157&sSearch_string=Transplantation Healthfinder™

Healthfinder™ is an additional source sponsored by the U.S. Department of Health and Human Services which 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:

Guidelines 35

·

Organ Donation Web Site Summary: Administered by the Health Resources and Services Administration (HRSA), this site provides information and resources on organ donation and transplantation issues. Source: Health Resources and Services Administration, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=1386

·

Solid Organ Transplantation Summary: The Division of Transplantation (DOT), Health Resources and Services Administration (HRSA) has responsibility within the department of Health and Human Services for public education to increase Source: Office of Special Programs, Health Resources and Services Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=3108

·

Solid Organ Transplantation: Glossary Of Terms Summary: This glossary defines key terms used in the bone marrow and organ donation and transplant arena, and is designed to simplify complex scientific terms. Source: Office of Special Programs, Health Resources and Services Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=888

·

Transplantation (Journal) Summary: This bi-monthly journal features articles and reports related to advances in transplantation surgery. Source: American Society of Transplantation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=5131

36 Transplantation

The NIH Search Utility After browsing the references listed at the beginning of this chapter, you may want to explore the NIH Search Utility. This allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEBSPACE. 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 transplantation. 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. 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 that often link to government sites are available to the public. 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

·

drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html

·

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

·

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

·

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

·

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

·

Yahoo.com: http://health.yahoo.com/health

·

WebMDÒHealth: http://my.webmd.com/health_topics

Vocabulary Builder The material in this chapter may have contained a number of unfamiliar words. The following Vocabulary Builder introduces you to terms used in this chapter that have not been covered in the previous chapter: Anemia: A reduction in the number of circulating erythrocytes or in the

Guidelines 37

quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH]

Anorectal: Pertaining to the anus and rectum or to the junction region between the two. [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 Tlymphocytes, 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] Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [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] Biliary: Pertaining to the bile, to the bile ducts, or to the gallbladder. [EU] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiopulmonary: Pertaining to the heart and lungs. [EU] Cardiovascular: Pertaining to the heart and blood vessels. [EU] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cirrhosis: Liver disease characterized pathologically by loss of the normal microscopic lobular architecture, with fibrosis and nodular regeneration. The term is sometimes used to refer to chronic interstitial inflammation of any organ. [EU] Cornea: The transparent structure forming the anterior part of the fibrous tunic of the eye. It consists of five layers : (1) the anterior corneal epithelium, continuous with that of the conjunctiva, (2) the anterior limiting layer (Bowman's membrane), (3) the substantia propria, or stroma, (4) the posterior limiting layer (Descemet's membrane), and (5) the endothelium of the anterior chamber, called also keratoderma. [EU] Curative: Tending to overcome disease and promote recovery. [EU] 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]

38 Transplantation

Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Glucose: D-glucose, a monosaccharide (hexose), C6H12O6, also known as dextrose (q.v.), found in certain foodstuffs, especially fruits, and in the normal blood of all animals. It is the end product of carbohydrate metabolism and is the chief source of energy for living organisms, its utilization being controlled by insulin. Excess glucose is converted to glycogen and stored in the liver and muscles for use as needed and, beyond that, is converted to fat and stored as adipose tissue. Glucose appears in the urine in diabetes mellitus. [EU] Heart Transplantation: The transference of a heart from one human or animal to another. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hepatitis: Inflammation of the liver. [EU] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [NIH] Hypertension: Persistently high arterial blood pressure. Various criteria for its threshold have been suggested, ranging from 140 mm. Hg systolic and 90 mm. Hg diastolic to as high as 200 mm. Hg systolic and 110 mm. Hg diastolic. Hypertension may have no known cause (essential or idiopathic h.) or be associated with other primary diseases (secondary h.). [EU] Immunogenetics: A branch of genetics which deals with the genetic basis of the immune response. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU]

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 insulindependent diabetes mellitus. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]

Guidelines 39

Malformation: A morphologic defect resulting from an intrinsically abnormal developmental process. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Motility: The ability to move spontaneously. [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Neurologic: Pertaining to neurology or to the nervous system. [EU] Osteoporosis: Reduction in the amount of bone mass, leading to fractures after minimal trauma. [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 Transplantation: The transference of a pancreas from one human or animal to another. [NIH] Pneumonia: Inflammation of the lungs with consolidation. [EU] Postoperative: Occurring after a surgical operation. [EU] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Pulmonary: Pertaining to the lungs. [EU] Reflux: A backward or return flow. [EU] Systemic: Pertaining to or affecting the body as a whole. [EU] Thoracic: Pertaining to or affecting the chest. [EU] Thrombosis: The formation, development, or presence of a thrombus. [EU] Tolerance: 1. the ability to endure unusually large doses of a drug or toxin. 2. acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU]

Toxic: Pertaining to, due to, or of the nature of a poison or toxin; manifesting the symptoms of severe infection. [EU] Transplantation: The grafting of tissues taken from the patient's own body or from another. [EU] Vaccination: The introduction of vaccine into the body for the purpose of inducing immunity. Coined originally to apply to the injection of smallpox

40 Transplantation

vaccine, the term has come to mean any immunizing procedure in which vaccine is injected. [EU] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] 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 substancespecific 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]

Seeking Guidance 41

CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people. These associations can become invaluable sources of information and advice. Many associations offer aftercare support, financial assistance, and other important services.8 In addition to support groups, your physician can be a valuable source of guidance and support. Therefore, finding a physician that can work with your unique situation is a very important aspect of your care. In this chapter, we direct you to resources that can help you find patient organizations and medical specialists. We begin by describing how to find associations and peer groups that can help you better understand transplantation. The chapter ends with a discussion on how to find a doctor that is right for you.

Associations and Transplantation9 Having an unfamiliar procedure such as transplantation can often produce anxiety and fear. The emotional distress can often be as taxing as the physical distress. Everyone has different ways of dealing with treatments or surgical procedures. Your attitude, your expectations, and how well you cope with your condition can all influence your well-being. This is true for both minor and major procedures. Associations and support groups have Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 9 This section has been adapted from http://wwww.ahcpr.gov/consumer/diaginf5.htm. 8

42 Transplantation

been found to help individuals cope with social, physical, and emotional aspects of transplantation. In addition to associations or groups that your doctor might recommend, we suggest that you consider the following list (if there is a fee for an association, you may want to check with your insurance provider to find out if the cost will be covered): ·

American Organ Transplant Association Address: American Organ Transplant Association 3335 Cartwright Road, Missouri City, TX 77459 Telephone: (281) 261-2682 Toll-free: (800) 546-5268 Fax: (281) 499-2315 Email: [email protected] Web Site: http://freeweb.pdq.net/talltex7 Background: The American Organ Transplant Association (AOTA) is a nonprofit organization dedicated to helping defray out-of-pocket expenses for organ transplant recipients. Founded in 1987, the Association also seeks to generate increased public awareness of organ transplantation and to provide information on the need, importance, and success of transplantation. AOTA engages in fund-raising, supplies necessary support services to affected individuals, provides referrals to appropriate agencies, and lobbies for government legislation on behalf of the transplant community. In addition, AOTA arranges air transportation for over 60 patients and family members per year to and from transplant centers for evaluation and check-ups; discounted rental cars for affected individuals and hospital personnel; free transportation to hospitals for patients anywhere in the country; and free hotel accommodations for three nights for family members who accompany patients to the hospital. AOTA offers a variety of materials including brochures, a regular newsletter, and a booklet entitled 'Life After Transplantation.'.

·

American Society of Transplant Physicians Address: American Society of Transplant Physicians 6900 Grove Road, Thorofare, NJ 08086-9447 Telephone: (609) 848-6205 Toll-free: (800) 489-3863 Fax: (609) 848-4016 Email: [email protected] Web Site: http://www.astp.org/

Seeking Guidance 43

Background: The American Society of Transplant Physicians (ATP) is an organization of transplant professionals dedicated to research, education, advocacy and patient care in transplantation science and medicine. The American Society of Transplant Physicians comprises 1,300 transplant physicians and scientists within the specialties of nephrology, gastroenterology, immunology, cardiology, pulmonology, surgery and pediatrics, who are in private practice and university settings with an active interest in transplantation medicine. These physicians are active in research and the management of transplant patients from the onset of end-stage disease to post-transplantation. These physicians are integral members of the 'transplant team' and in many cases, are the directors of their transplant program. ASTP membership also includes scientists who are involved in basic research that translates from 'bench to bedside,' improving the care of transplant patients. ·

Children's Organ Transplant Association, Inc Address: Children's Organ Transplant Association, Inc. 2501 COTA Drive, Bloomington, IN 47403 Telephone: (812) 336-8872 Toll-free: (800) 366-2682 Fax: (812) 336-8885 Email: [email protected] Web Site: http://www.cota.org Background: Children's Organ Transplant Association, Inc. (COTA) is a voluntary health organization whose primary mission is to ensure that no US citizen is ever denied a life-saving transplant or access to a transplant waiting list due solely to lack of funds. COTA's secondary focus is to promote organ donations and to provide public education in all aspects of the organ donation process. COTA works with individuals of all ages, not just children. The Association provides local campaigns with onsite staff assistance for start up; free donation containers and COTA flyers; fund raising advice and support; and campaign start-up kits. Founded in 1986, COTA assists in the coordination of hospital selection, patient transportation, and other transplant needs as requested. In order to qualify for COTA assistance, an individual must be a US citizen and in need of a life-saving transplant. Educational materials include brochures and fact sheets.

·

Eye Bank Association of America Address: Eye Bank Association of America 1015 18th Street, NW, Suite 1010, Washington, DC 20036

44 Transplantation

Telephone: (202) 775-4999 Toll-free: (800) 441-1280 Fax: (202) 429-6036 Email: [email protected] Web Site: http://www.restoresight.org/ Background: The Eye Bank Association of America (EBAA) is a not-forprofit organization dedicated to the restoration of sight through the promotion and advancement of eye banking. An eye bank retrieves, evaluates, and distributes eyes donated for corneal transplantation, research, and education. Member eye banks around the world make possible thousands of corneal transplants annually. The cornea is the front, clear portion of the eye through which light passes. Corneal blindness is a form of visual impairment caused when the cornea becomes clouded, scarred, or misshapen. This condition may be the result of disease, infection, or injury. Established in 1961 and consisting of 108 members, EBAA promotes research and professional education and provides a newsletter, brochures, and pamphlets. EBAA also maintains a web site at http://www.restoresight.org. ·

Living Bank International Address: Living Bank International P.O. Box 6725, Houston, TX 772656725 Telephone: (713) 961-9431 Toll-free: (800) 528-2971 Fax: (713) 961-0979 Email: [email protected] Web Site: http://www.livingbank.org Background: The Living Bank International is a nonprofit organization dedicated to the enhancement of organ and tissue donorship and transplantation. Established in 1968, Living Bank International works toward its goal of motivating and facilitating the commitment of enough organ and tissue donors so that no one must die or suffer for lack of a donation. The functions of the Living Bank are educating the public regarding the donation and utilization of organs and tissues; providing international donor commitment and automated registration services; and providing an information center to support appropriate agencies in maximum utilization of donated organs and tissues. Consisting of 350,000 members, the organization produces educational materials including a newsletter entitled 'The Bank Account' and an annual report entitled 'The Living Bank.' Programs include the Donor Education Program, which develops public service messages and supplies information for articles, newspapers, magazines, radio and television

Seeking Guidance 45

shows; the Local Living Banker Program, which recruits volunteers from all across America to work in the communities; and the Corporate and Association Program in which the leadership of large national corporations are approached to encourage their employees or members and their families to register. The Living Bank International can be reached at its e-mail address at infoatlivingbank.org or its web site address at http://www.livingbank.org. ·

National Association of Patients on Hemodialysis and Transplantation Address: National Association of Patients on Hemodialysis and Transplantation 150 Nassau Street, New York, NY 10038 Telephone: (212) 619-2720 Toll-free: (800) 622-9010

·

National Foundation For Transplants Address: National Foundation For Transplants 1102 Brookfield, Suite 202, Memphis, TN 38119 Telephone: (901) 684-1697 Toll-free: (800) 489-3863 Fax: (901) 684-1128 Email: [email protected] Web Site: http://www.transplants.org Background: The National Foundation for Transplants (NFT), formerly the Organ Transplant Fund, Inc., is a national not-for-profit organization dedicated to helping individuals who are in need of organ or bone marrow transplants through financial assistance, advocacy, and emotional support. The National Foundation for Transplants was established in 1983 in Memphis, TN as the Liver Organ Transplant Fund to assist an individual in the local area who was in critical need of a liver transplant, but unable to afford the procedure. The small group of volunteers who founded NFT went to work to raise philanthropic contributions to pay for the transplant and related expenses. Hearing of the success of this first effort, other candidates for liver and other types of transplants turned to the new organization for assistance in raising the funds needed to help pay for their transplants. What began as a local limited endeavor evolved into an organization that is helping hundreds of organ and tissue transplant candidates and recipients nationwide. NFT provides candidates with fund-raising training and advice that can enable a patient campaign to raise the money needed for transplant and related expenses. The assistance provided by NFT ranges from helping to organize the volunteer fund-raising efforts, to counseling on the use of various fund-raising techniques and approaches, to acknowledging the

46 Transplantation

charitable donations to the campaigns. In assisting with the patient campaigns, NFT also helps with publicity, negotiates bills, and processes payments to hospitals, physicians, pharmacies, and other providers of transplant-related services. Another NFT program is the 'Celebration of Life' Campaigns that focus on the ongoing financial needs to transplant recipients, whose transplant-related expenses (e.g., life-sustaining immunosuppressant medication costs) pose continuing monetary obstacles. 'Celebration of Life' Campaigns are created as mini- models of the patient campaigns and are implemented on a long-term basis, through the sustained efforts of transplant recipients and their volunteers. Additionally, emergency funds and short-terms assistance are available to assist with airfare, lodging, insurance premiums, home health care, and other transplant services and/or equipment. The National Foundation for Transplants also publishes 'Reaching Out To Help,' a quarterly newsletter and maintains a site on the World Wide Web at http://www.transplants.org.

Finding More Associations There are a number of directories that list additional medical associations that you may find useful. While not all of these directories will provide different information than what is listed above, by consulting all of them, you will have nearly exhausted all sources for patient associations. 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 transplantation. 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.

DIRLINE A comprehensive source of information on associations is the DIRLINE database maintained by the National Library of Medicine. The database comprises some 10,000 records of organizations, research centers, and government institutes and associations which primarily focus on health and biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov/. Simply type in “transplantation” (or a synonym)

Seeking Guidance 47

or the name of a topic, and the site will list information contained in the database on all relevant organizations.

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 “transplantation”. 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.” By making these selections and typing in “transplantation” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with transplantation. You should check back periodically with this database since it is updated every 3 months.

Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms for people having different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site: http://boards.webmd.com/roundtable. These online self-help communities can help you connect with a network of people whose concerns are similar to yours. Online support groups are places where people can talk informally. If you read about a novel approach, consult with your doctor or other healthcare providers, as the treatments or discoveries you hear about may not be scientifically proven to be safe and effective.

Finding Doctors One of the most important aspects of your treatment will be the relationship between you and your doctor or specialist. All patients having transplantation must go through the process of selecting a physician. While this process will vary from person to person, the Agency for Healthcare

48 Transplantation

Research and Quality makes a number of suggestions, including the following:10 ·

If you are in a managed care plan, check the plan’s list of doctors first.

·

Ask doctors or other health professionals who work with doctors, such as hospital nurses, for referrals.

·

Call a hospital’s doctor referral service, but keep in mind that these services usually refer you to doctors on staff at that particular hospital. The services do not have information on the quality of care that these doctors provide.

·

Some local medical societies offer lists of member doctors. Again, these lists do not have information on the quality of care that these doctors provide.

Additional steps you can take to locate doctors include the following: ·

Check with the associations listed earlier in this chapter.

·

Information on doctors in some states is available on the Internet at http://www.docboard.org. This Web site is run by “Administrators in Medicine,” a group of state medical board directors.

·

The American Board of Medical Specialties can tell you if your doctor is board certified. “Certified” means that the doctor has completed a training program in a specialty and has passed an exam, or “board,” to assess his or her knowledge, skills, and experience to provide quality patient care in that specialty. Primary care doctors may also be certified as specialists. The AMBS Web site is located at http://www.abms.org/newsearch.asp.11 You can also contact the ABMS by phone at 1-866-ASK-ABMS.

·

You can call the American Medical Association (AMA) at 800-665-2882 for information on training, specialties, and board certification for many licensed doctors in the United States. This information also can be found in “Physician Select” at the AMA’s Web site: http://www.amaassn.org/aps/amahg.htm.

This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. 11 While board certification is a good measure of a doctor’s knowledge, it is possible to receive quality care from doctors who are not board certified. 10

Seeking Guidance 49

Finding Specialists The American Academy of Allergy, Asthma, and Immunology (AAAAI) maintains a Physician Referral System on its Web site (http://www.aaaai.org/). The Referral System contains contact information for the organization’s 6,000 members, all medical professionals specializing in the treatment of allergies, asthma, or infectious diseases. To use this free service, go to the search form located at http://www.aaaai.org/scripts/find-adoc/main.asp and select the search criteria you would like to use by clicking on the circle to the left of the option. Then type in the information you are looking for such as the physician’s location, zip code, name, or specialty. Click the “Search” button. If your query returns information about particular physicians, click on the physician’s name for more information. If the previous sources did not meet your needs, you may want to log on to the Web site of the National Organization for Rare Disorders (NORD) at http://www.rarediseases.org/. NORD maintains a database of doctors with expertise in various rare diseases. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.

Selecting Your Doctor12 When you have compiled a list of prospective doctors, call each of their offices. First, ask if the doctor accepts your health insurance plan and if he or she is taking new patients. If the doctor is not covered by your plan, ask yourself if you are prepared to pay the extra costs. The next step is to schedule a visit with your chosen physician. During the first visit you will have the opportunity to evaluate your doctor and to find out if you feel comfortable with him or her. Ask yourself, did the doctor: ·

Give me a chance to ask questions about transplantation?

·

Really listen to my questions?

·

Answer in terms I understood?

·

Show respect for me?

·

Ask me questions?

·

Make me feel comfortable?

12 This

section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

50 Transplantation

·

Address the health problem(s) I came with?

·

Ask me my preferences about different alternatives to transplantation?

·

Spend enough time with me?

Trust your instincts when deciding if the doctor is right for you. But remember, it might take time for the relationship to develop. It takes more than one visit for you and your doctor to get to know each other.

Working with Your Doctor13 Research has shown that patients who have good relationships with their doctors tend to be more satisfied with their care and have better results. Here are some tips to help you and your doctor become partners: ·

You know important things about your symptoms and your health history. Tell your doctor what you think he or she needs to know.

·

It is important to tell your doctor personal information, even if it makes you feel embarrassed or uncomfortable.

·

Bring a “health history” list with you (and keep it up to date).

·

Always bring any medications you are currently taking with you to the appointment, or you can bring a list of your medications including dosage and frequency information. Talk about any allergies or reactions you have had to your medications.

·

Tell your doctor about any natural or alternative medicines you are taking.

·

Bring other medical information, such as x-ray films, test results, and medical records.

·

Ask questions. If you don’t, your doctor will assume that you understood everything that was said.

·

Write down your questions before your visit. List the most important ones first to make sure that they are addressed.

·

Consider bringing a friend with you to the appointment to help you ask questions. This person can also help you understand and/or remember the answers.

This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

13

Seeking Guidance 51

·

Ask your doctor to draw pictures if you think that this would help you understand.

·

Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.

·

Let your doctor know if you need more time. If there is not time that day, perhaps you can speak to a nurse or physician assistant on staff or schedule a telephone appointment.

·

Take information home. Ask for written instructions. Your doctor may also have brochures and audio and videotapes that can help you.

·

After leaving the doctor’s office, take responsibility for your care. If you have questions, call. If your symptoms get worse or if you have problems with your medication, call. If you had tests and do not hear from your doctor, call for your test results. If your doctor recommended that you have certain tests, schedule an appointment to get them done. If your doctor said you should see an additional specialist, make an appointment.

By following these steps, you will enhance the relationship you will have with your physician.

Broader Health-Related Resources In addition to the references above, the NIH has set up guidance Web sites that can help patients find healthcare professionals. These include:14 ·

Caregivers: http://www.nlm.nih.gov/medlineplus/caregivers.html

·

Choosing a Doctor or Healthcare Service: http://www.nlm.nih.gov/medlineplus/choosingadoctororhealthcareserv ice.html

·

Hospitals and Health Facilities: http://www.nlm.nih.gov/medlineplus/healthfacilities.html

You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.

14

52 Transplantation

Vocabulary Builder The following vocabulary builder provides definitions of words used in this chapter that have not been defined in previous chapters: Anxiety: The unpleasant emotional state consisting of psychophysiological responses to anticipation of unreal or imagined danger, ostensibly resulting from unrecognized intrapsychic conflict. Physiological concomitants include increased heart rate, altered respiration rate, sweating, trembling, weakness, and fatigue; psychological concomitants include feelings of impending danger, powerlessness, apprehension, and tension. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Arteries: The vessels carrying blood away from the heart. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] 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] Cardiac: Pertaining to the heart. [EU] Cyanosis: A bluish discoloration, applied especially to such discoloration of skin and mucous membranes due to excessive concentration of reduced haemoglobin in the blood. [EU] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Immunity: The condition of being immune; the protection against infectious disease conferred either by the immune response generated by immunization or previous infection or by other nonimmunologic factors (innate i.). [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] Membrane: A thin layer of tissue which covers a surface, lines a cavity or divides a space or organ. [EU] Ocular: 1. of, pertaining to, or affecting the eye. 2. eyepiece. [EU] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and

Seeking Guidance 53

diseases. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Porphyria: A pathological state in man and some lower animals that is often due to genetic factors, is characterized by abnormalities of porphyrin metabolism, and results in the excretion of large quantities of porphyrins in the urine and in extreme sensitivity to light. [EU] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]

Retinopathy: 1. retinitis (= inflammation of the retina). 2. retinosis (= degenerative, noninflammatory condition of the retina). [EU] Transfusion: The introduction of whole blood or blood component directly into the blood stream. [EU] Urinary: Pertaining to the urine; containing or secreting urine. [EU] Urology: A surgical specialty concerned with the study, diagnosis, and treatment of diseases of the urinary tract in both sexes and the genital tract in the male. It includes the specialty of andrology which addresses both male genital diseases and male infertility. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viruses: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. [NIH]

Clinical Trials 55

CHAPTER 3. CLINICAL TRIALS AND TRANSPLANTATION Overview Very few medical conditions have a single treatment. The basic treatment guidelines that your physician has discussed with you, or those that you have found using the techniques discussed in Chapter 1, may provide you with all that you will require. For some patients, current treatments can be enhanced with new or innovative techniques currently under investigation. In this chapter, we will describe how clinical trials work and show you how to keep informed of trials concerning transplantation.

What Is a Clinical Trial?15 Clinical trials involve the participation of people in medical research. Most medical research begins with studies in test tubes and on animals. Treatments that show promise in these early studies may then be tried with people. The only sure way to find out whether a new treatment is safe, effective, and better than transplantation is to try it on patients in a clinical trial.

What Kinds of Clinical Trials Are There? Clinical trials are carried out in three phases:

The discussion in this chapter has been adapted from the NIH and the NEI: www.nei.nih.gov/netrials/ctivr.htm.

15

56 Transplantation

·

Phase I. Researchers first conduct Phase I trials with small numbers of patients and healthy volunteers. If the new treatment is a medication, researchers also try to determine how much of it can be given safely.

·

Phase II. Researchers conduct Phase II trials in small numbers of patients to find out the effect of a new treatment.

·

Phase III. Finally, researchers conduct Phase III trials to find out how new treatments compare with standard treatments already being used. Phase III trials also help to determine if new treatments have any side effects. These trials--which may involve hundreds, perhaps thousands, of people--can also compare new treatments with no treatment.

How Is a Clinical Trial Conducted? Various organizations support clinical trials at medical centers, hospitals, universities, and doctors’ offices across the United States. The “principal investigator” is the researcher in charge of the study at each facility participating in the clinical trial. Most clinical trial researchers are medical doctors, academic researchers, and specialists. The “clinic coordinator” knows all about how the study works and makes all the arrangements for your visits. All doctors and researchers who take part in the study on transplantation carefully follow a detailed treatment plan called a protocol. This plan fully explains how the doctors will treat you in the study. The “protocol” ensures that all patients are treated in the same way, no matter where they receive care. Clinical trials are controlled. This means that researchers compare the effects of the new treatment with those of the standard treatment. In some cases, when no standard treatment exists, the new treatment is compared with no treatment. Patients who receive the new treatment are in the treatment group. Patients who receive a standard treatment or no treatment are in the “control” group. In some clinical trials, patients in the treatment group get a new medication while those in the control group get a placebo. A placebo is a harmless substance, a “dummy” pill, that has no effect. In other clinical trials, where a new surgery or device (not a medicine) is being tested, patients in the control group may receive a “sham treatment.” This treatment, like a placebo, has no effect and does not harm patients.

Clinical Trials 57

Researchers assign patients “randomly” to the treatment or control group. This is like flipping a coin to decide which patients are in each group. If you choose to participate in a clinical trial, you will not know which group you will be appointed to. The chance of any patient getting the new treatment is about 50 percent. You cannot request to receive the new treatment instead of the placebo or sham treatment. Often, you will not know until the study is over whether you have been in the treatment group or the control group. This is called a “masked” study. In some trials, neither doctors nor patients know who is getting which treatment. This is called a “double masked” study. These types of trials help to ensure that the perceptions of the patients or doctors will not affect the study results. Natural History Studies Unlike clinical trials in which patient volunteers may receive new treatments, natural history studies provide important information to researchers on how medical conditions develop over time or how effective a certain procedure is. A natural history study follows patient volunteers to see how factors such as age, sex, race, or family history might make some people better candidates for transplantation. A natural history study may also tell researchers if diet, lifestyle, or occupation play a role in how a treatment affects patients.

What Is Expected of Patients in a Clinical Trial? Not everyone can take part in a clinical trial for a specific procedure or treatment. Each study enrolls patients with certain features or eligibility criteria. These criteria may include the type and stage of disease or disorder, as well as, the age and previous treatment history of the patient. You or your doctor can contact the sponsoring organization to find out more about specific clinical trials and their eligibility criteria. If you are interested in joining a clinical trial, your doctor must contact one of the trial’s investigators and provide details about your diagnosis and medical history. If you participate in a clinical trial, you may be required to have a number of medical tests. You may also need to take medications and/or undergo surgery. Depending upon the treatment and the examination procedure, you may be required to receive inpatient hospital care. Or, you may have to return to the medical facility for follow-up examinations. These exams help find out how well the treatment is working. Follow-up studies can take months or years. However, the success of the clinical trial often depends on

58 Transplantation

learning what happens to patients over a long period of time. Only patients who continue to return for follow-up examinations can provide this important long-term information.

Recent Trials on Transplantation The National Institutes of Health and other organizations sponsor trials on various procedures and treatments. Because funding for research goes to the medical areas that show promising research opportunities, it is not possible for the NIH or others to sponsor clinical trials for every procedure and treatment at all times. The following lists recent trials dedicated to transplantation.16 If the trial listed by the NIH is still recruiting, you may be eligible. If it is no longer recruiting or has been completed, then you can contact the sponsors to learn more about the study and, if published, the results. Further information on the trial is available at the Web site indicated. Please note that some trials may no longer be recruiting patients or are otherwise closed. Before contacting sponsors of a clinical trial, consult with your physician who can help you determine if you might benefit from participation. ·

Long-term administration of sirolimus (rapamunetm) in solid organ transplant recipients study Condition(s): Organ Transplantation Study Status: This study is currently recruiting patients. Sponsor(s): Wyeth-Ayerst Research Purpose - Excerpt: To evaluate the safety of long-term administration of sirolimus oral solution for up to 5 additional years, or until the tablet formulation is commercially available (whichever occurs first) in solid organ transplant recipients who are currently receiving sirolimus and who have completed clinical trials with sirolimus (with or without cyclosporine (CsA). To evaluate the pharmacokinetics and safety of longterm administration of sirolimus tablets administered for up to 5 years, or until the tablet formulation is commercially available in solid organ transplant recipients who are currently receiving sirolimus and who have completed clinical trials with sirolimus (with or without CsA) or who are currently enrolled in protocol 0468E1-306-US. Phase(s): Phase III Study Type: Interventional

16

These are listed at www.ClinicalTrials.gov.

Clinical Trials 59

Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00037531;jsessionid=B906E49 4710395A12311C0E584126017

Benefits and Risks17 What Are the Benefits of Participating in a Clinical Trial? If you are interested in a clinical trial, it is important to realize that your participation can bring many benefits to you and society at large: ·

A new treatment could be more effective than the current treatment. Although only half of the participants in a clinical trial receive the experimental treatment, if the new treatment is proved to be more effective and safer than the current treatment, then those patients who did not receive the new treatment during the clinical trial may be among the first to benefit from it when the study is over.

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If the treatment is effective, then it may improve health or prevent diseases or disorders.

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Clinical trial patients receive the highest quality of medical care. Experts watch them closely during the study and may continue to follow them after the study is over.

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People who take part in trials contribute to scientific discoveries that may help other people. In cases where certain diseases or disorders run in families, your participation may lead to better care or prevention for your family members. The Informed Consent

Once you agree to take part in a clinical trial, you will be asked to sign an “informed consent.” This document explains a clinical trial’s risks and benefits, the researcher’s expectations of you, and your rights as a patient.

This section has been adapted from ClinicalTrials.gov, a service of the National Institutes of Health: http://www.clinicaltrials.gov/ct/gui/c/a1r/info/whatis?JServSessionIdzone_ct=9jmun6f291. 17

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What Are the Risks? Clinical trials may involve risks as well as benefits. Whether or not a new treatment will work cannot be known ahead of time. There is always a chance that a new treatment may not work better than a standard treatment. There is also the possibility that it may be harmful. The treatment you receive may cause side effects that are serious enough to require medical attention.

How Is Patient Safety Protected? Clinical trials can raise fears of the unknown. Understanding the safeguards that protect patients can ease some of these fears. Before a clinical trial begins, researchers must get approval from their hospital’s Institutional Review Board (IRB), an advisory group that makes sure a clinical trial is designed to protect patient safety. During a clinical trial, doctors will closely watch you to see if the treatment is working and if you are experiencing any side effects. All the results are carefully recorded and reviewed. In many cases, experts from the Data and Safety Monitoring Committee carefully monitor each clinical trial and can recommend that a study be stopped at any time. You will only be asked to take part in a clinical trial as a volunteer giving informed consent.

What Are a Patient’s Rights in a Clinical Trial? If you are eligible for a clinical trial, you will be given information to help you decide whether or not you want to participate. As a patient, you have the right to: ·

Information on all known risks and benefits of the treatments in the study.

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Know how the researchers plan to carry out the study, for how long, and where.

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Know what is expected of you.

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Know any costs involved for you or your insurance provider.

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Know before any of your medical or personal information is shared with other researchers involved in the clinical trial.

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Talk openly with doctors and ask any questions.

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After you join a clinical trial, you have the right to: ·

Leave the study at any time. Participation is strictly voluntary. However, you should not enroll if you do not plan to complete the study.

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Receive any new information about the new treatment.

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Continue to ask questions and get answers.

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Maintain your privacy. Your name will not appear in any reports based on the study.

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Know whether you participated in the treatment group or the control group (once the study has been completed). What about Costs?

In some clinical trials, the research facility pays for treatment costs and other associated expenses. You or your insurance provider may have to pay for costs that are considered standard care. These things may include inpatient hospital care, laboratory and other tests, and medical procedures. You also may need to pay for travel between your home and the clinic. You should find out about costs before committing to participation in the trial. If you have health insurance, find out exactly what it will cover. If you don’t have health insurance, or if your insurance company will not cover your costs, talk to the clinic staff about other options for covering the cost of your care. What Questions Should You Ask before Deciding to Join a Clinical Trial? Questions you should ask when thinking about joining a clinical trial include the following: ·

What is the purpose of the clinical trial?

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What are the standard treatments? Why do researchers think the new treatment may be better? What is likely to happen to me with or without the new treatment?

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What tests and treatments will I need? Will I need surgery? Medication? Hospitalization?

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How long will the treatment last? How often will I have to come back for follow-up exams?

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What are the treatment’s possible benefits to my condition? What are the short- and long-term risks? What are the possible side effects?

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·

Will the treatment be uncomfortable? Will it make me feel sick? If so, for how long?

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How will my health be monitored?

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Where will I need to go for the clinical trial? How will I get there?

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How much will it cost to be in the study? What costs are covered by the study? How much will my health insurance cover?

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Will I be able to see my own doctor? Who will be in charge of my care?

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Will taking part in the study affect my daily life? Do I have time to participate?

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How do I feel about taking part in a clinical trial? Are there family members or friends who may benefit from my contributions to new medical knowledge?

Keeping Current on Clinical Trials Various government agencies maintain databases on trials. The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide patients, family members, and physicians with current information about clinical research across the broadest number of diseases and procedures. 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 their Web site (www.clinicaltrials.gov) and search by “transplantation” (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 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/

General References The following references describe clinical trials and experimental medical research. They have been selected to ensure that they are likely to be available from your local or online bookseller or university medical library. These references are usually written for healthcare professionals, so you may consider consulting with a librarian or bookseller who might recommend a particular reference. The following includes some of the most readily available references (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

A Guide to Patient Recruitment : Today’s Best Practices & Proven Strategies by Diana L. Anderson; Paperback - 350 pages (2001), CenterWatch, Inc.; ISBN: 1930624115; http://www.amazon.com/exec/obidos/ASIN/1930624115/icongroupinterna

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A Step-By-Step Guide to Clinical Trials by Marilyn Mulay, R.N., M.S., OCN; Spiral-bound - 143 pages Spiral edition (2001), Jones & Bartlett Pub; ISBN: 0763715697; http://www.amazon.com/exec/obidos/ASIN/0763715697/icongroupinterna

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The CenterWatch Directory of Drugs in Clinical Trials by CenterWatch; Paperback - 656 pages (2000), CenterWatch, Inc.; ISBN: 0967302935; http://www.amazon.com/exec/obidos/ASIN/0967302935/icongroupinterna

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The Complete Guide to Informed Consent in Clinical Trials by Terry Hartnett (Editor); Paperback - 164 pages (2000), PharmSource Information Services, Inc.; ISBN: 0970153309; http://www.amazon.com/exec/obidos/ASIN/0970153309/icongroupinterna

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Dictionary for Clinical Trials by Simon Day; Paperback - 228 pages (1999), John Wiley & Sons; ISBN: 0471985961; http://www.amazon.com/exec/obidos/ASIN/0471985961/icongroupinterna

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Extending Medicare Reimbursement in Clinical Trials by Institute of Medicine Staff (Editor), et al; Paperback 1st edition (2000), National Academy Press; ISBN: 0309068886; http://www.amazon.com/exec/obidos/ASIN/0309068886/icongroupinterna

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·

Handbook of Clinical Trials by Marcus Flather (Editor); Paperback (2001), Remedica Pub Ltd; ISBN: 1901346293; http://www.amazon.com/exec/obidos/ASIN/1901346293/icongroupinterna

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Agammaglobulinemia: An immunologic deficiency state characterized by an extremely low level of generally all classes of gamma-globulin in the blood. [NIH] Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. [NIH] Antibody: An immunoglobulin molecule that has a specific amino acid sequence by virtue of which it interacts only with the antigen that induced its synthesis in cells of the lymphoid series (especially plasma cells), or with antigen closely related to it. Antibodies are classified according to their ode of action as agglutinins, bacteriolysins, haemolysins, opsonins, precipitins, etc. [EU] Antidiabetic: An agent that prevents or alleviates diabetes. [EU] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Arteritis: Inflammation of an artery. [NIH] Aspiration: The act of inhaling. [EU] Beclomethasone: An anti-inflammatory, synthetic glucocorticoid. It is used topically as an anti-inflammatory agent and in aerosol form for the treatment of asthma. [NIH] Benign: Not malignant; not recurrent; favourable for recovery. [EU] Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU]

Clinical Trials 65

Catheter: A tubular, flexible, surgical instrument for withdrawing fluids from (or introducing fluids into) a cavity of the body, especially one for introduction into the bladder through the urethra for the withdraw of urine. [EU]

Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Chemotherapy: The treatment of disease by means of chemicals that have a specific toxic effect upon the disease - producing microorganisms or that selectively destroy cancerous tissue. [EU] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Hypersensitivity: A state of altered reactivity in which the body reacts with an exaggerated immune response to a foreign substance. Hypersensitivity reactions are classified as immediate or delayed, types I and IV, respectively, in the Gell and Coombs classification (q.v.) of immune responses. [EU] 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] Infuse: To pour (a liquid) into something. [EU] Infusion: The therapeutic introduction of a fluid other than blood, as saline solution, solution, into a vein. [EU] Kinetic: Pertaining to or producing motion. [EU] Lymphocytic: Pertaining to, characterized by, or of the nature of lymphocytes. [EU] Lymphoma: Any neoplastic disorder of the lymphoid tissue, the term lymphoma often is used alone to denote malignant lymphoma. [EU] Lymphopenia: Reduction in the number of lymphocytes. [NIH] Malignant: Tending to become progressively worse and to result in death. Having the properties of anaplasia, invasion, and metastasis; said of

66 Transplantation

tumours. [EU] 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 tumour arising from the melanocytic system of the skin and other organs. When used alone the term refers to malignant melanoma. [EU] Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer - medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Metastasis: 1. the transfer of disease from one organ or part to another not directly connected with it. It may be due either to the transfer of pathogenic microorganisms (e.g., tubercle bacilli) or to transfer of cells, as in malignant tumours. The capacity to metastasize is a characteristic of all malignant tumours. 2. Pl. metastases. A growth of pathogenic microorganisms or of abnormal cells distant from the site primarily involved by the morbid process. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Myeloma: A tumour composed of cells of the type normally found in the bone marrow. [EU] Nephropathy: Disease of the kidneys. [EU] Neutropenia: Leukopenia in which the decrease in white blood cells is chiefly in neutrophils. [EU] Osteopetrosis: Excessive formation of dense trabecular bone leading to pathological fractures, osteitis, splenomegaly with infarct, anemia, and extramedullary hemopoiesis. [NIH] Pharmacokinetics: The action of drugs in the body over a period of time, including the processes of absorption, distribution, localization in tissues, biotransformation, and excretion. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of YEASTS. [NIH] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH]

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Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH]

Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The treatment of disease by ionizing radiation. [EU] Refractory: Not readily yielding to treatment. [EU] Remission: A diminution or abatement of the symptoms of a disease; also the period during which such diminution occurs. [EU] Rheumatoid: Resembling rheumatism. [EU] 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] 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] Sterility: 1. the inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. the state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] 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] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU]

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PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL

ABOUT PART II In Part II, we introduce you to additional resources and advanced research on transplantation. All too often, patients who conduct their own research are overwhelmed by the difficulty in finding and organizing information. The purpose of the following chapters is to provide you an organized and structured format to help you find additional information resources on transplantation. In Part II, as in Part I, our objective is not to interpret the latest advances on transplantation or render an opinion. Rather, our goal is to give you access to original research and to increase your awareness of sources you may not have already considered. In this way, you will come across the advanced materials often referred to in pamphlets, books, or other general works. Once again, some of this material is technical in nature, so consultation with a professional familiar with transplantation is suggested.

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CHAPTER 4. STUDIES ON TRANSPLANTATION Overview Every year, academic studies are published on transplantation or related procedures. Broadly speaking, there are two types of studies. The first are peer reviewed. Generally, the content of these studies has been reviewed by scientists or physicians. Peer-reviewed studies are typically published in scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals. In this chapter, we will show you how to locate peer-reviewed references and studies on transplantation. We will begin by discussing research that has been summarized and is free to view by the public via the Internet. We then show you how to generate a bibliography on transplantation and teach you how to keep current on new studies as they are published or undertaken by the scientific community.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and transplantation, 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

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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 in “transplantation” (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 a sample of what you can expect from this type of search: ·

Transplantation in the Patient with Hepatitis C Source: JASN. Journal of the American Society of Nephrology. 11(7): 1343-1353. July 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-6423. Summary: Liver disease is one of the leading causes of death in long term survivors after kidney (renal) transplantation. Hepatitis C virus (HCV) infection is currently the main cause of chronic liver disease in this group. This article discusses the use of transplantation in the patient with hepatitis C. The authors first review the basics of HCV infection: the virus, epidemiology, diagnostic tests, natural history, extrahepatic manifestations, and treatment. The authors then consider these same topics for HCV in patients on dialysis. Factors that may influence the risk of HCV infection in dialysis patients include the number of blood units transfused, the length of dialysis therapy, and the type of renal replacement therapy used. The management of HCV infection in dialysis patients on the waiting list has not been completely standardized. Morbidity and mortality from HCV infection after kidney transplantation are marked, affecting both patient and graft (transplant) survival. In the evaluation of the severity of HCV infection, liver tests, liver biopsy, and virologic tests are helpful. The rate of response to interferon therapy is usually higher in dialysis patients than in the general population. In patients with severe chronic hepatitis, a second liver biopsy may be required before entry on the waiting list for a kidney transplantation. Patients with liver cirrhosis (scarring) are considered for simultaneous liver and kidney transplantation. In HCV positive patients, administration of immunosuppression posttransplant should be reduced to the lowest possible levels, and close monitoring for infections is mandatory. Although the long term survival rates are lower in HCV positive compared with HCV negative graft recipients, kidney transplantation still remains the best option for HCV positive patients with end stage renal disease (ESRD). 1 figure. 4 tables. 91 references.

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Federally Funded Research on Transplantation The U.S. Government supports a variety of research studies relating to transplantation and associated procedures. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.18 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. Visit the CRISP Web site at http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket. You can perform targeted searches by various criteria including geography, date, as well as topics related to transplantation and related treatments. 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 transplantation and related treatments. In some cases, therefore, it may be difficult to understand how some basic or fundamental research could eventually translate into medical practice. The following sample is typical of the type of information found when searching the CRISP database for transplantation: ·

Project Title: Centers for Clinical Research On Transplantation Principal Investigator & Institution: Feig, Steven; Medicine; University of California Los Angeles Box 951361, 405 Hilgard Ave Los Angeles, Ca 90095 Timing: Fiscal Year 2000; Project Start 0-SEP-1996; Project End 1-DEC2004 Summary: This study is designed to determine if stem and progenitor cells from umbilical cord blood units (UCBUs) are a clinically acceptable alternative to those from marrow or peripheral blood for unrelated-donor allogeneic transplantation. Questions to be answered about UCBU transplantation include: 1) can children unrelated to the neonate-donors be transplanted with a graft failure rate no greater than 5-10 percent? 2) can adults and larger children (>40 Kg) also be transplanted successfully (all successful matched sib and matched unrelated-donor cord blood transplants to date have been for patients weighing less than 40 Kg)? 3) is graft-vs-host disease (GvHD) usually mild and easily manageable? 4)

18 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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how much and what kind of HLA disparity can be tolerated? 5) is there enough graft-vs-leukemia (GvL) effect to prevent relapse? 6) what is the course of immune reconstitution? To answer these and other questions about UCBU transplantation will require establishing: a) two to four collection and storage centers (Cord Blood Banks - CBBs) to provide the necessary resource by collecting, processing, cryopreserving and distributing human umbilical cord blood for transplantation to unrelated recipients; b) six to eight Cord Blood Transplant Centers (CBTCs) to follow common protocols for the transplantation of cord blood stem and progenitor cells; and c) a Medical Coordinating Center (MCC) to manage donor searches, facilitate the provision of cord blood units for transplants and collect and analyze data from these transplants. The purpose of this program is to accelerate and oversee clinical research in the rapidly emerging use of umbilical cord blood in place of marrow for transplantation. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Combined Bone Marrow and Organ Transplantation in Humans Principal Investigator & Institution: Fung, John J.; Professor of Surgery; Surgery; University of Pittsburgh at Pittsburgh 4200 5Th Ave Pittsburgh, Pa 15260 Timing: Fiscal Year 2000; Project Start 1-APR-1996; Project End 1-MAR2001 Summary: (Adapted from investigator's abstract) The investigators have shown previously that after whole organ transplantation, resident bone marrow- derived "passenger leukocytes" migrate out of the graft into the recipient and establish microchimerism. Furthermore, the ubiquitous presence of the donor chimeric cells in the tissues of long functioning allograft recipients, suggested that these cells may play a seminal role in graft acceptance and the induction of donor-specific tolerance. In a direct extension of this "natural" phenomenon, they have augmented the leukocyte load conveyed by the transplanted organs by treating a pilot group of 89 human recipients of liver, kidney, heart, lung, and pancreas allografts with simultaneous infusion of unmodified bone marrow cells (3 - 5 x 108/kg body weight). Fifty-nine patients in whom consent to harvest donor vertebral bodies was not available, served as contemporaneous controls. The patients did not receive any cytoablative or cytoreductive conditioning prior to transplantation, and were maintained on routine immunosuppression with TacrolimusTM and steroids after transplantation. The adjuvant procedure of bone marrow augmentation was safe. The patient and graft survival, according to the

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investigators, was substantially improved in the augmented group as compared to the controls. The frequency and severity of rejection was also comparable in both study and control groups. Furthermore, a higher level of chimerism and increased frequency of donor-specific immune modulation was witnessed in the augmented patients. Based on these and other observations, they hypothesize that both short and long-term allograft survival and function will improve in bone marrow augmented patients. Additionally, augmentation of chimerism may also reduce the rate of chronic rejection and most importantly endow the investigators with the capacity to wean or eventually withdraw immuno-suppression. They propose a systematic evaluation of donor bone marrow augmentation in liver transplant recipients and to compare the outcome with that of non-augmented contemporaneous controls. In addition, the outcome in the bone marrow-liver cohort will be compared with that of bone marrow augmented recipients of other organs (i.e., kidney, heart, pancreas, lung, etc.); each of these will also acquire their own nonaugmented organ-specific controls. The primary end-points that are to be examined are: (a) organ function and survival, (b) patient survival, and (c) the ability to reduce or withdraw immunosuppression. Secondarily, they also wish to monitor the frequency and severity of rejection, as well as that of GVHD. They will serially quantitate levels of donor cell chimerism and assess the immune status of these patients. These primary and secondary end-points will be correlated to obtain comprehensive information regarding the eventual outcome of bone-marrow augmented and control patients. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: In Utero Transplantation for Lysosomal Storage Disease Principal Investigator & Institution: Abkowitz, Janis L.; Associate Professor; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2000; Project Start 0-SEP-1994; Project End 1-AUG2003 Summary: Post-natal marrow or peripheral blood stem cell transplantation can effectively treat many genetic disorders which involve blood cells, but is not universally available because of its high cost, moderate risk, and the lack of suitable donors of hematopoietic stem cells. As importantly, in some diseases, such as the lysosomal storage disorders, neurologic toxicity occurs by birth, which is not reversible by transplantation. The investigators plan to study the in utero therapy of alpha-mannosidosis in cats. Besides transplanting hematopoietic stem cells from adult cats to domestic cat fetuses, they propose two novel approaches, the in utero transplantation of macrophage precursor cells

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and in utero gene transfer (with FeLV-pseudotyped, retroviral vectors containing marker genes and/or MANB cDNA). The investigators will also study the kinetics of tissue macrophage engraftment in a murine ROSA26 transplantation model, to identify the immediate precursor cell of microglia in brain, Kuppffer cells in liver, and alveolar macrophages in lung. The investigators will define the cellular mechanisms which mediate lodgment. The results of experiments in this murine model will be applied in the in utero transplantation studies of alpha-mannosidosis in cats. The investigators are hopeful that these studies will provide alternative approaches for the therapy of lysosomal storage disorders. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Prevention of Osteoporosis after Organ Transplantation Principal Investigator & Institution: Shane, Elizabeth J.; Professor of Clinical Medicine; Medicine; Columbia University Health Sciences Ogc New York, Ny 10032 Timing: Fiscal Year 2000; Project Start 1-APR-1999; Project End 1-MAR2002 Summary: Osteoporosis and fragility fractures affect 40-50 percent of patients who have had organ transplantation. Improved survival of transplant recipients and expansion of transplantation programs make it likely that the incidence of transplantation osteoporosis will grow substantially. Over the past five years, new insights have been gained into the natural history, demographic and biochemical features of bone loss and fracture after cardiac transplantation, many of which are applicable to other types of organ transplantation. It is now known that the significant declines in lumbar spine and hip bone density (8-10 percent) and fractures (25-40 percent) occur primarily during the initial 612 months after transplantation. Although women, older patients and those with low pretransplant bone mass are at increased risk, men also fracture frequently. Moreover, many patients fracture despite normal pretransplant bone density. The early post-transplant period is characterized by increases in markers of bone resorption and decreases in both serum 1,25(OH)2vitamin D and osteocalcin, a marker of bone formation, all of which are associated with more rapid rates of cancelleous bone loss. The purpose of this proposal is to use these data to design a rational approach to the prevention of bone loss and fractures after transplantation. The specific aims of the proposal are to evaluate the efficacy and safety of the active metabolite of vitamin D, 1,25(OH)2D (calcitriol) and the antiresorptive bisphosphonate drug, alendronate, in the prevention of bone loss at the spine and hip after cardiac transplantation; to characterize the effects of these drugs on biochemical

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indices of bone and mineral metabolism during the first year after cardiac transplantation; and to establish the incidence of vertebral fracture during the first year after cardiac transplantation in patients treated with either calcitriol or alendronate. These specific aims will be addressed in a prospective, double-blind, design in which approximately 120 cardiac recipients at Columbia-Presbyterian Medical Center will be randomized shortly after transplantation to receive either A. active alendronate and placebo calcitriol or B. placebo alendronate and active calcitriol for the duration of the first post-transplant year. The goals of the study will be accomplished using timed serial measurements of bone density (spine and hip; by DEXA), spine radiographs and biochemical assays of calciotropic hormones and bone turnover markers. It is expected that this research will lead to rational programs for prevention of this crippling form of osteoporosis. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Suppression

Transplantation

Tolerance

Induced

by

Linked

Principal Investigator & Institution: Davies, Joanna D.; Assistant Professor; Scripps Research Institute 10550 N Torrey Pines Rd San Diego, Ca 92037 Timing: Fiscal Year 2001; Project Start 5-AUG-2001; Project End 7-DEC2001 Summary: (provided by applicant): The only therapy available for end stage organ failure is organ transplantation. Without immunosuppressive drugs the transplanted organ would be rejected within days of transplantation. Current therapies have shown an enormous improvement in transplant survival over the last two decades. However, these therapies result in non-specific suppression of the immune system leaving the patient open to opportunistic infection and under an increased risk of developing cancer. Clearly, new therapies that result in specific suppression of only the graft-specific response for the lifetime of the recipient are acutely needed. In murine models of transplantation CD4- and CD8-specific monoclonal antibody treatment given at the time of grafting can prevent graft rejection. Tolerance is graft antigen-specific and induces CD4+ regulatory cells that are capable of preventing (suppressing) non-tolerant cells from responding to graft antigens but only if the tolerant and non-tolerant cells see their respective antigens on the same graft. This is termed "suppression by linked recognition". In this application we hope to develop a model of pre-transplant tolerance induction to a non-transplantation antigen to promote tolerance to a transplant by linked recognition. Using a murine model of islet

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transplantation we propose to induce antigen-specific tolerance to ovalbumin (OVA) with non-depleting CD4- and CD8-specific monoclonal antibodies (mAb). When tolerance to OVA is established we will test the ability of OVA-induced suppressor cells to suppress a transplantation antigen-specific response by grafting with an islet allograft that does or does not express OVA under the control of the rat insulin promoter. We will further challenge this system by testing its ability to induce islet transplantation tolerance in diabetic mice. In the course of these studies we hope to develop a new therapeutic strategy ultimately aimed to prevent transplantation. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

E-Journals: PubMed Central19 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).20 Access to this growing archive of e-journals is free and unrestricted.21 To search, go to http://www.pubmedcentral.nih.gov/index.html#search, and type “transplantation” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for transplantation in the PubMed Central database: ·

Activation and adoptive transfer of Epstein --Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease by Rajiv Khanna, Scott Bell, Martina Sherritt, Andrew Galbraith, Scott R. Burrows, Lee Rafter, Belinda Clarke, Richard Slaughter, Michael C. Falk, Jo Douglass, Trevor Williams, Suzanne L. Elliott, and Denis J. Moss; 1999 August 31 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=17898

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html. 20 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. 21 The value of PubMed Central, in addition to its role as an archive, lies 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. 19

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Allografts of Tumor Nuclear Transplantation Embryos: Differentiation Competence by JM Lust, DL Carlson, R Kowles, L Rollins-Smith, JW Williams, III, and RG McKinnell; 1991 August 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=52193

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Biventricular Resynchronization as an Unusual Bridge to Transplantation: Acute Effects by Edgardo J. Kaplinsky, Ricardo Pesce, Mariano Favaloro, and Sergio V. Perrone; 2001 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=101216

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Clinical Significance of Expression of Human Cytomegalovirus pp67 Late Transcript in Heart, Lung, and Bone Marrow Transplant Recipients as Determined by Nucleic Acid Sequence-Based Amplification by Giuseppe Gerna, Fausto Baldanti, Jaap M. Middeldorp, Milena Furione, Maurizio Zavattoni, Daniele Lilleri, and Maria Grazia Revello; 1999 April http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88622&ren dertype=external

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Comparative Quantitation of Cytomegalovirus (CMV) DNA in Solid Organ Transplant Recipients with CMV Infection by Using Two HighThroughput Automated Systems by Raymund R. Razonable, Robert A. Brown, Mark J. Espy, Antonio Rivero, Walter Kremers, Jennie Wilson, Cynthia Groettum, Thomas F. Smith, and Carlos V. Paya; 2001 December http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88568&ren dertype=external

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Comparison of Quantitative Cytomegalovirus (CMV) PCR in Plasma and CMV Antigenemia Assay: Clinical Utility of the Prototype AMPLICOR CMV MONITOR Test in Transplant Recipients by Angela M. Caliendo, Kirsten St. George, Shaw-Yi Kao, Jessica Allega, Ban-Hock Tan, Robert LaFontaine, Larry Bui, and Charles R. Rinaldo; 2000 June http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86743&ren dertype=external

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Contamination of Transplantable Human Tumor-Bearing Lines by Helicobacter hepaticus and Its Elimination by Kazuo Goto, Ken-Ichi Ishihara, Ayako Kuzuoka, Yasuyuki Ohnishi, and Toshio Itoh; 2001 October http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88412&ren dertype=external

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Definition of HLA-DQ as a transplantation antigen by Effie W. Petersdorf, Gary M. Longton, Claudio Anasetti, Eric M. Mickelson, Anajane G. Smith, Paul J. Martin, and John A. Hansen; 1996 December 24 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=26409

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Developmental Failure of Chimeric Embryos Expressing High Levels of H-2Dd Transplantation Antigens by L Jaffe, EJ Robertson, and EK Bikoff; 1992 July 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=49410

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Gene Therapy Via Primary Myoblasts: Long-Term Expression of Factor IX Protein Following Transplantation in vivo by Y Dai, M Roman, RK Naviaux, and IM Verma; 1992 November 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=50448

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Genetically Modified Keratinocytes Transplanted to Wounds Reconstitute the Epidermis by PM Vogt, S Thompson, C Andree, P Liu, K Breuing, D Hatzis, H Brown, RC Mulligan, and E Eriksson; 1994 September 27 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=44801

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Genetically Modified Skin Fibroblasts Persist Long After Transplantation but Gradually Inactivate Introduced Genes by TD Palmer, GJ Rosman, WRA Osborne, and AD Miller; 1991 February 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=51011

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Growth Characteristics and Expansion of Human Umbilical Cord Blood and Estimation of Its Potential for Transplantation in Adults by HE Broxmeyer, G Hangoc, S Cooper, RC Ribeiro, V Graves, M Yoder, J Wagner, S Vadhan-Raj, L Benninger, P Rubinstein, and ER Broun; 1992 May 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=49023

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High Levels of Epstein-Barr Virus DNA in Blood of Solid-Organ Transplant Recipients and Their Value in Predicting Posttransplant Lymphoproliferative Disorders by Fausto Baldanti, Paolo Grossi, Milena Furione, Lavinia Simoncini, Antonella Sarasini, Patrizia Comoli, Rita Maccario, Roberto Fiocchi, and Giuseppe Gerna; 2000 February http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86158&ren dertype=external

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Immunologic Basis of Transplant-Associated Arteriosclerosis by C Shi, W Lee, Q He, D Zhang, DL Fletcher, JB Newell, and E Haber; 1996 April 30 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=39485

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In vivo Induction of Antigen-Specific Transplantation Tolerance to Qa1a by Exposure to Alloantigen in the Absence of T-Cell Help by MA Rees, AS Rosenberg, TI Munitz, and A Singer; 1990 April 1 http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=53771&action =stream&blobtype=file&blobname=[PNASPDFPath]/1990/8707/pdf/pq002765.pdf

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Long-Term Transplantation of Canine Keratinocytes Made Resistant to G418 Through Retrovirus-Mediated Gene Transfer by MED Flowers, MAR Stockschlaeder, FG Schuening, D Niederwieser, R Hackman, AD Miller, and R Storb; 1990 March 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=53684

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Production of Germ-Line Chimeras in Zebrafish by Cell Transplants from Genetically Pigmented to Albino Embryos by S Lin, W Long, J Chen, and N Hopkins; 1992 May 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=49114

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Transplantation of a 17-Amino Acid [alpha]-Helical DNA-Binding Domain Into an Antibody Molecule Confers Sequence-Dependent DNA Recognition by KE McLane, DR Burton, and P Ghazal; 1995 May 23 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=41879

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Transplantation of an Oligodendrocyte Cell Line Leading to Extensive Myelination by U Tontsch, DR Archer, M DuBois-Dalcq, and ID Duncan; 1994 November 22 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=45282

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Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization by Christoph Kalka, Haruchika Masuda, Tomono Takahashi, Wiltrud M. Kalka-Moll, Marcy Silver, Marianne Kearney, Tong Li, Jeffrey M. Isner, and Takayuki Asahara; 2000 March 28 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=16255

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Transplantation of Glial Cells Enhances Action Potential Conduction of Amyelinated Spinal Cord Axons in the Myelin-Deficient Rat by DA Utzschneider, DR Archer, JD Kocsis, SG Waxman, and ID Duncan; 1994 January 4 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=42884

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Transplantation of Wheat Germ Agglutinin-Positive Hematopoietic Cells to Prevent or Induce Systemic Autoimmune Disease by EE Sardina, K Sugiura, S Ikehara, and RA Good; 1991 April 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=51417

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Transplantation Tolerance is Unrelated to Superantigen-Dependent Deletion and Anergy by J Salaun, A Bandeira, I Khazaal, O BurlenDefranoux, V Thomas-Vaslin, M Coltey, NML Douarin, and A Coutinho; 1992 November 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=50350

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Transplantation Tolerance: Fooling Mother Nature by M Suthanthiran; 1996 October 29 http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=37943&action =stream&blobtype=file&blobname=[PNASPDFPath]/1996/9322/pdf/pq012072.pdf

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. 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 the public.22 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 relating to transplantation, simply go to the PubMed Web site at www.ncbi.nlm.nih.gov/pubmed. Type “transplantation” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “transplantation” (hyperlinks lead to article summaries):

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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Interaction between cyclosporine and Hypericum perforatum (St. John's wort) after organ transplantation. Author(s): Moschella C, Jaber BL. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2001 November; 38(5): 1105-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11684566&dopt=Abstract

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Isolation, short-term culture, and transplantation of small hepatocytelike progenitor cells from retrorsine-exposed rats. Author(s): Gordon GJ, Butz GM, Grisham JW, Coleman WB. Source: Transplantation. 2002 April 27; 73(8): 1236-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11981414&dopt=Abstract

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Modified cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone therapy for posttransplantation lymphoproliferative disease in pediatric patients undergoing solid organ transplantation. Author(s): Suryanarayan K, Natkunam Y, Berry G, Bangs CD, Cherry A, Dahl G. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2001 October; 23(7): 452-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11878581&dopt=Abstract

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Philosophical and ethical issues in human organ transplantation. Author(s): Mackenzie KM. Source: British Journal of Nursing (Mark Allen Publishing). 2001 April 12-25; 10(7): 433-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12070387&dopt=Abstract

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St John's Wort supplements endanger the success of organ transplantation. Author(s): Ernst E. Source: Archives of Surgery (Chicago, Ill. : 1960). 2002 March; 137(3): 3169. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11888457&dopt=Abstract

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The effects of transplantation of osteoblastic cells with bone morphogenetic protein (BMP)/carrier complex on bone repair. Author(s): Tamura S, Kataoka H, Matsui Y, Shionoya Y, Ohno K, Michi KI, Takahashi K, Yamaguchi A. Source: Bone. 2001 August; 29(2): 169-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11502479&dopt=Abstract

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The practices of organ transplantation: a critique. Author(s): Tonti-Filippini N. Source: Australas Cathol Rec. 1990 January; 67(1): 58-66. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11652564&dopt=Abstract

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Transplantation for accidental acute high-dose total body neutron- and gamma-radiation exposure. Author(s): Chiba S, Saito A, Ogawa S, Takeuchi K, Kumano K, Seo S, Suzuki T, Tanaka Y, Saito T, Izutsu K, Yuji K, Masuda S, Futami S, Nishida M, Suzuki G, Gale RP, Fukayama M, Maekawa K, Hirai H. Source: Bone Marrow Transplantation. 2002 June; 29(11): 935-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12080361&dopt=Abstract

Vocabulary Builder Abscess: A localized collection of pus caused by suppuration buried in tissues, organs, or confined spaces. [EU] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Alternaria: A mitosporic Loculoascomycetes fungal genus including several plant pathogens and at least one species which produces a highly phytotoxic antibiotic. Its teleomorph is Lewia. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Antioxidant:

One of many widely used synthetic or natural substances

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added to a product to prevent or delay its deterioration by action of oxygen in the air. Rubber, paints, vegetable oils, and prepared foods commonly contain antioxidants. [EU] Arginine: An essential amino acid that is physiologically active in the Lform. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Aspergillosis: Infections with fungi of the genus aspergillus. [NIH] Atrophy: A wasting away; a diminution in the size of a cell, tissue, organ, or part. [EU] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [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] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiolitis: Inflammation of the bronchioles. [NIH] Carcinoma: A malignant new growth made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. [EU] Chimera: An individual that contains cell populations derived from different zygotes. [NIH] Cholangitis: Inflammation of a bile duct. [EU] Cholinergic: Resembling acetylcholine in pharmacological stimulated by or releasing acetylcholine or a related compound. [EU]

action;

Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chondrogenesis: The formation of cartilage. This process is directed by chondrocytes which continually divide and lay down matrix during development. It is sometimes a precursor to osteogenesis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Cryopreservation: Preservation of cells, tissues, organs, or embryos by freezing. In histological preparations, cryopreservation or cryofixation is used to maintain the existing form, structure, and chemical composition of all the constituent elements of the specimens. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a

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paracrine or autocrine rather than endocrine manner. [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] Cytotoxic: Pertaining to or exhibiting cytotoxicity. [EU] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dysplasia: Abnormality of development; in pathology, alteration in size, shape, and organization of adult cells. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Embryo: In animals, those derivatives of the fertilized ovum that eventually become the offspring, during their period of most rapid development, i.e., after the long axis appears until all major structures are represented. In man, the developing organism is an embryo from about two weeks after fertilization to the end of seventh or eighth week. [EU] Encephalitis: Inflammation of the brain. [EU] Endothelium: The layer of epithelial cells that lines the cavities of the heart and of the blood and lymph vessels, and the serous cavities of the body, originating from the mesoderm. [EU] Enterocytozoon: A genus of parasitic protozoa in the family Enterocytozoonidae, which infects humans. Enterocytozoon bieneusi has been found in the intestines of patients with AIDS. [NIH] Enzyme: A protein molecule that catalyses chemical reactions of other substances without itself being destroyed or altered upon completion of the reactions. Enzymes are classified according to the recommendations of the Nomenclature Committee of the International Union of Biochemistry. Each enzyme is assigned a recommended name and an Enzyme Commission (EC) number. They are divided into six main groups; oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding.

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Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] 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] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: The formation of fibrous tissue; fibroid or fibrous degeneration [EU] 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] 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] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Haemopoietic: Haematopoietic; pertaining to or effecting the formation of blood cells. [EU] Helicobacter: A genus of gram-negative, spiral-shaped bacteria that is pathogenic and has been isolated from the intestinal tract of mammals, including humans. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH]

Hepatic: Pertaining to the liver. [EU] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hormones: Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various endocrine glands and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects. [NIH]

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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] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hypotension: Abnormally low blood pressure; seen in shock but not necessarily indicative of it. [EU] Hypoventilation: A state in which there is a reduced amount of air entering the pulmonary alveoli. [EU] Hypoxemia: Deficient oxygenation of the blood; hypoxia. [EU] Idarubicin: An orally administered anthracycline antibiotic. The compound has shown activity against breast cancer, lymphomas and leukemias, together with potential for reduced cardiac toxicity. [NIH] Immunization: The induction of immunity. [EU] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [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] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]

Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU]

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Legionella: Gram-negative aerobic rods, isolated from surface water, mud, or thermally polluted lakes or streams. It is pathogenic for man and it has no known soil or animal sources. [NIH] Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Lipid: Any of a heterogeneous group of flats and fatlike substances characterized by being water-insoluble and being extractable by nonpolar (or fat) solvents such as alcohol, ether, chloroform, benzene, etc. All contain as a major constituent aliphatic hydrocarbons. The lipids, which are easily stored in the body, serve as a source of fuel, are an important constituent of cell structure, and serve other biological functions. Lipids may be considered to include fatty acids, neutral fats, waxes, and steroids. Compound lipids comprise the glycolipids, lipoproteins, and phospholipids. [EU] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Mannosidosis: Inborn error of metabolism marked by a defect in alphamannosidase activity that results in lysosomal accumulation of mannose-rich substrates. Virtually all patients have psychomotor retardation, facial coarsening, and some degree of dysostosis multiplex. It is thought to be an autosomal recessive disorder. [NIH] Mediastinitis: Inflammation of the mediastinum, the area between the pleural sacs. [NIH] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Metabolite: process. [EU]

Any substance produced by metabolism or by a metabolic

Mucosa: A mucous membrane, or tunica mucosa. [EU]

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Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neural: 1. pertaining to a nerve or to the nerves. 2. situated in the region of the spinal axis, as the neutral arch. [EU] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Oryzias: A genus of cyprinodontid fish that is an egg layer as opposed to others of the same order which are livebearers. It is used extensively in testing carcinogens. [NIH] Osteodystrophy: Defective bone formation. [EU] Osteonecrosis: Death of a bone or part of a bone, either atraumatic or posttraumatic. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins C-MOS. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Papillomavirus: A genus of papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH]

Parathyroid: 1. situated beside the thyroid gland. 2. one of the parathyroid glands. 3. a sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Parenteral: Not through the alimentary canal but rather by injection through

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some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Pathogen: Any disease-producing microorganism. [EU] Polyomavirus: A genus of the family papovaviridae consisting of potentially oncogenic viruses normally present in the host as a latent infection. The virus is oncogenic in hosts different from the species of origin. [NIH]

Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Receptor: 1. a molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., cell-surface receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and cytoplasmic receptors for steroid hormones. 2. a sensory nerve terminal that responds to stimuli of various kinds. [EU] Recurrence: The return of a sign, symptom, or disease after a remission. [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] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] 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] Sarcoma: A tumour made up of a substance like the embryonic connective tissue; tissue composed of closely packed cells embedded in a fibrillar or

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homogeneous substance. Sarcomas are often highly malignant. [EU] Serum: The clear portion of any body fluid; the clear fluid moistening serous membranes. 2. blood serum; the clear liquid that separates from blood on clotting. 3. immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU] Somatic: 1. pertaining to or characteristic of the soma or body. 2. pertaining to the body wall in contrast to the viscera. [EU] 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] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU] Symptomatic: 1. pertaining to or of the nature of a symptom. 2. indicative (of a particular disease or disorder). 3. exhibiting the symptoms of a particular disease but having a different cause. 4. directed at the allying of symptoms, as symptomatic treatment. [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU]

Thrombolytic: 1. dissolving or splitting up a thrombus. 2. a thrombolytic agent. [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]

Trichoderma: A mitosporic fungal genus frequently found in soil and on wood. It is sometimes used for controlling pathogenic fungi. Its teleomorph is Hypocrea. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH] Tumour: 1. swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. a new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Uterus: The hollow muscular organ in female mammals in which the fertilized ovum normally becomes embedded and in which the developing embryo and fetus is nourished. In the nongravid human, it is a pear-shaped structure; about 3 inches in length, consisting of a body, fundus, isthmus, and cervix. Its cavity opens into the vagina below, and into the uterine tube

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on either side at the cornu. It is supported by direct attachment to the vagina and by indirect attachment to various other nearby pelvic structures. Called also metra. [EU] Vaccine: A suspension of attenuated or killed microorganisms (bacteria, viruses, or rickettsiae), administered for the prevention, amelioration or treatment of infectious diseases. [EU] Ventricular: Pertaining to a ventricle. [EU] Vertebral: Of or pertaining to a vertebra. [EU] Viremia: The presence of viruses in the blood. [NIH] Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes. [NIH]

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CHAPTER 5. PATENTS ON TRANSPLANTATION Overview You can learn about innovations relating to transplantation by reading recent patents and patent applications. 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.23 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 to patients 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 to patients. 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.

23Adapted

from The U. S. Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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Patents on Transplantation By performing a patent search focusing on transplantation, 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 example of the type of information that you can expect to obtain from a patent search on transplantation: ·

Method instruments and kit for autologous transplantation Inventor(s): Vibe-Hansen; Henrik (Lyngby, DK), Lundsgaard; Charlotte (Clampenborg, DK), Osther; Kurt B. (Scottsdale, AZ), Idouraine; Ahmed (Chandler, AZ) Assignee(s): Verigen Transplantation Service International (VTSI) AG (DE) Patent Number: 6,379,367 Date filed: October 17, 2000 Abstract: Method for the effective transplantation of chondrocytes/cartilage to an articular joint surface defect is taught, as well as a description of certain instruments and kit for practicing the invention. Excerpt(s): The instant invention concerns the field of chondrocyte transplantation, bone and cartilage grafting, healing, joint repair and the prevention of arthritic pathologies. In particular methods for the preparation of the graft site, instruments for such preparation and for the autologous transplantation of cells to the prepared graft site. ... Despite the advances in cultivating chondrocytes, and manipulating bone and cartilage, there has not been great success with the attempts to transplant cartilage or chondrocytes for the repair of damaged articulating surfaces. The teachings of the instant invention provide for effective, and efficient means of promoting the transplantation of cartilage and/or chondrocytes into a defect in an articulating joint or other cartilage covered bone surface, whereby cartilage is regenerated to fix the defect. The instant invention also provides for surgical instruments which are designed prepare the graft site so as to facilitate the efficient integration of grafted

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material to the graft site. ... The instant invention provides a method for the effective treatment of articulating joint surface cartilage by the transplantation of chondrocytes in a suitable matrix, to a surface to be treated, with a hemostatic barrier and a cell-free covering-patch comprising; first placing a hemostatic barrier proximal to the surface to be treated, placing chondrocytes in a suitable matrix upon the surface to be treated distal to the hemostatic barrier, covering the surface to be treated with a cell-free covering-patch. A hemostatic barrier, as will be further described below, is a barrier which inhibits the penetration of vascularizing cells and tissue into the grafted material. In particular, the instant method provides for a hemostatic barrier that is a resorbable, semi-permeable material which inhibits or prohibits vascular infiltration through the barrier. In one embodiment the hemostatic barrier contains collagen. Cell-free, is used herein as in the art, and means a material that is substantially free from intact cells which are capable of further cell division, promulgation or biological activty. In a preferred embodiment, a cell-free material is free from all intact nucleated cells. In one embodiment, the instant method encompasses the use of a cell-free covering patch which contains a semi-permeable collagen matrix. In one preferred embodiment of the method, the porous surface of the cell-free covering-patch is directed towards the implant material. Web site: http://www.delphion.com/details?pn=US06379367__ ·

Costimulatory blockade and mixed chimerism in allo-transplantation Inventor(s): Sayegh; Mohamed (Westwood, MA), Sykes; Megan (Charlestown, MA) Assignee(s): The General Hospital Corporation (Charlestown, MA) Patent Number: 6,280,957 Date filed: February 4, 1999 Abstract: Use of the blockade of costimulation and hematopoietic stem cells in allograft transplantation. Excerpt(s): The invention relates to tissue and organ transplantation. ... The field of organ transplantation has enjoyed substantial progress during the last two decades, resulting in marked improvements in shortterm graft survival. Organ transplant recipients, however, still face substantial risks of long-term morbidity and mortality. Though modern immunosuppressive regimens have led to a dramatic reduction of the incidence of acute rejection episodes, they have yet to achieve a similar effect for chronic rejection, which is still the leading cause of graft loss during long-term follow-up. In addition, the requirement for life-long

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immunosuppressive drug therapy carries a significant risk of severe side effects, including tumors, infections and metabolic disorders. The reliable induction of donor-specific tolerance would solve both problems by obviating the need for chronic non-specific immunosuppression and by abrogating detrimental immunological reactions against the allograft. ... Although methods in which blockers of both pathways are administered may usually eliminate the need for other preparative steps, some embodiments include the inactivation of thymocytes or T cells, which can be performed prior to hematopoietic stem cell or graft transplantation. In preferred embodiments the method includes diminishing or inhibiting thymocyte or T cell activity, preferably the activity of thymic or lymph node T cells by administering to the recipient a short course of an immunosuppressive agent, e.g., a chemical or drug, e.g., cyclosporine, sufficient to inactivate thymocytes or T cells, preferably thymic or lymph node T cells. The duration of the short course of immunosuppressive agent is: approximately equal to or less than 30, 40, 60, 120, or 365 days; approximately equal to or less than 8-12 days, preferably about 10 days; approximately equal to or less than two, three, four, five, or ten times the 8-12 or 10 day period. The short course can begin: before or at about the time the treatment to induce tolerance is begun, e.g., at about the time stem cells are introduced into the recipient; on the day the treatment to induce tolerance is begun, e.g., on the day stem cells are introduced into the recipient; within 1, 2, 4, 6, 8, 10, or 30 days before or after the treatment to induce tolerance is begun, e.g., within 1, 2, 4, 6, 8, 10, or 30 days before or after stem cells are introduced into the recipient. The short course of an immunosuppressive can be administered in conjunction with an anti-T cell antibody The short course of an immunosuppressive should be sufficient in concentration and duration to inactivate T cells, e.g., thymic or lymph node T cells, which would not be inactivated by antibody-based inactivation of T cells, e.g., inactivation by intravenous administration of ATG antibody, or similar, preparations. Web site: http://www.delphion.com/details?pn=US06280957__ ·

Methods for preventing, inhibiting or treating graft rejection reactions in graft-versus-host disease (GVHD) and organ transplantation Inventor(s): Yamauchi; Toshihiko (Ibaraki, JP), Ishibashi; Akira (Ibaraki, JP), Tokuhara; Naoki (Ibaraki, JP), Nagai; Mitsuo (Ibaraki, JP) Assignee(s): Eisai Co., Ltd. (Tokyo, JP) Patent Number: 6,258,811 Date filed: April 2, 1999

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Abstract: The present invention provides remedies for graft-versus-host disease (GVHD) and graft rejection reactions in organ transplantation which comprise retinoic acid receptor (RAR) agonists as an active ingredient. Main examples thereof include 9-(4-methoxy-2,3,6trimethylphenyl)-7,8-dimethylnona-2,4,6,8-tetraen-1-oic acid, 4-[(E)-2(5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl)propenyl]b enzoic acid, 4-{2-[5-(4,7-dimethylbenzofuran-2-yl)pyrroyl]}benzoic acid, 4-{2-[5(5-chloro-7-ethylbenzofuran-2-yl)pyrrolyl]}benzoic acid and 4-{2-[5-(4,7dimethylbenzothiophen-2-yl)pyrrolyl]}benzoic acid. Excerpt(s): The present invention relates to methods for preventing, inhibiting or treating graft-versus-host disease (GVHD) and graft rejection reactions in organ transplantation. ... In bone marrow transplantation or blood transfusion, or organ transplantation from a donor to a recipient having no histocompatibility with the donor, the donor's lymphocytes migrate into the recipient. If the recipient cannot reject the donor's lymphocytes, the donor's lymphocytes take and proliferate in the recipient's body. Then the lymphocytes attack tissues with the guidance of antigens carried exclusively by the recipient, thus inducing disorders. ... In 1959, Mathe et al. reported for the first time graft-versus-host disease (GVHD) in a leukemic patient after having bone marrow transplantation. The major symptoms of GVHD include frequent fever, anthema, diarrhea, vomiturition, anorexia, abdominal pain and hepatopathy. GVHD breaks out in patients having non-autogenous myeloma cells and induces in some cases lethal diseases such as systemic erythroderma or hepatic insufficiency. When an immunodeficient patient has the transplantation of an organ which is rich in immunocompetent cells, there arises a high risk of the onset of graft-versus-host reactions. Therefore, it is an important problem to prevent and treat GVHD in infants or children who suffer from primary immunodeficiency and are going to have bone marrow transplantation for reconstructing the immune system or patients who are going to have bone marrow transplantation for treating malignant diseases. Web site: http://www.delphion.com/details?pn=US06258811__

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·

Method for examining chronic rejection reactions following organ transplantation and method for determining urine components Inventor(s): Koyama; Isamu (Tokyo, JP), Yasumura; Tadaki (Shiga, JP), Nemoto; Kyuichi (Tochigi, JP), Mae; Takako (Tokyo, JP), Saiga; Kan (Tokyo, JP), Takagi; Hisako (Gunma, JP), Isoda; Atsuko (Gunma, JP), Tanabe; Toshio (Gunma, JP) Assignee(s): Nippon Kayaku Kabushiki Kaisha (Tokyo, JP) Patent Number: 6,210,912 Date filed: February 12, 1999 Abstract: A method for detecting the onset of chronic rejection at an early stage after organ transplantation, characterized by assaying nitrogen trioxide (NO.sub.3), matrix metalloproteinase (MMP)-2 or the precursor thereof in body fluids drawn out of body. Excerpt(s): The present invention relates to methods for detecting the onset of chronic rejection after organ transplantation by examining body fluids drawn out of body, and more specifically, the present invention relates to methods for detecting rejection (chronic rejection) emerging at the chronic stage after organ transplantation by assaying nitrogen trioxide (NO.sub.3), matrix metalloproteinase-2 (referred to as "MMP-2") or the precursor thereof in body fluids, and a method for assaying MMP2 or the precursor thereof in urine. ... In patients with kidney transplantation, generally, chronic rejection is diagnosed by renal biopsy. However, the patients are suffered from periodic renal biopsy, which may deteriorate the renal function concomitantly. Furthermore, such chronic rejection proceeds slowly, with the resultant poor subjective symptoms, and therefore, most patients reject painful renal biopsy. ... It is an object of the present invention to provide simple methods capable of detecting chronic rejection at its early stage after organ transplantation. Web site: http://www.delphion.com/details?pn=US06210912__

·

Method for preparing organs for transplantation after cryopreservation Inventor(s): Fahy; Gregory M. (Gaithersburg, MD), Khirabadi; Bijan (Rockville, MD), Okouchi; Yasumitsu (Hazelwood, MO), Maciag; Thomas (Rockville, MD) Assignee(s): The American National Red Cross (Washington, DC) Patent Number: 6,187,529 Date filed: April 28, 1998

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Abstract: The invention relates to the field of organ and tissue perfusion. More particularly, the present invention relates to a method for preparing organs, such as the kidney and liver, for cryopreservation through the introduction of vitrifiable concentrations of cryoprotectant into them. To prepare the organ for cryopreservation, the donor human or animal, is treated in the usual manner and may also be treated with iloprost, or other vasodilators, and/or transforming growth factor .beta.1. Alternatively, or additionally, the organ which is to be cryopreserved can be administered iloprost, or other vasodilators, and/or transforming growth factor .beta.1 directly into its artery. The invention also relates to preparing organs for transplantation by a method for the removal of the cryoprotectant therefrom using low (such as raffinose, sucrose, mannitol, etc.), medium (such as agents with intermediate molecular weights of around 600-2,000) and high (such as hydroxyethyl starch) molecular weight agents osmotic buffering agents. The invention is also directed to new post-transplantation treatments such as the use of transforming growth factor .beta.1, N-acetylcysteine and aurothioglucose. Excerpt(s): This invention relates to the field of organ perfusion. More particularly, it relates to a computer controlled apparatus and method for perfusing isolated animal, including human, organs. Still more particularly, this invention relates to an apparatus and methods for introducing vitrifiable concentrations of cryoprotective agents into isolated organs or tissues in preparation for their cryopreservation and for removing these agents from the organs and tissues after their cryopreservation in preparation for their transplantation into an animal, including into a human. ... Organ preservation at cryogenic temperatures would permit the reduction of the wastage of valuable human organs and would facilitate better matching of donor and recipient, a factor which continues to be important despite the many recent advances in controlling rejection (see, Takiff et al., Transplantation 47:102-105 (1989); Gilks et al., Transplantation 43:669-674 (1987)). Furthermore, most techniques now being explored for inducing recipient immunological tolerance of a specific donor organ would be facilitated by the availability of more time for recipient preparation. ... In one embodiment, the present invention is directed to a computer-controlled apparatus and methods for perfusing a human or other animal organ, such as a kidney, liver, heart, etc., with a perfusate, and may include preparing the organ for such perfusion. The perfusion of the organ may be done for any one of a number of reasons including, but not limited to, for example: to prepare the organ for cryopreservation; to prepare the organ for transplantation after its cryopreservation; to preserve it by conventional means above 0.degree. C.; to keep it alive temporarily at high temperatures to study its physiology; to test the organ's viability; to attempt resuscitation of the

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organ; and to fix the organ for structural studies. The apparatus and methods may also be used to superfuse an organ or tissue slice. In another embodiment, this invention is directed to the treatment of the donor animal and/or the about-to-be donated organ with iloprost and/or other drugs to prepare it for perfusion. In another embodiment, this invention is directed to an apparatus and method which is used to prepare the organ for cryopreservation, such as by vitrification. In another embodiment, this invention is directed to an apparatus and methods for preparing an organ for transplantation into an appropriate host after its cryopreservation. Web site: http://www.delphion.com/details?pn=US06187529__ ·

Method for preventing tissue damage associated with graft-versus-host or host-versus-graft disease following transplantation Inventor(s): McDonald; George B. (Bellevue, WA) Assignee(s): Institute for Drug Research, Inc. (New York, NY) Patent Number: 6,096,731 Date filed: September 10, 1998 Abstract: A method for preventing tissue damage associated with graftversus-host disease in a patient having undergone hematopoietic cell transplantation, and host-versus-graft disease in a patient having undergone organ allograft transplantation. The method includes orally administering to the patient a prophylactically effective amount of a topically active corticosteroid, such as beclomethasone dipropionate, for a period of time following hematopoietic cell or organ allograft transplantation, and prior to the presentation of symptoms associated with graft-versus-host disease or host-versus-graft disease. Representative tissues includes tissue of the intestine and liver, while representative tissue damage includes inflammation thereof. Excerpt(s): This invention is directed to the prevention of tissue damage, such as damage to the intestine or liver caused by graft-versus-host disease following hematopoietic cell transplantation, or caused by hostversus-graft disease following intestinal or liver transplantation, by oral administration of a prophylactically effective amount of a topically active cortico steroid, such as beclomethasone dipropionate (BDP). ... Acute graft-versus-host disease (GVHD) is a complication of allogeneic hematopoietic cell transplantation in which tissues of the host, most frequently the skin, liver and intestine, are damaged by lymphocytes from the donor. The risk and severity of this immune-mediated condition are directly related to the degree of mismatch between a host and the

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donor of hematopoietic cells. For example, GVHD develops in up to 30% of recipients of human leukocyte antigen (HLA)-matched sibling marrow, in up to 60% of recipients of HLA-matched unrelated donor marrow, and in a higher percentage of recipient of HLA-mismatched marrow. Patients with mild intestinal GVHD present with anorexia, nausea, vomiting, abdominal pain and diarrhea, whereas patients with severe GVHD are disabled by these symptoms. If untreated, symptoms of intestinal GVHD persist and often progress; spontaneous remissions are unusual. In its most severe form, GVHD leads to necrosis and exfoliation of most of the epithelial cells of the intestinal mucosa, a frequently fatal condition. ... Recently, investigators have reported the results of a phase I trial of topically active corticosteroid, beclomethasone dipropionate (BDP), for the treatment of patients with intestinal GVHD (Baehr et al., Transplantation 60:1231-1238, 1995). In this trial, BDP capsules were given orally, 8 mg daily, half as enteric-coated capsules designed to dissolve in the alkaline pH of the upper small intestine, and half of the capsules that dissolve in the stomach. Significant improvement was found in the appetite, oral intake, nausea, and diarrhea over the course of therapy with oral BDP alone and with oral BDP added to prednisone therapy. However, the time to improvement in patients receiving BDP as monotherapy was 7-10 days, which is longer than the response usually seen with prednisone therapy. Web site: http://www.delphion.com/details?pn=US06096731__ ·

Cells with multiple altered epitopes on a surface antigen for use in transplantation Inventor(s): Chappel; Scott C. (Milton, MA) Assignee(s): Diacrin, Inc. (Charlestown, MA) Patent Number: 6,096,537 Date filed: October 7, 1997 Abstract: Cells suitable for transplantation which have at least two different epitopes on a surface antigen altered prior to transplantation to inhibit rejection of the cells following transplantation into an allogeneic or xenogeneic recipient are disclosed. These cells are more successfully transplanted than cells which have only a single epitope on the surface antigen altered. Preferably, the antigen on the cell surface which is altered is an MHC class I antigen. Two different epitopes on an MHC class I antigen can be altered by contacting the cell with two molecules, such as antibodies or fragments thereof (e.g., F(ab').sub.2 fragments), which bind to two different epitopes on the antigen. Preferred epitopes

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on human MHC class I antigens to be altered are epitopes recognized by the monoclonal antibodies W6/32 and PT85. Improved methods for transplantation utilizing cells which have at least two different epitopes on a surface antigen altered prior to transplantation are also disclosed. Excerpt(s): A number of diseases are treated by the transplantation of tissue donated by other humans (allografts) or obtained from animals (xenografts). For example, insulin-dependent diabetes is often treated by transplantation of insulin-secreting pancreatic islet cells. While the transplanted cells may have the capacity to perform the desired function (e.g., secretion of insulin in response to rising levels of glucose), the graft typically fails as a result of immunological rejection. Shortly after transplantation, cells of the immune system of the recipient recognize the allogeneic or xenogeneic cells as foreign and proceed to attack the graft through both humoral and cellular routes. Allogeneic or xenogeneic cells are initially recognized by the recipient's immune system through antigenic determinants expressed on the surface of the cells. The predominant antigens recognized as "non-self" are major histocompatibility complex class I and class II antigens (MHC class I and class II). MHC class I antigens are expressed on virtually all parenchymal cells (e.g., pancreatic islet cells). In contrast, MHC class II antigens are expressed on a limited number of cell types, primarily B cells, macrophages, dendritic cells, Langerhans cells and thymic epithelium. The interaction of foreign MHC antigens with the T cell receptor on host T cells causes these cells to become activated. Following activation, the T cells proliferate and induce effector functions which result in cell lysis and destruction of the transplanted cells. ... For transplantation to be a viable therapeutic option, approaches are needed to inhibit rejection of transplanted cells by the immune system of the recipient. One method for inhibiting this rejection process is by administration of drugs that suppress the function of the immune system. While drugs such as cyclophosphamide and cyclosporin effectively inhibit the actions of the immune system and thus allow graft acceptance, their use can cause generalized, non-specific immunosuppression in the graft recipient which leaves the recipient susceptible to other disorders such as infection and tumor growth. Additionally, administration of immunsuppressive drugs is often accompanied by other serious side effects such as renal failure and hypertension. ... It has been shown that it is possible to alter an antigen on the surface of a cell prior to transplantation to "mask" the antigen from normal recognition by cells of the recipient's immune system (see Faustman and Coe (1991) Science 252:1700-1702 and WO 92/04033). For example, MHC class I antigens on transplanted cells can be altered by contacting the cells with a molecule which binds to the antigen, such as an antibody or fragment thereof (e.g., a F(ab')2 fragment)

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prior to transplantation. This alteration of MHC class I antigens modifies the interaction between the antigens on the cells and T lymphocytes in the recipient following transplantation to thereby inhibit rejection of the transplanted cells. Additional methods for reducing the immunogenicity of an allograft or xenograft to inhibit rejection of the graft following transplantation in a host are needed. Web site: http://www.delphion.com/details?pn=US06096537__ ·

Cell compositions for use in transplantation Inventor(s): Quesenberry; Peter J. (Shrewsbury, MA) Assignee(s): University of Massachusetts (Boston, MA) Patent Number: 6,068,836 Date filed: August 25, 1997 Abstract: Methods for the preparation of bone marrow stem cell compositions for use in transplantation therapy and ex vivo gene therapy of a mammal. The methods involve the use of quiescent stem cells for transplantation therapy and quiescent transfected stem cells for ex vivo gene therapy. Excerpt(s): Bone marrow transplantation is often accompanied by marrow cytotoxic therapy to create marrow space or niches. The usual method of creating such niches is by irradiation and/or chemotherapy treatment. This practice has been challenged by Brecher, Saxe and colleagues, who demonstrated that bone marrow cells (e.g., hematopoietic stem cells) engraft into normal non-myeloablated hosts (Brecher, G. et al. (1982) PNAS USA 79:5085; and Saxe, D. F. et al. (1984) Exp. Hematol. 12:277). These investigators showed varying levels of engraftment up to 25% after infusion of normal bone marrow into nonmyeloablated hosts. ... One theoretical approach to transplantation involves procurement of stem cells for transplantation followed by expansion of the stem cells to increase their number prior to infusion into the host. Cellular expansion and/or induction into active cell cycling is accomplished by contacting cytokines or other agents, such as 5fluorouracil, with the stem cells in vivo, if expansion occurs prior to collection of stem cells; or in vitro, if expansion occurs following collection of stem cells. Long-term repopulation of bone marrow with cytokine-treated cells has been assessed in vivo (Bodine D. M., Blood, 79:913, 1992; Szilvassy S. J. and Cory, S., Blood 84:74, 1994; Li, C. L. and Johnson, G. R. Blood 84:408, 1994; and Ramshaw, H. S. et al., Experimental Hematology, 22:823, No. 548, 1994). ... There is a great need for methodologies to enhance engraftment of stem cells in a host

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mammal for the purpose of improved human bone marrow transplantation therapy as well as for improved human ex vivo gene therapy. Web site: http://www.delphion.com/details?pn=US06068836__ ·

Retinal pigment epithelium transplantation Inventor(s): Liu; Yao (Philadelphia, PA) Assignee(s): Photogenesis, Inc. (Los Angeles) Patent Number: 6,045,791 Date filed: May 19, 1995 Abstract: An implant is provided for transplantation to the subretinal area of a host's eye comprising a laminate of a monolayer of retinal pigment epithelium (RPE) cells and a non-toxic, flexible support that, upon exposure to a set of predetermined conditions, will not impede normal eye tissue function. A method for preparing a population of RPE cells for transplantation to the subretinal area of a host eye is also provided. The method includes the steps of providing donor tissue comprising RPE cells, harvesting from that tissue RPE cells, and apposing the harvested RPE cells as a monolayer to a non-toxic, flexible support that, upon transplantation to the subretinal area and exposure to a set of predetermined conditions, will not impede normal eye tissue function of the host eye and the transplanted population. A method for transplanting the above implant is also provided, comprising providing the implant, making an incision through a host's eye, at least partially detaching the retina to permit access to the subretinal area, and positioning the implant in the accessed area. Excerpt(s): The present invention relates in general to cell and tissue transplantation techniques. More particularly, the present invention is directed to techniques for transplanting populations of retinal pigment epithelium (RPE) cells as a monolayer to the subretinal region of the eye, and to methods for preparing implants comprising monolayers of RPE cells for transplantation. ... In an effort to recover what was previously thought to be an irreparably injured retina, researchers have suggested various forms of grafts and transplantation techniques, none of which constitute an effective manner for reconstructing a dystrophic retina. The transplantation of retinal cells to the eye can be traced to a report by Royo et al., Growth 23: 313-336 (1959) in which embryonic retina was transplanted to the anterior chamber of the maternal eye. A variety of cells were reported to survive, including photoreceptors. Subsequently del Cerro was able to repeat and extend these experiments (del Cerro et

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al., Invest. Ophthalmol. Vis. Sci. 26: 1182-1185, 1985). Soon afterward Turner, et al. Dev. Brain Res. 26:91-104 (1986) showed that neonatal retinal tissue could be transplanted into retinal wounds. ... Li and Turner, Exp. Eye Res. 47:911 (1988) have proposed the transplantation of retinal pigment epithelium (RPE) into the subretinal space as a therapeutic approach in the RCS dystrophic rat to replace defective mutant RPE cells with their healthy wild-type counterparts. According to their approach, RPE were isolated from 6- to 8-day old black eyed rats and grafted into the subretinal space by using a lesion paradigm which penetrates through the sclera and choroid. A 1 .mu.l bolus injection of RPE (40,00060,000 cells) was made at the incision site into the subretinal space by means of a 10 .mu.l syringe to which was attached a 30 gauge needle. However, while this technique is marginally appropriate for immature RPE cells, with mature cells it leads to activation and transformation of these cells which damages eye and retinal tissue. Web site: http://www.delphion.com/details?pn=US06045791__

Patent Applications on Transplantation As of December 2000, U.S. patent applications are open to public viewing.24 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 transplantation: ·

Method, instruments, and kit for autologous transplantation Inventor(s): Vibe-Hansen, Henrik ; (Lyngby, DK), Lundsgaard, Charlotte ; (Clampenborg, DK), Osther, Kurt B. ; (Scottsdale, AZ), Idouraine, Ahmed ; (Chandler, AZ) Correspondence: Morgan, Lewis & Bockius LLP; 1701 Market Street; Philadelphia; PA; 19103-2921; US Patent Application Number: 20020091396 Date filed: March 6, 2002 Abstract: Method for the effective transplantation of chondrocytes/cartilage to an articular joint surface defect is taught, as well as a description of certain instruments and kit for practicing the invention.

24

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

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Excerpt(s): The instant invention concerns the field of chondrocyte transplantation, bone and cartilage grafting, healing, joint repair and the prevention of arthritic pathologies. In particular methods for the preparation of the graft site, instruments for such preparation and for the autologous transplantation of cells to the prepared graft site. ... Despite the advances in cultivating chondrocytes, and manipulating bone and cartilage, there has not been great success with the attempts to transplant cartilage or chondrocytes for the repair of damaged articulating surfaces. The teachings of the instant invention provide for effective, and efficient means of promoting the transplantation of cartilage and/or chondrocytes into a defect in an articulating joint or other cartilage covered bone surface, whereby cartilage is regenerated to fix the defect. The instant invention also provides for surgical instruments which are designed prepare the graft site so as to facilitate the efficient integration of grafted material to the graft site. ... The instant invention provides a method for the effective treatment of articulating joint surface cartilage by the transplantation of chondrocytes in a suitable matrix, to a surface to be treated, with a hemostatic barrier and a cell-free covering-patch comprising; first placing a hemostatic barrier proximal to the surface to be treated, placing chondrocytes in a suitable matrix upon the surface to be treated distal to the hemostatic barrier, covering the surface to be treated with a cell-free covering-patch. A hemostatic barrier, as will be further described below, is a barrier which inhibits the penetration of vascularizing cells and tissue into the grafted material. In particular, the instant method provides for a hemostatic barrier that is a resorbable, semi-permeable material which inhibits or prohibits vascular infiltration through the barrier. In one embodiment the hemostatic barrier contains collagen. Cell-free, is used herein as in the art, and means a material that is substantially free from intact cells which are capable of further cell division, promulgation or biological activity. In a preferred embodiment, a cell-free material is free from all intact nucleated cells. In one embodiment, the instant method encompasses the use of a cell-free covering patch which contains a semi-permeable collagen matrix. In one preferred embodiment of the method, the porous surface of the cell-free covering-patch is directed towards the implant material. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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·

Method for in Transplantation

Vitro

Preconditioning

of

Myoblasts

before

Inventor(s): Tremblay, Jacques P. ; (Quebec, CA) Correspondence: Birch Stewart Kolasch & Birch; Po Box 747; Falls Church; VA; 22040-0747; US Patent Application Number: 20020012657 Date filed: June 9, 1999 Abstract: A method of pretreating healthy donor's myoblast cultures with growth or trophic factors like basic fibroblast growth factor (bFGF) and with concanavalin A on transplantation to subjects suffering of myopathy like muscular dystrophy is disclosed and claimed. Recipient muscles show a higher percentage of functional cells, a four-fold increase, demonstrated by the higher incidence of dystrophin-positive fibers, and does not require previous preconditioning of recipient muscles by irradiation or toxin administration. The recipient subjects were immunosuppressed with FK 506. When growing myoblasts with 20 .mu.g/ml concanavalin A or 100 ng/ml TPA for two to four days, migration of donor cells in recipient tissue was increased by 3-4 fold.This suggests that, when using primary cultures, metalloproteases are secreted by fibroblasts, resulting in a greater degradation of the extracellular matrix. Both metalloproteases and bFGF appear beneficial for the success of the transplantation. The use of recombinant myoblast expressing metalloproteases is also contemplated. Excerpt(s): The present invention is a method for preconditioning healthy donor's myoblasts in vitro before transplantation thereof in compatible patients suffering of recessive myopathies, particularly of muscular dystrophy. This in vitro preconditioning improves the success of the transplantation while not requiring an in vivo preconditioning of the patient's muscle by irradiation or by administering muscular toxin. ... Duchenne muscular dystrophy (DMD) is a progressive disease characterized by the lack of dystrophin under the sarcolemmal membrane.sup.6,19,28,37. One possible way to introduce dystrophin in the muscle fibers of the patients to limit the degeneration is to transplant myoblasts obtained from normal subjects.sup.30,34,35. Several groups have tried myoblast transplantations to DMD patients but poor graft success was observed.sup.17,22,24,38. Even in experimental myoblast transplantation using mdx mice, an animal model of DMD.sup.10,25,29, large amount of dystrophin-positive fibers were observed only when nude mdx mice were previously irradiated to prevent regeneration of the muscle fibers by host myoblasts.sup.32,43. High percentage of dystrophin-positive fibers was also observed in mdx mice

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immunosuppressed with FK 506 and in SCID mice, in both cases muscles were previously damaged by notexin injection and irradiated.sup.23,27. These results indicate that to obtain successful myoblast transplantation, it is necessary to have not only an immunodeficient mouse or a mouse adequately immunosuppressed but also a host muscle which has been adequately preconditioned. It is, however, impossible in clinical studies to use damaging treatments such as marcaine, notexin and irradiation. If good myoblast transplantation results can be obtained without using such techniques, this would be very helpful for myoblast transplantation in humans. ... Recently there has been an increasing interest on the effects of basic fibroblast growth factor (bFGF) and other growth factors on myoblast cultures and myoblast cell lines.sup.1,4,5. Basic FGF has been reported to both stimulate proliferation and inhibit differentiation of skeletal myoblasts in vitro.sup.15,16. Other growth or trophic factors like insulin growth factor I, transferrin, platelet-derived growth factor, epidermal growth factor, adrenocorticotrophin and macrophage colonystimulating factor as well as C kinase proteins activators or agonists by which the effect of bFGF is mediated.sup.20 may also have similar or even better effects than bFGF on the success of myoblast transplantation.sup.7. The use of these stimulating properties to enhance the success of transplantation by in vitro preconditioning of donor's cells and to replace at least partially the use of previously known methods of in vivo preconditioning of recipients' cells has never been suggested before. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Transplantation of Neural Cells for the Treatment of Chronic Pain or Spasticity Inventor(s): DINSMORE, JONATHAN ; (BROOKLINE, MA), SIEGAN, JULIE ; (BOSTON, MA) Correspondence: LAHIVE & COCKFIELD; 28 STATE STREET; BOSTON; MA; 02109; US Patent Application Number: 20010055587 Date filed: September 30, 1998 Abstract: Methods for using neural cells to treat chronic pain and/or spasticity are described. The neural cells can be derived from any mammal, and are preferably human or porcine in origin. The neural cells preferably are serotonergic cells or are gamma-aminobutryic acid (GABA)-producing cells. Neural cells can be obtained from adult, juvenile, embryonic or fetal donors. Neural cells can be modified to be

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suitable for transplantation into a subject. For example, the neural cells can be modified such that an antigen (e.g., an MHC class I antigen) on the cell surface which is capable of stimulating an immune response against the cell in a subject is altered (e.g., by contact with an anti-MHC class I antibody, or a fragment or derivative thereof) to inhibit rejection of the cell when introduced into the subject or can be genetically modified to produce a factor. In one embodiment, the neural cells are obtained from a pig which is essentially free from organisms or substances which are capable of transmitting infection or disease to the recipient subject. The neural cells of the present invention can be used to treat chronic pain and/or spasticity by delivering the cells into the spinal cord of a subject. Excerpt(s): As used herein, the term "primary" includes cells which are not transformed or immortalized. The primary cells for use in the instant methods do not display the abnormal growth characteristics of tumor cells of neural origin (such as neuroblastoma cells), e.g., the cells can be contact inhibited, are not dedifferentiated, and/or do not display anchorage independent growth. Primary cells can be used after removal from a donor or can be cultured prior to transplantation into a subject. ... The term "subject" includes mammals, e.g., primates (such as humans, and monkeys). The term "xenogeneic" as used herein refers to transplantation of cells from a donor of one species into a subject of a different species, e.g., porcine neural cells can be administered to a subject in an amount suitable to treat chronic pain and/or spasticity. ... The cells of the invention can be selected for transplantation based upon their ability to produce a desired chemical mediator, such as a factor which controls nerve excitation, e.g., preferred cells are serotonergic (i.e., secrete 5 hydroxy-tryptamine (5HT)) or secrete gamma-aminobutyric acid (GABA). The presence or absence of such factors can be readily assayed using techniques which are known in the art, e.g., using a bioassay or an immunoassay. For example, a rabbit polyclonal antiGABA antibody (Sigma, St. Louis, Mo.) can be used as described by Ibuki et al. (1997. Neuroscience 76:845) or an anti-5-HT antibody can be used (available from Incstar) as described by Eaton et al. (1997. Pain 72:59) in order to detect production of factors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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·

Method for Providing Pathogen-Free Porcine Tissue Suitable for Human Transplantation Inventor(s): Hunter, Richard ; (Princeton, NJ), Egan, E. Michael ; (Brookline, MA) Correspondence: Fish And Richardson; 225 Franklin Street; Boston; MA; 021102804 Patent Application Number: 20010049827 Date filed: August 4, 1997 Abstract: Methods for providing a pathogen-free pig or pig fetus as a donor of tissue, cells and/or organs to a recipient human. Animals are free of zoonotic pathogens. When fetal tissues are used for transplantation, donor animals are free from zoonotic pathogens, pathogens able to cross the placental barrier, and tissue-specific pathogens, e.g., neurotropic pathogens. Tissues, cells and organs from pigs free of the above-listed pathogens are suitable for transplantation into humans, include fetal neuronal cells for treatment of Parkinson's disease and islet cells for treatment of islet insufficiency-related diseases. Excerpt(s): This invention relates to the production and use of animals as a source of tissues, cells and organs for transplantation to a human recipient. ... Non-human animals are a potential source of donor tissue, cells and organs for transplantation into human recipients (xenografts). A major factor in achieving successful transplantation is the prevention of graft rejection. Long term administration of immunosuppressive drugs has been found to cause increased susceptibility to infection, renal failure, hypertension, and tumor growth. More recent methods of preventing graft rejection include modifying, masking or eliminating antigens capable of causing a T-lymphocyte-mediated response in the human host (e.g., U.S. Pat. No. 5,283,058). ... Recently developed methods for disease treatment include transplantation of specific cells or tissue to a host in need thereof. For example, islet cell transplantation has been successfully performed in animals made diabetic by prior treatment with drugs which destroy pancreatic .beta. cells. Successful transplantation in these animals has been shown to restore normal blood glucose regulation. Recent techniques have been developed for intracerebral transplantation of human fetal dopaminergic neurons in the treatment of Parkinson's disease. Transplantation of fetal neurons from human tissue requires the collection and dissection of tens of human fetuses in various states of surgical disruption. Donors are screened for transmissible diseases, but many human pathogens could escape detection under these relatively uncontrolled collection schemes.

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

CD25 binding molecules for use in the treatment of manifestations of rejection in transplantation Inventor(s): Feutren, Gilles ; (Mulhouse, FR), Howell, Richard Kimberley ; (Macclesfield, GB), Marbach, Peter ; (Therwil, CH), Roberts, Andrew ; (Southwater, GB), Schreier, Max H. ; (Basel, CH), Schreier, Karin ; (Basel, CH), Schreier, Daniel Mark ; (Basel, CH), Schreier, Anja Bettina ; (Basel, CH), Schulz, Manfred ; (Lorrach, DE) Correspondence: Thomas Hoxie; Novartis Corporation; Patent And Trademark Dept; 564 Morris Avenue; Summit; NJ; 079011027 Patent Application Number: 20010041179 Date filed: May 22, 2001 Abstract: Administration of monoclonal antibodies specific for IL-2R to xenograft recipients, or long-term to immunosuppression-intolerant or non-compliant patients over a period of time beyond the very early phase of organ transplantation, prevents transplant rejection. Excerpt(s): The invention is directed to the use of a CD25 binding molecule in the treatment of rejection in transplantation. ... A serious problem following transplantation is associated with the fact that transplant patients receive a long-term immunosuppression, a so-called triple therapy composed of a calcineurin inhibitor like cyclosporin A or FK-506, a steroid and a concomitant immunosuppressant like azathioprine, mycophenolic acid, mycophenolate mofetil, a 15deoxyspergualine, rapamycin or 40-0-(2-hydroxy)ethyl-rapamycin (RAD001). Some patients, in particular juvenile and adolescent patients, however, have difficulties in accepting the constraints of the treatment and show poor compliance. Others are intolerant to calcineurin inhibitors, and develop severe adverse side effects, e.g. renal disfunction, hirsutism, gingival hyperplasia and hypertension. As a result many patients decrease the dosage of the respective medication or stop it entirely. The result for both groups is an unsatisfactory level of immunosuppression with the threat of losing the transplant. ... Monoclonal antibodies specific for the interleukin-2 receptor (IL-2R) are currently used for the so-called induction treatment, i.e. as prophylactic short-term immunosuppressants for single or multiple administration in the very early phase following transplantation, e.g. shortly before the transplantation and up to 3 months after transplantation. Surprisingly, it has now been discovered that the administration of monoclonal antibodies specific for IL-2R over a period of time beyond the very early

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phase following transplantation to immunosuppression-intolerant or non-compliant patients decreases the risk of transplant rejection resulting from a reduced level of immunosuppression, especially from reduced levels of calcineurin inhibition. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Cloned ungulate embryos and animals, use of cells, tissues and organs thereof for transplantation therapies including parkinson's disease Inventor(s): Stice, Steven L. ; (Belchertown, MA), Cibelli, Jose ; (Amherst, MA), Robl, James M. ; (Belchertown, MA) Correspondence: Pillsbury Winthrop LLP; Intellectual Property Group; East Tower, Ninth Floor; 1100 New York Avenue, N.W.; Washington; DC; 20005-3918; US Patent Application Number: 20010039667 Date filed: May 1, 2001 Abstract: Methods and cell lines for cloning ungulate embryos and offspring, in particular bovines and porcines, are provided. The resultant fetuses, embryos or offspring are especially useful for the expression of desired heterologous DNAs, and may be used as a source of cells or tissue for transplantation therapy for the treatment of diseases such as Parkinson's disease. Excerpt(s): The present invention relates to cloning procedures in which cell nuclei derived from differentiated fetal or adult bovine cells, which include non-serum starved differentiated fetal or adult bovine cells, are transplanted into enucleated oocytes of the same species as the donor nuclei. The nuclei are reprogrammed to direct the development of cloned embryos, which can then be transferred into recipient females to produce fetuses and offspring, or used to produce cultured inner cell mass cells (CICM). Fetuses and animals derived from a single clonal line offer a safe and genetically modifiable source of transplantation tissue. The cloned embryos can also be combined with fertilized embryos to produce chimeric embryos, fetuses and/or offspring. ... The following publications, patent applications and patents are cited in this application as superscript numbers: 11. Fissore, et al., Mol. Reprod. Dev. 46:176-189 (1997) 14. Graham, Wister Inot. Symp. Monogr. 9:19 (1969) 25. Saito, et al., Roux's Arch. Dev. Biol. 201:134-141 (1992) 30. Stice and Robl, Mol. Reprod. Dev. 25:272-280 (1990) 33. Wall, et al., Development of porcine ova that were centrifuged to permit visualization of pronuclei and nuclei, Biol. Reprod. 32:645-651 (1985) 38. Prather, et al., U.S. Pat. No. 4,994,384, issued Feb. 19, 1991. 39. Wheeler, U.S. Pat. No. 5,057,420, issued Oct. 15,

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1991. 40. Rosenkrans, Jr., et al., U.S. Pat. No. 5,096,822, issued Mar. 17, 1992. 41. C. R. Freed et al., Arch. Neurol. 47, 505 (1990). 42. O. Lindvall et al., Science 247, 574 (1990). 43. C. R. Freed et al., N. Engl. J. Med. 327, 1549 (1992). 44. D. D. Spencer et al., ibid. 327, 1541 (1992). 45. H. Widner et al., ibid. 327, 1556 (1992). 46. M. Peschanski et al., Brain 117, 487 (1994). 47. J. H. Kordower et al., ibid. 332, 1118 (1995). 48. O. V. Kopyov et al., Cell Transplantation 5, 327 (1996). 49. T. B. Feeman et al., in Progress in Brain Research, D. M. Gash, J. R. Sladek, Eds. (Elsevier, N.Y., 1988), pp.. 473477. 50. T. K. Huffaker et al., Exp. Brain Res. 77, 329 (1989). 51. T. B. Freeman, L. Brandeis, J. Pearson, E. S. Flamm, in Cell and Tissue Transplantation into the Adult Brain, Ann. N.Y. Acad. Sci., E. C. Azmetia, A. Bjorklund, Eds. (N.Y. Academy of Sciences, New York, 1987), pp. 699702. 52. A. Bjorklund, U. Stenevi, S. B. Dunnett, F. H. Gage, Nature 298, 652 (1982). 53. W. R. Galpern, L. H. Burns, T. W. Deacon, J. Dinsmore, O. Isacson, Exp. Neurol. 140, 1 (1996). 54. T. Deacon et al., Nature Med. 3, 350 (1997). 55. E. D. Clarkson, W. M. Zawada, C. R. Freed, Cell Tissue Res. 289, 207 (1997). 56. T. H. Park, C. Mytil_neou, Brain Res. 559, 83 (1992). 57. K. D. Beck, B. Knusel, F. Hefti, Neuroscience 52, 855 (1993). 58. W. Fawcett, R. A. Barker, S. B. Dunnett, Exp. Brain Res. 106, 275 (1995). 59. C. Hyman et al., Nature 350, 230 (1991). 60. H. Takayama et al., Nature Med. 1, 53 (1995). 61. U.S. Pat. No. 5,698,446. 62. C. Patience, Y. Takeuchi, R. A. Weiss, Nature Med. 3, 282 (1997). 63. W. M. Zawada, D. L, Kirschman, J. J. Cohen, K. A. Heidenreich, C. R. Freed, Exp. Neurol. 140, 60 (1996). 64. M. Abercrombie, The Anatomical Record 94, 239 (1946). ... Genetic modification of ungulates such as cattle or pigs could be useful in increasing the efficiency of meat and/or milk production and generate a useful source of cells and tissues for xenotransplantation. An ideal system for producing transgenic animals for such applications would be highly efficient and use small numbers of recipient animals to produce transgenics. It would allow the insertion of a transgene or the detection of a specific DNA sequence, into a specific genotype. The insertion or deletion would preferably be into a predetermined site, e.g., effected via homologous recombination, which insertion or deletion would confer high expression and not affect general viability and productivity of the animal. Furthermore, the identification of a locus for insertion would allow multiple lines to be produced and crossed to produce homozygotes and new genetic background could easily be added to the transgenic line by the production of new transgenics at any time. Therefore, the ideal system would likely require the transfection and selection of cells that could be easily grown in culture yet retain the potency to form germ cells and pass the gene to subsequent generations. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with transplantation, you can access the U.S. Patent Office archive via the Internet at no cost to you. This archive is available at the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” You will see two broad options: (1) Patent Grants, and (2) Patent Applications. To see a list of granted patents, perform the following steps: Under “Patent Grants,” click “Quick Search.” Then, type “transplantation” (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 transplantation. You can also use this procedure to view pending patent applications concerning transplantation. Simply go back to the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” Select “Quick Search” under “Patent Applications.” Then proceed with the steps listed above.

Vocabulary Builder 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] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Alkaline: Having the reactions of an alkali. [EU] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Collagen: The protein substance of the white fibres (collagenous fibres) of skin, tendon, bone, cartilage, and all other connective tissue; composed of molecules of tropocollagen (q.v.), it is converted into gelatin by boiling. collagenous pertaining to collagen; forming or producing collagen. [EU] Dendritic: 1. branched like a tree. 2. pertaining to or possessing dendrites. [EU]

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Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as SPECTRIN and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Epithelium: The covering of internal and external surfaces of the body, including the lining of vessels and other small cavities. It consists of cells joined by small amounts of cementing substances. Epithelium is classified into types on the basis of the number of layers deep and the shape of the superficial cells. [EU] 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] Exfoliation: A falling off in scales or layers. [EU] Extracellular: Outside a cell or cells. [EU] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] GABA: The most common inhibitory neurotransmitter in the central nervous system. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hirsutism: Abnormal hairiness, especially an adult male pattern of hair distribution in women. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygote: identical. [NIH]

An individual in which both alleles at a given locus are

Humoral: Of, relating to, proceeding from, or involving a bodily humour now often used of endocrine factors as opposed to neural or somatic. [EU]

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Hyperplasia: The abnormal multiplication or increase in the number of normal cells in normal arrangement in a tissue. [EU] Iloprost: An eicosanoid, derived from the cyclooxygenase pathway of arachidonic acid metabolism. It is a stable and synthetic analog of epoprostenol, but with a longer half-life than the parent compound. Its actions are similar to prostacyclin. Iloprost produces vasodilation and inhibits platelet aggregation. [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] Immunocompetence: The ability of lymphoid cells to mount a humoral or cellular immune response when challenged by antigen. [NIH] Incision: 1. cleft, cut, gash. 2. an act or action of incising. [EU] 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] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intravenous: Within a vein or veins. [EU] Mannitol: A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. [NIH] Medicament: A medicinal substance or agent. [EU] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Myopathy: Any disease of a muscle. [EU] Nausea: An unpleasant sensation, vaguely referred to the epigastrium and abdomen, and often culminating in vomiting. [EU] 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

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nucleic acids and found in all living cells. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [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] Photoreceptors: Cells specialized to detect and transduce light. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Quiescent: Marked by a state of inactivity or repose. [EU] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Recombinant: 1. a cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU]

Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU]

Sclera: The tough white outer coat of the eyeball, covering approximately the posterior five-sixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] 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] 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] Vegetative: 1. concerned with growth and with nutrition. 2. functioning involuntarily or unconsciously, as the vegetative nervous system. 3. resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. of, pertaining to, or characteristic of plants. [EU] Ventral: 1. pertaining to the belly or to any venter. 2. denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU]

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CHAPTER 6. BOOKS ON TRANSPLANTATION Overview This chapter provides bibliographic book references relating to transplantation. You have many options to locate books on transplantation. The simplest method is to go to your local bookseller and inquire about titles that they have in stock or can special order for you. Some patients, however, feel uncomfortable approaching their local booksellers and prefer online sources (e.g. www.amazon.com and www.bn.com). In addition to online booksellers, excellent sources for book titles on transplantation include the Combined Health Information Database and the National Library of Medicine. Once you have found a title that interests you, visit your local public or medical library to see if it is 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 “transplantation” (or synonyms) into the “For these words:” box. You will only receive results on books. You should check back periodically with this database which is updated every 3 months. The following is a typical result when searching for books on transplantation:

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·

Stepping Into a New Life: A Transplant Recipient's Guide to LongTerm Care Source: East Hanover, NJ: Novartis Pharmaceuticals Corporation. 1997. 35 p. Contact: Available from Transplant Recipients International Organization, Inc. (TRIO). 1000 16th Street, NW, Suite 602, Washington, DC 20036-5705. (800) TRIO-386 or (202) 293-0980. Fax (202) 293-0873. Email: [email protected]. PRICE: Single copy free. Summary: This booklet outlines a care plan for transplant patients who have reached the 6 month posttransplant mark. The first 6 months after transplant are characterized by a close connection with one's transplant team. The booklet emphasizes that this connection will evolve and that patients must make a commitment to their own health care and to keeping their new organ stable and functioning. Most important, patients must be committed to taking the prescribed dose of medication each and every day for the rest of their lives. The booklet describes the transfer of medical care from the transplant team to the community health professional, strategies to maintain stability and to avoid complications (such as transplant rejection), and ways to improve quality of life. The latter section discusses the importance of nutrition and exercise, the role of employment and health insurance, travel, romance and parenthood, and networking with other transplant recipients. The booklet includes a glossary of important terms, blank space for readers to record their questions and concerns, and the full prescribing information for Neoral (cyclosporine) capsules and oral solution. Throughout the booklet, the authors emphasize the importance of patient compliance to the medication regimens as the crucial factor for long term success with the transplant.

·

UNOS Organ Procurement, Preservation and Distribution in Transplantation. 2nd ed Source: Richmond, VA: United Network for Organ Sharing (UNOS). 1996. 419 p. Contact: Available from United Network for Organ Sharing (UNOS). 1100 Boulders Parkway, Suite 500, Richmond, VA 23225-8770. (888) 8946361 or (804) 330-8541. Fax (804)330-8593. Website: www.unos.org. PRICE: $70.00 plus shipping and handling. Summary: This 34 chapter book offers the current recommendations and standards of procurement, preservation, and distribution of organs and tissues as established and carried out by the United Network for Organ Sharing (UNOS). The author starts with a history of UNOS and

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transplantation, transplantation as a frontier for bioethics and bioscience and the legal aspects of organ and tissue procurement and transplantation. Following are descriptions of a medical examiner's review of organ and tissue donation, organ procurement organizations, brain death determination, donor evaluation for organ and tissue procurement, and cadaver donor management. The author then discusses organ and tissue removal for the kidney, liver, pancreas, small bowel, heart, and lung. Also covered are organ preservation, the nonheartbeating donor, coordination of the single and multiple organ donor, histocompatibility testing for transplantation, serologic testing in the organ and tissue donor, organ sharing (the UNOS Organ Center), and the transportation, packaging, and labeling of cadaveric organs. Also covered are donor family support programs, requirements of OPTN (Organ Procurement and Transplantation Network) membership, and data requirements of OPTN members. Other chapters include the educational aspects of organ procurement; the procurement and processing of bone, tissue and aortic valve allografts; corneal procurement for transplantation; embalming the organ and tissue donor; present alternatives to the cadaver organ shortage; and the future of transplantation. Each chapter offers extensive references and black and white figures and photographs, where applicable. ·

Puzzle People: Memoirs of a Transplant Surgeon Source: Pittsburgh, PA: University of Pittsburgh Press. 1992. 371 p. Contact: Available from Cup Services. P.O. Box 6525, Ithaca, NY 14851. (800) 666-2211. PRICE: $24.95 plus shipping and handling. ISBN: 082293714X. Summary: This book is the autobiography of Dr. Thomas Starzl, a pioneer in the field of liver transplantation. The author offers his position on many controversial issues, including brain death, randomized trials for experimental drugs, the costs of transplant operations, and the system for selecting organ recipients. Through the use of stories, anecdotes, and photographs, Dr. Starzl tells the history of liver transplantation and addresses the moral and ethical issues raised by transplantation. A subject index concludes the volume.

·

Organ Transplants: A Patient's Guide Source: Cambridge, MA: Harvard University Press. 1991. 261 p. Contact: Available from Harvard University Press. 79 Garden Street, Cambridge, MA 02138-9983. (617) 495-2577 or (617) 495-2480. PRICE: $24.95 plus shipping and handling. ISBN: 067464235X.

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Summary: This book provides the reader with a general overview of the organ transplantation process, utilizing the experience and set-up of the Massachusetts General Hospital Transplantation Service as a representative institution. Topics include a history of human organ transplantation; a review of transplant immunology and antirejection drugs; a survey of the national organ donor network; a description of the hospital transplant team; the process of harvesting donor organs; the realities of surgery and recovery; a review of potential complications; and hints for transplant recipients and their families on how to cope with emotional and financial stress. The authors include case studies of patients' experiences before and after transplantation, and they depict how patients and their families interact with the hospital's medical team. A subject index concludes the volume. ·

Transplantation Drug Manual. 3rd ed Source: Georgetown, TX: Landes Bioscience. 1999. 133 p. Contact: Available from Landes Bioscience. 810 South Church Street, Georgetown, TX 78626. (512) 863-7762. Fax (512) 863-0081. Website: www.landesbioscience.com. PRICE: $45.00. ISBN: 1570595933. Summary: This book compiles practical information on the wide array of pharmaceutical agents currently available to treat patients who have undergone transplantation. Drugs discussed include both those used for immunosuppression and those used to minimize posttransplant complications. An introductory chapter offers a working guide to immunosuppression, providing an overview of current agents and a brief discussion of investigational agents. The remaining eight chapters cover antimicrobials (antibiotics, antivirals, antifungals), cardiovascular agents, antiosteoporosis agents, antiplatelets (including aspirin), diabetes agents, ulcer prophylaxis and treatment, diuretics, and other concomitant agents. The information is presented primarily in chart format, with the following provided for each drug: the brand name, company, class, mechanism of action, indications, contraindications, warnings, special precautions, adverse reactions, drug interactions, formulation, and dosage. The book is spiral bound and concludes with a subject index.

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

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all published books (e.g. Books in PrintÒ). The following have been recently listed with online booksellers as relating to transplantation (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): ·

Anesthesia and Organ Transplantation by Simon Gelman (Editor) (1987); ISBN: 0030115043; http://www.amazon.com/exec/obidos/ASIN/0030115043/icongroupin terna

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Anesthesia and Transplantation Surgery: Contemporary Anesthesia Practice by Brunell R., Jr Brown, Jack G. Copeland (Editor) (1987); ISBN: 0803612796; http://www.amazon.com/exec/obidos/ASIN/0803612796/icongroupin terna

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Biological Principles of Tissue Banking by Rudolf Klen (1982); ISBN: 0080244130; http://www.amazon.com/exec/obidos/ASIN/0080244130/icongroupin terna

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Catastrophic Diseases: Who Decides What?: A Psychosocial and Legal Analysis of the Problems Posed by Hemodialysis and Organ Transplantation by Jay Katz, Alexander Morgan Capron (1979); ISBN: 0878556869; http://www.amazon.com/exec/obidos/ASIN/0878556869/icongroupin terna

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Enzyme Activation in Blood-Perfused Artificial Organs (Developments in Hematology and Immunology, 11) by H. Scmid-Schonbein, et al (1985); ISBN: 0898387043; http://www.amazon.com/exec/obidos/ASIN/0898387043/icongroupin terna

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Hepatic Transplantation: Anesthetic and Perioperative Management by Peter M. Winter (Editor), Yoo Goo Kang (Editor) (1986); ISBN: 0275921298; http://www.amazon.com/exec/obidos/ASIN/0275921298/icongroupin terna

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Immunobiology of Transplantation, Cancer, and Pregnancy by Prasanta K. Ray (Editor) (1983); ISBN: 0080259944; http://www.amazon.com/exec/obidos/ASIN/0080259944/icongroupin terna

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Manual of Vascular Access, Organ Donation and Transplantation (Comprehensive Manuals of Surgical Specialties) by Richard L. Simmons, et al (1984); ISBN: 0387909656;

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http://www.amazon.com/exec/obidos/ASIN/0387909656/icongroupin terna ·

Proceedings of the European Dialysis and Transplant Association by A. M. Davison (1984); ISBN: 0272797693; http://www.amazon.com/exec/obidos/ASIN/0272797693/icongroupin terna

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Progress in Transplantation by Peter J. Morris, Nicholas L. Tilney (Editor) (1986); ISBN: 0443034494; http://www.amazon.com/exec/obidos/ASIN/0443034494/icongroupin terna

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Tissue Typing and Organ Transplantation: Proceedings by Symposium on Tissue Typing and Organ Transplantation University of min (1973); ISBN: 0127751602; http://www.amazon.com/exec/obidos/ASIN/0127751602/icongroupin terna

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Transplantation and Clinical Immunology: Immunosuppression by Jean-Louis Touraine (Editor), et al (1984); ISBN: 0444903739; http://www.amazon.com/exec/obidos/ASIN/0444903739/icongroupin terna

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Transplantation in the 1980s by Rex L. Jamison (Editor) (1984); ISBN: 0275914364; http://www.amazon.com/exec/obidos/ASIN/0275914364/icongroupin terna

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Transplantation Today: Proceedings of the 9th International Congress on the Transplantation Society by Transplantation Society (1983); ISBN: 0808916033; http://www.amazon.com/exec/obidos/ASIN/0808916033/icongroupin terna

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'We Have a Donor': The Bold New World of Organ Transplanting by Mark Dowie (1988); ISBN: 0312023162; http://www.amazon.com/exec/obidos/ASIN/0312023162/icongroupin terna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type

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“transplantation” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:25 ·

Courage to fail: a social view of organ transplants and dialysis. Author: Renée C. Fox, Judith P. Swazey; with a new introduction by the authors; Year: 2002; New Brunswick, N.J.: Transaction Publishers, c2002; ISBN: 0765807416 (pbk.: alk. paper) http://www.amazon.com/exec/obidos/ASIN/0765807416/icongroupin terna

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Immunological tolerance and transplantation: papers of a theme issue. Author: compiled and edited by P.J. Morris and K.J. Wood; Year: 2001; London: Royal Society, c2001

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Non-myeloablative allogeneic transplantation. Author: edited by Asad Bashey, Edward D. Ball; Year: 2002; Boston: Kluwer Academic Publishers, c2002; ISBN: 0792376463 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0792376463/icongroupin terna

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Raising the dead: organ transplants, ethics, and society. Author: Ronald Munson; Year: 2002; New York: Oxford University Press, 2002; ISBN: 0195132998 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0195132998/icongroupin terna

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Scarce goods: justice, fairness, and organ transplantation. Author: Tom Koch; Year: 2002; Westport, Conn.: Praeger, 2002; ISBN: 0275974324 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0275974324/icongroupin terna

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Solid organ transplantation: a handbook for primary health care providers. Author: Sandra A. Cupples, Linda Ohler, editors; Year: 2002; New York: Springer Pub. Co., c2002; ISBN: 0826119069

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a “Books” button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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http://www.amazon.com/exec/obidos/ASIN/0826119069/icongroupin terna ·

Transplantation and changing management of organ failure: proceedings of the 32nd International Conference on Transplantation and Changing Management of Organ Failure [sic], 25-26 May 2000. Author: edited by Pierre Cochat; Year: 2000; Dordrecht; Boston: Kluwer Academic Publishers, c2000; ISBN: 0792364201 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0792364201/icongroupin terna

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Transplantation sourcebook: basic consumer health information about organ and tissue transplantation: including physical and financial preparations, procedures and issues relating to specific solid organ and tissue transplants, rehabilitation, pediatric. Author: Conference on Transplantation and Clinical Immunology (32nd: 2000); Year: 2002; Detroit, MI: Omnigraphics, c2002; ISBN: 0780803221 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0780803221/icongroupin terna

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Transplantation surgery: current dilemmas. Author: edited by John L.R. Forsythe; Year: 2001; London; New York: W. B. Saunders, 2001; ISBN: 0702025887 http://www.amazon.com/exec/obidos/ASIN/0702025887/icongroupin terna

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Twice dead: organ transplants and the reinvention of death. Author: Margaret Lock; Year: 2002; Berkeley: University of California Press, c2002; ISBN: 0520226054 http://www.amazon.com/exec/obidos/ASIN/0520226054/icongroupin terna

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Wrapped in mourning: the gift of life and organ donor family trauma. Author: Sue Holtkamp; Year: 2002; New York, NY: Brunner-Routledge, c2002; ISBN: 1583910565 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/1583910565/icongroupin terna

Chapters on Transplantation Frequently, transplantation will be discussed within a book, perhaps within a specific chapter. In order to find chapters that are specifically dealing with transplantation, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and transplantation using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book

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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.” By making these selections and typing in “transplantation” (or synonyms) into the “For these words:” box, you will only receive results on chapters in books. The following is a typical result when searching for book chapters on transplantation: ·

Organ Transplant Source: in American College of Sports Medicine. ACSM's Exercise Management for Persons with Chronic Diseases and Disabilities. Champaign, IL: Human Kinetics. 1997. p. 137-140. Contact: Available from Human Kinetics. 1607 North Market Street, P.O. Box 5076, Champaign, IL 61825-5076. (800) 747-4457 or (217) 351-5076. Fax (217) 351-2674. PRICE: $39.00. Summary: This chapter, from a book of sports medicine and exercise management for people with chronic diseases and disabilities, provides information about organ transplantation. The author notes that individuals presenting for organ transplant are typically deconditioned, since the progression of the disease prevents significant physical activity. The author discusses the effects of organ transplant on the exercise response, the effects of exercise training, management and medications, recommendations for exercise testing, and recommendations for exercise programming. Exercise training should begin soon after transplant and should incorporate activity and lifestyle into the patient's 'new life.' Although gradual progression is essential, aerobic activities are tolerated well. Since transplant recipients present in a significantly deconditioned state, most will need strength training. Joint discomfort may be experienced by those on high doses of prednisone and during the 'taper' phase of the immunosuppression management. Activities that do not involve weights may be best tolerated. Many recipients are able to progress to jogging and other sporting activities without difficulty. The author recommends that some low-level activities be continued during rejection episodes to maintain a pattern of activity and counteract musclewasting effects of the prednisone. Prednisone affects muscle metabolism so that a longer period is necessary for strength gain. Therefore, strength training programs may have to incorporate a slower rate of progression to allow for this longer adaptation time. 2 tables. 3 references. (AA-M).

·

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.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to transplantation have been published that consolidate information across various sources. These too might be useful in gaining access to additional information on transplantation. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:26 ·

National Transplant Resource Directory Source: Pittsburgh, PA: Stadtlanders Pharmacy. 1998. 12 p. Contact: Available from Stadtlanders Pharmacy. Social Services Department, 600 Penn Center Boulevard, Pittsburgh, PA 15235-9931. (800) 238-7828. PRICE: Single copy free. Summary: This directory was created to assist transplant recipients, their families, and health care professionals with locating national transplant resources. The first section of the directory lists resources for coverage for health care and medications, including COBRA; high risk insurance pools; Medicaid coverages, including SSI, Medicaid, and QMB; Medicare; Medicare HMOs; Medicare Supplemental Insurance (Medigap policy);

You will need to limit your search to “Directories” and transplantation using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by”. For publication date, select “All Years”, select language and the format option “Directory”. By making these selections and typing in “transplantation” (or synonyms) into the “For these words:” box, you will only receive results on directories dealing with transplantation. You should check back periodically with this database as it is updated every three months.

26

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state kidney programs; state pharmaceutical assistance programs; and the Veterans Administration. The second section lists resources for educational information, financial grants, fundraising, and medication grants. Each entry notes the organization name, address, and telephone number, along with a brief description of the types of activities and resources offered. ·

Transplant Support Group Directory Source: Minnetonka, MN: Chronimed Pharmacy. 199x. [40 p.]. Contact: Available from Chronimed Pharmacy. 13911 Ridgedale Drive, Minnetonka, MN 55305, Attn.: Becky Irwin. (800) 444-5951, ext. 3736. PRICE: Single copy free. Summary: This directory lists transplant support groups in the United States. The groups are organized by state. If the group is specific to a certain kind of transplant, that information is noted at the end of the listing. Entries include the name of the group, an organizer or coordinator's name, the address, telephone number, and any special focus. The directory is revised annually.

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Organ Transplant National Resources Source: Farmingdale, NY: APP (American Preferred Plan). 1995. 2 p. Contact: Available from APP. P.O. Box 9019, Farmingdale, NY 11735. (800) 227-1195. PRICE: Single copy free. Summary: This bookmark provides information on national organ transplant resources. The bookmark is from the American Preferred Plan, a free membership organization delivering prescription medications directly to patients and physicians and providing linkages to community resources and national support networks. The bookmark lists resource centers and support groups; drug assistance telephone numbers; educational services; and financial assistance. For each entry, the bookmark notes the name, address, and telephone number of the organization and briefly notes the activities of the group. The bookmark is printed on laminated lightweight cardstock.

Vocabulary Builder Aerobic: 1. having molecular oxygen present. 2. growing, living, or occurring in the presence of molecular oxygen. 3. requiring oxygen for respiration. [EU]

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Antibiotic: A chemical substance produced by a microorganism which has the capacity, in dilute solutions, to inhibit the growth of or to kill other microorganisms. Antibiotics that are sufficiently nontoxic to the host are used as chemotherapeutic agents in the treatment of infectious diseases of man, animals and plants. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Colitis: Inflammation of the colon. [EU] Dietetics: The study and regulation of the diet. [NIH] Dilatation: The condition, as of an orifice or tubular structure, of being dilated or stretched beyond the normal dimensions. [EU] Embalming: Process of preserving a dead body to protect it from decay. [NIH] Fistula: An abnormal passage or communication, usually between two internal organs, or leading from an internal organ to the surface of the body; frequently designated according to the organs or parts with which it communicates, as anovaginal, brochocutaneous, hepatopleural, pulmonoperitoneal, rectovaginal, urethrovaginal, and the like. Such passages are frequently created experimentally for the purpose of obtaining body secretions for physiologic study. [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] 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] Perioperative: Pertaining to the period extending from the time of hospitalization for surgery to the time of discharge. [EU] Preoperative: Preceding an operation. [EU] Prophylaxis: The prevention of disease; preventive treatment. [EU] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Resection: Excision of a portion or all of an organ or other structure. [EU] Sensitization: 1. administration of antigen to induce a primary immune response; priming; immunization. 2. exposure to allergen that results in the

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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] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Ulcer: A local defect, or excavation, of the surface of an organ or tissue; which is produced by the sloughing of inflammatory necrotic tissue. [EU]

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CHAPTER 7. MULTIMEDIA ON TRANSPLANTATION Overview Information on transplantation can come in a variety of formats. Among multimedia sources, video productions, slides, audiotapes, and computer databases are often available. In this chapter, we show you how to keep current on multimedia sources of information on transplantation. 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. If you see an interesting item, visit your local medical library to check on the availability of the title.

Video Recordings Most medical procedures and treatments do not have a video dedicated to them. If they do, they are often rather technical in nature. An excellent source of multimedia information on transplantation is the Combined Health Information Database. You will need to limit your search to “video recording” and “transplantation” 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.).” By making these selections and typing “transplantation” (or synonyms) into the “For these words:” box, you will only receive results on video productions. The following is a typical result when searching for video recordings on transplantation:

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·

Caring for the Transplant Patient Source: Toronto, Ontario, Canada: Medical Audio Visual Communications, Inc. 1994. (videocassettes). Contact: Available from Medical Audio Visual Communications, Inc. Suite 240, 2315 Whirlpool Street, Niagara Falls, NY 14305. Or P.O. Box 84548, 2336 Bloor Street West, Toronto, Ontario M6S 1TO, Canada. (800) 757-4868 or (905) 602-1160. Fax (905) 602-8720. PRICE: $700.00 (Canadian); contact producer for current price in American dollars. Summary: This series of three videocassettes provides information for nurses and other medical personnel who are caring for a transplant patient. The three programs cover asking for organ donations, pre-and postoperative care, and patient education and support. Along with the necessary clinical information, the videos feature family members and patients discussing their transplant experiences. (AA-M).

·

Stadtlanders Stars for Life Fitness Video: Designed Especially for Transplant Recipients Source: Pittsburgh, PA: Stadtlanders Pharmacy. 1994. Contact: Available from Stadtlanders Pharmacy. 600 Penn Center Boulevard, Pittsburgh, PA 15235-5810. (800) 238-7828 or (412) 825-8155. Fax: (412) 825-8160. PRICE: Single copy free. Summary: This videotape presents exercise instructions and advice for transplant recipients who have been out of the hospital for at least 8 weeks, are otherwise in good health, and have permission from their physician to participate in an aerobic program. The videotape presents a low-impact fitness program designed to improve circulation, increase stamina, strengthen muscles, and be fun. The workout features two levels of intensity, so viewers can choose the one that is most appropriate for themselves. The program includes a warm-up and stretch section; an aerobics section; a set of abdominal exercises; and a cool-down section. The accompanying syllabus discusses the importance of regular exercise after transplant; ideas for a bone-building workout; the Borg scale; and the members of the Stars for Life fitness team depicted in the videotape program.

·

Long Island Transplant: A Decade of Progress, A Century of Hope Source: Chapel Hill, NC: Health Sciences Consortium. 1992. Contact: Available from Health Sciences Consortium (HSC). 201 Silver Cedar Court, Chapel Hill, NC 27514-1517. (919) 942-8731. PRICE: $195, HSC members $136.50. Order Number N911-VI-062.

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Summary: More than 20,000 people suffer from end stage kidney disease. For many of these people a kidney transplant would either save their lives or greatly improve the quality of their lives. In this program, transplant recipients and those waiting for organs discuss issues that they are facing. (AA). ·

Home Care for Transplant Patients Source: Minneapolis, MN: University of Minnesota Hospital and Clinic. 1991. (videocassette and handbook). Contact: Available from University of Minnesota Hospital and Clinic. Ms. Lauren Johnson, Nursing Services, Harvard Street at East River Road, Box 603, Minneapolis, MN 55455. (612) 626-6137. PRICE: $125 (for videocassette and handbook). Summary: This patient education videocassette, a companion to the Handbook for Transplant Patients, reviews the information that every transplant patient needs in order to make the transition from hospital to home care. Topics in the handbook include the health care team, questions to ask, health records, medications, outpatient procedures, immune complications, nutrition guidelines, general health, emotional health, and diabetes after transplant. The majority of this videotape focuses on the medications involved in post-transplant care.

·

People Like Us: Transplantation: Choosing a Treatment That's Right for You. [Gente Como Nosotros: Trasplantes: Como escoger el tratamiento adecuado para Ud] Source: New York, NY: National Kidney Foundation, Inc. 1994. (instructional package). Contact: Available from Amgen, Inc. 1840 DeHavilland Drive, Thousand Oaks, CA 91320-1789. (800) 282-6436. PRICE: Part of an instructional package free to dialysis centers, transplantation centers, and hospitals with dialysis or transplantation units. Summary: This videotape and booklet package is part of a patient education program designed to educate patients and their families about kidney disease and its options for treatment. In this segment, a comprehensive view of transplantation as a treatment for kidney disease is presented. Team members discuss the transplant evaluation process and the matching of organs from either living-related or cadaveric donors. A transplant coordinator addresses the waiting period, and the transplant surgeon discusses what takes place in the operation. Other topics include the role of immunosuppressive medications, the signs of acute rejection, post-transplant diet, side effects of medications, and long-

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term medical follow-up. As in the other segments, the viewer sees interviews with actual patients relating their own experiences. The booklet reiterates the material covered in the videotape and includes a quiz for self-testing, a glossary, and blank spaces to record questions and information about health care team members. (AA-M).

Bibliography: Multimedia on Transplantation The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in transplantation (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on transplantation. For more information, follow the hyperlink indicated: ·

List for life. Source: a presentation of Films for the Humanities & Sciences; ABC News Productions; Year: 2001; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c2001

·

Minds of medicine. [videorecording]. Year: 2000; Format: Heart; [Detroit, Mich.]: Henry Ford Medical System, [2000]

·

Status of NIH-sponsored basic and clinical research on transplantation . Year: 2000; Format: Electronic resource; [Bethesda, Md.]: Dept. of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, [2000]

·

Transplant. Source: a presentation of Films for the Humanities & Sciences; a Whiteford-Hadary, University of Maryland, School of Medicine, Tapestry International production; produced in association with Discovery Channel; Year: 2002; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c2002

Vocabulary Builder Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. The chief signs of arterial aneurysm are the formation of a pulsating tumour, and often a bruit (aneurysmal bruit) heard over the

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swelling. Sometimes there are symptoms from pressure on contiguous parts. [EU]

Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, poly- and heterosaccharides. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Glomerulonephritis: A variety of nephritis characterized by inflammation of the capillary loops in the glomeruli of the kidney. It occurs in acute, subacute, and chronic forms and may be secondary to haemolytic streptococcal infection. Evidence also supports possible immune or autoimmune mechanisms. [EU] Heredity: 1. the genetic transmission of a particular quality or trait from parent to offspring. 2. the genetic constitution of an individual. [EU] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Impotence: The inability to perform sexual intercourse. [NIH] Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Neuropathy: A general term denoting functional disturbances and/or pathological changes in the peripheral nervous system. The etiology may be known e.g. arsenical n., diabetic n., ischemic n., traumatic n.) or unknown. Encephalopathy and myelopathy are corresponding terms relating to involvement of the brain and spinal cord, respectively. The term is also used to designate noninflammatory lesions in the peripheral nervous system, in contrast to inflammatory lesions (neuritis). [EU] Nocturia: Excessive urination at night. [EU]

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Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU] 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] 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]

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CHAPTER 8. PERIODICALS TRANSPLANTATION

AND

NEWS

ON

Overview Keeping up on the news relating to transplantation can be challenging. Subscribing to targeted periodicals can be an effective way to stay abreast of recent developments on transplantation. Periodicals include newsletters, magazines, and academic journals. In this chapter, we suggest a number of news sources and present various periodicals that cover transplantation beyond and including those which are published by patient associations mentioned earlier. We will first focus on news services, and then on periodicals. News services, press releases, and newsletters generally use more accessible language, so if you do chose to subscribe to one of the more technical periodicals, make sure that it uses language you can easily follow.

News Services & Press Releases Well before articles show up in newsletters or the popular press, they may appear in the form of a press release or a public relations announcement. One of the simplest ways of tracking press releases on transplantation is to search the news wires. News wires are used by professional journalists, and have existed since the invention of the telegraph. Today, there are several major “wires” that are used by companies, universities, and other organizations to announce new medical breakthroughs. 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.

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PR Newswire Perhaps the broadest of the wires is PR Newswire Association, Inc. To access this archive, simply go to http://www.prnewswire.com. Below the search box, select the option “The last 30 days.” In the search box, type “transplantation” or synonyms. The search results are shown by order of relevance. When reading these press releases, do not forget that the sponsor of the release may be a company or organization that is trying to sell a particular product or therapy. Their views, therefore, may be biased. The following is typical of press releases that can be found on PR Newswire: ·

International Congress of The Transplantation Society August 25-30 a Forum for Cutting-Edge Research Findings Summary: MIAMI, July 10 /PRNewswire/ -- New findings in clinical and basic science transplantation research will be presented for the first time at the XIX International Congress of The Transplantation Society August 25 - 30, among them results of a study that treated diabetic children with a combination of cells from a pig's pancreas and testes, and findings from three separate studies with a common goal in mind: to wean organ transplant patients off all anti-rejection drugs less than one year after transplantation, defying the tenet that such drugs are required for life. The congress will take place at the Westin Diplomat Resort and Spa in Hollywood, Fla., located on the coast between Miami and Ft. Lauderdale. A staffed press room will be on site, and press briefings and media availabilities will be held each day. As with other congresses, a familiar theme of discussion will be the worldwide organ donor shortage crisis -- in some countries with active transplant centers there are less than 10 or 20 cadaveric organ donors a year -- but at this congress, much of the discussion also will focus on the repercussions of the organ shortage. Thousands of patients continue to die each year awaiting transplantation, and in response, surgeons are beginning to rely more on living donors. In the United States alone, the numbers have increased more than 12 percent from 2000. But in some parts of the world, these numbers are part and parcel to a growing black market for organs from living donors. The practice of buying and selling organs is of particular concern to The Transplantation Society, the field's only international society, with more than 3,000 members from 65 countries, including those where such black markets exist.

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Among the many research studies to be presented at the congress and featured in the press room are: -- A team from Mexico and Canada will report that some diabetic children were able to stop daily insulin injections after receiving infusions of pig cells, which were given without immunosuppression, while Italian researchers will report that transplanting human pancreatic islets cells can reduce the complications of diabetes 10 years after transplantation. Additional studies focusing on cell transplantation for the treatment of diabetes include those examining the promise of embryonic stem cells and ways that islets, which are particularly prone to rejection, can be engineered to protect against such an immune response. -- Tolerance, the permanent acceptance of the transplanted graft without the need for drugs, is considered the Holy Grail of transplantation. Results will be presented from innovative trials in the United States and India that suggest the untenable goal is seemingly near. Using different novel methods, the researchers attempted to "expedite" the process and began weaning patients off immunosuppressive drugs just months after transplantation. Teams from the United States, France and Italy also will present results of their studies -- among the few of their kind -- with cohorts of patients off all immunosuppression. -- Not since the world's first hand transplant recipient demanded that surgeons remove the donor graft has the French team discussed the patient's course of chronic rejection at an international scientific forum. The French researchers will present results of the patient's pathology studies as well as a two-year update on the world's first double-hand transplant. Teams from the United States, Italy and China will report on their clinical experience with hand transplantation as well. -- Just when will organs from pigs be ready for transplantation into humans? Several reports have suggested some of the major immunological hurdles have been overcome, and a litter of cloned "knock-out" pigs born about six months ago could bring in the next generation of organ donors. Those active in the field of xenotransplantation, or cross-species transplantation, and cloning will provide an update on where the field stands. Researchers will also report on the promise of cellular xenotransplantation, including one study from the United Kingdom looking at neural stem cells from the developing brain of pigs to treat Parkinson's. Another study from Argentina

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suggests that pig liver cells might survive and function if transplanted in-utero, representing a potential way to treat liver diseases involving inborn metabolism errors. -- According to one study, an organ preservation system being tested in the United States indicates "marginal" kidneys could indeed be safely transplanted, thus greatly expanding the number of organs available for transplantation. Another experimental device developed in Germany makes use of stem cells isolated from discarded livers to treat patients in acute liver failure until a donor liver can be found. Still, some European transplant centers have found organs from older donors -- even those over the age of 80 -- to be an effective way to expand the donor pool. Results of these and other studies will be reported. -- Adult stem cells derived from bone marrow may be able to restore function to damaged heart tissue resulting from heart attack, according to a German study using a mouse model. -- Increasingly, organ transplants are being performed in HIV-positive patients with end-stage organ failure. Centers in the United States and Europe will report their results, while one U.S. center will talk about progress developing a gene therapy approach for treating HIV. -- What type of insurance a patient has may contribute to the success of the transplant, according to one study that looked at how various socioeconomic factors contributed to transplant success. Results of this U.S. study will be presented. The preliminary scientific program, press registration and hotel information are available at http://www.txmiami2002.com. Special hotel rates are available only until July 18. Abstracts will be posted approximately three weeks prior to the congress and embargoed until time and date of presentation, unless otherwise specified. The press room schedule and details of daily highlights will be available at http://www.txmiami2002.com as soon as they are confirmed and also will be posted on the Web sites for EurekAlert! (http://www.eurekalert.org) and AlphaGalileo (http://www.alphagalileo.org). To receive updates and news releases by e-mail or fax, please contact Lisa Rossi at [email protected] or 412624-3184 (fax). A total of 2,373 abstracts were submitted to the XIX Congress, with 555 (22 percent) accepted as oral presentations and 1,091 abstracts (46

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percent) accepted for presentation as posters. An additional 555 abstracts (23 percent) were accepted for publication only in the abstract book. All abstracts will be published in a supplement to the journal Transplantation. In addition, authors of the 200 highest-scoring abstracts will be invited to publish their work as a regular article in a separate issue of Transplantation. The Transplantation Society was founded in 1966 and serves as the principal international forum for the advancement of both basic and clinical transplantation science. Among its current and former members are six Nobel Laureates. The president of the society is Dr. Carl Groth of the Karolinska Institute in Stockholm. Co-chairs of the congress are Dr. Camillo Ricordi of the Diabetes Research Institute at the University of Miami School of Medicine and Dr. Domingo Casadei of the Instituto de Nefrologia in Buenos Aires. The International Congress is held every two years. This year's congress had originally been scheduled to take place in Buenos Aires, but due to Argentina's unstable economy, its location was changed earlier this year to the Miami site. The 2004 congress will be held in Vienna.

CONTACT: Lisa Rossi of the International Congress of The Transplantation Society, +1-412-916-3315, or fax: +1-412-624-3184, or [email protected].

Reuters The Reuters’ Medical News database can be very useful in exploring news archives relating to transplantation. While some of the listed articles are free to view, others can be purchased for a nominal fee. To access this archive, go to http://www.reutershealth.com/frame2/arch.html and search by “transplantation” (or synonyms). The following was recently listed in this archive for transplantation: ·

Britain faces transplant organ shortage Source: Reuters Health eLine Date: August 05, 2002 http://www.reuters.gov/archive/2002/08/05/eline/links/20020805elin 024.html

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·

Donor heartbeat not required for transplant success Source: Reuters Health eLine Date: July 24, 2002 http://www.reuters.gov/archive/2002/07/24/eline/links/20020724elin 006.html

·

Cyclosporine microemulsion helpful in tacrolimus-intolerant transplant patients Source: Reuters Medical News Date: July 11, 2002 http://www.reuters.gov/archive/2002/07/11/professional/links/20020 711clin003.html

·

Roche transplant drug wins European approval. Source: Reuters Industry Breifing Date: July 05, 2002 http://www.reuters.gov/archive/2002/07/05/business/links/20020705 rglt004.html

·

Immunoabsorption therapy shows promise in sensitized transplant recipients Source: Reuters Industry Breifing Date: May 27, 2002 http://www.reuters.gov/archive/2002/05/27/business/links/20020527 drgd001.html

·

Transplant surgeons urge pilot study of payment to defray organ donation cost Source: Reuters Industry Breifing Date: April 30, 2002 http://www.reuters.gov/archive/2002/04/30/business/links/20020430 ethc001.html

·

Filtering blood may allow more transplants: study Source: Reuters Health eLine Date: April 30, 2002 http://www.reuters.gov/archive/2002/04/30/eline/links/20020430elin 040.html

·

UK transplant success rates show no improvement Source: Reuters Health eLine Date: April 22, 2002 http://www.reuters.gov/archive/2002/04/22/eline/links/20020422elin 009.html

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·

Simple blood test can spot organ transplant recipients prone to rejection Source: Reuters Medical News Date: April 15, 2002 http://www.reuters.gov/archive/2002/04/15/professional/links/20020 415clin001.html

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 their 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.

Internet Wire Internet Wire is more focused on technology than the other wires. To access this site, go to http://www.internetwire.com and use the “Search Archive” option. Type in “transplantation” (or synonyms). As this service is oriented to technology, you may wish to search for press releases covering diagnostic procedures or tests that you may have read about.

Search Engines Free-to-view news can also be found in the news section of your favorite search engines (see the health news page at Yahoo: http://dir.yahoo.com/Health/News_and_Media/, or use this Web site’s general news search page http://news.yahoo.com/. Type in “transplantation” (or synonyms). If you know the name of a company that has business

148 Transplantation

interests related to transplantation, you can go to any stock trading Web site (such as www.etrade.com) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. 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 “transplantation” (or synonyms).

Newsletters on Transplantation Given their focus on current and relevant developments, newsletters are often more useful to patients than academic articles. You can find newsletters using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Your investigation must limit the search to “Newsletter” and “transplantation.” 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.” By making these selections and typing in “transplantation” or synonyms into the “For these words:” box, you will only receive results on newsletters. The following list was generated using the options described above: ·

New Horizons Pre-Transplant Issues and Information Source: Kansas City, MO: Kidney Transplant Patient Partnering Program, Roche Laboratories. 1997. 5 p. Contact: Available from Kidney Transplant Patient Partnering Program. P.O. Box 16514, Kansas City, MO 64133. (800) 893-1995. Price: Free subscription. Summary: This newsletter is designed to provide spouses and other caregivers with information about kidney transplantation. The publication is based on the concept that family members who are informed about what's happening will be more understanding of the person undergoing the transplant and less fearful about the outcome. The newsletter is published three times per year and is part of the Kidney Transplant Patient Partnering Program (KTPPP), a free educational service of Roche Laboratories. This issue includes an article on coping as a caregiver, including practical suggestions for every day activities that

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can help caregivers and families get through this difficult time. Another article outlines the criteria of a 'healthy' living donor and the types of outpatient testing that any potential donor must undergo. Two additional articles cover how to take medications safely and accurately, and why it is important for everyone to promote organ donation awareness. One sidebar (perforated for removal from the newsletter) lists the instructional and patient support materials available from the KTPPP. The Kidney Transplant Patient Partnering Program was developed to help patients and their families understand and cope with the many physical and psychological issues that arise because of the kidney transplant process. (AA-M). ·

Transplant Support Groups: Sharing and Caring Source: Milestones. 2(5): 1-2. 1997. Contact: Available from Milestones. P.O. Box 16514, Kansas City, MO 64133. Summary: This brief article from a newsletter for patients who have received a kidney transplant describes the importance of transplant support groups. The support groups consist of fellow patients and their families who have been through the experience of transplantation. The article reviews the reasons why joining a support group is a good strategy: people there understand the patient's fears, concerns, and everyday struggles; the support of caring group members can allow the patient to release pent up emotions; support groups share practical suggestions for dealing with side effects, where to get medications, and how to cope with medications; support groups often have educational programs and guest speakers to help patients better understand their condition; and helping others can often help a patient feel better about his or her situation. The article emphasizes that all support groups are not the same; patients are encouraged to try more than one if their first experience does not suit their personality or needs. Patients can locate a support group with the help of the transplant team coordinator or social worker, from the telephone directory, or from the National Kidney Foundation Information Center (800-622-9010). The Internet is also a good source for discussion lists and chat groups for kidney transplant patients and their families. The newsletter publisher also has a website (www.ktppp.com ).

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Newsletter Articles If you choose not to subscribe to a newsletter, you can nevertheless find references to newsletter articles. We recommend that you use the Combined Health Information Database, while limiting your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” By making these selections, and typing in “transplantation” (or synonyms) into the “For these words:” box, you will only receive results on newsletter articles. You should check back periodically with this database as it is updated every 3 months. The following is a typical result when searching for newsletter articles on transplantation: ·

Questions and Answers: Infection Risks Post-Transplant Source: CLASS Notes. p. 5-6. Spring 1998. Contact: Available from Children's Liver Association for Support Services (C.L.A.S.S.). 26444 Emerald Dove Drive, Valencia, CA 91355. (877) 6898256. (661) 255-0353. E-mail: [email protected]. Website: www.classkids.org. Summary: This newsletter article answers the concerns of one parent who writes to ask how to handle infection control in her daughter after the child receives a liver transplant. The parent is worried that drugs given to the child to prevent rejection of her new liver will leave her vulnerable to infectious diseases. The physician who addresses these concerns notes that precautions against infection must be individualized for each patient. Different patients are on different amounts of immunosuppression, and the more immunosuppression a patient has received the more precautions are necessary. Since the chance of rejection is highest during the first 3 months after a transplant, higher doses of immunosuppression are used, and therefore the risk of infection is highest during this time period. The most common infections after a transplant are viral infection; bacterial infections are also fairly common after a transplant (but most can be easily treated with antibiotics). The article concludes with a discussion of chicken pox, a viral infection that requires special consideration. If the patient is immune to chicken pox, the likelihood of having a problem later on is much less since this virus generally causes chicken pox only once. A vaccine is available for chicken pox and many transplant centers are starting to vaccinate children who

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will some day need a transplant in order to general immunity and prevent future infections. The vaccine is a live virus though, so it cannot be given once the child is on immunosuppression. Other topics covered in the article are childcare, having pets, and the types of immunosuppressant drugs that are usually prescribed. ·

Keep Yourself Covered: What Everyone Should Know About Health Insurance and Transplantation Source: Transplant Chronicles. 4(4): 5. 1997. Contact: Available from National Kidney Foundation. 30 East 33rd Street, New York, NY 10016. (800) 622-9010. Summary: No matter when a transplant is performed and regardless of the patient's income or type of insurance, most transplant patients require ongoing care and antirejection medications. This brief newsletter article reminds readers about the terminology that can be involved in health coverage options. Seven terms are defined and discussed: employer insurance, Medicare (Parts A and B), Medigap, high-risk insurance, Medicaid (medical assistance), drug programs, and the Transplant Foundation. For each organization mentioned, the author provides a tollfree telephone number for readers needing more information. The author reminds readers that social workers may also be aware of other local, state, or national programs that are available. The author also emphasizes that one should never have to compromise health care because of a lack of coverage.

·

Psychosocial Issues in Transplantation Source: Clinical Strategies: The AKF Newsletter for Nephrology Professionals. 3(2): 7, 11, 14. Fall 1996. Contact: Available from American Kidney Fund. 6110 Executive Boulevard, Suite 1010, Rockville, MD 20852. (800) 638-8299 or (301) 8813052. Fax (301) 881-0898. Summary: This newsletter article describes some of the psychosocial issues involved in each stage of the kidney transplantation process, notably those issues involving living donors. The author explores the pretransplant decision-making; the waiting period during which potential living donors are being evaluated; feelings when a living donor is rejected because of medical mismatch; the waiting period for cadaveric transplantation; hospitalization and immediate post-operative feelings and care; post-transplant followup, including adjusting to the drug therapy and fighting graft rejection; and long-term adjustment considerations, including finances. The author concludes that transplant

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centers can prepare patients and their families for these stages by offering them contact with others who have traveled the same path, with ongoing transplant support groups, educational seminars, and, when necessary, individual or family sessions with the transplant social worker. ·

Improving Transplant Outcomes Source: Clinical Strategies: The AKF Newsletter for Nephrology Professionals. 3(2): 4, 12. Fall 1996. Contact: Available from American Kidney Fund. 6110 Executive Boulevard, Suite 1010, Rockville, MD 20852. (800) 638-8299 or (301) 8813052. Fax (301) 881-0898. Summary: This newsletter article describes a variety of means to improve transplant outcomes, particularly for kidney transplantation. The author describes how much of the improvement in transplant outcomes can be attributed to the development of better immunosuppressive drugs; 10 new drugs in various developmental phases are discussed. The author first reviews the standard immunosuppressive drugs and their side effects. These drugs include corticosteroid, azathioprine, and cyclosporine (the original format, Sandimmune, as well as the new formulation, Neoral). The newer drugs reviewed are FK-506 (Prograf); rapamycin; mycophenolate mofetil (Cellcept); mizoribine; brequinar; ATG; OKT3; and deoxyspergualin. The author concludes that, because of the diverse mechanisms of these immunosuppressants, creative and effective strategies will be needed in the future to minimize the risk of infection and malignant disease and to maximize the prevention and control of graft rejection. 1 table. (AA-M).

Academic Periodicals covering Transplantation Academic periodicals can be a highly technical yet valuable source of information on transplantation. We have compiled the following list of periodicals known to publish articles relating to transplantation and which are currently indexed within the National Library of Medicine’s PubMed database (follow hyperlinks to view more information, summaries, etc., for each). In addition to these sources, to keep current on articles written on transplantation published by any of the periodicals listed below, you can simply follow the hyperlink indicated or go to the following Web site: www.ncbi.nlm.nih.gov/pubmed. Type the periodical’s name into the search box to find the latest studies published.

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If you want complete details about the historical contents of a periodical, you can also visit the 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.” The following is a sample of periodicals which publish articles on transplantation: ·

Acta Haematologica. (Acta Haematol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ac ta+Haematologica&dispmax=20&dispstart=0

·

Best Practice & Research. Clinical Haematology. (Best Pract Res Clin Haematol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Best+ Practice+&+Research.+Clinical+Haematology&dispmax=20&dispstart=0

·

Experimental Hematology. (Exp Hematol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ex perimental+Hematology&dispmax=20&dispstart=0

·

Journal of Clinical Immunology. (J Clin Immunol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Jo urnal+of+Clinical+Immunology&dispmax=20&dispstart=0

·

Kidney International. (Kidney Int) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ki dney+International&dispmax=20&dispstart=0

·

Leukemia & Lymphoma. (Leuk Lymphoma) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Le ukemia+&+Lymphoma&dispmax=20&dispstart=0

·

Seminars in Oncology. (Semin Oncol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Se minars+in+Oncology&dispmax=20&dispstart=0

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·

The Journal of Nutrition. (J Nutr) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Th e+Journal+of+Nutrition&dispmax=20&dispstart=0

Vocabulary Builder Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [NIH] Hydration: The condition of being combined with water. [EU] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Varicella: Chicken pox. [EU]

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CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES Overview Doctors and medical researchers rely on a number of information sources to learn about procedures and treatments. Many will subscribe to journals or newsletters published by their professional associations or refer to specialized textbooks or clinical guides published for the medical profession. In this chapter, we focus on databases and Internet-based guidelines created or written for this professional audience.

NIH Guidelines For the more common medical procedures and treatments, the National Institutes of Health publish guidelines that are frequently consulted by physicians. Publications are typically written by one or more of the various NIH Institutes. For physician guidelines, commonly referred to as “clinical” or “professional” guidelines, you can visit the following Institutes: ·

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

·

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

·

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

·

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

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·

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

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.27 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:28 ·

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

·

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

·

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

·

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

·

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

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). 28 See http://www.nlm.nih.gov/databases/databases.html. 27

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·

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

·

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

·

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

·

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

·

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

·

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

·

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

While all of the above references may be of interest to physicians who conduct research on transplantation, the following are particularly noteworthy. The Combined Health Information Database A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to “Brochure/Pamphlet,” “Fact Sheet,” or “Information Package” and transplantation using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years,” select your preferred language, and the format option “Fact Sheet.” By making these selections and typing “transplantation” (or synonyms) into

158 Transplantation

the “For these words:” box above, you will only receive results on fact sheets dealing with transplantation. The following is a sample result: ·

Public Education in Organ and Tissue Donation: Review and Recommendations: A Planning Tool for the Transplant Community Source: Madison, WI: Medical Media Associates, Inc. 1991. 42 p. Contact: Available from Life Options Rehabilitation Program. Medical Education Institute, Inc, 414 D'Onofrid Drive., Suite 200, Madison, WI 53719. (608) 833-8033. E-mail: [email protected]. PRICE: Single copy free. Summary: This report presents information and guidelines for people who are seeking to educate their communities about organ and tissue donation. The report is the result of a study commissioned to review pertinent research on public awareness and attitudes about organ donation; to review public education programs currently in use throughout the United States; and to confirm, revise, or expand upon strategic recommendations already in place for public education in organ donation. Profiles of two programs are included: Dow Chemical Company's 'Take Initiative Program,' and the American Red Cross' program, 'Buddies for Life.' 49 references.

·

A Guide to State Organ Transplant Activities in the United States Source: Rockville, MD: U.S. Department of Health and Human Services, Health Resources and Services Administration. December 1990. 6 p. Contact: Available from U.S. Department of Health and Human Services, Health Resources and Services Administration. Division of Organ Transplantation, Bureau of Health Resources Development, Parklawn Building, Room 11A22, 5600 Fishers Lane, Rockville, MD 20857. PRICE: Single copy free. Summary: This guidebook is designed to provide comprehensive, state by state profiles of all public and private sector resources available to assist transplant candidates, recipients, and their families, as well as potential organ donors. Public sector resources are described, including the Medicaid program, state kidney programs, state general medical assistance programs, state health risk pools, and state educational initiatives. Also briefly mentioned are private sector resources in the areas of patient services and educational programs. One appendix lists the Medicaid coverage of solid organ transplants by state; not all states provide Medicaid coverage for all organ transplants.

Physician Guidelines and Databases 159

·

[LifeNet Transplant Services Information Package] Source: Virginia Beach, VA: LifeNet Transplant Services. 199x. 24 p. Contact: Available from LifeNet Transplant Services. 5809 Ward Court, Virginia Beach, VA 23455. (804) 464-4761 or (800) TISSUE-1, fax (804) 4645721. PRICE: Single copy free. Summary: This information packet provides information from and about LifeNet Transplant Services, an organ procurement organization (OPO) that serves as a local organ and tissue recovery program for the eastern Virginia area. In addition to five fact sheets outlining the activities and services of LifeNet, the information packet includes a bumper sticker (Organ Donation: The Only Cost is a Little Love) and five brochures: a listing of the Virginia Transplant Council with the poem To Remember Me; LifeNet's general brochure about organ donation, with a blank organ donor card; a general brochure about the United Network for Organ Sharing (UNOS); the Virginia Transplant Council's general brochure about organ donation, with two blank organ donor cards; and a scriptographic booklet about organ and tissue donation.

·

How to Promote Organ-Tissue Donation Through the African American Church: Guidelines and Resource Kit Source: New York, NY: New York Organ Donor Network. 1996. (information kit). Contact: Available from New York Organ Donor Network. 475 Riverside Drive, Suite 1244, New York, NY 10115-1244. (800) GIFT-4-NY or (212) 870-2240. Fax (212) 870-3299. PRICE: $39.50 to clergy; Single copy free to clergy in New York Service Area. Summary: This clergy resource kit is designed to increase the understanding of the role clergy can play in educating their congregations and communities regarding organ and tissue donation and transplantation. Designed especially for the African American community, the kit recognizes that the clergy has a strong presence in this population and plays a variety of roles as communicators, teachers, healers, ethicists, and theologians. The introductory materials describe the New York Regional Transplant Program (recently renamed as the New York Organ Donor Network) and offer statistics on organ donation and ethnicity. The handbook then outlines recommended clergy participation, empowering ideas for awareness programs, the human resources and materials that NYODN can provide for the church, points to consider when presenting, where to disseminate information, slogans, questions most frequently asked, myths and misconceptions, brain death questions and answers, a brief history of solid organs and tissue

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transplants, and general religious beliefs (of the main religions in the United States) concerning organ donation. The handbook then offers information about outreach and educational programs that have taken place in the New York area, including press releases that were used to publicize these activities. Another section includes evaluation and questionnaire forms to gather feedback about donor education programs. A lengthy resource section reprints related sermons, articles, and other publications that may be of use to clergy in planning and implementing organ donation education programs. The handbook includes a glossary of terms, and resource materials including a bookmark, brochure, button, fan, and poster. The materials are gathered in a loose leaf notebook format. ·

Nurses Can Bridge the Gap Between Life and Death Source: Richmond, VA: UNOS. 1995. 6 p. Contact: Available from UNOS. P.O. Box 13770, Education Department, Richmond, VA 23225. (804) 330-8541. Fax (804) 330-8593. PRICE: $0.60 each for 1-50 copies, plus shipping; discounts available for larger orders. Summary: This brochure reminds nurses of the critical role they can play in addressing the current shortage of donated organs for transplantation. When a patient dies, the nurse is in a unique position to provide not only emotional support to a family in a time of crisis, but also resources and information about organ and tissue donation to assist them in their decision making. Written in a question-and-answer format, the brochure covers topics including the number of patients waiting for organ transplantation; who can be considered as an organ and tissue donor; which organs and tissues can be donated for transplantation; success rates for organ transplants; and brain death criteria and legal considerations. Other topics addressed include psychosocial factors related to donating a loved one's organs; how organ and tissue donation and transplantation is administered in the U.S.; donor organ allocation; the recovery of organs and tissues and the cost considerations involved; how to offer donation as an option to a grieving family; and required request legislation.

·

People Like Us. [Gente Como Nosotros] Source: New York, NY: National Kidney Foundation, Inc. 1994. (instructional package). Contact: Available from Amgen, Inc. 1840 DeHavilland Drive, Thousand Oaks, CA 91320-1789. (800) 282-6436. PRICE: Single package free to

Physician Guidelines and Databases 161

dialysis centers, transplantation centers, and hospitals with dialysis or transplantation units. Summary: This patient education program is designed to assist health care professionals in educating patients and their families about kidney disease and its options for treatment. The program includes seven videotapes, a complete patient education library of brochures, a patient record guide, and a Leader's Guide. A basic theme of the program is that choosing a treatment is a personal decision based on a variety of considerations, and always made with the help and input of a concerned and dedicated health care team. The seven segments cover an overview of kidney disease and its treatment, peritoneal dialysis, hemodialysis, the role of good nutrition, coping with kidney disease, the role of erythropoietin in treating anemia, and kidney transplantation. The patient's record charts are included to help document a patient's participation in this program. The Leader's Guide provides important background information on the program, describes each of its components, and suggests how best to use the program in dialysis and transplant centers. ·

Guide to State Organ Transplant Activities in the United States Source: Rockville, MD: Public Health Service. 1990. 184 p. Contact: Available from U.S. Department of Health and Human Services. Public Health Service, Health Resources and Services Administration, Bureau of Health Resources Development, Parklawn Building, 5600 Fishers Lane, Room 11A-22, Rockville, MD 20857. PRICE: Single copy free. Summary: The purpose of this guidebook is to provide comprehensive, state-by-state profiles of public and private sector resources available to assist transplant candidates, recipients and their families, as well as potential organ donors. Section A of the guidebook provides a general introduction to the public programs and private organizations that currently assist in this area. Section B, organized by state, contains profiles that describe in more detail the nature of the resources that are available in each state to assist residents with organ donation and transplantation. This section explains how to gain access to these programs and who to contact for further information. Section B also includes the addresses and phone numbers of the medical transplant centers, tissue typing laboratories, and organ procurement organizations that exist in each state. The guide also may be useful for government officials, voluntary health organizations, organ procurement organizations, and health care providers.

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·

Organ Transplants: Increased Effort Needed to Boost Supply and Ensure Equitable Distribution of Organs Source: Washington, DC: United States General Accounting Office. 1993. 94 p. Contact: Available from United States General Accounting Office. P.O. Box 6015, Gaithersburg, MD 20884-6015. (202) 512-6000. PRICE: Single copy free. Order Number: GAO/HRD-93-56. Summary: This report responds to a provision of the Transplant Amendments Act of 1990 that required the U.S. General Accounting Office (GAO) to study the effectiveness of the organ procurement and allocation system. In this report, the GAO addresses whether organs are being equitably distributed; whether organ procurement organizations (OPOs) are obtaining an adequate number of potential donors; and whether the Department of Health and Human Services (HHS) is adequately monitoring these organizations' organ procurement and allocation efforts. The GAO surveyed the allocation and procurement policies of the 68 OPOs, interviewed officials and reviewed records at 10 OPOs, and interviewed numerous people involved in the field of organ transplantation. The report includes four chapters: an executive summary, the organ allocation process and equity, procurement rates at OPOs, and conclusions and recommendations. 3 figures. 16 tables. 12 appendices. 25 references.

·

Annual Report on the U.S. Scientific Registry for Organ Transplantation and the Organ Procurement and Transplantation Network Source: Richmond, VA: UNOS. 1990. 163 p. Contact: Available from UNOS United Network for Organ Sharing. Rebecca Woddell, Research and Policy Department, 1100 Boulders Parkway, Suite 500, P.O Box 13770, Richmond, VA 23225. (804) 330-8500. PRICE: $10. Summary: This report provides data reported by all organ transplant programs, histocompatibility laboratories, and organ procurement organizations throughout the U.S. on all types of organ transplants for the years 1988 and 1989. Sections include an executive summary, data on organ donation and procurement, the national transplant waiting list, transplantation, transplant outcomes, and organ disposition. Heart-lung, liver, pancreas, and kidney transplants are included. Extensive figures and tables illustrate the statistical data provided. Eleven appendixes reproduce some of the raw data.

Physician Guidelines and Databases 163

The NLM Gateway29 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.30 One target audience for the Gateway is the Internet user who is new to NLM’s online resources and does not know what information is available or how best to search for it. This audience may include physicians and other healthcare providers, researchers, librarians, students, and, increasingly, patients, their families, and the public.31 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “transplantation” (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 Items Found Journal Articles 345134 Books / Periodicals / Audio Visual 2567 Consumer Health 293 Meeting Abstracts 3093 Other Collections 100 Total 351187

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x. 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). 31 Other users may find the Gateway useful for an overall search of NLM’s information resources. Some searchers may locate what they need immediately, while others will utilize the Gateway as an adjunct tool to other NLM search services such as PubMed® and MEDLINEplus®. The Gateway connects users with multiple NLM retrieval systems while also providing a search interface for its own collections. These collections include various types of information that do not logically belong in PubMed, LOCATORplus, or other established NLM retrieval systems (e.g., meeting announcements and pre-1966 journal citations). The Gateway will provide access to the information found in an increasing number of NLM retrieval systems in several phases. 29 30

164 Transplantation

HSTAT32 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.33 HSTAT’s audience includes healthcare providers, health service researchers, policy makers, insurance companies, consumers, and the information professionals who serve these groups. HSTAT provides access to a wide variety of publications, including clinical practice guidelines, quick-reference 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.34 Simply search by “transplantation” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists35 Some patients may wish to have access to 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. To this end, we recommend “Coffee Break,” 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.36 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.37 This site has new Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. The HSTAT URL is http://hstat.nlm.nih.gov/. 34 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. 35 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 36 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. 37 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. 32 33

Physician Guidelines and Databases 165

articles every few weeks, so it can be considered an online magazine of sorts, and intended for general background information. You can access the Coffee Break Web site at 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 a few 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/.

·

Image Engine: Multimedia electronic medical record system that integrates a wide range of digitized clinical images with textual data stored in the University of Pittsburgh Medical Center’s MARS electronic medical record system; see the following Web site: http://www.cml.upmc.edu/cml/imageengine/imageEngine.html.

·

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

·

MedWeaver: Prototype system that allows users to search differential diagnoses for any list of signs and symptoms, to search medical literature, and to explore relevant Web sites; see http://www.med.virginia.edu/~wmd4n/medweaver.html.

·

Metaphrase: Middleware component intended for use by both caregivers and medical records personnel. It converts the informal language generally used by caregivers into terms from formal, controlled vocabularies; see the following Web site: http://www.lexical.com/Metaphrase.html.

Specialized References The following books are specialized references written for professionals interested in transplantation (sorted alphabetically by title, hyperlinks provide rankings, information, and reviews at Amazon.com): ·

2003 Pocket Book of Infectious Disease Therapy by John G. Bartlett; 12th edition (June 15, 2003), Lippincott, Williams & Wilkins Publishers; ISBN: 0781738962; http://www.amazon.com/exec/obidos/ASIN/0781738962/icongroupinterna

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·

Immunology and Evolution of Infectious Disease by Steven A. Frank; Paperback – 352 pages (August 2002), Princeton University Press; ISBN: 0691095957; http://www.amazon.com/exec/obidos/ASIN/0691095957/icongroupinterna

·

Infectious Disease Epidemiology: Theory and Practice by Kenrad E. Nelson, et al; Hardcover – 600 pages (May 2000), Aspen Publishers, Inc.; ISBN: 083421766X; http://www.amazon.com/exec/obidos/ASIN/083421766X/icongroupinterna

·

Infectious Disease Pearls (The Pearls Series) by Steven A. Sahn (Editor), et al; Paperback – 250 pages (November 1998), Hanley & Belfus; ISBN: 1560532033; http://www.amazon.com/exec/obidos/ASIN/1560532033/icongroupinterna

·

Manual of Clinical Problems in Infectious Disease by Nelson M. Gantz, et al; Spiral-bound -- 523 pages, 4th edition (May 15, 1999), Lippincott Williams & Wilkins Publishers; ISBN: 0781719100; http://www.amazon.com/exec/obidos/ASIN/0781719100/icongroupinterna

·

Mims’ Pathogenesis of Infectious Disease by Cedric A. Mims, et al; Paperback -- 474 pages, 5th edition (January 15, 2001), Academic Press; ISBN: 0124982654; http://www.amazon.com/exec/obidos/ASIN/0124982654/icongroupinterna

·

A Practical Approach to Infectious Diseases by Richard E. Reese, M.D. (Editor), Robert F. Betts, M.D. (Editor); Paperback, 4th edition (September 1996), Little Brown & Co.; ISBN: 0316737216; http://www.amazon.com/exec/obidos/ASIN/0316737216/icongroupinterna

Vocabulary Builder 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] Exocrine: 1. secreting outwardly, via a duct;. [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] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH]

Xerostomia: Dryness of the mouth from salivary gland dysfunction, as in Sjögren's syndrome. [EU]

Dissertations 167

CHAPTER 10. DISSERTATIONS ON TRANSPLANTATION Overview University researchers are active in studying almost all known medical procedures and treatments. The result of research is often published in the form of Doctoral or Master’s dissertations. You should understand, therefore, that applied diagnostic procedures and/or therapies can take many years to develop after the thesis that proposed the new technique or approach was written. In this chapter, we will give you a bibliography on recent dissertations relating to transplantation. You can read about these in more detail using the Internet or your local medical library. We will also provide you with information on how to use the Internet to stay current on dissertations.

Dissertations on Transplantation ProQuest Digital Dissertations is the largest archive of academic dissertations available. From this archive, we have compiled the following list covering dissertations devoted to transplantation. You will see that the information provided includes the dissertation’s title, its author, and the author’s institution. To read more about the following, simply use the Internet address indicated. The following covers recent dissertations dealing with transplantation: ·

A Hermeneutical Study of the Medical Treatment Decision for End Stage Renal Disease Patients and Their Families (organ

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Transplantation, Dialysis) by Sloan, Rebecca S., Phd from University of Kentucky, 1996, 232 pages http://wwwlib.umi.com/dissertations/fullcit/9616128 ·

A Study of the Effect of Transplantation upon Attitudes toward the United States of Southern Italians in New York City As Revealed by Survivors of the Mass - Migration, 1887-1915 by Winsey, Valentine Rossilli, Phd from New York University, 1966, 373 pages http://wwwlib.umi.com/dissertations/fullcit/6704916

·

An Exploration of Educational Needs and Educational Deficits in a Regional Organ Procurement Program (transplantation) by Mckenna, Barbara Ann, Edd from The University of Rochester, 1993, 408 pages http://wwwlib.umi.com/dissertations/fullcit/9328307

·

Blood Donors' Attitudes, Knowledge, and Awareness of Others Concerning Organ Transplantation and Donation (organ Donation) by Denti, Jeanne Marie, Phd from Syracuse University, 1989, 225 pages http://wwwlib.umi.com/dissertations/fullcit/8919515

Keeping Current As previously mentioned, an effective way to stay current on dissertations dedicated to transplantation is to use the database called ProQuest Digital Dissertations via the Internet, located at the following Web address: http://wwwlib.umi.com/dissertations. The site allows you to freely access the last two years of citations and abstracts. Ask your medical librarian if the library has full and unlimited access to this database. From the library, you should be able to do more complete searches than with the limited 2-year access available to the general public.

169

PART III. APPENDICES

ABOUT PART III Part III is a collection of appendices on general medical topics which may be of interest to patients undergoing transplantation.

Researching Your Medications 171

APPENDIX A. RESEARCHING YOUR MEDICATIONS Overview There are a number of sources available on new or existing medications which could be prescribed to patients undergoing transplantation. Often these medications can be taken in preparation for transplantation, or immediately following it. While a number of hard copy or CD-Rom resources are available to patients and physicians for research purposes, a more flexible method is to use Internet-based databases. In this chapter, we will begin with a general overview of medications. We will then proceed to outline official recommendations on how you should view your medications. You may also want to research medications that you are currently taking for other conditions as they may interact with medications prescribed specifically for transplantation. Research can give you information on the side effects, interactions, and limitations of prescription drugs used in conjunction with transplantation. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

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Your Medications: The Basics38 Taking medicines is not always as simple as swallowing a pill. It can involve many steps and decisions each day. The AHCRQ recommends that patients take part in treatment decisions. Do not be afraid to ask questions and talk about your concerns. By taking a moment to ask questions early, you may avoid problems later. Here are some points to cover each time a new medicine is prescribed: ·

Ask about all parts of your treatment, including diet changes, exercise, and medicines.

·

Ask about the risks and benefits of each medicine or other treatment you might receive.

·

Ask how often you or your doctor will check for side effects from a given medication.

Do not hesitate to ask what is important to you about your medicines. You may want a medicine with the fewest side effects, or the fewest doses to take each day. You may care most about cost, or how the medicine might affect your daily activities. Or, you may want the medicine your doctor believes will work the best. Telling your doctor will help him or her select the best medication for you. Do not be afraid to “bother” your doctor with your concerns and questions about your medications. You can also talk to a nurse or a pharmacist. Feel free to bring a friend or family member with you when you visit your doctor. Talking over your options with someone you trust can help you make better choices, especially if you are not feeling well. Specifically, ask your doctor the following: ·

The name of the medicine and what it is supposed to do.

·

How and when to take the medicine, how much to take, and for how long.

·

What food, drinks, other medicines, or activities you should avoid while taking the medicine.

·

What side effects the medicine may have, and what to do if they occur.

·

If you can get a refill, and how often.

·

About any terms or directions you do not understand.

·

What to do if you miss a dose.

38

This section is adapted from AHCRQ: http://www.ahcpr.gov/consumer/ncpiebro.htm.

Researching Your Medications 173

·

If there is written information you can take home (most pharmacies have information sheets on your prescription medicines; some even offer large-print or Spanish versions).

Do not forget to tell your doctor about all the medicines you are currently taking. This includes prescription medicines and the medicines that you buy over the counter. Then your doctor can avoid giving you a new medicine that may not work well with the medications you take now. When talking to your doctor, you may wish to prepare a list of medicines you currently take, the reason you take them, and how you take them. Be sure to include the following information for each: ·

Name of medicine

·

Reason taken

·

Dosage

·

Time(s) of day

Also include any over-the-counter medicines, such as: ·

Laxatives

·

Diet pills

·

Vitamins

·

Cold medicine

·

Aspirin or other pain, headache, or fever medicine

·

Cough medicine

·

Allergy relief medicine

·

Antacids

·

Sleeping pills

·

Others (include names)

Learning More about Your Medications Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications your doctor has recommended. 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

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non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at www.usp.org. The USP currently provides standards for over 3,700 medications. The resulting USP DIÒ Advice for the PatientÒ can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database.39 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 Pharmacopoeia (USP). It is important to read the disclaimer by the USP (http://www.nlm.nih.gov/medlineplus/drugdisclaimer.html) before using the information provided. Of course, we as editors cannot be certain as to what medications you are taking. Therefore, we have compiled a list of medications associated with transplantation. Once again, due to space limitations, we only list a sample of medications and provide hyperlinks to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to transplantation: Anti-Thymocyte Globulin (Rabbit) ·

Systemic - U.S. Brands: Thymoglobulin http://www.nlm.nih.gov/medlineplus/druginfo/antithymocytegl obulinrabbitsys500099.html

Atovaquone ·

Systemic - U.S. Brands: Mepron http://www.nlm.nih.gov/medlineplus/druginfo/atovaquonesyst emic202648.html

Though cumbersome, the FDA database can be freely browsed at the following site: www.fda.gov/cder/da/da.htm.

39

Researching Your Medications 175

Azathioprine ·

Systemic - U.S. Brands: Imuran http://www.nlm.nih.gov/medlineplus/druginfo/azathioprinesys temic202077.html

Basiliximab ·

Systemic - U.S. Brands: Simulect http://www.nlm.nih.gov/medlineplus/druginfo/basiliximabsyste mic203592.html

Busulfan ·

Systemic - U.S. Brands: Busulfex; Myleran http://www.nlm.nih.gov/medlineplus/druginfo/busulfansystemi c202101.html

Colony Stimulating Factors ·

Systemic - U.S. Brands: Leukine; Neupogen http://www.nlm.nih.gov/medlineplus/druginfo/colonystimulati ngfactorssystem202628.html

Cyclophosphamide ·

Systemic - U.S. Brands: Cytoxan; Neosar http://www.nlm.nih.gov/medlineplus/druginfo/cyclophosphami desystemic202174.html

Cyclosporine ·

Systemic - U.S. Brands: Neoral; Sandimmune; SangCya http://www.nlm.nih.gov/medlineplus/druginfo/cyclosporinesys temic202176.html

Daclizumab ·

Systemic - U.S. Brands: Zenapax http://www.nlm.nih.gov/medlineplus/druginfo/daclizumabsyst emic203435.html

Ganciclovir ·

Systemic - U.S. Brands: Cytovene; Cytovene-IV http://www.nlm.nih.gov/medlineplus/druginfo/ganciclovirsyste mic202255.html

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Granisetron ·

Systemic - U.S. Brands: Kytril http://www.nlm.nih.gov/medlineplus/druginfo/granisetronsyste mic202724.html

Mycophenolate ·

Systemic - U.S. Brands: CellCept http://www.nlm.nih.gov/medlineplus/druginfo/mycophenolates ystemic203436.html

Sirolimus ·

Systemic - U.S. Brands: Rapamune http://www.nlm.nih.gov/medlineplus/druginfo/sirolimussystem ic500028.html

Tacrolimus ·

Systemic - U.S. Brands: Prograf http://www.nlm.nih.gov/medlineplus/druginfo/tacrolimussyste mic202914.html

Ursodiol ·

Systemic - U.S. Brands: Actigall http://www.nlm.nih.gov/medlineplus/druginfo/ursodiolsystemi c202587.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. You may be able to access these sources from your local medical library or your doctor’s office.

Reuters Health Drug Database The Reuters Health Drug Database can be searched by keyword at the hyperlink: http://www.reutershealth.com/frame2/drug.html. The following medications are listed in the Reuters’ database as associated with transplantation (including those with contraindications):40 40

Adapted from A to Z Drug Facts by Facts and Comparisons.

Researching Your Medications 177

·

Acyclovir http://www.reutershealth.com/atoz/html/Acyclovir.htm

·

Amphotericin B http://www.reutershealth.com/atoz/html/Amphotericin_B.htm

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Azathioprine http://www.reutershealth.com/atoz/html/Azathioprine.htm

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Basiliximab http://www.reutershealth.com/atoz/html/Basiliximab.htm

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Chlorhexidine Gluconate http://www.reutershealth.com/atoz/html/Chlorhexidine_Gluconate.htm

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Cyclosporine http://www.reutershealth.com/atoz/html/Cyclosporine.htm

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Cyclosporine(Cyclosporin A) http://www.reutershealth.com/atoz/html/Cyclosporine(Cyclosporin_ A).htm

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Filgrastim http://www.reutershealth.com/atoz/html/Filgrastim.htm

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Filgrastim (G-CSF) http://www.reutershealth.com/atoz/html/Filgrastim_(G-CSF).htm

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Fluconazole http://www.reutershealth.com/atoz/html/Fluconazole.htm

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Ganciclovir http://www.reutershealth.com/atoz/html/Ganciclovir.htm

·

Ganciclovir (DHPG) http://www.reutershealth.com/atoz/html/Ganciclovir_(DHPG).htm

·

Immune Globulin Intravenous http://www.reutershealth.com/atoz/html/Immune_Globulin_Intraven ous.htm

·

Immune Globulin Intravenous (IGIV) http://www.reutershealth.com/atoz/html/Immune_Globulin_Intraven ous_(IGIV).htm

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Immune Globulin IV http://www.reutershealth.com/atoz/html/Immune_Globulin_IV.htm

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Itraconazole http://www.reutershealth.com/atoz/html/Itraconazole.htm

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·

Mycophenolate Mofetil http://www.reutershealth.com/atoz/html/Mycophenolate_Mofetil.htm

·

Pneumococcal Vaccine Polyvalent http://www.reutershealth.com/atoz/html/Pneumococcal_Vaccine_Poly valent.htm

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Sargramostim http://www.reutershealth.com/atoz/html/Sargramostim.htm

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Sirolimus http://www.reutershealth.com/atoz/html/Sirolimus.htm

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Somatropin http://www.reutershealth.com/atoz/html/Somatropin.htm

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Tacrolimus http://www.reutershealth.com/atoz/html/Tacrolimus.htm

·

Trovafloxacin Mesylate Alatrofloxacin Mesylate http://www.reutershealth.com/atoz/html/Trovafloxacin_Mesylate_Ala trofloxacin_Mesylate.htm

Mosby’s GenRx Mosby’s GenRx 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. Information can be obtained at the following hyperlink: http://www.genrx.com/Mosby/PhyGenRx/group.html.

Physicians Desk Reference The Physicians Desk Reference database (also available in CD-Rom and book format) is a full-text drug database. The database is searchable by brand name, generic name or by indication. It features multiple drug interactions reports. Information can be obtained at the following hyperlink: http://physician.pdr.net/physician/templates/en/acl/psuser_t.htm.

Other Web Sites A number of additional Web sites discuss drug information. As an example, you may like to look at www.drugs.com which reproduces the information

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in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. which allows users to download articles on various drugs and therapeutics for a nominal fee: http://www.medletter.com/.

Contraindications and Interactions (Hidden Dangers) Some of the medications mentioned in the previous discussions can be problematic for patients undergoing transplantation--not because they are used in the treatment process, but because of contraindications, or side effects. You should ask your physician about any contraindications, especially as these might apply to other medications that you may be taking for common ailments. Drug-drug interactions occur when two or more drugs react with each other. This drug-drug interaction may cause you to experience an unexpected side effect. Drug interactions may make your medications less effective, cause unexpected side effects, or increase the action of a particular drug. Some drug interactions can even be harmful to you. Be sure to read the label every time you use a nonprescription or prescription drug, and take the time to learn about drug interactions. These precautions may be critical to your health. You can reduce the risk of potentially harmful drug interactions and side effects with a little bit of knowledge and common sense. Drug labels contain important information about ingredients, uses, warnings, and directions which you should take the time to read and understand. Labels also include warnings about possible drug interactions. Further, drug labels may change as new information becomes available. This is why it’s especially important to read the label every time you use a medication. When your doctor prescribes a new drug, discuss all over-thecounter and prescription medications, dietary supplements, vitamins, botanicals, minerals and herbals you take as well as the foods you eat. Ask your pharmacist for the package insert for each prescription drug you take. The package insert provides more information about potential drug interactions.

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A Final Warning At some point, you may hear of alternative medications from friends, relatives, or in the news media. Advertisements may suggest that certain alternative drugs can produce positive results for patients. Exercise caution-some of these drugs may have fraudulent claims, and others may actually hurt you. The Food and Drug Administration (FDA) is the official U.S. agency charged with discovering which medications are likely to benefit patients having transplantation. The FDA warns patients to watch out for41: ·

Secret formulas (real scientists share what they know)

·

Amazing breakthroughs or miracle cures (real breakthroughs don’t happen very often; when they do, real scientists do not call them amazing or miracles)

·

Quick, painless, or guaranteed cures

·

If it sounds too good to be true, it probably isn’t true.

If you have any questions about any kind of 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, 1888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

General References In addition to the resources provided earlier in this chapter, the following general references describe medications (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

Antimicrobial Pharmacodynamics in Theory and Clinical Practice by C. H. Nightingale (Editor), et al; Hardcover – 416 pages, 1st edition (January 15, 2002), Marcel Dekker; ISBN: 0824705610; http://www.amazon.com/exec/obidos/ASIN/0824705610/icongroupinterna

·

Antimicrobial Therapy and Vaccines by Victor L. Yu (Editor), et al; Hardcover - 1460 pages, 1st edition (January 15, 1999), Lippincott, Williams & Wilkins; ISBN: 068330061X; http://www.amazon.com/exec/obidos/asin/068330061x/icongroupinterna

This section has been adapted from http://www.fda.gov/opacom/lowlit/medfraud.html.

41

Researching Your Medications 181

·

Essentials of Antimicrobial Pharmacology: A Guide to Fundamentals for Practice by Paul H. Axelsen; Paperback – 141 pages, 1st edition (January 15, 2002), Humana Press; ISBN: 0896038424; http://www.amazon.com/exec/obidos/ASIN/0896038424/icongroupinterna

·

Macrolide Antibiotics: Chemistry, Biology, and Practice by Satoshi Omura (Editor); Hardcover – 768 pages, 2nd edition (June 15, 2002), Academic Press; ISBN: 0125264518; http://www.amazon.com/exec/obidos/ASIN/0125264518/icongroupinterna

·

Management of Antimicrobials in Infectious Diseases: Impact of Antibiotic Resistance by Arch G. Mainous, Ph.D. (Editor), et al; Hardcover – 350 pages, 1st edition (January 15, 2001), Humana Press; ISBN: 0896038211; http://www.amazon.com/exec/obidos/ASIN/0896038211/icongroupinterna

·

Vaccines by Stanley A., Md. Plotkin (Editor), et al; Hardcover - 1230 pages, 3rd edition (February 15, 1999), W B Saunders Co.; ISBN: 0721674437; http://www.amazon.com/exec/obidos/ASIN/0721674437/icongroupinterna

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: 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] Amphotericin B: Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela. [NIH] Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [NIH] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH]

Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU]

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APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE Overview Some individuals with seek alternatives to transplantation; as a result, complementary and alternative medicine (CAM) is one of the most contentious aspects of modern medical practice. You may have heard of these treatments on the radio or on television. Maybe you have seen articles written about these treatments in magazines, newspapers, or books. Perhaps your friends or doctor have mentioned alternatives. In this chapter, we will begin by giving you a broad perspective on complementary and alternative therapies. Next, we will introduce you to official information sources on CAM relating to transplantation. Finally, at the conclusion of this chapter, we will provide a list of readings on transplantation from various authors. We will begin, however, with the National Center for Complementary and Alternative Medicine’s (NCCAM) overview of complementary and alternative medicine.

What Is CAM?42 Complementary and alternative medicine (CAM) covers a broad range of healing philosophies, approaches, and therapies. Generally, it is defined as those treatments and healthcare practices which are not taught in medical schools, used in hospitals, or reimbursed by medical insurance companies. Many CAM therapies are termed “holistic,” which generally means that the healthcare practitioner considers the whole person, including physical, mental, emotional, and spiritual health. Some of these therapies are also 42

Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/faq/index.html#what-is.

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known as “preventive,” which means that the practitioner educates and treats the person to prevent health problems from arising, rather than treating symptoms after problems have occurred. People use CAM treatments and therapies in a variety of ways. Therapies are used alone (often referred to as alternative), in combination with other alternative therapies, or in addition to conventional treatment (sometimes referred to as complementary). Complementary and alternative medicine, or “integrative medicine,” includes a broad range of healing philosophies, approaches, and therapies. Some approaches are consistent with physiological principles of Western medicine, while others constitute healing systems with non-Western origins. While some therapies are far outside the realm of accepted Western medical theory and practice, others are becoming established in mainstream medicine. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease. Some commonly used methods of complementary or alternative therapy include mind/body control interventions such as visualization and relaxation, manual healing including acupressure and massage, homeopathy, vitamins or herbal products, and acupuncture.

What Are the Domains of Alternative Medicine?43 The list of CAM practices changes continually. The reason being is that these new practices and therapies are often proved to be safe and effective, and therefore become generally accepted as “mainstream” healthcare practices. Today, CAM practices may be grouped within five major domains: (1) alternative medical systems, (2) mind-body interventions, (3) biologicallybased treatments, (4) manipulative and body-based methods, and (5) energy therapies. The individual systems and treatments comprising these categories are too numerous to list in this sourcebook. Thus, only limited examples are provided within each.

Alternative Medical Systems Alternative medical systems involve complete systems of theory and practice that have evolved independent of, and often prior to, conventional biomedical approaches. Many are traditional systems of medicine that are 43

Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/classify/index.html.

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practiced by individual cultures throughout the world, including a number of venerable Asian approaches. Traditional oriental medicine emphasizes the balance or disturbances of qi (pronounced chi) or vital energy in health and disease, respectively. Traditional oriental medicine consists of a group of techniques and methods including acupuncture, herbal medicine, oriental massage, and qi gong (a form of energy therapy). Acupuncture involves stimulating specific anatomic points in the body for therapeutic purposes, usually by puncturing the skin with a thin needle. Ayurveda is India’s traditional system of medicine. Ayurvedic medicine (meaning “science of life”) is a comprehensive system of medicine that places equal emphasis on body, mind, and spirit. Ayurveda strives to restore the innate harmony of the individual. Some of the primary Ayurvedic treatments include diet, exercise, meditation, herbs, massage, exposure to sunlight, and controlled breathing. Other traditional healing systems have been developed by the world’s indigenous populations. These populations include Native American, Aboriginal, African, Middle Eastern, Tibetan, and Central and South American cultures. Homeopathy and naturopathy are also examples of complete alternative medicine systems. Homeopathic medicine is an unconventional Western system that is based on the principle that “like cures like,” i.e., that the same substance that in large doses produces the symptoms of an illness, in very minute doses cures it. Homeopathic health practitioners believe that the more dilute the remedy, the greater its potency. Therefore, they use small doses of specially prepared plant extracts and minerals to stimulate the body’s defense mechanisms and healing processes in order to treat illness. Naturopathic medicine is based on the theory that disease is a manifestation of alterations in the processes by which the body naturally heals itself and emphasizes health restoration rather than disease treatment. Naturopathic physicians employ an array of healing practices, including the following: diet and clinical nutrition, homeopathy, acupuncture, herbal medicine, hydrotherapy (the use of water in a range of temperatures and methods of applications), spinal and soft-tissue manipulation, physical therapies (such as those involving electrical currents, ultrasound, and light), therapeutic counseling, and pharmacology.

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Mind-Body Interventions Mind-body interventions employ a variety of techniques designed to facilitate the mind’s capacity to affect bodily function and symptoms. Only a select group of mind-body interventions having well-documented theoretical foundations are considered CAM. For example, patient education and cognitive-behavioral approaches are now considered “mainstream.” On the other hand, complementary and alternative medicine includes meditation, certain uses of hypnosis, dance, music, and art therapy, as well as prayer and mental healing.

Biological-Based Therapies This category of CAM includes natural and biological-based practices, interventions, and products, many of which overlap with conventional medicine’s use of dietary supplements. This category includes herbal, special dietary, orthomolecular, and individual biological therapies. Herbal therapy employs an individual herb or a mixture of herbs for healing purposes. An herb is a plant or plant part that produces and contains chemical substances that act upon the body. Special diet therapies, such as those proposed by Drs. Atkins, Ornish, Pritikin, and Weil, are believed to prevent and/or control illness as well as promote health. Orthomolecular therapies aim to treat disease with varying concentrations of chemicals such as magnesium, melatonin, and mega-doses of vitamins. Biological therapies include, for example, the use of laetrile and shark cartilage to treat cancer and the use of bee pollen to treat autoimmune and inflammatory diseases.

Manipulative and Body-Based Methods This category includes methods that are based on manipulation and/or movement of the body. For example, chiropractors focus on the relationship between structure and function, primarily pertaining to the spine, and how that relationship affects the preservation and restoration of health. Chiropractors use manipulative therapy as an integral treatment tool. In contrast, osteopaths place particular emphasis on the musculoskeletal system and practice osteopathic manipulation. Osteopaths believe that all of the body’s systems work together and that disturbances in one system may have an impact upon function elsewhere in the body. Massage therapists manipulate the soft tissues of the body to normalize those tissues.

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Energy Therapies Energy therapies focus on energy fields originating within the body (biofields) or those from other sources (electromagnetic fields). Biofield therapies are intended to affect energy fields (the existence of which is not yet experimentally proven) that surround and penetrate the human body. Some forms of energy therapy manipulate biofields by applying pressure and/or manipulating the body by placing the hands in or through these fields. Examples include Qi gong, Reiki and Therapeutic Touch. Qi gong is a component of traditional oriental medicine that combines movement, meditation, and regulation of breathing to enhance the flow of vital energy (qi) in the body, improve blood circulation, and enhance immune function. Reiki, the Japanese word representing Universal Life Energy, is based on the belief that, by channeling spiritual energy through the practitioner, the spirit is healed and, in turn, heals the physical body. Therapeutic Touch is derived from the ancient technique of “laying-on of hands.” It is based on the premises that the therapist’s healing force affects the patient’s recovery and that healing is promoted when the body’s energies are in balance. By passing their hands over the patient, these healers identify energy imbalances. Bioelectromagnetic-based therapies involve the unconventional use of electromagnetic fields to treat illnesses or manage pain. These therapies are often used to treat asthma, cancer, and migraine headaches. Types of electromagnetic fields which are manipulated in these therapies include pulsed fields, magnetic fields, and alternating current or direct current fields.

Can Alternatives Affect My Treatment? A critical issue in pursuing complementary alternatives mentioned thus far is the risk that these might have undesirable interactions with your medical treatment. It becomes all the more important to speak with your doctor who can offer advice on the use of alternatives. Official sources confirm this view. Though written for women, we find that the National Women’s Health Information Center’s advice on pursuing alternative medicine is appropriate for patients of both genders and all ages.44

44

Adapted from http://www.4woman.gov/faq/alternative.htm.

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Is It Okay to Want Both Traditional and Alternative or Complementary Medicine? Should you wish to explore non-traditional types of treatment, be sure to discuss all issues concerning treatments and therapies with your healthcare provider, whether a physician or practitioner of complementary and alternative medicine. Competent healthcare management requires knowledge of both conventional and alternative therapies you are taking for the practitioner to have a complete picture of your treatment plan. The decision to use complementary and alternative treatments is an important one. Consider before selecting an alternative therapy, the safety and effectiveness of the therapy or treatment, the expertise and qualifications of the healthcare practitioner, and the quality of delivery. These topics should be considered when selecting any practitioner or therapy.

Finding CAM References on Transplantation Having read the previous discussion, you may be wondering which complementary or alternative treatments might be appropriate when considering having transplantation. For the remainder of this chapter, we will direct you to a number of official sources which can assist you in researching studies and publications. Some of these articles are rather technical, so some patience may be required.

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

Bucillamine, a thiol antioxidant, prevents transplantation-associated reperfusion injury.

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Author(s): Amersi F, Nelson SK, Shen XD, Kato H, Melinek J, KupiecWeglinski JW, Horwitz LD, Busuttil RW, Horwitz MA. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 June 25; 99(13): 8915-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12084933&dopt=Abstract

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

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

·

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

·

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

·

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

·

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

·

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

·

Healthnotes: http://www.thedacare.org/healthnotes/

·

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

·

TPN.com: http://www.tnp.com/

·

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

·

WebMDÒHealth: http://my.webmd.com/drugs_and_herbs

·

WellNet: http://www.wellnet.ca/herbsa-c.htm

·

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

The following is a specific Web list relating to Transplantation; 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:

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·

General Overview Alopecia Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Alo peciacc.html Amyloidosis Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Am yloidosiscc.html Bone Cancer Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Can cerBonecc.html Bone Marrow Disorders Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Mye loproliferativeDisorderscc.html Brain Cancer Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Can cerBraincc.html Breast Cancer Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Cancer_Breast.ht m

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Burns Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Bur nscc.html Cancer, Bone Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Can cerBonecc.html Cancer, Brain Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Can cerBraincc.html Cancer, Prostate Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Can cerProstatecc.html Cardiomyopathy Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Cardiomyopathy. htm Cardiomyopathy Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000274.html Cardiovascular Disease Overview Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Cardiovascular_Di sease.htm

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Chronic Myelogenous Leukemia Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Mye loproliferativeDisorderscc.html Chronic Obstructive Pulmonary Disease Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/COPD.htm Congestive Heart Failure Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Congestive_Heart. htm Congestive Heart Failure Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Con gestiveHeartFailurecc.html Cystic Fibrosis Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Cys ticFibrosiscc.html Depression (Mild to Moderate) Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000280.html Diabetes Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Diabetes.htm

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Hair Loss Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Alo peciacc.html Heart Failure, Congestive Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Con gestiveHeartFailurecc.html Hepatitis Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Hepatitis.htm High Cholesterol Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000278.html Histoplasmosis Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Hist oplasmosiscc.html Immune Function Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Immune_Function .htm Leukemia Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Leu kemiacc.html

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Liver Cirrhosis Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Liver_Cirrhosis.ht m Lymphoma Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Ly mphomacc.html Myelofibrosis Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Mye loproliferativeDisorderscc.html Myeloproliferative Disorders Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Mye loproliferativeDisorderscc.html Parasitic Infection, Histoplasmosis Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Hist oplasmosiscc.html Polycythemia Vera Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Mye loproliferativeDisorderscc.html

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Prostate Cancer Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Can cerProstatecc.html Pulmonary Hypertension Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Pri maryPulmonaryHypertensioncc.html Sarcoidosis Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Sarc oidosiscc.html Scleroderma Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Scle rodermacc.html Sickle Cell Anemia Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Sickle_Cell_Anem ia.htm Thrombocytosis Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Mye loproliferativeDisorderscc.html

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Vitiligo Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Vitiligo.htm ·

Alternative Therapy Cell Therapy Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Therapy/Cell_Therapy.htm Naturopathy Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsModalities/Nat uropathycm.html Transference treatment Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/t.html

·

Herbs and Supplements Acidophilus and Other Probiotics Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000089.html Angkak Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/R edYeastRicecs.html Ashwagandha Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000099.html

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Astragalus Alternative names: Astragalus membranaceus Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/InteractiveMedicine/ConsHerbs/Interacti ons/Astragalusch.html Astragalus Alternative names: Astragalus membranaceus, Astragalus membranaceus var. mongholicus, Huang-qi, Milk-Vetch Root Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Astragal usch.html Astragalus membranaceus Alternative names: Astragalus Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/InteractiveMedicine/ConsHerbs/Interacti ons/Astragalusch.html Astragalus membranaceus Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Astragal usch.html Astragalus mongholicus Alternative names: Astragalus Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/InteractiveMedicine/ConsHerbs/Interacti ons/Astragalusch.html

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Astragalus mongholicus Alternative names: Astragalus membranaceus, Astragalus membranaceus var. mongholicus, Huang-qi, Milk-Vetch Root Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Astragal usch.html Azathioprine Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Azathioprine.htm Beni-koji Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/R edYeastRicecs.html Cat's Claw Alternative names: Uncaria tomentosa Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/CatsCla wch.html Chemotherapy Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Chemotherapy.htm Corticosteroids Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Corticosteroids.htm Cyclophosphamide Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Cyclophosphamide.htm

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Cyclosporine Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Cyclosporine.htm Cyclosporine Alternative names: Neoral, Sandimmune Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000361.html DHA Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/D ocosahexaenoicAcidDHAcs.html DHA Alternative names: Docosahexaenoic Acid (DHA) Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/InteractiveMedicine/ConsSupplements/In teractions/DocosahexaenoicAcidDHAcs.html Docetaxel Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Docetaxel.htm Docosahexaenoic Acid (DHA) Alternative names: DHA Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/InteractiveMedicine/ConsSupplements/In teractions/DocosahexaenoicAcidDHAcs.html

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Docosahexaenoic Acid (DHA) Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/D ocosahexaenoicAcidDHAcs.html Eicosapentaenoic Acid (EPA) Alternative names: EPA Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/InteractiveMedicine/ConsSupplements/In teractions/EicosapentaenoicAcidEPAcs.html Eicosapentaenoic Acid (EPA) Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/Ei cosapentaenoicAcidEPAcs.html Eleuthero Alternative names: Siberian Ginseng, Eleuthero; Acanthopanax/Eleutherococcus senticosus Rupr. & Maxim. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ EPA Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/Ei cosapentaenoicAcidEPAcs.html EPA Alternative names: Eicosapentaenoic Acid (EPA) Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/InteractiveMedicine/ConsSupplements/In teractions/EicosapentaenoicAcidEPAcs.html

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Fluorouracil Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Fluorouracil.htm Ginger Alternative names: Zingiber officinale Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Gingerch .html Hong Qu Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/R edYeastRicecs.html Huang-qi Alternative names: Astragalus Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/InteractiveMedicine/ConsHerbs/Interacti ons/Astragalusch.html Huang-qi Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Astragal usch.html Hung-chu Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/R edYeastRicecs.html

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Hypericum perforatum Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/StJohns Wortch.html IP-6 Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/IP-6.htm Klamathweed Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/StJohns Wortch.html Labetalol Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Labetalol.htm Melatonin Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/M elatonincs.html Methotrexate Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Methotrexate.htm Milk Thistle Alternative names: Silybum marianum, St. Mary's Thistle Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/MilkThis tlech.html

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Milk-Vetch Root Alternative names: Astragalus Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/InteractiveMedicine/ConsHerbs/Interacti ons/Astragalusch.html Milk-Vetch Root Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Astragal usch.html Monascus Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/R edYeastRicecs.html Oral Corticosteroids Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Corticosteroids_Oral. htm Paclitaxel Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Paclitaxel.htm Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/

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Piper nigrum Alternative names: Black Pepper Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Plantago psyllium Alternative names: Psyllium, Ispaghula; Plantago psyllium/ovata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Pyruvate Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Pyruvate.htm Red Koji Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/R edYeastRicecs.html Red Leaven Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/R edYeastRicecs.html Red Rice Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/R edYeastRicecs.html

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Red Yeast Rice Alternative names: Angkak, Beni-koju, Hong Qu, Hung-chu, Monascus, Red Leaven, Red Rice, Red Koji, Zhitai, Xue Zhi Kang Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/R edYeastRicecs.html Red yeast rice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525, 10054,00.html Sambucus Alternative names: Black Elderberry; Sambucus nigra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ SAMe Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/SAMe.htm Silybum marianum Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/MilkThis tlech.html St. John's Wort Alternative names: Hypericum perforatum, Klamathweed Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/StJohns Wortch.html

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St. John's Wort Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000237.html St. Mary's Thistle Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/MilkThis tlech.html Tanacetum Alternative names: Feverfew; Tanacetum parthenium (L.) Schultz-Bip. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Uncaria tomentosa Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/CatsCla wch.html Zhitai Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/R edYeastRicecs.html Zingiber officinale Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Gingerch .html

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Zue Zhi Kang Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/R edYeastRicecs.html

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at: www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources. The following additional references describe, in broad terms, alternative and complementary medicine (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · Antibiotic Crisis, Antibiotic Alternatives by Leon Chaitow; Hardcover – 240 pages (October 1998), Thorsons Publishing; ISBN: 0722537727; http://www.amazon.com/exec/obidos/ASIN/0722537727/icongroupinterna · Natural Alternatives to Antibiotics by John McKenna; Paperback – 176 pages (November 1998), Avery Penguin Putnam; ISBN: 0895298392; http://www.amazon.com/exec/obidos/ASIN/0895298392/icongroupinterna For additional information on complementary and alternative medicine, ask your doctor or write to: National Institutes of Health National Center for Complementary and Alternative Medicine Clearinghouse P. O. Box 8218 Silver Spring, MD 20907-8218

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters:

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Alopecia: Baldness; absence of the hair from skin areas where it normally is present. [EU] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Labetalol: Blocker of both alpha- and beta-adrenergic receptors that is used as an antihypertensive. [NIH] Parasitic: Pertaining to, of the nature of, or caused by a parasite. [EU] Plantago: Three different species of Plantago or plantain, P. psyllium, P. ovata and P. indica. The seeds swell in water and are used as laxatives. [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] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Thrombocytosis: Increased numbers of platelets in the peripheral blood. [EU] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH]

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APPENDIX C. RESEARCHING NUTRITION Overview Since the time of Hippocrates, doctors have understood the importance of diet and nutrition to patients’ health and well-being. Since then, they have accumulated an impressive archive of studies and knowledge dedicated to this subject. Based on their experience, doctors and healthcare providers may recommend particular dietary supplements to patients having transplantation. Any dietary recommendation is based on a patient’s age, body mass, gender, lifestyle, eating habits, food preferences, and health condition. It is therefore likely that different patients having transplantation may be given different recommendations. Some recommendations may be directly related to transplantation, while others may be more related to the patient’s general health. These recommendations, themselves, may differ from what official sources recommend for the average person. In this chapter we will begin by briefly reviewing the essentials of diet and nutrition that will broadly frame more detailed discussions of transplantation. We will then show you how to find studies dedicated specifically to nutrition and transplantation.

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Food and Nutrition: General Principles What Are Essential Foods? Food is generally viewed by official sources as consisting of six basic elements: (1) fluids, (2) carbohydrates, (3) protein, (4) fats, (5) vitamins, and (6) minerals. Consuming a combination of these elements is considered to be a healthy diet: ·

Fluids are essential to human life as 80-percent of the body is composed of water. Water is lost via urination, sweating, diarrhea, vomiting, diuretics (drugs that increase urination), caffeine, and physical exertion.

·

Carbohydrates are the main source for human energy (thermoregulation) and the bulk of typical diets. They are mostly classified as being either simple or complex. Simple carbohydrates include sugars which are often consumed in the form of cookies, candies, or cakes. Complex carbohydrates consist of starches and dietary fibers. Starches are consumed in the form of pastas, breads, potatoes, rice, and other foods. Soluble fibers can be eaten in the form of certain vegetables, fruits, oats, and legumes. Insoluble fibers include brown rice, whole grains, certain fruits, wheat bran and legumes.

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Proteins are eaten to build and repair human tissues. Some foods that are high in protein are also high in fat and calories. Food sources for protein include nuts, meat, fish, cheese, and other dairy products.

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Fats are consumed for both energy and the absorption of certain vitamins. There are many types of fats, with many general publications recommending the intake of unsaturated fats or those low in cholesterol.

Vitamins and minerals are fundamental to human health, growth, and, in some cases, disease prevention. Most are consumed in your diet (exceptions being vitamins K and D which are produced by intestinal bacteria and sunlight on the skin, respectively). Each vitamin and mineral plays a different role in health. The following outlines essential vitamins: ·

Vitamin A is important to the health of your eyes, hair, bones, and skin; sources of vitamin A include foods such as eggs, carrots, and cantaloupe.

·

Vitamin B1, also known as thiamine, is important for your nervous system and energy production; food sources for thiamine include meat, peas, fortified cereals, bread, and whole grains.

·

Vitamin B2, also known as riboflavin, is important for your nervous system and muscles, but is also involved in the release of proteins from

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nutrients; food sources for riboflavin include dairy products, leafy vegetables, meat, and eggs. ·

Vitamin B3, also known as niacin, is important for healthy skin and helps the body use energy; food sources for niacin include peas, peanuts, fish, and whole grains

·

Vitamin B6, also known as pyridoxine, is important for the regulation of cells in the nervous system and is vital for blood formation; food sources for pyridoxine include bananas, whole grains, meat, and fish.

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Vitamin B12 is vital for a healthy nervous system and for the growth of red blood cells in bone marrow; food sources for vitamin B12 include yeast, milk, fish, eggs, and meat.

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Vitamin C allows the body’s immune system to fight various diseases, strengthens body tissue, and improves the body’s use of iron; food sources for vitamin C include a wide variety of fruits and vegetables.

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Vitamin D helps the body absorb calcium which strengthens bones and teeth; food sources for vitamin D include oily fish and dairy products.

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Vitamin E can help protect certain organs and tissues from various degenerative diseases; food sources for vitamin E include margarine, vegetables, eggs, and fish.

·

Vitamin K is essential for bone formation and blood clotting; common food sources for vitamin K include leafy green vegetables.

·

Folic Acid maintains healthy cells and blood and, when taken by a pregnant woman, can prevent her fetus from developing neural tube defects; food sources for folic acid include nuts, fortified breads, leafy green vegetables, and whole grains.

It should be noted that one can overdose on certain vitamins which become toxic if consumed in excess (e.g. vitamin A, D, E and K). Like vitamins, minerals are chemicals that are required by the body to remain in good health. Because the human body does not manufacture these chemicals internally, we obtain them from food and other dietary sources. The more important minerals include: ·

Calcium is needed for healthy bones, teeth, and muscles, but also helps the nervous system function; food sources for calcium include dry beans, peas, eggs, and dairy products.

·

Chromium is helpful in regulating sugar levels in blood; food sources for chromium include egg yolks, raw sugar, cheese, nuts, beets, whole grains, and meat.

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·

Fluoride is used by the body to help prevent tooth decay and to reinforce bone strength; sources of fluoride include drinking water and certain brands of toothpaste.

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Iodine helps regulate the body’s use of energy by synthesizing into the hormone thyroxine; food sources include leafy green vegetables, nuts, egg yolks, and red meat.

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Iron helps maintain muscles and the formation of red blood cells and certain proteins; food sources for iron include meat, dairy products, eggs, and leafy green vegetables.

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Magnesium is important for the production of DNA, as well as for healthy teeth, bones, muscles, and nerves; food sources for magnesium include dried fruit, dark green vegetables, nuts, and seafood.

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Phosphorous is used by the body to work with calcium to form bones and teeth; food sources for phosphorous include eggs, meat, cereals, and dairy products.

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Selenium primarily helps maintain normal heart and liver functions; food sources for selenium include wholegrain cereals, fish, meat, and dairy products.

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Zinc helps wounds heal, the formation of sperm, and encourage rapid growth and energy; food sources include dried beans, shellfish, eggs, and nuts.

The United States government periodically publishes recommended diets and consumption levels of the various elements of food. Again, your doctor may encourage deviations from the average official recommendation. To learn more about basic dietary guidelines, visit the Web site: http://www.health.gov/dietaryguidelines/. Based on these guidelines, many foods are required to list the nutrition levels on the food’s packaging. Labeling Requirements are listed at the following site maintained by the Food and Drug Administration: http://www.cfsan.fda.gov/~dms/labcons.html. When interpreting these requirements, the government recommends that consumers become familiar with the following abbreviations before reading FDA literature:45 ·

DVs (Daily Values): A new dietary reference term that will appear on the food label. It is made up of two sets of references, DRVs and RDIs.

·

DRVs (Daily Reference Values): A set of dietary references that applies to fat, saturated fat, cholesterol, carbohydrate, protein, fiber, sodium, and potassium.

45

Adapted from the FDA: http://www.fda.gov/fdac/special/foodlabel/dvs.html.

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·

RDIs (Reference Daily Intakes): A set of dietary references based on the Recommended Dietary Allowances for essential vitamins and minerals and, in selected groups, protein. The name “RDI” replaces the term “U.S. RDA.”

·

RDAs (Recommended Dietary Allowances): A set of estimated nutrient allowances established by the National Academy of Sciences. It is updated periodically to reflect current scientific knowledge. What Are Dietary Supplements?46

Dietary supplements are widely available through many commercial sources, including health food stores, grocery stores, pharmacies, and by mail. Dietary supplements are provided in many forms including tablets, capsules, powders, gel-tabs, extracts, and liquids. Historically in the United States, the most prevalent type of dietary supplement was a multivitamin/mineral tablet or capsule that was available in pharmacies, either by prescription or “over the counter.” Supplements containing strictly herbal preparations were less widely available. Currently in the United States, a wide array of supplement products are available, including vitamin, mineral, other nutrients, and botanical supplements as well as ingredients and extracts of animal and plant origin. According to the Office of Dietary Supplements (ODS), dietary supplements can have an important impact on the prevention and management of disease and on the maintenance of health.47 The ODS notes that considerable research on the effects of dietary supplements has been conducted in Asia and Europe where the use of plant products, in particular, has a long tradition. However, the overwhelming majority of supplements have not been studied scientifically. To explore the role of dietary supplements in the improvement of health care, the ODS plans, organizes, and supports conferences, workshops, and symposia on scientific topics related to dietary supplements. The ODS often works in conjunction with other NIH Institutes

This discussion has been adapted from the NIH: http://ods.od.nih.gov/whatare/whatare.html. 47 Adapted from http://ods.od.nih.gov/about/about.html. The Dietary Supplement Health and Education Act defines dietary supplements as “a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, mineral, amino acid, herb or other botanical; or a dietary substance for use to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any ingredient described above; and intended for ingestion in the form of a capsule, powder, softgel, or gelcap, and not represented as a conventional food or as a sole item of a meal or the diet.” 46

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and Centers, other government agencies, professional organizations, and public advocacy groups. To learn more about official information on dietary supplements, visit the ODS site at http://ods.od.nih.gov/whatare/whatare.html. Or contact: The Office of 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]

Finding Studies on Transplantation The NIH maintains an office dedicated to patient nutrition and diet. 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). 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.48 IBIDS is available to the public free of charge through the ODS Internet page: 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. We recommend that you start with the Consumer Database. While you may not find references for the topics that are of most interest to you, check back periodically as this database is frequently updated. More studies can be found by searching the Full IBIDS Database. Healthcare professionals and researchers generally use the third option, which lists peer-reviewed citations. In all cases, we suggest that you take advantage of the “Advanced Search” option that allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “transplantation” (or synonyms) 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.

48

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into the search box. To narrow the search, you can also select the “Title” field. The following information is typical of that found when using the “Full IBIDS Database” when searching using “transplantation” (or a synonym): ·

Cells of porcine epidermis and corneal epithelium are not recognized by human natural anti-alfa-galactoside IgG. Author(s): Karlova Univ., Prague (Czech Republic). Anatomicky Ustav Source: Hrdlickova Cela, E. Smetana, K. Plzak, J. Holikova, Z. Andre, S. Hrebicek, M. Hodanova, K. Dvorankova, B. Motlik, J. Gabius, H.J. FoliaBiologica (Czech Republic). (December 2001). volume 47(6) page 200-205. swine human physiology transplantation skin eyes epithelium liver cells tears immunoglobulins alpha galactosidase beta galactosidase melibiose lactoferrin immunoblotting 0015-5500 Summary: porcin physiologie humaine transplantation peau oeil epithelium foie cellule larme immunoglobuline alpha galactosidase beta galactosidase melibiose lactoferrine immunoblotting

Additional physician-oriented references include: ·

Effects of extending the duration of postgrafting immunosuppression and substituting granulocyte-colony-stimulating factor-mobilized peripheral blood mononuclear cells for marrow in allogeneic engraftment in a nonmyeloablative canine transplantation model. Author(s): Clinical Research Division, Fred Hutchinson Cancer Research Center Washington, Seattle 98109-1024, USA. Source: Zaucha, J M Yu, C Zellmer, E Takatu, A Junghanss, C Little, M T Storb, R Biol-Blood-Marrow-Transplant. 2001; 7(9): 513-6 1083-8791

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.thedacare.org/healthnotes/

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

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

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WebMDÒHealth: http://my.webmd.com/nutrition

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

The following is a specific Web list relating to Transplantation; 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:

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·

Vitamins Folic Acid Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Folic_Acid.htm Vitamin B3 Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000188.html

·

Minerals Cisplatin Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Cisplatin.htm Potassium Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/P otassiumcs.html Vanadium Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Vanadium.htm Zinc Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000128.html

·

Food and Diet Omega-3 Fatty Acids Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/InteractiveMedicine/ConsSupplements/In teractions/Omega3FattyAcidscs.html

218 Transplantation

Omega-3 Fatty Acids Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/O mega3FattyAcidscs.html Omega-6 Fatty Acids Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/O mega6FattyAcidscs.html Oysters Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,160,0 0.html

Vocabulary Builder The following vocabulary builder defines words used in the references in this chapter that have not been defined in previous chapters: Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Innervation: 1. the distribution or supply of nerves to a part. 2. the supply of nervous energy or of nerve stimulus sent to a part. [EU] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH]

Researching Nutrition 219

Overdose: 1. to administer an excessive dose. 2. an excessive dose. [EU] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Somatomedins: Insulin-like polypeptides made by the liver and some fibroblasts and released into the blood when stimulated by somatotropin. They cause sulfate incorporation into collagen, RNA, and DNA synthesis, which are prerequisites to cell division and growth of the organism. [NIH] Thermoregulation: Heat regulation. [EU] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of mycobacterium. [NIH] Vanadium: Vanadium. A metallic element with the atomic symbol V, atomic number 23, and atomic weight 50.94. It is used in the manufacture of vanadium steel. Prolonged exposure can lead to chronic intoxication caused by absorption usually via the lungs. [NIH]

Finding Medical Libraries 221

APPENDIX D. FINDING MEDICAL LIBRARIES Overview At a medical library you can find medical texts and reference books, consumer health publications, specialty newspapers and magazines, as well as medical journals. In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Before going to the library, highlight the references mentioned in this sourcebook that you find interesting. Focus on those items that are not available via the Internet, and ask the reference librarian for help with your search. He or she may know of additional resources that could be helpful to you. Most importantly, 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. NLM’s interlibrary loan services are only available to libraries. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.49

49

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

222 Transplantation

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 Open to the Public In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries that are generally open to the public and have reference facilities. The following is the NLM’s list plus hyperlinks to each library Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of 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):50 ·

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

·

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute), http://www.asmi.org/LIBRARY.HTM

·

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

·

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

·

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

·

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

·

California: Gateway Health Library (Sutter Gould Medical Foundation)

·

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

50

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

Finding Medical Libraries 223

·

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

·

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

·

California: San José PlaneTree Health Library, http://planetreesanjose.org/

·

California: Sutter Resource Library (Sutter Hospitals Foundation), http://go.sutterhealth.org/comm/resc-library/sac-resources.html

·

California: University of California, Davis. Health Sciences Libraries

·

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System), http://www.valleycare.com/library.html

·

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

·

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.exempla.org/conslib.htm

·

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/

·

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

·

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute), http://www.christianacare.org/health_guide/health_guide_pmri_health _info.cfm

·

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

·

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

·

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

·

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

224 Transplantation

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

Maine: Parkview Hospital, http://www.parkviewhospital.org/communit.htm#Library

·

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

·

Maine: Stephens Memorial Hospital Health Information Library (Western Maine Health), http://www.wmhcc.com/hil_frame.html

·

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

·

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre), http://www.deerlodge.mb.ca/library/libraryservices.shtml

Finding Medical Libraries 225

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center), http://www.cancer.med.umich.edu/learn/leares.htm

·

Michigan: Sladen Library & Center for Health Information Resources Consumer Health Information, http://www.sladen.hfhs.org/library/consumer/index.html

·

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center), http://www.saintpatrick.org/chi/librarydetail.php3?ID=41

226 Transplantation

·

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

·

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

·

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

·

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

·

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

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

Oklahoma: Saint Francis Health System Patient/Family Resource Center (Saint Francis Health System), http://www.sfhtulsa.com/patientfamilycenter/default.asp

Finding Medical Libraries 227

·

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

·

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

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

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

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

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

·

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

·

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

·

Quebec, Canada: Medical Library (Montreal General Hospital), http://ww2.mcgill.ca/mghlib/

·

South Dakota: Rapid City Regional Hospital - Health Information Center (Rapid City Regional Hospital, Health Information Center), http://www.rcrh.org/education/LibraryResourcesConsumers.htm

·

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

·

Texas: Matustik Family Resource Center (Cook Children’s Health Care System), http://www.cookchildrens.com/Matustik_Library.html

·

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

·

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center), http://www.swmedctr.com/Home/

Your Rights and Insurance 229

APPENDIX E. YOUR RIGHTS AND INSURANCE Overview Any patient undergoing transplantation faces a series of issues related more to the healthcare industry than to the medical procedure itself. This appendix covers two important topics in this regard: your rights and responsibilities as a patient, and how to get the most out of your medical insurance plan.

Your Rights as a Patient The President’s Advisory Commission on Consumer Protection and Quality in the Healthcare Industry has created the following summary of your rights as a patient.51

Information Disclosure Consumers have the right to receive accurate, easily understood information. Some consumers require assistance in making informed decisions about health plans, health professionals, and healthcare facilities. Such information includes: ·

Health plans. Covered benefits, cost-sharing, and procedures for resolving complaints, licensure, certification, and accreditation status, comparable measures of quality and consumer satisfaction, provider

51Adapted

from Consumer Bill of Rights and Responsibilities: http://www.hcqualitycommission.gov/press/cbor.html#head1.

230 Transplantation

network composition, the procedures that govern access to specialists and emergency services, and care management information. ·

Health professionals. Education, board certification, and recertification, years of practice, experience performing certain procedures, and comparable measures of quality and consumer satisfaction.

·

Healthcare facilities. Experience in performing certain procedures and services, accreditation status, comparable measures of quality, worker, and consumer satisfaction, and procedures for resolving complaints.

·

Consumer assistance programs. Programs must be carefully structured to promote consumer confidence and to work cooperatively with health plans, providers, payers, and regulators. Desirable characteristics of such programs are sponsorship that ensures accountability to the interests of consumers and stable, adequate funding. Choice of Providers and Plans

Consumers have the right to a choice of healthcare providers that is sufficient to ensure access to appropriate high-quality healthcare. To ensure such choice, the Commission recommends the following: ·

Provider network adequacy. All health plan networks should provide access to sufficient numbers and types of providers to assure that all covered services will be accessible without unreasonable delay -including access to emergency services 24 hours a day and 7 days a week. If a health plan has an insufficient number or type of providers to provide a covered benefit with the appropriate degree of specialization, the plan should ensure that the consumer obtains the benefit outside the network at no greater cost than if the benefit were obtained from participating providers.

·

Women’s health services. Women should be able to choose a qualified provider offered by a plan -- such as gynecologists, certified nurse midwives, and other qualified healthcare providers -- for the provision of covered care necessary to provide routine and preventative women’s healthcare services.

·

Access to specialists. Consumers having complex or serious medical procedures who require frequent specialty care should have direct access to a qualified specialist of their choice within a plan’s network of providers. Authorizations, when required, should be for an adequate number of direct access visits under an approved treatment plan.

Your Rights and Insurance 231

·

Transitional care. Consumers who are undergoing a course of treatment for a chronic or disabling condition (or who are in the second or third trimester of a pregnancy) at the time they involuntarily change health plans or at a time when a provider is terminated by a plan for other than cause should be able to continue seeing their current specialty providers for up to 90 days (or through completion of postpartum care) to allow for transition of care.

·

Choice of health plans. Public and private group purchasers should, wherever feasible, offer consumers a choice of high-quality health insurance plans.

Access to Emergency Services Consumers have the right to access emergency healthcare services when and where the need arises. Health plans should provide payment when a consumer presents to an emergency department with acute symptoms of sufficient severity--including severe pain--such that a “prudent layperson” could reasonably expect the absence of medical attention to result in placing that consumer’s health in serious jeopardy, serious impairment to bodily functions, or serious dysfunction of any bodily organ or part. Participation in Treatment Decisions Consumers have the right and responsibility to fully participate in all decisions related to their healthcare. Consumers who are unable to fully participate in treatment decisions have the right to be represented by parents, guardians, family members, or other conservators. Physicians and other health professionals should: ·

Provide patients with sufficient information and opportunity to decide among treatment options consistent with the informed consent process.

·

Discuss all treatment options with a patient in a culturally competent manner, including the option of no treatment at all.

·

Ensure that persons with disabilities have effective communications with members of the health system in making such decisions.

·

Discuss all current treatments a consumer may be undergoing.

·

Discuss all risks, nontreatment.

benefits,

and

consequences

to

treatment

or

232 Transplantation

·

Give patients the opportunity to refuse treatment and to express preferences about future treatment decisions.

·

Discuss the use of advance directives -- both living wills and durable powers of attorney for healthcare -- with patients and their designated family members.

·

Abide by the decisions made by their patients and/or their designated representatives consistent with the informed consent process.

Health plans, health providers, and healthcare facilities should: ·

Disclose to consumers factors -- such as methods of compensation, ownership of or interest in healthcare facilities, or matters of conscience -that could influence advice or treatment decisions.

·

Assure that provider contracts do not contain any so-called “gag clauses” or other contractual mechanisms that restrict healthcare providers’ ability to communicate with and advise patients about medically necessary treatment options.

·

Be prohibited from penalizing or seeking retribution against healthcare professionals or other health workers for advocating on behalf of their patients.

Respect and Nondiscrimination Consumers have the right to considerate, respectful care from all members of the healthcare industry at all times and under all circumstances. An environment of mutual respect is essential to maintain a quality healthcare system. To assure that right, the Commission recommends the following: ·

Consumers must not be discriminated against in the delivery of healthcare services consistent with the benefits covered in their policy, or as required by law, based on race, ethnicity, national origin, religion, sex, age, mental or physical disability, sexual orientation, genetic information, or source of payment.

·

Consumers eligible for coverage under the terms and conditions of a health plan or program, or as required by law, must not be discriminated against in marketing and enrollment practices based on race, ethnicity, national origin, religion, sex, age, mental or physical disability, sexual orientation, genetic information, or source of payment.

Your Rights and Insurance 233

Confidentiality of Health Information Consumers have the right to communicate with healthcare providers in confidence and to have the confidentiality of their individually identifiable healthcare information protected. Consumers also have the right to review and copy their own medical records and request amendments to their records.

Complaints and Appeals Consumers have the right to a fair and efficient process for resolving differences with their health plans, healthcare providers, and the institutions that serve them, including a rigorous system of internal review and an independent system of external review. A free copy of the Patient’s Bill of Rights is available from the American Hospital Association.52

Patient Responsibilities Treatment is a two-way street between you and your healthcare providers. To underscore the importance of finance in modern healthcare as well as your responsibility for the financial aspects of your care, the President’s Advisory Commission on Consumer Protection and Quality in the Healthcare Industry has proposed that patients understand the following “Consumer Responsibilities.”53 In a healthcare system that protects consumers’ rights, it is reasonable to expect and encourage consumers to assume certain responsibilities. Greater individual involvement by the consumer in his or her care increases the likelihood of achieving the best outcome and helps support a quality-oriented, cost-conscious environment. Such responsibilities include: ·

Take responsibility for maximizing healthy habits such as exercising, not smoking, and eating a healthy diet.

·

Work collaboratively with healthcare providers in developing and carrying out agreed-upon treatment plans.

·

Disclose relevant information and clearly communicate wants and needs.

To order your free copy of the Patient’s Bill of Rights, telephone 312-422-3000 or visit the American Hospital Association’s Web site: http://www.aha.org. Click on “Resource Center,” go to “Search” at bottom of page, and then type in “Patient’s Bill of Rights.” The Patient’s Bill of Rights is also available from Fax on Demand, at 312-422-2020, document number 471124. 53 Adapted from http://www.hcqualitycommission.gov/press/cbor.html#head1. 52

234 Transplantation

·

Use your health insurance plan’s internal complaint and appeal processes to address your concerns.

·

Avoid knowingly spreading disease.

·

Recognize the reality of risks, the limits of the medical science, and the human fallibility of the healthcare professional.

·

Be aware of a healthcare provider’s obligation to be reasonably efficient and equitable in providing care to other patients and the community.

·

Become knowledgeable about your health plan’s coverage and options (when available) including all covered benefits, limitations, and exclusions, rules regarding use of network providers, coverage and referral rules, appropriate processes to secure additional information, and the process to appeal coverage decisions.

·

Show respect for other patients and health workers.

·

Make a good-faith effort to meet financial obligations.

·

Abide by administrative and operational procedures of health plans, healthcare providers, and Government health benefit programs.

Choosing an Insurance Plan There are a number of official government agencies that help consumers understand their healthcare insurance choices.54 The U.S. Department of Labor, in particular, recommends ten ways to make your health benefits choices work best for you.55 1. Your options are important. There are many different types of health benefit plans. Find out which one your employer offers, then check out the plan, or plans, offered. Your employer’s human resource office, the health plan administrator, or your union can provide information to help you match your needs and preferences with the available plans. The more information you have, the better your healthcare decisions will be. 2. Reviewing the benefits available. Do the plans offered cover preventive care, well-baby care, vision or dental care? Are there deductibles? Answers to these questions can help determine the out-of-pocket expenses you may More information about quality across programs is provided at the following AHRQ Web site: http://www.ahrq.gov/consumer/qntascii/qnthplan.htm. 55 Adapted from the Department of Labor: http://www.dol.gov/dol/pwba/public/pubs/health/top10-text.html. 54

Your Rights and Insurance 235

face. Matching your needs and those of your family members will result in the best possible benefits. Cheapest may not always be best. Your goal is high quality health benefits. 3. Look for quality. The quality of healthcare services varies, but quality can be measured. You should consider the quality of healthcare in deciding among the healthcare plans or options available to you. Not all health plans, doctors, hospitals and other providers give the highest quality care. Fortunately, there is quality information you can use right now to help you compare your healthcare choices. Find out how you can measure quality. Consult the U.S. Department of Health and Human Services publication “Your Guide to Choosing Quality Health Care” on the Internet at www.ahcpr.gov/consumer. 4. Your plan’s summary plan description (SPD) provides a wealth of information. Your health plan administrator can provide you with a copy of your plan’s SPD. It outlines your benefits and your legal rights under the Employee Retirement Income Security Act (ERISA), the federal law that protects your health benefits. It should contain information about the coverage of dependents, what services will require a co-pay, and the circumstances under which your employer can change or terminate a health benefits plan. Save the SPD and all other health plan brochures and documents, along with memos or correspondence from your employer relating to health benefits. 5. Assess your benefit coverage as your family status changes. Marriage, divorce, childbirth or adoption, and the death of a spouse are all life events that may signal a need to change your health benefits. You, your spouse and dependent children may be eligible for a special enrollment period under provisions of the Health Insurance Portability and Accountability Act (HIPAA). Even without life-changing events, the information provided by your employer should tell you how you can change benefits or switch plans, if more than one plan is offered. If your spouse’s employer also offers a health benefits package, consider coordinating both plans for maximum coverage. 6. Changing jobs and other life events can affect your health benefits. Under the Consolidated Omnibus Budget Reconciliation Act (COBRA), you, your covered spouse, and your dependent children may be eligible to purchase extended health coverage under your employer’s plan if you lose your job, change employers, get divorced, or upon occurrence of certain other events. Coverage can range from 18 to 36 months depending on your situation. COBRA applies to most employers with 20 or more workers and

236 Transplantation

requires your plan to notify you of your rights. Most plans require eligible individuals to make their COBRA election within 60 days of the plan’s notice. Be sure to follow up with your plan sponsor if you don’t receive notice, and make sure you respond within the allotted time. 7. HIPAA can also help if you are changing jobs, particularly if you have a medical condition. HIPAA generally limits pre-existing condition exclusions to a maximum of 12 months (18 months for late enrollees). HIPAA also requires this maximum period to be reduced by the length of time you had prior “creditable coverage.” You should receive a certificate documenting your prior creditable coverage from your old plan when coverage ends. 8. Plan for retirement. Before you retire, find out what health benefits, if any, extend to you and your spouse during your retirement years. Consult with your employer’s human resources office, your union, the plan administrator, and check your SPD. Make sure there is no conflicting information among these sources about the benefits you will receive or the circumstances under which they can change or be eliminated. With this information in hand, you can make other important choices, like finding out if you are eligible for Medicare and Medigap insurance coverage. 9. Know how to file an appeal if your health benefits claim is denied. Understand how your plan handles grievances and where to make appeals of the plan’s decisions. Keep records and copies of correspondence. Check your health benefits package and your SPD to determine who is responsible for handling problems with benefit claims. Contact PWBA for customer service assistance if you are unable to obtain a response to your complaint. 10. You can take steps to improve the quality of the healthcare and the health benefits you receive. Look for and use things like Quality Reports and Accreditation Reports whenever you can. Quality reports may contain consumer ratings -- how satisfied consumers are with the doctors in their plan, for instance-- and clinical performance measures -- how well a healthcare organization prevents and treats illness. Accreditation reports provide information on how accredited organizations meet national standards, and often include clinical performance measures. Look for these quality measures whenever possible. Consult “Your Guide to Choosing Quality Health Care” on the Internet at www.ahcpr.gov/consumer.

Your Rights and Insurance 237

Medicare and Medicaid Illness strikes both rich and poor families. For low-income families, Medicaid is available to defer the costs of treatment. The Health Care Financing Administration (HCFA) administers Medicare, the nation’s largest health insurance program, which covers 39 million Americans. In the following pages, you will learn the basics about Medicare insurance as well as useful contact information on how to find more in-depth information about Medicaid.56 Who is Eligible for Medicare? Generally, you are eligible for Medicare if you or your spouse worked for at least 10 years in Medicare-covered employment and you are 65 years old and a citizen or permanent resident of the United States. You might also qualify for coverage if you are under age 65 but have a disability or EndStage Renal disease (permanent kidney failure requiring dialysis or transplant). Here are some simple guidelines: You can get Part A at age 65 without having to pay premiums if: ·

You are already receiving retirement benefits from Social Security or the Railroad Retirement Board.

·

You are eligible to receive Social Security or Railroad benefits but have not yet filed for them.

·

You or your spouse had Medicare-covered government employment.

If you are under 65, you can get Part A without having to pay premiums if: ·

You have received Social Security or Railroad Retirement Board disability benefit for 24 months.

·

You are a kidney dialysis or kidney transplant patient.

Medicare has two parts: ·

Part A (Hospital Insurance). Most people do not have to pay for Part A.

·

Part B (Medical Insurance). Most people pay monthly for Part B.

This section has been adapted from the Official U.S. Site for Medicare Information: http://www.medicare.gov/Basics/Overview.asp.

56

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Part A (Hospital Insurance) Helps Pay For: Inpatient hospital care, care in critical access hospitals (small facilities that give limited outpatient and inpatient services to people in rural areas) and skilled nursing facilities, hospice care, and some home healthcare. Cost: Most people get Part A automatically when they turn age 65. You do not have to pay a monthly payment called a premium for Part A because you or a spouse paid Medicare taxes while you were working. If you (or your spouse) did not pay Medicare taxes while you were working and you are age 65 or older, you still may be able to buy Part A. If you are not sure you have Part A, look on your red, white, and blue Medicare card. It will show “Hospital Part A” on the lower left corner of the card. You can also call the Social Security Administration toll free at 1-800-772-1213 or call your local Social Security office for more information about buying Part A. If you get benefits from the Railroad Retirement Board, call your local RRB office or 1-800-808-0772. For more information, call your Fiscal Intermediary about Part A bills and services. The phone number for the Fiscal Intermediary office in your area can be obtained from the following Web site: http://www.medicare.gov/Contacts/home.asp. Part B (Medical Insurance) Helps Pay For: Doctors, services, outpatient hospital care, and some other medical services that Part A does not cover, such as the services of physical and occupational therapists, and some home healthcare. Part B helps pay for covered services and supplies when they are medically necessary. Cost: As of 2001, you pay the Medicare Part B premium of $50.00 per month. In some cases this amount may be higher if you did not choose Part B when you first became eligible at age 65. The cost of Part B may go up 10% for each 12-month period that you were eligible for Part B but declined coverage, except in special cases. You will have to pay the extra 10% cost for the rest of your life. Enrolling in Part B is your choice. You can sign up for Part B anytime during a 7-month period that begins 3 months before you turn 65. Visit your local Social Security office, or call the Social Security Administration at 1-800-7721213 to sign up. If you choose to enroll in Part B, the premium is usually taken out of your monthly Social Security, Railroad Retirement, or Civil Service Retirement payment. If you do not receive any of the above

Your Rights and Insurance 239

payments, Medicare sends you a bill for your part B premium every 3 months. You should receive your Medicare premium bill in the mail by the 10th of the month. If you do not, call the Social Security Administration at 1800-772-1213, or your local Social Security office. If you get benefits from the Railroad Retirement Board, call your local RRB office or 1-800-808-0772. For more information, call your Medicare carrier about bills and services. The phone number for the Medicare carrier in your area can be found at the following Web site: http://www.medicare.gov/Contacts/home.asp. You may have choices in how you get your healthcare including the Original Medicare Plan, Medicare Managed Care Plans (like HMOs), and Medicare Private Fee-for-Service Plans. Medicaid Medicaid is a joint federal and state program that helps pay medical costs for some people with low incomes and limited resources. Medicaid programs vary from state to state. People on Medicaid may also get coverage for nursing home care and outpatient prescription drugs which are not covered by Medicare. You can find more information about Medicaid on the HCFA.gov Web site at http://www.hcfa.gov/medicaid/medicaid.htm. States also have programs that pay some or all of Medicare’s premiums and may also pay Medicare deductibles and coinsurance for certain people who have Medicare and a low income. To qualify, you must have: ·

Part A (Hospital Insurance),

·

Assets, such as bank accounts, stocks, and bonds that are not more than $4,000 for a single person, or $6,000 for a couple, and

·

A monthly income that is below certain limits.

For more information on these programs, look at the Medicare Savings Programs brochure, http://www.medicare.gov/Library/PDFNavigation/PDFInterim.asp?Langua ge=English&Type=Pub&PubID=10126. There are also Prescription Drug Assistance Programs available. Find information on these programs which offer discounts or free medications to individuals in need at http://www.medicare.gov/Prescription/Home.asp.

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NORD’s Medication Assistance Programs Finally, the National Organization for Rare Disorders, Inc. (NORD) administers medication programs sponsored by humanitarian-minded pharmaceutical and biotechnology companies to help uninsured or underinsured individuals secure life-saving or life-sustaining drugs.57 NORD programs ensure that certain vital drugs are available “to those individuals whose income is too high to qualify for Medicaid but too low to pay for their prescribed medications.” The program has standards for fairness, equity, and unbiased eligibility. It currently covers some 14 programs for nine pharmaceutical companies. NORD also offers early access programs for investigational new drugs (IND) under the approved “Treatment INDs” programs of the Food and Drug Administration (FDA). In these programs, a limited number of individuals can receive investigational drugs that have yet to be approved by the FDA. These programs are generally designed for rare treatments. For more information, visit www.rarediseases.org.

Additional Resources In addition to the references already listed in this chapter, you may need more information on health insurance, hospitals, or the healthcare system in general. The NIH has set up an excellent guidance Web site that addresses these and other issues. Topics include:58 ·

Health Insurance: http://www.nlm.nih.gov/medlineplus/healthinsurance.html

·

Health Statistics: http://www.nlm.nih.gov/medlineplus/healthstatistics.html

·

HMO and Managed Care: http://www.nlm.nih.gov/medlineplus/managedcare.html

·

Hospice Care: http://www.nlm.nih.gov/medlineplus/hospicecare.html

·

Medicaid: http://www.nlm.nih.gov/medlineplus/medicaid.html

·

Medicare: http://www.nlm.nih.gov/medlineplus/medicare.html

·

Nursing Homes and Long-term Care: http://www.nlm.nih.gov/medlineplus/nursinghomes.html

Adapted from NORD: http://www.rarediseases.org/cgibin/nord/progserv#patient?id=rPIzL9oD&mv_pc=30. 58 You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html. 57

Your Rights and Insurance 241

·

Patient’s Rights, Confidentiality, Informed Consent, Ombudsman Programs, Privacy and Patient Issues: http://www.nlm.nih.gov/medlineplus/patientissues.html

·

Veteran’s Health, Persian Gulf War, Gulf War Syndrome, Agent Orange: http://www.nlm.nih.gov/medlineplus/veteranshealth.html

Vocabulary Builder Malaise: A vague feeling of bodily discomfort. [EU] Palpation: Application of fingers with light pressure to the surface of the body to determine consistence of parts beneath in physical diagnosis; includes palpation for determining the outlines of organs. [NIH]

Online Glossaries 243

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries and glossaries. The National Library of Medicine has compiled the following list of online dictionaries: ·

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

·

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

·

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

·

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

·

On-line Medical Dictionary (CancerWEB): http://www.graylab.ac.uk/omd/

·

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

·

Terms and Definitions (Office of Rare Diseases): http://rarediseases.info.nih.gov/ord/glossary_a-e.html

Beyond these, MEDLINEplus contains a very user-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia Web site address is 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). Topics of interest can be researched by using keywords before continuing elsewhere, as these basic definitions and concepts will be useful in more advanced areas of research. You may choose to print various pages specifically relating to transplantation and keep them on file. The NIH, in particular, suggests that patients undergoing transplantation visit the following Web sites in the ADAM Medical Encyclopedia: ·

Basic Guidelines for Transplantation

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Transplant rejection Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000815.htm ·

Signs & Symptoms for Transplantation Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Malaise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003089.htm

·

Diagnostics and Tests for Transplantation Abdominal MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003796.htm Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Fibrin degradation products Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003655.htm Histocompatibility antigens Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003550.htm Myocardial biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003873.htm

Online Glossaries 245

Renal biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003907.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm ·

Nutrition for Transplantation Proteins Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002467.htm

·

Background Topics for Transplantation Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Antibodies Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002223.htm Antigen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002224.htm Immune response Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000821.htm Palpation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002284.htm Toxins Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002331.htm

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Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries and glossaries: ·

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

·

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

·

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

·

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

Glossary 247

TRANSPLANTATION GLOSSARY The following is a complete glossary of terms used in this sourcebook. The definitions are derived from official public sources including the National Institutes of Health [NIH] and the European Union [EU]. After this glossary, we list a number of additional hardbound and electronic glossaries and dictionaries that you may wish to consult. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abscess: A localized collection of pus caused by suppuration buried in tissues, organs, or confined spaces. [EU] Accommodation: distances. [EU]

Adjustment, especially that of the eye for various

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] 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] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Aerobic: 1. having molecular oxygen present. 2. growing, living, or occurring in the presence of molecular oxygen. 3. requiring oxygen for respiration. [EU] Agammaglobulinemia: An immunologic deficiency state characterized by an extremely low level of generally all classes of gamma-globulin in the blood. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone,

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restoring some of the bone loss as a result of osteoporosis. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alopecia: Baldness; absence of the hair from skin areas where it normally is present. [EU] Alternaria: A mitosporic Loculoascomycetes fungal genus including several plant pathogens and at least one species which produces a highly phytotoxic antibiotic. Its teleomorph is Lewia. [NIH] Amphotericin B: Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela. [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] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH]

Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. The chief signs of arterial aneurysm are the formation of a pulsating tumour, and often a bruit (aneurysmal bruit) heard over the swelling. Sometimes there are symptoms from pressure on contiguous parts. [EU]

Anorectal: Pertaining to the anus and rectum or to the junction region between the two. [EU] Anorexia: Lack or loss of the appetite for food. [EU] Antibiotic: A chemical substance produced by a microorganism which has the capacity, in dilute solutions, to inhibit the growth of or to kill other microorganisms. Antibiotics that are sufficiently nontoxic to the host are used as chemotherapeutic agents in the treatment of infectious diseases of man, animals and plants. [EU] Antibody: An immunoglobulin molecule that has a specific amino acid sequence by virtue of which it interacts only with the antigen that induced its synthesis in cells of the lymphoid series (especially plasma cells), or with antigen closely related to it. Antibodies are classified according to their ode of action as agglutinins, bacteriolysins, haemolysins, opsonins, precipitins, etc. [EU] Antidiabetic: An agent that prevents or alleviates diabetes. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of

Glossary 249

that response, that is, with specific antibody or specifically sensitized Tlymphocytes, 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] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antioxidant: One of many widely used synthetic or natural substances added to a product to prevent or delay its deterioration by action of oxygen in the air. Rubber, paints, vegetable oils, and prepared foods commonly contain antioxidants. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anxiety: The unpleasant emotional state consisting of psychophysiological responses to anticipation of unreal or imagined danger, ostensibly resulting from unrecognized intrapsychic conflict. Physiological concomitants include increased heart rate, altered respiration rate, sweating, trembling, weakness, and fatigue; psychological concomitants include feelings of impending danger, powerlessness, apprehension, and tension. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Arginine: An essential amino acid that is physiologically active in the Lform. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arteritis: Inflammation of an artery. [NIH] Aspergillosis: Infections with fungi of the genus aspergillus. [NIH] Aspiration: The act of inhaling. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Atrial: Pertaining to an atrium. [EU] Atrophy: A wasting away; a diminution in the size of a cell, tissue, organ, or part. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autoimmunity:

Process whereby the immune system reacts against the

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body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Beclomethasone: An anti-inflammatory, synthetic glucocorticoid. It is used topically as an anti-inflammatory agent and in aerosol form for the treatment of asthma. [NIH] Benign: Not malignant; not recurrent; favourable for recovery. [EU] Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [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] Biliary: Pertaining to the bile, to the bile ducts, or to the gallbladder. [EU] 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] Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiolitis: Inflammation of the bronchioles. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, poly- and heterosaccharides. [EU] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carcinoma: A malignant new growth made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. [EU]

Glossary 251

Cardiac: Pertaining to the heart. [EU] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiopulmonary: Pertaining to the heart and lungs. [EU] Cardiovascular: Pertaining to the heart and blood vessels. [EU] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catheter: A tubular, flexible, surgical instrument for withdrawing fluids from (or introducing fluids into) a cavity of the body, especially one for introduction into the bladder through the urethra for the withdraw of urine. [EU]

Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Chemotherapy: The treatment of disease by means of chemicals that have a specific toxic effect upon the disease - producing microorganisms or that selectively destroy cancerous tissue. [EU] Chimera: An individual that contains cell populations derived from different zygotes. [NIH] Cholangitis: Inflammation of a bile duct. [EU] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholinergic: Resembling acetylcholine in pharmacological stimulated by or releasing acetylcholine or a related compound. [EU]

action;

Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chondrogenesis: The formation of cartilage. This process is directed by chondrocytes which continually divide and lay down matrix during development. It is sometimes a precursor to osteogenesis. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Cirrhosis: Liver disease characterized pathologically by loss of the normal microscopic lobular architecture, with fibrosis and nodular regeneration. The term is sometimes used to refer to chronic interstitial inflammation of any organ. [EU]

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Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Colitis: Inflammation of the colon. [EU] Collagen: The protein substance of the white fibres (collagenous fibres) of skin, tendon, bone, cartilage, and all other connective tissue; composed of molecules of tropocollagen (q.v.), it is converted into gelatin by boiling. collagenous pertaining to collagen; forming or producing collagen. [EU] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Cornea: The transparent structure forming the anterior part of the fibrous tunic of the eye. It consists of five layers : (1) the anterior corneal epithelium, continuous with that of the conjunctiva, (2) the anterior limiting layer (Bowman's membrane), (3) the substantia propria, or stroma, (4) the posterior limiting layer (Descemet's membrane), and (5) the endothelium of the anterior chamber, called also keratoderma. [EU] Cryopreservation: Preservation of cells, tissues, organs, or embryos by freezing. In histological preparations, cryopreservation or cryofixation is used to maintain the existing form, structure, and chemical composition of all the constituent elements of the specimens. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyanosis: A bluish discoloration, applied especially to such discoloration of skin and mucous membranes due to excessive concentration of reduced haemoglobin in the blood. [EU] 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] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH]

Glossary 253

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] Cytotoxic: Pertaining to or exhibiting cytotoxicity. [EU] Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [NIH] Dendritic: 1. branched like a tree. 2. pertaining to or possessing dendrites. [EU]

Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dietetics: The study and regulation of the diet. [NIH] Dilatation: The condition, as of an orifice or tubular structure, of being dilated or stretched beyond the normal dimensions. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dysplasia: Abnormality of development; in pathology, alteration in size, shape, and organization of adult cells. [EU] Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as SPECTRIN and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Embalming: Process of preserving a dead body to protect it from decay. [NIH]

Embryo: In animals, those derivatives of the fertilized ovum that eventually become the offspring, during their period of most rapid development, i.e.,

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after the long axis appears until all major structures are represented. In man, the developing organism is an embryo from about two weeks after fertilization to the end of seventh or eighth week. [EU] Encephalitis: Inflammation of the brain. [EU] Endothelium: The layer of epithelial cells that lines the cavities of the heart and of the blood and lymph vessels, and the serous cavities of the body, originating from the mesoderm. [EU] Enterocytozoon: A genus of parasitic protozoa in the family Enterocytozoonidae, which infects humans. Enterocytozoon bieneusi has been found in the intestines of patients with AIDS. [NIH] Enzyme: A protein molecule that catalyses chemical reactions of other substances without itself being destroyed or altered upon completion of the reactions. Enzymes are classified according to the recommendations of the Nomenclature Committee of the International Union of Biochemistry. Each enzyme is assigned a recommended name and an Enzyme Commission (EC) number. They are divided into six main groups; oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epithelium: The covering of internal and external surfaces of the body, including the lining of vessels and other small cavities. It consists of cells joined by small amounts of cementing substances. Epithelium is classified into types on the basis of the number of layers deep and the shape of the superficial cells. [EU] Epitopes: Sites on an antigen that interact with specific antibodies. [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] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [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] Exfoliation: A falling off in scales or layers. [EU] Exocrine: 1. secreting outwardly, via a duct;. [EU]

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Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: The formation of fibrous tissue; fibroid or fibrous degeneration [EU] Fistula: An abnormal passage or communication, usually between two internal organs, or leading from an internal organ to the surface of the body; frequently designated according to the organs or parts with which it communicates, as anovaginal, brochocutaneous, hepatopleural, pulmonoperitoneal, rectovaginal, urethrovaginal, and the like. Such passages are frequently created experimentally for the purpose of obtaining body secretions for physiologic study. [EU] Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [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] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] GABA: The most common inhibitory neurotransmitter in the central nervous system. [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] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis.

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They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glomerulonephritis: A variety of nephritis characterized by inflammation of the capillary loops in the glomeruli of the kidney. It occurs in acute, subacute, and chronic forms and may be secondary to haemolytic streptococcal infection. Evidence also supports possible immune or autoimmune mechanisms. [EU] Glucose: D-glucose, a monosaccharide (hexose), C6H12O6, also known as dextrose (q.v.), found in certain foodstuffs, especially fruits, and in the normal blood of all animals. It is the end product of carbohydrate metabolism and is the chief source of energy for living organisms, its utilization being controlled by insulin. Excess glucose is converted to glycogen and stored in the liver and muscles for use as needed and, beyond that, is converted to fat and stored as adipose tissue. Glucose appears in the urine in diabetes mellitus. [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] Haemopoietic: Haematopoietic; pertaining to or effecting the formation of blood cells. [EU] Helicobacter: A genus of gram-negative, spiral-shaped bacteria that is pathogenic and has been isolated from the intestinal tract of mammals, including humans. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH]

Hepatic: Pertaining to the liver. [EU] Hepatitis: Inflammation of the liver. [EU] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH]

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Heredity: 1. the genetic transmission of a particular quality or trait from parent to offspring. 2. the genetic constitution of an individual. [EU] Hirsutism: Abnormal hairiness, especially an adult male pattern of hair distribution in women. [EU] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [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] Homozygote: identical. [NIH]

An individual in which both alleles at a given locus are

Hormones: Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various endocrine glands and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects. [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] 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] Hydration: The condition of being combined with water. [EU] Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [NIH] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH]

Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperplasia: The abnormal multiplication or increase in the number of normal cells in normal arrangement in a tissue. [EU] Hypersensitivity: A state of altered reactivity in which the body reacts with an exaggerated immune response to a foreign substance. Hypersensitivity reactions are classified as immediate or delayed, types I and IV, respectively, in the Gell and Coombs classification (q.v.) of immune responses. [EU]

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Hypertension: Persistently high arterial blood pressure. Various criteria for its threshold have been suggested, ranging from 140 mm. Hg systolic and 90 mm. Hg diastolic to as high as 200 mm. Hg systolic and 110 mm. Hg diastolic. Hypertension may have no known cause (essential or idiopathic h.) or be associated with other primary diseases (secondary h.). [EU] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypotension: Abnormally low blood pressure; seen in shock but not necessarily indicative of it. [EU] Hypoventilation: A state in which there is a reduced amount of air entering the pulmonary alveoli. [EU] 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] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Idarubicin: An orally administered anthracycline antibiotic. The compound has shown activity against breast cancer, lymphomas and leukemias, together with potential for reduced cardiac toxicity. [NIH] Iloprost: An eicosanoid, derived from the cyclooxygenase pathway of arachidonic acid metabolism. It is a stable and synthetic analog of epoprostenol, but with a longer half-life than the parent compound. Its actions are similar to prostacyclin. Iloprost produces vasodilation and inhibits platelet aggregation. [NIH] Immunity: The condition of being immune; the protection against infectious disease conferred either by the immune response generated by immunization or previous infection or by other nonimmunologic factors (innate i.). [EU] Immunization: The induction of immunity. [EU] 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] Immunocompetence: The ability of lymphoid cells to mount a humoral or cellular immune response when challenged by antigen. [NIH] Immunogenetics: A branch of genetics which deals with the genetic basis of the immune response. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH]

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Immunosuppressant: An agent capable of suppressing immune responses. [EU]

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] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [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: 1. cleft, cut, gash. 2. an act or action of incising. [EU] 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] Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] 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] Infuse: To pour (a liquid) into something. [EU] Infusion: The therapeutic introduction of a fluid other than blood, as saline solution, solution, into a vein. [EU] Innervation: 1. the distribution or supply of nerves to a part. 2. the supply of nervous energy or of nerve stimulus sent to a part. [EU] 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

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of protein and lipid metabolism. Insulin is used as a drug to control insulindependent diabetes mellitus. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intravenous: Within a vein or veins. [EU] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]

Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH]

Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Kinetic: Pertaining to or producing motion. [EU] Labetalol: Blocker of both alpha- and beta-adrenergic receptors that is used as an antihypertensive. [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] Legionella: Gram-negative aerobic rods, isolated from surface water, mud, or thermally polluted lakes or streams. It is pathogenic for man and it has no known soil or animal sources. [NIH] Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU]

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Lipid: Any of a heterogeneous group of flats and fatlike substances characterized by being water-insoluble and being extractable by nonpolar (or fat) solvents such as alcohol, ether, chloroform, benzene, etc. All contain as a major constituent aliphatic hydrocarbons. The lipids, which are easily stored in the body, serve as a source of fuel, are an important constituent of cell structure, and serve other biological functions. Lipids may be considered to include fatty acids, neutral fats, waxes, and steroids. Compound lipids comprise the glycolipids, lipoproteins, and phospholipids. [EU] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]

Lymphocytic: Pertaining to, characterized by, or of the nature of lymphocytes. [EU] Lymphoma: Any neoplastic disorder of the lymphoid tissue, the term lymphoma often is used alone to denote malignant lymphoma. [EU] Lymphopenia: Reduction in the number of lymphocytes. [NIH] Malaise: A vague feeling of bodily discomfort. [EU] Malformation: A morphologic defect resulting from an intrinsically abnormal developmental process. [EU] Malignant: Tending to become progressively worse and to result in death. Having the properties of anaplasia, invasion, and metastasis; said of tumours. [EU] Mannitol: A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. [NIH] Mannosidosis: Inborn error of metabolism marked by a defect in alphamannosidase activity that results in lysosomal accumulation of mannose-rich substrates. Virtually all patients have psychomotor retardation, facial

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coarsening, and some degree of dysostosis multiplex. It is thought to be an autosomal recessive disorder. [NIH] Mediastinitis: Inflammation of the mediastinum, the area between the pleural sacs. [NIH] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medicament: A medicinal substance or agent. [EU] 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 tumour arising from the melanocytic system of the skin and other organs. When used alone the term refers to malignant melanoma. [EU] Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer - medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Membrane: A thin layer of tissue which covers a surface, lines a cavity or divides a space or organ. [EU] Metabolite: process. [EU]

Any substance produced by metabolism or by a metabolic

Metastasis: 1. the transfer of disease from one organ or part to another not directly connected with it. It may be due either to the transfer of pathogenic microorganisms (e.g., tubercle bacilli) or to transfer of cells, as in malignant tumours. The capacity to metastasize is a characteristic of all malignant tumours. 2. Pl. metastases. A growth of pathogenic microorganisms or of abnormal cells distant from the site primarily involved by the morbid process. [EU] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae,

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archaea, and viruses. [NIH] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Monotherapy: A therapy which uses only one drug. [EU] Motility: The ability to move spontaneously. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Myeloma: A tumour composed of cells of the type normally found in the bone marrow. [EU] Myopathy: Any disease of a muscle. [EU] Nausea: An unpleasant sensation, vaguely referred to the epigastrium and abdomen, and often culminating in vomiting. [EU] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Neural: 1. pertaining to a nerve or to the nerves. 2. situated in the region of the spinal axis, as the neutral arch. [EU] Neurologic: Pertaining to neurology or to the nervous system. [EU] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A general term denoting functional disturbances and/or pathological changes in the peripheral nervous system. The etiology may be known e.g. arsenical n., diabetic n., ischemic n., traumatic n.) or unknown. Encephalopathy and myelopathy are corresponding terms relating to involvement of the brain and spinal cord, respectively. The term is also used to designate noninflammatory lesions in the peripheral nervous system, in

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contrast to inflammatory lesions (neuritis). [EU] Neutropenia: Leukopenia in which the decrease in white blood cells is chiefly in neutrophils. [EU] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] 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] Nocturia: Excessive urination at night. [EU] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Ocular: 1. of, pertaining to, or affecting the eye. 2. eyepiece. [EU] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [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] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU] Oryzias: A genus of cyprinodontid fish that is an egg layer as opposed to others of the same order which are livebearers. It is used extensively in testing carcinogens. [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] Osteodystrophy: Defective bone formation. [EU] Osteonecrosis: Death of a bone or part of a bone, either atraumatic or posttraumatic. [NIH] Osteopetrosis: Excessive formation of dense trabecular bone leading to pathological fractures, osteitis, splenomegaly with infarct, anemia, and extramedullary hemopoiesis. [NIH] Osteoporosis: Reduction in the amount of bone mass, leading to fractures after minimal trauma. [EU] Ovalbumin: An albumin obtained from the white of eggs. It is a member of

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the serpin superfamily. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: 1. to administer an excessive dose. 2. an excessive dose. [EU] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins C-MOS. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palpation: Application of fingers with light pressure to the surface of the body to determine consistence of parts beneath in physical diagnosis; includes palpation for determining the outlines of organs. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the islets of langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Papillomavirus: A genus of papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH]

Parasitic: Pertaining to, of the nature of, or caused by a parasite. [EU] Parathyroid: 1. situated beside the thyroid gland. 2. one of the parathyroid glands. 3. a sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Pathogen: Any disease-producing microorganism. [EU] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Perioperative: Pertaining to the period extending from the time of hospitalization for surgery to the time of discharge. [EU] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of

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actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacokinetics: The action of drugs in the body over a period of time, including the processes of absorption, distribution, localization in tissues, biotransformation, and excretion. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Photoreceptors: Cells specialized to detect and transduce light. [NIH] Plantago: Three different species of Plantago or plantain, P. psyllium, P. ovata and P. indica. The seeds swell in water and are used as laxatives. [NIH] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Pneumonia: Inflammation of the lungs with consolidation. [EU] Polyomavirus: A genus of the family papovaviridae consisting of potentially oncogenic viruses normally present in the host as a latent infection. The virus is oncogenic in hosts different from the species of origin. [NIH]

Porphyria: A pathological state in man and some lower animals that is often due to genetic factors, is characterized by abnormalities of porphyrin metabolism, and results in the excretion of large quantities of porphyrins in the urine and in extreme sensitivity to light. [EU] 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] Postoperative: Occurring after a surgical operation. [EU] 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] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisone:

A synthetic anti-inflammatory glucocorticoid derived from

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cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH]

Preoperative: Preceding an operation. [EU] Prophylaxis: The prevention of disease; preventive treatment. [EU] 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] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]

Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Pulmonary: Pertaining to the lungs. [EU] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The treatment of disease by ionizing radiation. [EU] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: 1. a molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., cell-surface receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and cytoplasmic receptors for steroid hormones. 2. a sensory nerve terminal that responds to stimuli of various kinds. [EU] Recombinant: 1. a cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reflux: A backward or return flow. [EU] Refractory: Not readily yielding to treatment. [EU]

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Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU]

Remission: A diminution or abatement of the symptoms of a disease; also the period during which such diminution occurs. [EU] 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] Resection: Excision of a portion or all of an organ or other structure. [EU] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU]

Retinopathy: 1. retinitis (= inflammation of the retina). 2. retinosis (= degenerative, noninflammatory condition of the retina). [EU] Rheumatoid: Resembling rheumatism. [EU] 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] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcoma: A tumour made up of a substance like the embryonic connective tissue; tissue composed of closely packed cells embedded in a fibrillar or homogeneous substance. Sarcomas are often highly malignant. [EU] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior five-sixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] 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

Glossary 269

substance of the blood to the elaboration of a new chemical substance. 2. any substance produced by secretion. [EU] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] 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] Serum: The clear portion of any body fluid; the clear fluid moistening serous membranes. 2. blood serum; the clear liquid that separates from blood on clotting. 3. immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU] 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] Somatic: 1. pertaining to or characteristic of the soma or body. 2. pertaining to the body wall in contrast to the viscera. [EU] Somatomedins: Insulin-like polypeptides made by the liver and some fibroblasts and released into the blood when stimulated by somatotropin. They cause sulfate incorporation into collagen, RNA, and DNA synthesis, which are prerequisites to cell division and growth of the organism. [NIH] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] 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] 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] Sterility: 1. the inability to produce offspring, i.e., the inability to conceive

270 Transplantation

(female s.) or to induce conception (male s.). 2. the state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU] Symptomatic: 1. pertaining to or of the nature of a symptom. 2. indicative (of a particular disease or disorder). 3. exhibiting the symptoms of a particular disease but having a different cause. 4. directed at the allying of symptoms, as symptomatic treatment. [EU] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU]

Systemic: Pertaining to or affecting the body as a whole. [EU] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Thermoregulation: Heat regulation. [EU] Thoracic: Pertaining to or affecting the chest. [EU] Thrombocytosis: Increased numbers of platelets in the peripheral blood. [EU] Thrombolytic: 1. dissolving or splitting up a thrombus. 2. a thrombolytic agent. [EU] Thrombosis: The formation, development, or presence of a thrombus. [EU] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tolerance: 1. the ability to endure unusually large doses of a drug or toxin.

Glossary 271

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]

Toxic: Pertaining to, due to, or of the nature of a poison or toxin; manifesting the symptoms of severe infection. [EU] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [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]

Transfusion: The introduction of whole blood or blood component directly into the blood stream. [EU] Trichoderma: A mitosporic fungal genus frequently found in soil and on wood. It is sometimes used for controlling pathogenic fungi. Its teleomorph is Hypocrea. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of mycobacterium. [NIH] Tumour: 1. swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. a new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Ulcer: A local defect, or excavation, of the surface of an organ or tissue; which is produced by the sloughing of inflammatory necrotic tissue. [EU] Urinary: Pertaining to the urine; containing or secreting urine. [EU] Urology: A surgical specialty concerned with the study, diagnosis, and treatment of diseases of the urinary tract in both sexes and the genital tract in the male. It includes the specialty of andrology which addresses both male genital diseases and male infertility. [NIH] Uterus: The hollow muscular organ in female mammals in which the fertilized ovum normally becomes embedded and in which the developing embryo and fetus is nourished. In the nongravid human, it is a pear-shaped structure; about 3 inches in length, consisting of a body, fundus, isthmus, and cervix. Its cavity opens into the vagina below, and into the uterine tube on either side at the cornu. It is supported by direct attachment to the vagina and by indirect attachment to various other nearby pelvic structures. Called also metra. [EU] Vaccination: The introduction of vaccine into the body for the purpose of inducing immunity. Coined originally to apply to the injection of smallpox vaccine, the term has come to mean any immunizing procedure in which

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vaccine is injected. [EU] Vaccine: A suspension of attenuated or killed microorganisms (bacteria, viruses, or rickettsiae), administered for the prevention, amelioration or treatment of infectious diseases. [EU] Vanadium: Vanadium. A metallic element with the atomic symbol V, atomic number 23, and atomic weight 50.94. It is used in the manufacture of vanadium steel. Prolonged exposure can lead to chronic intoxication caused by absorption usually via the lungs. [NIH] Varicella: Chicken pox. [EU] Vasculitis: Inflammation of a vessel, angiitis. [EU] Vegetative: 1. concerned with growth and with nutrition. 2. functioning involuntarily or unconsciously, as the vegetative nervous system. 3. resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. of, pertaining to, or characteristic of plants. [EU] Venous: Of or pertaining to the veins. [EU] Ventral: 1. pertaining to the belly or to any venter. 2. denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricular: Pertaining to a ventricle. [EU] Vertebral: Of or pertaining to a vertebra. [EU] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viremia: The presence of viruses in the blood. [NIH] Viruses: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] 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 substancespecific 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] Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes. [NIH]

Glossary 273

Xerostomia: Dryness of the mouth from salivary gland dysfunction, as in Sjögren's syndrome. [EU] Zebrafish: A species of North American fishes of the family Cyprinidae. They are used in embryological studies and to study the effects of certain chemicals on development. [NIH]

General Dictionaries and Glossaries While the above glossary is essentially complete, the dictionaries listed here cover virtually all aspects of medicine, from basic words and phrases to more advanced terms (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

Dictionary of Medical Acronymns & Abbreviations by Stanley Jablonski (Editor), Paperback, 4th edition (2001), Lippincott Williams & Wilkins Publishers, ISBN: 1560534605, http://www.amazon.com/exec/obidos/ASIN/1560534605/icongroupinterna

·

Dictionary of Medical Terms : For the Nonmedical Person (Dictionary of Medical Terms for the Nonmedical Person, Ed 4) by Mikel A. Rothenberg, M.D, et al, Paperback - 544 pages, 4th edition (2000), Barrons Educational Series, ISBN: 0764112015, http://www.amazon.com/exec/obidos/ASIN/0764112015/icongroupinterna

·

A Dictionary of the History of Medicine by A. Sebastian, CD-Rom edition (2001), CRC Press-Parthenon Publishers, ISBN: 185070368X, http://www.amazon.com/exec/obidos/ASIN/185070368X/icongroupinterna

·

Dorland’s Illustrated Medical Dictionary (Standard Version) by Dorland, et al, Hardcover - 2088 pages, 29th edition (2000), W B Saunders Co, ISBN: 0721662544, http://www.amazon.com/exec/obidos/ASIN/0721662544/icongroupinterna

·

Dorland’s Electronic Medical Dictionary by Dorland, et al, Software, 29th Book & CD-Rom edition (2000), Harcourt Health Sciences, ISBN: 0721694934, http://www.amazon.com/exec/obidos/ASIN/0721694934/icongroupinterna

·

Dorland’s Pocket Medical Dictionary (Dorland’s Pocket Medical Dictionary, 26th Ed) Hardcover - 912 pages, 26th edition (2001), W B Saunders Co, ISBN: 0721682812, http://www.amazon.com/exec/obidos/ASIN/0721682812/icongroupinterna /103-4193558-7304618

·

Melloni’s Illustrated Medical Dictionary (Melloni’s Illustrated Medical Dictionary, 4th Ed) by Melloni, Hardcover, 4th edition (2001), CRC Press-

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Parthenon Publishers, ISBN: 85070094X, http://www.amazon.com/exec/obidos/ASIN/85070094X/icongroupinterna ·

Stedman’s Electronic Medical Dictionary Version 5.0 (CD-ROM for Windows and Macintosh, Individual) by Stedmans, CD-ROM edition (2000), Lippincott Williams & Wilkins Publishers, ISBN: 0781726328, http://www.amazon.com/exec/obidos/ASIN/0781726328/icongroupinterna

·

Stedman’s Medical Dictionary by Thomas Lathrop Stedman, Hardcover 2098 pages, 27th edition (2000), Lippincott, Williams & Wilkins, ISBN: 068340007X, http://www.amazon.com/exec/obidos/ASIN/068340007X/icongroupinterna

·

Tabers Cyclopedic Medical Dictionary (Thumb Index) by Donald Venes (Editor), et al, Hardcover - 2439 pages, 19th edition (2001), F A Davis Co, ISBN: 0803606540, http://www.amazon.com/exec/obidos/ASIN/0803606540/icongroupinterna

Index 275

INDEX A Abdomen .............................118, 119, 263 Abdominal................39, 99, 103, 136, 265 Acetylcysteine......................................101 Adenosine......................................84, 247 Adjuvant.................................................74 Aerobic ..........................89, 129, 136, 260 Alendronate ...........................................76 Alkaline ................................................103 Alopecia.........................................65, 252 Anatomical.....................................90, 265 Anemia ........11, 18, 66, 67, 161, 264, 270 Anesthesia.............................................32 Aneurysm ....................................138, 248 Anorexia ........................................99, 103 Antibiotic ..84, 88, 119, 181, 248, 258, 269 Antibody .......37, 77, 85, 89, 98, 104, 111, 117, 118, 133, 249, 252, 257, 258, 262, 269 Antifungal.......67, 181, 248, 255, 260, 269 Antigen .......64, 77, 79, 86, 89, 103, 104, 111, 117, 118, 132, 248, 254, 257, 258, 262, 269 Antioxidant...........................................188 Antiviral ....88, 91, 116, 181, 247, 259, 268 Anxiety...................................................41 Arterial ...........38, 132, 138, 248, 249, 258 Aspergillosis ................................181, 260 Assay...........................................118, 258 B Bacteria ......37, 39, 87, 93, 119, 210, 218, 249, 256, 262, 269, 272 Beclomethasone..................................102 Bile....37, 67, 85, 132, 218, 250, 251, 256, 260, 270 Biliary...........................139, 218, 250, 256 Biochemical ...........................76, 181, 265 Biopsy............................72, 100, 244, 245 C Calculi ..........................................166, 256 Capsules..............................103, 122, 213 Carbohydrate.........................38, 212, 256 Cardiac ......67, 76, 88, 119, 258, 268, 270 Cardiology .............................................43 Cardiovascular.....................................124 Cataract .........................................64, 251 Chemotherapy .....................................105 Cholesterol .......29, 67, 89, 166, 210, 212, 257, 261, 270 Chondrocytes ........................96, 107, 108 Choroid ................................................107

Chronic... 33, 37, 72, 75, 89, 97, 100, 110, 111, 129, 139, 143, 219, 231, 251, 256, 260, 272 Cirrhosis................................................ 72 Cisplatin ...................................... 218, 252 Collagen ....... 87, 97, 108, 116, 219, 252, 255, 269 Cornea .................................. 44, 119, 268 Cryopreservation .......... 85, 100, 101, 252 Curative................................. 11, 218, 264 Cyclophosphamide ....................... 83, 104 Cytokines .............................. 67, 105, 269 Cytomegalovirus ........................... 87, 255 Cytotoxic ....................................... 78, 105 D Dendritic................................ 66, 104, 262 Dilatation ..................................... 138, 248 Distal ............................. 97, 108, 119, 267 Dystrophin........................... 109, 117, 253 Dystrophy...................... 19, 109, 117, 253 E Electrolyte ................................... 140, 266 Embalming .......................................... 123 Embryo.............. 65, 86, 92, 254, 259, 271 Endothelium .................................. 37, 252 Enzyme ......................................... 86, 254 Epidermal............................................ 110 Epithelium ..... 37, 90, 104, 106, 215, 252, 265 Epitopes .............................................. 103 Erythropoietin...................................... 161 Excitation ............................ 111, 117, 254 Exfoliation ........................................... 103 Exocrine ........................................ 39, 265 Exogenous .................................... 87, 255 Extracellular .......................... 87, 109, 255 F Fathers.................................................. 32 Fatigue .......................................... 52, 249 Fibroblasts .......................... 109, 219, 269 Fibrosis ......................... 37, 208, 251, 268 Fistula ........................................... 38, 255 Fluorescence ................................ 87, 255 Fluorouracil ......................................... 105 G Gastrointestinal ............................. 38, 255 Genotype .............................. 66, 115, 266 Ginseng............................................... 203 Glucose................. 38, 104, 112, 256, 259 H Hepatic.................................................. 99

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Hepatitis...........................................32, 72 Hirsutism..............................................113 Histocompatibility...........99, 104, 123, 162 Homologous ................115, 133, 269, 270 Hormones ...67, 77, 85, 91, 154, 252, 265, 267, 270 Humoral ...............................104, 118, 258 Hydroxyurea ..........................................33 Hyperbaric .....................................88, 257 Hyperplasia..........................................113 Hypersensitivity ...........................133, 269 Hypertension .................15, 104, 112, 113 Hypoxia..........................................88, 258 I Immunity ..................39, 88, 151, 258, 271 Immunization ....52, 88, 92, 132, 258, 259, 269 Immunoassay ......................................111 Immunosuppressant ...32, 33, 46, 67, 113, 117, 118, 151, 255, 262, 269 Incision ..........................88, 106, 107, 260 Induction ......74, 77, 88, 98, 105, 113, 258 Infertility .........................................53, 271 Infiltration .......................................97, 108 Inflammation ...37, 53, 102, 139, 251, 256, 268 Infusion ..........................................74, 105 Insulin ...... 18, 38, 78, 104, 110, 143, 256, 260 Interstitial .......................................37, 251 Intravenous..............................91, 98, 265 Ischemia ........................................91, 268 L Lethal .....................................................99 Lipid .................................38, 89, 260, 261 Lipoprotein.....................................89, 261 Lumbar ..................................................76 Lupus .....................................................15 Lymphoma.....................................65, 261 M Malignant ....... 64, 65, 66, 85, 92, 99, 152, 250, 255, 261, 262, 268 Mannitol ...............................................101 Mannosidosis.........................................75 Mediator...............................................111 Melanoma......................................66, 262 Membrane ......37, 89, 109, 116, 117, 119, 251, 252, 253, 263, 264 Metabolite ......................................76, 213 Metastasis .....................................65, 261 Microbiology ................................218, 262 Molecular .......1 7, 91, 101, 131, 156, 164, 247, 267 Monotherapy........................................103 Mucosa ......38, 89, 92, 103, 261, 263, 270 Myeloma ................................................99

Myopathy ............................................ 109 N Nausea................................................ 103 Neonatal.............................................. 107 Neoplastic ..................................... 65, 261 Neural ......... 110, 111, 117, 143, 211, 257 Neurologic............................... 65, 75, 256 Neurology...................................... 39, 263 Neuronal ............................................. 112 Neurons ................ 90, 112, 133, 263, 270 Niacin .................................................. 211 Nitrogen .................. 65, 66, 100, 252, 262 O Oocytes............................................... 114 Osmotic............................................... 101 Osteoporosis..................... 30, 64, 76, 247 Ovalbumin............................................. 78 Overdose ............................................ 211 P Palpation ..................................... 241, 265 Pancreas ....... 4, 18, 38, 39, 74, 123, 130, 142, 162, 259 Parasitic .......................... 86, 92, 254, 271 Parathyroid.................................... 90, 265 Pathogen............................................. 112 Pediatrics .............................................. 43 Pharmacokinetics ................................. 58 Phenotype..................................... 66, 266 Photoreceptors ................................... 106 Pneumonia............................................ 32 Posterior....... 37, 39, 116, 119, 251, 252, 265, 268 Postoperative .............................. 130, 136 Potassium ........................................... 212 Precursor ........................ 75, 85, 100, 251 Prednisone............................ 83, 103, 129 Progressive ........................... 92, 109, 271 Prophylaxis ......................................... 124 Proteins.... 37, 85, 88, 110, 117, 118, 210, 212, 249, 252, 253, 257, 264 Proximal ........................ 97, 108, 117, 253 Pulmonary............................... 32, 88, 258 Q Quiescent............................ 105, 208, 272 R Receptor ................. 37, 99, 104, 113, 249 Regeneration ........................ 37, 109, 251 Remission ..................................... 91, 267 Reperfusion........................... 91, 188, 268 Resorption............................................. 76 Resuscitation ...................................... 101 Riboflavin ............................................ 210 S Sclera.................................................. 107 Secretion............................... 67, 104, 269 Selenium ............................................. 212

Index 277

Serum ..............................76, 92, 114, 269 Sirolimus................................................58 Somatic........................................117, 257 Spasticity .....................................110, 111 Species .....84, 91, 92, 111, 114, 143, 208, 219, 248, 266, 269, 271, 273 Spices ....................................................30 Sterility...........................65, 139, 252, 259 Steroid ...........................91, 102, 113, 267 Stomach ................................38, 103, 255 Symptomatic..................................92, 270 Systemic .....15, 52, 92, 99, 208, 249, 268, 270 T Thermoregulation ................................210 Thrombolytic ..................................92, 270 Thrombosis............................................32 Thyroxine.............................................212 Tolerance....... 14, 15, 39, 74, 77, 98, 101, 127, 271

Toxic .... 12, 65, 66, 67, 88, 106, 211, 219, 251, 259, 262, 269, 271 Toxicity.................................... 75, 88, 258 Transfusion ........................................... 99 Tuberculosis.................................. 38, 261 Tumour.... 66, 91, 138, 248, 262, 263, 268 U Ulcer.................................................... 124 Urinary ............ 53, 85, 139, 250, 252, 271 V Vaccination ..................................... 18, 19 Vaccine ................... 39, 84, 150, 247, 271 Vanadium.................................... 219, 272 Vegetative ................................... 119, 272 Venous........................................ 132, 249 Vertebral ......................................... 74, 77 Viral..................................... 116, 150, 247 Viruses ..... 39, 91, 93, 132, 181, 218, 247, 249, 262, 263, 266, 268, 272

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