THE OFFICIAL PATIENT’S SOURCEBOOK
on
HEMOCHROMATOSIS
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 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 Hemochromatosis: 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: 0-597-83219-6 1. Hemochromatosis-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem 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:
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Dedication To the healthcare professionals dedicating their time and efforts to the study of hemochromatosis.
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 hemochromatosis. 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 hemochromatosis, Official Patient’s Sourcebooks are available for the following related topics: ·
The Official Patient's Sourcebook on Cystocele
·
The Official Patient's Sourcebook on Glomerular Disease
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The Official Patient's Sourcebook on Goodpasture Syndrome
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The Official Patient's Sourcebook on Hematuria
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The Official Patient's Sourcebook on Immune Thrombocytopenic Purpura
·
The Official Patient's Sourcebook on Impotence
·
The Official Patient's Sourcebook on Interstitial Cystitis
·
The Official Patient's Sourcebook on Kidney Failure
·
The Official Patient's Sourcebook on Kidney Stones
·
The Official Patient's Sourcebook on Lupus Nephritis
·
The Official Patient's Sourcebook on Nephrotic Syndrome
·
The Official Patient's Sourcebook on Peyronie
·
The Official Patient's Sourcebook on Polycystic Kidney Disease
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The Official Patient's Sourcebook on Prostate Enlargement
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The Official Patient's Sourcebook on Prostatitis
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The Official Patient's Sourcebook on Proteinuria
·
The Official Patient's Sourcebook on Pyelonephritis
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The Official Patient's Sourcebook on Renal Osteodystrophy
·
The Official Patient's Sourcebook on Renal Tubular Acidosis
·
The Official Patient's Sourcebook on Simple Kidney Cysts
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The Official Patient's Sourcebook on Urinary Incontinence
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The Official Patient's Sourcebook on Urinary Incontinence for Women
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The Official Patient's Sourcebook on Urinary Incontinence with Children
·
The Official Patient's Sourcebook on Urinary Tract Infection in Children
·
The Official Patient's Sourcebook on Urinary Tract Infections in Adults
·
The Official Patient's Sourcebook on Vasectomy
·
The Official Patient's Sourcebook on Vesicoureteral Reflux
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 HEMOCHROMATOSIS: GUIDELINES ............................................ 9 Overview ....................................................................................................................................... 9 What Is Hemochromatosis? ........................................................................................................ 11 Causes.......................................................................................................................................... 12 Risk Factors ................................................................................................................................. 13 Symptoms .................................................................................................................................... 13 Diagnosis ..................................................................................................................................... 14 Treatment .................................................................................................................................... 14 Tests for Hemachromatosis.......................................................................................................... 15 Research....................................................................................................................................... 16 For More Information.................................................................................................................. 17 More Guideline Sources .............................................................................................................. 18 Vocabulary Builder...................................................................................................................... 30 CHAPTER 2. SEEKING GUIDANCE ................................................................................................... 33 Overview ..................................................................................................................................... 33 Associations and Hemochromatosis ............................................................................................ 33 Finding More Associations ......................................................................................................... 40 Finding Doctors........................................................................................................................... 41 Finding a Urologist ..................................................................................................................... 42 Selecting Your Doctor ................................................................................................................. 43 Working with Your Doctor ......................................................................................................... 44 Broader Health-Related Resources .............................................................................................. 45 Vocabulary Builder...................................................................................................................... 45
CHAPTER 3. CLINICAL TRIALS AND HEMOCHROMATOSIS ........ 47 Overview ..................................................................................................................................... 47 Recent Trials on Hemochromatosis ............................................................................................. 50 Benefits and Risks........................................................................................................................ 55 Keeping Current on Clinical Trials ............................................................................................. 58 General References....................................................................................................................... 59 Vocabulary Builder...................................................................................................................... 60 PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL ........................... 63 CHAPTER 4. STUDIES ON HEMOCHROMATOSIS ............................................................................. 65 Overview ..................................................................................................................................... 65 The Combined Health Information Database .............................................................................. 65 Federally-Funded Research on Hemochromatosis ....................................................................... 75 E-Journals: PubMed Central ....................................................................................................... 83 The National Library of Medicine: PubMed................................................................................ 86 Vocabulary Builder...................................................................................................................... 87 CHAPTER 5. PATENTS ON HEMOCHROMATOSIS ............................................................................ 93 Overview ..................................................................................................................................... 93 Patents on Hemochromatosis ...................................................................................................... 94 Patent Applications on Hemochromatosis................................................................................. 100
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Keeping Current ........................................................................................................................ 100 Vocabulary Builder.................................................................................................................... 100 CHAPTER 6. BOOKS ON HEMOCHROMATOSIS .............................................................................. 103 Overview ................................................................................................................................... 103 Book Summaries: Federal Agencies ........................................................................................... 103 Book Summaries: Online Booksellers ........................................................................................ 108 The National Library of Medicine Book Index........................................................................... 109 Chapters on Hemochromatosis .................................................................................................. 111 General Home References .......................................................................................................... 116 Vocabulary Builder.................................................................................................................... 116 CHAPTER 7. MULTIMEDIA ON HEMOCHROMATOSIS ................................................................... 121 Overview ................................................................................................................................... 121 Video Recordings....................................................................................................................... 121 Bibliography: Multimedia on Hemochromatosis ....................................................................... 122 Vocabulary Builder.................................................................................................................... 123 CHAPTER 8. PERIODICALS AND NEWS ON HEMOCHROMATOSIS ................................................ 125 Overview ................................................................................................................................... 125 News Services & Press Releases ................................................................................................ 125 Newsletter Articles .................................................................................................................... 132 Academic Periodicals covering Hemochromatosis..................................................................... 135 Vocabulary Builder.................................................................................................................... 136 CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES .............................................................. 137 Overview ................................................................................................................................... 137 NIH Guidelines ......................................................................................................................... 137 NIH Databases .......................................................................................................................... 138 Other Commercial Databases .................................................................................................... 144 The Genome Project and Hemochromatosis .............................................................................. 144 Specialized References ............................................................................................................... 149 CHAPTER 10. DISSERTATIONS ON HEMOCHROMATOSIS ............................................................. 151 Overview ................................................................................................................................... 151 Dissertations on Hemochromatosis ........................................................................................... 151 Keeping Current ........................................................................................................................ 152 PART III. APPENDICES .............................................................................................................. 153 APPENDIX A. RESEARCHING YOUR MEDICATIONS ..................................................................... 155 Overview ................................................................................................................................... 155 Your Medications: The Basics ................................................................................................... 156 Learning More about Your Medications ................................................................................... 158 Commercial Databases............................................................................................................... 159 Contraindications and Interactions (Hidden Dangers)............................................................. 160 A Final Warning ....................................................................................................................... 161 General References..................................................................................................................... 162 APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ............................................................... 163 Overview ................................................................................................................................... 163 What Is CAM? .......................................................................................................................... 163 What Are the Domains of Alternative Medicine? ..................................................................... 164 Can Alternatives Affect My Treatment?................................................................................... 167 Finding CAM References on Hemochromatosis........................................................................ 168 Additional Web Resources......................................................................................................... 176 General References..................................................................................................................... 178 Vocabulary Builder.................................................................................................................... 179 APPENDIX C. RESEARCHING NUTRITION..................................................................................... 181 Overview ................................................................................................................................... 181 Food and Nutrition: General Principles .................................................................................... 182
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Finding Studies on Hemochromatosis....................................................................................... 186 Federal Resources on Nutrition................................................................................................. 189 Additional Web Resources......................................................................................................... 190 Vocabulary Builder.................................................................................................................... 190 APPENDIX D. FINDING MEDICAL LIBRARIES ............................................................................... 193 Overview ................................................................................................................................... 193 Preparation ................................................................................................................................ 193 Finding a Local Medical Library ............................................................................................... 194 Medical Libraries Open to the Public ........................................................................................ 194 APPENDIX E. YOUR RIGHTS AND INSURANCE ............................................................................. 201 Overview ................................................................................................................................... 201 Your Rights as a Patient............................................................................................................ 201 Patient Responsibilities ............................................................................................................. 205 Choosing an Insurance Plan...................................................................................................... 206 Medicare and Medicaid ............................................................................................................. 208 NORD’s Medication Assistance Programs............................................................................... 211 Additional Resources................................................................................................................. 212 Vocabulary Builder.................................................................................................................... 213 ONLINE GLOSSARIES ............................................................................................................... 215 Online Dictionary Directories................................................................................................... 220 HEMOCHROMATOSIS GLOSSARY....................................................................................... 221 General Dictionaries and Glossaries ......................................................................................... 235 INDEX.............................................................................................................................................. 237
Introduction
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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
Hemochromatosis
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 Hemochromatosis 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 hemochromatosis, 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 hemochromatosis. 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 hemochromatosis 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 hemochromatosis (e.g. finding guidelines on diagnosis, treatments, and prognosis), followed by a number of topics, including information on how to get in touch with organizations, associations, or other patient networks dedicated to hemochromatosis. It also gives you sources of information that can help you find a doctor in your local area specializing in treating hemochromatosis. Collectively, the material presented in Part I is a complete primer on basic research topics for patients with hemochromatosis. Part II moves on to advanced research dedicated to hemochromatosis. 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 hemochromatosis. 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 with hemochromatosis or related disorders. The appendices are dedicated to more pragmatic issues faced by many patients with hemochromatosis. 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 with hemochromatosis.
Scope While this sourcebook covers hemochromatosis, your doctor, research publications, and specialists may refer to your condition using a variety of terms. Therefore, you should understand that hemochromatosis is often considered a synonym or a condition closely related to the following: ·
Bronze Diabetes
·
Cirrhosis, Congenital Pigmentary
4
Hemochromatosis
·
Familial Hemochromatosis
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Hemochromatosis Syndrome
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Hemosiderosis
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Iron Overload Disease
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Primary Hemochromatosis
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Troisier-hanot-chauffard Syndrome
In addition to synonyms and related conditions, physicians may refer to hemochromatosis using certain coding systems. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) is the most commonly used system of classification for the world’s illnesses. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for hemochromatosis:4 ·
275.0 disorders of iron metabolism
·
275.0 hemochromatosis
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 hemochromatosis. 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 covering most illnesses. Some are written by patients or their family members. These generally take a layperson’s approach to understanding and coping with an illness or disorder. 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 This list is based on the official version of the World Health Organization’s 9th Revision, International Classification of Diseases (ICD-9). According to the National Technical Information Service, “ICD-9CM extensions, interpretations, modifications, addenda, or errata other than those approved by the U.S. Public Health Service and the Health Care Financing Administration are not to be considered official and should not be utilized. Continuous maintenance of the ICD-9-CM is the responsibility of the federal government.”
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 diagnosed with hemochromatosis 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 hemochromatosis is even indexed in search engines, a nonsystematic 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 hemochromatosis, 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. In this way, we wish you the best in your efforts to incorporate this educational approach into your treatment plan. The Editors
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PART I: THE ESSENTIALS
ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on hemochromatosis. The essentials of a disease typically include the definition or description of the disease, a discussion of who it affects, the signs or symptoms associated with the disease, tests or diagnostic procedures that might be specific to the disease, and treatments for the disease. Your doctor or healthcare provider may have already explained the essentials of hemochromatosis to you or even given you a pamphlet or brochure describing hemochromatosis. 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
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CHAPTER 1. THE ESSENTIALS ON HEMOCHROMATOSIS: GUIDELINES Overview Official agencies, as well as federally-funded institutions supported by national grants, frequently publish a variety of guidelines on hemochromatosis. 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 hemochromatosis 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 hemochromatosis. 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 Hemochromatosis
There is no guarantee that any one Institute will have a guideline on a specific disease, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare diseases. 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 hemochromatosis and associated conditions: ·
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 Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
Among these, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is particularly noteworthy. The NIDDK’s mission is to conduct and support research on many of the most serious diseases affecting public health.6 The Institute supports much of the clinical research on the diseases of internal medicine and related subspecialty fields as well as many basic science disciplines. The NIDDK’s Division of Intramural Research encompasses the broad spectrum of metabolic diseases such as diabetes, inborn errors of metabolism, endocrine disorders, mineral metabolism, digestive diseases, nutrition, urology and renal disease, and hematology. Basic research studies include biochemistry, nutrition, pathology, histochemistry, chemistry, physical, chemical, and molecular biology, pharmacology, and toxicology. NIDDK extramural research is organized into divisions of program areas: ·
Division of Diabetes, Endocrinology, and Metabolic Diseases
·
Division of Digestive Diseases and Nutrition
·
Division of Kidney, Urologic, and Hematologic Diseases
The Division of Extramural Activities provides administrative support and overall coordination. A fifth division, the Division of Nutrition Research Coordination, coordinates government nutrition research efforts. The Institute supports basic and clinical research through investigator-initiated This paragraph has been adapted from the NIDDK: http://www.niddk.nih.gov/welcome/mission.htm. “Adapted” signifies that a passage is reproduced exactly or slightly edited for this book. 6
Guidelines 11
grants, program project and center grants, and career development and training awards. The Institute also supports research and development projects and large-scale clinical trials through contracts. The following patient guideline was recently published by the NIDDK on hemochromatosis.
What Is Hemochromatosis? 7 Hemochromatosis, the most common form of iron overload disease, is an inherited disorder that causes the body to absorb and store too much iron. The extra iron builds up in organs and damages them. Without treatment, the disease can cause these organs to fail. Iron is an essential nutrient found in many foods. The greatest amount is found in red meat and iron-fortified bread and cereal. In the body, iron becomes part of hemoglobin, a molecule in the blood that transports oxygen from the lungs to all body tissues. Healthy people usually absorb about 10 percent of the iron contained in the food they eat. People with hemochromatosis absorb about 20 percent. The body has no natural way to rid itself of excess iron, so extra iron is stored in body tissues, especially the liver, heart, and pancreas.
Adapted from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): http://www.niddk.nih.gov/health/digest/pubs/hemochrom/hemochromatosis.htm. 7
12 Hemochromatosis
Causes Genetic hemochromatosis is mainly associated with a defect in a gene called HFE, which regulates the amount of iron absorbed from food. Two mutations, named C282Y and H63D, can cause hemochromatosis. The genetic defect is present at birth, but symptoms rarely appear before adulthood. A person who inherits the defective gene from both parents develops hemochromatosis. A person who inherits the defective gene from only one parent is a carrier for the disease but usually does not develop it. However, carriers might have a slight increase in iron absorption. Scientists hope that further study of HFE will reveal how the body normally metabolizes iron. They also want to learn how iron injures cells and whether it contributes to organ damage in other diseases, such as alcoholic liver disease, hepatitis C, porphyria cutanea tarda, heart disease, reproductive disorders, cancer, autoimmune hepatitis, diabetes, and joint disease. Juvenile hemochromatosis and neonatal hemochromatosis are two forms of the disease that are not caused by an HFE defect. Their cause is unknown. The juvenile form leads to severe iron overload and liver and heart disease in adolescents and young adults between the ages of 15 and 30, and the neonatal form causes the same problems in infants.
Guidelines 13
Risk Factors Hemochromatosis is one of the most common genetic disorders in the United States. It most often affects Caucasians of Northern European descent, although other ethnic groups are also affected. About 5 people in 1,000 (0.5 percent) of the U.S. Caucasian population carry two copies of the hemochromatosis gene and are susceptible to developing the disease. One person in 8 to 12 is a carrier of the abnormal gene. Hemochromatosis is less common in African Americans, Asian Americans, Hispanic Americans, and American Indians. Men are about five times more likely to be diagnosed with hemochromatosis than women. Men also tend to develop problems from the excess iron at a younger age.
Symptoms Joint pain is the most common complaint of people with hemochromatosis. Other common symptoms include fatigue, lack of energy, abdominal pain, loss of sex drive, and heart problems. Symptoms tend to occur in men between the ages of 30 and 50 and in women over age 50. However, many people have no symptoms when they are diagnosed. If the disease is not detected early and treated, iron will accumulate in body tissues and may eventually lead to serious problems such as ·
Arthritis.
·
Liver disease, including enlarged liver, hepatitis, cirrhosis, cancer, and liver failure.
·
Heart abnormalities, such as irregular heart rhythms or congestive heart failure.
·
Impotence.
·
Early menopause.
·
Abnormal pigmentation of the skin, making it look gray or bronze.
·
Damage to the pancreas, possibly causing diabetes.
·
Thyroid deficiency.
·
Damage to the adrenal gland.
14 Hemochromatosis
Diagnosis A thorough medical history, physical examination, and routine blood tests help rule out other conditions that could be causing the symptoms. This information often provides helpful clues, such as a family history of arthritis or unexplained liver disease. Blood tests can determine whether the amount of iron stored in the body is too high. The transferrin saturation test determines how much iron is bound to the protein that carries iron in the blood. The serum ferritin test shows the level of iron in the liver. If either of these tests shows higher than normal levels of iron in the body, doctors can order a special blood test to detect the HFE mutation, which will help confirm the diagnosis. (If the mutation is not present, hemochromatosis is not the reason for the iron buildup, and the doctor will look for other causes.) A liver biopsy, in which a tiny piece of liver tissue is removed and examined under a microscope, will disclose how much iron has accumulated in the liver and whether it is damaged. Hemochromatosis is often undiagnosed and untreated. It is considered rare and doctors may not think to test for it. The initial symptoms can be diverse and vague and can mimic the symptoms of many other diseases. Also, doctors may focus on the conditions caused by hemochromatosis--arthritis, liver disease, heart disease, or diabetes--rather than on the underlying iron overload. However, if hemochromatosis is diagnosed and treated before organ damage has occurred, a person can live a normal, healthy life. Hemochromatosis is usually treated by a specialist in liver disorders (hepatologist), digestive disorders (gastroenterologist), or blood disorders (hematologist). Because of the other problems associated with hemochromatosis, several other specialists may be on the treatment team, such as an endocrinologist, cardiologist, or rheumatologist. Internists or family practitioners can also treat the disease.
Treatment Treatment is simple, inexpensive, and safe. The first step is to rid the body of excess iron. The process is called phlebotomy, which means removing blood. Depending on how severe the iron overload is, a pint of blood will be taken once or twice a week for several months to a year, and occasionally longer. Blood ferritin levels will be tested after every 4 phlebotomies to monitor iron levels. The goal is to bring blood ferritin levels to the low end of normal and
Guidelines 15
keep them there. Depending on the lab, that means less than 9 to 50 micrograms of blood ferritin per liter. Depending on the amount of overload at diagnosis, reaching normal levels can take up to 100 phlebotomies. Once iron levels return to normal, maintenance therapy, which involves giving a pint of blood every 1 to 4 months for life, begins. Some people may need it more often. An annual blood ferritin test will help determine how often blood should be removed. The earlier hemochromatosis is diagnosed and treated, the better. If treatment begins before any organs are damaged, associated conditions-such as liver disease, heart disease, arthritis, and diabetes--can be prevented. The outlook for people who already have these conditions at diagnosis depends on the degree of organ damage. For example, treating hemochromatosis can stop the progression of liver disease in its early stages, which means a normal life expectancy. However, if cirrhosis has developed, the person’s risk of developing liver cancer is high, even if iron stores are reduced to normal levels. People who have complications of hemochromatosis may want to consider getting treatment from a specialized hemochromatosis center. These centers are located throughout the country. Information is available from the organizations listed under For More Information. People with hemochromatosis should not take iron supplements. Those who have liver damage should not drink alcoholic beverages because they further damage the liver. Although treatment cannot cure the conditions associated with hemochromatosis, it will help most of them. The main exception is arthritis, which does not improve even after excess iron is removed.
Tests for Hemachromatosis Screening for hemochromatosis (testing people who have no symptoms) is not a routine part of medical care or checkups. However, researchers and public health officials do have some suggestions: ·
Brothers and sisters of people who have hemochromatosis should have their blood tested to see if they have the disease or are carriers.
·
Parents, children, and other close relatives of people who have the disease should consider testing.
16 Hemochromatosis
·
Doctors should consider testing people who have joint disease, severe and continuing fatigue, heart disease, elevated liver enzymes, impotence, and diabetes, because these conditions may result from hemochromatosis.
Since the genetic defect is common and early detection and treatment are so effective, some researchers and education and advocacy groups have suggested that widespread screening for hemochromatosis would be costeffective and should be conducted. However, a simple, inexpensive, and accurate test for routine screening does not yet exist, and the available options have limitations. For example, the genetic test provides a definitive diagnosis, but it is expensive. The blood test for transferrin saturation is widely available and relatively inexpensive, but it may have to be done twice with careful handling to confirm a diagnosis.
Research Current research in hemochromatosis is concentrated in four areas: ·
Genetics. Scientists are working to understand more about how the HFE gene normally regulates iron levels.
·
Pathogenesis. Scientists are studying how iron injures body cells. Iron is an essential nutrient, but above a certain level it can damage or even kill the cell.
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Epidemiology. Research is underway to explain why the amounts of iron people normally store in their bodies differ and why day-to-day fluctuations in an individual’s own iron stores occur. Research is also being conducted to determine how many people with the defective HFE gene go on to develop symptoms, as well as why some people develop symptoms and others do not.
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Screening and Testing. Scientists are working to determine at what age testing is most effective, which groups should be tested, and what the best tests for widespread screening are.
Guidelines 17
For More Information Information about hemochromatosis is available from these organizations: American Hemochromatosis Society, Inc. 777 East Atlantic Avenue Suite Z-363 Delray Beach, FL 33483-5352 Tel: (888) 655-IRON (4766) or (561) 266-9037 Fax: (561) 278-0171 Email:
[email protected] Internet: www.americanhs.org American Liver Foundation 75 Maiden Lane Suite 603 New York, NY 10038-4810 Tel: (800) GO-LIVER (465-4837) Email:
[email protected] Internet: www.liverfoundation.org The Hemochromatosis Foundation, Inc. P.O. Box 8569 Albany, NY 12208 (Please send a self-addressed, stamped envelope to receive materials.) Tel: (518) 489-0972 Fax: (518) 489-0227 Internet: www.hemochromatosis.org Iron Overload Diseases Association, Inc. 433 Westwind Drive North Palm Beach, FL 33408-5123 Tel: (561) 840-8512 or (561) 840-8513 Fax: (561) 842-9881 Email:
[email protected] Internet: www.ironoverload.org National Organization for Rare Disorders, Inc. (NORD) P.O. Box 8923 New Fairfield, CT 06812-8923 Tel: (203) 746-6518 or (800) 999-6673
18 Hemochromatosis
Fax: (203) 746-6481 Internet: www.rarediseases.org National Digestive Diseases Information Clearinghouse 2 Information Way Bethesda, MD 20892-3570 Email:
[email protected] The National Digestive Diseases Information Clearinghouse (NDDIC) is a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). NIDDK is part of the National Institutes of Health under the U.S. Department of Health and Human Services. Established in 1980, the clearinghouse provides information about digestive diseases to people with digestive disorders and to their families, health care professionals, and the public. NDDIC answers inquiries; develops, reviews, and distributes publications; and works closely with professional and patient organizations and Government agencies to coordinate resources about digestive diseases. Publications produced by the clearinghouse are carefully reviewed for scientific accuracy, content, and readability.
More Guideline Sources The guideline above on hemochromatosis 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 hemochromatosis. 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 with hemochromatosis. 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.
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
Guidelines 19
can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following as being relevant to hemochromatosis: ·
Guides On hemochromatosis Hemochromatosis http://www.nlm.nih.gov/medlineplus/hemochromatosis.html Hemochromatosis http://www.nlm.nih.gov/medlineplus/ency/article/000327.htm
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Guides on Human Anatomy and Systems Genetics/Birth Defects Topics http://www.nlm.nih.gov/medlineplus/geneticsbirthdefects.html Digestive System Topics http://www.nlm.nih.gov/medlineplus/digestivesystem.html Blood/Lymphatic System Topics http://www.nlm.nih.gov/medlineplus/bloodlymphaticsystem.html
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Other Guides Blood/Blood Transfusion http://www.nlm.nih.gov/medlineplus/bloodbloodtransfusion.html Genetic Disorders http://www.nlm.nih.gov/medlineplus/geneticdisorders.html Liver disease http://www.nlm.nih.gov/medlineplus/ency/article/000205.htm Cirrhosis http://www.nlm.nih.gov/medlineplus/ency/article/000255.htm Portacaval shunt http://www.nlm.nih.gov/medlineplus/ency/article/001112.htm Hepatocellular carcinoma http://www.nlm.nih.gov/medlineplus/ency/article/000280.htm Hypogonadism http://www.nlm.nih.gov/medlineplus/ency/article/001195.htm Hypopituitarism http://www.nlm.nih.gov/medlineplus/ency/article/000343.htm Restrictive cardiomyopathy http://www.nlm.nih.gov/medlineplus/ency/article/000189.htm
20 Hemochromatosis
Pituitary infarction http://www.nlm.nih.gov/medlineplus/ency/article/001167.htm Within the health topic page dedicated to hemochromatosis, the following was recently recommended to patients: ·
General/Overviews Hemochromatosis: Frequently Asked Questions Source: National Center for Chronic Disease Prevention and Health Promotion http://www.cdc.gov/nccdphp/dnpa/hemochromatosis/faq.htm Hereditary Hemochromatosis: Too Much Iron Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00834
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Diagnosis/Symptoms Detection: Iron Panel Tests Source: Iron Disorders Institute http://www.irondisorders.org/disorders/hem/detection_ironpanel. htm Diagnosis: How Do You Find Out Source: Iron Overload Diseases Association http://www.ironoverload.org/diagnosis.html Hemochromatosis: 16 Facts You Should Know Source: Iron Overload Diseases Association http://www.ironoverload.org/facts.html
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Treatment Treatment and Maintenance Source: Iron Overload Diseases Association http://www.ironoverload.org/treatment.html Treatments: Phlebotomy Source: Iron Disorders Institute http://www.irondisorders.org/treatments/phl/index.htm
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Nutrition Diet & Blood Disposal Source: Iron Overload Diseases Association http://www.ironoverload.org/diet.html
Guidelines 21
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Specific Conditions/Aspects Hereditary Hemochromatosis: Genetics Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00833 Iron Overload Disease Due to Hereditary Hemochromatosis Source: National Center for Chronic Disease Prevention and Health Promotion http://www.cdc.gov/nccdphp/dnpa/hemochromatosis/hereditary. htm
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Children Juvenile Hemochromatosis Source: Iron Disorders Institute http://www.irondisorders.org/disorders/jvh/index.htm
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From the National Institutes of Health Hemochromatosis Source: National Digestive Diseases Information Clearinghouse http://www.niddk.nih.gov/health/digest/pubs/hemochrom/hemo chromatosis.htm
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Organizations Iron Disorders Institute http://www.irondisorders.org/ Iron Overload Diseases Association http://www.ironoverload.org/ National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/index.htm National Institute of Diabetes and Digestive and Kidney Diseases http://www.niddk.nih.gov/
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Prevention/Screening Screening for Iron Overload Due to Hereditary Hemochromatosis Source: National Center for Chronic Disease Prevention and Health Promotion http://www.cdc.gov/nccdphp/dnpa/hemochromatosis/screening.h tm
22 Hemochromatosis
·
Research Study Finds Hemochromatosis Patients' Blood is as Safe as Other Donated Blood Source: National Heart, Lung, and Blood Institute http://www.nih.gov/news/pr/sep2001/nhlbi-25.htm
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 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 hemochromatosis and related conditions. 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: ·
Guide to Treatment: Hemochromatosis Iron Overload Source: Greenville, SC: Iron Disorders Institute. 1999. 17 p. Contact: Available from Iron Disorders Institute. P.O. Box 2031, Greenville, SC 29602. (888) 565-IRON. Website: www.irondisorders.org. Price: Single copy free. Summary: Hemochromatosis is a genetic metabolic disorder in which an individual absorbs and retains too much iron. Increased iron absorption in the gastrointestinal tract may cause lifelong excessive iron absorption and accumulation, and serious health effects, including arthritis, cirrhosis, diabetes, impotence, heart failure, and death can result. This brochure offers readers a guide to the treatment for hemochromatosis. Topics include diagnostic tests, the technique of phlebotomy (removing blood), estimating the number of treatments, dietary considerations,
Guidelines 23
foods high in iron, the patient care team, and treatment journals. For patients with serious iron overload, phlebotomy is necessary because it removes about 250 milligrams of iron with each treatment. The brochure describes each step of the phlebotomy treatment, from undergoing pretreatment blood tests, to preparing the arm for blood extraction, measuring the amount of blood removed, providing postprocedure care, and handling the removed blood (which is under the same guidelines as contaminated blood). The brochure outlines four phases of therapy (including maintenance) and what the patient can expect during each phase; the issue of vitamin supplementation is also addressed. Supplements may include vitamin E, B complex (without C) plus extra B6, folic acid, and B12. Dietary changes include educating oneself about the amounts of iron in foods and adjusting intake appropriately. Meat contains the most easily absorbable form of iron; vegetables and grains have a type of iron that is not easily absorbed. The brochure includes a list of common foods with their iron content (the amount in a standard serving). The brochure also includes a blank treatment journal for recording one's phlebotomy procedures and a blank lined page for recording important phone numbers. The brochure concludes with a brief description of the Iron Disorders Institute (IDI), founded to limit pain, suffering, and unnecessary death from common and often misdiagnosed disorders of iron, such as anemia of chronic disease, porphyria cutanea tarda, iron loading anemia, iron deficiency anemia, African siderosis, and hereditary hemochromatosis. 7 figures. 2 tables. ·
Guide to Diagnosis: Hemochromatosis Iron Overload Source: Greenville, SC: Iron Disorders Institute. 1999. [2 p.]. Contact: Available from Iron Disorders Institute. P.O. Box 2031, Greenville, SC 29602. (888) 565-IRON. Website: www.irondisorders.org. Price: Single copy free. Summary: Hemochromatosis (HHC) is a genetic metabolic disorder in which an individual absorbs and retains too much iron. Increased iron absorption in the gastrointestinal tract may cause lifelong excessive iron absorption and accumulation, and serious health effects, including arthritis, cirrhosis, diabetes, impotence, heart failure, and death can result. This brochure offers readers a guide to the diagnosis of HHC. Topics include symptoms, risk factors, candidacy for liver biopsy, tests for body iron status overload, DNA tests, indications for genetic testing, and the importance of working closely with one's physician. Chronic fatigue is generally the first and most common symptom associated with iron overload. Liver biopsy may be recommended if the patient's liver enzymes are elevated and ferritin is about 1,000 ng per milliliter. Liver
24 Hemochromatosis
biopsy is the only way to determine the extent of cirrhosis or fibrosis and formerly was the standard for diagnosing hemochromatosis. Trial phlebotomy (blood removal) is also a way to diagnose HHC. A patient who can tolerate several phlebotomies without developing anemia can be diagnosed with HHC. Genetic typing tests for HHC are available as well. Children do not need to be genetically tested. Once it is determined that parents are carriers or homozygous, offspring should be screened routinely using transferrin saturation percentage and ferritin test levels. The brochure notes that most patients with HHC can be diagnosed and treated by a family practice physician; however, specialists may also be necessary to treat chronic disease that may have developed as a result of iron overload. The brochure concludes with a brief description of the Iron Disorders Institute (IDI), founded to limit pain, suffering, and unnecessary death from common and often misdiagnosed disorders of iron, such as anemia of chronic disease, porphyria cutanea tarda, iron loading anemia, iron deficiency anemia, African siderosis, and HHC. ·
ABC's of Pediatric Hereditary Hemochromatosis Source: Delray Beach, FL: American Hemochromatosis Society. 1999. [4 p]. Contact: Available from American Hemochromatosis Society. 777 East Atlantic Avenue, PMB Z-363, Delray Beach, FL 33483-5352. (888) 655IRON or (561) 266-9038. Fax (561) 266-9038. E-mail:
[email protected]. Website: www.americanhs.org. Price: Single copy free; bulk copies available. Summary: This brochure familiarizes readers with pediatric hereditary hemochromatosis and the Children HHelping Children (CHHC) Screening and Awareness Project. The mission of CHHC is to identify children who have a clinical iron overload and hereditary hemochromatosis (HH) through proper iron tests and DNA (genetic) testing. This testing can afford the earliest possible diagnosis of the disease and can identify the genetic risk factor in children in order to prevent organ damage or premature death during childhood or adulthood. The brochure educates parents about screening, prenatal or preconception testing, and ongoing monitoring of children. Recent research has shown that HH is the most common genetic disease in the United States, although many people are silent carriers of the genetic mutation. HH can cause children or adults to load and store excess iron from a normal diet. Unless treated, excess iron can damage vital body organs (notably the liver) and eventually cause death. Ideally, children should be DNA screened at birth and children aged two years or older should be screened annually with blood tests to check their iron storage levels. Couples planning a pregnancy, or expectant parents, should have
Guidelines 25
genetic testing for HH to predict (or confirm) the genetic status of the fetus (as well as themselves). DNA testing can be performed through a lab using either a blood or tissue sample (the latter can be used for children and adults and involves cheek tissue, so is painless). Children in high risk categories, including those with diabetes, fatigue, liver disease, cancer, and heart disease, should particularly be tested for HH. With early diagnosis, proper treatment and management, the symptoms and premature death caused by HH are preventable in children and adults. The brochure includes the contact information for the American Hemochromatosis Society and the CHHC program. 7 references. ·
What Every Senior Should Know About Hereditary Hemochromatosis Source: Delray Beach, FL: American Hemochromatosis Society. 1999. [4 p]. Contact: Available from American Hemochromatosis Society. 777 East Atlantic Avenue, PMB Z-363, Delray Beach, FL 33483-5352. (888) 655IRON or (561) 266-9038. Fax (561) 266-9038. E-mail:
[email protected]. Website: www.americanhs.org. Price: Single copy free; bulk copies available. Summary: This brochure familiarizes readers with hereditary hemochromatosis and the Seniors HHelping Seniors (SHHS) Screening and Awareness Project. The mission of SHHS is to identify seniors who have a clinical iron overload (phenotype) and or the hereditary hemochromatosis (SS) gene mutations through proper iron tests and DNA (genetic) testing. The project provides awareness through educational resources for physicians and patients, data for researchers, as well as opportunities for emotional support for people with the disease. Recent research has shown that HH is the most common genetic disease in the United States, although many people are silent carriers of the genetic mutation. HH can cause children or adults to load and store excess iron from a normal diet. Unless treated, excess iron can damage vital body organs (notably the liver) and eventually cause death. The brochure recommends that seniors should be careful not to take iron supplements, or vitamins containing iron, without first checking their iron storage status with their doctor. DNA testing can be performed through a lab using either a blood or tissue sample (the latter can be used for children and adults and involves cheek tissue, so is painless). Treatment requires weekly phlebotomy (bloodletting), similar to a blood donation, until blood levels are stabilized, then a maintenance treatment program of 3 to 4 phlebotomies a year for the rest of the patient's life. The brochure reiterates the importance of testing which can afford the earliest possible diagnosis of the disease and can identify the genetic risk factor in order to prevent organ damage or premature death. The brochure
26 Hemochromatosis
includes the contact information for the American Hemochromatosis Society and the SHHS program. 5 references. ·
Hemochromatosis (HH) Source: Richmond, BC, Canada: Canadian Hemochromatosis Society. 1997. 2 p. Contact: Available from Canadian Hemochromatosis Society. 272-7000 Minoru Boulevard, Richmond, BC, Canada V6Y 3Z5. (604) 279-7135. Fax (604) 279-7138. E-mail:
[email protected]. Price: Single copy free. Summary: This brochure describes hemochromatosis (HH), a genetic disorder that results in an overload of iron in the body. Iron accumulates over a number of years and collects in vital organs, such as the heart, liver, and pancreas, causing damage and, in some cases, total destruction. Symptoms include chronic fatigue, arthritis, diabetes, enlarged liver, cirrhosis, weight loss, mood swings, irregular heartbeat, abdominal pain and distention, menstrual irregularities, loss of body hair, impotence, testicular atrophy, changes in skin color, and jaundice. The brochure discusses the incidence of HH in Canada, treatment options, diagnostic tests, family screening, and monitoring of children. HH patients can be successfully treated by regular blood withdrawals (phlebotomies), which will reduce the buildup of excess iron. If diagnosed early enough, iron buildup can be stopped in time and irreversible damage to vital organs will be avoided.
·
Hemochromatosis: Not So Rare Source: Cedar Grove, NJ: American Liver Foundation, Inc. 199x. 2 p. Contact: Available from American Liver Foundation. 1425 Pompton Avenue, Cedar Grove, NJ 07009. (800) 223-0179 or (201) 256-2550. Price: $0.50 each; $6 for 25 copies; $12 for 50 copies (as of 1995); discounts available for larger quantities. Summary: Hemochromatosis is a hereditary disease which causes the body to absorb and store too much iron. The wide range of symptoms, varying from person to person, makes diagnosis difficult. Blood tests for serum iron and total iron binding capacity are good screening devices. A follow-up test is the serum ferritin level. If these tests are consistently high, a liver biopsy should be done. Hemochromatosis is treated by removing one to two pints of blood each week until iron stores go down to a normal level. Therapy should then be continued every two to four months for life. Those who are treated early can look forward to a completely normal, active life. When the illness has advanced to the stage of cirrhosis, the situation is more serious. A person with blood relatives
Guidelines 27
with hemochromatosis should be tested with the various blood tests even if there are no symptoms.
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 “hemochromatosis” or synonyms. The following was recently posted: ·
ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). Source: American College of Cardiology/American Heart Association.; 1995 November 1 (revised 2001 Dec); 56 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2340&sSearch_string=hemochromatosis
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ACR Appropriateness Criteria™ for liver lesion characterization. Source: American College of Radiology.; 1998; 7 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1633&sSearch_string=hemochromatosis
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Identification, referral, and support of elders with genetic conditions. Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core.; 1999; 31 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1194&sSearch_string=hemochromatosis
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Preventive counseling and education. Source: Institute for Clinical Systems Improvement.; 1995 May (revised 2001 Mar); 61 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2101&sSearch_string=hemochromatosis
28 Hemochromatosis
·
The management of diabetes mellitus in the primary care setting. Source: Department of Defense/Veterans Health Administration.; 1999 December; 147 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1809&sSearch_string=hemochromatosis
·
The pharmacologic management of chronic heart failure. Source: Department of Veterans Administration.; 2001 February; 42 pages
Affairs/Veterans
Health
http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2253&sSearch_string=hemochromatosis 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: ·
Hemochromatosis Summary: This fact sheet presents a general overview on Hemochromatosis -- a hereditary disease with symptoms that include fatigue, abdominal pain, jaundice (yellowing of skin and eyes), and a change in skin Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=994
·
Hemochromatosis, Hereditary (HH) Summary: The information presented here is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and Source: National Center for Biotechnology Information, National Library of Medicine http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=1031
Guidelines 29
·
Overview of Hemochromatosis Summary: A consumer health education fact sheet about hemochromatosis, a disorder of iron metabolism that is known to exacerbate or cause cirrhosis of the liver, cardiac diseases and other chronic illnesses. Source: Office of Genomics and Disease Prevention, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=2919
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 hemochromatosis. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.
Additional Web Sources A number of Web sites 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
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drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
30 Hemochromatosis
·
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDÒHealth: http://my.webmd.com/health_topics
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 quantity of hemoglobin. [NIH] Atrophy: A wasting away; a diminution in the size of a cell, tissue, organ, or part. [EU] Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Cardiology: The study of the heart, its physiology, and its functions. [NIH] 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] 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] Distention: The state of being distended or enlarged; the act of distending. [EU]
Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [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] 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]
Guidelines 31
Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fibrosis: The formation of fibrous tissue; fibroid or fibrous degeneration [EU] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] 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] Hypogonadism: A condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [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] Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU] Menopause: Cessation of menstruation in the human female, occurring usually around the age of 50. [EU] Microgram: A unit of mass (weight) of the metric system, being onemillionth of a gram (10-6 gm.) or one one-thousandth of a milligram (10-3 mg.). [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Neonatal: Pertaining to the first four weeks after birth. [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] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Pigmentation: 1. the deposition of colouring matter; the coloration or discoloration of a part by pigment. 2. coloration, especially abnormally increased coloration, by melanin. [EU] Porphyria: A pathological state in man and some lower animals that is often
32 Hemochromatosis
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] Prenatal: Existing or occurring before birth, with reference to the fetus. [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] 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] Siderosis: The deposition of iron in a tissue. In the eye, the iron may be deposited in the stroma adjacent to the Descemet's membrane. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] 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] 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]
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CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people with hemochromatosis. These associations can become invaluable sources of information and advice. Many associations offer aftercare support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.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 and cope with hemochromatosis. The chapter ends with a discussion on how to find a doctor that is right for you.
Associations and Hemochromatosis As mentioned by the Agency for Healthcare Research and Quality, sometimes the emotional side of an illness can be as taxing as the physical side.9 You may have fears or feel overwhelmed by your situation. Everyone has different ways of dealing with disease or physical injury. Your attitude, your expectations, and how well you cope with your condition can all 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://www.ahcpr.gov/consumer/diaginf5.htm. 8
34 Hemochromatosis
influence your well-being. This is true for both minor conditions and serious illnesses. For example, a study on female breast cancer survivors revealed that women who participated in support groups lived longer and experienced better quality of life when compared with women who did not participate. In the support group, women learned coping skills and had the opportunity to share their feelings with other women in the same situation. 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 Hemochromatosis Society (AHS) Telephone: (561) 266-9037 Toll-free: (888) 655-4766 Fax: (561) 266-9038 Email:
[email protected] Web Site: http://www.americanhs.or Background: The American Hemochromatosis Society (AHS) is a not-forprofit voluntary organization dedicated to educate the public, medical community and media by distributing the most current information available on hereditary hemochromatosis (HH) including DNA screening for HH and pediatric HH as well as to facilitate patient empowerment through an on-line network. Hereditary Hemochromatosis is a metabolic disorder characterized by excessive absorption of iron which eventually damages numerous organs. Established in 1998, the objectives of AHS are banning genetic discrimination, population screening and newborn screening with genetic testing for HH and compassionate support of all patients with Hereditary Hemochromatosis. Consisting of 500 members, educational materials include What Every Senior Should Know About Hereditary Hemochromatosis and The ABC s of Pediatric Hereditary Hemochromatosis.
·
American Liver Foundation Address: American Liver Foundation 75 Maiden Lane, Suite 603, New York, NY 10038 Telephone: (212) 668-1000 Toll-free: (800) 465-4837 Fax: (973) 256-3214 Email:
[email protected] Web Site: http://www.liverfoundation.or
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Background: The American Liver Foundation is a national voluntary notfor-profit organization dedicated to the prevention, treatment, and cure of diseases of the liver through programs of research and education. Established in 1976, the Foundation's activities include support groups, patient advocacy, support of medical research, and patient and professional education. Educational materials include brochures on Hepatitis, Cirrhosis, Biliary Atresia, liver transplantation, gallstones, and Hereditary Hemochromatosis. Fact sheets are also available on a variety of liver diseases including Alagille Syndrome, Alpha-1-Antitrypsin Deficiency, Cancer of the Liver, Fatty Liver, Gilbert Syndrome, Primary Biliary Cirrhosis, Porphyria, and others. Videotapes produced by the Foundation include 'A Healthy Liver: A Happier Life,' 'Foundations for Decision Making,' 'Hepatitis B: Patient Information,' 'Hepatitis C: A Guide for Primary Care Physicians,' and 'The Visionaries.' The Foundation also offers liver wellness and substance abuse prevention programs to elementary schools and corporations. ·
British Liver Trust Address: British Liver Trust Ransomes Europark, Ipswich, Suffolk, 1P3 9QG, United Kingdom Telephone: 01473 276326 Toll-free: 0808 800 1000 Fax: 01473 276327 Web Site: http://www.britishlivertrust.org.u Background: The British Liver Trust is a nonprofit organization in the United Kingdom that is dedicated to helping adults with all forms of liver disease. The Trust is committed to promoting and funding liver disease research, publishing current information for affected individuals and family members, and supporting all individuals affected by liver disease and those who care for them. To fulfill its mission and objectives, the British Liver Trust offers a variety of programs and services including confidential telephone helplines, a nationwide network of support groups, annual national support group conferences, a web site on the Internet, and several publications, including informational leaflets and a regular newsletter entitled 'Liver Focus.' The Trust also supports training conferences for managers and health and safety officers concerning employee protection against infection from bloodborne viruses (i.e., including those that cause different forms of hepatitis) and has promoted the development of the British Liver Trust Liver Nurses' Forum, a national organization open to any nurse who works with liver patients or who has a special interest in liver disease. The Nurses' Forum is committed to conducting biannual meetings, offering an annual
36 Hemochromatosis
conference where nurses are encouraged to present their own research and to discuss issues of special relevance to liver nurses, promoting informal links between members, and publishing a regular newsletter. The British Liver Trust's web site discusses the organization's mission, goals, and services; offers news updates and access to research information; posts recent editions of its newsletter; and provides understandable information on different forms of liver disease. Relevant area(s) of interest: Hemochromatosis ·
Canadian Hemochromatosis Society Address: Canadian Hemochromatosis Society 272-7000 Boulevard, Richmond, British Columbia, V6Y 3Z5, Canada
Minoru
Telephone: (604) 279-7135 Toll-free: (877) 223-4766 Fax: (604) 279-7138 Email:
[email protected] Web Site: http://home.istar.ca/~chct Background: The Canadian Hemochromatosis Society (CHS) is a nonprofit support organization dedicated to providing information and support to individuals and families affected by hereditary hemochromatosis. Hereditary hemochromatosis (HH) is a metabolic disorder characterized by excessive absorption of iron. Without appropriate treatment, excess iron may accumulate in the liver, heart, pancreas, and other organs, resulting in possible multiple organ dysfunction and tissue damage. Established in 1982, the Society is committed to increasing awareness among the Canadian public and the medical community about the importance of early screening for and diagnosis of hemochromatosis. The Society maintains a central registry of all reported cases of hereditary hemochromatosis and provides information regarding appropriate screening and diagnostic testing. CHS also publishes a biannual newsletter that is distributed to doctors and interested individuals all over the world. Its membership questionnaire includes specific questions designed to assist researchers. Other publications include a pamphlet entitled 'Iron Overload? Too Much of a Good Thing Can Kill You...' and a series of fact sheets. The Society maintains a site on the World Wide Web at http://home.istar.ca/~chcts. Relevant area(s) of interest: Bronze Diabetes, Cirrhosis, Congenital Pigmentary, Familial Hemochromatosis, Hemochromatosis Syndrome, Iron Overload Disease, Primary Hemochromatosis
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·
Canadian Liver Foundation Address: Canadian Liver Foundation 365 Bloor Street, Suite 200, Toronto, Ontario, M4W 3L4, Canada Telephone: (416) 964-4935 Toll-free: (800) 563-5483 Fax: (416) 964-0024 Email:
[email protected] Web Site: http://www.liver.c Background: The Canadian Liver Foundation (CLF) is a not-for-profit health organization committed to reducing the incidence and impact of liver disease by providing support for research and education into the causes, diagnosis, prevention and treatment of more than 100 diseases of the liver. Established in 1969, the CLF has established 30 chapters across Canada and provides information in both English and French. Some of the liver diseases discussed in brochures and medical information sheets available from CLF include gallstones, hemochromatosis, primary biliary cirrhosis, several forms of hepatitis, porphyria, fatty liver, and liver cancer. Further information is provided on liver transplantation, the effects of sodium, and management of variceal bleeding. The Foundation also produces a newsletter and maintains World Wide Web site at http://www.liver.ca. Relevant area(s) of interest: Hemochromatosis
·
Children's Liver Disease Foundation (UK) Address: Children's Liver Disease Foundation (UK) AXA Equity and Law House, 35-37 Great Charles Street Queensway, Birmingham, B3 3JY, United Kingdom Telephone: 0121 212 3839 Toll-free: (877) 223-4766 Fax: 0121 212 4300 EWeb Site: http://www.childliverdisease.or Background: The Children's Liver Disease Foundation (UK) is a voluntary not- for-profit organization in the United Kingdom that was established in 1980. The Foundation is committed to providing emotional support to children, adolescents, and families affected by liver disease; promoting research into the causes of pediatric liver disease; creating a greater awareness of such disorders and conditions in the health care communities and the public; and promoting the development of means of early diagnosis and cure. The Children's Liver Disease Foundation is also dedicated to providing understandable information on pediatric liver disease through general informational brochures including 'A Guide to
38 Hemochromatosis
the Liver' and 'Signs and Symptoms of Liver Disease' as well as a leaflet series on specific pediatric liver diseases and conditions, such as Alagille syndrome; neonatal hepatitis; hepatitis A, B, C, and E; biliary atresia; and others. The Foundation's web site on the Internet discusses the organization's mission, goals, and services; enables interested individuals, family members, and health care professionals to make specific inquiries; and provides access to the Foundation's publication series. Relevant area(s) of interest: Hemochromatosis ·
Hemochromatosis Foundation, Inc Address: Hemochromatosis Foundation, Inc. P.O. Box 8569, Albany, NY 12208-2569 Telephone: (518) 489-0972 Fax: (518) 489-0227 Web Site: http://www.hemochromatosis.or Background: The Hemochromatosis Foundation is a national not-forprofit organization dedicated to finding a cure for Hemochromatosis. Hereditary Hemochromatosis (HH) is a metabolic disorder characterized by increased absorption of dietary iron. Without appropriate treatment, excessive iron may accumulate in the liver, heart, pancreas, and other organs, causing organ dysfunction and tissue damage. Established in 1971, the Foundation is committed to fostering understanding of the disease by supporting activities that encourage research; advising legislative and regulatory bodies at the local and federal levels; increasing general awareness of Hemochromatosis to help ensure early diagnosis and prompt treatment; and improving the quality of life for affected individuals and family members. The Foundation also establishes local chapters; sponsors discussion groups where people share their experiences; and provides physician referrals, general information, and local contacts. Educational materials produced by the Foundation include a brochure series.
·
Iron Overload Diseases Association, Inc Address: Iron Overload Diseases Association, Inc. 433 Westwind Drive, North Palm Beach, FL 33408-5123 Telephone: (561) 840-8512 Fax: (561) 842-9881 Email:
[email protected]
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Web Site: http://www.ironoverload.or Background: Iron Overload Diseases Association, Inc. is a voluntary notfor-profit organization dedicated to leading the search for individuals who have undiagnosed Hemochromatosis and preventing the health problems that may result. Hereditary Hemochromatosis is a metabolic disorder characterized by increased absorption of dietary iron. Without appropriate treatment, excessive iron may accumulate in the liver, heart, pancreas, and other organs, causing organ dysfunction and tissue damage. Established in 1981, the Association is also committed to providing information and support to affected individuals and their families; educating the general public; promoting and supporting research; and pressing for earlier diagnosis and more effective treatment for Hemochromatosis. The Association acts as an international clearinghouse for affected individuals, family members, and physicians; provides telephone consultations; offers referrals to genetic counseling and support groups; promotes patient advocacy; and conducts an annual medical symposium as well as conference meetings between patients and health care professionals. The Iron Overload Diseases Association also provides a variety of educational and support materials including books, brochures, fact sheets, and a bimonthly newsletter entitled 'Ironic Blood.'. Relevant area(s) of interest: Iron Overload Disease ·
Metabolic Information Network (PHYSICIAN CALLS ONLY) Address: Metabolic Information Network (PHYSICIAN CALLS ONLY) P.O. Box 670847, Dallas, TX 75367-0847 Telephone: (214) 696-2188 Toll-free: (800) 945-2188 Fax: (214) 696-3258 Email:
[email protected] Background: The Metabolic Information Network (MIN) is a not-forprofit organization dedicated to facilitating research and enhancing care of families affected by inborn errors of metabolism. Established in 1989, the organization publishes a newsletter, a directory, and reports. The Network maintains a Case Register for 10 groups of disorders (representing 86 diagnoses); a physician directory for 200 inborn errors of metabolism; and a listing of worldwide genetic, and a listing of worldwide genetic metabolic patient registries and patient databases. Research investigators and other health care professionals may use the MIN database. Information in the case database for any genetic metabolic disorder includes contact information, relevant diagnoses based on McKusick Codes, 1CD9 codes, and whether tracking/outcome assessment is performed. The progress of these cases is tracked on an
40 Hemochromatosis
annual basis. The MIN case and master databases contain no patient names. Research investigators and other professionals may obtain individual case details only by contacting physicians associated with a particular case recorded in the database.
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 hemochromatosis. 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 “hemochromatosis” (or a synonym) 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 “hemochromatosis”. 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
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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 “hemochromatosis” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with hemochromatosis. You should check back periodically with this database since it is updated every 3 months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by specific diseases. You can access this database at the following Web site: http://www.rarediseases.org/cgi-bin/nord/searchpage. Select the option called “Organizational Database (ODB)” and type “hemochromatosis” (or a synonym) in the search box. Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms for people with 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 with hemochromatosis must go through the process of selecting a physician. While this process will vary from person to person, the Agency for Healthcare 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.
10
This section is adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.
42 Hemochromatosis
·
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 11 http://www.abms.org/newsearch.asp. 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.
Finding a Urologist The American Urological Association (AUA) provides the public with a freeto-use “Find A Urologist” service to help patients find member urologists in their area. The database can be searched by physician name, city, U.S. State, or country and is available via the AUA’s Web site located at http://www.auanet.org/patient_info/find_urologist/index.cfm. According to the AUA: “The American Urological Association is the professional 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. 11
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association for urologists. As the premier professional association for the advancement of urologic patient care, the AUA is pleased to provide Find A Urologist, an on-line referral service for patients to use when looking for a urologist. All of our active members are certified by the American Board of Urology, which is an important distinction of the urologist’s commitment to continuing education and superior patient care.”12 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 Doctor13 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 hemochromatosis?
·
Really listen to my questions?
·
Answer in terms I understood?
·
Show respect for me?
·
Ask me questions?
·
Make me feel comfortable?
·
Address the health problem(s) I came with?
·
Ask me my preferences about different kinds of treatments for hemochromatosis?
·
Spend enough time with me?
Quotation taken from the AACE’s Web site: http://www.aace.com/memsearch.php. section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. 12
13 This
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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 Doctor14 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.
·
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.
This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.
14
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·
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:15 ·
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
Vocabulary Builder The following vocabulary builder provides definitions of words used in this chapter that have not been defined in previous chapters: Biliary: Pertaining to the bile, to the bile ducts, or to the gallbladder. [EU] Registries:
The systems and processes involved in the establishment,
You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.
15
46 Hemochromatosis
support, management, and operation of registers, e.g., disease registers. [NIH] Transplantation: The grafting of tissues taken from the patient's own body or from another. [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]
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CHAPTER 3. CLINICAL TRIALS AND HEMOCHROMATOSIS 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 hemochromatosis.
What Is a Clinical Trial?16 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 other treatments for hemochromatosis 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: ·
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.
16
The discussion in this chapter has been adapted from the NIH and the NEI: www.nei.nih.gov/netrials/ctivr.htm.
48 Hemochromatosis
·
Phase II. Researchers conduct Phase II trials in small numbers of patients to find out the effect of a new treatment on hemochromatosis.
·
Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for hemochromatosis 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 hemochromatosis 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 on hemochromatosis. 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 on hemochromatosis and does not harm patients. 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
Clinical Trials 49
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 hemochromatosis develops over time. A natural history study follows patient volunteers to see how factors such as age, sex, race, or family history might make some people more or less at risk for hemochromatosis. A natural history study may also tell researchers if diet, lifestyle, or occupation affects how a disease or disorder develops and progresses. Results from these studies provide information that helps answer questions such as: How fast will a disease or disorder usually progress? How bad will the condition become? Will treatment be needed? What Is Expected of Patients in a Clinical Trial? Not everyone can take part in a clinical trial for a specific disease or disorder. 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 learning what happens to patients over a long period of time. Only patients
50 Hemochromatosis
who continue to return for follow-up examinations can provide this important long-term information.
Recent Trials on Hemochromatosis The National Institutes of Health and other organizations sponsor trials on various diseases and disorders. 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 disease and disorder at all times. The following lists recent trials dedicated to hemochromatosis.17 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. ·
Evaluation of Patients with Liver Disease Condition(s): Biliary Liver Cirrhosis,; Hemochromatosis; Hepatitis; Hepatolenticular Degeneration; Liver Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: The proposed study aims to evaluate, investigate, and follow-up patients suffering from acute and chronic liver disease. The study will focus on understanding diseases affecting the liver. Patients participating in the study will first undergo a routine check-up as an outpatient. They will be asked to provide blood and urine samples for laboratory testing and will undergo an ultrasound of the liver. Ultrasound examinations use sound waves to determine the size and texture of the liver. After the initial visit subjects will be requested to follow-up once a year at the outpatient department for a similar checkup. Additional tests may be requested throughout the study to provide information for other research studies and individual consent will be requested. These tests may include liver biopsies, skin biopsies, and / or specialized blood, plasma, and lymphocyte examinations. Subjects that qualify for medications presently being studied may be offered the opportunity to benefit from experimental therapy. Study Type: Observational
17
These are listed at www.ClinicalTrials.gov.
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Contact(s): Maryland; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001971 ·
Study of the Pathogenesis of Porphyria Cutanea Tarda Condition(s): Porphyria Cutanea Tarda Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); University of Texas Purpose - Excerpt: Objectives: I. Determine the effect of standard treatments on various predisposing factors in patients with porphyria cutanea tarda (PCT). II. Investigate alcohol history, smoking, liver dysfunction and its etiology, estrogen use, and family history of PCT in these patients. III. Study the relationships of excess iron and the hemochromatosis gene to PCT, including clinical features and risk of recurrence in these patients. IV. Assess hepatitis C virus infections in these patients. V. Assess vitamin C levels in these patients before and after treatment. VI. Assess dietary habits in these patients. VII. Assess activity of cytochrome P450 enzymes (CYP) in vivo in these patients. VIII. Study polymorphic genes for enzymes that metabolize foreign chemicals, including CYP enzymes and glutathione transferases in these patients. Study Type: Observational Contact(s): Texas; University of Texas Medical Branch, Galveston, Texas, 77555-0209, United States; Recruiting; Karl Elmo Anderson 409-772-4661. Study chairs or principal investigators: Karl Elmo Anderson, Study Chair; University of Texas Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005103
·
Treatment of Hemochromatosis Condition(s): Hemochromatosis Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This study will evaluate the effectiveness of a test called MCV in guiding phlebotomy (blood drawing) therapy in patients with hemochromatosis-an inherited disorder that causes too much iron to be absorbed by the intestine. The excess damages body tissues, most severely in the liver, heart, pancreas and joints. Because iron is carried in
52 Hemochromatosis
the hemoglobin of red blood cells, removing blood can effectively lower the body's iron stores. Patients with hemochromatosis undergo weekly phlebotomy treatments (1 pint per session) to deplete iron stores. This usually requires 10 to 50 treatments, after which blood is drawn every 8 to 12 weeks to prevent a re-build up of iron. A test that measures ferritin a protein involved in storing iron - is commonly used to guide phlebotomy therapy in hemochromatosis patients. This study will compare the usefulness of the ferritin test with that of MCV, which measures red blood cell size, in guiding phlebotomy therapy. In addition, the study will 1) examine whether keeping iron levels low during maintenance therapy can help heal severe liver disease and improve arthritis in affected patients, and 2) design a system for making blood collected from hemochromatosis donors available for transfusion into other patients. Patients 21 years and older with diagnosed hemochromatosis or very high iron levels suggesting possible hemochromatosis may be eligible for this study. Candidates will have a history, physical evaluation, review of medical records and blood tests, and complete a symptoms questionnaire. Participants will have the following procedures: - Phlebotomy therapy every 1 to 2 weeks, depending on iron levels - Blood sample collection for blood cell counts and iron studies at every phlebotomy session - Blood sample collection (about 2 tablespoons) every 1 to 2 weeks after iron stores have been depleted - Phlebotomy every 8 to 12 weeks after iron stores are used up to prevent re-build up of excess iron With each blood donation that will be made available for transfusion to other patients, participants will answer the same health history screening questions and undergo the same blood tests given to all regular volunteer blood donors. These include screening for the HIV and hepatitis viruses and for syphilis. Patients who meet height and weight requirements may be asked to consider "double red cell" donations using apheresis. In this procedure, whole blood is collected through a needle placed in an arm vein, similar to routine phlebotomy. The blood then circulates through a machine that separates it into its components. The red cells are removed and the rest of the blood is returned to the body, either through the same needle or through a second needle in the other arm. Patients who have very high iron levels or an enlarged liver will be offered evaluation by the NIH Liver Service. Those judged to be at increased risk for cirrhosis may be advised to undergo a liver biopsy. If cirrhosis is found, the patient will be asked to consider a repeat biopsy after 3 to 5 years of continuous iron depletion to see if scarring has improved. Patients with arthritis will be offered evaluation by the NIH Arthritis Service and, depending on symptoms, may be advised to have X-ray studies or a joint biopsy. Study Type: Observational
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Contact(s): Maryland; Warren G. Magnuson Clinical Center (CC), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00007150 ·
Deferoxamine for the Treatment of Hemochromatosis Condition(s): Diabetes Mellitus; Heart Disease; Hemochromatosis; Thalassemia Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: When patients receive repeated blood transfusions the level of iron in the patient's blood can rise. When iron is processed in the body a protein known as hemosiderin can begin collecting in the organs. If too much hemosiderin collects in the organs they can begin to malfunction. This condition is called transfusional hemochromatosis. An organ of particular importance in transfusional hemochromatosis is the heart. Patients born with diseases requiring blood transfusions at birth begin to develop heart problems in their teens. These patients typically only live for 17 years. Adults that require transfusions can begin experiencing heart problems after 100-200 units of backed red blood cells. Deferoxamine (Desferal) is a drug that binds to iron and allows it to be excreted from the body. It is the only effective way to remove iron from patients who have been overloaded with iron because of multiple transfusions. Previous studies have lead researchers to believe that deferoxamine, when given as an injection under the skin (subcutaneous), can be delay or prevent heart complications. Researchers plan to continue studying patients receiving deferoxamine as treatment for the prevention of heart complications associated with repeated blood transfusions. In this study researchers will attempt; 1)To determine if deferoxamine, given regularly, can indefinitely prevent the heart, liver, and endocrine complications associated with transfusional hemochromatosis 2)To determine whether heart disease caused by transfusional hemochromatosis can be reversed by intensive treatment with deferoxamine. Study Type: Observational Contact(s): Maryland; National Heart, Lung and Blood Institute (NHLBI), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010
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Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001203 ·
Hemochromatosis--Genetic Prevalence and Penetrance Condition(s): Blood Disease; Hemochromatosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To examine the cost effectiveness of hereditary hemochromatosis (HH) screening in primary care. Study Type: Epidemiology, Genetic Epidemiology Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006312
·
Evaluation of Subcutaneous Desferrioxamine as Treatment for Transfusional Hemochromatosis Condition(s): Anemia (Iron-Loading); beta-Thalassemia; Hematologic Diseases; Hemoglobinopathies; Thalassemia; Iron overload; Hemochromatosis Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine whether deferoxamine prevented the complications of transfusional iron overload. Phase(s): Phase II Study Type: Treatment Contact(s):. Study chairs or principal investigators: Young, Neal, Principal Investigator; Laboratory of Hematology, NHLBI Bethesda, Maryland, United States Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00000595
·
Hemochromatosis and Iron Overload Screening Study (HEIRS) Condition(s): Blood Disease; Hemochromatosis; Iron overload Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the prevalence, genetic and environmental determinants, and potential clinical, personal, and societal impact of iron overload and hereditary hemochromatosis, in a multicenter, multiethnic, primary care-based sample of 100,000 adults. The
Clinical Trials 55
study is conducted by the Division of Epidemiology and Clinical Applications of the NHLBI, the Division of Blood Diseases and Resources of the NHLBI, and the Ethical, Legal, and Social Implications (ELSI) Research Program of the NHGRI. Study Type: Genetic Epidemiology, Epidemiology Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005541 ·
Statistical Basis for Hemochromatosis Screening Condition(s): Blood Disease; Hemochromatosis Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine optimal values for transferrin saturation for use in population screening for hereditary hemochromatosis. Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005559
Benefits and Risks
18
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 for hemochromatosis. 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.
18 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.
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·
People who take part in trials contribute to scientific discoveries that may help other people with hemochromatosis. 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.
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.
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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.
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.
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What 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 for hemochromatosis? 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 conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with
Clinical Trials 59
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 “hemochromatosis” (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 diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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
·
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: Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Biliary: Pertaining to the bile, to the bile ducts, or to the gallbladder. [EU] Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Chronic: Persisting over a long period of time. [EU] 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] Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the form of its mesylate. [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
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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] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hepatitis: Inflammation of the liver. [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] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] 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] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Syphilis: A contagious venereal disease caused by the spirochete treponema pallidum. [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] Transfusion: The introduction of whole blood or blood component directly into the blood stream. [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]
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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 hemochromatosis. 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 hemochromatosis. In Part II, as in Part I, our objective is not to interpret the latest advances on hemochromatosis 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 hemochromatosis is suggested.
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CHAPTER 4. STUDIES ON HEMOCHROMATOSIS Overview Every year, academic studies are published on hemochromatosis or related conditions. 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 hemochromatosis. 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 hemochromatosis 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 hemochromatosis, 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 “hemochromatosis” (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: ·
Hemochromatosis: Diagnosis and Management Source: Gastroenterology 120(3): 718-725. February 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: Hereditary hemochromatosis (HH) is a common inherited disorder of iron metabolism that is characterized by increased gastrointestinal iron absorption with subsequent tissue iron deposition. This article reviews the diagnosis and management of HH. Although the autosomal recessive inheritance pattern of HH has been recognized for more than 25 years, identification of the responsible gene (HFE) did not happen until 1996. The identification of HFE has established the foundation for a better understanding of the molecular and cellular biology of iron homeostasis (balance in the body) and its altered regulation in people with HH. Additionally, the ability to accurately diagnose iron overload disorders has been strengthened, family screening has been improved, and evaluation of patients with other forms of liver disease complicated by moderate to severe iron overload is now possible. The author notes that the role of HFE testing in generalized population screening for HH is still in the process of being determined. The author stresses the importance of distinguishing HH from other syndromes of iron overload. Several symptoms (e.g., fatigue, malaise, abdominal pain, arthralgias, and impotence) and clinical findings (e.g., hepatomegaly, abnormal liver enzymes, skin pigmentation, diabetes, and cardiomegaly) have been identified in patients with fully established HH, and all physicians should be aware of these symptoms and findings. Many patients with HH have abnormal serum iron values before the development of any significant symptoms or clinical findings, and liver biopsy is less important in these patients. 2 figures. 3 tables. 59 references.
·
Diagnosis and Management of Hemochromatosis Source: Hepatology. 33(5): 1321-1328. May 2001.
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Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Hereditary hemochromatosis (HH) is a disorder characterized by iron accumulation in the body's organs; if left untreated, iron overload can result in organ damage. This article presents the AASLD (American Association for the Study of Liver Diseases) Practice Guidelines for the diagnosis and management of hemochromatosis. These guidelines provide data supported, peer reviewed recommendations for the care of patients with hemochromatosis. HH is one of the few genetic disorders in which phenotypic manifestations (organ damage) are delayed to adult life. However, sensitive and specific phenotypic and genotypic testing now allows diagnosis of HH while it is still a disorder of iron metabolism and before it results in end organ damage. Five recommendations are provided: undertake initial screening (by measurement of transferrin saturation after an overnight fast) of individuals with suspected iron overload and those over the age of 20 years who are first degree relatives of known cases of HH; perform genotyping to detect HFE mutations on all individuals who have abnormal iron studies; use liver biopsy in patients with suspected HH when documentation of hepatic iron concentration (HIC) and the stage of fibrosis is necessary or to rule out other causes of liver disease; undertake regular phlebotomies on all patients with HH who have evidence of iron overload, until iron stores are depleted; and treat secondary iron overload based on the underlying cause. The practical clinical guidelines provided in this article offer a cost effective, preemptive diagnostic approach whereby early identification of individuals at risk and initiation of life saving phlebotomy therapy in the presymptomatic stage of the disorder are facilitated. The article includes an algorithm for patient care management. 1 figure. 6 tables. 50 references. ·
Genetic Testing in Hemochromatosis Source: Practical Gastroenterology. 25(9): 44, 47-48, 50, 52, 54, 56. September 2001. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: Hereditary hemochromatosis (HH) is an inherited disorder in which the regulation of intestinal iron absorption is lost. Over several decades, iron accumulates and damages multiple organs such as the liver, pancreas, and heart. The identification of the gene responsible for HH (called HFE) has placed this disorder on the cutting edge of molecular medicine. Although this discovery has led to many advances in the understanding of the genetics, pathophysiology and clinical
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consequences of HH, many questions remain. This article reviews genetic testing in HH. The authors stresses that appropriate management of HH in the modern era requires gastroenterologists and hepatologists (liver specialists) to have an understanding not only of the medical aspects of HH but also of the issues involved in genetic testing. Before embarking on genetic testing, a physician must be willing and able to manage the implications of genetic testing. Despite a normal life expectancy when diagnosed before the development of cirrhosis or diabetes, insurance discrimination remains a concern. Patient confusion about the interpretation of results is common, as are ethical considerations such as the disclosure of positive results to family members. The author also comments on some unresolved issues in HH, in the areas of liver transplantation, hepatitis C, cardiovascular disease, and diabetes mellitus. An algorithm for the diagnosis of HH using genetic testing is provided. 2 figures. 3 tables. 29 references. ·
HFE-Associated Hereditary Hemochromatosis Source: Canadian Journal of Gastroenterology. 14(2): 121-125. February 2000. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail:
[email protected]. Summary: This article reviews the current thinking on hereditary hemochromatosis, a common inherited disorder of iron metabolism. Screening studies indicate that there is a prevalence of one in 200 to 400, depending on the population studied, and a carrier rate of about 1 in 7 to 1 in 10. The gene for hereditary hemochromatosis (HFE) was identified in 1996 and two candidate mutations; the C282Y mutation has been shown to be responsible for the majority of the hereditary hemochromatosis cases worldwide. The gene discovery has led to rapid advances in the field of iron metabolism. Although the basic defect is still not fully understood, much is known about the sequence of events leading to iron overload. The authors contend that hereditary hemochromatosis is a major candidate for population screening and meets the screening criteria of the World Health Organization (WHO). It is one of the most prevalent genetic diseases in white populations, and, importantly, early diagnosis and simple effective treatment allow normal life expectancy. The authors conclude that the discovery of the HFE gene and the frequency of the single C282Y mutation as a cause of most cases of hereditary hemochromatosis allow the possibility of widespread genetic testing. However, the logistics and the psychological and social consequence of this, coupled with incomplete expression of the genotype, necessitate
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further studies before population screening can be justified. 1 figure. 57 references. ·
Hereditary Hemochromatosis Source: Physician Assistant. p. 31-40, 43-44. February 1999. Contact: Available from Springhouse Corporation. Physician Assistant, P.O. Box 908, Springhouse, PA 19477. (215) 646-8700. Fax (215) 646-4399. Summary: This continuing education article familiarizes physician assistants with hereditary hemochromatosis (HHC), one of the most common genetic disorders in the United States. HHC is an autosomal recessive condition associated with primary overabsorption of iron from the gastrointestinal tract. It may cause lifelong excessive iron absorption and accumulation and serious health effects including arthritis, cirrhosis, diabetes, impotence, myocardial infarction, and death. HHC is often considered primarily a disease of European men. However, iron overloading occurs in all ethnic groups. HHC eventually causes serious illness and death if untreated. Complications can be avoided by routine screening before clinical symptoms develop. HHC is effectively treated by the early use of therapeutic phlebotomy. The cornerstone of screening is measurement of serum transferrin saturation and the serum ferritin level. A DNA based test for the hemochromatosis gene is commercially available, but its place in the diagnosis of HHC is still being evaluated. Appended to the article is a study guide and a posttest for earning continuing medical education (CME) credits. 4 figures. 1 table. 22 references.
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Detecting Hereditary Hemochromatosis Source: Nurse Practitioner. 25(7): 64, 69, 73-74, 76. July 2000. Contact: Available from Nurse Practitioner. Circulation Department, P.O. Box 5053, Brentwood, TN 37024-5053. (800) 490-6580. Fax (615) 377-0525. Summary: This article reviews the diagnosis of hereditary hemochromatosis (HH), the most commonly inherited autosomal recessive disorder. Hemochromatosis is a current or potential progression of abnormally high accumulations of iron in the liver. If left untreated, the condition can lead to chronic or irreversible hepatic (liver) fibrosis, cirrhosis (scarring), hepatocellular carcinoma (liver cancer), arthritis, and organ failure. Common signs and symptoms seen in the primary care setting include fatigue, weakness, abdominal pain, palpitations, skin pigmentation (coloring) changes, and arthropathy, but any symptom associated with organ damage may be reported. Because prompt intervention can cease or reverse the debilitating effects of iron
70 Hemochromatosis
overload, prompt disease diagnosis and treatments are imperative. The author notes that often an HH diagnosis is delayed in asymptomatic patients or patients with vague complaints of fatigue and arthropathy. The goal is to identify patients prior to symptom onset and organ damage; recent gene typing studies have made this a possibility. Early manifestations of HH include vague symptoms of weakness, fatigue, weight loss, skin pigmentation changes, abdominal pain, loss of libido, and diabetes mellitus symptoms. Advanced physical signs include liver and spleen enlargement, skin pigmentation changes, spider angiomas, arthropathy, ascites, cardiac arrhythmias, heart failure, testicular atrophy, and jaundice. Because HH is an inherited disorder, the family history should be specific and complete. Routine assays are the most commonly used testing. A definitive diagnosis is made via liver biopsy. Patients with HH should be instructed to increase their dietary protein, as hemoglobin is 96 percent protein; folic acid of 1 mg daily will assist in hemoglobin formation. Vitamin or mineral supplements that contain iron should be avoided. And because alcohol is a hepatotoxin and wine contains iron, alcohol should be avoided. 1 figure. 31 references. ·
Molecular Medicine and Hemochromatosis: At the Crossroads. [Summary of a Conference Sponsored by the Division of Digestive Diseases and Nutrition and the Division of Kidney, Urology, and Hematology of the Source: Gastroenterology. 116(1): 193-207. January 1999. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Hereditary hemochromatosis is a common inherited disorder of iron metabolism marked by progressive iron loading of parenchymal cells in the liver, pancreas, heart, and other organs and ultimately resulting in organ failure. This article presents a summary of a conference on molecular medicine and hemochromatosis held in May 1998 in Bethesda, Maryland, and sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The article reports on the discovery of the hemochromatosis gene (HFE), noting that the molecular tests for identifying mutations in HFE provide a better means for diagnosis, family testing, and population screening. Further, characterization of the HFE gene may provide insights into the regulation of normal iron absorption and metabolism. Identification of this gene is also likely to provide clues to the mechanisms of cell injury by iron and its role in modulating or creating cell injury in other diseases, such as alcoholic liver disease, nonalcoholic steatohepatitis, hepatitis C, and porphyria cutanea tarda. The conference was held to review the current
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understanding of hemochromatosis, the HFE gene, iron absorption, and metabolism, and to describe how these advances affect the diagnosis and management of this disease. 5 figures. 5 tables. 101 references. ·
HFE Genotype in Patients with Hemochromatosis and Other Liver Diseases Source: Annals of Internal Medicine. 130(12): 953-962. June 15, 1999. Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org. Summary: Hereditary hemochromatosis (HH) is a common inherited disorder of iron metabolism. The gene HFE, which contains two missense mutations (C282Y and H63D), was recently identified. This article reports on a study undertaken to determine how HFE genotyping for the C282Y and H63D mutations contributes to the diagnosis of hemochromatosis and to determine the prevalence of HFE mutations in a group of patients with liver disease. The cross sectional study featured 66 patients with HH and 132 referred patients with other liver diseases. Of the 66 patients with HH diagnosed on the basis of serum iron studies and liver biopsy findings, 60 patients (91 percent) were C282Y homozygotes, 2 patients (3 percent) were compound heterozygotes, 1 patient (1.5 percent) was a C282Y heterozygote, 2 patients (3 percent) were H63D heterozygotes, and 1 patient (1.5 percent) was negative for both mutations. Of the 132 patients with liver disease, 6 patients (5 percent) were C282Y homozygotes, 8 patients (6 percent) were compound heterozygotes, and 87 patients (66 percent) were negative for both mutations. All 66 C282Y homozygotes had an elevated hepatic iron concentration, and 65 of the 66 patients (98 percent) had a transferrin saturation of at least 45 percent. Ten of the 66 patients (15 percent) had a hepatic iron index less than 1.9 mmol/kg per year; hemochromatosis was not suspected in 6 of the 10 patients before genotying. Cirrhosis (scarring) or substantial hepatic fibrosis was not seen in any of the 19 patients younger than 40 years of age who were homozygous for the C282Y mutation. The authors conclude that while all 66 patients homozygous for the C282Y mutation of HFE had an elevated hepatic iron concentration, approximately 15 percent of these patients did not meet a previous diagnostic criterion for hemochromatosis. Determination of HFE genotype is clinically useful in patients with liver disease and suspected iron overload and may lead to identification of otherwise unsuspected C282Y homozygotes. 2 figures. 4 tables. 32 references.
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Hemochromatosis: Advances in Molecular Genetics and Clinical Diagnosis Source: Journal of Clinical Gastroenterology. 27(1): 41-46. July 1998. Contact: Available from Lippincott-Raven Publishers. P.O. Box 1550, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Summary: Hereditary hemochromatosis (HH) is a human leukocyte antigen-linked inherited disease that is characterized by an inappropriately high absorption of iron by the gastrointestinal mucosa. This article reviews the advances in molecular genetics and clinical diagnosis of HH. The spectrum of disease presentation is changing, with more and more patients now being identified before they present with symptoms of the complications of iron overload. A candidate gene for HH, called HFE, was identified in 1996, and a test for the gene is commercially available. The authors propose an algorithm for the evaluation of patients for HH. Early diagnosis and appropriate therapy can prevent significant morbidity and mortality associated with the development of end-organ complications of HH and treatment is simple, inexpensive, safe, and effective. Patients should be advised to undergo weekly phlebotomy of 500 ml of whole blood (equivalent to approximately 200 to 250 mg of iron). Once initial therapeutic phlebotomy has been completed, patients usually require maintenance phlebotomy to prevent re-accumulation of iron (most patients require one unit of blood to be removed every 2 to 3 months). 2 figures. 1 table. 30 references. (AA-M).
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Hereditary Hemochromatosis: Gene Discovery and Its Implications for Population-Based Screening Source: JAMA. Journal of American Medical Association. 280(2): 172-178. July 8, 1998. Summary: This article reports the results of an expert panel convened to evaluate the role of genetic testing in screening for hereditary hemochromatosis to help guide clinicians, policymakers, and researchers. The panel, whose members had expertise in epidemiology, genetics, hepatology, iron overload disorders, molecular biology, public health, and the ethical, legal, and social implications surrounding the discovery and use of genetic information, convened in March 1997 by the Centers for Disease Control and Prevention (CDC) and the National Human Genome Research Institute (NHGRI). The group reviewed the clinical presentation, natural history, and genetics of hemochromatosis, including current data on the candidate gene that causes it, and on the ethical and health policy implications of genetic testing for this disorder. Genetic
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testing is not recommended at this time in population-based screening for hereditary hemochromatosis, because of uncertainties about prevalence and penetrance of such mutations and the optimal care of asymptomatic people carrying HFE mutations. In addition, use of a genetic screening test raises concerns over possible stigmatization and discrimination. Tests for HFE mutations may play a role in confirming the diagnosis of hereditary hemochromatosis in persons with elevated serum iron measures, but even this use is limited by uncertainty about genotype-phenotype correlations. 3 tables. 61 references. (AA-M). ·
Hemochromatosis: Its Detection Is Not Ironclad Source: Gastroenterology Nursing. 21(5): 210-212. September-October 1998. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (410) 528-8555. Summary: This article familiarizes gastroenterology or endoscopy nurses with hemochromatosis. Hereditary hemochromatosis (HHC) results in an inappropriate increase in iron absorption from the intestines. This increased absorption occurs throughout the life of the affected individual and is silent in its early stages. The author reviews the diagnostic tests used to confirm HHC. Because the liver is the primary organ involved, the prognosis is directly dependent on the toxic damage the liver sustains. The presence of cirrhosis (liver scarring) and the amount and duration of iron excess will determine the outcome of most of the complications of HHC, including liver cancer. The author discusses how other organs are affected by iron overload and how they exhibit signs of toxicity. Treatment is aimed at removing excess iron stores to prevent tissue damage and should begin as soon as a diagnosis is made. Phlebotomy (blood removal) is necessary for an extended period of time, often weekly or biweekly, since each unit removes 200 to 250 mg of iron. The patient's signs and symptoms are monitored during treatment, and the hematocrit is checked weekly. The goal of therapy is to return to normal iron stores without too great an impact on the patient's quality of life. Patient education efforts must focus on the importance of continued followup treatment. The article concludes with information about general health education and promotion. 5 references.
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Clinical Features of Genetic Hemochromatosis in Women Compared with Men Source: Annals of Internal Medicine. 127(2): 105-110. July 15, 1997.
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Summary: The clinical expression of hemochromatosis is presumed to be less frequent and less severe in women than in men because of the iron loss associated with menses and pregnancy. This article reports on research undertaken to test this hypothesis by comparing the clinical features of women who have genetic hemochromatosis with those of men who have the disease. The cross-sectional study measured age at presentation, clinical symptoms, transferrin saturation, serum ferritin level, hepatic iron concentration, and hepatic iron index in 176 women and 176 men with hemochromatosis, matched for year of birth. Hepatic iron concentration and hepatic iron index were similar in men and women. Women had lower serum ferritin levels than men did, and less iron removed by venesections. Compared with women, men had a higher incidence of cirrhosis and diabetes. Compared with men, women had a higher incidence of fatigue and pigmentation. Hepatic iron concentration and hepatic iron index were greater in women in whom menstruation had stopped before 50 years of age. The authors conclude that homozygous hemochromatosis is slightly underexpressed in women, although severe disease can be present, including cirrhosis. The clinical features in women are different than those seen in men. Women with genetic hemochromatosis can and do develop progressive iron overload and clinical symptoms despite menstruation and pregnancy. Recognizing the nonspecific nature of presenting symptoms in women is essential for early diagnosis and treatment. 4 tables. 24 references. (AA-M). ·
Hemochromatosis: When Your Blood Has Too Much Iron Source: American Family Physician. 53(8): 2631-2632. June 1996. Summary: This patient information fact sheet provides readers with basic information about hemochromatosis, a blood disease that causes the body to absorb too much iron. This extra iron collects in different parts of the body and may cause damage to the heart, liver, pancreas, and joints. The fact sheet, written in nontechnical language, covers symptoms, diagnostic tests, treatment options, dietary recommendations, and prevention of long-term complications. The fact sheet concludes with the address and telephone number of the Hemochromatosis Foundation. The fact sheet is designed to be photocopied and distributed by health care professionals to their patients.
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Management of Hemochromatosis Source: Annals of Internal Medicine. 129(11): 932-938. December 1, 1998. Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org.
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Summary: This article reviews how the complications of iron overload in hemochromatosis (an inherited propensity to absorb excess iron) can be avoided by early diagnosis and appropriate management. Therapeutic phlebotomy (blood removal) is used to remove excess iron and maintain low normal body iron stores, and it should be initiated in men with serum ferritin levels of 300 micrograms per liter or more, and in women with serum ferritin levels of 200 micrograms per liter or more, regardless of the presence or absence of symptoms. Typically, therapeutic phlebotomy consists of removal of 1 unit of blood weekly until the serum feritin level is 10 to 20 micrograms per liter; and maintenance of the serum ferritin level at 50 micrograms per liter or less thereafter by periodic removal of blood. Hyperferritinemia (too much iron in the blood) attributable to iron overload is resolved by therapeutic phlebotomy. When applied before iron overload becomes severe, this treatment also prevents complications of iron overload, including hepatic cirrhosis (liver scarring), primary liver cancer, diabetes mellitus, hypogonadotrophic hypogonadism, joint disease, and cardiomyopathy. In patients with established iron overload disease, weakness, fatigue, increased hepatic enzyme concentrations, right upper quadrant pain, and hyperpigmentation are often substantially alleviated by therapeutic phlebotomy. Patients with liver disease, joint disease, diabetes mellitus and other endocrine abnormalities, and cardiac abnormalities often require additional, specific management. Dietary management of hemochromatosis includes avoidance of medicinal iron, mineral supplements, excess vitamin C, and uncooked seafoods. This can reduce the rate of iron reaccumulation, reduce retention of nonferrous metals, and help reduce complications of liver disease, diabetes mellitus, and Vibrio infection. This comprehensive approach to the management of hemochromatosis can decrease the frequency and severity of iron overload, improve quality of life, and increase longevity. 4 tables. 86 references.
Federally-Funded Research on Hemochromatosis The U.S. Government supports a variety of research studies relating to hemochromatosis and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.19 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 19
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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 hemochromatosis and related conditions. 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 hemochromatosis and related conditions. 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 hemochromatosis: ·
Project Title: Cloning of the Hemochromatosis Locus Principal Investigator & Institution: Bowlus, Christopher L.; Internal Medicine; University of California Davis Davis, Ca 95616 Timing: Fiscal Year 2000; Project Start 9-AUG-1996; Project End 0-JUN2001 Summary: Hemochromatosis is a common genetic disorder of iron metabolism that leads to cirrhosis, diabetes and cardiomyopathy. Early diagnosis and treatment with phlebotomy prevents these sequelae. Many investigators have advocated screening of the population with serum iron studies to identify presymptomatic individuals. Liver biopsy, however, is necessary to make the diagnosis. Identification of the gene would permit definitive diagnosis without liver biopsy. The disease is inherited in an autosomal recessive pattern and the gene has been localized near the HLA region on the short arm of chromosome 6. This grant application is a proposal to identify and map hemochromatosis candidate genes from the distal region of the hemochromatosis critical region. Using genomic clones such as Yeast Artificial Chromosomes (YACs), genes will be identified by cDNA hybridization selection. These genes as well as polymorphic markers will be hybridized back to digested YACs in order to generate a transcription map of the region. Based on genetic mapping of the hemochromatosis locus, candidate genes can then be analyzed for mutations in affected individuals, eventually leading to the identification of the gene responsible for hemochromatosis.
and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Mechanisms
Diabetes
in
Hemochromatosis:
Prevalence
and
Principal Investigator & Institution: Mcclain, Donald A.; Professor/Director; Internal Medicine; University of Utah 110 Park Bldg Salt Lake City, Ut 84112 Timing: Fiscal Year 2002; Project Start 1-MAR-2002; Project End 1-OCT2006 Summary: Although the hemochromatosis gene (HFE) has been identified there is little information about the diabetes that often accompanies the disease. We hypothesize nondiabetic homozygotes for mutations in HFE will exhibit a defect in insulin secretion as iron overload develops. This notion is supported by preliminary data obtained in HFE mutant mice. The insulin deficiency will progress to type 2 diabetes only if insulin resistance also occurs, either from cirrhosis or inheritance of type 2 diabetes genes. Insulin resistance from cirrhosis is hypothesized to result from excess carbohydrate delivery to peripheral tissues, resulting in excess hexosamine generation, an established cause of insulin resistance. Our specific aims are to: 1. Determine the prevalence of impaired glucose intolerance (IGT) and diabetes in clinically unselected individuals with hemochromatosis by oral glucose tolerance criteria. 2. Determine if a defect in insulin secretion exists in nondiabetic homozygotes with or without iron overload. This will be accomplished using the frequently sampled intravenous glucose tolerance test (FSIVGTT) with insulin levels. Reversibility of the defect will be examined after subjects have undergone phlebotomy. The hypothesis will be verified in studies of isolated islets from mice carrying disrupted or mutant HFE genes. 3. Using animal models, determine if diabetes in hemochromatosis results only when insulin resistance is superimposed on an iron- mediated defect in insulin secretion. 4. Determine the sequence and relative contributions of insulin resistance and hepatic glucose production (HGP) in the evolution of diabetes in human hemochromatosis. Insulin resistance and HGP will be quantified by the hyperinsulinemic euglycemic clamp and stable isotope techniques in subjects with hemochromatosis who have normal or IGT, with or without hepatic involvement. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
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Project Title: Hemochromatosis Registry Principal Investigator & Institution: Kowdley, Kris V.; Associate Professor; Medicine; University of Washington 3935 University Way Ne Seattle, Wa 98195 Timing: Fiscal Year 2000; Project Start 1-MAR-1999; Project End 8-FEB2002 Summary: 1. How the proposed research will contribute to meeting the goals and objectives of the PA: This study proposal will meet several of the goals and objectives of the PA. The core of the project is aimed at exploring the application of a new laboratory method (DNA-based genotyping for the newly discovered hemochromatosis gene) in identifying patients with end-stage liver disease and hereditary hemochromatosis from other patients with end- stage liver disease and hepatic iron overload. Genetic testing for this mutation is already clinically available and being used, but there are limited studies examining the utility and role of genetic testing and clinical practice. The current application will help bring this new laboratory into the clinical setting in an immediate way. The current study will also serve as a pilot study to examine the impact of iron overload on outcome after liver transplantation If increased hepatic iron overload is found to be a predictor of poor outcome after liver transplantation, then the findings of the trial will serve as the basis for a randomized, cooperative group clinical trial of iron reduction prior to liver transplantation. Iron overload is influenced by diet and nutrition, which is described as an area of special interest for this PA. Therefore, this clinical trial meets all the stated goals of the PA. 2. Specific Aims To determine survival and cause of death in patients with hepatic iron overload undergoing liver transplantation who are homozygous for the C282Y mutation, which is present in most patients with hereditary hemochromatosis. To determine survival and cause of death in patients with hepatic iron overload undergoing liver transplantation who lack the C282Y mutation. To examine the predictive value of serum transferrin-iron saturation and serum ferritin for hepatic iron overload in end-stage liver disease. 3. Rationale for selection of the general methods and approaches to accomplish the specific aims: Although hepatic iron overload is common, most liver transplant centers do not have enough patients with well characterized iron overload and particularly patients with genetically confirmed hereditary hemochromatosis at their individual center to study outcome after liver transplantation in a meaningful. A multi-center study of this type is therefor necessary to enroll an adequate number of patients and achieve an adequate sample size to definitively test the hypotheses and address the specific aims. We have chosen a prospective
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and retrospective study design intentionally. Subjects who are found to have significant hepatic iron overload at the time of transplant can be retrospectively entered into the study. Subjects with a known diagnosis of hereditary hemochromatosis as defined in the inclusion criteria can be entered prospectively or retrospectively. Subjects who are identified prospectively using serum transferrin-saturation or ferritin will be followed prospectively. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Mechanisms
Hemochromatosis--Epidemiology
and
Molecular
Principal Investigator & Institution: Beutler, Ernest N.; Chairman; Scripps Research Institute 10550 N Torrey Pines Rd San Diego, Ca 92037 Timing: Fiscal Year 2000; Project Start 8-APR-1998; Project End 1-MAR2003 Summary: Hereditary hemochromatosis, a disease characterized by excess iron absorption leading to diabetes, cardiomyopathy, cirrhosis, and arthropathies, is arguably the most common clinically important genetic disorder of Europeans. Recently an HLA Class 1 gene, HLA-H was implicated in the etiology of this disease. Over 80 percent of hemochromatosis patients are homozygous for a C282Y mutation. Compound heterozygotes for C282Y and H62D appear to have an increased incidence of the disease. Sixty-thousand adults undergoing health care screening in the Kaiser-Permanente system will be screened, determining serum iron, iron binding capacity, ferritin, and mutations in HLA-H. Patients classified as having hemochromatosis will be phlebotomized to remove excess iron and to measure iron stores. This will establish the relationship between genotype, age, sex and clinical state, and size of iron stores, and provide data that can be used to guide programs screening for hemochromatosis. The hypotheses that heterozygotes are more susceptible to cardiovascular disease and other disorders and that they are benefited by being less susceptible to iron deficiency anemia will be tested using the extensive Kaiser-Permanente database. Hemochromatosis mutations, other than those known, will be sought. The HLA-H gene product may function like other HLA class 1 genes, binding peptides and associating with proteins such as beta2 microglobulin, calreticulin, transporter associated with antigen processing (TAP) and tapascin. Alternatively, it may function as a signaling molecule, like the Fc receptor. Determining how the HLA-H gene product functions should provide insight into its role in maintaining iron homeostasis. This will be done by using immunoprecipitating HLAH containing complexes, determining HLA-H Fc receptor signaling
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properties and measuring the binding of peptides and other small molecules by HLA-H. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Hereditary Hemochromatosis Principal Investigator & Institution: Kushner, James P.; Professor of Medicine; University of Utah 110 Park Bldg Salt Lake City, Ut 84112 Timing: Fiscal Year 2001 Summary: These investigators have ascertained one of the largest collection of pedigrees with hereditary iron overload. Over 300 families have been ascertained. Extensive phenotypic analyses have been completed and genotyping studies have demonstrated that approximately 90% of the pedigrees have iron overload associated with homozygosity for the cysteine 282 tyrosine mutation of the HFE gene. The current focus is to test the hypothesis that hemochromatosis is a disease caused by malregulated cellular iron export. Epstein-Barr Virus (EBV) transformed lymphocytes have been generated from at least one member of every pedigree and an in vitro system has been devised to analyze cellular iron export. The human macrophage model of regulated iron export (based on animal models of genetic iron overload) is also being developed utilizing macrophages isolated from bone marrow aspirations of patients with hemochromatosis associated with the ancestral HFE mutation and those with other mutations of the HFE locus or no HFE associated mutations. These in vitro cell culture models are in developmental state at the present. A large clinical phenotyping study has been completed and demonstrated that approximately half of the patients with hemochromatosis developed disease related morbidity. A manuscript has been submitted describing this study and provided ample documentation that morbidity is a common consequence of homozygosity for hemochromatosis gene mutations, thus justifying large-scale population screening studies. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
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Project Title: Mucosal Iron Uptake and Transfer in Hemochromatosis Principal Investigator & Institution: Janghorbani, Morteza; Biochemanalysis Corporation 2201 W Campbell Park Dr Chicago, Il 60612 Timing: Fiscal Year 1999; Project Start 0-SEP-1999; Project End 9-SEP-2002 Summary: The long-term objectives of this project are to develop a noninvasive and accurate method for the measurement of mucosal uptake and transfer of iron labeled with a non-radioactive (stable) isotope for
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general-purpose use with hereditary hemochromatosis (HHC) patients. The method is based on ingesting a single gelatin capsule containing labeled (58Fe) ferrous sulfate, the non-absorbable marker dysprosium chloride (DyCl3), and the visual marker FD&C#1 (brilliant blue) followed by the measurement of initial mucosal uptake by analysis of a small portion of the first visually marked stool for labeled iron and Dy. Wholebody retention of absorbed labeled iron is measured from either incorporation of the ingested isotope in circulating red cells, or measured of the ratio for 58Fe/57Fe in plasma 1-3 hours after injection of a small dose of 57 Fe- transferrin concurrently with the oral dose. The specific aims of the proposed phase-I research are to demonstrate the feasibility of this approach in ten patients with uncomplicated iron-deficiency. PROPOSED COMMERCIAL APPLICATIONS: This research will lead to a method for routine use in hemochromatosis patients. It has applications in confirming diagnosis, predicting prognosis, and many aspects of hemochromatosis research. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: SFT Function and Regulation in Hemochromatosis Principal Investigator & Institution: Wessling-Resnick, Marianne; Professor; Nutrition; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2000; Project Start 5-SEP-1999; Project End 1-AUG2004 Summary: Hereditary hemochromatosis is a genetic disorder that promotes increased intestinal absorption and progressive tissue deposition of iron resulting in cirrhosis of the liver, hepatic carcinoma, congestive heart failure, endocrinopathies and premature death. It is estimated that 1 in 200-to-400 people in the US are homozygous for this disease which is the most common defective genetic trait known in humans, more prevalent than cystic fibrosis, phenylketonuria and muscular dystrophy combined. Iron assimilation is a tightly regulated process that is limited to prevent harmful effects due to overload of this toxic metal and therefore a reciprocal relationship exists between body iron stores and dietary iron absorption, although the molecular basis for ion homeostasis remains unknown. Many studies of the molecular basis for hemochromatosis have evaluated the expression of factors involved in iron metabolism , including transferrin, transferrin receptor, ferritin and IRPs, but strong evidence to support their abnormal regulation in this disease is lacking. We recently identified SFT (Stimulator of Fe Transport) as a facilitator of non-transferrin-bound iron uptake. Our preliminary results demonstrate that SFT expression is down- regulated
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at both the mRNA and protein level in response to iron-loading. However, in the course of these studies, we made the significant discovery that SFT mRNA is 5-fold higher in liver from hemochromatosis patients despite the deposition of iron that occurs in this tissue. Thus, our working hypothesis is that malregulated expression of SFT contributes to the etiology of hemochromatosis. The proposed research will specifically evaluate our hypothesis through the following goals: 1) determination of SFT activity in iron transport by hepatocytes and intestinal enterocytes; 2) examination of interactions of interactions with the hemochromatosis protein Hfe that may modulate SFT expression and function in these cells; and 3) characterization of the mechanism that regulates SFT expression. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Functional Domains of the Transferrin Receptor Principal Investigator & Institution: Enns, Caroline A.; ; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2000 Summary: The goals of this project are to understand how the interactions between the transferring receptor (TfR) and transferrin (Tf) and the TfR and the hemochromatosis gene product regulate iron transport into cells. The long term goal of my research is to understand the structure and function of this important receptor. The uptake of iron into mammalian cells involves the binding of Tf to the TfR, followed by internalization of the receptor-Tf complex. Iron uptake is essential for cell division and as a result the TfR has been identified as a proliferation specific marker. It is present on rapidly dividing cells. The uptake of iron into the body and into cells is tightly controlled. Too little iron in mammals results in anemia and failure to thrive. Too much iron results in iron toxicity due to oxidative damage. Hereditary hemochromatosis is a disease of iron overload. Excess iron damages organs and results in liver failure, adult onset diabetes, arthritis and heart failure. It is the most common inherited disease in people of European descent affecting approximately 1 in 400 individuals. Recently the gene was identified and found to bind to the TfR. Key to understanding the regulation of iron uptake is understanding the interactions between the hemochromatosis gene product and between Tf and the TfR. The specific goals of this study application are: to map the interactions between these proteins; to determine how the TfR potentiates the release of iron in the endosome; to determine how the hemochromatosis gene product alters the interaction between Tf and the TfR; and finally to determine the limiting factors in the uptake of iron into cells.
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Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Iron Overload and Hereditary Hemochromotosis Study Principal Investigator & Institution: Acton, Ronald T.; Microbiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2000; Project Start 1-JAN-2000; Project End 0-JAN2005 Summary: The Iron Overload and Hereditary Hemochromatosis Study is an epidemiologic study of the prevalence, genetic and environmental determinants, and potential clinical, personal, and societal impact of iron overload and hereditary hemochromatosis in a multi-center, multi-ethnic, primary care-based sample of 100,000 adults. The information will be used to determine the feasibility and potential individual and public health benefits and risks of primary care-based screening and intervention for iron overload and hereditary hemochromatosis. The 100,000 participants will be recruited from five field centers for screening. Following the screening, a clinical examination will be conducted in selected individuals. The final component of the study is a family study which will use genome scanning and assessment of linkage to identify genetic variants related to the expression of iron overload and hereditary hemochromatosis disorders. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
E-Journals: PubMed Central20 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).21 Access to this growing archive of e-journals is free and unrestricted.22 To search, go to http://www.pubmedcentral.nih.gov/index.html#search, and type “hemochromatosis” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for hemochromatosis in the PubMed Central database: Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html. 21 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. 22 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. 20
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Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary hemochromatosis by Seppo Parkkila, Abdul Waheed, Robert S. Britton, Bruce R. Bacon, Xiao Yan Zhou, Shunji Tomatsu, Robert E. Fleming, and William S. Sly; 1997 November 25 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=24286
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Commentary:Hepcidin: A putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease by Robert E. Fleming and William S. Sly; 2001 July 17 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=37412
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Experimental hemochromatosis due to MHC class I HFE deficiency: Immune status and iron metabolism by Seiamak Bahram, Susan Gilfillan, Lukas C. Kuhn, Remy Moret, Johannes B. Schulze, Annette Lebeau, and Klaus Schumann; 1999 November 9 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=23944
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Hereditary hemochromatosis: Effects of C282Y and H63D mutations on association with [beta]2-microglobulin, intracellular processing, and cell surface expression of the HFE protein in COS-7 cells by Abdul Waheed, Seppo Parkkila, Xiao Yan Zhou, Shunji Tomatsu, Zenta Tsuchihashi, John N. Feder, Randall C. Schatzman, Robert S. Britton, Bruce R. Bacon, and William S. Sly; 1997 November 11 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=24956
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HFE gene knockout produces mouse model of hereditary hemochromatosis by Xiao Yan Zhou, Shunji Tomatsu, Robert E. Fleming, Seppo Parkkila, Abdul Waheed, Jinxing Jiang, Ying Fei, Elizabeth M. Brunt, David A. Ruddy, Cynthia E. Prass, Randall C. Schatzman, Rosemary O'Neill, Robert S. Britton, Bruce R. Bacon, and William S. Sly; 1998 March 3 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=19387
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Immunohistochemistry of HLA-H, the protein defective in patients with hereditary hemochromatosis, reveals unique pattern of expression in gastrointestinal tract by Seppo Parkkila, Abdul Waheed, Robert S. Britton, John N. Feder, Zenta Tsuchihashi, Randall C. Schatzman, Bruce R. Bacon, and William S. Sly; 1997 March 18 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=20123
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Increased p53 mutation load in nontumorous human liver of Wilson disease and hemochromatosis: Oxyradical overload diseases by S. Perwez Hussain, Kamran Raja, Paul A. Amstad, Mark Sawyer, Laura J. Trudel, Gerald N. Wogan, Lorne J. Hofseth, Peter G. Shields, Timothy R. Billiar, Christian Trautwein, Thomas Hohler, Peter R. Galle, David H. Phillips, Rodney Markin, Aizen J. Marrogi, and Curtis C. Harris; 2000 November 7 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=18839
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Mechanism of increased iron absorption in murine model of hereditary hemochromatosis: Increased duodenal expression of the iron transporter DMT1 by Robert E. Fleming, Mary C. Migas, XiaoYan Zhou, Jinxing Jiang, Robert S. Britton, Elizabeth M. Brunt, Shunji Tomatsu, Abdul Waheed, Bruce R. Bacon, and William S. Sly; 1999 March 16 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=15909
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Mouse strain differences determine severity of iron accumulation in Hfe knockout model of hereditary hemochromatosis by Robert E. Fleming, Christopher C. Holden, Shunji Tomatsu, Abdul Waheed, Elizabeth M. Brunt, Robert S. Britton, Bruce R. Bacon, Derry C. Roopenian, and William S. Sly; 2001 February 27 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=30203
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The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding by John N. Feder, David M. Penny, Alivelu Irrinki, Vince K. Lee, Jose A. Lebron, Nicole Watson, Zenta Tsuchihashi, Elliott Sigal, Pamela J. Bjorkman, and Randall C. Schatzman; 1998 February 17 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=19050
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Transferrin receptor 2: Continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis by Robert E. Fleming, Mary C. Migas, Christopher C. Holden, Abdul Waheed, Robert S. Britton, Shunji Tomatsu, Bruce R. Bacon, and William S. Sly; 2000 February 29 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=15780
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Transferrin receptor is negatively modulated by the hemochromatosis protein HFE: Implications for cellular iron homeostasis by Luisa SalterCid, Anders Brunmark, Yuanhao Li, Didier Leturcq, Per A. Peterson, Michael R. Jackson, and Young Yang; 1999 May 11 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=21877
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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine. 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.23 If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with hemochromatosis, simply go to the PubMed Web site at www.ncbi.nlm.nih.gov/pubmed. Type “hemochromatosis” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “hemochromatosis” (hyperlinks lead to article summaries): ·
Diabetic ketoacidosis and hypogonadotropic hypogonadism in association with transfusional hemochromatosis in a man with betathalassemia major. Author(s): Lu JY, Chang CC, Tsai HC, Lin KS, Tsang YM, Huang KM. Source: J Formos Med Assoc. 2001 July; 100(7): 492-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11579617&dopt=Abstract
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Hemochromatosis and dietary iron supplementation: implications from US mortality, morbidity, and health survey data. Author(s): Gable CB. Source: J Am Diet Assoc. 1992 February; 92(2): 208-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1737903&dopt=Abstract
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Turner's syndrome and hypogonadotrophic thalassemia major and hemochromatosis.
hypogonadism:
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.
23
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Author(s): Afonso Lopes L, Benador D, Wacker P, Wyss M, Sizonenko PC. Source: J Pediatr Endocrinol Metab. 1995 January-March; 8(1): 73-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7584702&dopt=Abstract
Vocabulary Builder 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] Arrhythmia: Any variation from the normal rhythm of the heart beat, including sinus arrhythmia, premature beat, heart block, atrial fibrillation, atrial flutter, pulsus alternans, and paroxysmal tachycardia. [EU] Arthralgia: Pain in a joint. [EU] Arthropathy: Any joint disease. [EU] Ascites: Effusion and accumulation of serous fluid in the abdominal cavity; called also abdominal or peritoneal dropsy, hydroperitonia, and hydrops abdominis. [EU] 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] Asymptomatic: Showing or causing no symptoms. [EU] 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] 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] Cardiomegaly: Cardiac hypertrophy. [EU]
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Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Confusion: Disturbed orientation in regard to time, place, or person, sometimes accompanied by disordered consciousness. [EU] Criterion: A standard by which something may be judged. [EU] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dysprosium: Dysprosium. An element of the rare earth family that has the atomic symbol Dy, atomic number 66, and atomic weight 162.50. Dysprosium is a silvery metal used primarily in the form of various salts. [NIH]
Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Endoscopy: Visual inspection of any cavity of the body by means of an endoscope. [EU] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] 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] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with
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graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hemosiderosis: Conditions in which there is a generalized increase in the iron stores of body tissues, particularly of liver and the reticuloendothelial system, without demonstrable tissue damage. The name refers to the presence of stainable iron in the tissue in the form of hemosiderin. [NIH] Hepatic: Pertaining to the liver. [EU] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatomegaly: Enlargement of the liver. [EU] Heterozygote: An individual having different alleles at one or more loci in homologous chromosome segments. [NIH] Homeostasis: A tendency to stability in the normal body states (internal environment) of the organism. It is achieved by a system of control mechanisms activated by negative feedback; e.g. a high level of carbon dioxide in extracellular fluid triggers increased pulmonary ventilation, which in turn causes a decrease in carbon dioxide concentration. [EU] Homozygote: identical. [NIH]
An individual in which both alleles at a given locus are
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] Hyperpigmentation: Excessive pigmentation of the skin, usually as a result of increased melanization of the epidermis rather than as a result of an increased number of melanocytes. Etiology is varied and the condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulindependent diabetes mellitus. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
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Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Malaise: A vague feeling of bodily discomfort. [EU] Menstruation: The cyclic, physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus; it is under hormonal control and normally recurs, usually at approximately four-week intervals, in the absence of pregnancy during the reproductive period (puberty through menopause) of the female of the human and a few species of primates. It is the culmination of the menstrual cycle. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Oral: Pertaining to the mouth, taken through or applied in the mouth, as an oral medication or an oral thermometer. [EU] Palpitation: A subjective sensation of an unduly rapid or irregular heart beat. [EU] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]
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] 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
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substance produced by secretion. [EU] 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] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Vibrio: A genus of vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH]
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CHAPTER 5. PATENTS ON HEMOCHROMATOSIS Overview You can learn about innovations relating to hemochromatosis 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.24 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 with hemochromatosis 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 with hemochromatosis. 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.
24Adapted
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 Hemochromatosis By performing a patent search focusing on hemochromatosis, 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 hemochromatosis: ·
Erythrocyte parameters in hemochromatosis Inventor(s): Barton; James C. (3828 Brook Hollow La., Birmingham, AL 35243), Bertoli; Luigi F. (26,2700 Arlington Ave. South, Birmingham, AL 35206), Rothenberg; Barry E. (149 12th St., Delmar, CA 92014) Assignee(s): none reported Patent Number: 6,268,217 Date filed: November 12, 1999 Abstract: The invention provides a method of diagnosing hemochromatosis or a predisposition thereto by detecting an increase in erythrocyte parameters such as mean corpuscular volume or mean corpuscular hemoglobin compared to normal individuals unaffected by hemochromatosis. Excerpt(s): Hemochromatosis is a common hereditary disorder that affects approximately 0.5% of persons of western European descent. In various populations, 60%-100% of cases are attributable to homozygosity for a missense mutation (cDNA nucleotide 845 G6A; C282Y) in HFE, a major histocompatibility class I gene on chromosome 6p. Some patients are compound heterozygotes for C282Y and another HFE allele (cDNA nucleotide 187 C6G; H63D), or are H63D homozygotes. However, C282Y and H63D are not known to occur on the same chromosome. Other persons with a hemochromatosis phenotype are homozygous for H63D, are heterozygous for C282Y or H63D, or are presumed to have an HFE or other mutation that is not presently detectable (wild-type; wt/wt). Regardless of HFE genotype, persons with a hemochromatosis phenotype usually have increased iron saturation of plasma transferrin, typically absorb increased quantities of iron, and often develop multisystem disease due to iron overload. ... The invention is based on
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the discovery that peripheral blood erythrocyte parameters in hemochromatosis patients or those at risk of developing hemochromatosis is distinguished from the erythrocyte parameters of normal individuals. Hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MNCHC) values were significantly higher in hemochromatosis patients compared to normal control individuals. Accordingly, the invention provides a methods of diagnosing hemochromatosis or a predisposition thereto by detecting altered erythrocyte parameters. ... A method of diagnosing hemochromatosis or a predisposition thereto in a mammal is carried out by determining the mean corpuscular volume (MCV) value of a blood sample from the mammal. An an increase of at least 5% compared to a normal control value indicates that said mammal has hemochromatosis or is predisposed to developing hemochromatosis. A normal control value or range is one obtained by testing an individual or pool of individuals who are wt/wt. Individuals used to determine a normal control value or range are neither homozygous nor heterozygous for a genetic mutation associated with hemochromatosis such as C282Y or H63D of the HFE gene. Preferably, the increase is at least 7%, more preferably at least 7.5%, more preferably at least 8%, more preferably at least 9%, and most preferably at least 10% higher than a normal control value or range. Preferably, the erythrocyte profile of the tested individual does not indicate an anemic condition. For example, a red blood cell count (RBC), hematocrit (Hct), or hemoglobin concentration (Hb) should be within a normal range but the MCV value is elevated compared to a normal value or range to indicate a diagnosis of hemochromatosis. Web site: http://www.delphion.com/details?pn=US06268217__ ·
Hereditary hemochromatosis gene Inventor(s): Thomas; Winston J. (San Mateo, CA), Drayna; Dennis T. (San Mateo, CA), Feder; John N. (Mountain View, CA), Gnirke; Andreas (San Carlos, CA), Ruddy; David (San Francisco, CA), Tsuchihashi; Zenta (Menlo Park, CA), Wolff; Roger K. (Belmont, CA) Assignee(s): Mercator Genetics, Inc. (Menlo Park, CA) Patent Number: 6,025,130 Date filed: May 23, 1996 Abstract: The invention relates generally to the gene, and mutations thereto, that are responsible for the disease hereditary hemochromatosis (HH). More particularly, the invention relates to the identification,
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isolation, and cloning of the DNA sequence corresponding to the normal and mutant HH genes, as well as the characterization of their transcripts and gene products. The invention also relates to methods and the like for screening for HH homozygotes and further relates to HH diagnosis, prenatal screening and diagnosis, and therapies of HH disease, including gene therapeutics, protein and antibody based therapeutics, and small molecule therapeutics. Excerpt(s): The invention relates generally to the gene, and mutations thereto, that are responsible for the disease hereditary hemochromatosis (HH). More particularly, the invention relates to the identification, isolation, and cloning of the DNA sequence corresponding to the normal and mutant HH genes, as well as the characterization of their transcripts and predicted gene products. The invention also relates to methods and the like for screening for HH homozygotes and further relates to HH diagnosis, prenatal screening and diagnosis, and therapies of HH disease, including gene therapeutics, protein and antibody based therapeutics, and small molecule therapeutics. ... Hereditary hemochromatosis (HH) is an inherited disorder of iron metabolism wherein the body accumulates excess iron. In symptomatic individuals, this excess iron leads to deleterious effects by being deposited in a variety of organs leading to their failure, and resulting in cirrhosis, diabetes, sterility, and other serious illnesses. Neither the precise physiological mechanism of iron overaccumulation nor the gene which is defective in this disease has been described. ... The need for such diagnostics is documented, for example, in Barton, J. C. et al. Nature Medicine 2:394-395 (1996); Finch, C. A. West J Med 153:323-325 (1990); McCusick, V. Mendelian Inheritance in Man pp. 1882-1887, 11th ed., (Johns Hopkins University Press, Baltimore (1994)); Report of a Joint World Health Organization/Hemochromatosis Foundation/French Hemochromatosis Association Meeting on the Prevention and Control of Hemochromatosis (1993); Edwards, C. Q. et al. New Engl J Med 328:1616-1620 (1993); Bacon, B. R. New Engl J Med 326:126-127 (1992); Balan, V. et al. Gastroenterology 107:453-459 (1994); Phatak, P. D. et al. Arch Int Med 154:769-776 (1994). Web site: http://www.delphion.com/details?pn=US06025130__
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·
Method to diagnose hereditary hemochromatosis Inventor(s): Drayna; Dennis T. (San Mateo, CA), Feder; John N. (Mountain View, CA), Gnirke; Andreas (San Carlos, CA), Kimmel; Bruce E. (San Mateo, CA), Thomas; Winston J. (San Mateo, CA), Wolff; Roger K. (San Francisco, CA) Assignee(s): Mercator Genetics, Inc. (Menlo Park, CA) Patent Number: 5,753,438 Date filed: May 8, 1995 Abstract: New genetic markers for the presence of a mutation in the common hereditary hemochromatosis (HH) gene are disclosed. The multiplicity of markers permits definition of genotypes characteristic of carriers and homozygotes containing this mutation in their genomic DNA. Excerpt(s): The invention relates to genetic tests for subjects carrying one or two copies of a mutated gene associated with hereditary hemochromatosis. More specifically, the invention concerns utilization of new markers associated with a common mutation in this gene which indicate the presence or absence of the mutation. ... Hereditary hemochromatosis (HH) is an inherited disorder of iron metabolism wherein the body accumulates excess iron. In symptomatic individuals, this excess iron leads to deleterious effects by being deposited in a variety of organs leading to their failure, and resulting in cirrhosis, diabetes, sterility, and other serious illnesses. Neither the precise physiological mechanism of iron overaccumulation nor the gene which is defective in this disease is known. ... Thus, in one aspect, the invention is directed to a method to determine the likelihood of the presence or absence of a hereditary hemochromatosis (HH) gene mutation in an individual, which method comprises obtaining genomic DNA from the cells of said individual and assessing said DNA for the presence or absence of a genotype defined by at least one nonoptional marker comprising the following microsatellite repeat alleles: 19D9:205; 18B4:235; 1A2:239; 1E4:271; 24E2:245; 2B8:206; 3321-1:197; 4073-1:182; 4440-1:180; and 44402:139. In the notation employed for the microsatellite repeat alleles, the number subsequent to the colon indicates the number of nucleotides in the HH-associated allele between and including the flanking primers when the primers are those illustrated herein. The absence of this genotype indicates the likelihood of the absence of the HH gene mutation in the genome of said individual. The presence of this genotype indicates the likelihood of the presence of this HH gene mutation in the genome of said individual.
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Web site: http://www.delphion.com/details?pn=US05753438__ ·
Hereditary hemochromatosis diagnostic markers and diagnostic methods Inventor(s): Tsuchihashi; Zenta (Menlo Park, CA), Gnirke; Andreas (San Carlos, CA), Thomas; Winston J. (San Mateo, CA), Drayna; Dennis T. (San Mateo, CA), Ruddy; David (San Francisco, CA), Wolff; Roger K. (Belmont, CA), Feder; John N. (San Callos, CA) Assignee(s): Mercator Genetics (Menlo Park, CA) Patent Number: 5,712,098 Date filed: April 16, 1996 Abstract: A single base-pair polymorphism involving a mutation from Guanine (G), in individuals unaffected by the hereditary hemochromatosis (HH) gene defect, to Adeninc (A), in individuals affected by the HH gene defect is disclosed. The presence or absence of the polymorphic allele is highly predictive of whether an individual is at risk from HH: the polymorphism is present in 82% of affected individuals and only 4% of a random population screen. Methods of diagnosis, markers, and primers are disclosed and claimed in accordance with the present invention. Excerpt(s): The invention relates to a genetic test for identifying subjects carrying one or two copies of a mutated gene causing hereditary hemochromatosis. More specifically, the invention concerns utilization of a new marker that has an allele in association with a common mutation in this gene which indicates the presence or absence of the mutation. ... Hereditary hemochromatosis (HH) is an inherited disorder of iron metabolism wherein the body accumulates excess iron. In symptomatic individuals, this excess iron leads to deleterious effects by being deposited in a variety of organs leading to their failure, and resulting in cirrhosis, diabetes, sterility, and other serious illnesses. Neither the precise physiological mechanism of iron overaccumulation nor the gene which is defective in this disease is known. ... The need for such diagnostics is documented, for example, in Finch, C. A. West J Med 153:323-325 (1990); McCusick, V. et al. Mendelian Inheritance in Man pp. 1882-1887, 11th ed., (Johns Hopkins University Press, Baltimore (1994)); Report of a Joint World Health Organization/Hemochromatosis Foundation/French Hemochromatosis Association Meeting on the Prevention and Control of Heraochromatosis, 1993; Edwards, C. Q. et al. New Engl J Med328:1616-1620 (1993); Bacon, B. R. New Engl J
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Med326:126-127 (1992); Balan, V. et al. Gastroenterology 107:453-459 (1994); Phatak, P. D. et al. Arch Int Med 154:769-776 (1994). Web site: http://www.delphion.com/details?pn=US05712098__ ·
Methods to identify hemochromatosis Inventor(s): Rothenberg; Barry E. (P.O. Box 997, Del Mar, CA 92014) Assignee(s): none reported Patent Number: 5,674,681 Date filed: December 6, 1994 Abstract: The present invention provides methods to identify hemochromatosis in an individual. For example, the invention provides a method of detecting reduced association of .beta..sub.2 -microglobulin with a nonclassical MHC class I heavy chain molecule or a mutation in nonclassical MHC class I heavy chain-encoding DNA which results in a reduction of .beta..sub.2 -microglobulin-heavy chain association indicating that the individual tested has or is at risk of having hemochromatosis. Excerpt(s): The current paradigm for MHC gene function provides several theories to explain a role for MHC genes in autoimmune disease. They include the inappropriate expression of class II MHC molecules in cells eliciting the autoimmune response or aberrant recognition of selfpeptides by particular MHC gene products. Such theories, however, remain to be proven. In addition, the current paradigm fails to provide a useful hypothesis to explain the basis for an MHC-associated iron storage disease known as hemochromatosis. This disease is known from animal studies and from the genomic structure of several class I genes to involve an MHC encoded class I molecule since deletion of the .beta..sub.2 M gene in these animals results in the disease. ... The invention further provides methods to diagnose a genetic basis for hemochromatosis by detecting a mutation in a class I MHC molecule that reduces it's ability to associate with .beta..sub.2 microglobulin. ... The knowledge that a selfrecognition molecule is a leczyme and that it has been selected through evolution to recognize and modify a carbohydrate structure such as a carbohydrate ligand provides new methods to treat disease states resulting from such self-recognition leczymes. Such disease states include, for example, autoimmunity, hemochromatosis, inflammation, transplantation rejection, and infections. In many of the above disease states, disease results from aberrant recognition of self-carbohydrate structures by lymphocytes. Thus, the administration of a carbohydrate ligand that can bind to the aberrant self-recognition molecule of an
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individual provides a means to disrupt the aberrant self-recognition cycle mediating the disease. Web site: http://www.delphion.com/details?pn=US05674681__
Patent Applications on Hemochromatosis As of December 2000, U.S. patent applications are open to public viewing.25 Applications are patent requests which have yet to be granted (the process to achieve a patent can take several years).
Keeping Current In order to stay informed about patents and patent applications dealing with hemochromatosis, 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 “hemochromatosis” (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 hemochromatosis. You can also use this procedure to view pending patent applications concerning hemochromatosis. Simply go back to 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 Aberrant: Wandering or deviating from the usual or normal course. [EU] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [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 25
This has been a common practice outside the United States prior to December 2000.
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antigen closely related to it. Antibodies are classified according to their ode of action as agglutinins, bacteriolysins, haemolysins, opsonins, precipitins, etc. [EU] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] 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] 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]
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CHAPTER 6. BOOKS ON HEMOCHROMATOSIS Overview This chapter provides bibliographic book references relating to hemochromatosis. You have many options to locate books on hemochromatosis. 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 hemochromatosis 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 to 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 “hemochromatosis” (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 hemochromatosis:
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·
Liver Disorders Sourcebook Source: Detroit, MI: Omnigraphics. 2000. 591 p. Contact: Available from Omnigraphics, Inc. 615 Griswold, Detroit, MI 48226. (800) 234-1340. Fax (800) 875-1340. Price: $78.00 plus shipping and handling. ISBN: 0780802403. Summary: This Sourcebook provides basic health care information about liver functions, guidelines for liver health, and tests that assess liver distress. The book also presents the symptoms, treatments, and preventive measures available for liver cancer; hepatitis A, B, C, D and E; genetically based liver diseases; and other liver diseases. The liver transplantation process is explained. Specific topics include strategies for protecting the liver, risk factors, common laboratory tests in liver disease, liver biopsy, cancer tumor markers, cirrhosis (scarring of the liver), infectious agents and parasites, pregnancy and the liver, jaundice in the healthy newborn, the liver's response to drugs, alcohol and the liver, acetaminophen, herbs and alternative medicine, galactosemia, Gaucher disease, hereditary hemochromatosis, Niemann-Pick disease, Wilson's disease, biliary atresia, cystic disease of the liver, fatty liver, gallstones, primary biliary cirrhosis, primary sclerosing cholangitis, organ donation, and the bioartificial liver. A glossary, a directory of organizations and support groups with up to date contact information (including websites and email addresses), a listing of transplant centers, and a subject index conclude the volume.
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Schiff's Diseases of the Liver. 8th ed Source: Hagerstown, MD: Lippincott Williams and Wilkins. 1999. 2 v., 1760 p. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030. Fax (301) 824-7390. Price: $229.00 plus shipping and handling. ISBN: 0397587694. Summary: This classic textbook on diseases of the liver emphases both the medical and surgical aspects of the diagnosis and management of liver diseases. Divided into 12 parts, the text covers general considerations, the consequences of liver disease, the cholestatic disorders, hepatitis, autoimmune liver disease, alcohol and drug induced diseases, genetic and metabolic diseases, vascular diseases and trauma, benign and malignant tumors, the liver in pregnancy and childhood, infectious and granulomatous disorders, and transplantation. In this 8th edition, the authors continue to chart the progress of scientific advances in the care of patients with liver disease. The authors identify and discuss the current challenges faced by investigators and clinicians, including the
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need for a vaccine to prevent hepatitis C; the development of ways to successfully support patients who have acute liver failure; the creation of effective, well tolerated treatments for chronic hepatitis B and C; and the development of genetically based tests to diagnose Wilson's disease, hemochromatosis, and the broad array of metabolic errors. Each chapter in the two volume set is written by experts in the field of hepatology and each is illustrated with figures, tables, and black and white photographs. Each chapter also contains extensive references. A section of color plates is included and a subject index is found at the end of each volume. ·
Clinical Practice of Gastroenterology. Volume Two Source: Philadelphia, PA: Current Medicine. 1999. 861 p. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 8746418 or (407) 352-3445. Website: www.wbsaunders.com. Price: $235.00 plus shipping and handling. ISBN: 0443065209 (two volume set); 0443065217 (volume 1); 0443065225 (volume 2). Summary: This lengthy textbook brings practitioners up to date on the complexities of gastroenterology practice, focusing on the essentials of patient care. This second volume includes 113 chapters in five sections: liver, gallbladder and biliary tract, pancreas, pediatric gastroenterology, and special topics. Specific topics include hepatic (liver) structure and function, jaundice, viral hepatitis, alcoholic liver injury, liver tumors, parasitic diseases of the liver, Wilson's disease, hemochromatosis, the pregnancy patient with liver disease, portal hypertension, hepatic encephalopathy, fulminant hepatic failure, liver transplantation, the anatomy of the gallbladder and biliary tract, gallstones, laparoscopic cholecystectomy (gallbladder removal), cholecystitis (gallbladder infection), primary sclerosing cholangitis, biliary obstruction, pancreatic anatomy and physiology, acute pancreatitis, pancreatic fistulas and ascites (fluid accumulation), chronic pancreatitis, cancer of the pancreas, endoscopic retrograde cholangiopancreatography, esophageal atresia, gastroesophageal reflux in infants and children, achalasia and esophageal motility disorders, caustic and foreign body ingestion, vomiting, chronic abdominal pain, gastritis and peptic ulcer disease in children, malabsorption syndromes in children, inflammatory bowel disease in children and adolescents, acute appendicitis, cystic fibrosis, constipation and fecal soiling (incontinence), hepatitis in children, liver transplantation in children, failure to thrive, pediatric AIDS, the gastrointestinal manifestations of AIDS, the evaluation and management of acute upper gastrointestinal bleeding, principles of endoscopy, eating disorders, nutritional assessment, enteral and parenteral nutrition,
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gastrointestinal diseases in the elderly and in pregnancy, nosocomial infections, and the psychosocial aspects of gastroenterology (doctor patient interactions). The chapters include figures, algorithms, charts, graphs, radiographs, endoscopic pictures, intraoperative photographs, photomicrographs, tables, and extensive references. The volume concludes with a detailed subject index and a section of color plates. ·
Evidence Based Gastroenterology and Hepatology Source: London, UK: BMJ Publishing Group. 1999. 557 p. Contact: Available from BMJ Publishing Group. BMA Books, BMA House, Tavistock Square, London WCIH 9JR. Fax 44 (0)20 7383 6402. Email:
[email protected]. Website: www.bmjbooks.com. Price: Contact publisher for price. ISBN: 0727911821. Summary: This book emphasizes the approaches of evidence based medicine in gastroenterology (the study of the gastrointestinal tract and gastrointestinal diseases) and hepatology (the study of the liver and liver diseases). The authors use clinical epidemiology to present the strongest and most current evidence for interventions for the major diseases of the gastrointestinal tract and liver. Thirty chapters are included: an introduction to evidence based gastroenterology and hepatology; gastroesophageal reflux disease (GERD); ulcer disease and Helicobacter pylori; ulcer disease and nonsteroidal antiinflammatory drugs; treatment options for non-variceal gastrointestinal hemorrhage; the diagnosis and treatment of functional dyspepsia (indigestion); the diagnosis, treatment, and prognosis of celiac disease (gluten intolerance); the treatment of Crohn's disease; the diagnosis, prognosis, and treatment of ulcerative colitis (UC); pouchitis after restorative proctocolectomy; metabolic bone disease in gastrointestinal disorders; colorectal cancer in UC and the role of surveillance; population based screening and surveillance for colorectal cancer; irritable bowel syndrome (IBS); the surgical treatment of gallstone disease; the prognosis and treatment of acute pancreatitis; hepatitis C; hepatitis B; the screening and treatment of alcoholic liver disease; hemochromatosis and Wilson disease; primary biliary cirrhosis (PBC); autoimmune hepatitis; primary sclerosing cholangitis (PSC); the prevention and treatment of portal hypertensive bleeding; ascites, hepatorenal syndrome, and spontaneous bacterial peritonitis; hepatic encephalopathy; hepatocellular carcinoma; fulminant hepatic failure; the prevention and treatment of rejection after liver transplantation; and the prevention and treatment of infection after liver transplantation. Each chapter features the grading of recommendations and levels of evidence used by the authors to note the research basis on which their clinical guidelines are formed. Chapters conclude with extensive reference lists;
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the text concludes with a subject index. A glossary of acronyms is also provided. ·
Handbook of Liver Disease Source: Philadelphia, PA: Churchill-Livingstone. 1998. 534 p. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522. Fax (800) 874-6418. E-mail:
[email protected]. Price: $73.00 plus shipping and handling. ISBN: 0443055203. Summary: This comprehensive handbook in outline format offers easy access to information on the full range of liver disorders, and covers symptoms, signs, differential diagnoses, and treatments. A total of 34 chapters cover the following topics: assessment of liver function and diagnostic studies, acute liver failure, chronic viral hepatitis, acute viral hepatitis, autoimmune hepatitis, alcoholic liver disease, fatty liver and nonalcoholic steatohepatitis, drug induced and toxic liver disease, cirrhosis and portal hypertension, portal hypertension and gastrointestinal bleeding, ascites and spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy, primary biliary cirrhosis, primary sclerosing cholangitis, hemochromatosis, Wilson's disease and related disorders, alpha 1 antitrypsin deficiency and other metabolic liver diseases, Budd Chiari syndrome and other vascular disorders, the liver in heart failure, the liver in pregnancy, the liver in systemic disease, pediatric liver disease, liver disease in the elderly, HIV and the liver, granulomatous liver disease, hepatic tumors, hepatic abscesses and cysts, other infections involving the liver, surgery in the patient with liver disease and postoperative jaundice, liver transplantation, cholelithiasis and cholecystitis, diseases of the bile ducts, and tumors of the biliary tract. The book features lists that summarize key information and numerous figures and tables on topics such as acetaminophen toxicity, classifications of chronic hepatitis, and indications for liver transplantation. Each chapter was written by an acknowledged expert in the field and includes references for additional study. A subject index concludes the volume.
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Encyclopedia of Alcoholism. 2nd ed Source: New York, NY: Facts on File, Inc. 1991. 346 p. Contact: Available from Facts on File, Inc. 460 Park Avenue South, New York, NY 10016. (212) 683-2244. Price: $45. Shipping and handling free if prepaid. ISBN: 081601955X.
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Summary: This volume presents a dictionary approach to information about alcoholism. With more than 600 entries, the encyclopedia defines and explains all facets of alcoholism: biological, medical and psychological areas, its social and economic impact, legal implications, terminology used in the treatment of the disease, slang, organizations that deal with alcoholism, various theories on the causes of the disease, and the prevalence of alcohol abuse around the world and what different countries have tried to do about controlling it. Entries of interest to those in the field of digestive diseases include those about alcoholic hepatitis, alcoholic liver disease, alcoholic myopathy, black Americans, blood sugar, cirrhosis, diabetes, diseases, gastrointestinal tract, hemochromatosis, hypoglycemia, intestine, liver, Mallory-Weiss syndrome, nutrition, pancreas, post-necrotic cirrhosis, stomach, and Switzerland. Appendices include tables and figures and sources of information. A subject index is included. 620 references.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes & Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in PrintÒ). The following have been recently listed with online booksellers as relating to hemochromatosis (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): ·
Cooking With Less Iron: Easy-To-Prepare, Reasonably Priced Meals That Reduce the Amount of Iron in Your Diet by Cheryl Garrison; ISBN: 1581822235; http://www.amazon.com/exec/obidos/ASIN/1581822235/icongroupin terna
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Hemochromatosis : proceedings of the first international conference ; ISBN: 0897664485; http://www.amazon.com/exec/obidos/ASIN/0897664485/icongroupin terna
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Hemochromatosis : Proceedings of the First International Conference (Annals of the New York Academy of Sciences, Vol 526) by Lewis R. Weintraub, et al (1988); ISBN: 0897664477; http://www.amazon.com/exec/obidos/ASIN/0897664477/icongroupin terna
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Hemochromatosis: Genetics, Pathophysiology, Diagnosis and Treatment by James C. Barton (Editor), Corwin Q. Edwards (Editor); ISBN: 0521593808; http://www.amazon.com/exec/obidos/ASIN/0521593808/icongroupin terna
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Living with Hemochromatosis by Gregory Everson (2003); ISBN: 157826104X; http://www.amazon.com/exec/obidos/ASIN/157826104X/icongroupi nterna
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Progress in Iron Research (Advances in Experimental Medicine and Biology, 356) by Chaim Hershko, et al (1994); ISBN: 0306447290; http://www.amazon.com/exec/obidos/ASIN/0306447290/icongroupin terna
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The Bronze Killer : The Story of a Family's Fight Against a Very Common Enemy - Hemochromatosis by Marie Warder (1989); ISBN: 0889258856; http://www.amazon.com/exec/obidos/ASIN/0889258856/icongroupin terna
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The Iron Disorders Institute Guide to Hemochromatosis by Cheryl D. Garrison (Editor), et al (2001); ISBN: 1581821603; http://www.amazon.com/exec/obidos/ASIN/1581821603/icongroupin terna
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The Iron Elephant (Iron Overload and health) by Roberta Crawford (2000); ISBN: 0963254707; http://www.amazon.com/exec/obidos/ASIN/0963254707/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 “hemochromatosis” (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:26 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
26
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Adventures in the iron trade; inaugural lecture ... delivered 22 October 1969. Author: Bothwell, Thomas H. (Thomas Hamilton); Year: 1969; Johannesburg, Witwatersand Univ. Press, 1969
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Area postrema; a contribution to its normal and pathological anatomy, especially in haemochromatosis. Author: Cammermeyer, Jan, 1911-; Year: 1945; Oslo, Dybwad, 1945
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Clinical disorders of iron metabolism, by Ernest Beutler [et al.]. Author: Beutler, Ernest, 1928-; Year: 1963; New York, Grune & Stratton [c1963]
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Clinical disorders of iron metabolism. Author: Virgil F. Fairbanks, John L. Fahey, Ernest Beutler; Year: 1971; New York: Grune & Stratton, c1971; ISBN: 0808906771 http://www.amazon.com/exec/obidos/ASIN/0808906771/icongroupin terna
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Cost-effective hemochromatosis screening in primary care: abstract, executive summary and final report. Author: [Pradyumna D. Phatak]; Year: 1998; [Rockville, Md.: Agency for Health Care Policy and Research], 1998
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Haemochromatosis. Author: Sheldon, J. H. (Joseph Harold); Year: 1935; London, Oxford Univ. Press, 1935
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Hemochromatosis: genetics, pathophysiology, diagnosis and treatment. Author: edited by James C. Barton and Corwin Q. Edwards; Year: 2000; Cambridge: Cambridge University Press, 2000; ISBN: 0521593808 http://www.amazon.com/exec/obidos/ASIN/0521593808/icongroupin terna
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Hemochromatosis: proceedings of the first international conference. Author: edited by Lewis R. Weintraub, Corwin Q. Edwards, and Margaret Krikker; Year: 1988; New York, N.Y.: New York Academy of Sciences, 1988; ISBN: 0897664477 http://www.amazon.com/exec/obidos/ASIN/0897664477/icongroupin terna
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Hemochromatosis and hemosiderosis. Author: MacDonald, Richard Annis, 1928-; Year: 1964; Springfield, Ill., Thomas [c1964]
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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Hemochromatosis; its relation to the metabolism of iron and copper. Author: Dry, Thomas Jan, 1903-; Year: 1932; [Minneapolis] 1932
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Hereditary haemochromatosis. Author: Ken Campbell; Year: 1999; London: NT Books, c1999; ISBN: 1902499581
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Hypochromic iron loading anemia with secondary hemochromatosis. Author: Byrd, Richard Bourne, 1929-; Year: 1960; [Minneapolis] 1960
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Prevention and control of hemochromatosis: improved diagnosis: report of a joint WHO. Author: Hemochromatosis Foundation/Canadian, French, and UK hemochromatosis associations meeting, St. Malo, France, 18 June 1997; Year: 1998; [Geneva?]: World Health Organization, Human Genetics Programme, Division of Noncommunicable Diseases, c1998
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Progress in iron research. Author: edited by Chaim Hershko, Abraham M. Konijn, and Philip Aisen; Year: 1994; New York: Plenum Press, c1994; ISBN: 0306447290 http://www.amazon.com/exec/obidos/ASIN/0306447290/icongroupin terna
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Report of a Joint WHO. Author: Hemochromatosis Foundation/French Hemochromatosis Association Meeting on the Prevention and Control of Hemochromatosis: Kiryat Anavim, Israel, 27 April 1993; Year: 1994; [Geneva?]: World Health Organization, Hereditary Diseases Programme, Division of Noncommunicable Diseases, c1994
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Transfusion management of some common heritable blood disorders. Author: editors, Emanuel Hackel, Robert G. Westphal, Susan M. Wilson; Year: 1992; Bethesda, Md.: American Association of Blood Banks, 1992; ISBN: 1563950103 http://www.amazon.com/exec/obidos/ASIN/1563950103/icongroupin terna
Chapters on Hemochromatosis Frequently, hemochromatosis will be discussed within a book, perhaps within a specific chapter. In order to find chapters that are specifically dealing with hemochromatosis, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and hemochromatosis using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” By making these selections and
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typing in “hemochromatosis” (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 hemochromatosis: ·
Haematology Source: in Maddison, P.J.; et al., Eds. Oxford Textbook of Rheumatology. Volume 1. New York, NY: Oxford University Press, Inc. 1993. p. 367-375. Contact: Available from Oxford University Press, Inc., New York, NY. Summary: This chapter for health professionals focuses on the interpretation of hematological data as it relates to rheumatic disease. Problems with techniques of examining blood cells are examined. Anemias in rheumatoid arthritis and other autoimmune diseases are described. Thrombocytosis and thrombocytopenia in rheumatoid arthritis and platelet abnormalities in systemic lupus are discussed. White blood cell abnormalities in rheumatic disease are identified, including Flety's syndrome, leucopenia, and leucocytosis. Coagulation abnormalities in systemic lupus are described, including lupus anticoagulant. The impact of acute phase reactants on the erythrocyte sedimentation rate (ESR) is examined. Causes of a high ESR are identified. Primary blood disorders are discussed, including coagulation disorders, hematological malignancies, hemoglobinopathies, hemochromatosis, and disorders presenting as gout. 22 references, 1 figure, and 7 tables.
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Liver Disease Source: in King, J.E., ed. Mayo Clinic on Digestive Health. Rochester, MN: Mayo Clinic. 2000. p. 151-166. Contact: Available from Mayo Clinic Health Information. 5505 36th Street, SE, Grand Rapids, MI 49512. (800) 291-1128. Website: www.mayoclinic.com. Price: $14.95 plus shipping and handling. ISBN: 1893005046. Summary: This chapter on liver disease is from a comprehensive guidebook from the Mayo Clinic that focuses on a variety of digestive symptoms, including heartburn, abdominal pain, constipation, and diarrhea, and the common conditions that are often responsible for these symptoms. Written in nontechnical language, the book includes practical information on how the digestive system works, factors that can interfere with its normal functioning, and how to prevent digestive problems. The first section of the chapter focuses on hepatitis, including the key signs and symptoms of hepatitis, notably fatigue, loss of appetite, nausea, unexplained weight loss, and yellowing of skin and eyes (jaundice). The authors describe the different types of hepatitis (alcohol or drug induced,
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hepatitis A, hepatitis B, hepatitis C, hepatitis D and E, autoimmune hepatitis, and nonalcoholic steatohepatitis); review the blood tests (liver function tests) that may be used to help diagnose or monitor hepatitis; and discuss treatment options, including corticosteroids, interferon, lamivudine, and liver transplantation. A final section reviews healthy lifestyle approaches for living with hepatitis, and strategies for preventing the disease. The next section of the chapter addresses hemochromatosis (a genetic abnormality that causes the intestines to absorb too much iron), noting that the symptoms can include fatigue, joint pain, impotence (erectile dysfunction) or loss of sex drive, increased skin pigmentation (bronzing), and increased thirst and urination. This section also reviews diagnosis, determining whether screening is necessary for family members of patients with hemochromatosis, and the use of diet therapy (reduced iron intake) to help treat the disease. One sidebar mentions Wilson's disease and alpha 1 antitrypsin deficiency as other inherited liver disease. The last section of the chapter addresses cirrhosis, a condition in which scar tissue forms in the liver and keeps it from functioning normally. 1 figure. ·
Liver, Biliary Tract, and Pancreas Source: in Tierney, L.M.; McPhee, S.J.; Papadakis, M.A., eds. Current Medical Diagnosis and Treatment 1999. 38th ed. Stamford, CT: Appleton and Lange. 1999. p. 638-677. Contact: Available from McGraw-Hill Companies. 1221 Avenue of the Americas, New York, NY 10020. (800) 352-3566 or (212) 512-4100. Fax (212) 512-4105. Website: www.mcgraw-hill.com. Price: $47.50 plus shipping and handling. ISBN: 0838515509. Summary: This chapter on the liver, biliary tract, and pancreas is from a general medical textbook that is designed as a single source reference for practitioners in both hospital and ambulatory settings. The textbook offers extensive coverage of all primary care topics, including gynecology, obstetrics, dermatology, ophthalmology, otolaryngology, psychiatry, neurology, and urology. This chapter covers jaundice, viral hepatitis (all types), chronic hepatitis, alcoholic hepatitis, drug and toxin induced liver disease, fatty liver and nonalcoholic steatohepatitis, cirrhosis, primary biliary cirrhosis, hemochromatosis, Wilson's disease, hepatic vein obstruction (Budd Chiari syndrome), the liver in heart failure, noncirrhotic portal hypertension, hepatic abscess (amebic and pyogenic), hepatocellular carcinoma, benign liver neoplasms, cholelithiasis, acute cholecystitis, cystic duct syndromes, choledocholithiasis and cholangitis, biliary stricture, primary sclerosing cholangitis, carcinoma of the biliary tract, acute pancreatitis, chronic
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pancreatitis, and carcinoma of the pancreas and the periampullary area. For each topic, the author discusses the symptoms, diagnostic methods, classification, prevention, treatment, prognosis. Each section offers relevant references for that particular topic. The chapter concludes with a list of relevant World Wide Web sites. 3 figures. 7 tables. 97 references. ·
Prevalence and Incidence of Secondary and Other Types of Diabetes Source: in Harris, M.I., et al., eds., for the National Diabetes Data Group (NDDG). Diabetes in America. 2nd ed. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. 1995. p. 69-84. Contact: Available from National Diabetes Information Clearinghouse (NDIC). 1 Information Way, Bethesda, MD 20892-3560. (800) 860-8747 or (301) 654-3327. E-mail:
[email protected]. Price: $20.00. Also available at http://www.niddk.nih.gov/. Summary: This chapter on the prevalence and incidence of secondary and other types of diabetes is from a compilation and assessment of data on diabetes and its complications in the United States. The prevalence of these secondary types is approximately 1 to 2 percent of all diabetes. The extent of glucose intolerance in patients with secondary forms of diabetes can vary widely, presenting as overt diabetes that is insulin-requiring or noninsulin-requiring, simulating IDDM or NIDDM, or as milder forms such as impaired glucose tolerance (IGT) or minimally abnormal glucose tolerance. Topics include diabetes secondary to pancreatic diseases, malnutrition-related diabetes, hemochromatosis, acromegaly, isolated growth hormone deficiency, Cushing's syndrome, pheochromocytoma, primary hyperaldosteronism, hyperthyroidism, tumors of endocrine pancreas or gut, polyendocrine autoimmunity syndromes, and POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes) syndrome. The author also discusses diabetogenic drugs, chemical agents, and toxins, including diuretics and beta-adrenergic antagonists, diphenylhydantoins, glucocorticoids, oral contraceptives, progestins, pentamidine, Vacor, nicotinic acid, cyclosporin, and opiates. The author concludes with a discussion of genetic syndromes related to secondary diabetes. 2 figures. 7 tables. 147 references. (AA-M).
·
Metabolic Conditions and Nutrition Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 298-309.
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Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail:
[email protected]. Website: www.bh.com. Price: $110.00. ISBN: 0723610568. Summary: This chapter on metabolic conditions and nutrition is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. Topics include inborn errors of metabolism, Suxamethonium (Scoline) sensitivity, malignant hyperthermia (a disorder characterized by a rapid rise in temperature when the patient has a general anesthetic or another drug that can trigger an attack), neuroleptic malignant syndrome, hyperlipoproteinemia (hyperlipidemia), hypolipoproteinemias, the porphyrias, hemochromatosis, homocytinuria, glycogen storage disease (GSD), gingival swelling due to metabolic deposits, dietary disorders, obesity, lactovegetarianism, malnutrition, and pica (the ingestion of unusual objects or substances). For each condition, the authors discuss general aspects, diagnosis and management issues, dental aspects, and patient care strategies. The chapter includes a summary of the points covered. 1 appendix. 2 figures. 7 tables. 27 references. ·
Oral Manifestations of Metabolic Disorders Source: in Bork, K., et al. Diseases of the Oral Mucosa and the Lips. Orlando, FL: W.B. Saunders Company. 1993. p. 357-364. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522 (individuals) or (800) 782-4479 (schools); Fax (800) 874-6418 or (407) 3523445; http://www.wbsaunders.com. Price: $99.00 plus shipping and handling. ISBN: 0721640397. Summary: This chapter, from a textbook on diseases of the oral mucosa and the lips, discusses the oral manifestations of metabolic disorders. Disorders covered are gout, lipid abnormalities, hyperlipoproteinemias, mucinoses, amyloidosis, lipoid proteinosis, Fabry's disease, Gaucher's disease, porphyrias, cystic fibrosis, and hemochromatosis. For each disorder, the authors describe the clinical features and present brief diagnostic and therapeutic recommendations. Full-color photographs illustrate the chapter; references are provided for some sections. 10 figures. 1 table. 24 references.
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General Home References In addition to references for hemochromatosis, you may want a general home medical guide that spans all aspects of home healthcare. The following list is a recent sample of such guides (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · Urodynamics Made Easy by Christopher R. Chapple, Scott A. MacDiarmid; Paperback -- 2nd edition (April 15, 2000), Churchill Livingstone; ISBN: 0443054630; http://www.amazon.com/exec/obidos/ASIN/0443054630/icongroupinterna
Vocabulary Builder Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Appendicitis: Acute inflammation of the vermiform appendix. [NIH] Benign: Not malignant; not recurrent; favourable for recovery. [EU] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] Cholangitis: Inflammation of a bile duct. [EU] Cholecystectomy: Surgical removal of the gallbladder. [NIH] Cholecystitis: Inflammation of the gallbladder. [EU] Cholelithiasis: The presence or formation of gallstones. [EU] Coagulation: 1. the process of clot formation. 2. in colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. in surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Colitis: Inflammation of the colon. [EU] Colorectal: Pertaining to or affecting the colon and rectum. [EU]
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Constipation: Infrequent or difficult evacuation of the faeces. [EU] Contraceptive: conception. [EU]
An agent that diminishes the likelihood of or prevents
Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Dyspepsia: Impairment of the power of function of digestion; usually applied to epigastric discomfort following meals. [EU] Encephalopathy: Any degenerative disease of the brain. [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] Gastritis: Inflammation of the stomach. [EU] Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [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] Gynecology: A medical-surgical specialty concerned with the physiology and disorders primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Helicobacter: A genus of gram-negative, spiral-shaped bacteria that is pathogenic and has been isolated from the intestinal tract of mammals, including humans. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hyperaldosteronism: Aldosteronism. [EU] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hypertension: Persistently high arterial blood pressure. Various criteria for its threshold have been suggested, ranging from 140 mm. Hg systolic and 90
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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] Hyperthermia: Abnormally high body temperature, especially that induced for therapeutic purposes. [EU] Hyperthyroidism: 1. excessive functional activity of the thyroid gland. 2. the abnormal condition resulting from hyperthyroidism marked by increased metabolic rate, enlargement of the thyroid gland, rapid heart rate, high blood pressure, and various secondary symptoms. [EU] Hypolipoproteinemia: The presence of abnormally low levels of lipoproteins in the serum. [NIH] Incontinence: Inability to control excretory functions, as defecation (faecal i.) or urination (urinary i.). [EU] Ingestion: The act of taking food, medicines, etc., into the body, by mouth. [EU]
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] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]
Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignant: Tending to become progressively worse and to result in death. Having the properties of anaplasia, invasion, and metastasis; said of tumours. [EU] Motility: The ability to move spontaneously. [EU] Nausea: An unpleasant sensation, vaguely referred to the epigastrium and abdomen, and often culminating in vomiting. [EU] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally
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occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Parasitic: Pertaining to, of the nature of, or caused by a parasite. [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] Pentamidine: Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of Pneumocystis carinii pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects. [NIH]
Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Postoperative: Occurring after a surgical operation. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Reflux: A backward or return flow. [EU]
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Retrograde: 1. moving backward or against the usual direction of flow. 2. degenerating, deteriorating, or catabolic. [EU] Rheumatoid: Resembling rheumatism. [EU] Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue structures which pertain to a variety of musculoskeletal disorders, such as arthritis. [NIH] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [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] Surgical: Of, pertaining to, or correctable by surgery. [EU] Thrombocytopenia: Decrease in the number of blood platelets. [EU] Thrombocytosis: Increased numbers of platelets in the peripheral blood. [EU] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] 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] Vaccine: A suspension of attenuated or killed microorganisms (bacteria, viruses, or rickettsiae), administered for the prevention, amelioration or treatment of infectious diseases. [EU]
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CHAPTER 7. MULTIMEDIA ON HEMOCHROMATOSIS Overview Information on hemochromatosis 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 hemochromatosis. 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 diseases 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 hemochromatosis is the Combined Health Information Database. You will need to limit your search to “video recording” and “hemochromatosis” 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 “hemochromatosis” (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 hemochromatosis:
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·
Gastroenterology Update Source: Mt. Laurel, NJ: CME Conference Video, Inc. 1992. (videocassettes and syllabus). Contact: Available from P.O. Box 5077, Cherry Hill, NJ 08034-5077. (800) 284-8433. Fax (800) 284-5964. Price: $375. Group practice packages available. Summary: This video education program reviews clinical gastroenterology, emphasizing recent developments in diagnosis and treatment. Topics covered include oropharyngeal dysphagia; the pathogenesis of gastroesophageal reflux; esophageal motility disorders; hemochromatosis; cholestatic liver disease; viral hepatitis; the management of malignant esophageal obstruction; clinical and therapeutic assessment in inflammatory bowel disease (IBD); and nutritional support in IBD. The video program includes numerous case presentations, including with patients presenting with colorectal cancer, esophageal varices, portal hypertension, reflux esophagitis, and druginduced esophageal injury.
Bibliography: Multimedia on Hemochromatosis 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 hemochromatosis (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 hemochromatosis. For more information, follow the hyperlink indicated: ·
Dermatologic signs of systemic diseases. Source: Roger Harrison Brodkin; Year: 1970; Format: Slide; New York: Medcom, c1970
·
Genetics and public health: the future is now. Source: Centers for Disease Control and Prevention, UNC School of Public Health; Year: 2000; Format: Videorecording; [Atlanta, Ga.]: Public Health Training Network, [2000]
·
Metabolic and nutritional diseases. Source: Roger Harrison Brodkin; Year: 1979; Format: Slide; [New York]: Medcom, c1979
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·
Pathogenesis and management of hemochromatosis. Source: a National Medical Audiovisual Center production; Year: 1969; Format: Motion picture; [United States]: U.S. Dept. of Health, Education, and Welfare, Public Health Service, 1969
·
Pathology of diabetes. Source: Ralph E. Yodaiken; Year: 1974; Format: Slide; New York: Medcom, c1974
·
Radiology of degenerative joint disease. Source: Harold G. Jacobson, Neil H. Messinger; Year: 1973; Format: Slide; New York: Medcom, c1973
·
Roentgen cardiology of adults, part 2. Source: William T. Meszaros; Year: 1970; Format: Slide; [Chicago: Meszaros: for sale by Micro X-Ray Recorder, Inc., Medical Film Slide Division, 1970?]
Vocabulary Builder Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dysphagia: Difficulty in swallowing. [EU] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH]
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CHAPTER 8. PERIODICALS HEMOCHROMATOSIS
AND
NEWS
ON
Overview Keeping up on the news relating to hemochromatosis can be challenging. Subscribing to targeted periodicals can be an effective way to stay abreast of recent developments on hemochromatosis. Periodicals include newsletters, magazines, and academic journals. In this chapter, we suggest a number of news sources and present various periodicals that cover hemochromatosis 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 hemochromatosis 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 “hemochromatosis” 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: ·
Nanogen and Bio-Rad Sign Licensing Agreement to Detect Iron Overload Disease Summary: HERCULES, Calif. and SAN DIEGO, Calif., June 25 /PRNewswire-FirstCall/ -- Bio-Rad Laboratories, Inc. (Amex: BIO; BIO.B) and Nanogen, Inc. (Nasdaq: NGEN) announced today that they have entered into a worldwide, non-exclusive license agreement for the two most common gene mutations for the diagnosis of Hereditary Hemochromatosis (HH), a disorder resulting in excessive iron build-up in tissues and major organs of the body. Under the terms of the agreement, Bio-Rad granted Nanogen a license to the C282Y and H63D mutations of the HFE gene for use on Nanogen's proprietary NanoChip(R) System. Specific financial terms of the license have not been disclosed. HH (iron overload disease) is one of the most common genetic disorders in the world. It is estimated that approximately 32 million people in the United States are carriers of the genetic trait responsible for the disorder. Over time, these iron deposits can cause irreversible organ damage and lead to cirrhosis of the liver, hypothyroidism, cardiomyopathy, diabetes mellitus, arthritis, impotence, and death. Although more than a million Americans are clinically affected by the disorder, very few of those -only about two percent -- are ever diagnosed due to vague symptoms and a lack of awareness. "Bio-Rad is very pleased to continue our broad licensing efforts to help expand awareness and testing for this treatable, yet under-diagnosed disease," said John Goetz, Vice President of Bio-Rad's the company's Clinical Diagnostics Group. "The demand for molecular-based tests used to detect genetic disorders continues to increase, and we believe the agreement with Nanogen will help accelerate that trend by providing
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laboratories a greater variety of licensed hemochromatosis testing options." "This agreement with Bio-Rad strengthens our patent portfolio in the area of molecular detection and analysis and enables Nanogen to introduce the diagnostic market's first 3 SNP multiplex Analyte Specific Reagent (ASR) during 2002 for the simultaneous detection of the three most common mutations associated with HH," said Dr. Randy White, Chief Executive Officer of Nanogen. "Because many important genetic diseases, such as HH or cystic fibrosis, involve complex mutational analyses, we believe our technology platform is ideally suited to the expansion of genetic predisposition testing, which continues to grow due to the increasing amounts of genetic information from the Human Genome Project and other related efforts." The discovery of the HFE gene in 1996 made DNA testing a valuable tool in the early diagnosis of HH. Approximately 94% of the mutations associated with the disease can be detected by using molecular DNA studies. Treatment for both symptomatic and pre-symptomatic patients consists of removing blood from the patient in order to lower the level of iron. Early diagnosis followed by early and regular treatment can prevent iron overload and provide patients with a normal life expectancy. Bio-Rad Laboratories, Inc. (http://www.bio-rad.com) is a multinational manufacturer and distributor of life science research products and clinical diagnostics. The company is world renowned among hospitals, universities, major research institutions, biotechnology and pharmaceutical firms for its commitment to quality and customer service. It is based in Hercules, California, and serves more than 70,000 research and industry customers worldwide through a network of more than 30 wholly owned subsidiary offices. Nanogen, Inc. (http://www.nanogen.com) Nanogen's goal is to become the leading provider of molecular diagnostic products. The Company is seeking to establish the NanoChip(R) System as the standard platform for the detection of genetic mutations and to develop applications for future clinical use. To date, the Company has developed one ASR for the detection of Factor V Leiden, and internally validated five research protocols, four associated with cardiovascular disease and one associated with hereditary hemochromatosis, the most common form of iron overload disease. Nanogen markets its NanoChip(R) Molecular Biology
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Workstation to scientists and genomics laboratories. The NanoChip(R) System is intended for laboratory use only. This press release contains forward-looking statements that are subject to risks and uncertainties that could cause actual results to differ materially from those set forth in the forward-looking statements, including whether patents owned or licensed by the Company will be developed into products, whether the Company's NanoChip(R) System can be successfully further commercialized, whether other products under development can be successfully developed and commercialized, whether results reported by our customers or partners can be identically replicated, whether ASRs currently sold by the Company will become FDA-approved molecular diagnostic test kits, whether Nanogen will be successful in developing additional ASRs and protocols utilizing the NanoChip(R) System, and other risks and uncertainties discussed under the caption "Factors That May Affect Results" and elsewhere in the Company's Form 10-K for the year ended December 31, 2001 filed with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof. The Company disclaims any intent or obligation to update these forward-looking statements.
Reuters The Reuters’ Medical News database can be very useful in exploring news archives relating to hemochromatosis. 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 “hemochromatosis” (or synonyms). The following was recently listed in this archive for hemochromatosis: ·
Several genetic mutations may cause hemochromatosis Source: Reuters Medical News Date: September 02, 1999 http://www.reuters.gov/archive/1999/09/02/professional/links/19990 902epid001.html
·
Duodenal metal transporter overexpressed in patients with hereditary hemochromatosis Source: Reuters Medical News Date: June 23, 1999 http://www.reuters.gov/archive/1999/06/23/professional/links/19990 623clin012.html
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·
Genotyping may help to identify early hereditary hemochromatosis Source: Reuters Medical News Date: June 16, 1999 http://www.reuters.gov/archive/1999/06/16/professional/links/19990 616clin007.html
·
Use of blood from patients with hemochromatosis could ease blood shortage Source: Reuters Medical News Date: January 14, 1999 http://www.reuters.gov/archive/1999/01/14/professional/links/19990 114plcy003.html
·
Prevalence of hemochromatosis put at 1 in 200 in US Source: Reuters Medical News Date: December 02, 1998 http://www.reuters.gov/archive/1998/12/02/professional/links/19981 202epid001.html
·
"The Time Has Come" For Universal Hemochromatosis Screening Source: Reuters Medical News Date: March 02, 1998 http://www.reuters.gov/archive/1998/03/02/professional/links/19980 302clin001.html
·
Hemochromatosis Gene Product Complexes With Transferrin Receptor Source: Reuters Medical News Date: February 19, 1998 http://www.reuters.gov/archive/1998/02/19/professional/links/19980 219scie004.html
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SmithKline Unit To Develop Progenitor Hereditary Hemochromatosis Test Source: Reuters Medical News Date: September 23, 1997 http://www.reuters.gov/archive/1997/09/23/professional/links/19970 923inds003.html
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Features Of Hemochromatosis In Women And Men Compared Source: Reuters Medical News Date: July 17, 1997 http://www.reuters.gov/archive/1997/07/17/professional/links/19970 717clin005.html
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·
CDC Officials Call For Widespread Screening For Hemochromatosis Source: Reuters Medical News Date: March 10, 1997 http://www.reuters.gov/archive/1997/03/10/professional/links/19970 310plcy001.html
·
Prevalence Of Hemochromatosis In Hispanics Similar To Caucasians Source: Reuters Medical News Date: November 15, 1996 http://www.reuters.gov/archive/1996/11/15/professional/links/19961 115epid006.html
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Scientists Identify Gene For Hemochromatosis Source: Reuters Medical News Date: July 30, 1996 http://www.reuters.gov/archive/1996/07/30/professional/links/19960 730scie002.html
·
Early Therapy Key To Long-Term Survival In Hemochromatosis Patients Source: Reuters Medical News Date: April 23, 1996 http://www.reuters.gov/archive/1996/04/23/professional/links/19960 423clin006.html
·
Excess alcohol use greatly increases cirrhosis risk in hemochromatosis patients Source: Reuters Medical News Date: March 12, 2002 http://www.reuters.gov/archive/2002/03/12/professional/links/20020 312clin015.html
·
Hemochromatosis gene mutations do not affect progression of chronic hepatitis C Source: Reuters Medical News Date: January 30, 2002 http://www.reuters.gov/archive/2002/01/30/professional/links/20020 130epid003.html
·
Most people with hemochromatosis gene mutation do not develop clinical disease Source: Reuters Medical News Date: January 18, 2002 http://www.reuters.gov/archive/2002/01/18/professional/links/20020 118clin005.html
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·
Hemochromatosis gene mutations tied to lower life expectancy Source: Reuters Medical News Date: November 20, 2001 http://www.reuters.gov/archive/2001/11/20/professional/links/20011 120epid005.html
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American Medical Labs to market new Bio-Rad hemochromatosis test Source: Reuters Industry Breifing Date: May 09, 2001 http://www.reuters.gov/archive/2001/05/09/business/links/20010509 inds015.html
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Relatives of hemochromatosis patients may have undetected related conditions Source: Reuters Medical News Date: November 27, 2000 http://www.reuters.gov/archive/2000/11/27/professional/links/20001 127epid001.html
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July is hemochromatosis month Source: Reuters Health eLine Date: July 10, 2000 http://www.reuters.gov/archive/2000/07/10/eline/links/20000710elin 011.html
·
Hemochromatosis gene carriers at risk of cardiovascular death Source: Reuters Medical News Date: September 21, 1999 http://www.reuters.gov/archive/1999/09/21/professional/links/19990 921epid001.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 http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within their search engine.
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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 “hemochromatosis” (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 “hemochromatosis” (or synonyms). If you know the name of a company that is relevant to hemochromatosis, 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 “hemochromatosis” (or synonyms).
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 to the following hyperlink: http://chid.nih.gov/detail/detail.html.
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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 “hemochromatosis” (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 hemochromatosis: ·
Liver Tests: Simple Blood Tests Can Reveal a Lot Source: Mayo Clinic Health Letter. 18(5): 1-3. May 2000. Contact: Available from Mayo Clinic Health Letter. Subscription Services, P.O. Box 53889, Boulder, CO 80322-3889. (800) 333-9037 or (303) 604-1465. Summary: This article, from a health newsletter, reviews the liver function tests that are used to monitor liver health and disease. The author begins by reviewing the healthy functions of the liver, including regulating the composition of the blood, manufacturing vital nutrients (such as cholesterol, vitamin A, certain proteins, bile), and neutralizing toxic substances. Sometimes there is an obvious sign of a problem, such as jaundice, which is a buildup of bilirubin in the blood, resulting in a yellow appearance of the skin and eyes. The various liver tests basically screen for three types of abnormalities: liver cell damage, reduced protein levels in the blood, and failure to eliminate certain substances from the blood. Information from the blood tests, combined with a thorough physical exam and sometimes diagnostic imaging, may be enough to reach a specific diagnosis; sometimes a liver biopsy is added to the list of diagnostic tests. Some of the more common liver disorders that are detected with these tests are viral hepatitis, alcohol or drug related liver disease, liver cancer, nonalcoholic steatohepatitis (a form of fatty liver), and hemochromatosis (high amounts of iron stored in the body). One sidebar reviews the drugs that can lead to liver toxicity. The author concludes that mild liver test abnormalities are normal; however, significantly abnormal test results should never be ignored. 1 figure.
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Liver Transplantation Source: idInsight. 2(3): 9. 1999. Contact: Available from Iron Disorders Institute. P.O. Box 2031, Greenville, SC 29602. (864) 241-0111. Fax (864) 244-2104. Website: www.irondisorders.org.
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Summary: When quality of life deteriorates because of advanced liver disease and the patient is not responding to therapies such as radiofrequency ablation, cryoablation, chemotherapy, and radiation, liver transplantation may be necessary to survive. This brief newsletter article, from the Iron Disorders Institute, reviews the use of liver transplantation. The author discusses preoperative care and testing, determining patient candidacy, the different types of liver transplantation (split liver, living related), and the signs of liver disease. Most donor livers come from cadavers; these livers must be recovered promptly and transplanted with 12 to 24 hours. Candidates for liver transplantation include patients with chronic liver disease such as cirrhosis, drug induced liver disease, Wilsons disease, hemochromatosis, acquired iron overload, some vascular diseases that contribute to liver failure, and primary liver cancer. The author notes that reducing the patient's iron levels with therapeutic phlebotomy (blood removal) can diminish the chances of developing liver cancer in those with cirrhosis of hemochromatosis. The article concludes with the contact number for the United Network for Organ Sharing (804-330-8500, www.unos.org) and two recommended websites for general
