THE 2002 OFFICIAL PATIENT’S SOURCEBOOK
on
USCULAR YSTROPHY 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 2002 Official Patient’s Sourcebook on Muscular Dystrophy: 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: 0-597-83210-2 1. Muscular Dystrophy-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 muscular dystrophy.
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 muscular dystrophy. 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 muscular dystrophy, Official Patient’s Sourcebooks are available for the following related topics: ·
The Official Patient's Sourcebook on Avascular Necrosis
·
The Official Patient's Sourcebook on Growth Plate Fractures
·
The Official Patient's Sourcebook on Osteogenesis Imperfecta
·
The Official Patient's Sourcebook on Osteoporosis
·
The Official Patient's Sourcebook on Scoliosis
·
The Official Patient's Sourcebook on Sjogren's Syndrome
·
The Official Patient's Sourcebook on Spinal Stenosis
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................................................................................................... 5
PART I: THE ESSENTIALS ................................................. 7 CHAPTER 1. THE ESSENTIALS ON MUSCULAR DYSTROPHY: GUIDELINES ........................................................................................... 9
Overview............................................................................................................... 9 What Is Muscular Dystrophy (MD)?................................................................ 10 Is There Any Treatment? ................................................................................... 11 What Is the Prognosis?....................................................................................... 11 What Research Is Being Done? .......................................................................... 11 More Guideline Sources ..................................................................................... 12 Vocabulary Builder............................................................................................. 18
CHAPTER 2. SEEKING GUIDANCE ....................................................... 21
Overview............................................................................................................. 21 Associations and Muscular Dystrophy .............................................................. 21 Finding More Associations................................................................................. 33 Finding Doctors.................................................................................................. 34 Selecting Your Doctor ........................................................................................ 36 Working with Your Doctor ................................................................................ 36 Broader Health-Related Resources ..................................................................... 38 Vocabulary Builder............................................................................................. 38
CHAPTER 3. CLINICAL TRIALS AND MUSCULAR DYSTROPHY ............................................................................................................. 41
Overview............................................................................................................. 41 Recent Trials on Muscular Dystrophy............................................................... 44 Benefits and Risks............................................................................................... 50 Keeping Current on Clinical Trials.................................................................... 53 General References.............................................................................................. 54 Vocabulary Builder............................................................................................. 55
PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL.................................................. 57 CHAPTER 4. STUDIES ON MUSCULAR DYSTROPHY ............................ 59
Overview............................................................................................................. 59 The Combined Health Information Database ..................................................... 59 Federally-Funded Research on Muscular Dystrophy ........................................ 63
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E-Journals: PubMed Central .............................................................................. 76 The National Library of Medicine: PubMed ...................................................... 79 Vocabulary Builder............................................................................................. 80
CHAPTER 5. PATENTS ON MUSCULAR DYSTROPHY ........................... 85
Overview............................................................................................................. 85 Patents on Muscular Dystrophy ........................................................................ 86 Patent Applications on Muscular Dystrophy .................................................. 103 Keeping Current ............................................................................................... 104 Vocabulary Builder........................................................................................... 104
CHAPTER 6. BOOKS ON MUSCULAR DYSTROPHY ............................. 107
Overview........................................................................................................... 107 Book Summaries: Federal Agencies .................................................................. 107 Book Summaries: Online Booksellers ............................................................... 108 The National Library of Medicine Book Index ................................................. 111 Chapters on Muscular Dystrophy.................................................................... 115 Directories......................................................................................................... 117 General Home References ................................................................................. 119 Vocabulary Builder........................................................................................... 120
CHAPTER 7. MULTIMEDIA ON MUSCULAR DYSTROPHY .................. 123
Overview........................................................................................................... 123 Video Recordings .............................................................................................. 123 Bibliography: Multimedia on Muscular Dystrophy ........................................ 124 Vocabulary Builder........................................................................................... 127
CHAPTER 8. PERIODICALS AND NEWS ON MUSCULAR DYSTROPHY 129
Overview........................................................................................................... 129 News Services & Press Releases ....................................................................... 129 Newsletters on Muscular Dystrophy ............................................................... 136 Academic Periodicals covering Muscular Dystrophy ...................................... 137 Vocabulary Builder........................................................................................... 139
CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES ................... 141
Overview........................................................................................................... 141 NIH Guidelines................................................................................................. 141 NIH Databases.................................................................................................. 142 Other Commercial Databases ........................................................................... 146 The Genome Project and Muscular Dystrophy................................................ 146 Specialized References....................................................................................... 151 Vocabulary Builder........................................................................................... 153
CHAPTER 10. DISSERTATIONS ON MUSCULAR DYSTROPHY ............ 155
Overview........................................................................................................... 155 Dissertations on Muscular Dystrophy............................................................. 155 Keeping Current ............................................................................................... 156 Vocabulary Builder........................................................................................... 157
PART III. APPENDICES .................................................. 159
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APPENDIX A. RESEARCHING YOUR MEDICATIONS.......................... 161
Overview........................................................................................................... 161 Your Medications: The Basics .......................................................................... 162 Learning More about Your Medications .......................................................... 164 Commercial Databases...................................................................................... 165 Contraindications and Interactions (Hidden Dangers) ................................... 166 A Final Warning .............................................................................................. 168 General References............................................................................................ 168 Vocabulary Builder........................................................................................... 169
APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ................... 171
Overview........................................................................................................... 171 What Is CAM? ................................................................................................. 171 What Are the Domains of Alternative Medicine?............................................ 172 Can Alternatives Affect My Treatment? ......................................................... 175 Finding CAM References on Muscular Dystrophy ......................................... 176 Additional Web Resources................................................................................ 183 General References............................................................................................ 188
APPENDIX C. RESEARCHING NUTRITION ......................................... 191
Overview........................................................................................................... 191 Food and Nutrition: General Principles........................................................... 192 Finding Studies on Muscular Dystrophy ........................................................ 196 Federal Resources on Nutrition........................................................................ 200 Additional Web Resources................................................................................ 201 Vocabulary Builder........................................................................................... 205
APPENDIX D. FINDING MEDICAL LIBRARIES.................................... 207
Overview........................................................................................................... 207 Preparation ....................................................................................................... 207 Finding a Local Medical Library ...................................................................... 208 Medical Libraries Open to the Public............................................................... 208
APPENDIX E. YOUR RIGHTS AND INSURANCE ................................. 215
Overview........................................................................................................... 215 Your Rights as a Patient................................................................................... 215 Patient Responsibilities .................................................................................... 219 Choosing an Insurance Plan............................................................................. 220 Medicare and Medicaid .................................................................................... 222 NORD’s Medication Assistance Programs ..................................................... 225 Additional Resources ........................................................................................ 226
ONLINE GLOSSARIES.................................................... 227 Online Dictionary Directories.......................................................................... 232
MUSCULAR DYSTROPHY GLOSSARY ..................... 233 General Dictionaries and Glossaries ................................................................ 247
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INDEX................................................................................... 249
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
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Muscular Dystrophy
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 2002 Official Patient’s Sourcebook on Muscular Dystrophy 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 muscular dystrophy, 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 muscular dystrophy. 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 muscular dystrophy 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
Introduction
3
appropriate 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 muscular dystrophy (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 muscular dystrophy. It also gives you sources of information that can help you find a doctor in your local area specializing in treating muscular dystrophy. Collectively, the material presented in Part I is a complete primer on basic research topics for patients with muscular dystrophy. Part II moves on to advanced research dedicated to muscular dystrophy. 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 muscular dystrophy. 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 muscular dystrophy or related disorders. The appendices are dedicated to more pragmatic issues faced by many patients with muscular dystrophy. 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 muscular dystrophy.
Scope While this sourcebook covers muscular dystrophy, your doctor, research publications, and specialists may refer to your condition using a variety of terms. Therefore, you should understand that muscular dystrophy is often considered a synonym or a condition closely related to the following: ·
Distal Muscular Dystrophy
·
Duchenne's Muscular Dystrophy
4
Muscular Dystrophy
·
Erb's Muscular Dystrophy
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Facioscapulohumeral Disease
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Fukuyama Syndrome
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Gower's Syndrome
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Inherited Myopathy
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Landouzy-dejerine Disease
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Landouzy-dejerine Dystrophy
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Landouzy-déjèrine Dystrophy
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Limb-girdle Muscular Dystrophy
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Myotonic Muscular Dystrophy
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Ocular Muscular Dystrophy
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Oculopharyngeal Muscular Dystrophy
·
Pseudohypertrophic Muscular Dystrophy
·
Steinert's Disease
In addition to synonyms and related conditions, physicians may refer to muscular dystrophy 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 muscular dystrophy:4 ·
359 muscular dystrophies and other myopathies
·
359.0 congenital muscular dystrophy
·
359.1 hereditary progressive muscular dystrophy
· 359.2 myotonic dystrophy 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 muscular dystrophy. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.
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
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 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 muscular dystrophy 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 muscular dystrophy is even indexed in search engines, a non-systematic approach often leads to frustration and disappointment. With this sourcebook, we hope to direct you to the information you need that you would not likely find using popular Web directories. Beyond Web listings, in many cases we will reproduce brief summaries or abstracts of available reference materials. These abstracts often contain distilled information on topics of discussion. Before beginning your search for information, it is important for you to realize that muscular dystrophy is considered a relatively uncommon condition. Because of this, far less research is conducted on muscular dystrophy compared to other health problems afflicting larger populations, like breast cancer or heart disease. Nevertheless, this sourcebook will prove useful for two reasons. First, if more information does become available on muscular dystrophy, the sources given in this book will be the most likely to report or make such information available. Second, some will find it important to know about patient support, symptom management, or diagnostic procedures that may be relevant to both muscular dystrophy and other conditions. By using the sources listed in the following chapters, selfdirected research can be conducted on broader topics that are related to muscular dystrophy but not readily uncovered using general Internet search engines (e.g. www.google.com or www.yahoo.com). In this way, we have
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Muscular Dystrophy
designed this sourcebook to complement these general search engines that can provide useful information and access to online patient support groups.5 While we focus on the more scientific aspects of muscular dystrophy, 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
For example, one can simply go to www.google.com, or other general search engines (e.g. www.yahoo.com, www.aol.com, http://www.msn.com/) and type in “muscular dystrophy support group” to find any active online support groups dedicated to muscular dystrophy.
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7
PART I: THE ESSENTIALS
ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on muscular dystrophy. 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 muscular dystrophy to you or even given you a pamphlet or brochure describing muscular dystrophy. Now you are searching for more in-depth 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 MUSCULAR DYSTROPHY: GUIDELINES Overview Official agencies, as well as federally-funded institutions supported by national grants, frequently publish a variety of guidelines on muscular dystrophy. 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 muscular dystrophy 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)6 The National Institutes of Health (NIH) is the first place to search for relatively current patient guidelines and fact sheets on muscular dystrophy. 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.
6
Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.
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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 muscular dystrophy 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 Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines at http://www.nih.gov/niams/healthinfo/
Among those listed above, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is especially noteworthy. The mission of NIAMS, a part of the National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. The National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse is a public service sponsored by the NIAMS that provides health information and information sources. The NIAMS provides the following guideline concerning muscular dystrophy.7
What Is Muscular Dystrophy (MD)?8 Muscular dystrophy (MD) refers to a group of genetic diseases characterized by progressive weakness and degeneration of the skeletal or voluntary muscles which control movement. The muscles of the heart and some other involuntary muscles are also affected in some forms of MD, and a few forms involve other organs as well. The major forms of MD include myotonic, Duchenne, Becker, limb-girdle, facioscapulohumeral, congenital, oculopharyngeal, distal and Emery-Dreifuss. Duchenne is the most common 7 This and other passages are adapted from the NIH and NIAMS (http://www.niams.nih.gov/hi/index.htm). “Adapted” signifies that the text is reproduced with attribution, with some or no editorial adjustments. 8 Adapted from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): http://www.ninds.nih.gov/health_and_medical/disorders/md.htm.
Guidelines 11
form of MD affecting children, and myotonic MD is the most common form affecting adults. MD can affect people of all ages. Although some forms first become apparent in infancy or childhood, others may not appear until middle age or later.
Is There Any Treatment? There is no specific treatment for any of the forms of MD. Physical therapy to prevent contractures (a condition in which shortened muscles around joints cause abnormal and sometimes painful positioning of the joints), orthoses (orthopedic appliances used for support) and corrective orthopedic surgery may be needed to improve the quality of life in some cases. The cardiac problems that occur with Emery-Dreifuss MD and myotonic MD may require a pacemaker. The myotonia (delayed relaxation of a muscle after a strong contraction) occurring in myotonic MD may be treated with medications such as phenytoin or quinine.
What Is the Prognosis? The prognosis of MD varies according to the type of MD and the progression of the disorder. Some cases may be mild and very slowly progressive, with normal lifespan, while other cases may have more marked progression of muscle weakness, functional disability and loss of ambulation. Life expectancy may depend on the degree of progression and late respiratory deficit. In Duchenne MD, death usually occurs in the late teens to early 20s.
What Research Is Being Done? The NINDS supports a broad program of research on MD. The goals of these studies are to increase understanding of MD and its cause(s), develop better therapies, and, ultimately, find ways to prevent and cure the disorder.
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Organizations Facioscapulohumeral Dystrophy (FSHD) Society 3 Westwood Road Lexington, MA 02420
[email protected] http://www.fshsociety.org Tel: 781-860-0501 Fax: 781-860-0599 Muscular Dystrophy Association 3300 East Sunrise Drive Tucson, AZ 85718-3208
[email protected] http://www.mdausa.org/ Tel: 520-529-2000 800-572-1717 Fax: 520-529-5300 Muscular Dystrophy Family Foundation 2330 North Meridien Street Indianapolis, IN 46208
[email protected] http://www.mdff.org Tel: 317-923-6333 800-544-1213 Fax: 317-923-6334 Parent Project for Muscular Dystrophy Research 1012 North University Blvd. Middletown, OH 45042
[email protected] http://www.parentprojectmd.org Tel: 413-424-0696 800-714-KIDS (5437) Fax: 513-425-9907
More Guideline Sources The guideline above on muscular dystrophy 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 muscular dystrophy. 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
Guidelines 13
muscular dystrophy. 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. 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 muscular dystrophy 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: ·
FSHD [Facioscapulohumeral Muscular Dystrophy] Source: Lexington, MA: FSH Society, Inc. 1997. 12 p. Contact: Available from FSH Society, Inc. Administrative Office, 3 Westwood Road, Lexington, MA 02420. (781) 860-0501. Fax (781) 8600599. Web Site: fshsociety.org. PRICE: Single copy free.
14 Muscular Dystrophy
Summary: This brochure for people with facioscapulohumeral muscular dystrophy (FSHD) uses a question and answer format to provide information on the cause, symptoms, prognosis, and treatment of this autosomal dominant inherited disease. The estimated occurrence of FSHD is one in 20,000. Most people who have FSHD inherited a chromosome 4 genetic mutation from a parent with the disease. FSHD is characterized by progressive weakening and loss of skeletal muscle. Symptoms are usually first seen in the face, shoulders, and upper arms. Muscles in the neck, torso, and lower limbs eventually weaken also. People with the disease typically begin to notice muscle weakness during adolescence, and a physician can usually recognize and diagnose the disease by the age of 20. An infantile form of FSHD may occur in rare instances. Prognosis is variable, and there is no treatment or cure for FSHD, physical, occupational, and nutrition therapy may be beneficial. Surgery to attach the scapulae to the back may be performed in some cases. The brochure also provides information on the FSH Society. 1 figure. ·
Facts About Friedreich's Ataxia Source: Tucson, AZ: Muscular Dystrophy Association. 1999. 16 p. Contact: Available from Muscular Dystrophy Association. Publications Department, 3300 East Sunrise Drive, Tucson, AZ 85718. (800) 572-1717 or (520) 529-2000. Website: www.mdausa.org. PRICE: Single copy free. Summary: This brochure describes Friedreich's ataxia (FRDA), an inherited progressive disorder of the nervous system that affects balance, coordination, movement, and sensation. Ataxia refers to a loss of coordination and is usually the earliest and most prominent characteristic of the disease. Increasing impairment of balance and movement eventually lead to the loss of the ability to walk; speech and swallowing difficulties may occur as well. The brochure is written in a question and answer format and covers incidence, heredity, recessive inheritance, symptoms, treatment options, disease progression, speech and swallowing problems associated with FRDA, how FRDA affects the heart, genetic testing, and the role of the Muscular Dystrophy Association (MDA). The brochure concludes with a brief description of the purpose and programs of the MDA. 7 figures.
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Augmentative Communication: Consumers Source: Rockville, MD: American Speech-Language-Hearing Association (ASHA). 199x. 36 p.
Guidelines 15
Contact: Available from American Speech-Language-Hearing Association (ASHA). Product Sales, 10801 Rockville Pike, Rockville, MD 20852. (888) 498-6699. TTY (301) 897-0157. Website: www.asha.org. PRICE: $1.50 per booklet. Item Number 0210251. Summary: This consumer information booklet describes the use of augmentative communication for people who can hear but have little or no usable speech. Such severe communication disabilities can result from severe language delay, cerebral palsy, mental retardation, autism, traumatic brain injury (TBI), or stroke. In addition, a variety of specific neuromuscular disorders, such as amyotrophic lateral sclerosis (ALS), dystonia, Huntington's disease, multiple sclerosis, and muscular dystrophy can also cause severe speech problems. Augmentative communication is defined as any method other than speech, to send a message from one person to another. Techniques of augmentative communication range from specialized gestures and sign language to communication aids such as sign boards to highly specialized computerbased techniques. The booklet emphasizes the implementation of an effective augmentative communication system, regardless of level of sophistication, requires a detailed multidisciplinary assessment, training for the user(s), and regular re-evaluation. The booklet outlines the roles of members of the patient care team, including the speech language pathologist, the occupational therapist, the physical therapist, physicians, the educator, social worker, psychologist, rehabilitation engineer, computer programmer, vocational counselor, audiologist, orthotist, and manufacturers or distributors of communication devices. The author encourages readers to become active partners in their own care or the care of their children with communication disorders. The booklet includes a resource list of professional and consumer groups concerned with augmentative communication. An appendix provides a glossary of some of the terms used in augmentative communication. The booklet is illustrated with black and white photographs.
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 “muscular dystrophy” or synonyms. The following was recently posted: ·
ACC/AHA guidelines for implantation of cardiac pacemakers and antiarrhythmia devices: a report of the American College of
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Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Pacemaker Implantation). Source: American College of Cardiology/American Heart Association.; 1998 April (reviewed 2000); 34 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 0495&sSearch_string=muscular+dystrophy ·
Clinical practice guidelines for the use of chemotherapy and radiotherapy protectants. Source: American Society of Clinical Oncology.; 1999 October; 23 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1376&sSearch_string=muscular+dystrophy
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Evaluation anesthesia.
and
preparation
of
pediatric
patients
undergoing
Source: American Academy of Pediatrics.; 1996 September; 12 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 0999&sSearch_string=muscular+dystrophy ·
Practice advisory on the treatment of amyotrophic lateral sclerosis with riluzole. Source: American Academy of Neurology.; 1997; 3 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 0652&sSearch_string=muscular+dystrophy
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Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Source: American Academy of Neurology.; 2000 July; 9 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2052&sSearch_string=muscular+dystrophy 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
Guidelines 17
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: ·
FAQ - About Loving Paws Dogs Summary: Loving Paws Dogs are service dogs trained for disabled children (specifically muscular dystrophy, cerebral palsy and spina bifida) up to aged 18. This information answers questions about the program. Source: Loving Paws Assistance Dogs http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=4239
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Muscular Dystrophy Summary: Muscular dystrophy (MD) refers to a group of genetic diseases characterized by progressive weakness and degeneration of the skeletal or voluntary muscles which control movement. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=749
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Treating Scoliosis in Muscular Dystrophy Summary: Written especially for children with muscular dystrophy, this booklet provides information concerning scoliosis treatments. Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=4097
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 muscular dystrophy. The drawbacks of this approach are
18 Muscular Dystrophy
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
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDÒHealth: http://my.webmd.com/health_topics
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: Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH]
Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH]
Guidelines 19
Ataxia: Failure of muscular coordination; irregularity of muscular action. [EU]
Cardiac: Pertaining to the heart. [EU] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Chemotherapy: The treatment of disease by means of chemicals that have a specific toxic effect upon the disease - producing microorganisms or that selectively destroy cancerous tissue. [EU] Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibres. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Electrodiagnosis: Diagnosis of disease states by recording the spontaneous electrical activity of tissues or organs or by the response to stimulation of electrically excitable tissue. [NIH] Gestures: Movement of a part of the body for the purpose of communication. [NIH] Heredity: 1. the genetic transmission of a particular quality or trait from parent to offspring. 2. the genetic constitution of an individual. [EU] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Infantile: Pertaining to an infant or to infancy. [EU] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Myopathy: Any disease of a muscle. [EU] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU]
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Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Radiotherapy: The treatment of disease by ionizing radiation. [EU] Respiratory: Pertaining to respiration. [EU] Riluzole: A glutamate antagonist that has reported anticonvulsant activity. It has been shown to prolong the survival of patients with amyotrophic lateral sclerosis and has been approved in the United States to treat patients with ALS. [NIH] Sclerosis: A induration, or hardening; especially hardening of a part from inflammation and in diseases of the interstitial substance. The term is used chiefly for such a hardening of the nervous system due to hyperplasia of the connective tissue or to designate hardening of the blood vessels. [EU]
Seeking Guidance 21
CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people with muscular dystrophy. 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.9 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 muscular dystrophy. The chapter ends with a discussion on how to find a doctor that is right for you.
Associations and Muscular Dystrophy 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.10 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. 10 This section has been adapted from http://www.ahcpr.gov/consumer/diaginf5.htm. 9
22 Muscular Dystrophy
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): ·
Challenge Air For Kids and Friends Address: Challenge Air For Kids and Friends Love Field North Concourse, 8008 Cedar Springs Road, Suite N106 LB24, Dallas, TX 75235 Telephone: (214) 351-3353 Toll-free: (800) 714-5437 Fax: (214) 351-4565 Email:
[email protected] Web Site: http://www.challengeair.co Background: Challenge Air for Kids and Friends is a national nonprofit organization dedicated to providing motivational, occupational, recreational, and educational therapy to disabled, disadvantaged, and seriously ill children through the experience of flight with a disabled pilot free of charge. Challenge Air was established in 1993 by a pilot who lost the use of his legs when his plane crashed while returning from a combat mission over Vietnam. The purpose of the flights is to provide enjoyable experiences and to demonstrate that the human spirit can prevail over any physical or mental obstacle. Challenge Air organizes day long events that allow groups of children to enjoy motivational flights, food, and other fun. Events have include handicapped athletic groups, therapy programs, social service organizations, and more. A typical Challenge Air fly day serves more than 150 children and their families. Each program is underwritten by individual, corporate, and philanthropic donations. Challenge Air has flown over 4,000 children in 15 states as well as Canada. Challenge Air has several materials available including brochures, pamphlets, videos, and a newsletter. Challenge Air also has a web site at http://www.challengeair.com. Relevant area(s) of interest: Muscular Dystrophy
Seeking Guidance 23
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Citizens For Independence In Living And Breathing Telephone: (416) 227-0623 Toll-free: (800) 714-5437 Fax: (416) 277-062 Background: The Citizens For Independence In Living and Breathing (CILB) is a not-for-profit organization dedicated to promoting choice, control, and independence through education and information for both current and prospective ventilator users with neuromuscular disorders. CILB was established in 1988, when community action funding enabled the Canadian Paraplegic Association to investigate the needs of severely disabled individuals including ventilator users. CILB assists the community by providing information concerning the choice of independent living options available to individuals who are capable of directing their own services; publishing and disseminating information about living with a ventilator and alternative ventilation techniques; providing information about available community services, attendant services, health care, education, employment, and recreation; providing information regarding funding for the hiring and training of attendants; and assisting in the development of support networks for users, families, and others who require assistance. CILB consists of 65 active members who participate in various advisory committees and groups such as Ontario Ministries including Health, Community and Social Services, Housing, and Education and Citizenship; the Canadian Standards Association; and District Health Councils. Educational materials include pamphlets, CILB conference session tapes, and videotapes.
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Disabled Sports USA Address: Disabled Sports USA 451 Hungerford Drive, Suite 100, Rockville, MD 20850 Telephone: (301) 217-0960 Toll-free: 1 800 656 632 Fax: (301) 217-0968 Email:
[email protected] Web Site: http://www.dsusa.org/~dsusa/dsusa.htm Background: Disabled Sports USA (DS/USA) is a not-for-profit organization dedicated to ensuring that disabled people have access to sports, recreation, and physical education programs from preschool through college to elite sports levels. Established in 1967 by disabled Vietnam veterans, DS/USA serves people with physical disabilities that restrict mobility, including amputations, weakness or paralysis of both legs (paraplegia), paralysis of all four limbs (quadriplegia), cerebral palsy, head injury, multiple sclerosis, muscular dystrophy, spina bifida,
24 Muscular Dystrophy
stroke, and visual impairment. DS/USA consists of more than 60,000 members and 80 chapters around the United States. Educational materials include a general information packet, a newsletter entitled 'Disabled Sports USA Update,' and a sports magazine entitled 'Challenge.' Program activities include sporting activities and events, patient education (e.g., workshops), and patient networking. DS/USA maintains a web site at http://www.dsusa.org/~dsusa/dsusa.html. ·
European Alliance of Muscular Dystrophy Associations Address: European Alliance of Muscular Dystrophy Associations 7-11 Prescott Place, London, SW4 6BS, United Kingdom Telephone: 44 171 720 8055 Toll-free: 1 800 656 632 Fax: 44 171 498 8963 Email:
[email protected] Web Site: http://www.sonnet.co.uk/eamda Background: The European Alliance of Muscular Dystrophy Associations (EAMDA) is a nonprofit organization that was established in 1971. The organization consists of delegates from its over 30 member associations and primarily serves as an information network, providing advice about neuromuscular conditions and offering information, support, and resources to families, caregivers, and professionals throughout Europe. Muscular dystrophy refers to a group of genetic disorders characterized by progressive degeneration of muscle fibers, resulting in associated weakness, disability, and deformity. The different forms of muscular dystrophy may be categorized based upon age at onset, specific muscle groups affected, rate of disease progression, and mode of inheritance. Forms of muscular dystrophy include Becker muscular dystrophy, Duchenne muscular dystrophy, and ocular myopathies. The EAMDA includes a Youth Organization, known as the EYO, that is made up of delegates who represent the young people in their own national associations. The EYO is committed to providing assistance and support for young people with muscular dystrophy; promoting networking among affected youths, encouraging the exchange of information and mutual support; and providing assistance to the National Youth Organizations concerning the different aspects of these disorders, such as quality of life issues, self image, and medical intervention. The EAMDA also offers a variety of educational materials including fact sheets on the different forms of muscular dystrophy, a regular newsletter, and several additional publications. The EAMDA's web site on the Internet provides information on the Alliance and its Youth Organization; access to MD fact sheets, the EAMDA newsletter, and a glossary of MD-related terms;
Seeking Guidance 25
contact information for neuromuscular disorder support groups; and links to additional sources of information and support. Relevant area(s) of interest: Muscular Dystrophy ·
Facio-Scapulo-Humeral Society, Inc Address: Facio-Scapulo-Humeral Society, Inc. 3 Westwood Road, Lexington, MA 02420 Telephone: (781) 860-0501 Toll-free: (800) 433-5255 Fax: (781) 860-0599 Email:
[email protected] Web Site: http://www.fshsociety.or Background: Facio-Scapulo-Humeral Society, Inc. (FSH Society) is a voluntary not- for-profit organization created to address issues and needs specifically related to Facio-Scapulo-Humeral Muscular Dystrophy (FSHD), a rare inherited neuromuscular disorder. Established in 1989, the Facio-Scapulo-Humeral Society is dedicated to encouraging and promoting ongoing scientific and clinical research and development into the nature of Facio-Scapulo-Humeral Syndrome through solicitation of grants and contributions from private foundations, the pharmaceutical industry, and others. The Society also seeks to develop educational programs aimed at the medical community, government bodies, and the public. The Society accumulates and disseminates timely information about FSHD and actively cooperates with related organizations to foster communication among all interested parties. In addition, Facio-ScapuloHumeral Society promotes professional education; provides appropriate referrals including to support groups; and promotes patient advocacy and legislation beneficial to individuals with FSHD. The Society offers a variety of educational and support materials including brochures, fact sheets, and a newsletter. The FSH Society provies grants for research on FSHD.
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March of Dimes Birth Defects Foundation Address: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue, White Plains, NY 10605 Telephone: (914) 428-7100 Toll-free: (888) 663-4637 Fax: (914) 997-4763 Email:
[email protected] Web Site: http://www.modimes.or
26 Muscular Dystrophy
Background: The March of Dimes Birth Defects Foundation is a national not-for- profit organization that was established in 1938. The mission of the Foundation is to improve the health of babies by preventing birth defects and infant mortality. Through the Campaign for Healthier Babies, the March of Dimes funds programs of research, community services, education, and advocacy. Educational programs that seek to prevent birth defects are important to the Foundation and to that end it produces a wide variety of printed informational materials and videos. The March of Dimes public health educational materials provide information encouraging health- enhancing behaviors that lead to a healthy pregnancy and a healthy baby. ·
Muscular Dystrophy Association Address: Telephone: (520) 529-2000 Toll-free: (800) 572-1717 Fax: (520) 529-5300 Email:
[email protected] Web Site: http://www.mdausa.or Background: Established in 1950, the Muscular Dystrophy Association (MDA) is a non-profit, voluntary health agency dedicated to providing comprehensive medical services to individuals affected by neuromuscular diseases. MDA provides these services at 240 hospitalaffiliated clinics across the United States. The Association s worldwide research program, which funds approximately 400 individual scientific investigations each year, represents the largest single initiative to advance current knowledge of neuromuscular diseases and to find cures and treatments for this group of diseases. At facilities in MDA's hospitalaffiliated clinics, affected individuals receive diagnosis and follow-up care from specialists in neuromuscular diseases. In addition to its medical services and research programs, MDA conducts educational programs for the public and for medical professionals. The Association publishes and distributes a wide variety of print materials. MDA also sponsors scientific symposia as well as other meetings of specialists in the field of neuromuscular disorders. Relevant area(s) of interest: Muscular Dystrophy
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Muscular Dystrophy Association (Australia) Address: Muscular Dystrophy Association (Australia) GPO Box 9932, Melbourne, 3001, Australia Telephone: 61 3 9370 0477 Toll-free: 1 800 656 632
Seeking Guidance 27
Fax: 61 3 9370 0393 Email:
[email protected] Web Site: http://www.mda.org.a Background: The Muscular Dystrophy Association (MDA) is a not-forprofit organization in Australia that was founded in the early 1970s by a group of people affected by muscular dystrophy (MD). Muscular dystrophy refers to a group of genetic disorders characterized by progressive degeneration of muscle fibers, resulting in associated weakness, disability, and deformity. The different forms of muscular dystrophy may be categorized based upon age at onset, specific muscle groups affected, rate of disease progression, and mode of inheritance. The Muscular Dystrophy Association is committed to improving the quality of life of individuals with muscular dystrophy and other neuromuscular diseases. To fulfill its mission and objectives, the Association provides a variety of educational materials, conducts MDA camps for children and adults with neuromuscular disorders, and promotes and supports research. The Association's materials include information sheets on different forms of muscular dystrophy, parents guides, glossaries, and materials discussing the various aspects of these disorders. The Association also maintains a web site on the Internet that provides understandable information on muscular dystrophy, a FAQ ('frequently asked questions') area, a guestbook area for online visitors, and links to additional sources of information and support. In 1985, the Association established the Muscular Dystrophy Research Foundation to help ensure sufficient funding to accelerate research and to provide funds required for treatment programs. The MDA, in association with St. Vincents Hospital and the Department of Medicine, Melbourne University, is also affiliated with the Melbourne Neuromuscular Research Centre, and sponsors scientific research seminars and conferences. Relevant area(s) of interest: Muscular Dystrophy ·
Muscular Dystrophy Association of Canada Address: Telephone: 416-488-2699 Toll-free: (800) 567-2873 EFax: 416-488-7523 Web Site: http://www.mdac.c Background: The Muscular Dystrophy Association of Canada (MDAC) is not-for-profit voluntary organization dedicated to eliminating neuromuscular disorders and alleviating the associated symptoms. 'Neuromuscular disorders' are a group of diseases affecting the body s
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ability to move due to an underlying neurological disease. Whether the problem originates within the motor nerve cell, the nerve, or the muscle, the most commonly experienced symptoms are varying degrees of progressive muscle weakness and wasting. There are over 40 nerve and muscle disorders covered under the umbrella of the Muscular Dystrophy Association of Canada. Founded in 1954, the Association s three main goals are funding research that will ultimately result in discovering the causes, treatments, and cures for muscular dystrophy and other neuromuscular disorders; providing support services that assist individuals and families affected by neuromuscular disorders; and providing information to affected individuals, their families, health care professionals, educators, and the general public as to the nature and management of neuromuscular disorders. Services provided by MDAC include the dissemination of information, advocacy, referrals, travel assistance, and some financial assistance with mobility equipment. MDAC also houses donated equipment for use by clients upon request. Informational brochures include 'What Is Spinal Muscular Atrophy?,' 'What Is Myotonic Dystrophy?,' and 'What Is Muscular Dystrophy?'. MDAC also publishes a news magazine entitled 'CONNECTIONS' that features information and articles on various neuromuscular disorders and on related topics such as research, genetics, parenting, and coping with a disability. Additionally, the organization provides advocacy services in resolving individual or community problems. Such issues might involve education, employment, or transportation. Relevant area(s) of interest: Muscular Dystrophy ·
Muscular Dystrophy Group of Great Britain and Northern Ireland Address: Muscular Dystrophy Group of Great Britain and Northern Ireland 7-11 Prescott Place, London, SW4 6BS, United Kingdom Telephone: 0171 720 8055 Toll-free: 1 800 656 632 Fax: 0171 498 0670 Email:
[email protected] Web Site: http://www.sonnet.co.uk/muscular-dystroph Background: The Muscular Dystrophy Group of Great Britain and Northern Ireland (MDG) is a voluntary research organization dedicated to identifying the causes of muscular dystrophy and allied conditions in order to develop treatments that will alleviate symptoms while working to discover a cure. Muscular Dystrophy (MD) is a group of rare inherited muscle wasting diseases. In some forms of MD, muscles of the hips and shoulders are weakened, walking abnormalities (ataxia) develop, and mild mental retardation may be present. MDG was established in 1959
Seeking Guidance 29
and is affiliated with two other organizations, the European Alliance of MDA and the World Alliance of MDA. The MDG currently provides funding for seven Muscle Centers that are designed to provide comprehensive medical care to individuals with neuromuscular conditions, and to provide researchers within and between the Centers with medical data and samples that will assist research. There are two types of MDG grants to centers, a Research Servicing Grant which supports costs such as equipment servicing, specialist technicians, secretarial staff, etc. and a Medical Services Grant which provides computing facilities and secretarial staff. Educational materials include an annual review covering different areas of concern for people affected by Muscular Dystrophy. MDG can be reached on the world wide web at http://WWW.sonnet.co.uk/muscular-dystrophy. Relevant area(s) of interest: Muscular Dystrophy ·
Muscular Dystrophy Ireland Address: Muscular Dystrophy Ireland Carmichael House, North Brunswick Street, Dublin 7, , Ireland Telephone: 353 1 8721501 Toll-free: (800) 714-5437 Fax: 353 1 8724482 Email:
[email protected] Web Site: http://www.mdi.ie Background: Muscular Dystrophy Ireland (MDI) is a national voluntary nonprofit organization with a membership of approximately 500 individuals and families throughout Ireland. The organization's primary objective is to provide support to people with muscular dystrophy and their families through the provision of a range of services, including counseling, respite services, holidays, youth activities, and independent living and training opportunities. Muscular dystrophy is a collective term referring to a variety of genetic neuromuscular disorders characterized by progressive degeneration and weakening of muscles. The different forms of muscular dystrophy may be categorized based upon age at onset, specific muscle groups affected, rate of disease progression, and mode of inheritance. Muscular Dystrophy Ireland was founded in 1972 and currently has a head office as well as two divisional offices. In addition to providing supportive services, the MDI is committed to promoting and supporting research, conducting annual general meetings, organizing special youth activities for its younger members, and offering a variety of educational materials including the 'MDI Magazine.' Muscular Dystrophy Ireland also maintains a web site on the Internet that discusses the organization's mission, objectives, and services; offers a
30 Muscular Dystrophy
guestbook area for online visitors; and provides linkage to additional sources of information and support. Relevant area(s) of interest: Muscular Dystrophy ·
Parent Project for Muscular Dystrophy Research Address: Telephone: (513) 424-7452. Toll-free: (800) 714-543 Fax: (513) 425-9907. Background: The Parent Project for Muscular Dystrophy Research is a not-for-profit national health organization dedicated to funding ongoing medical research to find a cure for Duchenne Muscular Dystrophy. Duchenne Muscular Dystrophy is a chronic, progressive, inherited form of muscular dystrophy usually beginning in early childhood; it is characterized by enlargement of muscles, weakness in the pelvis and shoulders, muscular atrophy, and additional symptoms. Established in 1994, the organization's scientific review board is in place to channel funding to those areas currently lacking in research funding. The Parent Project provides current information on Duchenne Muscular Dystrophy and related disorders such as Becker Muscular Dystrophy through brochures and audio-visual materials. Relevant area(s) of interest: Muscular Dystrophy
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Parent Project for Muscular Dystrophy Research, Inc Address: Parent Project for Muscular Dystrophy Research, Inc. 125 Marymont Court, Middletown, OH 45042 Telephone: (513) 424-7452 Toll-free: (800) 714-5437 Fax: (513) 425-9907 Email:
[email protected] Web Site: http://www.parentdmd.or Background: The Parent Project for Muscular Dystrophy Research, Inc. (formerly the Parent Project for Duchenne Muscular Dystrophy) is a notfor-profit national health organization dedicated to funding ongoing medical research to find a cure for Duchenne Muscular Dystrophy. Duchenne Muscular Dystrophy is a chronic, progressive, inherited form of muscular dystrophy usually beginning in early childhood; it is characterized by enlargement of muscles, weakness in the pelvis and shoulders, muscular atrophy, and additional symptoms. Established in 1994, the organization has a scientific review board in place to channel funding to those areas currently lacking in research funding. The Parent
Seeking Guidance 31
Project provides current information on Duchenne Muscular Dystrophy and related disorders such as Becker Muscular Dystrophy through brochures and audio-visual materials. Relevant area(s) of interest: Muscular Dystrophy ·
Scapuloperoneal Disease Association Address: Scapuloperoneal Disease Association 610 Navesink Avenue, Ocean Gate, NJ 08740 Telephone: (908) 269-0357 Toll-free: (800) 826-0826 Fax: (908) 269- 035 Background: The Scapuloperoneal Disease Association (SPDA) is an international self-help and research organization dedicated to providing information, assistance, and support to individuals and family members affected by Scapuloperoneal Muscular Dystrophy. Scapuloperoneal Muscular Dystrophy, a rare inherited muscular dystrophy that may become apparent early in life, is characterized by slowly progressive muscle weakness of the upper arms and shoulder blade area (scapula) as well as certain leg muscle groups below the knee (peroneal). Established in 1994, the SPDA provides networking services that enable affected individuals and family members to exchange information, support and resources; promotes basic and clinical research development; fosters communication among related organizations; serves to represent individuals and family members affected by Scapuloperoneal Muscular Dystrophy; and accumulates and disseminates information and materials concerning this disorder.
·
Shriners Hospitals for Children Address: Shriners Hospitals for Children P.O. Box 31356, Tampa, FL 33613-3356 Telephone: (813) 281-0300 Toll-free: (800) 237-5055 Fax: (813) 281-8496 Web Site: http://www.shrinershq.or Background: The Shriners Hospital for Children and the Shriners Burn Institutes are a network of pediatric hospitals that provide no-cost medical care to children with orthopedic problems or burn injuries. Shriners Hospital conducts research on orthopedic treatment and burn care and trains healthcare professionals in the treatment of orthopedic disabilities and burn injuries. Established in 1922, the hospitals are substantially funded through the Shriners Hospital for Children
32 Muscular Dystrophy
endowment fund. The hospitals treat children with a variety of diseases including (but not limited to) scoliosis, osteogenesis imperfecta, Legg Calve Perthes, and others. Burns and spinal injuries are also treated. Shriners Hospital consists of 23 chapters and offers educational materials such as 'Between Us' magazine, '20 Questions,' and 'The Story of Shriners Hospitals.' In addition, the organization assists in training physicians and other medical professionals in the treatment of orthopedic disabilities and burn injuries. The Shriners also operate a World Wide Web site at http://www.shrinershq.org. Relevant area(s) of interest: Muscular Dystrophy, Scoliosis ·
Society for Muscular Dystrophy Information International Address: Society for Muscular Dystrophy Information International P.O. Box 479, Bridgewater, Nova Scotia, B4V 2X6, Canada Telephone: (902) 685-3961 Toll-free: (800) 714-5437 Fax: (902) 685-3962 Email:
[email protected] Web Site: Non Background: The Society for Muscular Dystrophy Information International (SMDI) is a not-for-profit registered Canadian charity dedicated to assisting people in helping themselves by reducing the national and international isolation of individuals and organizations concerned with neuromuscular disorders/disabilities (e.g., muscular dystrophy and over 50 allied disorders). In general, 'neuromuscular disorder' is a term used to describe a group of over 50 diseases affecting the body's motor neurons (nerves and muscles). Symptoms may include varying degrees of progressive muscle weakness and loss of muscle mass (wasting). SMDI was established in 1983 to provide a non-technical information link for individuals with neuromuscular disorders and for organizations around the world; to link people with other people and organizations concerned with their disorder; to share information to assist people in helping themselves; and to create increased public awareness of this group of disorders. The Society publishes two biannual newsletters entitled 'SMDI International Newsletter,' a publication for those concerned with muscular dystrophy or the allied disorders and 'Access - Able Information,' a quarterly disability information resource publication. In addition to educational materials, brochures and referrals are available. Relevant area(s) of interest: Muscular Dystrophy
Seeking Guidance 33
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 muscular dystrophy. 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 “muscular dystrophy” (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 “muscular dystrophy”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” By making these selections and typing in “muscular dystrophy” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with muscular dystrophy. You should check back periodically with this database since it is updated every 3 months.
34 Muscular Dystrophy
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 “muscular dystrophy” (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. The following Internet sites may be of particular interest: ·
The Muscular Dystrophy Adult Support Group www.onyx.org/mdasg.htm
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FSH-Muscular Dystrophy Support Group www.fsh-group.org
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Muscular Dystrophy Association Support Group www.ggc.org/mdasup.html
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 muscular dystrophy 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:11 ·
If you are in a managed care plan, check the plan's list of doctors first.
11
This section is adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.
Seeking Guidance 35
·
Ask doctors or other health professionals who work with doctors, such as hospital nurses, for referrals.
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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.
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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.
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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 12 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.
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.
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. 12
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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 muscular dystrophy?
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Really listen to my questions?
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Answer in terms I understood?
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Show respect for me?
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Ask me questions?
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Make me feel comfortable?
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Address the health problem(s) I came with?
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Ask me my preferences about different kinds of treatments for muscular dystrophy?
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Spend enough time with me?
Trust your instincts when deciding if the doctor is right for you. But remember, it might take time for the relationship to develop. It takes more than one visit for you and your doctor to get to know each other.
Working with Your 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.
13 This
section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. 14 This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.
Seeking Guidance 37
·
Bring a “health history” list with you (and keep it up to date).
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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.
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Tell your doctor about any natural or alternative medicines you are taking.
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Bring other medical information, such as x-ray films, test results, and medical records.
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Ask questions. If you don't, your doctor will assume that you understood everything that was said.
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Write down your questions before your visit. List the most important ones first to make sure that they are addressed.
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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.
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Ask your doctor to draw pictures if you think that this would help you understand.
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Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.
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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.
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Take information home. Ask for written instructions. Your doctor may also have brochures and audio and videotapes that can help you.
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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.
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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
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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: Atrophy: A wasting away; a diminution in the size of a cell, tissue, organ, or part. [EU] Blindness: The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Hyperphagia: Ingestion of a greater than optimal quantity of food. [NIH] Hypogonadism: A condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [EU] You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.
15
Seeking Guidance 39
Hypotonia: A condition of diminished tone of the skeletal muscles; diminished resistance of muscles to passive stretching. [EU] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Nasal: Pertaining to the nose. [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Oral: Pertaining to the mouth, taken through or applied in the mouth, as an oral medication or an oral thermometer. [EU] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Paralysis: Loss or impairment of motor function in a part due to lesion of the neural or muscular mechanism; also by analogy, impairment of sensory function (sensory paralysis). In addition to the types named below, paralysis is further distinguished as traumatic, syphilitic, toxic, etc., according to its cause; or as obturator, ulnar, etc., according to the nerve part, or muscle specially affected. [EU] Paraplegia: Paralysis of the legs and lower part of the body. [EU] Quadriplegia: Severe or complete loss of motor function in all four limbs which may result from brain diseases; spinal cord diseases; peripheral nervous system diseases; neuromuscular diseases; or rarely muscular diseases. The locked-in syndrome is characterized by quadriplegia in combination with cranial muscle paralysis. Consciousness is spared and the only retained voluntary motor activity may be limited eye movements. This condition is usually caused by a lesion in the upper brain stem which injures the descending cortico-spinal and cortico-bulbar tracts. [NIH] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Ventilation: 1. in respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. in psychiatry, verbalization of one's emotional problems. [EU]
Clinical Trials 41
CHAPTER 3. CLINICAL TRIALS AND MUSCULAR DYSTROPHY 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 muscular dystrophy. 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 muscular dystrophy 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.
The discussion in this chapter has been adapted from the NIH and the NEI: www.nei.nih.gov/netrials/ctivr.htm.
16
42 Muscular Dystrophy
·
Phase II. Researchers conduct Phase II trials in small numbers of patients to find out the effect of a new treatment on muscular dystrophy.
·
Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for muscular dystrophy 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 muscular dystrophy 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 muscular dystrophy. 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 muscular dystrophy 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
43
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 muscular dystrophy 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 muscular dystrophy. 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
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who continue to return for follow-up examinations can provide this important long-term information.
Recent Trials on Muscular Dystrophy 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 muscular dystrophy.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. ·
A multicenter randomized placebo-controlled double-blind study to assess efficacy and safety of glutamine and creatine monohydrate in Duchenne muscular dystrophy (DMD) Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Children's National Medical Center Purpose - Excerpt: To establish a collaborative group of clinical trial centers, with standardized equipment and protocols, able to conduct both drug and gene therapy trials in DMD. To evaluate the therapeutic effect of glutamine and creatine monohydrate on muscle strength in children with DMD. To validate the use of QMT (quantitative muscle strength testing) and gait analysis in children with DMD as reliable tools to quantify muscle strength, monitor disease progression and assess therapeutic response. Phase(s): Phase III Study Type: Interventional Contact(s): Missouri; Washington University School of Medicine, St. Louis, Missouri, 63110, United States; Recruiting; Alan Pestronk, M.D. 314-362-6981
[email protected]; Alan Pestronk, M.D., Principal Investigator
17
These are listed at www.ClinicalTrials.gov.
45
Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00018109 ·
An open-label pilot study of Coenzyme Q10 in steroid-treated Duchenne muscular dystrophy Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is currently recruiting patients. Sponsor(s): Cooperative International Neuromuscular Research Group Purpose - Excerpt: This study will help to determine the safety and efficacy of the nutritional supplement Coenzyme Q10 when added to steroids as a treatment for Duchenne muscular dystrophy (DMD). Boys with DMD who are enrolled in this study will should be on a stable dose of steroids for at least six months, and will remain on their usual dose throughout the study. They will complete two screening visits within a one-week period, and if enrolled will then have their strength tested monthly for three months before beginning therapy with Coenzyme Q10. Once Coenzyme Q10 therapy is started, participants will have their strength tested monthly for six months. Following the six month treatment period, participants will be given the option to remain on Coenzyme Q10 until the study is completed. Phase(s): Phase II Study Type: Interventional Contact(s): Erik K Henricson, MPH 202-884-3813 EHenricson@ cnmcresearch.org Diana M Escolar, MD 202-884-6080 DEscolar@ cnmcresearch.org; District of Columbia; Children's National Medical Center, Washington, District of Columbia, 20010, United States; Recruiting; Erik K Henricson, MPH 202-884-3813 EHenricson@ cnmcresearch.org; Diana M Escolar, MD, Principal Investigator Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00033189
·
Clinical trial of creatine in amyotrophic lateral sclerosis [ALS] Condition(s): Amyotrophic Lateral Sclerosis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Muscular Dystrophy Association Purpose - Excerpt: The purpose of this study is to evaluate the safety and effectiveness of creatine treatment in amyotrophic lateral sclerosis (ALS). There is currently no known effective treatment for ALS. It is known that nerve cells die in the brains and spinal cords of patients with ALS but the cause of the cell death is unknown. It has been shown that there is
46 Muscular Dystrophy
overactive nerve activity due to increased levels of a chemical called glutamate and that there is abnormal cellular metabolism along with increased production of substance called "free radicals." Improving cellular metabolism and readjusting the activity of glutamate in the brain may be beneficial to ALS patients. Creatine is a naturally occurring compound, which improves energy metabolism in cells. Creatine has been given to patients with energy metabolism defects in their muscles, and to athletes. Creatine improves survival in a mouse model of ALS. Three human subjects with ALS have received creatine for up to six months without any side effects. Overall, creatine has been well tolerated and safe. Phase(s): Phase II Study Type: Interventional Contact(s): Alan Pestronk, M.D. 1-314-362-6981
[email protected];
[email protected]; Missouri; Washington University, St. Louis, Missouri, 63110, United States; Recruiting; Alan Pestronk, M.D. 314-362-6981 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005674 ·
Creatine and Glutamine in Steroid-Naive Duchenne Muscular Dystrophy Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is currently recruiting patients. Sponsor(s): Cooperative International Neuromuscular Research Group Purpose - Excerpt: This study will help to determine the effectiveness of glutamine and creatine as a possible therapy for DMD. Boys with DMD who are enrolled in this trial will be randomly chosen to receive creatine monohydrate or glutamine or an inactive placebo orally for six months. Once a month during the six-month treatment period, the study participants will have their muscle strength evaluated using manual and computerized testing methods. This study will be conducted at several CINRG Centers throughout the U.S., Belgium, Israel and Puerto Rico. This study is supported by the Muscular Dystrophy Association. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00016653
47
·
KUL0401: An open-label pilot study of Oxatomide in steroid-naive Duchenne muscular dystrophy Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is currently recruiting patients. Sponsor(s): Cooperative International Neuromuscular Research Group Purpose - Excerpt: This study will help to determine the safety and efficacy of the mast cell stabilizer Oxatomide as a treatment for Duchenne muscular dystrophy (DMD). Boys with DMD who are enrolled in this study will should not have taken steroids to treat DMD for at least twelve months, and should not have taken any nutritional supplements for at least three months. Subjects will complete a two screening visits within a one-week period, and if enrolled will then have their strength tested monthly for three months before beginning therapy with Oxatomide. Once Oxatomide therapy is started, participants will have their strength tested monthly for six months. Following the six month treatment period, participants will be given the option to remain on Oxatomide until the study is completed. Phase(s): Phase II Study Type: Interventional Contact(s): Erik K Henricson, MPH 202-884-3813 EHenricson@ cnmcresearch.org Diana M Escolar, MD 202-884-6080 DEscolar@ cnmcresearch.org; District of Columbia; Children's National Medical Center, Washington, District of Columbia, 20010, United States; Recruiting; Erik K Henricson, MPH 202-884-3813 EHenricson@ cnmcresearch.org; Diana M Escolar, MD, Principal Investigator Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00033813
·
Study of Inherited Neurological Disorders Condition(s): Ataxia; Motor Neuron Disease; Muscular Disease; Muscular Dystrophy; Peripheral Nervous System Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study is designed to learn more about the natural history of inherited neurological disorders and the role of heredity in their development. It will examine the genetics, symptoms, disease progression, treatment, and psychological and behavioral impact of diseases in the following categories: hereditary peripheral neuropathies; hereditary myopathies; muscular dystrophies; hereditary motor neuron
48 Muscular Dystrophy
disorders; mitochondrial myopathies; ataxias; hereditary neurocognitive disorders; inherited neurological disorders without known diagnosis; and others. Many of these diseases, which affect the brain, spinal cord, muscles, and nerves, are rare and poorly understood. Children and adults of all ages with various inherited neurological disorders may be eligible for this study. Participants will undergo a detailed medical and family history, and a family tree will be drawn. They will also have a physical and neurological examination that may include blood test and urine tests, an EEG (brain wave recordings), psychological tests, and speech and language and rehabilitation evaluations. A blood sample or skin biopsy may be taken for genetic testing. Depending on the individual patient's symptoms, imaging tests such as X-rays, CT or MRI scans and muscle and nerve testing may also be done. Information from this study may provide a better understanding of the genetic underpinnings of these disorders, contributing to improved diagnosis, treatment, and genetic counseling, and perhaps leading to additional studies in these areas. Study Type: Observational Contact(s): Maryland; National Institute of Neurological Disorders and Stroke (NINDS), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004568 ·
Randomized Study of Albuterol in Patients with Facioscapulohumeral Muscular Dystrophy Condition(s): Muscular Dystrophy, Facioscapulohumeral Study Status: This study is no longer recruiting patients. Sponsor(s): FDA Office of Orphan Products Development; Ohio State University Purpose - Excerpt: Objectives: I. Determine whether albuterol increases strength in patients with facioscapulohumeral dystrophy as measured by quantitative voluntary isometric contraction testing. II. Determine whether albuterol increases muscle mass in this patient population as determined by 24 hour urinary creatinine excretion and dual energy xray absorptiometry (DEXA). III. Examine the long term safety of albuterol in this patient population. Study Type: Interventional Contact(s): John T. Kissel 614-293-8000. Study chairs or principal investigators: John T. Kissel, Study Chair; Ohio State University
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Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004685 ·
Phase III Randomized, Double-Blind Study of Prednisone for Duchenne Muscular Dystrophy Condition(s): Duchenne Muscular Dystrophy Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); National Institute of Neurological Disorders and Stroke (NINDS); University of Rochester Purpose - Excerpt: Objectives: I. Characterize the effect of prednisone on muscle protein metabolism in patients with Duchenne muscular dystrophy. II. Determine whether prednisone changes levels of insulinlike growth factor 1, growth hormone, and insulin. III. Characterize the effect of prednisone on muscle morphometry and muscle localization of utrophin. IV. Compare the prednisone response in patients with Duchenne muscular dystrophy to that seen in normal individuals and in patients with facioscapulohumeral dystrophy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004646
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Study of Muscle Wasting and Altered Metabolism in Patients with Myotonic Dystrophy Condition(s): Muscular Dystrophy Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); University of Rochester Purpose - Excerpt: Objectives: I. Examine the interrelationships between muscle wasting (phenotype), the degree of myotonic dystrophy (DM) gene expression (genotype) in patients with DM. II. Characterize the insulin resistance in these patients. III. Assess the glucose uptake in the leg and forearm tissues of these patients. IV. Determine the stability of the DM gene lesion in muscles over a 5-10 year period. Study Type: Observational Contact(s):. Study chairs or principal investigators: Richard T. Moxley, III, Study Chair; University of Rochester Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004769
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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 muscular dystrophy. Although only half of the participants in a clinical trial receive the experimental treatment, if the new treatment is proved to be more effective and safer than the current treatment, then those patients who did not receive the new treatment during the clinical trial may be among the first to benefit from it when the study is over.
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If the treatment is effective, then it may improve health or prevent diseases or disorders.
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Clinical trial patients receive the highest quality of medical care. Experts watch them closely during the study and may continue to follow them after the study is over.
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People who take part in trials contribute to scientific discoveries that may help other people with muscular dystrophy. 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
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=9jmun6f2 91. 18
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receive may cause side effects that are serious enough to require medical attention.
How Is Patient Safety Protected? Clinical trials can raise fears of the unknown. Understanding the safeguards that protect patients can ease some of these fears. Before a clinical trial begins, researchers must get approval from their hospital's Institutional Review Board (IRB), an advisory group that makes sure a clinical trial is designed to protect patient safety. During a clinical trial, doctors will closely watch you to see if the treatment is working and if you are experiencing any side effects. All the results are carefully recorded and reviewed. In many cases, experts from the Data and Safety Monitoring Committee carefully monitor each clinical trial and can recommend that a study be stopped at any time. You will only be asked to take part in a clinical trial as a volunteer giving informed consent. What Are a Patient's Rights in a Clinical Trial? If you are eligible for a clinical trial, you will be given information to help you decide whether or not you want to participate. As a patient, you have the right to: ·
Information on all known risks and benefits of the treatments in the study.
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Know how the researchers plan to carry out the study, for how long, and where.
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Know what is expected of you.
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Know any costs involved for you or your insurance provider.
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Know before any of your medical or personal information is shared with other researchers involved in the clinical trial.
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Talk openly with doctors and ask any questions.
After you join a clinical trial, you have the right to: ·
Leave the study at any time. Participation is strictly voluntary. However, you should not enroll if you do not plan to complete the study.
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Receive any new information about the new treatment.
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Continue to ask questions and get answers.
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·
Maintain your privacy. Your name will not appear in any reports based on the study.
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Know whether you participated in the treatment group or the control group (once the study has been completed).
What about Costs? In some clinical trials, the research facility pays for treatment costs and other associated expenses. You or your insurance provider may have to pay for costs that are considered standard care. These things may include inpatient hospital care, laboratory and other tests, and medical procedures. You also may need to pay for travel between your home and the clinic. You should find out about costs before committing to participation in the trial. If you have health insurance, find out exactly what it will cover. If you don't have health insurance, or if your insurance company will not cover your costs, talk to the clinic staff about other options for covering the cost of your care. What 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 muscular dystrophy? 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 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 “muscular dystrophy” (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 arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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General References The following references describe clinical trials and experimental medical research. They have been selected to ensure that they are likely to be available from your local or online bookseller or university medical library. These references are usually written for healthcare professionals, so you may consider consulting with a librarian or bookseller who might recommend a particular reference. The following includes some of the most readily available references (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·
A Guide to Patient Recruitment : Today's Best Practices & Proven Strategies by Diana L. Anderson; Paperback - 350 pages (2001), CenterWatch, Inc.; ISBN: 1930624115; http://www.amazon.com/exec/obidos/ASIN/1930624115/icongroupinterna
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A Step-By-Step Guide to Clinical Trials by Marilyn Mulay, R.N., M.S., OCN; Spiral-bound - 143 pages Spiral edition (2001), Jones & Bartlett Pub; ISBN: 0763715697; http://www.amazon.com/exec/obidos/ASIN/0763715697/icongroupinterna
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The CenterWatch Directory of Drugs in Clinical Trials by CenterWatch; Paperback - 656 pages (2000), CenterWatch, Inc.; ISBN: 0967302935; http://www.amazon.com/exec/obidos/ASIN/0967302935/icongroupinterna
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The Complete Guide to Informed Consent in Clinical Trials by Terry Hartnett (Editor); Paperback - 164 pages (2000), PharmSource Information Services, Inc.; ISBN: 0970153309; http://www.amazon.com/exec/obidos/ASIN/0970153309/icongroupinterna
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Dictionary for Clinical Trials by Simon Day; Paperback - 228 pages (1999), John Wiley & Sons; ISBN: 0471985961; http://www.amazon.com/exec/obidos/ASIN/0471985961/icongroupinterna
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Extending Medicare Reimbursement in Clinical Trials by Institute of Medicine Staff (Editor), et al; Paperback 1st edition (2000), National Academy Press; ISBN: 0309068886; http://www.amazon.com/exec/obidos/ASIN/0309068886/icongroupinterna
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Handbook of Clinical Trials by Marcus Flather (Editor); Paperback (2001), Remedica Pub Ltd; ISBN: 1901346293; http://www.amazon.com/exec/obidos/ASIN/1901346293/icongroupinterna
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Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Albuterol: A racemic mixture with a 1:1 ratio of the r-isomer, levalbuterol, and s-albuterol. It is a short-acting beta2-adrenergic agonist with its main clinical use in asthma. [NIH] Ataxia: Failure of muscular coordination; irregularity of muscular action. [EU]
Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Gait: Manner or style of walking. [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] Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Heredity: 1. the genetic transmission of a particular quality or trait from parent to offspring. 2. the genetic constitution of an individual. [EU] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator
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of protein and lipid metabolism. Insulin is used as a drug to control insulindependent diabetes mellitus. [NIH] Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU] Localization: 1. the determination of the site or place of any process or lesion. 2. restriction to a circumscribed or limited area. 3. prelocalization. [EU] Neuromuscular: Pertaining to muscles and nerves. [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] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH]
Sclerosis: A induration, or hardening; especially hardening of a part from inflammation and in diseases of the interstitial substance. The term is used chiefly for such a hardening of the nervous system due to hyperplasia of the connective tissue or to designate hardening of the blood vessels. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Urinary: Pertaining to the urine; containing or secreting urine. [EU]
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PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL
ABOUT PART II In Part II, we introduce you to additional resources and advanced research on muscular dystrophy. 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 muscular dystrophy. In Part II, as in Part I, our objective is not to interpret the latest advances on muscular dystrophy 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 muscular dystrophy is suggested.
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CHAPTER 4. STUDIES ON MUSCULAR DYSTROPHY Overview Every year, academic studies are published on muscular dystrophy 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 muscular dystrophy. 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 muscular dystrophy 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 muscular dystrophy, 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 “muscular dystrophy” (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: ·
Inflammatory Myopathies (Polymyositis, Dermatomyositis, Inclusion Body Myositis) Source: Comprehensive Therapy. 24(10): 494-502. October 1998. Summary: This journal article provides health professionals with information on the symptoms, clinical features, laboratory findings, pathology, pathogenesis, differential diagnosis, and treatment of inflammatory myopathies, which are acquired diseases of muscle with various origins. The major inflammatory autoimmune myopathies are polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM). Patients with inflammatory myopathies characteristically have progressive proximal weakness and wasting. Some patients may also have pain. Patients with DM may also have the classical heliotrope skin rash. Patients with IBM have weakness with early involvement of hand muscles, and they frequently have elevated muscle enzymes in their serum. Although the exact etiology of the inflammatory myopathies is unclear, it has been hypothesized that viral infection triggers the autoimmune process. Laboratory findings include elevated creatine kinase and other muscle enzymes, as well as an elevated erythrocyte sedimentation rate. Some patients have pulmonary fibrosis and an associated neoplasm. Findings on electromyography studies include normal nerve conduction velocities, increased insertional activity, and the presence of denervation potentials at rest on needle examination. The muscle pathology of PM and DM includes necrosis with regeneration and invasion of inflammatory cells into the interstitial and perivascular areas. Muscle biopsy in patients who have IBM shows rimmed vacuoles and necrosis. The differential diagnosis of PM and DM includes other inflammatory myopathies, polymyalgia rheumatica, parasite infection, limb girdle muscular dystrophy, fibromyalgia, chronic fatigue, fasciitis, hypothyroidism, carnitine deficiency, acid maltase deficiency, progressive muscular atrophy, neuropathy, myasthenia gravis, and myopathies from steroids and other drugs. Treatment options include corticosteroids and immunosuppressive agents. 14 figures, 5 tables, and 35 references.
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·
Coenzyme Q10 (Monograph) Source: Alternative Medicine Review. 3(1): 58-61. February 1998. Summary: This monograph on Coenzyme Q10, also known as ubiquinone or CoQ10, contains a review of the biochemistry, pharmacokinetics, and mechanisms of action. It discusses the clinical indication for use of Coenzyme Q10 for several conditions, including cancer, immune system dysfunction, periodontal disease, gastric ulcers, muscular dystrophy, allergies, cardiovascular disease, and diabetes mellitus. Dosage, deficiency of Coenzyme Q10 in the body, toxicity, and drug/nutrient interactions are all described. This monograph contains 1 illustration and 42 references.
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Evaluating the Infant Swallow Source: Advance for Speech-Language Pathologists [and] Audiologists. 7(28): 5, 13. July 14, 1997. Contact: Available from Merion Publications, Inc. 650 Park Avenue, Box 61556, King of Prussia, PA 19406-0956. (800) 355-1088 or (610) 265-7812. Summary: This article describes the steps involved in evaluating the infant swallow. Questions concerning anatomy, maturation, physiology, and neurophysiology remain for researchers and clinicians engaged in studying and diagnosing the infant swallow. Topics include the swallowing risk factors in babies with neurological problems, structural problems that can lead to dysphagia (including laryngeal cleft, congenital achalasia, myotonic dystrophy, cerebral palsy, cranial facial nerve abnormalities, and muscular dystrophy), indications for a videofluorscopy study, calibrating digital fluoroscopy instruments for use on infants and children (in order to reduce the radiation exposure), noninvasive modalities used to study parts of the infant swallow, refusal to eat, psychological components of feeding, and needing to have more speech language pathologists active in the neonatal intensive care unit. The article concludes with the address of the clinician interviewed.
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Effects of Myotonic Dystrophy and Duchenne Muscular Dystrophy on the Orofacial Muscles and Dentofacial Morphology Source: Acta Odontologica Scandanavica. 56(6): 369-374. December 1998. Summary: This article reviews two of the less rare myopathies: myotonic dystrophy (MyD) and Duchenne muscular dystrophy (DMD), and their effect on the orofacial muscles and dentofacial morphology. A high prevalence of malocclusions was found among the patients affected by these diseases. The development of the malocclusions in MyD patients
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seems to be strongly related to the vertical aberration of their craniofacial growth due to the involvement of the masticatory muscles in association with the possibly less affected suprahyoid musculature. Thus, a new situation is established around the teeth transversely. The lowered tongue is not in a position to counterbalance the forces developed during the lowering of the mandible by the stretched facial musculature. This may affect the teeth transversely, decreasing the width of the palate and causing posterior crossbite. The lowered position of the mandible, in combination with the decreased biting forces, may permit an overeruption of the posterior teeth, with increased palatal vault height and development of anterior open bite. The development of the malocclusions in DMD patients also seems to be strongly related to the involvement of the orofacial muscles by the disease. However, the posterior crossbite is not developed owing to the narrow maxillary (upper jaw) arch, as is the case in MyD patients. On the contrary, the posterior crossbite in DMD is due to the transversal expansion of the mandibular arch, possibly because of the decreased tonus of the masseter muscle near the molars, in combination with the enlarged hypotonic tongue and the predominance of the less affected orbicularis oris muscle. 2 figures. 33 references. ·
Preliminary Study Into the Dental Health Status of Multiple Sclerosis Patients Source: Special Care in Dentistry. 13(3): 96-101. 1993. Contact: Available from Academy of Dentistry for People with Disabilities. 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2661. Summary: This article reports on a preliminary study that examined the dental health status of 22 volunteer patients with Muscular Dystrophy (MS). A questionnaire collected data regarding medical and dental histories and socio-demographic information. Extra-oral and intra-oral examinations were carried out on all subjects to determine the particular dental treatment needs of this group. Instruments used included the Decayed, Missing, or Filled Teeth Index (DMFT) and the Community Periodontal Index of Treatment Needs (CPITN). The DMFT and CPITN scores for this group did not indicate that MS patients were more susceptible to dental caries or periodontal disease. However, the prevalence of trigeminal neuralgia and symptoms of Temporomandibular Joint (TMJ) dysfunction in the group studied indicated that these conditions may be manifest in persons with MS and warrant further investigations. 8 tables 25 references. (AA-M).
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Federally-Funded Research on Muscular Dystrophy The U.S. Government supports a variety of research studies relating to muscular dystrophy and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.19 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 muscular dystrophy 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 muscular dystrophy 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 muscular dystrophy: ·
Project Title: Dystrophy
Bioengineering
Research
Partnership--Muscular
Principal Investigator & Institution: Sweeney, H L.; Professor and Chairman; Physiology; University of Pennsylvania 1 College Hall Philadelphia, Pa 19104 Timing: Fiscal Year 2000; Project Start 0-SEP-2000; Project End 1-AUG2005 Summary: (Applicant's abstract verbatim) The goal of this BRP is to utilize a number of aspects of bioengineering in order to develop tools and therapeutics for the treatment and monitoring of muscular dystrophies. The project is collaboration between three investigators and includes the following areas of bioengineering relevant to the PA: 1) cell and tissue engineering, 2) imaging and 3) therapeutics. Collectively we will delineate factors that when expressed in muscle may slow that rate of degeneration that is concomitant with either the complete (Duchenne muscular dystrophy) or partial (Becker muscular dystrophy) loss of 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 and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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dystrophin. These studies will utilize the mdx mouse as the animal model for dystrophin deficiency. The long-term goal is to gain the understanding and tools necessary to develop adeno-associated (AAV)based gene therapy for Duchenne and Becker muscular dystrophies. Three parallel lines of investigation (each directed by one of the three investigators) are proposed: Section 1: a dissection the mechanical role of dystrophin and muscle adhesion proteins (directed by Dennis Discher); Section 2: an assessment of the functional benefits of restoring adhesion molecules to dystrophic muscle using recombinant adeno-associated virus gene delivery (directed by H. Lee Sweeney, Ph.D.); and Section 3: development of non-invasive methods for monitoring therapeutic benefits of dystrophin gene transfer (directed by Glenn Walter, Ph.D.). Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Caveolin-3 and Muscular Dystrophy Principal Investigator & Institution: Lisanti, Michael P.; Molecular Pharmacology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2000; Project Start 1-APR-2000; Project End 1-MAR2005 Summary: The long-term objective of this proposal is to understand the role of muscle caveolae and caveolin-3 i) in normal muscle development; and ii) in the pathogenesis of muscle dystrophy. Caveolae are "little caves" at the surface of cells. It has been proposed that caveolae function as message centers" for regulating signal transduction. Caveolin-3, a muscle-specific caveolin-related protein, is the principal structural protein of caveolae membrane domains in striated muscle cell types (cardiac and skeletal). Recently, we identified a novel autosomal dominant form of limb girdle muscular dystrophy (LGMD-1C) in humans that is due to mutations within the coding sequence of the human caveolin-3 gene (3p25). The aim of this proposal is to test the hypothesis that caveolin-3 expression is important for normal muscle development and that changes in caveolin-3 expression (either upregulation or down-regulation) can result in muscular dystrophy phenotype. In order to test this hypothesis,, we will use a variety of complementary in vivo approaches, such as the use of caveolin-3 antisenses in cultured cells and the development of mouse animal models. The specific aims of the project are: 1) To determine the role of caveolin-3 mutations in the pathogenesis of LGMD- 1C. We will examine the phenotypic behavior of LGMD-1C mutations of caveolin-3 after heterologous expression in NIH 3T3 cells, as compared with wild-type caveolin-3; 2) To develop transgenic mouse models that over wild-type caveolin-3 and LGMD-1C mutant forms of caveolin-3. We will over-
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express wild type and LGMD-1C mutant forms of caveolin- 3 as transgenes in mice and assess their effects on skeletal muscle. As caveolin-3 levels are up-regulated in Duchenne's muscular dystrophy, these experiments will help us evaluate if caveolin-3 up-regulation contributes to the pathogenesis of this diseases; and 3) To examine if caveolin-3 expression is required for normal muscle development. Using an anti-sense approach, we will abrogate caveolin-3 expression in C2C12 cells, a skeletal myoblast cell line that differentiates in culture. We will then assess the effects of caveolin-3 down-regulation on C2C12 myoblast fusion and myotube formation. In addition, through a targeted gene disruption approach, we will create and characterize "knock-out" mice that lack caveolin-3 gene expression. It is expected that these studies will contribute fundamen6tal knowledge toward understanding the role of muscle cell caveolae in normal muscle development and muscular dystrophy. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Gene Therapy for Duchenne Muscular Dystrophy Principal Investigator & Institution: Wolff, Jon A.; Professor; Pediatrics; University of Wisconsin Madison 500 Lincoln Dr Madison, Wi 53706 Timing: Fiscal Year 2000; Project Start 0-SEP-2000; Project End 1-AUG2005 Summary: (Copied from Applicant Abstract): Gene therapy promises to be a cure for the muscular dystrophies, such as Duchenne muscular dystrophy. Studies by my laboratory and others indicate that the transfer of the normal human dystrophin gene into dystrophic muscle (in the mouse model) prevents the death of the myofiber. The critical problem now is how to deliver the normal dystrophin gene to enough of the muscle cells and have it stably expressed in order to effect a cure. We have spectacular preliminary results that show that plasmid DNA can be delivered via a blood vessel into more than 10 percent of the muscle cells throughout the leg of a rat. This percentage of transfected muscle cells approaches the critical minimum percentage necessary to be curative in children with Duchenne muscular dystrophy. With this approach, multiple administrations should be possible, ensuring that a sufficient number of cells would be converted to dystrophin-positivity. Our studies also indicate that this approach should lead to stable expression of the gene. We have shown that the intravascular injection of naked plasmid DNA (pDNA) into the femoral artery of rats leads to very high foreign gene expression in skeletal muscle throughout the leg and without damaging the muscle. Previous experience with naked DNA and adenoviral vectors showed that the gene transfer efficiency decreased
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substantially when going from the young mouse, to adult mouse and then adult rat. The fact that we can achieve very efficient expression in an adult rat is quite encouraging. The objective of this proposal is to extend this approach to larger animals, non-human primates and the dog and its associated Duchenne model. If successful in primates and dogs, a human clinical trial in patients with Duchenne muscular dystrophy could begin in the near future. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Limb Girdle Muscular Dystrophy Gene Therapy Principal Investigator & Institution: Campbell, Kevin P.; ; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2000 Summary: Autosomal recessive limb-girdle muscular dystrophy (ARLGMD) refers to a number of genetically and clinically heterogenous neuromuscular disorders that affect mainly skeletal muscle. Over the last few years, it has become clear that a number of genes encoding protein components of the sarcoglycan complex are responsible for several forms of AR-LGMDs. The sarcoglycans are expressed at the sarcolemma of muscle fibers and, along with other proteins, constitute the dystrophinglycoprotein complex (DGC). These proteins are believed to play a role in maintaining the normal architecture of the muscle cell membrane by constituting a link between the subsarcolemmal cytoskeleton and the extracellular matrix. In particular, we have shown that alpha-sarcoglycan, a 50 kDa component of the DGC, is a deficient in skeletal muscle from patients having limb- girdle muscular dystrophy type 2D, and that the expression of all the other sarcoglycan proteins is also strongly reduced in muscle from these patients. Although these findings constitute great progress in our understanding of the genetic basis for AR-LGMDs, there have been no improvements in the treatment of these invalidating diseases. The long-term goal of this research proposal is the development of a gene transfer strategy for AR-LGMDs. We recently generated an animal model for LGMD2D by disrupting the alpha-sarcoglycan gene in mice and preliminary analyses of homozygous mutant mice indicate that their skeletal muscle displays a dystrophic phenotype, as expected, thus providing a valuable animal mode for LGMD2D. The overall objective of this pilot project is to develop a virally-mediated gene transfer of alphasarcoglycan and to investigate its therapeutic potential in alphasarcoglycan deficient mice. Our first aim will be the construction of recombinant adenovirus and adeno-associated virus vectors containing the human alpha-sarcoglycan deficient mice. Our first aim will be the construction of recombinant adenovirus and adeno-associated virus
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vectors containing the human alpha- sarcoglycan cDNA. These vectors will first be tested for their ability to induce expression of alphasarcoglycan, both in cultured myoblasts and myotubes. We will then proceed to in vivo experiments designed to test the following hypotheses: i) direct intra-muscular injections of adenoviral- based vectors containing the alpha-sarcoglycan cDNA will efficiently allow expression of the protein and restoration of the DGC in of skeletal muscle of mutant mice (Aim 2) and ii) gene transfer of alpha-sarcoglycan will support functional restoration of muscle fibers in these mice (Aim 3). Overall, the experiments outlined in our proposal will yield new information about alpha-sarcoglycan and the potential for virally-mediated alphasarcoglycan gene transfer in mutant mice. In addition, our findings should constitute a foundation for future investigations directed towards developing gene therapy for LGMD2D patients. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Muscle Response to Stress in Canine Muscular Dystrophy Principal Investigator & Institution: Childers, Martin K.; Phys Med and Rehabilitation; University of Missouri Columbia 105 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2000; Project Start 1-MAR-1999; Project End 8-FEB2003 Summary: This project will provide the applicant with the research skills required to develop and assess rehabilitation treatments that enhance function for patients with muscular dystrophy. Throughout a doctoral program in physiology, a major portion of effort will be devoted to a mentored research project which will examine the relationship between mechanical stress and muscle fiber injury in a canine homolog of Duchenne muscular dystrophy. The central hypothesis of this research is that fiber damage in dystrophin-deficient muscle results, in part, from an exaggerated response to mechanical stress incurred during contraction. Furthermore, muscles involved in lengthening contractions are subject to greater stress than other muscles, and are preferentially injured. The central hypothesis will be tested in selected hindlimb muscles of dystrophic dogs by evaluating cellular and physiological features of muscle fiber response to varying levels of imposed stress. Although the mdx mouse is more readily available and a more commonly used experimental model, the dystrophic dog expresses clinical features analogous to humans with Duchenne muscular dystrophy. Aim 1 will correlate muscle membrane damage with myofiber necrosis: Aim 2 will compare regenerative features in muscles involved in lengthening contractions with muscles involved in shortening contractions: Aim 3 will
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determine if a lower threshold to stress-induced injury exists in dystrophic fibers compared to controls: and Aim 4 will determine if reducing mechanical stress during growth will eliminate or decrease the exaggerated fiber necrosis and remodeling seen in the adult gastrocnemius muscle. It is anticipated that findings will improve the understanding of how dystrophic muscle responds to physical stress resulting in improved treatment for patients with Duchenne muscular dystrophy. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Myeloid Cell Function in Muscular Dystrophy Principal Investigator & Institution: Tidball, James G.; Professor; Physiological Sciences; University of California Los Angeles 405 Hilgard Ave Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 4-SEP-2001; Project End 1-AUG2006 Summary: (provided by applicant): Duchenne muscular dystrophy (DMD) is the most common, inherited, lethal disease of childhood. Although mutations in the dystrophin gene are primarily responsible for DMD and animal models of DMD, many features of dystrophinopathies indicate that secondary processes can contribute substantially to pathology. Recent findings have indicated that the immune system can contribute significantly to the pathological progression of dystrophindeficiency in the mdx mouse model of the disease. The long-term goal of our studies of the pathology of dystrophin-deficiency is to identify the specific immune cells and mechanisms that promote the pathology of dystrophin-deficiencies, after which we will use that information for the development of immune-based therapeutics. Although our preliminary data implicate both myeloid and lymphoid cells in promoting the dystrophic pathology, the studies proposed here will focus on cytotoxic mechanisms that are mediated by macrophages and eosinophils in dystrophic muscle. Our rationale for focusing on these specific myeloid cells is that our preliminary findings strongly implicate these cells in promoting the pathology of dystrophin-deficiency through both innate and acquired immune responses. Our general strategy will be to assess the effect on muscle pathology of depletion of specific myeloid cell populations from the dystrophic mdx mouse. In addition, the effect of those depletions on the lifespan of the dystrophic mdx/utrophindeficient mice will be assessed because these mice die from muscular dystrophy at an early age. We will also test whether introducing null mutations of the inducible nitric oxide synthase gene or major basic protein gene into mdx mice will reduce muscle pathology, because our
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findings implicate cytotoxic pathways in the mdx pathology that involve the products of these genes. Results of the study proposed here will permit us to determine whether therapeutic approaches that are based on reducing myeloid cell mediated pathology can be productive approaches to the treatment of these forms of muscular dystrophy. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Calpain Regulation of Muscle Necrosis and Regeneration Principal Investigator & Institution: Spencer, Melissa J.; Assistant Professor; Physiological Sciences; University of California Los Angeles 405 Hilgard Ave Los Angeles, Ca 90024 Timing: Fiscal Year 2000; Project Start 0-SEP-1998; Project End 1-AUG2001 Summary: Many previous investigations have provided correlative data suggesting that calpains play key roles in muscle cell necrosis and regeneration in muscular dystrophy and in muscle cell fusion. However, little experimental data exist to substantiate calpains' hypothetical roles in these processes. In this investigation, transgenic models will be employed to examine the individual roles that the three calpain isoforms play in normal growth and development of muscle, and in the pathological process of mdx dystrophy. This will involve the creation of transgenic mice that overexpress isoforms of calpain in a muscle-specific manner. The investigation proposed here is significant both in the new knowledge that it will contribute to our understanding of the functions of the calpain family of proteases in muscle, but also in providing information that is essential to understanding the pathophysiology of LGMD 2A (Limb Girdle Muscular Dystrophy 2A), which results from a calpain 3 mutation, and DMD (Duchenne Muscular Dystrophy), which involves increased expression and activation of calpains. The following specific aims are to be accomplished in this investigation: Specific Aim 1. Transgenic C57 mice, that overexpress the large subunit of calpains 1, 2 or 3, will be generated to investigate the roles of calpains in normal growth and development of muscle. Specific Aim 2. Transgenic mdx mice, that overexpress the large subunit of calpains 1, 2 or 3, will be generated to investigate the roles of calpains in muscle necrosis, regeneration and repair in muscular dystrophy. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
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Project Title: Dystrophin Replacement in MDX Mice Principal Investigator & Institution: Chamberlain, Jeffrey S.; Professor; Human Genetics; University of Michigan at Ann Arbor Ann Arbor, Mi 48109
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Timing: Fiscal Year 2000; Project Start 1-APR-1991; Project End 1-DEC2000 Summary: (Adapted from applicant's abstract): Duchenne muscular dystrophy (DMD) is an X-linked recessive, lethal disorder caused by mutations in the dystrophin gene. Considerable progress has been made both in understanding the function of dystrophin, and in demonstrating the feasibility of gene therapy for DMD. Nonetheless, numerous obstacles remain before gene therapy can be effectively applied to this common genetic disease. These obstacles include a lack of data on the reversibility of the dystrophic pathology, limited ability of viral vectors to carry the enormous dystrophin gene or cDNA, and questions about the effectiveness of inefficient delivery methods of dystrophin vectors. This application proposes to address these concerns by generating several novel strains of transgenic mice. The ability to modulate the dystrophic phenotype will also be explored using viral delivery of dystrophin and several death protectors to mdx mice, a model for DMD. Transgenic mice that express moderate levels of dystrophin are able to prevent the development of dystrophy in the mdx mouse, a model for DMD. Delivery of adenoviral vectors expressing truncated dystrophins to neonatal, immune tolerant mice can also prevent muscular dystrophy near the site of injection. However, it has not been possible to demonstrate that the pathology can be halted or reversed in adult, dystrophic animals. Aim1 will address the feasibility of reversing muscular dystrophy at different stages of the disease by studying a transgenic mouse line that displays tetracycline-inducible dystrophin expression. Aim 2 will continue previous work aimed at understanding the structural basis of dystrophin functional domains, with the goal of developing severely truncated cDNAs that can be carried by a variety of promising viral vectors, such as adenoassociated viruses (AAV). Currently, the only vectors capable of carrying the full-length dystropin cDNA have problems with cytotoxicity, immune rejection or low titers. AAV efficiently infect muscle with no immune response, but have a limited cloning capacity. Aim 3 explores the ability to modulate dysrtophy by delivery of dystrophin with proteins that repress apoptosis and/or enhance muscle regeneration. Achieving uniform and efficient gene delivery to muscles using viral vectors is a daunting goal. The ability to modulate dystrophy and prolong muscle fiber longevity could greatly facilitate the effectiveness of dystrophin gene replacement strategies. These studies will provide new insights into both the structure of dystrophin and the mechanisms of dystrophic cell death and will help advance the development of gene therapy. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
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Project Title: Improved Diagnosis of the Muscular Dystrophies Principal Investigator & Institution: Hoffman, Eric P.; James Clark Professor of Pediatrics,; Children's Research Institute 111 Michigan Ave Nw Washington, Dc 20010 Timing: Fiscal Year 2000; Project Start 1-JAN-1991; Project End 0-NOV2003 Summary: This application is the second competitive renewal of this "Improved Diagnostics of the Muscular Dystrophies" grant. During the first award, we showed that primary dystrophinopathies caused the majority of cases of muscular dystrophy, specifically about 80% of male dystrophy patients, and 10% of female dystrophy patients. During the tenure of the second award period (Dec 95-present), we begin dissecting the cause of muscular dystrophy in patients with normal dystrophin. During the last two years, we have investigated muscular dystrophies caused by alpha- sarcoglycan, beta-sarcoglycan, gamma-sarcoglycan, delta-sarcoglycan, merosin, integrin-alpha7, and calpain III. Despite the advances in our understanding of the molecular basis of muscular dystrophy made by our laboratory and others, we can identify the underlying molecular basis for only about 30% of autosomal recessive cases; 70% of patients with normal dystrophin can not be assigned a specific molecular diagnosis. Thus, considerable work remains to identify the many genes causing muscular dystrophy, and this is the focus of this competitive renewal. Our laboratory serves as the major referral site for molecular diagnostics of the muscular dystrophies. Through our for gratis analysis of muscle biopsies for primary dystrophinopathies, and more recently sarcoglycanopathies and merosin disorders, we have assembled what is likely the most extensive tissue-bank of frozen muscle tissue and clinical records of muscular dystrophy patients in the world. 3,049 flash-frozen muscle biopsies from muscular dystrophy patients have been received by the laboratory and fully characterized by the laboratory for dystrophin expression, histopathology, and, in hundreds of cases, gene mutations. It is these well-characterized muscle biopsy specimens which form the starting material for the molecular studies proposed in this renewal application. The goals of this current application are: 1. To continue our successful candidate gene analyses in our large cohort of muscular dystrophy patients; 2. To use the newly emerging GeneChip system (Affymetrix) to determine the changes in gene expression resulting from mutations in specific muscular dystrophy genes as a means to understanding disease progression and pathophysiology; and 3. To use the Gene Chips to identify novel muscular dystrophy genes through specific changes in gene expression. The proposed research will lead to improved understand the etiology of
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muscular dystrophies and improved diagnosis of these disorders. The results will enable genetic counseling of patients and their families, and should facilitate efforts directed towards rational therapies. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Laminin Alpha 2 in Tissue Regeneration Principal Investigator & Institution: Engvall, Eva S.; Professor; Burnham Institute 10901 N Torrey Pines Rd San Diego, Ca 92037 Timing: Fiscal Year 2000; Project Start 1-MAR-1996; Project End 8-FEB2005 Summary: (Adapted from applicant's abstract) Tissue regeneration and repair are critical to longevity. Insufficient regeneration of muscle and nerve is a significant cause of morbidity in patients with muscular dystrophy and other muscle and nerve diseases and in the aging individual. The laminin subunit a2 is prominently expressed in striated muscle and peripheral nerve, and mutations in the lama2 gene cause a severe form of muscular dystrophy in humans (merosin-deficient congenital muscular dystrophy, MCMD) and mice. A mouse model for human MCMD was generated by disrupting the lama2 gene with the lacZ reporter gene. Homozygous mutant mice develop muscular dystrophy and peripheral neuropathy after birth. Absence of laminin a2 does not significantly affect myogenesis, but the differentiated laminin a2-deficient muscle are highly susceptible to injury upon contraction. Most important, in contrast to the apparent normal development, regeneration is severely compromised in the absence of laminin a2. It is proposed to use in vivo and in vitro models to analyze development and regeneration of skeletal muscle and peripheral nerve to determine which steps in the regeneration process are dependent on laminin a2. The regeneration-promoting effects of laminin a2 will be analyzed in transgenic mice with tissue-specific overexpression of a human LAMA2 transgene. To analyze the molecular pathways responsible for maturation and survival of skeletal muscle and Schwann cells, integrin and dystroglycan signaling pathways will be characterized by using the yeast 2-hybrid screening and affinity chromatography in combination with peptide mass mapping. The proposed research will result in new knowledge regarding important molecular mechanisms of muscle and nerve function and may help in devising new strategies for treatment of degenerative diseases of muscle and nerve based on promoting regeneration. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
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Project Title: Molecular Pathophysiology of Facioscapulohumeral Muscul Principal Investigator & Institution: Chen, Yi-Wen; Children's Research Institute 111 Michigan Ave Nw Washington, Dc 20010 Timing: Fiscal Year 2001; Project Start 8-SEP-2001; Project End 1-MAY2004 Summary: (provided by applicant): Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common inherited muscle diseases following Duchenne muscular dystrophy and myotonic dystrophy. The disorder is autosomal dominant with nearly complete penetrance (95%) by age 20. Severity of muscle involvement in FSHD is extremely variable, ranging from elderly individuals with mild facial weakness to wheelchair bound children. Besides variability between individual patients, FSHD patients often show enigmatic asymmetry of muscle involvement. This disease feature permits a novel experimental design, where progression of the disease can be studied within a single patient at a single time point. Previous studies showed a statistically significant correlation between severity of clinical presentation and the deletion of D4Z4 repeats on chromosome 4q35 in patients with FSHD. Current hypotheses center on a position effect of telomeric sequences on genes in or near the deletion site, however the molecular mechanisms underlying this disease are far from clear. In our study, we hypothesize that FSHD patient muscle shows a disease-specific expression profile, relative to other muscle disease (Duchenne muscular dystrophy, alpha-sarcoglycan deficiency, juvenile dermatomyositis, and dysferlin deficiency). In addition, we hypothesize that one can identify a subset of the FSHD-specific genes will be shown to correlate with progression of-muscle involvement in FSHD muscle by comparing expression changes correlated with clinicallyaffected vs. unaffected muscles within single dystrophy patients. In our preliminary data, we have defined an FSHD-specific set of 29 genes that are candidates for primary involvement of disease pathogenesis by using the HuGeneFL array (-6,000 full length genes). In this proposal, we plan to broaden the number of genes studied, so that a genome-wide set of genes implicated in the primary etiology can be defined. Specifically, we will extend our truly promising preliminary data to over 60,000 genes and EST sequences included on the Human genome U95A, B, C, D, E stock chips, as well as the > 2,000 human muscle ESTs on our customproduced MuscleChip. In addition, a custom glass slide array consisting of - 200 genes and ESTs from 4q35 and lOq26 will be used to identify FSHD region specific alterations in gene expression. All FHSD-specific ESTs identified will be characterized in detail. Further studies will likely include the delineation of a complete picture of the pathophysiology of
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FSHD, as well as identification of functional SNPs in the refined gene list that correlate with disease severity. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Phase I Clinical Trial Utilizing Gene Therapy for LGMD Principal Investigator & Institution: Kissel, John; Ohio State University Columbus, Oh 43210 Timing: Fiscal Year 2000; Project Start 1-DEC-1976; Project End 0-NOV2001 Summary: We propose to evaluate the safety of the gene therapy in Limb girdle muscular dystrophy, specifically alpha-sarcoglycan deficiency, using a recombinant, replication-deficient, adeno-associated viral delivery system. The primary objective of this study is to determine the safety of adeno-associated virus (AAV) delivered via needle injection into the extensor digitorum (EDB) muscle. The EDB is a small foot muscle without important function. Muscles on both feet will be injected. One foot will receive the alpha-sarcoglycan gene and the other an injection of sterile saline. This will be done in a double-blind manner without the investigators or the patient's knowledge of which side is receiving the gene vs placebo. Six weeks after injection both EDB muscles will biopsied to determine if the gene has been effective in replacing the missing protein. This will be the first human trial of gene therapy for any type of muscular dystrophy. Currently there is no medication that is known to be effective for the treatment of any of the forms of LGMD. If this study is successful, it will represent the first step in a series of studies directed more toward efficacy of gene therapy in this disease. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
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Project Title: Role of the Alpha 7 Beta 1 Integrin in Muscle Integrity Principal Investigator & Institution: Kaufman, Stephen J.; Professor; Cell and Structural Biology; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2001; Project Start 4-JAN-1997; Project End 1-AUG2006 Summary: (provided by applicant): The proper association of muscle fibers with laminin in the extracellular matrix is essential for normal muscle function. The alpha7Beta1 integrin and the dystrophinglycoprotein complex both bind laminin and appear to be complementary linkage systems between fibers and the extracellular matrix. Congenital and acquired defects in the dystrophin-glycoprotein complex underlie the pathology associated with Duchenne and other
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muscular dystrophies, as well as cardiomyopathies. Mutations in the human alpha7 gene cause an additional myopathy. We recently discovered that enhanced expression of the alpha7 integrin mediated linkage system can compensate for the absence of the dystrophinglycoprotein complex. Dystrophin/utrophin null mice develop an acute muscular dystrophy and die prematurely. Enhanced expression of the alpha7 integrin inhibits the development of muscular dystrophy and restores longevity to these animals. We propose to expand on this result and determine the level of alpha7Beta1 integrin that best prevents development of skeletal muscle pathology in these animals and whether transgene expression in the heart and smooth muscle can prevent cardiovascular disease. We will also analyze whether enhanced expression of the alpha7 integrin in the heart reduces development of cardiomyopathy associated with enterovirus-induced cleavage of dystrophin. Additional skeletal muscle and cardiomyopathies result from other defects in the dystrophin-glycoprotein linkage system. We will use transgenic animals that over-express the alpha7Beta1 integrin in different genetic backgrounds to determine whether the integrin can prevent these myopathies. Whereas mutations in the sarcoglycan genes perturb the dystrophin-glycoprotein transmembrane linkage system and cause cardiomyopathy and muscular dystrophy, we will determine whether over-expression of the alpha7 integrin can inhibit the development of muscle disease in sarcoglycan deficient mice. Likewise, we will assess whether enhanced integrin expression will ameliorate alpha2-laminin congenital muscular dystrophy. Lastly, experiments are proposed that aim at understanding the mechanism by which enhanced integrin expression inhibits development of muscle pathology. This research will reveal whether increasing alpha7 integrin levels in humans may be worth pursuing in the future as treatments for Duchenne and other muscular dystrophies and cardiomyopathies. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Structure-Function Analysis of Sarcospan Principal Investigator & Institution: Crosbie, Rachelle H.; Duchenne Musc Dyst Res Ctr; University of California Los Angeles 405 Hilgard Ave Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 4-SEP-2001; Project End 1-AUG2006 Summary: (provided by applicant): The broad, long-term objectives of this proposal are to understand the structure and function of a novel tetraspanin called SARCOSPAN. Sarcospan is an integral component of the dystrophin-glycoprotein complex and is highly expressed in skeletal
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and cardiac muscles, as well as many non-muscle tissues (Crosbie et al., 1997; Crosbie et al., 1998; Crosbie et al., 1999). The dystrophinglycoprotein complex (DGC) is a structural complex that spans the muscle plasma membrane and links the extracellular matrix with the intracellular cytoskeleton. This structural linkage is critical for normal muscle function as clearly demonstrated by the many forms of muscular dystrophy that result from mutations in the dystrophin-glycoprotein complex. Association of several signaling molecules with the DGC also suggests that this complex may play a role in mediating extracellularintracellular communications. Furthermore, lateral associations amongst membrane components of the DGC are critical for function of this complex. It is hypothesized that sarcospan facilitates protein-protein interactions within the dystrophin-glycoprotein complex. These protein interactions are clearly important for the physical linkage between the extracellular matrix and the intracellular actin network and for the prevention of muscular dystrophy. Human mutations within the sarcospan gene have not been identified in known cases of autosomal recessive muscular dystrophy (Crosbie et al., 2000). However, these mutation searches have only examined the ubiquitous form of SSPN, which has a broad expression pattern. Preliminary data demonstrates that a novel, muscle-specific form of SSPN is expressed in skeletal and cardiac muscles. We hypothesize that mutations within muscle-SSPN may cause novel forms of muscular dystrophy. Identification and characterization of this muscle-sarcospan will advance our understanding of the role of the dystrophin-glycoprotein complex in normal muscle and in the pathogenesis of muscular dystrophy. 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
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 20
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to http://www.pubmedcentral.nih.gov/index.html#search, and type “muscular dystrophy” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for muscular dystrophy in the PubMed Central database: ·
A 71-Kilodalton Protein is a Major Product of the Duchenne Muscular Dystrophy Gene in Brain and Other Nonmuscle Tissues by D Lederfein, Z Levy, N Augier, D Mornet, G Morris, O Fuchs, D Yaffe, and U Nudel; 1992 June 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=49288
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A second promoter provides an alternative target for therapeutic upregulation of utrophin in Duchenne muscular dystrophy by Edward A. Burton, Jonathon M. Tinsley, Paul J. Holzfeind, Nanda R. Rodrigues, and Kay E. Davies; 1999 November 23 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=24184
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Brain dystrophin-glycoprotein complex: Persistent expression of betadystroglycan, impaired oligomerization of Dp71 and up-regulation of utrophins in animal models of muscular dystrophy by Kevin Culligan, Louise Glover, Paul Dowling, and Kay Ohlendieck; 2001 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=29067
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Commentary:NO skeletal muscle derived relaxing factor in Duchenne muscular dystrophy by David S. Bredt; 1998 December 8 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=33925
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Detection of Dystrophin in the Postsynaptic Density of Rat Brain and Deficiency in a Mouse Model of Duchenne Muscular Dystrophy by T Kim, K Wu, J Xu, and IB Black; 1992 December 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=50609
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From the Cover:Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model by Bing Wang, Juan Li, and Xiao Xiao; 2000 December 5 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=17641
already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy by Mikael Sander, Bahman Chavoshan, Shannon A. Harris, Susan T. Iannaccone, James T. Stull, Gail D. Thomas, and Ronald G. Victor; 2000 December 5 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=17659
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Neuronal Nitric Oxide Synthase and Dystrophin-Deficient Muscular Dystrophy by W Chang, ST Iannaccone, KS Lau, BSS Masters, TJ McCabe, K McMillan, RC Padre, MJ Spencer, JG Tidball, and JT Stull; 1996 August 20 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=38609
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Possible Influences on the Expression of X Chromosome-Linked Dystrophin Abnormalities by Heterozogosity of Autosomal Recessive Fukuyama Congenital Muscular Dystrophy by AH Beggs, PE Neumann, K Arahata, E Arikawa, I Nonaka, MS Anderson, and LM Kunkel; 1992 January 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=48291
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Profound misregulation of muscle-specific gene expression in facioscapulohumeral muscular dystrophy by Rossella Tupler, Giovanni Perini, Maria Antonietta Pellegrino, and Michael R. Green; 1999 October 26 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=23032
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Social deprivation in Duchenne muscular dystrophy: population based study by Kate Bushby, Simon Raybould, Sara O'Donnell, and James G Steele; 2001 November 3 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=59456
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The role of basal and myogenic factors in the transcriptional activation of utrophin promoter A: implications for therapeutic up-regulation in Duchenne muscular dystrophy by Kelly J. Perkins, Edward A. Burton, and Kay E. Davies; 2001 December 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=96689&ren dertype=external
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Transgenic overexpression of caveolin-3 in skeletal muscle fibers induces a Duchenne-like muscular dystrophy phenotype by Ferruccio Galbiati, Daniela Volonte, Jeffrey B. Chu, Maomi Li, Samson W. Fine, Maofu Fu, Jorge Bermudez, Marina Pedemonte, Karen M. Weidenheim, Richard G. Pestell, Carlo Minetti, and Michael P. Lisanti; 2000 August 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=16926
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Ullrich scleroatonic muscular dystrophy is caused by recessive mutations in collagen type VI by Olga Camacho Vanegas, Enrico Bertini, Rui-Zhu Zhang, Stefania Petrini, Claudia Minosse, Patrizia Sabatelli, Betti Giusti, Mon-Li Chu, and Guglielmina Pepe; 2001 June 19 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=34700
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 muscular dystrophy, simply go to the PubMed Web site at www.ncbi.nlm.nih.gov/pubmed. Type “muscular dystrophy” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “muscular dystrophy” (hyperlinks lead to article summaries): ·
Breathing exercises for children with pseudohypertrophic muscular dystrophy. Author(s): Houser CR, Johnson DM. Source: Physical Therapy. 1971 July; 51(7): 751-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=4933570&dopt=Abstract
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Cell transplantation as an experimental treatment for Duchenne muscular dystrophy. Author(s): Law PK, Goodwin TG, Fang Q, Deering MB, Duggirala V, Larkin C, Florendo JA, Kirby DS, Li HJ, Chen M, et al.
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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Source: Cell Transplantation. 1993 November-December; 2(6): 485-505. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8167934&dopt=Abstract
Vocabulary Builder Acuity: Clarity or clearness, especially of the vision. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiovascular: Pertaining to the heart and blood vessels. [EU] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Collagen: The protein substance of the white fibres (collagenous fibres) of skin, tendon, bone, cartilage, and all other connective tissue; composed of molecules of tropocollagen (q.v.), it is converted into gelatin by boiling. collagenous pertaining to collagen; forming or producing collagen. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior
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(in humans) end of the body. [EU] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Pertaining to or exhibiting cytotoxicity. [EU] Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alphaactinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Electromyography: Recording of the changes in electric potential of muscle by means of surface or needle electrodes. [NIH] Enterovirus: A genus of the family picornaviridae whose members preferentially inhabit the intestinal tract of a variety of hosts. The genus contains many species. Newly described members of human enteroviruses are assigned continuous numbers with the species designated "human enterovirus". [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] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU]
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Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrosis: The formation of fibrous tissue; fibroid or fibrous degeneration [EU] Fluoroscopy: screen. [NIH]
Production of an image when x-rays strike a fluorescent
Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Masticatory: 1. subserving or pertaining to mastication; affecting the muscles of mastication. 2. a remedy to be chewed but not swallowed. [EU] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Membrane: A thin layer of tissue which covers a surface, lines a cavity or divides a space or organ. [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Necrosis: The sum of the morphological changes indicative of cell death and caused by the progressive degradative action of enzymes; it may affect groups of cells or part of a structure or an organ. [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH]
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Neuralgia: Paroxysmal pain which extends along the course of one or more nerves. Many varieties of neuralgia are distinguished according to the part affected or to the cause, as brachial, facial, occipital, supraorbital, etc., or anaemic, diabetic, gouty, malarial, syphilitic, etc. [EU] Neuropathy: A general term denoting functional disturbances and/or pathological changes in the peripheral nervous system. The etiology may be known e.g. arsenical n., diabetic n., ischemic n., traumatic n.) or unknown. Encephalopathy and myelopathy are corresponding terms relating to involvement of the brain and spinal cord, respectively. The term is also used to designate noninflammatory lesions in the peripheral nervous system, in contrast to inflammatory lesions (neuritis). [EU] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Perivascular: Situated around a vessel. [EU] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Pharmacokinetics: The action of drugs in the body over a period of time, including the processes of absorption, distribution, localization in tissues, biotransformation, and excretion. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of YEASTS. [NIH] Prophylaxis: The prevention of disease; preventive treatment. [EU] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]
Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pulmonary: Pertaining to the lungs. [EU] Recombinant: 1. a cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU]
Sedimentation: The act of causing the deposit of sediment, especially by the
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use of a centrifugal machine. [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] 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] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU]
Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Ubiquinone: A lipid-soluble benzoquinone which is involved in electron transport in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and 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] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viruses: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. [NIH]
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CHAPTER 5. PATENTS ON MUSCULAR DYSTROPHY Overview You can learn about innovations relating to muscular dystrophy 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 muscular dystrophy 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 muscular dystrophy. 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 Muscular Dystrophy By performing a patent search focusing on muscular dystrophy, 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 muscular dystrophy: ·
Gene replacement therapy for muscular dystrophy Inventor(s): Campbell; Kevin P. (Iowa City, IA), Holt; Kathleen H. (Corlville, IA), Duclos; Franck (Iowa City, IA), Lim; Leland E. (Iowa City, IA), Straub; Volker (Essen, IA), Davidson; Beverly (Iowa City, IA), Williamson; Roger (Iowa City, IA) Assignee(s): University of Iowa Research Foundation (Iowa City, IA) Patent Number: 6,262,035 Date filed: October 1, 1998 Abstract: Disclosed is a method for treating a patient suffering from the disease sarcoglycan-deficient limb-girdle muscular dystrophy by gene replacement therapy. Sarcoglycan gene replacement therapy produces extensive long-term expression of the sarcoglycan species which restores the entire sarcoglycan complex, results in the stable association of alph.alpha.-dystroglycan with the sarcolemma, and eliminates the morphological markers of limb-girdle muscular dystrophy. In another aspect, the invention relates to a method for determining a specific defective sarcoglycan species in the tissue of a patient. The method involves culture of muscle cells obtained from the patient, and the independent introduction of expression vectors encoding each of the sarcoglycan species, .alpha., .beta., .gamma., and .delta., into the cultured cells with subsequent assaying for restoration of the dystrophinglycoprotein complex. In another aspect, the invention relates to a mouse, and cells derived therefrom, homozygous for a disrupted .alpha.sarcoglycan gene. The disruption prevents the synthesis of functional .alpha.-sarcoglycan in cells of the mouse and results in the mutant mouse having no detectable sarcospan, .beta.-, .gamma.-, .delta.-sarcoglycan, and reduced .alpha.-dystroglycan in the sarcolemma of skeletal and
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cardiac muscles, and a reduction of dystrophin in skeletal muscle, when compared to tissue of a mouse lacking a disrupted .alpha.-sarcoglycan gene. In another aspect, the invention relates to methods for screening for therapeutic agents useful in the treatment of sarcoglycan-deficient limbgirdle muscular dystrophy. The methods involve administering a candidate therapeutic agent to a mouse, or cells derived therefrom, and assaying for therapeutic effects on the mouse or cells, with the determination of therapeutic effects being a reduction or reversal in disease progression, or a restoration of the dystroglycan complex. Excerpt(s): The term muscular dystrophy describes a group of diseases characterized by hereditary progressive muscle weakness and degeneration. Several muscular dystrophies are caused by mutations in genes that encode sarcolemmal proteins, including certain types of limbgirdle muscular dystrophy (LGMD). LGMD is genetically and clinically heterogeneous; it may be inherited in an autosomal dominant or recessive manner, and may have different rates of progression and severity. A unifying theme among the LGMDs is the initial involvement of the shoulder and pelvic girdle muscles, with relative sparing of most other muscle groups (Jackson et al., Pediatrics 41, 495-501 (1968); Bushby, K. M., Neuromusc Disord 5, 71-74 (1995)). ... The pace of discovery in the field of muscular dystrophy research has been rapid since the discovery of the Duchenne and Becker muscular dystrophy (DMD) gene in 1986 (Monaco et al., Nature 323, 646-650 (1986)). The DMD gene encodes dystrophin, a large cytoskeletal protein that together with other molecular components makes up the dystrophin-glycoprotein complex (DGC). The dystrophin-glycoprotein complex (DGC) is a large oligomeric complex of sarcolemmal proteins and glycoproteins in skeletal and cardiac muscle (Campbell, K. P. Cell 80, 675-679 (1995); Ozawa et al., Hum. Mol. Genet. 4, 1711-1716 (1995)). This complex consists of dystrophin, a large cytoskeletal protein which binds F-actin; .alpha.- and .beta.-dystroglycan, which bind laminin and the cysteine-rich region of dystrophin, respectively; .alpha.-, .beta.-, .gamma.-, and .delta.sarcoglycan (.delta.-SG), which form a distinct subcomplex; and sarcospan, a 25 kDa protein predicted to span the membrane four times (Crosbie et al., J. Biol. Chem. 272, 31221-31224 (1997). The DGC spans the sarcolemma and is believed to play an essential role in maintaining the normal architecture of the muscle sarcolemma by constituting a link between the subsarcolemmal cytoskeleton and the extracellular matrix. This structural linkage is thought to protect muscle fibers from the mechanical stress of contraction. ... Mutations in different components of the DGC lead to similar dystrophic features, suggesting that the function of the DGC as a whole is dependent on intact molecular interactions between its individual subunits. The loss of one component destroys the
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link, and leads to muscle fiber degeneration. Several components of the DGC have been implicated in several human muscular dystrophies (Straub et al., Curr. Opin. Neurol. 10, 168-175 (1997)). Mutations in dystrophin cause Duchenne and Becker muscular dystrophy (DMD) (Hoffman et al., Cell 51, 919-928 (1987)). Two forms of congenital muscular dystrophy are caused by mutations in the extracellular matrix protein laminin 2 (Helbling-Leclerc et al., Nature Genet. 11, 216-218 (1995); Allamand et al., Hum. Mol. Genet. 6, 747-752 (1997)). Mutations in each of .alpha.-, .beta.-, .gamma.-, and .delta.-SG cause autosomal recessive LGMD types 2D, 2E, 2C, and 2F, respectively (Roberds et al., Cell 78, 625-633 (1994); Piccolo et al., Nature Genet. 10, 243-245 (1995); Lim et al., Nature Genet. 11, 257-265 (1995); Bonneman et al., Nature Genet. 11, 266-273 (1995); Noguchi et al., Science 270, 819-822 (1995); Passos-Bueno et al., Hum. Mol. Genet. 5, 815-820 (1996); Nigro et al., Hum. Mol. Genet. 5, 1179-1186 (1996); Nigro et al., Nature Genet. 14, 195198 (1996)). Web site: http://www.delphion.com/details?pn=US06262035__ ·
Method for aiding in the diagnosis of in-frame deletion type congenital muscular dystrophy Inventor(s): Campbell; Kevin P. (Iowa City, IA), Allamand; Valerie (Iowa City, IA), Sunada; Yoshihide (Kawaguchi, JP), Straub; Volker (Iowa City, IA), Salih; Mustafa (Riyadh, SA) Assignee(s): University of Iowa Research Foundation (Iowa City, IA) Patent Number: 6,136,546 Date filed: April 9, 1998 Abstract: Disclosed are compositions and methods for aiding in the diagnosis of congenital muscular dystrophy associated with in-frame deletion in the laminin-2 .alpha.2 polypeptide chain in an individual. In a preferred diagnostic method embodiment, an experimental muscle tissue sample is provided from the individual and treated if necessary to render components available for antibody binding. The components of the sample are then separated on the basis of molecular weight. The separated protein components are then transferred to a solid support while maintaining the relative positions established in separation step. The transferred components are then stained with an affinity reagent which is known to bind to a C-terminal domain of the laminin-2 .alpha.2 polypeptide chain. Individual afflicted with congenital muscular dystrophy associated with in-frame deletion in the laminin-2 .alpha.2 polypeptide chain on the basis of positive staining in combination with
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reduced molecular weight of the laminin-2 .alpha.2 polypeptide chain relative to the wild-type laminin-2 .alpha.2 polypeptide chain. A preferred composition is a nucleic acid probe for the detection of merosin deletion-type congenital muscular dystrophy. The preferred nucleic acid probe is characterized by the ability to bind specifically to a mutant merosin nucleic acid sequence, the mutant merosin nucleic acid sequence comprising a T to C substitution at position 3973 +2 of the consensus donor splice site of exon 25. Excerpt(s): Laminins are a family of large extracellular glycoproteins which display a complex and still unclear repertoire of biological functions. Laminin-2, the isoform involved in congenital muscular dystrophy (CMD), is specifically expressed in the basal lamina of striated muscle and peripheral nerve. As are all members of the laminin family, it is composed of three chains: one heavy (.alpha.2) and two light chains (.beta.1 and .gamma.1) that assemble in a cross-shaped molecule with three short arms and one long arm. The C-terminal ends of each chain interact to form the triple stranded long arm of the molecule, stabilized by disulfide bonds, with a large globular (G) domain contributed to by the .alpha.2-chain. The .alpha.2-chain of laminin consists of 6 domains: I and II are part of the long arm; IIIa, IIIb and V contain cystein-rich EGFlike repeats and are predicted to have rigid rod-like structures; and IVa, IVb and VI are predicted to form globular structures. Laminin .alpha.2chain has been shown to be a native ligand for .alpha.-dystroglycan, an extracellular component of the dystrophin-associated glycoprotein complex (DGC). This complex constitutes a link between the subsarcolemmal skeleton and the extracellular matrix. A number of components of the DGC have now been shown to be involved in muscular dystrophies suggesting a crucial role of laminin-2 and the components of the DGC in maintaining the integrity of muscle cell function. ... Congenital muscular dystrophy (CMD) is a clinically and genetically heterogeneous group of autosomal recessive neuromuscular disorders of early onset. In the classic form of CMD, clinical manifestations are limited to skeletal muscle with no clinical involvement of the central nervous system (CNS) although changes in the white matter have been detected by MRI. The histological changes in muscle biopsies consist of connective tissue proliferation, large variation in the size of the muscle fibers as well as some necrotic and regenerating fibers. ... The present invention relates to compositions and methods for aiding in the diagnosis of congenital muscular dystrophy associated with inframe deletion in the laminin-2 .alpha.2 polypeptide chain in an individual. In a preferred diagnostic method embodiment, an experimental muscle tissue sample is provided from the individual and treated if necessary to render components available for antibody binding.
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The components of the sample are then separated on the basis of molecular weight. The separated protein components are then transferred to a solid support while maintaining the relative positions established in separation step. The transferred components are then stained with an affinity reagent which is known to bind to a C-terminal domain of the laminin-2 .alpha.2 polypeptide chain. Individual afflicted with congenital muscular dystrophy associated with in-frame deletion in the laminin-2 .alpha.2 polypeptide chain on the basis of positive staining in combination with reduced molecular weight of the laminin-2 .alpha.2 polypeptide chain relative to the wild-type laminin-2 .alpha.2 polypeptide chain. Web site: http://www.delphion.com/details?pn=US06136546__ ·
Merosin deficiency-type congenital muscular dystrophy Inventor(s): Campbell; Kevin P. (Iowa City, IA), Sunada; Yoshihide (Iowa City, IA), Tome; Fernando M. S. (Paris, FR), Fardeau; Michel (Sceaux, FR) Assignee(s): University of Iowa Research Foundation (Iowa City, IA) Patent Number: 5,863,743 Date filed: August 12, 1994 Abstract: Disclosed is a method for aiding in the diagnosis of merosin deficiency-type congenital muscular dystrophy (CMD). The method is based on the discovery of a previously unidentified form of CMD which is characterized by a substantial reduction in the levels of merosin in skeletal muscle tissue containing normal levels of dystrophin and dystrophin-associated proteins. Excerpt(s): Congenital muscular dystrophy (CMD), a very disabling muscle disease of early clinical onset, is the most frequent cause of severe neonatal hypotonia. Its manifestations are noticed at birth or in the first months of life and consist of muscle hypotonia, often associated with delayed motor milestones, severe and early contractures and joint deformities. Serum creatine kinase is raised, up to 30 times the normal values, in the early stage of the disease, and then rapidly decreases. The histological changes in the muscle biopsies consist of large variation in the size of muscle fibers, a few necrotic and regenerating fibers, marked increase in endomysial collagen tissue, and no specific ultrastructural features. The diagnosis of CMD has been based on the clinical picture and the morphological changes in the muscle biopsy, but it cannot be made with certainty, as other muscle disorders may present with similar clinico-pathological features. ... Within the group of diseases classified as CMD, various forms have been individualized. The two more common
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forms are the occidental and the Japanese, the latter being associated with severe mental disturbances, and usually referred to as Fukuyama congenital muscular dystrophy (FCMD). The genetic lesion responsible for FCMD has recently been mapped to chromosome 9. It is unknown whether or not the rare cases of CMD associated with mental retardation or central nervous system abnormalities observed in occidental countries belong to the same disease entity. The determination of the gene (or genes) responsible for the various forms of CMD is required in order to clearly delineate specific members of the currently ill-defined genus. ... The present invention is based on the identification of a novel disease etiology which is responsible for a previously undefined member of the congenital muscular dystrophy family. The novel etiology, referred to herein as merosin deficiency-type congenital muscular dystrophy, was identified through the study of levels of specific proteins in mammalian muscle tissue. Web site: http://www.delphion.com/details?pn=US05863743__ ·
Method of in vitro preconditioning healthy donor's myoblasts before transplantation thereof in compatible patients suffering of recessive myopathies like muscular dystrophy, for improving transplantation success Inventor(s): Tremblay; Jacques P. (Bernieres, CA) Assignee(s): Universite Laval (Quebec, CA) Patent Number: 5,833,978 Date filed: March 16, 1995 Abstract: A method of pretreating healthy donor's myoblast cultures with growth or trophic factors like basic fibroblast growth factor (bFGF) on transplantation to subjects suffering of recessive myopathy like muscular dystrophy is disclosed and claimed. Recipient muscles show a higher percentage of functional cells, demonstrated by the higher incidence of dystrophin-positive fibers, and does not require previous preconditioning of recipient muscles by irradiation or toxin administration. Donor mouse myoblasts expressing the reporter gene .beta.- galactosidase were grown with 100 ng/ml bFGF during the last two days before injecting them in the left tibialis anterior (TA) muscles of recipient MHC-compatible mdx mice, an experimental animal model of muscular dystrophy. Myoblasts from the same primary cultures were also grown without bFGF and injected in the right TA muscles as control. The recipient mice were immunosuppressed with FK 506. Twenty-eight days after myoblast transplantation, the percentage of .beta.-
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galactosidase-positive fibers was significantly higher (more than a 4 fold increase) following culture with bFGF than without bFGF. Almost all .beta.-galactosidase-positive-fibers were also dystrophin positive. Excerpt(s): The present invention is a method for preconditioning healthy donor's myoblasts in vitro before transplantation thereof in compatible patients suffering of recessive myopathies, particularly of muscular dystrophy. This in vitro preconditioning improves the success of the transplantation while not requiring an in vivo preconditioning of the patient's muscle by irradiation or by administering muscular toxin. ... Duchenne muscular dystrophy (DMD) is a progressive disease characterized by the lack of dystrophin under the sarcolemmal membrane.sup.6,19,28,37. One possible way to introduce dystrophin in the muscle fibers of the patients to limit the degeneration is to transplant myoblasts obtained from normal subjects.sup.30,34,35. Several groups have tried myoblast transplantations to DMD patients but poor graft success was observed.sup.17,22,24,38. Even in experimental myoblast transplantation using mdx mice, an animal model of DMD.sup.10,25,29, large amount of dystrophin-positive fibers were observed only when nude mdx mice were previously irradiated to prevent regeneration of the muscle fibers by host myoblasts.sup.32,43. High percentage of dystrophin-positive fibers was also observed in mdx mice immunosuppressed with FK 506 and in SCID mice, in both cases muscles were previously damaged by notexin injection and irradiated.sup.23,27. These results indicate that to obtain successful myoblast transplantation, it is necessary to have not only an immunodeficient mouse or a mouse adequately immunosuppressed but also a host muscle which has been adequately preconditioned. It is, however, impossible in clinical studies to use damaging treatments such as marcaine, notexin and irradiation. If good myoblast transplantation results can be obtained without using such techniques, this would be very helpful for myoblast transplantation in humans. ... The present invention relates to a method of in vitro preconditioning of myoblasts harvested from healthy donor's biopsy prior to their transplantation in patients affected by recessive myopathies, particularly by Duchenne muscular dystrophy (DMD). In a DMD animal model (mdx), compatible donor mouse myoblasts were grown in culture with muscular growth or trophic factors, particularly, basic Fibroblast Growth Factor (bFGF), before transplanting them in muscles of mdx mice without any previous damaging treatment. A four fold increase in the percentage of muscle fibers expressing dystrophin, which is indicative of functional muscle cells, was obtained with pretreatment with bFGF. These experimental results are expected to verify in naturally occurring dystrophy or other types of recessive myopathies in animal and human
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subjects, since the mdx mouse is an animal model wherein muscular dystrophy is naturally occurring. Web site: http://www.delphion.com/details?pn=US05833978__ ·
Changes in laminin subunit composition are diagnostic of Fukuyama congenital muscular dystrophy Inventor(s): Engvall; Eva (Rancho Santa Fe, CA), Arahata; Kiichi (Tokyo, JP) Assignee(s): La Jolla Cancer Research Foundation (La Jolla, CA) Patent Number: 5,780,244 Date filed: February 14, 1994 Abstract: The present invention relates to a method for detecting altered expression or localization of a cytoskeleton/basal lamina protein in a tissue sample obtained from an individual, wherein the altered expression or localization are associated with a muscular dystrophy such as Fukuyama congenital muscular dystrophy (FCMD). The invention provides an immunohistochemical method for detecting the expression and localization in a tissue, such as muscle, of laminin M (merosin), which is a protein component of the basal lamina, wherein certain defined changes are diagnostic of individuals predisposed to FCMD. The invention also provides a prenatal diagnostic screening procedure, using a tissue such as placenta, wherein the screening procedure can identify an individual predisposed to FCMD. The invention further provides methods for identifying an individual predisposed to other muscular dystrophies such as Walker-Warburg Syndrome (WWS) and muscle-eyebrain disease of the Finnish type (MEB). Excerpt(s): This invention relates generally to the field of medicine and more specifically to methods for detecting changes in the expression of laminin M protein and of M chain mRNA that are diagnostic of Fukuyama congenital muscular dystrophy (FCMD). The invention further relates to methods of identifying agents that can reduce or prevent the symptoms associated with FCMD and to methods of treating an FCMD patient. ... Primary deficiencies of protein components of the membrane cytoskeleton of muscle fibers include dystrophin and dystrophin-glycoprotein complexes, which are detected in Duchenne and Becker Muscular Dystrophy (Ibraghimov-Beskrovnaya et al. (1992); Ervasti et al., Nature 345:315-319 (1990); Ervasti and Campbell, Cell 66:1121-1131 (1991); Yoshida and Ozawa, J. Biochem. 108:748-752 (1990)). Secondary deficiencies also occur. For example, the laminin-binding 156 kdal DAG is markedly reduced in human Duchenne muscular dystrophy
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(DMD) and in muscle obtained from mdx mice, which are the murine equivalent of Duchenne/Becker muscular dystrophy in humans (Ervasti et al. (1990)). The lack of dystrophin protein in mdx mouse is due to a mutation in the dystrophin gene (Bulfield 1984), Hoffman et al., 1987). Although the mdx mouse has a much milder phenotype than human patients with dystrophin defects has provided a useful model system for studying the molecular mechanisms responsible for DMD in humans. ... Other forms of muscular dystrophy in humans are known. For example, a deficiency of a 50 kdal DAG component of the membrane cytoskeleton was observed in an autosomal recessive form of muscular dystrophy that is prevalent in North Africa (Matsumura et al., Nature 359:320-322 (1992)). Fukuyama congenital muscular dystrophy (FCMD) is an autosomal recessive form of congenital muscular dystrophy that is endemic to Japan and has an incidence of 6.9-11.9 per 100,000 births. FCMD is characterized by progressive muscle wasting and dystrophic muscle pathology. In addition, central nervous system involvement results in profound mental retardation associated with abnormal brain pathology such as neuronal and glial heterotopias (Kamoshita et al., Arch. Neurol. 33:513-516 (1976); Stern and Manson, Devel. Med. Child Neurol. 32:808-813 (1988); Fukuyama et al., Brain Devel. 13:1-29 (1981)). Other forms of muscular dystrophy such as muscle-eye-brain disease of the Finnish type (MEB) and Walker-Warburg Syndrome (WWS) also occur as autosomal recessive diseases and may be a result of the same genetic defect as FCMD ((Cook et al., J. Child. Neurol. 7:S51-63 (1992); Osawa et al., Acta Paediatr. (Japan) 33:261-269 (1991); Lenard, H. G., Acta Paediatr. (Japan) 33:256-260 (1991); Miller et al., Acta Neuropathol. (Berlin) 82:234-238 (1991); Yoshioka et al., Brain Devel. 12:423-426 (1990)). Web site: http://www.delphion.com/details?pn=US05780244__ ·
Diagnosis of myotonic muscular dystrophy Inventor(s): Caskey; C. Thomas (West University, TX), Fu; Ying-Hui (Columbus, OH), Friedman; David L. (Houston, TX), Pizzuti; Antonio (Milan, IT), Fenwick; Raymond G. (Sugarland, TX) Assignee(s): Baylor College of Medicine (Houston, TX) Patent Number: 5,552,282 Date filed: June 6, 1993 Abstract: The present invention includes a DNA clone from the myotonic muscular dystrophy gene, a cosmid probe to the myotonic dystrophy site, as well as methods of detecting myotonic muscular dystrophy using RFLP. The method involves the steps of digesting DNA from an
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individual to be tested with a restriction endonuclease and detecting the restriction fragment length polymorphism with hybridization to probes within the myotonic muscular locus and southern blot analysis. Alternatively, the myotonic muscular dystrophy gene can be measured by determining the amount of mRNA or measuring the amount of protein with an antibody. Further, the myotonic muscular dystrophy gene defect can be detected using either fluorescence in situ hybridization or pulsed field gel electrophoresis using the probes described herein. Excerpt(s): This invention relates to the field of molecular diagnosis of myotonic muscular dystrophy. ... The myotonic muscular dystrophy (DM) disease is the most common adult muscular dystrophy in man with a prevalence of 1 in 10,000. The disorder is inherited in an autosomal dominant manner with variable expression of symptoms from individual to individual within a given family. Furthermore, the phenomenon of anticipation (increasing disease severity over generations) is well documented for DM. This is particularly evident when an affected mother transmits the gene for the disease to her offspring. These offspring have a high incidence of mental retardation and profound infantile myotonia. Adult patients with DM manifest a pleiotropic set of symptoms including myotonia, cardiac arrhythmias, cataracts, frontal baldness, hypogonadism, and other endocrine dysfunctions. There is no evidence that myotonic muscular dystrophy may be caused by defects in more than one gene. ... A myotonic muscular dystrophy gene has been mapped to human chromosome position 19q13.3. Both a genetic and physical map of the region was developed by a group of investigators acting as a voluntary consortium under sponsorship of the Muscular Dystrophy Association. The genetic linkage studies identified two RFLP alleles, D10 and X75, which are polymerase chain reaction (PCR)-based dinucleotide polymorphisms and are tightly linked to DM. Web site: http://www.delphion.com/details?pn=US05552282__ ·
Method of treatment for muscular dystrophy Inventor(s): Antoku; Yasunobu (Kurume, JP), Tsukamoto; Kosuke (Kurume, JP), Koike; Fumihiko (Saga, JP), Sakai; Tetsuo (Yame, JP), Tanaka; Kaoru (Fukuoka, JP) Assignee(s): MinoPhagen Pharmaceutical Company (Tokyo, JP) Patent Number: 5,434,142 Date filed: August 24, 1993 Abstract: Administering to a patient of muscular dystrophy a pharmaceutical agent containing glycyrrhizin and/or a pharmaceutically
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acceptable salt thereof as effective components is effective against muscular dystrophy, particularly, Duchenne or Becker muscular dystrophy and is highly safe with less side effect. Excerpt(s): This invention relates to a method of treatment for muscular dystrophy and, more particularly, to a method of treatment for muscular dystrophy such as Duchenne muscular dystrophy, Becker muscular dystrophy and the like. ... The Duchenne muscular dystrophy is a sexlinked recessive disease occuring in childhood, in which muscle weakness and muscular wasting in the proximal parts of extremities and trunk are progressed, resulting in a death at about twenty. The Becker muscular dystrophy is also a sex-linked recessive disease showing the same symptoms, although its onset age is older and tile progression is slower, compared with the Duchenne type. ... Other muscular dystrophies include limb-girdle muscular dystrophy, facioscapulohumeral (FSH) muscular dystrophy, congenital muscular dystrophy, and the like. Web site: http://www.delphion.com/details?pn=US05434142__ ·
Measuring dystrophy
non-dystrophin
proteins
and
diagnosing
muscular
Inventor(s): Campbell; Kevin P. (Iowa City, IA), Ervasti; James M. (Iowa City, IA), Ohlendieck; Kay (Iowa City, IA), Gaver; Mitchell G. (Cockeysville, MD), Kahl; Steven D. (Iowa City, IA) Assignee(s): University of Iowa Research Foundation (Iowa City, IA) Patent Number: 5,413,910 Date filed: October 7, 1992 Abstract: The invention pertains to the dystrophin-glycoprotein complex of mammalian skeletal muscle and a method of isolating said complex. The components of the complex and methods of separating and isolating said components also pertain to the invention. In addition, the invention further relates to a method of diagnosing muscular dystrophy by detecting and quantifying the loss of a non-dystrophin component of the dystrophin-glycoprotein complex with said loss being indicative of muscular dystrophy. Excerpt(s): Muscular dystrophy refers to a group of genetically determined myopathies characterized by progressive atrophy or degeneration of increasing numbers of individual muscle cells. The structural changes observed histologically are essentially the same in the various types of muscular dystrophies. This may, perhaps, suggest a
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common etiology. However, the distribution of the affected muscles is quite distinctive. This, along with the mode of inheritance, forms the basis of the classification of these diseases. The muscular dystrophies are traditionally subdivided by the patterns of initial muscle involvement, which in turn correlates fairly well with the type of genetic transmission. The three major forms of muscular dystrophy are as follows: 1) Duchenne's Muscular Dystrophy which affects most skeletal muscle groups and is transmitted by an X-linked recessive gene; 2) Limb Girdle Muscular Dystrophy, affecting principally the pelvic and shoulder girdle muscles and is transmitted by an autosomal recessive gene; and 3) Facioscapulohumeral Muscular Dystrophy, involves the muscles of the face and shoulder girdle and is transmitted by an autosomal dominant gene. ... Recently, the defective gene responsible for Duchenne's Muscular Dystrophy (DMD) has been located on the X-chromosome. The DMD gene encodes for a large molecular weight protein product, called dystrophin. This protein is localized to the sarcolemmal membrane of normal skeletal muscle, but is absent from the skeletal muscle of people with DMD, as well as dogs and mice with dystrophic muscle. A more benign form of this X-linked recessive disease is Becker's Muscular Dystrophy which is caused by an abnormal DMD gene which encodes an abnormal dystrophin protein. The exact function of dystrophin and the reasons why its absence or abnormal structure results in necrosis of dystrophic muscle fibers have not been determined. However, the amino acid sequence of dystrophin suggests that it is a membrane cytoskeletal protein. ... The present technology for initial detection and diagnosis of Duchenne's or Becker's Muscular Dystrophy relies on the use of an immunological probe to identify the presence of dystrophin, the absence of dystrophin, or the abnormal molecular weight or content of dystrophin in human muscle biopsies. It is not uncommon for genetic diseases to involve the loss or abnormal synthesis of more than one component or protein. In the case of muscular dystrophy, proteins other than dystrophin may be involved which are translated from genes located on different chromosomes (X chromosomes and/or autosomal chromosomes), resulting in the different forms of muscular dystrophy. The identification of other potential proteins involved in muscular dystrophy and methods of quantifying these proteins would be immensely useful to clinicians for confirming diagnosis of Duchenne's and Becker's muscular dystrophy, as well as perhaps providing an initial diagnosis of other forms of muscular dystrophy. In addition, knowledge of the function of these proteins may lead to methods of predicting prognosis of disease progression and perhaps therapeutic treatments for patients with muscular dystrophy in all of its various forms. Web site: http://www.delphion.com/details?pn=US05413910__
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·
Method for assaying a human muscular dystrophy protein Inventor(s): Ishiguro; Tsuneo (Kawasaki, JP), Eguchi; Chikahiko (Kawasaki, JP) Assignee(s): Ajinomoto Co., Inc. (Tokyo, JP) Patent Number: 5,340,718 Date filed: January 27, 1993 Abstract: Methods and polypeptides for assaying human proteins associated with Duchenne muscular dystrophy, are disclosed. Excerpt(s): The present invention relates to a method for assaying dystrophin which is a protein defective in a human suffering from Duchenne muscular dystrophy (DMD) which is a hereditary disease. ... Duchenne muscular dystrophy is a hereditary disease which is developed almost only in males. A gene which is defective peculiarly to this disease is located on the X chromosome and its sequence has been elucidated [M. Konig, E. P. Hoffman, C. J. Bertelson, A. P. Monaco, C. Feenet and L. M. Kunkel: Cell, 50, 509 (1987), E. P. Hoffman, A. P. Monaco, C. C. Feeher and L. M. Kunkel, Science, 238, 347 (1987)]. If any antibody capable of specifically recognizing dystrophin which is a protein encoded by this gene is produced, a deletion or defect of dystrophin specific to this disease could be detected and such would be useful. A related method was tried by Hoffman et al., using the gene from mice suffering from a disease which is the same type as Duchenne muscular dystrophy [E. P. Hoffman, R. H. Brown, Jr. and L. M. Kunkel, Cell, 51, 919 (1987); E. P. Hoffman, C. M. Knudson, K. P. Campbell and L. M. Kunkel, Nature, 330, 754 (1987)]. However, the method of Hoffman et al. uses a gene from mice, the amino acid sequence of which is different by about 10% from that of humans, to produce the antibody so that it is inappropriate to determine dystrophin possessed by humans. Moreover, according to this method, protein having a high molecular weight such as 208 amino acid residues or 410 amino acid residues is used as an antigen and hence, the method has a shortcoming that an antibody capable of reacting not only with dystrophin but also with many other proteins is formed and that the antibody fails to specifically react with dystrophin alone. In order to compensate for the poor specificity of reaction, Hoffman et al. adopted a method using a specimen obtained by previously homogenizing cells to be tested followed by separating protein from the homogenate by electrophoresis, and then performing an antigen-antibody reaction with respect to the specimen. For this reason, the method encounters a drawback that operations are complicated and is thus unsatisfactory. ... In general, conventional methods for assaying dystrophin have drawbacks in that antibodies capable of specifically
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reacting only with dystrophin could not be obtained since a gene from a mouse, which is different from that of a human, has been used for preparation of the antibody. Further, operations are complicated since the method comprises using a specimen obtained by previously homogenizing cells to be tested and separating protein from the homogenate by electrophoresis and performing an antigen-antibody reaction with respect to the specimen. Therefore, the present inventors have made extensive investigations to discover a method for assaying the protein in cells in a simple manner, by preparing an antiserum capable of specifically reacting only with dystrophin or an antibody fraction separated from the antiserum using a part of dystrophin encoded by human Duchenne muscular dystrophy-associated gene and performing an antigen-antibody reaction between a substance to be tested and the antiserum or antibody fraction. Web site: http://www.delphion.com/details?pn=US05340718__ ·
Diagnosis of autosomal muscular dystrophy Inventor(s): Campbell; Kevin P. (Iowa City, IA), Matsumura; Kiichiro (Iowa City, IA) Assignee(s): Univ. of Iowa Research Foundation (Oakdale, IA) Patent Number: 5,308,752 Date filed: September 14, 1992 Abstract: Disclosed are methods for the diagnosis of autosomal muscular dystrophy through the analysis of muscle tissue using antibodies reactive with components of the dystrophin-glycoprotein complex. An experimental muscle tissue sample, treated if necessary to render components of the dystrophin-glycoprotein complex available for antibody binding, is contacted with an antibody which binds to a dystrophin-associated protein. The extent of antibody binding is determined, and compared to the extent of antibody binding to normal control tissue. A substantial reduction in the extent of binding to experimental tissue, as compared with normal control tissue, being diagnostic of autosomal muscular dystrophy. Among the autosomal muscular dystrophies which are detectable by the methods described herein are Fukuyama muscular dystrophy and severe childhood autosomal recessive muscular dystrophy. Excerpt(s): Severe childhood autosomal recessive muscular dystrophy (SCARMD) is a disease which is prevalent in North Africa. This progressive muscular dystrophy shares several clinical features with Duchenne's muscular dystrophy (DMD) including, for example, mode of
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onset, rapid progression, hypertrophy of calves and extremely high serum creatine kinase levels during the initial stages of the disease (see, e.g., Ben Hamida et al., J. Neurol Sci. 107: 60-64 (1992)). ... It has been demonstrated that Duchenne's muscular dystrophy is caused by a mutation or deletion which results in the absence of the dystrophin protein (Hoffman et al., Cell 51: 919-928 (1987)). Dystrophin has been shown to be associated with a large oligomeric complex of sarcolemmal glycoproteins (see, e.g., Ervasti and Campbell, Cell 66: 1121-1131 (1991)). The dystrophin-glycoprotein complex has been proposed to span the sarcolemma and provide a linkage between the subsarcolemmal cytoskeleton and the extracellular matrix. In DMD, the absence of dystrophin leads to a great reduction in all of the dystrophin-associated proteins. These observations have enabled, for example, the development of immunologically-based methods for the diagnosis of DMD. ... The subject invention relates to methods for the diagnosis of autosomal muscular dystrophy through the analysis of muscle tissue using antibodies reactive with components of the dystrophin-glycoprotein complex. An experimental muscle tissue sample, treated if necessary to render components of the dystrophin-glycoprotein complex available for antibody binding, is contacted with an antibody which binds to a dystrophin-associated protein. The extent of antibody binding is determined, and compared to the extent of antibody binding to normal control tissue. A substantial reduction in the extent of binding to experimental tissue, as compared with normal control tissue, has been determined to be diagnostic of autosomal muscular dystrophy. Web site: http://www.delphion.com/details?pn=US05308752__ ·
Muscular dystrophy protein, dystrophin Inventor(s): Kunkel; Louis M. (Hyde Park, MA), Monaco; Anthony (Boston, MA), Hoffman; Eric P. (Newton, MA), Koenig; Michel (Boston, MA) Assignee(s): The Children's Medical Center Corporation (Boston, MA) Patent Number: 5,239,060 Date filed: December 22, 1987 Abstract: The invention relates to a muscular dystrophy (MD) probe comprising a substantially purified single-stranded nucleic acid sequence capable of hybridizing to a region of DNA on a human X chromosome between the deletion break point at Xp21.3 and the translocation break point at X;11. The invention also relates to a 14 kb cDNA corresponding to the complete MD gene and probes produced therefrom useful in
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genetic methods of diagnosis of MD. Furthermore, the invention relates to the polypeptide, dystrophin, which corresponds to the MD gene product, and antibodies thereto that are useful in a variety of methods for immunodiagnosis of MD. Excerpt(s): Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder which affects about 1 in 3,300 males. Traits associated with DMD (DMD phenotype) are well known and may include elevated creatine phosphokinase levels in serum (at least 10.times. the normal level), delayed development of motor function, and muscle weakness characterized by the replacement of muscle fiber with adipose and fibrose tissue accompanied by a marked variation in muscle size. Until recently, carrier identification in DMD families generally was accomplished by detecting elevated levels of creatine phosphokinase in serum. ... Becker muscular dystrophy (BMD) is also an X-linked recessive genetic disorder, but occurs at only 10% of the frequency of DMD. BMD is a more benign form of muscular dystrophy which follows a less rapid clinical course than DMD. Both DMD and BMD are caused by mutations in the DMD gene located in the Xp21 region of the short arm of the human X chromosome. ... Outlier muscular dystrophy (OMD) is a mild Duchenne/severe Becker disorder. It forms a subgroup that comprises approximately 10 percent of individuals inflicted with DMD. Web site: http://www.delphion.com/details?pn=US05239060__ ·
Use of isopropylaminopyrimidine in the chemotherapy of muscular dystrophy, myopathy and myotonia Inventor(s): Huve; Pierre M. (3, rue Cernushi, 75017 Paris, FR) Assignee(s): none reported Patent Number: 4,416,885 Date filed: March 22, 1982 Abstract: A method for the chemotherapy of muscular dystrophy which includes administrating orally an effective amount of 2 isopropylaminopyrimidine. Excerpt(s): The present invention is directed to a new use of an existing compound. U.S. Pat. No. 4,073,895 relates to the use of a substituted salt of 2-aminopyrimidine. This patent in fact teaches that a particular salt of 2-aminopyrimidine, namely 2-isopropylaminopyrimidine orthophosphate (IAPP), is useful as an active agent for the treatment of neuropathies. Although this use is known, the particular efficacy of the salt against muscular dystrophy has yielded encouraging results. ... The
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invention broadly comprises a method for the chemotherapy of muscular dystrophy, which comprises administering either orally or by injection or administering by any method known to those skilled in the art an effective dosage of 2-isopropylaminopyrimidine or therapeutically acceptable salts of the same or the hydroxylated and oxygenated metabolites thereof. ... The dystrophic chicken homozygote was used for monitoring chemotherapy of muscular dystrophy. This particular animal line inherits dystrophy in a form as close as possible in causation and course to human dystrophy and also permits quantitative assessment of progress of the disease by several independent methods. Web site: http://www.delphion.com/details?pn=US04416885__ ·
Use of isopropylaminopyrimidine in the chemotherapy of muscular dystrophy, myopathy and mytonia Inventor(s): Huve; Pierre M. (Paris, FR) Assignee(s): Societe d'Etudes de Produits Chimiques (FR) Patent Number: 4,344,947 Date filed: October 29, 1980 Abstract: A method for the chemotherapy of muscular dystrophy which includes administrating an effective amount of 2 isopropylaminopyrimidine. Excerpt(s): The present invention is directed to a new use of an existing compound. U.S. Pat. No. 4,073,895 relates to the use of a substituted salt of 2 aminopyrimidine. This patent in fact teaches that a particular salt of 2 aminopyrimidine, namely 2 isopropylaminopyrimidine orthophosphate (IAPP), is useful as an active agent for the treatment of neuropathies. Although this use is known, the particular efficacy of the salt against muscular dystrophy has yielded unexpected and superior results. ... The invention broadly comprises a method for the chemotherapy of muscular dystrophy, which comprises administering an effective dosage of 2 isopropylaminopyrimidine or therapeutically acceptable salts of the same or the hydroxylated and oxygenated metabolites thereof. ... The dystrophic chicken homozygote was used for monitoring chemotherapy of muscular dystrophy. This particular animal line inherits dystrophy in a form as close as possible in causation and course to human dystrophy and also permits quantitative assessment of progress of the disease by several independent methods. Web site: http://www.delphion.com/details?pn=US04344947__
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Patent Applications on Muscular Dystrophy 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). The following patent applications have been filed since December 2000 relating to muscular dystrophy: ·
Pharmaceutical composition for treatment of duchenne muscular dystrophy Inventor(s): Matsuo, Masafumi ; (Kobe-shi, JP) Correspondence: Greenblum & Bernstein, P.L.C.; 1941 Roland Clarke Place; Reston; VA; 20191; US Patent Application Number: 20010056077 Date filed: July 31, 2001 Abstract: A therapeutic pharmaceutical composition for patients of Duchenne muscular dystrophy with entire loss of exon 20 in dystrophin mature mRNA is provided. The composition comprise as an active principle an antisense oligonucleotide consisting of a 20 to 50-nucleotide sequence against exon 19 of the dystrophin pre-mRNA. Excerpt(s): The present invention relates to the use of an antisense oligonucleotide for the manufacture of a therapeutic pharmaceutical composition for a certain hereditary disease, and more specifically to a therapeutic pharmaceutical composition for Duchenne muscular dystrophy intended to induce an exon skipping in the pre-mRNA of a certain abnormal dystrophin gene. ... Today, diagnosis has become available for some hereditary diseases caused by abnormal splicing of the corresponding pre-mRNA, and an intractable disease, muscular dystrophy, has come to draw particular attention. Muscular dystrophy is grossly classified into Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DMD is a hereditary muscular disease of highest incidence, occurring in one out of 3,500 newborn boys. Patients of DMD exhibit lowered muscular power in their infancy at first, and, after suffering from consistent muscular atrophy from then on, eventually die at the age of about 20. At present, no effective therapeutic drug is available for DMD, and therefore development of such a therapeutic has been longed for by patients all over the world. In 1987, dystrophin gene as the causative gene of DMD was found with the aid of retrospective genetics, and BMD also was found to occur from abnormality of the same dystrophin gene [Koenig, M. et al., Cell, 50:509-517(1987)]. As for BMD,
25
This has been a common practice outside the United States prior to December 2000.
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its onset is relatively late, which is noted in the adulthood, and, though a mild loss of muscular power is observed after the onset of the disease, nearly normal life is allowed. ... Thus, the present invention provides use of an antisense oligonucleotide for the manufacture of a therapeutic pharmaceutical composition for Duchenne muscular dystrophy with entire loss of exon 20 in the production of dystrophin mature mRNA, wherein said antisense oligonucleotide consists of a 20 to 50-nucleotide sequence against exon 19 of the dystrophin pre-mRNA. Use of such an antisense oligonucleotide as an active principle for a therapeutic pharmaceutical composition makes it possible, for a type of Duchenne muscular dystrophy having an entire loss of exon 20, to shift the amino acids reading frame in its mRNA from abnormal out-of-frame position to in-frame one, and this then enables to convert the disease to a less severe Becker muscular dystrophy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with muscular dystrophy, 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 “muscular dystrophy” (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 muscular dystrophy. You can also use this procedure to view pending patent applications concerning muscular dystrophy. Simply go to the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” Select “Quick Search” under “Patent Applications.” Then proceed with the steps listed above.
Vocabulary Builder 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
Patents 105
sequence by virtue of which it interacts only with the antigen that induced its synthesis in cells of the lymphoid series (especially plasma cells), or with antigen closely related to it. Antibodies are classified according to their ode of action as agglutinins, bacteriolysins, haemolysins, opsonins, precipitins, etc. [EU] 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] Benign: Not malignant; not recurrent; favourable for recovery. [EU] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] 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] Hypertrophy: Nutrition) the enlargement or overgrowth of an organ or part due to an increase in size of its constituent cells. [EU] Lesion: Any pathological or traumatic discontinuity of tissue or loss of
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function of a part. [EU] Localization: 1. the determination of the site or place of any process or lesion. 2. restriction to a circumscribed or limited area. 3. prelocalization. [EU] Metabolite: process. [EU]
Any substance produced by metabolism or by a metabolic
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] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU]
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CHAPTER 6. BOOKS ON MUSCULAR DYSTROPHY Overview This chapter provides bibliographic book references relating to muscular dystrophy. You have many options to locate books on muscular dystrophy. 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 muscular dystrophy 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 “muscular dystrophy” (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 muscular dystrophy:
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·
A-Z Reference Book of Syndromes and Inherited Disorders Source: London, England: Chapman and Hall. 1996. 394 p. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 2386777. Fax (800) 774-8398 or (619) 238-6789. E-mail:
[email protected]. Website: www.singpub.com. PRICE: $42.95 plus shipping and handling. ISBN: 0412641208. Summary: This book provides a practical reference for both caregivers and those with a syndrome or inherited disorder. The author describes the disorders and problems of both children and adults, and considers the day-to-day management of conditions. The book is written in nontechnical language while still providing enough detail for medical, nursing, and midwifery professionals. The syndromes and disorders are listed alphabetically by name. Those specifically related to deafness, communication, and speech and language include achondroplasia, Alport's syndrome, Apert's syndrome, Asperger's syndrome, Batten's disease, Beckwith-Wiedeman syndrome, CHARGE syndrome, Cockayne syndrome, Cornelia de Lange syndrome, Crouzon's syndrome, Down's syndrome, Duchenne muscular dystrophy, Edward's syndrome, EhlersDanlos syndrome, Fabry disease, fetal alcohol syndrome, Fragile X syndrome, Gilles de la Tourette syndrome, Goldenhar syndrome, Hunter's syndrome, Hurler's syndrome, Klinefelter's syndrome, LEOPARD syndrome, Moebius syndrome, Morquio's syndrome, neurofibromatosis, Niemann-Pick disease, Noonan's syndrome, osteogenesis imperfecta, Pierre-Robin syndrome, Prader-Willi syndrome, Rett's syndrome, Reye's syndrome, San Filippo syndrome, SmithMagenis syndrome, Stickler syndrome, Tay-Sachs disease, Treacher Collins syndrome, Turner's syndrome, Usher's syndrome, Waardenburg's syndrome, and William's syndrome. For each syndrome, the author lists alternative names, incidence, causation (etiology), characteristics or symptoms, management implications (treatment options), prognosis, and self-help groups to contact. Most groups listed are in England. The book concludes with three appendices that provide a discussion of genetics, a listing of regional genetics centers (in England), and a glossary of terms. A subject index is also included. (AA-M).
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
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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 muscular dystrophy (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): ·
Muscular Dystrophy Research: Advances and New Trends (International Congress Vol 527) by Howard Griffin (1980); ISBN: 044490168X; http://www.amazon.com/exec/obidos/ASIN/044490168X/icongroupi nterna
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Muscular Dystrophy : Proceedings of the International Symposium on Muscular Dystrophy, Held November 25-27, 1980 in Tokyo by International Symposium on Muscular Dystrophy (1983); ISBN: 0860083217; http://www.amazon.com/exec/obidos/ASIN/0860083217/icongroupin terna
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Muscular Dystrophy : Biomedical Aspects by S. and Ozawa, E. Ebashi (Editor) (1983); ISBN: 0387123423; http://www.amazon.com/exec/obidos/ASIN/0387123423/icongroupin terna
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Psychosocial Aspects of Muscular Dystrophy and Allied Diseases: Commitment to Life, Health, and Function by Leon I. Charash (1983); ISBN: 0398048118; http://www.amazon.com/exec/obidos/ASIN/0398048118/icongroupin terna
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Muscular Dystrophy and Allied Diseases : Impact on Patients, Family, and Staff (Current Thanatology) by Leon I. Charash (1985); ISBN: 0930194381; http://www.amazon.com/exec/obidos/ASIN/0930194381/icongroupin terna
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Readings in Muscular Dystrophy (1986); ISBN: 0895684020; http://www.amazon.com/exec/obidos/ASIN/0895684020/icongroupin terna
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Readings in Muscular Dystrophy by Douglas H. Ruben, Nancy R. MacCiomei (Editor) (1986); ISBN: 0582286581; http://www.amazon.com/exec/obidos/ASIN/0582286581/icongroupin terna
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Readings Muscular Dystrophy by Douglas Ruben (1986); ISBN: 058228659X;
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http://www.amazon.com/exec/obidos/ASIN/058228659X/icongroupi nterna ·
Ventilators and Muscular Dystrophy by Nancy C. Schock (1987); ISBN: 0931301033; http://www.amazon.com/exec/obidos/ASIN/0931301033/icongroupin terna
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Pathogenesis and Therapy of Duchenne and Becker Muscular Dystrophy by Byron A. Kakulas, Frank L. Mastaglia (Editor) (1990); ISBN: 0881675970; http://www.amazon.com/exec/obidos/ASIN/0881675970/icongroupin terna
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Muscular Dystrophy Research : From Molecular Diagnosis Toward Therapy : Proceedings (International Congress Series, No. 934) by A. Angelini, et al (1991); ISBN: 044481406X; http://www.amazon.com/exec/obidos/ASIN/044481406X/icongroupi nterna
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Muscular Dystrophy and Other Neuromuscular Disease : Psycholsocial Issues by Leon I. Charash, et al (1991); ISBN: 1560240776; http://www.amazon.com/exec/obidos/ASIN/1560240776/icongroupin terna
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The Will to Live: The Battle of a Young Boy Against Muscular Dystrophy by A.J. Mills (1992); ISBN: 0963392107; http://www.amazon.com/exec/obidos/ASIN/0963392107/icongroupin terna
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Duchenne Muscular Dystrophy : Animal Models and Genetic Manipulation by Byron Kakulas, et al (1992); ISBN: 0881679380; http://www.amazon.com/exec/obidos/ASIN/0881679380/icongroupin terna
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Molecular and Cell Biology of Muscular Dystrophy (Molecular and Cell Biology of Human Diseases, No 3) by Terence Partridge (Editor) (1993); ISBN: 0412434407; http://www.amazon.com/exec/obidos/ASIN/0412434407/icongroupin terna
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Multiple Sclerosis, Muscular Dystrophy & Als (Dr. Donsbach Tells You What You Need to Know About) by Kurt W. Donsbach, H. Rudolph Alseleben (1993); ISBN: 1569595666; http://www.amazon.com/exec/obidos/ASIN/1569595666/icongroupin terna
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Myoblast Transfer : Gene Therapy for Muscular Dystrophy (Medical Intelligence Unit) by Peter K. Law (1994); ISBN: 1879702762;
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http://www.amazon.com/exec/obidos/ASIN/1879702762/icongroupin terna ·
Duchenne Muscular Dystrophy by Alan E. Emery (1996); ISBN: 0192617982; http://www.amazon.com/exec/obidos/ASIN/0192617982/icongroupin terna
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Living With Muscular Dystrophy: Illness Experience, Activities of Daily Living, Coping, Quality of Life & Rehabilitation (Comprehensive Summaries Of) by Birgitta Natterlund (2001); ISBN: 9155449972; http://www.amazon.com/exec/obidos/ASIN/9155449972/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 “muscular dystrophy” (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 ·
Abstracts of communications: Eighth Symposium on Current Research in Muscular Dystrophy and Allied Neuromuscular Diseases, held at the University of Newcastle upon Tyne 3-5 January 1980. Author: Symposium on Current Research in Muscular Dystrophy and Allied Neuromuscular Diseases (8th: 1980: University of Newcastle upon Tyne); Year: 1980; London: Muscular Dystrophy Group of Great Britain, [1980?]
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Amyotrophic lateral sclerosis and other motor neuron diseases. Author: editor, Lewis P. Rowland; Year: 1991; New York: Raven Press, c1991; ISBN: 0881677485
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a “Books” button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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http://www.amazon.com/exec/obidos/ASIN/0881677485/icongroupin terna ·
Cellular and molecular biology of muscle development: proceedings of a Muscular Dystrophy Association-UCLA Symposium, held at Steamboat Springs, Colorado, April 3-10, 1988. Author: editors, Laurence H. Kedes, Frank E. Stockdale; Year: 1989; New York: Liss, c1989; ISBN: 084512692X http://www.amazon.com/exec/obidos/ASIN/084512692X/icongroupi nterna
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Composition and function of cell membranes: application to the pathophysiology of muscle diseases. Author: edited by Stewart Wolf and Allen K. Murray; Year: 1981; New York: Plenum, c1981; ISBN: 030640883X http://www.amazon.com/exec/obidos/ASIN/030640883X/icongroupi nterna
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Current research in muscular dystrophy, Japan: clinical researches; the proceedings of the Annual Meeting of Muscular Dystrophy Research Group, 1980, Tokyo. Author: Muscular Dystrophy Research Group (Japan). Meeting (1980: Tokyo, Japan); Year: 1981; [Tokyo?: s.n., 1981?]
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Current research in muscular dystrophy, Japan: the proceedings of the Annual Meeting of Muscular Dystrophy Research Group, 1978, 1979, Tokyo. Author: Muscular Dystrophy Research Group (Japan). Meeting (1978-1979: Tokyo, Japan); Year: 1980; [Tokyo?: s.n., 1980?]
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Disorders of the motor unit. Author: edited by Donald L. Schotland; Year: 1982; New York: Wiley, 1982; ISBN: 0471095079 http://www.amazon.com/exec/obidos/ASIN/0471095079/icongroupin terna
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Duchenne muscular dystrophy: animal models and genetic manipulation. Author: editors, Byron A. Kakulas, John McC. Howell, Allen D. Roses; Year: 1992; New York: Raven Press, c1992; ISBN: 0881679380 http://www.amazon.com/exec/obidos/ASIN/0881679380/icongroupin terna
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Duchenne muscular dystrophy. Author: Alan E.H. Emery; Year: 1993; Oxford; New York: Oxford University Press, 1993; ISBN: 0192623702 (hbk) http://www.amazon.com/exec/obidos/ASIN/0192623702/icongroupin terna
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Gene expression in muscle. Author: edited by Richard C. Strohman and Stewart Wolf; Year: 1985; New York: Plenum Press, c1985; ISBN: 0306418940
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Genetic analysis of the X chromosome: studies of Duchenne muscular dystrophy and related disorders. Author: edited by Henry F. Epstein and Stewart Wolf; Year: 1982; New York: Plenum Press, c1982; ISBN: 0306411296 http://www.amazon.com/exec/obidos/ASIN/0306411296/icongroupin terna
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History of a genetic disease: Duchenne muscular dystrophy or Meryon's disease. Author: Alan E.H. Emery & Marcia L.H. Emery; Year: 1995; London; New York: Royal Society of Medicine Press, c1995; ISBN: 1853152493
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Molecular and cell biology of muscular dystrophy. Author: edited by Terence Partridge; Year: 1993; London; New York: Chapman & Hall, 1993; ISBN: 0412434407 (hardback: alk. paper) http://www.amazon.com/exec/obidos/ASIN/0412434407/icongroupin terna
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Multiple sclerosis, muscular dystrophy & ALS. Author: Kurt W. Donsbach, H. Rudolph Alsleben; Year: 1993; [United States]: Rockland Corp., c1993; ISBN: 1569595666 http://www.amazon.com/exec/obidos/ASIN/1569595666/icongroupin terna
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Muscular dystrophy: biomedical aspects. Author: edited by Setsuro Ebashi and Eijiro Ozawa; Year: 1983; Tokyo: Japan Scientific Societies Press; Berlin; New York: Springer-Verlag, 1983; ISBN: 0387122423 (SpringerVerlag: U.S.)
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Muscular dystrophy: methods and protocols. Author: edited by Katherine M.D. Bushby and Louise V.B. Anderson; Year: 2001; Totowa, N.J.: Humana Press, c2001; ISBN: 0896036952 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0896036952/icongroupin terna
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Muscular dystrophy: proceedings of the International Symposium on Muscular Dystrophy, held November 25-27, 1980, in Tokyo. Author: edited by Setsuro Ebashi; Year: 1982; [Tokyo]: University of Tokyo Press, c1982; ISBN: 0860083217 http://www.amazon.com/exec/obidos/ASIN/0860083217/icongroupin terna
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Muscular dystrophy and other inherited diseases of skeletal muscle in animals. Author: edited by John B. Harris; Year: 1979; New York: New York Academy of Sciences, 1979; ISBN: 0897660056
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http://www.amazon.com/exec/obidos/ASIN/0897660056/icongroupin terna ·
Muscular dystrophy and other neuromuscular diseases: psychosocial issues. Author: Leon I. Charash ... [et al.], editors; Jill C. Crabtree, editor for the Foundation of Thanatology; Year: 1991; New York: Haworth Press, c1991; ISBN: 1560240776 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/1560240776/icongroupin terna
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Muscular dystrophy research: advances and new trends: proceedings ... Author: editors, C. Angelini, G.A. Danieli, D. Fontanari; Year: 1980; Amsterdam; Princeton, N.J.: Excerpta medica, 1980
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Muscular dystrophy research: from molecular diagnosis toward therapy: proceedings of the Satellite Symposium on Muscular Dystrophy Research 90, Venice, Italy, 14-15 September 1990, held in conjunction with the VIIth International Congress on Neuromuscul. Author: Satellite Symposium on Muscular Dystrophy Research 90 (1990: Venice, Italy); Year: 1991; Amsterdam; New York: Excerpta Medica; New York, NY, USA: Sole distributors for the USA and Canada, Elsevier Science Pub. Co., 1991; ISBN: 044481406X (alk. paper) http://www.amazon.com/exec/obidos/ASIN/044481406X/icongroupi nterna
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Myoblast transfer: gene therapy for muscular dystrophy. Author: Peter K. Law; Year: 1994; Austin: R.G. Landes; Boca Raton, FL: CRC Press [distributor], 1994; ISBN: 1879702762 (hard cover) http://www.amazon.com/exec/obidos/ASIN/1879702762/icongroupin terna
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Pathogenesis and therapy of Duchenne and Becker muscular dystrophy. Author: editors, Byron A. Kakulas, Frank L. Mastaglia; Year: 1990; New York: Raven Press, c1990; ISBN: 0881675970 http://www.amazon.com/exec/obidos/ASIN/0881675970/icongroupin terna
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Psychosocial aspects of muscular dystrophy and allied diseases: commitment to life, health, and function. Author: edited by Leon I. Charash ... [et al.]; with the editorial assistance of Lillian G. Kutscher; Year: 1983; Springfield, Ill., U.S.A.: Thomas, c1983; ISBN: 0398048118 http://www.amazon.com/exec/obidos/ASIN/0398048118/icongroupin terna
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Readings in muscular dystrophy. Author: Douglas H. Ruben, ed., Nancy R. Macciomei, ed; Year: 1986; New York: Longman, c1986; ISBN: 058228659X
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http://www.amazon.com/exec/obidos/ASIN/058228659X/icongroupi nterna ·
Research into the origin and treatment of muscular dystrophy: proceedings of a workshop held at "De Hooge Vuursche", Baarn, Holland, 24-27 February 1984. Author: editors, L.P. ten Kate, P.L. Pearson, A.M. Stadhouders; Year: 1984; Amsterdam; Princeton: Excerpta Medica, 1984; ISBN: 9021996715 http://www.amazon.com/exec/obidos/ASIN/9021996715/icongroupin terna
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Ventilators & muscular dystrophy. Author: by Nancy C. Schock and Agatha P. Colbert; Year: 1990; St. Louis, Mo.: Gazette International Networking Institute, 1990; ISBN: 0931301033 http://www.amazon.com/exec/obidos/ASIN/0931301033/icongroupin terna
Chapters on Muscular Dystrophy Frequently, muscular dystrophy will be discussed within a book, perhaps within a specific chapter. In order to find chapters that are specifically dealing with muscular dystrophy, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and muscular dystrophy using the “Detailed Search” option. Go directly 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 typing in “muscular dystrophy” (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 muscular dystrophy: ·
Muscular Dystrophy: Duchenne Muscular Dystrophy, Becker Muscular Dystrophy Source: in Plumridge, D., et al., eds. Student with a Genetic Disorder: Educational Implications for Special Education Teachers and for Physical Therapists, Occupational Therapists, and Speech Pathologists. Springfield, IL: Charles C Thomas Publisher. 1993. p. 180-185. Contact: Available from Charles C Thomas Publisher. 2600 South First Street, Springfield, IL 62794-9265. (212) 789-8980. Fax (217) 789-9130. PRICE: $75.95 plus shipping and handling (cloth); $39.95 plus shipping and handling (paper). ISBN: 0398058393.
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Summary: Both Duchenne and Becker muscular dystrophy are progressive muscle wasting conditions that primarily affect boys. This chapter on muscular dystrophy is from a text for special education teachers, physical therapists, occupational therapists, and speech pathologists on the educational implications of genetic disorders. Topics covered include the physical and characteristic features of the disorder, the genetics of the disorder, the cognitive and behavior profiles, the educational implications, physical therapy, occupational therapy, hearing and speech considerations, psychosocial issues, and prognosis. 5 references. ·
Myotonic Dystrophy: Steinert Muscular Dystrophy, Dytrophia Myotonica Source: in Plumridge, D., et al., eds. Student with a Genetic Disorder: Educational Implications for Special Education Teachers and for Physical Therapists, Occupational Therapists, and Speech Pathologists. Springfield, IL: Charles C Thomas Publisher. 1993. p. 186-191. Contact: Available from Charles C Thomas Publisher. 2600 South First Street, Springfield, IL 62794-9265. (217) 789-8980. Fax (217) 789-9130. PRICE: $75.95 plus shipping and handling (cloth); $39.95 plus shipping and handling (paper). ISBN: 0398058393. Summary: Myotonic dystrophy is a type of muscular dystrophy that affects other parts of the body in addition to muscles. This chapter on myotonic dystrophy is from a text for special education teachers, physical therapists, occupational therapists, and speech pathologists on the educational implications of genetic disorders. Topics covered include the physical and characteristic features of the disorder, the genetics of the disorder, the cognitive and behavior profiles, the educational implications, physical therapy, occupational therapy, hearing and speech considerations, psychosocial issues, and prognosis. 6 references.
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Neuromuscular Disorders Source: in Grundy, M.C.; Shaw, L.; and Hamilton, D.V. Illustrated Guide to Dental Care for the Medically Compromised Patient. St. Louis, MO: Mosby-Year Book, Inc. 1993. p. 87-88. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-9934. (800) 426-4545 or (314) 872-8370; Fax (800) 535-9935 or (314) 432-1380; E-mail:
[email protected]; http://www.mosby.com. PRICE: $24.95 plus shipping and handling. ISBN: 0815140223.
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Summary: This chapter, from an illustrated guide to dental care for medically compromised patients, discusses neuromuscular disorders. Topics covered include muscular dystrophy, myasthenia gravis, and Guillain-Barre syndrome. For each condition, the authors provide a brief description, the components of medical management, and suggestions for dental care.
Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to muscular dystrophy have been published that consolidate information across various sources. These too might be useful in gaining access to additional guidance on muscular dystrophy. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:27 ·
Sports, Anyone? Source: Alexandria, VA, Orthotics and Prosthetics National Office, 17 p., September 1994. Contact: Orthotics and Prosthetics National Office, 1650 King Street, Suite 500, Alexandria, VA 22314. (703) 836-7114. Summary: Sports, Anyone? gives detailed information on organizations that offer physical activities programs for individuals with disabilities. The National Handicapped Sports (NHS) and other U.S. Olympic Committee Disabled Sports Organizations offer training programs and conduct competitions that can give the disabled person the opportunity to compete in the Paralympic Games, which immediately follow the Olympics. Disabled Sports Organizations listed in the directory include the American Athletic Association of the Deaf (AAAD), the Dwarf Athletic Association of America (DAAA), the National Amputee Golf Association (NAGA), National Handicapped Sports (NHS), the United States Association of Blind Athletes (USABA), the United States Cerebral Palsy Athletic Association (USCPAA), the United States Les Autres Sports Association (USLASA) (which includes persons with such
You will need to limit your search to “Directories” and muscular dystrophy using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by”. For publication date, select “All Years”, select language and the format option “Directory”. By making these selections and typing in “muscular dystrophy” (or synonyms) into the “For these words:” box, you will only receive results on directories dealing with muscular dystrophy. You should check back periodically with this database as it is updated every three months.
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physical impairments as multiple sclerosis, muscular dystrophy, osteogenesis imperfecta, and other lesser-known disabilities), and Wheelchair Sports USA. Each entry includes address, telephone, and contact person information, eligibility criteria, a brief description of the organization, and the types of activities offered. The directory concludes with two inspirational essays, Rising to the Top and Essentials of Activity, which were written by disabled athletes, and provides information about the 1996 Paralympic Games in Atlanta, Georgia. ·
9Health Fair Referral Guide Source: Denver, CO, Nine Health Services, Inc., 216 p., 1994. Contact: Nine Health Services, Inc., 825 East Speer Boulevard, Suite 200, Denver, CO 80218. (303) 698-4455. Summary: 9Health Fair Referral Guide is a publication of Nine Health Services, Inc. in Denver, Colorado, and is primarily used as a resource guide by health professionals at 9Health Fairs across Colorado. The Guide was compiled as a general reference with an emphasis on agencies that serve individuals and families on a limited income. It does, however, have resources for all income levels. Each resource listed in the Referral Guide includes an address, phone number, available services and resources, and cost. Resources are listed in each of the following categories: Crisis and emergency numbers, acquired immune deficiency syndrome (AIDS), alopecia areata, Alzheimer's disease, arthritis, blood pressure screenings, cancer, cardiovascular, cerebral palsy, chiropractic, clinics, cystic fibrosis, dental care, dermatology, diabetes, disabled resources, eating disorders, epilepsy, general consumer information and education, government agencies, hearing, home health care, hospitals in metro Denver, immunizations, intestinal diseases, kidney disease, leukemia, living wills and related issues, lupus, medical societies, mental health, migrant health program, multiple sclerosis, muscular dystrophy, nutrition, orthodontics, ostomies, Parkinson's disease, physical therapy, podiatry, post-polio, prostate and testicular cancer, rehabilitation centers, respiratory diseases, runaways and shelters, safety, senior services, sexuality and family planning, sexually transmitted diseases, sickle cell anemia, shelter, smoking withdrawal and smokeless tobacco, social services agencies, speech and language, sports medicine, stress and grief, substance abuse (including alcohol and drug), suicide prevention, transplant resources, transportation, victim assistance, vision, and weight control. Resources are also listed for the following Colorado regions: Central and Mountain area, Eastern, Northern, Southern, and Western. Information numbers and referral services are also listed.
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Scientific Advisory Board, FSH Society, Inc Source: Lexington, MA: FacioScapuloHumeral Society, Inc. (FSH Society). 1995. [2 p.]. Contact: Available from FacioScapuloHumeral Society, Inc. (FSH Society). 3 Westwood Road, Lexington, MA 02173. (617) 860-0501. PRICE: Free. Summary: This directory lists the names, addresses and telephone numbers of the Scientific Advisory Board for the FacioScapuloHumeral Society, Inc. (FSH Society). The FSH Society, Inc. is a non-profit organization that addresses issues and needs specific to patients with facioscapulohumeral muscular dystrophy (FSHD).
General Home References In addition to references for muscular dystrophy, 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): · American College of Physicians Complete Home Medical Guide (with Interactive Human Anatomy CD-ROM) by David R. Goldmann (Editor), American College of Physicians; Hardcover - 1104 pages, Book & CD-Rom edition (1999), DK Publishing; ISBN: 0789444127; http://www.amazon.com/exec/obidos/ASIN/0789444127/icongroupinterna · The American Medical Association Guide to Home Caregiving by the American Medical Association (Editor); Paperback - 256 pages 1 edition (2001), John Wiley & Sons; ISBN: 0471414093; http://www.amazon.com/exec/obidos/ASIN/0471414093/icongroupinterna · Anatomica : The Complete Home Medical Reference by Peter Forrestal (Editor); Hardcover (2000), Book Sales; ISBN: 1740480309; http://www.amazon.com/exec/obidos/ASIN/1740480309/icongroupinterna · The HarperCollins Illustrated Medical Dictionary : The Complete Home Medical Dictionary by Ida G. Dox, et al; Paperback - 656 pages 4th edition (2001), Harper Resource; ISBN: 0062736469; http://www.amazon.com/exec/obidos/ASIN/0062736469/icongroupinterna · Mayo Clinic Guide to Self-Care: Answers for Everyday Health Problems by Philip Hagen, M.D. (Editor), et al; Paperback - 279 pages, 2nd edition (December 15, 1999), Kensington Publishing Corp.; ISBN: 0962786578; http://www.amazon.com/exec/obidos/ASIN/0962786578/icongroupinterna
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· The Merck Manual of Medical Information : Home Edition (Merck Manual of Medical Information Home Edition (Trade Paper) by Robert Berkow (Editor), Mark H. Beers, M.D. (Editor); Paperback - 1536 pages (2000), Pocket Books; ISBN: 0671027263; http://www.amazon.com/exec/obidos/ASIN/0671027263/icongroupinterna
Vocabulary Builder Alopecia: Baldness; absence of the hair from skin areas where it normally is present. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Hemidesmosomes: An anchoring junction of the cell to a non-cellular substrate, similar in morphology to halves of desmosomes. They are composed of specialized areas of the plasma membrane where intermediate filaments bind on the cytoplasmic face to the transmembrane linkers, integrins, via intracellular attachment proteins, while the extracellular domain of the integrins binds to extracellular matrix proteins. [NIH] Immunization: The induction of immunity. [EU] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]
Podiatry: A specialty concerned with the diagnosis and treatment of foot disorders and injuries and anatomic defects of the foot. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the
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deep layer of the triangular ligament, and rests upon the rectum. [NIH] Thanatology: The study of the theory, philosophy, and doctrine of death. [NIH]
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CHAPTER 7. MULTIMEDIA ON MUSCULAR DYSTROPHY Overview Information on muscular dystrophy 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 muscular dystrophy. 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 muscular dystrophy is the Combined Health Information Database. You will need to limit your search to “video recording” and “muscular dystrophy” 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 “muscular dystrophy” (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 muscular dystrophy:
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Doctor is In: Speech Source: Princeton, NJ: Films for the Humanities and Sciences. 1991. (videocassette). Contact: Available from Films for the Humanities and Sciences, Inc. P.O. Box 2053, Princeton, NJ 08543-2053. (800) 257-5726 or (609) 275-1400; Fax (609) 275-3767. PRICE: $140.00 each; $75.00 (rental); plus shipping and handling. Summary: This videocassette is one in a series of programs that explain and explore major health concerns. This program on speech and speech disorders introduces a woman recovering from a stroke, a child with muscular dystrophy, a man who has had his larynx removed, a child who stutters, and an immigrant trying to lose her Polish accent. The program explores how men and women can use their voices effectively and describes what happens when one loses the voice. A featured expert is Dr. Robert Sataloff, Professor of Otolaryngology at Jefferson Medical College in Philadelphia, editor of 'The Journal of Voice', and an opera singer. Host, Jamie Guth, also speaks with speech pathologists and a person who stutters and is helping others cope with the problem. (AAM).
Bibliography: Multimedia on Muscular Dystrophy 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 muscular dystrophy (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 muscular dystrophy. For more information, follow the hyperlink indicated: ·
Congenital and inherited diseases. Source: Grover M. Hutchins; Year: 1978; Format: Slide; [New York]: Medcom, c1978
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Disorder of motility. Source: Wayne State University College of Medicine and CIBA Pharmaceutical Products, Inc.; produced by Rex Fleming; Year: 1969; Format: Motion picture; [Summit, N. J.]: CIBA; [Detroit: for loan and sale by Wayne State Univ., c196-?]
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Disorders of gait. Source: from the Department of Neurology, College of Physicians and Surgeons, Columbia University and the Neurological Institute; prepared by T.J. Putnam and E. Herz; Year: 1948; Format: Motion picture; United States: King's Crown Press, [1948]
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Duchenne's pseudohypertrophic muscular dystrophy. Source: authors, Lynette Chandler, Shari Freshman, Jeanne Fischer; produced by Division of Physical Therapy, Dept. of Rehabilitation Medicine and Health Sciences Learning Resources Center, University of; Year: 1981; Format: Slide; [Seattle, Wash.]: The Division, c1981
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External intercostal muscle biopsy. Source: Radio-TV-Film Bureau, Medical-TV-Cinematography Division, Arizona Health Sciences Center, University of Arizona; Year: 1976; Format: Videorecording; Tucson, Ariz.: Arizona Board of Regents: [for sale by Health Sciences Center, Biomedical Communications], c1976
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Gait and musculoskeletal disorders. Source: Wayne State University College of Medicine and CIBA Pharmaceutical Products, Inc.; produced by Rex Fleming; Year: 1969; Format: Motion picture; [Summit, N. J.]: CIBA; [Detroit: for loan and sale by Wayne State Univ., c196-?]
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Gemini inheritance. Source: [presented by] Filmakers Library, Inc.; [produced by Yorkshire Television]; Year: 1990; Format: Videorecording; [England]: Yorkshire Television, c1990
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Genetic counseling. Source: National Institute of Neurological and Communicative Disorders & Stroke; Year: 1978; Format: Videorecording; [Bethesda, Md.]: The Institute; [Atlanta: for loan by National Medical Audiovisual Center; Washington: for sale by National Audiovisual Center, 1978]
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Genetic discoveries, disorders, and mutations. Source: a presentation of Films for the Humanities and Sciences; [presented by] Animated Biomedical Productions; Year: 2000; Format: Videorecording; Princeton, N.J.: Films for the Humanities and Sciences, c2000
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Limb girdle dystrophy. Source: College of Medicine, Ohio State University; [produced by] Medical Audio-Visual and Television Center; Year: 1977; Format: Videorecording; Columbus, Ohio: The University: [for sale by its Health Services Audio-Visual and Television Center], c1977
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Medical research : the celebrity edge. Source: a presentation of Films for the Humanities & Sciences; Year: 1998; Format: Videorecording; Princeton, N.J.: Films for the Humanities and Sciences, c1998
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Medical terminology: orthopedic disorders and surgery. Source: AuVid, inc; Year: 1974; Format: Sound recording; [Garden Grove, Calif.]: Au-Vid, [1974]
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Mobility problems of children. Source: Medical Electronic Educational Services, in cooperation with Western Wisconsin Technical Institute; Year: 1975; Format: Filmstrip; LaCrosse, Wi.: The Institute, c1975
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Muscular dystrophy and related conditions : differential diagnosis. Source: Muscular Dystrophy Associations of America; produced by Sturgis-Grant Productions; Year: 1966; Format: Motion picture; New York: The Associations; [Atlanta: for loan by National Medical Audiovisual Center], 1966
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Muscular dystrophy, the race for the gene. Source: a BBC TV production for the Open University, in association with Coronet/MTI Film and Video; Year: 1987; Format: Videorecording; [London, England]: Open University, c1987
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Muscular dystrophy. Source: the American Academy of Orthopaedic Surgeons; Year: 1976; Format: Slide; [Chicago, Ill.]: The Academy, [1976]
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Muscular dystrophy. Source: Trainex Corporation; Year: 1973; Format: Videorecording; Garden Grove, Calif.: Trainex, c1973
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Muscular dystrophy. Source: Trainex Corporation; Year: 1973; Format: Filmstrip; Garden Grove, Calif: Trainex, c1973
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Muscular dystrophy. Source: Donald L. Schotland; Year: 1971; Format: Slide; [New York]: Medcom, c1971
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Muscular dystrophy. Source: a Films for the Humanities and Sciences presentation; a production of the Dartmouth-Hitchcock Medical Center; Year: 1990; Format: Videorecording; Princeton, N.J.: Film for the Humanities & Sciences, c1990
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Neuro-muscular disorders. Source: Hospital for Sick Children, Toronto; [produced by] Division of Instructional Media Services, Faculty of Medicine, University of Toronto; Year: 1975; Format: Motion picture; Toronto: The Division, 1975
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Orthopedic and habilitation aspects and prevention of severe deformity in children and adolescents with neuromuscular diseases. Source: National Institutes of Health, Public Health Service, Dept. of Health, Education, and Welfare; Year: 1976; Format: Videorecording; [Bethesda, Md.]: The Institutes; [Atlanta: for loan by National Medical Audiovisual Center; Washington: for sale by National Audiovisual Center, 1976]
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Practical aspects of genetic counseling. Source: Academy of Health Sciences, United States Army Medical Department; Year: 1973; Format: Videorecording; Fort Sam Houston, Tex.: The Academy: [for loan by its Health Sciences Media Division], 1973
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Progressive muscular atrophies, dystrophies, and allied conditions. Source: by S. Philip Goodhart and Benjamin Harris Balser; Year: 1944; Format: Motion picture; [United States: Neuropsychiatric Division, Montefiore Hospital, 1944]
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Recombinant DNA technology and prenatal diagnosis of genetic disease. Source: with Haig Kazazian, Corinne D. Boehm, and Virginia Corson; Year: 1987; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1987
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Respiratory failure in neuromuscular disease. Source: Bertrand J. Shapiro; Year: 1974; Format: Slide; New York: Medcom, c1974
Vocabulary Builder Gait: Manner or style of walking. [NIH] Intercostal: Situated between the ribs. [EU] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Motility: The ability to move spontaneously. [EU] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH]
Periodicals and News 129
CHAPTER 8. PERIODICALS AND NEWS ON MUSCULAR DYSTROPHY Overview Keeping up on the news relating to muscular dystrophy can be challenging. Subscribing to targeted periodicals can be an effective way to stay abreast of recent developments on muscular dystrophy. Periodicals include newsletters, magazines, and academic journals. In this chapter, we suggest a number of news sources and present various periodicals that cover muscular dystrophy 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 muscular dystrophy 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 “muscular dystrophy” 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.
Reuters The Reuters' Medical News database can be very useful in exploring news archives relating to muscular dystrophy. 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 “muscular dystrophy” (or synonyms). The following was recently listed in this archive for muscular dystrophy: ·
Mouse study shows enzyme helps muscular dystrophy Source: Reuters Health eLine Date: April 19, 2002 http://www.reuters.gov/archive/2002/04/19/eline/links/20020419elin 019.html
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Gene therapy studied for muscular dystrophy Source: Reuters Health eLine Date: December 12, 2001 http://www.reuters.gov/archive/2001/12/12/eline/links/20011212elin 004.html
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Axcell, Mount Sinai in Alzheimer's, muscular dystrophy protein research pact Source: Reuters Industry Breifing Date: November 15, 2001 http://www.reuters.gov/archive/2001/11/15/business/links/20011115 inds008.html
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House approves muscular dystrophy research push Source: Reuters Medical News Date: September 25, 2001 http://www.reuters.gov/archive/2001/09/25/professional/links/20010 925legi001.html
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House approves muscular dystrophy funding bill Source: Reuters Industry Breifing Date: September 25, 2001 http://www.reuters.gov/archive/2001/09/25/business/links/20010925 legi002.html
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Mini-protein restores muscle function in murine model of muscular dystrophy Source: Reuters Industry Breifing Date: September 19, 2001 http://www.reuters.gov/archive/2001/09/19/business/links/20010919 scie002.html
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Gene therapy fights muscular dystrophy in mice Source: Reuters Health eLine Date: September 19, 2001 http://www.reuters.gov/archive/2001/09/19/eline/links/20010919elin 005.html
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Genetic cause found for type of muscular dystrophy Source: Reuters Medical News Date: August 03, 2001 http://www.reuters.gov/archive/2001/08/03/professional/links/20010 803scie001.html
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Gene mutation linked to form of muscular dystrophy Source: Reuters Health eLine Date: August 02, 2001 http://www.reuters.gov/archive/2001/08/02/eline/links/20010802elin 010.html
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FDA pulls fast track status from muscular dystrophy study Source: Reuters Industry Breifing Date: May 01, 2001 http://www.reuters.gov/archive/2001/05/01/business/links/20010501 rglt006.html
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Key signaling mechanism could point to muscular dystrophy treatment Source: Reuters Medical News Date: April 27, 2001 http://www.reuters.gov/archive/2001/04/27/professional/links/20010 427scie002.html
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Benefit seen with long-term deflazacort for Duchenne muscular dystrophy Source: Reuters Industry Breifing Date: February 27, 2001 http://www.reuters.gov/archive/2001/02/27/business/links/20010227 clin007.html
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Muscular dystrophy gene therapy works in mice Source: Reuters Health eLine Date: February 23, 2001 http://www.reuters.gov/archive/2001/02/23/eline/links/20010223elin 024.html
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Muscle growth factor might treat age-related muscle wasting, muscular dystrophy Source: Reuters Industry Breifing Date: February 08, 2001 http://www.reuters.gov/archive/2001/02/08/business/links/20010208 scie002.html
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Verapamil prevents cardiomyopathy in mice with limb-girdle muscular dystrophy Source: Reuters Medical News Date: January 23, 2001 http://www.reuters.gov/archive/2001/01/23/professional/links/20010 123scie005.html
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Gene therapy for muscular dystrophy promising Source: Reuters Health eLine Date: November 30, 2000 http://www.reuters.gov/archive/2000/11/30/eline/links/20001130elin 006.html
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Repeats in muscular dystrophy gene responsible for disease in mice Source: Reuters Industry Breifing Date: September 11, 2000 http://www.reuters.gov/archive/2000/09/11/business/links/20000911 scie002.html
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Unusual mutation linked to muscular dystrophy Source: Reuters Health eLine Date: September 07, 2000 http://www.reuters.gov/archive/2000/09/07/eline/links/20000907elin 014.html
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Chimeric oligonucleotide repairs mutation in dog model of muscular dystrophy Source: Reuters Medical News Date: June 02, 2000 http://www.reuters.gov/archive/2000/06/02/professional/links/20000 602scie003.html
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Gene for novel sarcomeric protein may be involved in muscular dystrophy Source: Reuters Medical News Date: December 17, 1999 http://www.reuters.gov/archive/1999/12/17/professional/links/19991 217scie005.html
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Muscular dystrophy gene linked to heart disorder Source: Reuters Health eLine Date: December 02, 1999 http://www.reuters.gov/archive/1999/12/02/eline/links/19991202elin 005.html
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Stem cell transplantation restores dystrophin in mouse muscular dystrophy model Source: Reuters Medical News Date: September 23, 1999 http://www.reuters.gov/archive/1999/09/23/professional/links/19990 923scie004.html
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Bone marrow transplantation for muscular dystrophy Source: Reuters Health eLine Date: September 22, 1999 http://www.reuters.gov/archive/1999/09/22/eline/links/19990922elin 011.html
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Loss of nitric-oxide signaling linked to etiology of muscular dystrophy Source: Reuters Medical News Date: August 16, 1999 http://www.reuters.gov/archive/1999/08/16/professional/links/19990 816scie002.html
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New clue to muscular dystrophy Source: Reuters Health eLine Date: December 07, 1998 http://www.reuters.gov/archive/1998/12/07/eline/links/19981207elin 011.html
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Gene associated with two types of muscular dystrophy identified Source: Reuters Medical News Date: September 03, 1998 http://www.reuters.gov/archive/1998/09/03/professional/links/19980 903scie001.html
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Utrophin Transgene Corrects Clinical Signs Of Muscular Dystrophy In Mouse Model Of The Disease Source: Reuters Medical News Date: April 28, 1998 http://www.reuters.gov/archive/1998/04/28/professional/links/19980 428drgd002.html
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Duchenne Muscular Dystrophy: Noninvasive Respiratory Protocol Effective Source: Reuters Medical News Date: October 31, 1997 http://www.reuters.gov/archive/1997/10/31/professional/links/19971 031clin007.html
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Duchenne Muscular Dystrophy: A Better Mouse Model Built Source: Reuters Medical News Date: August 25, 1997 http://www.reuters.gov/archive/1997/08/25/professional/links/19970 825scie001.html
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New Protein May Fight Muscular Dystrophy Source: Reuters Health eLine Date: December 04, 1996 http://www.reuters.gov/archive/1996/12/04/eline/links/19961204elin 004.html
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Upregulation Of Utrophin Relieves Muscular Dystrophy In Mice Source: Reuters Medical News Date: November 28, 1996 http://www.reuters.gov/archive/1996/11/28/professional/links/19961 128scie001.html
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Gene Therapy For Muscular Dystrophy Source: Reuters Health eLine Date: September 04, 1996 http://www.reuters.gov/archive/1996/09/04/eline/links/19960904elin 010.html
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Muscular Dystrophy Can Be Diagnosed By Skin Biopsy
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Genetic Basis Of Autosomal Recessive Muscular Dystrophy Identified Source: Reuters Medical News Date: November 03, 1995 http://www.reuters.gov/archive/1995/11/03/professional/links/19951 103clin003.html
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Initial Results Of Gene Therapy For Cystic Fibrosis and Duchenne's Muscular Dystrophy Disappointing Source: Reuters Medical News Date: September 28, 1995 http://www.reuters.gov/archive/1995/09/28/professional/links/19950 928clin005.html
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TGF-Beta-1 Expression Initiates Fibrosis In Duchenne Muscular Dystrophy Source: Reuters Medical News Date: August 22, 1995 http://www.reuters.gov/archive/1995/08/22/professional/links/19950 822clin003.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.
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.
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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 “muscular dystrophy” (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 “muscular dystrophy” (or synonyms). If you know the name of a company that is relevant to muscular dystrophy, 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 “muscular dystrophy” (or synonyms).
Newsletters on Muscular Dystrophy Given their focus on current and relevant developments, newsletters are often more useful to patients than academic articles. You can find newsletters using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Your investigation must limit the search to “Newsletter” and “muscular dystrophy.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” By making these selections and typing in “muscular dystrophy” or synonyms into the “For these words:” box, you will only receive results on newsletters. The following list was generated using the options described above:
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FSH Watch Source: Lexington, MA: FacioScapuloHumeral Society, Inc. (FSH Society). 1994. 28 p. (average). Contact: Available from FacioScapuloHumeral Society, Inc. (FSH Society). 3 Westwood Road, Lexington, MA 02173. (617) 860-0501. PRICE: Free with membership. Summary: This newsletter is intended for patients with facioscapulohumeral muscular dystrophy (FSHD), their families, and health professionals. A typical issue includes organization news and announcements, research and treatment updates, financial and legislative highlights, suggestions for coping with FSHD, publication reviews, and previews of upcoming seminars and programs.
Academic Periodicals covering Muscular Dystrophy Academic periodicals can be a highly technical yet valuable source of information on muscular dystrophy. We have compiled the following list of periodicals known to publish articles relating to muscular dystrophy and which are currently indexed within the National Library of Medicine's PubMed database (follow hyperlinks to view more information, summaries, etc., for each). In addition to these sources, to keep current on articles written on muscular dystrophy published by any of the periodicals listed below, you can simply follow the hyperlink indicated or go to the following Web site: www.ncbi.nlm.nih.gov/pubmed. Type the periodical's name into the search box to find the latest studies published. If you want complete details about the historical contents of a periodical, you can also visit http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/ you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.” The following is a sample of periodicals which publish articles on muscular dystrophy:
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Archives of Disease in Childhood. (Arch Dis Child) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ar chives+of+Disease+in+Childhood&dispmax=20&dispstart=0
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Archives of Neurology. (Arch Neurol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ar chives+of+Neurology&dispmax=20&dispstart=0
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Archives of Physical Medicine and Rehabilitation. (Arch Phys Med Rehabil) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ar chives+of+Physical+Medicine+and+Rehabilitation&dispmax=20&dispsta rt=0
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Cell Transplantation. (Cell Transplant) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ce ll+Transplantation&dispmax=20&dispstart=0
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Developmental Medicine and Child Neurology. (Dev Med Child Neurol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=De velopmental+Medicine+and+Child+Neurology&dispmax=20&dispstart= 0
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European Neurology. (Eur Neurol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Eu ropean+Neurology&dispmax=20&dispstart=0
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International Journal of Rehabilitation Research. Internationale Zeitschrift Fur Rehabilitationsforschung. Revue Internationale De Recherches De Readaptation. (Int J Rehabil Res) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Int ernational+Journal+of+Rehabilitation+Research.+Internationale+Zeitschr ift+Fur+Rehabilitationsforschung.+Revue+Internationale+De+Recherche s+De+Readaptation&dispmax=20&dispstart=0
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Journal of Child Neurology. (J Child Neurol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Jo urnal+of+Child+Neurology&dispmax=20&dispstart=0
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Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. (J Pediatr Hematol Oncol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Jo urnal+of+Pediatric+Hematology/Oncology+:+Official+Journal+of+the+ American+Society+of+Pediatric+Hematology/Oncology&dispmax=20& dispstart=0
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Physical Therapy. (Phys Ther) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ph ysical+Therapy&dispmax=20&dispstart=0
Vocabulary Builder Aromatic: Having a spicy odour. [EU] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Tremor: An involuntary trembling or quivering. [EU]
Physician Guidelines and Databases 141
CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES Overview Doctors and medical researchers rely on a number of information sources to help patients with their conditions. Many will subscribe to journals or newsletters published by their professional associations or refer to specialized textbooks or clinical guides published for the medical profession. In this chapter, we focus on databases and Internet-based guidelines created or written for this professional audience.
NIH Guidelines For the more common diseases, The National Institutes of Health publish guidelines that are frequently consulted by physicians. Publications are typically written by one or more of the various NIH Institutes. For physician guidelines, commonly referred to as “clinical” or “professional” guidelines, you can visit the following Institutes: ·
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.nih.gov/niams/healthinfo/
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.28 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:29 ·
Bioethics: Access to published literature on the ethical, legal and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to caner-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 29 See http://www.nlm.nih.gov/databases/databases.html. 28
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
·
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
·
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
While all of the above references may be of interest to physicians who study and treat muscular dystrophy, the following are particularly noteworthy.
The NLM Gateway30 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing “one-stop searching” for many of NLM's information resources or databases.31 One target audience for the Gateway is the Internet user who is new to NLM's online resources and does not know what information is available or how best to search for it. This audience may include physicians and other healthcare providers, Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x. The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).
30 31
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researchers, librarians, students, and, increasingly, patients, their families, and the public.32 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “muscular dystrophy” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Items Found Journal Articles 12195 Books / Periodicals / Audio Visual 171 Consumer Health 77 Meeting Abstracts 4 Other Collections 1 Total 12448
HSTAT33 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.34 HSTAT's audience includes healthcare providers, health service researchers, policy makers, insurance companies, consumers, and the information professionals who serve these groups. HSTAT provides access to a wide variety of publications, including clinical practice guidelines, quick-reference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ's
Other users may find the Gateway useful for an overall search of NLM's information resources. Some searchers may locate what they need immediately, while others will utilize the Gateway as an adjunct tool to other NLM search services such as PubMed® and MEDLINEplus®. The Gateway connects users with multiple NLM retrieval systems while also providing a search interface for its own collections. These collections include various types of information that do not logically belong in PubMed, LOCATORplus, or other established NLM retrieval systems (e.g., meeting announcements and pre-1966 journal citations). The Gateway will provide access to the information found in an increasing number of NLM retrieval systems in several phases. 33 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 34 The HSTAT URL is http://hstat.nlm.nih.gov/. 32
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Put Prevention Into Practice.35 Simply search by “muscular dystrophy” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists36 Some patients may wish to have access to a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. To this end, we recommend “Coffee Break,” a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.37 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.38 This site has new articles every few weeks, so it can be considered an online magazine of sorts, and intended for general background information. You can access the Coffee Break Web site at http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 36 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 37 The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 38 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 35
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Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are a few examples that may interest you: ·
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
·
Image Engine: Multimedia electronic medical record system that integrates a wide range of digitized clinical images with textual data stored in the University of Pittsburgh Medical Center's MARS electronic medical record system; see the following Web site: http://www.cml.upmc.edu/cml/imageengine/imageEngine.html.
·
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
·
MedWeaver: Prototype system that allows users to search differential diagnoses for any list of signs and symptoms, to search medical literature, and to explore relevant Web sites; see http://www.med.virginia.edu/~wmd4n/medweaver.html.
·
Metaphrase: Middleware component intended for use by both caregivers and medical records personnel. It converts the informal language generally used by caregivers into terms from formal, controlled vocabularies; see the following Web site: http://www.lexical.com/Metaphrase.html.
The Genome Project and Muscular Dystrophy With all the discussion in the press about the Human Genome Project, it is only natural that physicians, researchers, and patients want to know about how human genes relate to muscular dystrophy. In the following section, we will discuss databases and references used by physicians and scientists who work in this area.
Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for
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Biotechnology Information (NCBI).39 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI's Entrez database of MEDLINE articles and sequence information. Go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html to search the database. Type “muscular dystrophy” (or synonyms) in the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. By following these links, especially the link titled “Database Links,” you will be exposed to numerous specialized databases that are largely used by the scientific community. These databases are overly technical and seldom used by the general public, but offer an abundance of information. The following is an example of the results you can obtain from the OMIM for muscular dystrophy: ·
Aminoaciduria with Mental Deficiency, Dystrophy, Osteoporosis, and Acidosis Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?204730
·
Emery-dreifuss Muscular Dystrophy Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?310300
·
Emery-dreifuss Muscular Dystrophy, Autosomal Dominant Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?181350
·
Emery-dreifuss Muscular Dystrophy, Autosomal Recessive Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?604929
·
Epidermolysis Bullosa Simplex and Limb-girdle Muscular Dystrophy Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?226670
·
Facioscapulohumeral Muscular Dystrophy 1a Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?158900
Dwarfism,
Muscular
Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
39
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·
Facioscapulohumeral Muscular Dystrophy 1b Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?158901
·
Facioscapulohumeral Muscular Dystrophy Region Gene 1 Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?601278
·
Fukuyama Congenital Muscular Dystrophy Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?253800
·
Mental Retardation, Scapuloperoneal Muscular Dystrophy, and Lethal Cardiomyopathy Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?309660 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to re-visit it from time to time. The following systems and associated disorders are addressed: ·
Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
·
Nervous System: Mind and body. Examples: Alzheimer disease, Amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, Fragile X syndrome, Friedreich's ataxia, Huntington disease, NiemannPick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, Spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
·
Signals: Cellular messages. Examples: Ataxia telangiectasia, Baldness, Cockayne syndrome, Glaucoma, SRY: sex determination, Tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
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·
Transporters: Pumps and channels. Examples: Cystic Fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson's disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: ·
PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
·
Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
·
Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
·
Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
·
Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
·
PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
·
OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
·
Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
·
Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
·
ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
·
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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·
NCBI's Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” In the box next to “for,” enter “muscular dystrophy” (or synonyms) and click “Go.” Jablonski's Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database40 This online resource can be quite useful. It has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html you can also search across syndromes using an alphabetical index. You can also search at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database41 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB's mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 41 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html#mission. 40
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focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “muscular dystrophy” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms). This database is extremely technical as it was created for specialists. The articles are the results which are the most accessible to nonprofessionals and often listed under the heading “Citations.” The contact names are also accessible to non-professionals.
Specialized References The following books are specialized references written for professionals interested in muscular dystrophy (sorted alphabetically by title, hyperlinks provide rankings, information, and reviews at Amazon.com): · Approach to the Patient with a Musculoskeletal Disorder by Warren D. Blackburn; Paperback, 2nd edition (August 15, 2002), Professional Communications; ISBN: 188473572X; http://www.amazon.com/exec/obidos/ASIN/188473572X/icongroupinterna · Connective Tissue and Its Heritable Disorders: Molecular, Genetic, and Medical Aspects by Peter M. Royce (Editor), Beat Steinmann (Editor); Hardcover, 2nd edition (December 15, 2001), John Wiley & Sons; ISBN: 0471251852; http://www.amazon.com/exec/obidos/ASIN/0471251852/icongroupinterna · Current Diagnosis & Treatment in Orthopedics by Harry B. Skinner; Paperback - 720 pages, 2nd edition (May 26, 2000), McGraw-Hill Professional Publishing; ISBN: 0838503632; http://www.amazon.com/exec/obidos/ASIN/0838503632/icongroupinterna · Current Topics in Musculoskeletal Medicine: A Case Study Approach (Athletic Training Library) by Mark Decarlo (Editor), Kathy Oneacre, M.A. ATC (Editor); Paperback (March 15, 2001), Slack, Inc.; ISBN: 1556424345; http://www.amazon.com/exec/obidos/ASIN/1556424345/icongroupinterna · Diagnosis and Treatment of Movement Impairment Syndromes by Shirley Sahrmann; Hardcover - 384 pages, 1st edition (August 20, 2001), Mosby, Inc.; ISBN: 0801672058; http://www.amazon.com/exec/obidos/ASIN/0801672058/icongroupinterna
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· Diagnosis of Bone and Joint Disorders (5-Volume Set) by Donald Resnick; Hardcover - 5472 pages, 4th edition (March 8, 2002); W B Saunders Co; ISBN: 0721689213; http://www.amazon.com/exec/obidos/ASIN/0721689213/icongroupinterna · Essentials of Musculoskeletal Care by Walter B. Greene, MD (Editor), Robert K. Snider; Hardcover, 2nd edition (January 15, 2001), American Academy of Orthopaedic; ISBN: 0892032170; http://www.amazon.com/exec/obidos/ASIN/0892032170/icongroupinterna · Examination & Diagnosis of Musculoskeletal Disorders by Miranda Castrp; Hardcover, 1st edition (February 15, 2001), Thieme Medical Pub; ISBN: 0865777411; http://www.amazon.com/exec/obidos/ASIN/0865777411/icongroupinterna · Examination and Diagnosis of Musculoskeletal Disorders: Clinical Examination - Imaging Modalities by William H. M. Castro, et al; Hardcover - 464 pages, 1st edition (January 15, 2001), Thieme Medical Pub; ISBN: 1588900320; http://www.amazon.com/exec/obidos/ASIN/1588900320/icongroupinterna · Mechanical Loading of Bones and Joints by Hideaki Takahashi (Editor); Hardcover - 324 pages, 1st edition (July 15, 1999), Springer Verlag; ISBN: 4431702423; http://www.amazon.com/exec/obidos/ASIN/4431702423/icongroupinterna · Musculoskeletal Assessment: Joint Range of Motion and Manual Muscle Strength by Hazel M. Clarkson; Spiral-bound - 432 pages, 2nd edition (January 15, 2000), Lippincott Williams & Wilkins Publishers; ISBN: 0683303848; http://www.amazon.com/exec/obidos/ASIN/0683303848/icongroupinterna · Musculoskeletal Disorders: A Practical Guide for Diagnosis and Rehabilitation by Ralph M. Buschbacher (Editor); Hardcover, 2nd edition (March 15, 2002), Butterworth-Heinemann; ISBN: 0750673575; http://www.amazon.com/exec/obidos/ASIN/0750673575/icongroupinterna · Musculoskeletal Examination by Jeffrey Gross, et al; Paperback, 2nd edition (March 2002), Blackwell Science Inc; ISBN: 0632045582; http://www.amazon.com/exec/obidos/ASIN/0632045582/icongroupinterna · Orthopedic Biomechanics by Paul Brinckmann, et al; Hardcover (March 2002), Thieme Medical Pub; ISBN: 1588900800; http://www.amazon.com/exec/obidos/ASIN/1588900800/icongroupinterna · Orthopaedic Pathology by Vincent J. Vigorita, Bernard Ghelman; Hardcover - 718 pages (February 15, 1999), Lippincott Williams & Wilkins
Physician Guidelines and Databases 153
Publishers; ISBN: 078170040X; http://www.amazon.com/exec/obidos/ASIN/078170040X/icongroupinterna · Pathology of Skeletal Muscle by Stirling Carpenter, George Karpati; Hardcover, 2nd edition (January 15, 2001), Oxford University Press; ISBN: 0195063643; http://www.amazon.com/exec/obidos/ASIN/0195063643/icongroupinterna · Skeletal Trauma: Basic Science, Management, and Reconstruction by Bruce D. Browner (Editor); Hardcover, 3rd edition (August 2002), W B Saunders Co; ISBN: 0721694810; http://www.amazon.com/exec/obidos/ASIN/0721694810/icongroupinterna
Vocabulary Builder Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Osteoporosis: Reduction in the amount of bone mass, leading to fractures after minimal trauma. [EU]
Dissertations 155
CHAPTER 10. DISSERTATIONS ON MUSCULAR DYSTROPHY Overview University researchers are active in studying almost all known diseases. The result of research is often published in the form of Doctoral or Master's dissertations. You should understand, therefore, that applied diagnostic procedures and/or therapies can take many years to develop after the thesis that proposed the new technique or approach was written. In this chapter, we will give you a bibliography on recent dissertations relating to muscular dystrophy. You can read about these in more detail using the Internet or your local medical library. We will also provide you with information on how to use the Internet to stay current on dissertations.
Dissertations on Muscular Dystrophy ProQuest Digital Dissertations is the largest archive of academic dissertations available. From this archive, we have compiled the following list covering dissertations devoted to muscular dystrophy. You will see that the information provided includes the dissertation’s title, its author, and the author’s institution. To read more about the following, simply use the Internet address indicated. The following covers recent dissertations dealing with muscular dystrophy: ·
A Descriptive Analysis of 'the Jerry Lewis Labor Day Telethon for Muscular Dystrophy'. by Londino, Lawrence Joseph, Phd from The University of Michigan, 1978, 209 pages http://wwwlib.umi.com/dissertations/fullcit/7907126
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·
A Study of Selected Variables in Relation to Accidents of Muscular Dystrophy Children in Special Schools. by Nemarich, Samuel Peter, Phd from New York University, 1975, 168 pages http://wwwlib.umi.com/dissertations/fullcit/7601746
·
Limb Girdle Muscular Dystrophy in Unique Manitoba Populations by Weiler, Tracey; Phd from The University of Manitoba (canada), 2001, 280 pages http://wwwlib.umi.com/dissertations/fullcit/NQ62676
·
Living with Muscular Dystrophy: Illness Experience, Activities of Daily Living, Coping, Quality of Life and Rehabilitation by Natterlund, Birgitta; Phd from Uppsala Universitet (sweden), 2001, 91 pages http://wwwlib.umi.com/dissertations/fullcit/f475233
·
Maximal Isometric Strength on the Kinetic Communicator System for Duchenne Muscular Dystrophy Patients by Xie, Xiaoqing (steven); Da from Middle Tennessee State University, 2001, 123 pages http://wwwlib.umi.com/dissertations/fullcit/3030580
·
Studies of the Sarcoglycan Complex in Limb-girdle Muscular Dystrophy and the Bio 14.6 Hamster by Lim, Leland Edgar; Phd from The University of Iowa, 2000, 94 pages http://wwwlib.umi.com/dissertations/fullcit/9975654
·
The Effect of Physostigmine on Language Processes in Boys with Duchenne Muscular Dystrophy (memory) by Cameron, Thomas Hartley, Phd from The University of North Carolina at Chapel Hill, 1985, 108 pages http://wwwlib.umi.com/dissertations/fullcit/8527184
·
Three Wishes in Children with and without Duchenne Muscular Dystrophy by Nereo, Nancy E.; Phd from Columbia University, 2000, 147 pages http://wwwlib.umi.com/dissertations/fullcit/9956385
·
Visual Evoked Potentials in Duchenne Muscular Dystrophy by Benoff, Keith Richard; Phd from Yeshiva University, 2000, 341 pages http://wwwlib.umi.com/dissertations/fullcit/3022677
Keeping Current As previously mentioned, an effective way to stay current on dissertations dedicated to muscular dystrophy is to use the database called ProQuest Digital Dissertations via the Internet, located at the following Web address: http://wwwlib.umi.com/dissertations. The site allows you to freely access
Dissertations 157
the last two years of citations and abstracts. Ask your medical librarian if the library has full and unlimited access to this database. From the library, you should be able to do more complete searches than with the limited 2-year access available to the general public.
Vocabulary Builder Physostigmine: A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity. [NIH]
159
PART III. APPENDICES
ABOUT PART III Part III is a collection of appendices on general medical topics which may be of interest to patients with muscular dystrophy and related conditions.
Researching Your Medications 161
APPENDIX A. RESEARCHING YOUR MEDICATIONS Overview There are a number of sources available on new or existing medications which could be prescribed to patients with muscular dystrophy. While a number of hard copy or CD-Rom resources are available to patients and physicians for research purposes, a more flexible method is to use Internetbased databases. In this chapter, we will begin with a general overview of medications. We will then proceed to outline official recommendations on how you should view your medications. You may also want to research medications that you are currently taking for other conditions as they may interact with medications for muscular dystrophy. Research can give you information on the side effects, interactions, and limitations of prescription drugs used in the treatment of muscular dystrophy. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
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Your Medications: The Basics42 The Agency for Health Care Research and Quality has published extremely useful guidelines on how you can best participate in the medication aspects of muscular dystrophy. Taking medicines is not always as simple as swallowing a pill. It can involve many steps and decisions each day. The AHCRQ recommends that patients with muscular dystrophy take part in treatment decisions. Do not be afraid to ask questions and talk about your concerns. By taking a moment to ask questions early, you may avoid problems later. Here are some points to cover each time a new medicine is prescribed: ·
Ask about all parts of your treatment, including diet changes, exercise, and medicines.
·
Ask about the risks and benefits of each medicine or other treatment you might receive.
·
Ask how often you or your doctor will check for side effects from a given medication.
Do not hesitate to ask what is important to you about your medicines. You may want a medicine with the fewest side effects, or the fewest doses to take each day. You may care most about cost, or how the medicine might affect how you live or work. Or, you may want the medicine your doctor believes will work the best. Telling your doctor will help him or her select the best treatment for you. Do not be afraid to “bother” your doctor with your concerns and questions about medications for muscular dystrophy. You can also talk to a nurse or a pharmacist. They can help you better understand your treatment plan. Feel free to bring a friend or family member with you when you visit your doctor. Talking over your options with someone you trust can help you make better choices, especially if you are not feeling well. Specifically, ask your doctor the following: ·
The name of the medicine and what it is supposed to do.
·
How and when to take the medicine, how much to take, and for how long.
·
What food, drinks, other medicines, or activities you should avoid while taking the medicine.
·
What side effects the medicine may have, and what to do if they occur.
42
This section is adapted from AHCRQ: http://www.ahcpr.gov/consumer/ncpiebro.htm.
Researching Your Medications 163
·
If you can get a refill, and how often.
·
About any terms or directions you do not understand.
·
What to do if you miss a dose.
·
If there is written information you can take home (most pharmacies have information sheets on your prescription medicines; some even offer large-print or Spanish versions).
Do not forget to tell your doctor about all the medicines you are currently taking (not just those for muscular dystrophy). This includes prescription medicines and the medicines that you buy over the counter. Then your doctor can avoid giving you a new medicine that may not work well with the medications you take now. When talking to your doctor, you may wish to prepare a list of medicines you currently take, the reason you take them, and how you take them. Be sure to include the following information for each: ·
Name of medicine
·
Reason taken
·
Dosage
·
Time(s) of day
Also include any over-the-counter medicines, such as: ·
Laxatives
·
Diet pills
·
Vitamins
·
Cold medicine
·
Aspirin or other pain, headache, or fever medicine
·
Cough medicine
·
Allergy relief medicine
·
Antacids
·
Sleeping pills
·
Others (include names)
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Learning More about Your Medications Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications your doctor has recommended for muscular dystrophy. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the “U.S. Pharmacopeia (USP).” Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at www.usp.org. The USP currently provides standards for over 3,700 medications. The resulting USP DIÒ Advice for the PatientÒ can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration's (FDA) Drug Approvals database.43 While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopoeia. It is important to read the disclaimer by the United States Pharmacopoeia (http://www.nlm.nih.gov/medlineplus/drugdisclaimer.html) before using the information provided. Of course, we as editors cannot be certain as to what medications you are taking. Therefore, we have compiled a list of medications associated with the treatment of muscular dystrophy. Once again, due to space limitations, we only list a sample of medications and provide hyperlinks to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to muscular dystrophy:
Though cumbersome, the FDA database can be freely browsed at the following site: www.fda.gov/cder/da/da.htm.
43
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Anticonvulsants, Hydantoin ·
Systemic - U.S. Brands: Cerebyx; Dilantin; Dilantin Infatabs; Dilantin Kapseals; Dilantin-125; Mesantoin; Peganone; Phenytex http://www.nlm.nih.gov/medlineplus/druginfo/anticonvulsants hydantoinsystem202052.html
Clofibrate ·
Systemic - U.S. Brands: Abitrate; Atromid-S http://www.nlm.nih.gov/medlineplus/druginfo/clofibratesystem ic202150.html
Dantrolene ·
Systemic - U.S. Brands: Dantrium http://www.nlm.nih.gov/medlineplus/druginfo/dantrolenesyste mic202181.html
Lithium ·
Systemic - U.S. Brands: Cibalith-S; Eskalith; Lithane; Lithobid; Lithonate; Lithotabs http://www.nlm.nih.gov/medlineplus/druginfo/lithiumsystemic 202330.html
Vitamin E ·
Systemic - U.S. Brands: Amino-Opti-E; E-Complex-600; Liqui-E; Pheryl-E http://www.nlm.nih.gov/medlineplus/druginfo/vitaminesystemi c202598.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. You may be able to access these sources from your local medical library or your doctor's office.
Reuters Health Drug Database The Reuters Health Drug Database can be searched by keyword at the hyperlink: http://www.reutershealth.com/frame2/drug.html. The following
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medications are listed in the Reuters' database as associated with muscular dystrophy (including those with contraindications):44 ·
Prednisone http://www.reutershealth.com/atoz/html/Prednisone.htm
·
Verapamil HCI http://www.reutershealth.com/atoz/html/Verapamil_HCI.htm
Mosby's GenRx Mosby's GenRx database (also available on CD-Rom and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Information in Mosby's GenRx database can be obtained at the following hyperlink: http://www.genrx.com/Mosby/PhyGenRx/group.html. Physicians Desk Reference The Physicians Desk Reference database (also available in CD-Rom and book format) is a full-text drug database. The database is searchable by brand name, generic name or by indication. It features multiple drug interactions reports. Information can be obtained at the following hyperlink: http://physician.pdr.net/physician/templates/en/acl/psuser_t.htm.
Other Web Sites A number of additional Web sites discuss drug information. As an example, you may like to look at www.drugs.com which reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. which allows users to download articles on various drugs and therapeutics for a nominal fee: http://www.medletter.com/.
Contraindications and Interactions (Hidden Dangers) Some of the medications mentioned in the previous discussions can be problematic for patients with muscular dystrophy--not because they are 44
Adapted from A to Z Drug Facts by Facts and Comparisons.
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used in the treatment process, but because of contraindications, or side effects. Medications with contraindications are those that could react with drugs used to treat muscular dystrophy or potentially create deleterious side effects in patients with muscular dystrophy. You should ask your physician about any contraindications, especially as these might apply to other medications that you may be taking for common ailments. Drug-drug interactions occur when two or more drugs react with each other. This drug-drug interaction may cause you to experience an unexpected side effect. Drug interactions may make your medications less effective, cause unexpected side effects, or increase the action of a particular drug. Some drug interactions can even be harmful to you. Be sure to read the label every time you use a nonprescription or prescription drug, and take the time to learn about drug interactions. These precautions may be critical to your health. You can reduce the risk of potentially harmful drug interactions and side effects with a little bit of knowledge and common sense. Drug labels contain important information about ingredients, uses, warnings, and directions which you should take the time to read and understand. Labels also include warnings about possible drug interactions. Further, drug labels may change as new information becomes available. This is why it's especially important to read the label every time you use a medication. When your doctor prescribes a new drug, discuss all over-thecounter and prescription medications, dietary supplements, vitamins, botanicals, minerals and herbals you take as well as the foods you eat. Ask your pharmacist for the package insert for each prescription drug you take. The package insert provides more information about potential drug interactions.
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A Final Warning At some point, you may hear of alternative medications from friends, relatives, or in the news media. Advertisements may suggest that certain alternative drugs can produce positive results for patients with muscular dystrophy. Exercise caution--some of these drugs may have fraudulent claims, and others may actually hurt you. The Food and Drug Administration (FDA) is the official U.S. agency charged with discovering which medications are likely to improve the health of patients with muscular dystrophy. The FDA warns patients to watch out for45: ·
Secret formulas (real scientists share what they know)
·
Amazing breakthroughs or miracle cures (real breakthroughs don't happen very often; when they do, real scientists do not call them amazing or miracles)
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Quick, painless, or guaranteed cures
·
If it sounds too good to be true, it probably isn't true.
If you have any questions about any kind of medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
General References In addition to the resources provided earlier in this chapter, the following general references describe medications (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·
Complete Guide to Prescription and Nonprescription Drugs 2001 (Complete Guide to Prescription and Nonprescription Drugs, 2001) by H. Winter Griffith, Paperback 16th edition (2001), Medical Surveillance; ISBN: 0942447417; http://www.amazon.com/exec/obidos/ASIN/039952634X/icongroupinterna
·
The Essential Guide to Prescription Drugs, 2001 by James J. Rybacki, James W. Long; Paperback - 1274 pages (2001), Harper Resource; ISBN: 0060958162; http://www.amazon.com/exec/obidos/ASIN/0060958162/icongroupinterna
This section has been adapted from http://www.fda.gov/opacom/lowlit/medfraud.html.
45
Researching Your Medications 169
·
Handbook of Commonly Prescribed Drugs by G. John Digregorio, Edward J. Barbieri; Paperback 16th edition (2001), Medical Surveillance; ISBN: 0942447417; http://www.amazon.com/exec/obidos/ASIN/0942447417/icongroupinterna
·
Johns Hopkins Complete Home Encyclopedia of Drugs 2nd ed. by Simeon Margolis (Ed.), Johns Hopkins; Hardcover - 835 pages (2000), Rebus; ISBN: 0929661583; http://www.amazon.com/exec/obidos/ASIN/0929661583/icongroupinterna
·
Medical Pocket Reference: Drugs 2002 by Springhouse Paperback 1st edition (2001), Lippincott Williams & Wilkins Publishers; ISBN: 1582550964; http://www.amazon.com/exec/obidos/ASIN/1582550964/icongroupinterna
·
PDR by Medical Economics Staff, Medical Economics Staff Hardcover 3506 pages 55th edition (2000), Medical Economics Company; ISBN: 1563633752; http://www.amazon.com/exec/obidos/ASIN/1563633752/icongroupinterna
·
Pharmacy Simplified: A Glossary of Terms by James Grogan; Paperback 432 pages, 1st edition (2001), Delmar Publishers; ISBN: 0766828581; http://www.amazon.com/exec/obidos/ASIN/0766828581/icongroupinterna
·
Physician Federal Desk Reference by Christine B. Fraizer; Paperback 2nd edition (2001), Medicode Inc; ISBN: 1563373971; http://www.amazon.com/exec/obidos/ASIN/1563373971/icongroupinterna
·
Physician's Desk Reference Supplements Paperback - 300 pages, 53 edition (1999), ISBN: 1563632950; http://www.amazon.com/exec/obidos/ASIN/1563632950/icongroupinterna
Vocabulary Builder Dantrolene: Skeletal muscle relaxant that acts by interfering with excitationcontraction coupling in the muscle fiber. It is used in spasticity and other neuromuscular abnormalities. Although the mechanism of action is probably not central, dantrolene is usually grouped with the central muscle relaxants. [NIH]
Lithium: Lithium. An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH]
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APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE Overview Complementary and alternative medicine (CAM) is one of the most contentious aspects of modern medical practice. You may have heard of these treatments on the radio or on television. Maybe you have seen articles written about these treatments in magazines, newspapers, or books. Perhaps your friends or doctor have mentioned alternatives. In this chapter, we will begin by giving you a broad perspective on complementary and alternative therapies. Next, we will introduce you to official information sources on CAM relating to muscular dystrophy. Finally, at the conclusion of this chapter, we will provide a list of readings on muscular dystrophy from various authors. We will begin, however, with the National Center for Complementary and Alternative Medicine's (NCCAM) overview of complementary and alternative medicine.
What Is CAM?46 Complementary and alternative medicine (CAM) covers a broad range of healing philosophies, approaches, and therapies. Generally, it is defined as those treatments and healthcare practices which are not taught in medical schools, used in hospitals, or reimbursed by medical insurance companies. Many CAM therapies are termed “holistic,” which generally means that the healthcare practitioner considers the whole person, including physical, mental, emotional, and spiritual health. Some of these therapies are also known as “preventive,” which means that the practitioner educates and 46
Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/faq/index.html#what-is.
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treats the person to prevent health problems from arising, rather than treating symptoms after problems have occurred. People use CAM treatments and therapies in a variety of ways. Therapies are used alone (often referred to as alternative), in combination with other alternative therapies, or in addition to conventional treatment (sometimes referred to as complementary). Complementary and alternative medicine, or “integrative medicine,” includes a broad range of healing philosophies, approaches, and therapies. Some approaches are consistent with physiological principles of Western medicine, while others constitute healing systems with non-Western origins. While some therapies are far outside the realm of accepted Western medical theory and practice, others are becoming established in mainstream medicine. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease. Some commonly used methods of complementary or alternative therapy include mind/body control interventions such as visualization and relaxation, manual healing including acupressure and massage, homeopathy, vitamins or herbal products, and acupuncture.
What Are the Domains of Alternative Medicine?47 The list of CAM practices changes continually. The reason being is that these new practices and therapies are often proved to be safe and effective, and therefore become generally accepted as “mainstream” healthcare practices. Today, CAM practices may be grouped within five major domains: (1) alternative medical systems, (2) mind-body interventions, (3) biologicallybased treatments, (4) manipulative and body-based methods, and (5) energy therapies. The individual systems and treatments comprising these categories are too numerous to list in this sourcebook. Thus, only limited examples are provided within each. Alternative Medical Systems Alternative medical systems involve complete systems of theory and practice that have evolved independent of, and often prior to, conventional biomedical approaches. Many are traditional systems of medicine that are
47
Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/classify/index.html.
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practiced by individual cultures throughout the world, including a number of venerable Asian approaches. Traditional oriental medicine emphasizes the balance or disturbances of qi (pronounced chi) or vital energy in health and disease, respectively. Traditional oriental medicine consists of a group of techniques and methods including acupuncture, herbal medicine, oriental massage, and qi gong (a form of energy therapy). Acupuncture involves stimulating specific anatomic points in the body for therapeutic purposes, usually by puncturing the skin with a thin needle. Ayurveda is India's traditional system of medicine. Ayurvedic medicine (meaning “science of life”) is a comprehensive system of medicine that places equal emphasis on body, mind, and spirit. Ayurveda strives to restore the innate harmony of the individual. Some of the primary Ayurvedic treatments include diet, exercise, meditation, herbs, massage, exposure to sunlight, and controlled breathing. Other traditional healing systems have been developed by the world’s indigenous populations. These populations include Native American, Aboriginal, African, Middle Eastern, Tibetan, and Central and South American cultures. Homeopathy and naturopathy are also examples of complete alternative medicine systems. Homeopathic medicine is an unconventional Western system that is based on the principle that “like cures like,” i.e., that the same substance that in large doses produces the symptoms of an illness, in very minute doses cures it. Homeopathic health practitioners believe that the more dilute the remedy, the greater its potency. Therefore, they use small doses of specially prepared plant extracts and minerals to stimulate the body's defense mechanisms and healing processes in order to treat illness. Naturopathic medicine is based on the theory that disease is a manifestation of alterations in the processes by which the body naturally heals itself and emphasizes health restoration rather than disease treatment. Naturopathic physicians employ an array of healing practices, including the following: diet and clinical nutrition, homeopathy, acupuncture, herbal medicine, hydrotherapy (the use of water in a range of temperatures and methods of applications), spinal and soft-tissue manipulation, physical therapies (such as those involving electrical currents, ultrasound, and light), therapeutic counseling, and pharmacology.
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Mind-Body Interventions Mind-body interventions employ a variety of techniques designed to facilitate the mind's capacity to affect bodily function and symptoms. Only a select group of mind-body interventions having well-documented theoretical foundations are considered CAM. For example, patient education and cognitive-behavioral approaches are now considered “mainstream.” On the other hand, complementary and alternative medicine includes meditation, certain uses of hypnosis, dance, music, and art therapy, as well as prayer and mental healing.
Biological-Based Therapies This category of CAM includes natural and biological-based practices, interventions, and products, many of which overlap with conventional medicine's use of dietary supplements. This category includes herbal, special dietary, orthomolecular, and individual biological therapies. Herbal therapy employs an individual herb or a mixture of herbs for healing purposes. An herb is a plant or plant part that produces and contains chemical substances that act upon the body. Special diet therapies, such as those proposed by Drs. Atkins, Ornish, Pritikin, and Weil, are believed to prevent and/or control illness as well as promote health. Orthomolecular therapies aim to treat disease with varying concentrations of chemicals such as magnesium, melatonin, and mega-doses of vitamins. Biological therapies include, for example, the use of laetrile and shark cartilage to treat cancer and the use of bee pollen to treat autoimmune and inflammatory diseases.
Manipulative and Body-Based Methods This category includes methods that are based on manipulation and/or movement of the body. For example, chiropractors focus on the relationship between structure and function, primarily pertaining to the spine, and how that relationship affects the preservation and restoration of health. Chiropractors use manipulative therapy as an integral treatment tool. In contrast, osteopaths place particular emphasis on the musculoskeletal system and practice osteopathic manipulation. Osteopaths believe that all of the body's systems work together and that disturbances in one system may have an impact upon function elsewhere in the body. Massage therapists manipulate the soft tissues of the body to normalize those tissues.
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Energy Therapies Energy therapies focus on energy fields originating within the body (biofields) or those from other sources (electromagnetic fields). Biofield therapies are intended to affect energy fields (the existence of which is not yet experimentally proven) that surround and penetrate the human body. Some forms of energy therapy manipulate biofields by applying pressure and/or manipulating the body by placing the hands in or through these fields. Examples include Qi gong, Reiki and Therapeutic Touch. Qi gong is a component of traditional oriental medicine that combines movement, meditation, and regulation of breathing to enhance the flow of vital energy (qi) in the body, improve blood circulation, and enhance immune function. Reiki, the Japanese word representing Universal Life Energy, is based on the belief that, by channeling spiritual energy through the practitioner, the spirit is healed and, in turn, heals the physical body. Therapeutic Touch is derived from the ancient technique of “laying-on of hands.” It is based on the premises that the therapist’s healing force affects the patient's recovery and that healing is promoted when the body's energies are in balance. By passing their hands over the patient, these healers identify energy imbalances. Bioelectromagnetic-based therapies involve the unconventional use of electromagnetic fields to treat illnesses or manage pain. These therapies are often used to treat asthma, cancer, and migraine headaches. Types of electromagnetic fields which are manipulated in these therapies include pulsed fields, magnetic fields, and alternating current or direct current fields.
Can Alternatives Affect My Treatment? A critical issue in pursuing complementary alternatives mentioned thus far is the risk that these might have undesirable interactions with your medical treatment. It becomes all the more important to speak with your doctor who can offer advice on the use of alternatives. Official sources confirm this view. Though written for women, we find that the National Women’s Health Information Center’s advice on pursuing alternative medicine is appropriate for patients of both genders and all ages.48
48
Adapted from http://www.4woman.gov/faq/alternative.htm.
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Is It Okay to Want Both Traditional and Alternative Medicine? Should you wish to explore non-traditional types of treatment, be sure to discuss all issues concerning treatments and therapies with your healthcare provider, whether a physician or practitioner of complementary and alternative medicine. Competent healthcare management requires knowledge of both conventional and alternative therapies you are taking for the practitioner to have a complete picture of your treatment plan. The decision to use complementary and alternative treatments is an important one. Consider before selecting an alternative therapy, the safety and effectiveness of the therapy or treatment, the expertise and qualifications of the healthcare practitioner, and the quality of delivery. These topics should be considered when selecting any practitioner or therapy.
Finding CAM References on Muscular Dystrophy Having read the previous discussion, you may be wondering which complementary or alternative treatments might be appropriate for muscular dystrophy. For the remainder of this chapter, we will direct you to a number of official sources which can assist you in researching studies and publications. Some of these articles are rather technical, so some patience may be required. National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov) has created a link to the National Library of Medicine's databases to allow patients to search for articles that specifically relate to muscular dystrophy and complementary medicine. To search the database, go to the following Web site: www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “muscular dystrophy” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine (CAM) that are related to muscular dystrophy: ·
A case of ventricular fibrillation in the prone position during back stabilisation surgery in a boy with Duchenne's muscular dystrophy. Author(s): Reid JM, Appleton PJ.
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Source: Anaesthesia. 1999 April; 54(4): 364-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10455837&dopt=Abstract ·
Activity of creatine kinase in sera from healthy women, carriers of Duchenne muscular dystrophy and cord blood, determined by the "European" recommended method with NAC-EDTA activation. Author(s): Moss DW, Whitaker KB, Parmar C, Heckmatt J, Wikowski J, Sewry C, Dubowitz V. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1981 October 26; 116(2): 209-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6794955&dopt=Abstract
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Actomyosin alterations in Duchenne muscular dystrophy. Author(s): Samaha FJ. Source: Archives of Neurology. 1973 June; 28(6): 405-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=4267103&dopt=Abstract
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Breathing exercises for children with pseudohypertrophic muscular dystrophy. Author(s): Houser CR, Johnson DM. Source: Physical Therapy. 1971 July; 51(7): 751-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=4933570&dopt=Abstract
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Ca2+ transport in erythrocytes from patients with Duchenne muscular dystrophy. Author(s): Pijst HL, Scholte HR. Source: Journal of the Neurological Sciences. 1983 August-September; 60(3): 411-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6138395&dopt=Abstract
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Cell transplantation as an experimental treatment for Duchenne muscular dystrophy. Author(s): Law PK, Goodwin TG, Fang Q, Deering MB, Duggirala V, Larkin C, Florendo JA, Kirby DS, Li HJ, Chen M, et al.
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Source: Cell Transplantation. 1993 November-December; 2(6): 485-505. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8167934&dopt=Abstract ·
Corticosteroids in duchenne muscular dystrophy: a reappraisal. Author(s): Wong BL, Christopher C. Source: Journal of Child Neurology. 2002 March; 17(3): 183-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12026233&dopt=Abstract
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Cultural differences in family communication about Duchenne muscular dystrophy. Author(s): Fitzpatrick C, Barry C. Source: Developmental Medicine and Child Neurology. 1990 November; 32(11): 967-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2269406&dopt=Abstract
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Deficiency of a 180-kDa extracellular matrix protein in Fukuyama type congenital muscular dystrophy skeletal muscle. Author(s): Sunada Y, Saito F, Higuchi I, Matsumura K, Shimizu T. Source: Neuromuscular Disorders : Nmd. 2002 February; 12(2): 117-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11738352&dopt=Abstract
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Duchenne muscular dystrophy and concomitant metastatic alveolar rhabdomyosarcoma. Author(s): Rossbach HC, Lacson A, Grana NH, Barbosa JL. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1999 November-December; 21(6): 528-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10598666&dopt=Abstract
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Effects of electrical stimulation on muscles of children with Duchenne and Becker muscular dystrophy. Author(s): Zupan A, Gregoric M, Valencic V, Vandot S. Source: Neuropediatrics. 1993 August; 24(4): 189-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8232775&dopt=Abstract
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Effects of physical therapy program on vital capacity of patients with muscular dystrophy. Author(s): Adams MA, Chandler LS. Source: Physical Therapy. 1974 May; 54(5): 494-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=4607793&dopt=Abstract
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Efficacy of drug regimen exceeds electrostimulation in treatment of avian muscular dystrophy. Author(s): Hudecki MS, Povoski SP, Gregorio CC, Granchelli JA, Pollina CM. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 1995 June; 78(6): 2014-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7665393&dopt=Abstract
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Erythrocyte membrane autophosphorylation in Duchenne muscular dystrophy: effect of two methods of erythrocyte ghost preparation on results. Author(s): Roses AD. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1979 July 2; 95(1): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=509731&dopt=Abstract
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Feasibility, safety, and efficacy of myoblast transfer therapy on Duchenne muscular dystrophy boys. Author(s): Law PK, Goodwin TG, Fang Q, Duggirala V, Larkin C, Florendo JA, Kirby DS, Deering MB, Li HJ, Chen M, et al. Source: Cell Transplantation. 1992; 1(2-3): 235-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1344295&dopt=Abstract
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Hearing acuity in patients with muscular dystrophy. Author(s): Allen NR. Source: Developmental Medicine and Child Neurology. 1973 August; 15(4): 500-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=4732900&dopt=Abstract
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Hyperbaric oxygen therapy for muscular dystrophy. Author(s): Hirotani H, Kuyama T.
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Source: Nippon Geka Hokan. 1974 March; 43(2): 161-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=4473049&dopt=Abstract ·
Inspiratory muscle training in patients with Duchenne muscular dystrophy. Author(s): Wanke T, Toifl K, Merkle M, Formanek D, Lahrmann H, Zwick H. Source: Chest. 1994 February; 105(2): 475-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8306750&dopt=Abstract
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Muscle blood flow in Duchenne type muscular dystrophy, limb-girdle dystrophy, polymyositis, and in normal controls. Author(s): Paulson OB, Engel AG, Gomez MR. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1974 June; 37(6): 685-90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=4210685&dopt=Abstract
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Na+ + K+ ATPase of erythrocyte membranes in Duchenne muscular dystrophy. Author(s): Mawatari S, Igisu H, Kuroiwa Y, Miyoshino S. Source: Neurology. 1981 March; 31(3): 293-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6259557&dopt=Abstract
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Oral creatine supplementation in Duchenne muscular dystrophy: a clinical and 31P magnetic resonance spectroscopy study. Author(s): Felber S, Skladal D, Wyss M, Kremser C, Koller A, Sperl W. Source: Neurological Research. 2000 March; 22(2): 145-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10763500&dopt=Abstract
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Paraffin wax embedded muscle is suitable for the diagnosis of muscular dystrophy. Author(s): Sheriffs IN, Rampling D, Smith VV. Source: Journal of Clinical Pathology. 2001 July; 54(7): 517-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11429422&dopt=Abstract
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Progressive muscular dystrophy--Duchenne type. Controversies of the kinesitherapy treatment. Author(s): de Araujo Leitao AV, Duro LA, de Andrade Penque GM. Source: Rev Paul Med. 1995 September-October; 113(5): 995-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8729744&dopt=Abstract
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Pulmonary problems in Duchenne muscular dystrophy. Diagnosis, prophylaxis, and treatment. Author(s): Siegel IM. Source: Physical Therapy. 1975 February; 55(2): 160-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1096180&dopt=Abstract
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Pursed lips breathing improves ventilation in myotonic muscular dystrophy. Author(s): Ugalde V, Breslin EH, Walsh SA, Bonekat HW, Abresch RT, Carter GT. Source: Archives of Physical Medicine and Rehabilitation. 2000 April; 81(4): 472-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10768538&dopt=Abstract
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Pyruvic and lactic acid metabolism in muscular dystrophy, neuropathies and other neuromuscular disorders. Author(s): Goto I, Peters HA, Reese HH. Source: Am J Med Sci. 1967 April; 253(4): 431-48. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=4290040&dopt=Abstract
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Relating familial stress to the psychosocial adjustment of adolescents with Duchenne muscular dystrophy. Author(s): Reid DT, Renwick RM. Source: International Journal of Rehabilitation Research. Internationale Zeitschrift Fur Rehabilitationsforschung. Revue Internationale De Recherches De Readaptation. 2001 June; 24(2): 83-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11421396&dopt=Abstract
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Respiratory muscle training in Duchenne muscular dystrophy. Author(s): Rodillo E, Noble-Jamieson CM, Aber V, Heckmatt JZ, Muntoni F, Dubowitz V.
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Source: Archives of Disease in Childhood. 1989 May; 64(5): 736-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2658856&dopt=Abstract ·
Respiratory muscle training in Duchenne muscular dystrophy. Author(s): Smith PE, Coakley JH, Edwards RH. Source: Muscle & Nerve. 1988 July; 11(7): 784-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3405245&dopt=Abstract
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Reversal of impaired oxidative phosphorylation and calcium overloading in the in vitro cardiac mitochondria of CHF-146 dystrophic hamsters with hereditary muscular dystrophy. Author(s): Bhattacharya SK, Johnson PL, Thakar JH. Source: Journal of the Neurological Sciences. 1993 December 15; 120(2): 180-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8138808&dopt=Abstract
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Selenium metabolism and supplementation in patients with muscular dystrophy. Author(s): Jackson MJ, Coakley J, Stokes M, Edwards RH, Oster O. Source: Neurology. 1989 May; 39(5): 655-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2540451&dopt=Abstract
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Selenium supplementation in X-linked muscular dystrophy. Effects on erythrocyte and serum selenium and on erythrocyte glutathione peroxidase activity. Author(s): Gebre-Medhin M, Gustavson KH, Gamstorp I, Plantin LO. Source: Acta Paediatr Scand. 1985 November; 74(6): 886-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=4090964&dopt=Abstract
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Spectrin extractability from erythrocytes in Duchenne muscular dystrophy patients and carriers and in other myopathies. Author(s): Gargioni G, Chiaffoni G, Bonadonna G, Corradini P, Lechi C, de Grandis D, Zatti M.
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Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1985 February 15; 145(3): 259-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3987029&dopt=Abstract ·
Therapies in muscular dystrophy: current concepts and future prospects. Author(s): Urtizberea JA. Source: European Neurology. 2000; 43(3): 127-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10765050&dopt=Abstract
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Update on Duchenne muscular dystrophy. Author(s): Siegel IM. Source: Compr Ther. 1989 March; 15(3): 45-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2650976&dopt=Abstract
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Weaning from mechanical ventilation: successful use of modified inspiratory resistive training in muscular dystrophy. Author(s): Aldrich TK, Uhrlass RM. Source: Critical Care Medicine. 1987 March; 15(3): 247-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3816259&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: ·
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.comÒ: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.thedacare.org/healthnotes/
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Open Directory Project: http://dmoz.org/Health/Alternative/
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TPN.com: http://www.tnp.com/
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
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WebMDÒHealth: http://my.webmd.com/drugs_and_herbs
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WellNet: http://www.wellnet.ca/herbsa-c.htm
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html
The following is a specific Web list relating to muscular dystrophy; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: ·
General Overview Muscular dystrophy Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/InteractiveMedicine/ConsLookups/Uses/mu sculardystrophy.html Muscular Dystrophy Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html
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Alternative Therapy Trager approach Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,741, 00.html
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Herbs and Supplements Allopurinol Source: Healthnotes, Inc.; www.healthnotes.com
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Hyperlink: http://www.thedacare.org/healthnotes/Drug/Allopurinol.htm Arnica Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html BCAAs Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000102.html Black Cohosh Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Coenzyme Q10 Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Coenzyme_Q10.htm Coenzyme Q10 Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/Coen zymeQ10cs.html Coenzyme Q10 Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Coenzyme Q10 (CoQ10) Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000135.html CoQ10 Source: Integrative Medicine Communications; www.onemedicine.com
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Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/Coen zymeQ10cs.html Cramp Bark Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Cysteine Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Evening Primrose Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Hawthorn Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Herbal Medicine Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Horsetail Source: Integrative Medicine Communications; www.onemedicine.com
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Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Jamaica Dogwood Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Kelp Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Meadowsweet Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Rosemary Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html ·
Related Conditions Dysphagia Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Dysph agiacc.html Swallowing, Difficulty Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Dysph agiacc.html
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General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at: www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources. The following additional references describe, in broad terms, alternative and complementary medicine (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · Acupunture Treatment for Musculoskeletal Pain : A Textbook for Orthopedics and Anesthesia by Harris Gellman (Editor); Hardcover (May 2001), Harwood Academic Pub; ISBN: 9057025167; http://www.amazon.com/exec/obidos/ASIN/9057025167/icongroupinterna · Homeopathy for Musculoskeletal Healing by Asa Hershoff; Paperback 300 pages (January 1997), North Atlantic Books; ISBN: 1556432372; http://www.amazon.com/exec/obidos/ASIN/1556432372/icongroupinterna · Joint Pains: A Guide to Successful Herbal Remedies by Penelope Ody; Paperback - 172 pages (April 2002), Souvenir Press Ltd; ISBN: 0285636227; http://www.amazon.com/exec/obidos/ASIN/0285636227/icongroupinterna · Kinesiology of the Musculoskeletal System by Neumann, et al; Hardcover - 624 pages, 1st edition (March 22, 2002), Mosby, Inc.; ISBN: 0815163495; http://www.amazon.com/exec/obidos/ASIN/0815163495/icongroupinterna · Applied Kinesiology: A Training Manual and Reference Book of Basic Principles and Practices by Robert Frost, George J. Goodheart; Paperback 300 pages, 1st edition (March 21, 2002), Publishers Group West; ISBN: 1556433743; http://www.amazon.com/exec/obidos/ASIN/1556433743/icongroupinterna · Musculoskeletal Disorders : Healing Methods from Chinese Medicine, Orthopaedic Medicine and Osteopathy by Alon Marcus; Hardcover - 650 pages (January 1999), North Atlantic Books; ISBN: 1556432828; http://www.amazon.com/exec/obidos/ASIN/1556432828/icongroupinterna · The Posture Prescription : A Doctor's Rx for Eliminating Back, Muscle, and Joint Pain, Achieving Optimum Strength and Mobility, Living a Life of Fitne by Arthur White, MD, et al; Paperback - 256 pages, 1st edition (January 8, 2002), Three Rivers Pr; ISBN: 0609806319; http://www.amazon.com/exec/obidos/ASIN/0609806319/icongroupinterna
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For additional information on complementary and alternative medicine, ask your doctor or write to: National Institutes of Health National Center for Complementary and Alternative Medicine Clearinghouse P. O. Box 8218 Silver Spring, MD 20907-8218
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APPENDIX C. RESEARCHING NUTRITION Overview Since the time of Hippocrates, doctors have understood the importance of diet and nutrition to patients’ health and well-being. Since then, they have accumulated an impressive archive of studies and knowledge dedicated to this subject. Based on their experience, doctors and healthcare providers may recommend particular dietary supplements to patients with muscular dystrophy. Any dietary recommendation is based on a patient's age, body mass, gender, lifestyle, eating habits, food preferences, and health condition. It is therefore likely that different patients with muscular dystrophy may be given different recommendations. Some recommendations may be directly related to muscular dystrophy, while others may be more related to the patient's general health. These recommendations, themselves, may differ from what official sources recommend for the average person. In this chapter we will begin by briefly reviewing the essentials of diet and nutrition that will broadly frame more detailed discussions of muscular dystrophy. We will then show you how to find studies dedicated specifically to nutrition and muscular dystrophy.
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Food and Nutrition: General Principles What Are Essential Foods? Food is generally viewed by official sources as consisting of six basic elements: (1) fluids, (2) carbohydrates, (3) protein, (4) fats, (5) vitamins, and (6) minerals. Consuming a combination of these elements is considered to be a healthy diet: ·
Fluids are essential to human life as 80-percent of the body is composed of water. Water is lost via urination, sweating, diarrhea, vomiting, diuretics (drugs that increase urination), caffeine, and physical exertion.
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Carbohydrates are the main source for human energy (thermoregulation) and the bulk of typical diets. They are mostly classified as being either simple or complex. Simple carbohydrates include sugars which are often consumed in the form of cookies, candies, or cakes. Complex carbohydrates consist of starches and dietary fibers. Starches are consumed in the form of pastas, breads, potatoes, rice, and other foods. Soluble fibers can be eaten in the form of certain vegetables, fruits, oats, and legumes. Insoluble fibers include brown rice, whole grains, certain fruits, wheat bran and legumes.
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Proteins are eaten to build and repair human tissues. Some foods that are high in protein are also high in fat and calories. Food sources for protein include nuts, meat, fish, cheese, and other dairy products.
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Fats are consumed for both energy and the absorption of certain vitamins. There are many types of fats, with many general publications recommending the intake of unsaturated fats or those low in cholesterol.
Vitamins and minerals are fundamental to human health, growth, and, in some cases, disease prevention. Most are consumed in your diet (exceptions being vitamins K and D which are produced by intestinal bacteria and sunlight on the skin, respectively). Each vitamin and mineral plays a different role in health. The following outlines essential vitamins: ·
Vitamin A is important to the health of your eyes, hair, bones, and skin; sources of vitamin A include foods such as eggs, carrots, and cantaloupe.
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Vitamin B1, also known as thiamine, is important for your nervous system and energy production; food sources for thiamine include meat, peas, fortified cereals, bread, and whole grains.
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Vitamin B2, also known as riboflavin, is important for your nervous system and muscles, but is also involved in the release of proteins from
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nutrients; food sources for riboflavin include dairy products, leafy vegetables, meat, and eggs. ·
Vitamin B3, also known as niacin, is important for healthy skin and helps the body use energy; food sources for niacin include peas, peanuts, fish, and whole grains
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Vitamin B6, also known as pyridoxine, is important for the regulation of cells in the nervous system and is vital for blood formation; food sources for pyridoxine include bananas, whole grains, meat, and fish.
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Vitamin B12 is vital for a healthy nervous system and for the growth of red blood cells in bone marrow; food sources for vitamin B12 include yeast, milk, fish, eggs, and meat.
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Vitamin C allows the body's immune system to fight various diseases, strengthens body tissue, and improves the body's use of iron; food sources for vitamin C include a wide variety of fruits and vegetables.
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Vitamin D helps the body absorb calcium which strengthens bones and teeth; food sources for vitamin D include oily fish and dairy products.
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Vitamin E can help protect certain organs and tissues from various degenerative diseases; food sources for vitamin E include margarine, vegetables, eggs, and fish.
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Vitamin K is essential for bone formation and blood clotting; common food sources for vitamin K include leafy green vegetables.
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Folic Acid maintains healthy cells and blood and, when taken by a pregnant woman, can prevent her fetus from developing neural tube defects; food sources for folic acid include nuts, fortified breads, leafy green vegetables, and whole grains.
It should be noted that one can overdose on certain vitamins which become toxic if consumed in excess (e.g. vitamin A, D, E and K). Like vitamins, minerals are chemicals that are required by the body to remain in good health. Because the human body does not manufacture these chemicals internally, we obtain them from food and other dietary sources. The more important minerals include: ·
Calcium is needed for healthy bones, teeth, and muscles, but also helps the nervous system function; food sources for calcium include dry beans, peas, eggs, and dairy products.
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Chromium is helpful in regulating sugar levels in blood; food sources for chromium include egg yolks, raw sugar, cheese, nuts, beets, whole grains, and meat.
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Fluoride is used by the body to help prevent tooth decay and to reinforce bone strength; sources of fluoride include drinking water and certain brands of toothpaste.
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Iodine helps regulate the body's use of energy by synthesizing into the hormone thyroxine; food sources include leafy green vegetables, nuts, egg yolks, and red meat.
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Iron helps maintain muscles and the formation of red blood cells and certain proteins; food sources for iron include meat, dairy products, eggs, and leafy green vegetables.
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Magnesium is important for the production of DNA, as well as for healthy teeth, bones, muscles, and nerves; food sources for magnesium include dried fruit, dark green vegetables, nuts, and seafood.
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Phosphorous is used by the body to work with calcium to form bones and teeth; food sources for phosphorous include eggs, meat, cereals, and dairy products.
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Selenium primarily helps maintain normal heart and liver functions; food sources for selenium include wholegrain cereals, fish, meat, and dairy products.
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Zinc helps wounds heal, the formation of sperm, and encourage rapid growth and energy; food sources include dried beans, shellfish, eggs, and nuts.
The United States government periodically publishes recommended diets and consumption levels of the various elements of food. Again, your doctor may encourage deviations from the average official recommendation based on your specific condition. To learn more about basic dietary guidelines, visit the Web site: http://www.health.gov/dietaryguidelines/. Based on these guidelines, many foods are required to list the nutrition levels on the food’s packaging. Labeling Requirements are listed at the following site maintained by the Food and Drug Administration: http://www.cfsan.fda.gov/~dms/labcons.html. When interpreting these requirements, the government recommends that consumers become familiar with the following abbreviations before reading FDA literature:49 ·
DVs (Daily Values): A new dietary reference term that will appear on the food label. It is made up of two sets of references, DRVs and RDIs.
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DRVs (Daily Reference Values): A set of dietary references that applies to fat, saturated fat, cholesterol, carbohydrate, protein, fiber, sodium, and potassium.
49
Adapted from the FDA: http://www.fda.gov/fdac/special/foodlabel/dvs.html.
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·
RDIs (Reference Daily Intakes): A set of dietary references based on the Recommended Dietary Allowances for essential vitamins and minerals and, in selected groups, protein. The name “RDI” replaces the term “U.S. RDA.”
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RDAs (Recommended Dietary Allowances): A set of estimated nutrient allowances established by the National Academy of Sciences. It is updated periodically to reflect current scientific knowledge. What Are Dietary Supplements?50
Dietary supplements are widely available through many commercial sources, including health food stores, grocery stores, pharmacies, and by mail. Dietary supplements are provided in many forms including tablets, capsules, powders, gel-tabs, extracts, and liquids. Historically in the United States, the most prevalent type of dietary supplement was a multivitamin/mineral tablet or capsule that was available in pharmacies, either by prescription or “over the counter.” Supplements containing strictly herbal preparations were less widely available. Currently in the United States, a wide array of supplement products are available, including vitamin, mineral, other nutrients, and botanical supplements as well as ingredients and extracts of animal and plant origin. The Office of Dietary Supplements (ODS) of the National Institutes of Health is the official agency of the United States which has the expressed goal of acquiring “new knowledge to help prevent, detect, diagnose, and treat disease and disability, from the rarest genetic disorder to the common cold.”51 According to the ODS, dietary supplements can have an important impact on the prevention and management of disease and on the maintenance of health.52 The ODS notes that considerable research on the effects of dietary supplements has been conducted in Asia and Europe where This discussion has been adapted from the NIH: http://ods.od.nih.gov/whatare/whatare.html. 51 Contact: The Office of Dietary Supplements, National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: (301) 435-2920, Fax: (301) 480-1845, E-mail:
[email protected]. 52 Adapted from http://ods.od.nih.gov/about/about.html. The Dietary Supplement Health and Education Act defines dietary supplements as “a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, mineral, amino acid, herb or other botanical; or a dietary substance for use to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any ingredient described above; and intended for ingestion in the form of a capsule, powder, softgel, or gelcap, and not represented as a conventional food or as a sole item of a meal or the diet.” 50
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the use of plant products, in particular, has a long tradition. However, the overwhelming majority of supplements have not been studied scientifically. To explore the role of dietary supplements in the improvement of health care, the ODS plans, organizes, and supports conferences, workshops, and symposia on scientific topics related to dietary supplements. The ODS often works in conjunction with other NIH Institutes and Centers, other government agencies, professional organizations, and public advocacy groups. To learn more about official information on dietary supplements, visit the ODS site at http://ods.od.nih.gov/whatare/whatare.html. Or contact: The Office of Dietary Supplements National Institutes of Health Building 31, Room 1B29 31 Center Drive, MSC 2086 Bethesda, Maryland 20892-2086 Tel: (301) 435-2920 Fax: (301) 480-1845 E-mail:
[email protected]
Finding Studies on Muscular Dystrophy The NIH maintains an office dedicated to patient nutrition and diet. The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.53 IBIDS is available to the public free of charge through the ODS Internet page: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. We recommend that you start with the Consumer Database. While you may not find references for the topics that are of most interest to you, check back Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
53
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periodically as this database is frequently updated. More studies can be found by searching the Full IBIDS Database. Healthcare professionals and researchers generally use the third option, which lists peer-reviewed citations. In all cases, we suggest that you take advantage of the “Advanced Search” option that allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “muscular dystrophy” (or synonyms) into the search box. To narrow the search, you can also select the “Title” field. The following information is typical of that found when using the “Full IBIDS Database” when searching using “muscular dystrophy” (or a synonym): ·
A tetrodotoxin- and Mn2(+)-insensitive Na+ current in Duchenne muscular dystrophy. Author(s): Department of Physiology and Biophysics, Faculty of Medicine, University of Sherbrooke, Quebec, Canada. Source: Bkaily, G Jasmin, G Tautu, C Prochek, L Yamamoto, T Sculptoreanu, A Peyrow, M Jacques, D Muscle-Nerve. 1990 October; 13(10): 939-48 0148-639X
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Abnormal calcium homeostasis in Duchenne muscular dystrophy myotubes contracting in vitro. Author(s): Laboratoire de Physiologie Generale, URA CNRS 1869, Universite de Poitiers, France. Source: Imbert, N Cognard, C Duport, G Guillou, C Raymond, G CellCalcium. 1995 September; 18(3): 177-86 0143-4160
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Altered contents of tocopherols in chickens with inherited muscular dystrophy. Author(s): Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas, Austin 78712-1074. Source: Murphy, M E Kehrer, J P Biochem-Med-Metab-Biol. 1989 June; 41(3): 234-45 0885-4505
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Altered secretion of chondroitin sulfate proteoglycan in Duchenne muscular dystrophy cultures. Source: Hutchison, C J Yasin, R J-Neurol-Sci. 1987 June; 79(1-2): 77-81 0022-510X
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Becker and limb-girdle muscular dystrophy associated with pituitary dwarfism. Author(s): Department of Neurology, University of Florence, Italy. Source: Marconi, G Taiuti, R Sbrilli, C Pizzi, A J-Neurol. 1987 August; 234(6): 430-2 0340-5354
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Biochemical changes in progressive muscular dystrophy. XV. Distribution of radioactive glutamate and proximate composition of various components of skeletal muscle and liver in vitamin E-deficient dystrophic rabbits and 129/ReJ (dy/dy) mice. Author(s): Departement de Nutrition, Universite de Montreal, Quebec, Canada. Source: Srivastava, U S Goswami, T Exp-Biol. 1988; 47(3): 185-93 01768638
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Biochemical effect of naturally and experimental induced nutritional muscular dystrophy on copper and iron levels in plasmas of suckling Egyptian buffalo calves. Source: El Neweehy, T.K. Amer, H.A. Abd el Salam, S.A. Arch-ExpVeterinarmed. Leipzig, E. Ger. : S. Hirzel. 1985. volume 39 (6) page 859863. 0003-9055
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Calcium homeostasis and ultrastructural studies in a patient with limb girdle muscular dystrophy type 2C. Author(s): Muscular Dystrophy Research Laboratories, Newcastle General Hospital, Newcastle upon Tyne, UK. Source: Hassoni, A A Cullen, M J Neuropathol-Appl-Neurobiol. 1999 June; 25(3): 244-53 0305-1846
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Carnitine deficiency, mitochondrial dysfunction and the heart. Identical defect of oxidative phosphorylation in muscle mitochondria in cardiomyopathy due to carnitine loss and in Duchenne muscular dystrophy. Author(s): Department of Biochemistry I, Erasmus University Rotterdam, The Netherlands. Source: Scholte, H R Rodrigues Pereira, R Busch, H F Jennekens, F G Luyt Houwen, I E Vaandrager Verduin, M H Wien-Klin-Wochenschr. 1989 January 6; 101(1): 12-7 0043-5325
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Changes in cytosolic resting ionized calcium level and in calcium transients during in vitro development of normal and Duchenne muscular dystrophy cultured skeletal muscle measured by laser cytofluorimetry using indo-1. Author(s): Laboratoire de Physiologie Generale, URA CNRS n 290, Universite de Poitiers, France. Source: Rivet Bastide, M Imbert, N Cognard, C Duport, G Rideau, Y Raymond, G Cell-Calcium. 1993 July; 14(7): 563-71 0143-4160
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Clinical investigation in Duchenne muscular dystrophy: penicillamine and vitamin E. Author(s): Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN 37212.
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Source: Fenichel, G M Brooke, M H Griggs, R C Mendell, J R Miller, J P Moxley, R T 3rd Park, J H Provine, M A Florence, J Kaiser, K K et al. Muscle-Nerve. 1988 November; 11(11): 1164-8 0148-639X ·
Duchenne muscular dystrophy and concomitant metastatic alveolar rhabdomyosarcoma. Author(s): Division of Pediatric Hematology/Oncology, All Children's Hospital, University of South Florida College of Medicine, St. Petersburg, USA. Source: Rossbach, H C Lacson, A Grana, N H Barbosa, J L J-PediatrHematol-Oncol. 1999 Nov-December; 21(6): 528-30 1077-4114
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Duchenne muscular dystrophy: do both parents contribute genetically to the disease? Author(s): Naomi Bramson Medical Research Unit, University of Warwick, Coventry, U.K. Source: Field, E J Joyce, G J-Neurol-Sci. 1987 December; 82(1-3): 245-55 0022-510X
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Effect of intraperitoneal injection of glucose on glucose oxidation and energy expenditure in the mdx mouse model of duchenne muscular dystrophy. Author(s): Lab. de Neurobiologie des Regulations, C.N.R.S. URA 1860 College de France, 11 Pl. M. Berthelot, F-75231 Paris Cedex 05, France. Source: Mokhtarian, A Even, P C Pflugers-Arch. 1996 July; 432(3): 379-85 0031-6768
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Effects of iron deprivation on the pathology and stress protein expression in murine X-linked muscular dystrophy. Author(s): Department of Chemistry and Biochemistry, Rand Afrikaans University, Auckland Park 2006, Johannesburg (South Africa) Source: Bornman, L. Rossouw, H. Gericke, G.S. Polla, B.S. BiochemicalPharmacology (United Kingdom). (1998). volume 56(6) page 751-757. iron muscular dystrophy pathology stress proteins trace elements mice lipid peroxidation blood nutritional status creatine kinase heat shock proteins gene expression necrosis muscles
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Emerin, deficiency of which causes Emery-Dreifuss muscular dystrophy, is localized at the inner nuclear membrane. Author(s): Department of Anatomy II, National Defense Medical College, Saitama, Japan. Source: Yorifuji, H Tadano, Y Tsuchiya, Y Ogawa, M Goto, K Umetani, A Asaka, Y Arahata, K Neurogenetics. 1997 September; 1(2): 135-40 13646745
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·
Feeding problems in merosin deficient congenital muscular dystrophy. Author(s): Neuromuscular Unit, Department of Paediatrics and Neonatal Medicine, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK. Source: Philpot, J Bagnall, A King, C Dubowitz, V Muntoni, F Arch-DisChild. 1999 June; 80(6): 542-7 0003-9888
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Identifying and circumventing the defect in Duchenne muscular dystrophy: clinical and biochemical restoration after practical intervention. Author(s): Knightswood Hospital, Glasgow, U.K. Source: Thomson, W H Med-Hypotheses. 1987 October; 24(2): 187-90 0306-9877
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Immunohistochemical staining of dystrophin on formalin-fixed paraffin-embedded sections in Duchenne/Becker muscular dystrophy and manifesting carriers of Duchenne muscular dystrophy. Author(s): Department of Neurology, Institute of Clinical Medicine, University of Tsukuba, 305-8575, Tsukuba City, Japan. Source: Hoshino, S Ohkoshi, N Watanabe, M Shoji, S NeuromusculDisord. 2000 August; 10(6): 425-9 0960-8966
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Insulin-like growth factor-I and high protein diet decrease calpainmediated proteolysis in murine muscular dystrophy. Author(s): Department of Pediatrics, North Shore University HospitalNew York University School of Medicine, Manhasset 11030, USA. Source: Wingertzahn, M A Zdanowicz, M M Slonim, A E Proc-Soc-ExpBiol-Med. 1998 July; 218(3): 244-50 0037-9727
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: ·
healthfinder®, HHS's gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture's Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration's Web site for federal food safety information: www.foodsafety.gov
Researching Nutrition 201
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: ·
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.thedacare.org/healthnotes/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDÒHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html
The following is a specific Web list relating to muscular dystrophy; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation:
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·
Minerals Biotin Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/Vita minHBiotincs.html Calcium Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Carnitine Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000088.html Creatine Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Creatine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,100 20,00.html Creatine Monohydrate Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Creatine_Monohydrate. htm Creatine Monohydrate Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html
Researching Nutrition 203
Magnesium Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Potassium Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Selenium Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Vitamin H (Biotin) Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/Vita minHBiotincs.html ·
Food and Diet Cod Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Fats Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Fruit Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html
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Grains Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Legumes Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Saturated Fats Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Sea Vegetables Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Seeds Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Vegetables Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html Water Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Muscul arDystrophycc.html
Researching Nutrition 205
Vocabulary Builder The following vocabulary builder defines words used in the references in this chapter that have not been defined in previous chapters: Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, poly- and heterosaccharides. [EU] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [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] 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] 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] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a
206 Muscular Dystrophy
nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]
Lipid: Any of a heterogeneous group of flats and fatlike substances characterized by being water-insoluble and being extractable by nonpolar (or fat) solvents such as alcohol, ether, chloroform, benzene, etc. All contain as a major constituent aliphatic hydrocarbons. The lipids, which are easily stored in the body, serve as a source of fuel, are an important constituent of cell structure, and serve other biological functions. Lipids may be considered to include fatty acids, neutral fats, waxes, and steroids. Compound lipids comprise the glycolipids, lipoproteins, and phospholipids. [EU] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Overdose: 1. to administer an excessive dose. 2. an excessive dose. [EU] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU] Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Secretion: 1. the process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. any substance produced by secretion. [EU] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH]
Finding Medical Libraries 207
APPENDIX D. FINDING MEDICAL LIBRARIES Overview At a medical library you can find medical texts and reference books, consumer health publications, specialty newspapers and magazines, as well as medical journals. In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Before going to the library, highlight the references mentioned in this sourcebook that you find interesting. Focus on those items that are not available via the Internet, and ask the reference librarian for help with your search. He or she may know of additional resources that could be helpful to you. Most importantly, your local public library and medical libraries have Interlibrary Loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. NLM's interlibrary loan services are only available to libraries. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.54
54
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries Open to the Public In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries that are generally open to the public and have reference facilities. The following is the NLM’s list plus hyperlinks to each library Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located):55 ·
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute), http://www.asmi.org/LIBRARY.HTM
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos (Community Health Library of Los Gatos), http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://www-med.stanford.edu/healthlibrary/
55
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 209
·
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: San José PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation), http://go.sutterhealth.org/comm/resc-library/sac-resources.html
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California: University of California, Davis. Health Sciences Libraries
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System), http://www.valleycare.com/library.html
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California: Washington Community Health Resource Library (Washington Community Health Resource Library), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.exempla.org/conslib.htm
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute), http://www.christianacare.org/health_guide/health_guide_pmri_health _info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Northwestern Memorial Hospital, Health Learning Center), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital), http://www.centralbap.com/education/community/library.htm
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Kentucky: University of Kentucky - Health Information Library (University of Kentucky, Chandler Medical Center, Health Information Library), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical Library-Shreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center), http://www.mmc.org/library/
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Maine: Parkview Hospital, http://www.parkviewhospital.org/communit.htm#Library
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital Health Information Library (Western Maine Health), http://www.wmhcc.com/hil_frame.html
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre), http://www.deerlodge.mb.ca/library/libraryservices.shtml
Finding Medical Libraries 211
·
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Md., Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://medlibwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke's Hospital Health Sciences Library (St. Luke's Hospital), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources Consumer Health Information, http://www.sladen.hfhs.org/library/consumer/index.html
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center), http://www.saintpatrick.org/chi/librarydetail.php3?ID=41
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·
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) - provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas Clark County Library District), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: Saint Francis Health System Patient/Family Resource Center (Saint Francis Health System), http://www.sfhtulsa.com/patientfamilycenter/default.asp
Finding Medical Libraries 213
·
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System), http://www.hsls.pitt.edu/chi/hhrcinfo.html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://ww2.mcgill.ca/mghlib/
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South Dakota: Rapid City Regional Hospital - Health Information Center (Rapid City Regional Hospital, Health Information Center), http://www.rcrh.org/education/LibraryResourcesConsumers.htm
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Texas: Matustik Family Resource Center (Cook Children's Health Care System), http://www.cookchildrens.com/Matustik_Library.html
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center), http://www.swmedctr.com/Home/
Your Rights and Insurance 215
APPENDIX E. YOUR RIGHTS AND INSURANCE Overview Any patient with muscular dystrophy faces a series of issues related more to the healthcare industry than to the medical condition itself. This appendix covers two important topics in this regard: your rights and responsibilities as a patient, and how to get the most out of your medical insurance plan.
Your Rights as a Patient The President’s Advisory Commission on Consumer Protection and Quality in the Healthcare Industry has created the following summary of your rights as a patient.56 Information Disclosure Consumers have the right to receive accurate, easily understood information. Some consumers require assistance in making informed decisions about health plans, health professionals, and healthcare facilities. Such information includes: ·
Health plans. Covered benefits, cost-sharing, and procedures for resolving complaints, licensure, certification, and accreditation status, comparable measures of quality and consumer satisfaction, provider network composition, the procedures that govern access to specialists and emergency services, and care management information.
56Adapted
from Consumer Bill of Rights and Responsibilities: http://www.hcqualitycommission.gov/press/cbor.html#head1.
216 Muscular Dystrophy
·
Health professionals. Education, board certification, and recertification, years of practice, experience performing certain procedures, and comparable measures of quality and consumer satisfaction.
·
Healthcare facilities. Experience in performing certain procedures and services, accreditation status, comparable measures of quality, worker, and consumer satisfaction, and procedures for resolving complaints.
·
Consumer assistance programs. Programs must be carefully structured to promote consumer confidence and to work cooperatively with health plans, providers, payers, and regulators. Desirable characteristics of such programs are sponsorship that ensures accountability to the interests of consumers and stable, adequate funding.
Choice of Providers and Plans Consumers have the right to a choice of healthcare providers that is sufficient to ensure access to appropriate high-quality healthcare. To ensure such choice, the Commission recommends the following: ·
Provider network adequacy. All health plan networks should provide access to sufficient numbers and types of providers to assure that all covered services will be accessible without unreasonable delay -including access to emergency services 24 hours a day and 7 days a week. If a health plan has an insufficient number or type of providers to provide a covered benefit with the appropriate degree of specialization, the plan should ensure that the consumer obtains the benefit outside the network at no greater cost than if the benefit were obtained from participating providers.
·
Women's health services. Women should be able to choose a qualified provider offered by a plan -- such as gynecologists, certified nurse midwives, and other qualified healthcare providers -- for the provision of covered care necessary to provide routine and preventative women's healthcare services.
·
Access to specialists. Consumers with complex or serious medical conditions who require frequent specialty care should have direct access to a qualified specialist of their choice within a plan's network of providers. Authorizations, when required, should be for an adequate number of direct access visits under an approved treatment plan.
·
Transitional care. Consumers who are undergoing a course of treatment for a chronic or disabling condition (or who are in the second or third trimester of a pregnancy) at the time they involuntarily change health
Your Rights and Insurance 217
plans or at a time when a provider is terminated by a plan for other than cause should be able to continue seeing their current specialty providers for up to 90 days (or through completion of postpartum care) to allow for transition of care. ·
Choice of health plans. Public and private group purchasers should, wherever feasible, offer consumers a choice of high-quality health insurance plans.
Access to Emergency Services Consumers have the right to access emergency healthcare services when and where the need arises. Health plans should provide payment when a consumer presents to an emergency department with acute symptoms of sufficient severity--including severe pain--such that a “prudent layperson” could reasonably expect the absence of medical attention to result in placing that consumer's health in serious jeopardy, serious impairment to bodily functions, or serious dysfunction of any bodily organ or part.
Participation in Treatment Decisions Consumers have the right and responsibility to fully participate in all decisions related to their healthcare. Consumers who are unable to fully participate in treatment decisions have the right to be represented by parents, guardians, family members, or other conservators. Physicians and other health professionals should: ·
Provide patients with sufficient information and opportunity to decide among treatment options consistent with the informed consent process.
·
Discuss all treatment options with a patient in a culturally competent manner, including the option of no treatment at all.
·
Ensure that persons with disabilities have effective communications with members of the health system in making such decisions.
·
Discuss all current treatments a consumer may be undergoing.
·
Discuss all risks, nontreatment.
·
Give patients the opportunity to refuse treatment and to express preferences about future treatment decisions.
benefits,
and
consequences
to
treatment
or
218 Muscular Dystrophy
·
Discuss the use of advance directives -- both living wills and durable powers of attorney for healthcare -- with patients and their designated family members.
·
Abide by the decisions made by their patients and/or their designated representatives consistent with the informed consent process.
Health plans, health providers, and healthcare facilities should: ·
Disclose to consumers factors -- such as methods of compensation, ownership of or interest in healthcare facilities, or matters of conscience -that could influence advice or treatment decisions.
·
Assure that provider contracts do not contain any so-called “gag clauses” or other contractual mechanisms that restrict healthcare providers' ability to communicate with and advise patients about medically necessary treatment options.
·
Be prohibited from penalizing or seeking retribution against healthcare professionals or other health workers for advocating on behalf of their patients.
Respect and Nondiscrimination Consumers have the right to considerate, respectful care from all members of the healthcare industry at all times and under all circumstances. An environment of mutual respect is essential to maintain a quality healthcare system. To assure that right, the Commission recommends the following: ·
Consumers must not be discriminated against in the delivery of healthcare services consistent with the benefits covered in their policy, or as required by law, based on race, ethnicity, national origin, religion, sex, age, mental or physical disability, sexual orientation, genetic information, or source of payment.
·
Consumers eligible for coverage under the terms and conditions of a health plan or program, or as required by law, must not be discriminated against in marketing and enrollment practices based on race, ethnicity, national origin, religion, sex, age, mental or physical disability, sexual orientation, genetic information, or source of payment. Confidentiality of Health Information
Consumers have the right to communicate with healthcare providers in confidence and to have the confidentiality of their individually identifiable
Your Rights and Insurance 219
healthcare information protected. Consumers also have the right to review and copy their own medical records and request amendments to their records. Complaints and Appeals Consumers have the right to a fair and efficient process for resolving differences with their health plans, healthcare providers, and the institutions that serve them, including a rigorous system of internal review and an independent system of external review. A free copy of the Patient's Bill of Rights is available from the American Hospital Association.57
Patient Responsibilities Treatment is a two-way street between you and your healthcare providers. To underscore the importance of finance in modern healthcare as well as your responsibility for the financial aspects of your care, the President’s Advisory Commission on Consumer Protection and Quality in the Healthcare Industry has proposed that patients understand the following “Consumer Responsibilities.”58 In a healthcare system that protects consumers' rights, it is reasonable to expect and encourage consumers to assume certain responsibilities. Greater individual involvement by the consumer in his or her care increases the likelihood of achieving the best outcome and helps support a quality-oriented, cost-conscious environment. Such responsibilities include: ·
Take responsibility for maximizing healthy habits such as exercising, not smoking, and eating a healthy diet.
·
Work collaboratively with healthcare providers in developing and carrying out agreed-upon treatment plans.
·
Disclose relevant information and clearly communicate wants and needs.
·
Use your health insurance plan's internal complaint and appeal processes to address your concerns.
·
Avoid knowingly spreading disease.
57 To order your free copy of the Patient's Bill of Rights, telephone 312-422-3000 or visit the American Hospital Association’s Web site: http://www.aha.org. Click on “Resource Center,” go to “Search” at bottom of page, and then type in “Patient's Bill of Rights.” The Patient’s Bill of Rights is also available from Fax on Demand, at 312-422-2020, document number 471124. 58 Adapted from http://www.hcqualitycommission.gov/press/cbor.html#head1.
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·
Recognize the reality of risks, the limits of the medical science, and the human fallibility of the healthcare professional.
·
Be aware of a healthcare provider's obligation to be reasonably efficient and equitable in providing care to other patients and the community.
·
Become knowledgeable about your health plan’s coverage and options (when available) including all covered benefits, limitations, and exclusions, rules regarding use of network providers, coverage and referral rules, appropriate processes to secure additional information, and the process to appeal coverage decisions.
·
Show respect for other patients and health workers.
·
Make a good-faith effort to meet financial obligations.
·
Abide by administrative and operational procedures of health plans, healthcare providers, and Government health benefit programs.
Choosing an Insurance Plan There are a number of official government agencies that help consumers understand their healthcare insurance choices.59 The U.S. Department of Labor, in particular, recommends ten ways to make your health benefits choices work best for you.60 1. Your options are important. There are many different types of health benefit plans. Find out which one your employer offers, then check out the plan, or plans, offered. Your employer's human resource office, the health plan administrator, or your union can provide information to help you match your needs and preferences with the available plans. The more information you have, the better your healthcare decisions will be. 2. Reviewing the benefits available. Do the plans offered cover preventive care, well-baby care, vision or dental care? Are there deductibles? Answers to these questions can help determine the out-of-pocket expenses you may face. Matching your needs and those of your family members will result in the best possible benefits. Cheapest may not always be best. Your goal is high quality health benefits.
More information about quality across programs is provided at the following AHRQ Web site: http://www.ahrq.gov/consumer/qntascii/qnthplan.htm. 60 Adapted from the Department of Labor: http://www.dol.gov/dol/pwba/public/pubs/health/top10-text.html. 59
Your Rights and Insurance 221
3. Look for quality. The quality of healthcare services varies, but quality can be measured. You should consider the quality of healthcare in deciding among the healthcare plans or options available to you. Not all health plans, doctors, hospitals and other providers give the highest quality care. Fortunately, there is quality information you can use right now to help you compare your healthcare choices. Find out how you can measure quality. Consult the U.S. Department of Health and Human Services publication “Your Guide to Choosing Quality Health Care” on the Internet at www.ahcpr.gov/consumer. 4. Your plan's summary plan description (SPD) provides a wealth of information. Your health plan administrator can provide you with a copy of your plan’s SPD. It outlines your benefits and your legal rights under the Employee Retirement Income Security Act (ERISA), the federal law that protects your health benefits. It should contain information about the coverage of dependents, what services will require a co-pay, and the circumstances under which your employer can change or terminate a health benefits plan. Save the SPD and all other health plan brochures and documents, along with memos or correspondence from your employer relating to health benefits. 5. Assess your benefit coverage as your family status changes. Marriage, divorce, childbirth or adoption, and the death of a spouse are all life events that may signal a need to change your health benefits. You, your spouse and dependent children may be eligible for a special enrollment period under provisions of the Health Insurance Portability and Accountability Act (HIPAA). Even without life-changing events, the information provided by your employer should tell you how you can change benefits or switch plans, if more than one plan is offered. If your spouse's employer also offers a health benefits package, consider coordinating both plans for maximum coverage. 6. Changing jobs and other life events can affect your health benefits. Under the Consolidated Omnibus Budget Reconciliation Act (COBRA), you, your covered spouse, and your dependent children may be eligible to purchase extended health coverage under your employer's plan if you lose your job, change employers, get divorced, or upon occurrence of certain other events. Coverage can range from 18 to 36 months depending on your situation. COBRA applies to most employers with 20 or more workers and requires your plan to notify you of your rights. Most plans require eligible individuals to make their COBRA election within 60 days of the plan's notice. Be sure to follow up with your plan sponsor if you don't receive notice, and make sure you respond within the allotted time.
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7. HIPAA can also help if you are changing jobs, particularly if you have a medical condition. HIPAA generally limits pre-existing condition exclusions to a maximum of 12 months (18 months for late enrollees). HIPAA also requires this maximum period to be reduced by the length of time you had prior “creditable coverage.” You should receive a certificate documenting your prior creditable coverage from your old plan when coverage ends. 8. Plan for retirement. Before you retire, find out what health benefits, if any, extend to you and your spouse during your retirement years. Consult with your employer's human resources office, your union, the plan administrator, and check your SPD. Make sure there is no conflicting information among these sources about the benefits you will receive or the circumstances under which they can change or be eliminated. With this information in hand, you can make other important choices, like finding out if you are eligible for Medicare and Medigap insurance coverage. 9. Know how to file an appeal if your health benefits claim is denied. Understand how your plan handles grievances and where to make appeals of the plan's decisions. Keep records and copies of correspondence. Check your health benefits package and your SPD to determine who is responsible for handling problems with benefit claims. Contact PWBA for customer service assistance if you are unable to obtain a response to your complaint. 10. You can take steps to improve the quality of the healthcare and the health benefits you receive. Look for and use things like Quality Reports and Accreditation Reports whenever you can. Quality reports may contain consumer ratings -- how satisfied consumers are with the doctors in their plan, for instance-- and clinical performance measures -- how well a healthcare organization prevents and treats illness. Accreditation reports provide information on how accredited organizations meet national standards, and often include clinical performance measures. Look for these quality measures whenever possible. Consult “Your Guide to Choosing Quality Health Care” on the Internet at www.ahcpr.gov/consumer.
Medicare and Medicaid Illness strikes both rich and poor families. For low-income families, Medicaid is available to defer the costs of treatment. The Health Care Financing Administration (HCFA) administers Medicare, the nation's largest health insurance program, which covers 39 million Americans. In the following pages, you will learn the basics about Medicare insurance as well as useful
Your Rights and Insurance 223
contact information on how to find more in-depth information about Medicaid.61
Who is Eligible for Medicare? Generally, you are eligible for Medicare if you or your spouse worked for at least 10 years in Medicare-covered employment and you are 65 years old and a citizen or permanent resident of the United States. You might also qualify for coverage if you are under age 65 but have a disability or EndStage Renal disease (permanent kidney failure requiring dialysis or transplant). Here are some simple guidelines: You can get Part A at age 65 without having to pay premiums if: ·
You are already receiving retirement benefits from Social Security or the Railroad Retirement Board.
·
You are eligible to receive Social Security or Railroad benefits but have not yet filed for them.
·
You or your spouse had Medicare-covered government employment.
If you are under 65, you can get Part A without having to pay premiums if: ·
You have received Social Security or Railroad Retirement Board disability benefit for 24 months.
·
You are a kidney dialysis or kidney transplant patient.
Medicare has two parts: ·
Part A (Hospital Insurance). Most people do not have to pay for Part A.
·
Part B (Medical Insurance). Most people pay monthly for Part B. Part A (Hospital Insurance)
Helps Pay For: Inpatient hospital care, care in critical access hospitals (small facilities that give limited outpatient and inpatient services to people in rural areas) and skilled nursing facilities, hospice care, and some home healthcare.
This section has been adapted from the Official U.S. Site for Medicare Information: http://www.medicare.gov/Basics/Overview.asp.
61
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Cost: Most people get Part A automatically when they turn age 65. You do not have to pay a monthly payment called a premium for Part A because you or a spouse paid Medicare taxes while you were working. If you (or your spouse) did not pay Medicare taxes while you were working and you are age 65 or older, you still may be able to buy Part A. If you are not sure you have Part A, look on your red, white, and blue Medicare card. It will show “Hospital Part A” on the lower left corner of the card. You can also call the Social Security Administration toll free at 1-800-772-1213 or call your local Social Security office for more information about buying Part A. If you get benefits from the Railroad Retirement Board, call your local RRB office or 1-800-808-0772. For more information, call your Fiscal Intermediary about Part A bills and services. The phone number for the Fiscal Intermediary office in your area can be obtained from the following Web site: http://www.medicare.gov/Contacts/home.asp. Part B (Medical Insurance) Helps Pay For: Doctors, services, outpatient hospital care, and some other medical services that Part A does not cover, such as the services of physical and occupational therapists, and some home healthcare. Part B helps pay for covered services and supplies when they are medically necessary. Cost: As of 2001, you pay the Medicare Part B premium of $50.00 per month. In some cases this amount may be higher if you did not choose Part B when you first became eligible at age 65. The cost of Part B may go up 10% for each 12-month period that you were eligible for Part B but declined coverage, except in special cases. You will have to pay the extra 10% cost for the rest of your life. Enrolling in Part B is your choice. You can sign up for Part B anytime during a 7-month period that begins 3 months before you turn 65. Visit your local Social Security office, or call the Social Security Administration at 1-800-7721213 to sign up. If you choose to enroll in Part B, the premium is usually taken out of your monthly Social Security, Railroad Retirement, or Civil Service Retirement payment. If you do not receive any of the above payments, Medicare sends you a bill for your part B premium every 3 months. You should receive your Medicare premium bill in the mail by the 10th of the month. If you do not, call the Social Security Administration at 1800-772-1213, or your local Social Security office. If you get benefits from the Railroad Retirement Board, call your local RRB office or 1-800-808-0772. For more information, call your Medicare carrier about bills and services. The
Your Rights and Insurance 225
phone number for the Medicare carrier in your area can be found at the following Web site: http://www.medicare.gov/Contacts/home.asp. You may have choices in how you get your healthcare including the Original Medicare Plan, Medicare Managed Care Plans (like HMOs), and Medicare Private Fee-for-Service Plans.
Medicaid Medicaid is a joint federal and state program that helps pay medical costs for some people with low incomes and limited resources. Medicaid programs vary from state to state. People on Medicaid may also get coverage for nursing home care and outpatient prescription drugs which are not covered by Medicare. You can find more information about Medicaid on the HCFA.gov Web site at http://www.hcfa.gov/medicaid/medicaid.htm. States also have programs that pay some or all of Medicare's premiums and may also pay Medicare deductibles and coinsurance for certain people who have Medicare and a low income. To qualify, you must have: ·
Part A (Hospital Insurance),
·
Assets, such as bank accounts, stocks, and bonds that are not more than $4,000 for a single person, or $6,000 for a couple, and
·
A monthly income that is below certain limits.
For more information on these programs, look at the Medicare Savings Programs brochure, http://www.medicare.gov/Library/PDFNavigation/PDFInterim.asp?Langua ge=English&Type=Pub&PubID=10126. There are also Prescription Drug Assistance Programs available. Find information on these programs which offer discounts or free medications to individuals in need at http://www.medicare.gov/Prescription/Home.asp.
NORD’s Medication Assistance Programs Finally, the National Organization for Rare Disorders, Inc. (NORD) administers medication programs sponsored by humanitarian-minded pharmaceutical and biotechnology companies to help uninsured or underinsured individuals secure life-saving or life-sustaining drugs.62 NORD Adapted from NORD: http://www.rarediseases.org/cgibin/nord/progserv#patient?id=rPIzL9oD&mv_pc=30.
62
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programs ensure that certain vital drugs are available “to those individuals whose income is too high to qualify for Medicaid but too low to pay for their prescribed medications.” The program has standards for fairness, equity, and unbiased eligibility. It currently covers some 14 programs for nine pharmaceutical companies. NORD also offers early access programs for investigational new drugs (IND) under the approved “Treatment INDs” programs of the Food and Drug Administration (FDA). In these programs, a limited number of individuals can receive investigational drugs that have yet to be approved by the FDA. These programs are generally designed for rare diseases or disorders. For more information, visit www.rarediseases.org.
Additional Resources In addition to the references already listed in this chapter, you may need more information on health insurance, hospitals, or the healthcare system in general. The NIH has set up an excellent guidance Web site that addresses these and other issues. Topics include:63 ·
Health Insurance: http://www.nlm.nih.gov/medlineplus/healthinsurance.html
·
Health Statistics: http://www.nlm.nih.gov/medlineplus/healthstatistics.html
·
HMO and Managed Care: http://www.nlm.nih.gov/medlineplus/managedcare.html
·
Hospice Care: http://www.nlm.nih.gov/medlineplus/hospicecare.html
·
Medicaid: http://www.nlm.nih.gov/medlineplus/medicaid.html
·
Medicare: http://www.nlm.nih.gov/medlineplus/medicare.html
·
Nursing Homes and Long-term Care: http://www.nlm.nih.gov/medlineplus/nursinghomes.html
·
Patient's Rights, Confidentiality, Informed Consent, Ombudsman Programs, Privacy and Patient Issues: http://www.nlm.nih.gov/medlineplus/patientissues.html
You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.
63
Online Glossaries 227
ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries and glossaries. The National Library of Medicine has compiled the following list of online dictionaries: ·
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
·
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
·
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
·
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
·
On-line Medical Dictionary (CancerWEB): http://www.graylab.ac.uk/omd/
·
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
·
Terms and Definitions (Office of Rare Diseases): http://rarediseases.info.nih.gov/ord/glossary_a-e.html
Beyond these, MEDLINEplus contains a very user-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia Web site address is http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a) and drkoop.com (http://www.drkoop.com/). Topics of interest can be researched by using keywords before continuing elsewhere, as these basic definitions and concepts will be useful in more advanced areas of research. You may choose to print various pages specifically relating to muscular dystrophy and keep them on file. The NIH, in particular, suggests that patients with muscular dystrophy visit the following Web sites in the ADAM Medical Encyclopedia:
228 Muscular Dystrophy
·
Basic Guidelines for Muscular Dystrophy Muscular dystrophy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001190.htm Muscular dystrophy - resources Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002154.htm
·
Signs & Symptoms for Muscular Dystrophy Drooling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003048.htm Eyelid drooping Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003035.htm Hearing loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003044.htm Hyperthermia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Hypotonia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003298.htm Lordosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003278.htm Muscle contractures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm
Online Glossaries 229
Muscle weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm Problems walking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003199.htm Wasting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003188.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm ·
Diagnostics and Tests for Muscular Dystrophy Aldolase Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003566.htm ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm ANA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003535.htm AST Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003472.htm Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Chorionic villus sampling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003406.htm
230 Muscular Dystrophy
CPK Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003503.htm CPK isoenzymes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003504.htm Creatine kinase Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003503.htm Creatinine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003475.htm Creatinine - urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003610.htm Differential Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003657.htm ECG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003868.htm Electromyography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003929.htm EMG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003929.htm FSH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003710.htm
Online Glossaries 231
LDH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003471.htm LDH isoenzymes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003499.htm MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm Muscle biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003924.htm Myoglobin - serum Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003663.htm Myoglobin - urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003664.htm Serum CPK Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003503.htm ·
Background Topics for Muscular Dystrophy Gene Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002371.htm Genes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002371.htm Genetic counseling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002053.htm
232 Muscular Dystrophy
Inheritance Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002048.htm Muscular dystrophy - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002154.htm Prenatal diagnosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002053.htm Proximal Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002287.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries and glossaries: ·
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
·
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
·
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
·
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
Glossary 233
MUSCULAR DYSTROPHY GLOSSARY The following is a complete glossary of terms used in this sourcebook. The definitions are derived from official public sources including the National Institutes of Health [NIH] and the European Union [EU]. After this glossary, we list a number of additional hardbound and electronic glossaries and dictionaries that you may wish to consult. Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acuity: Clarity or clearness, especially of the vision. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH]
Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Alopecia: Baldness; absence of the hair from skin areas where it normally is present. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH]
Antibody: An immunoglobulin molecule that has a specific amino acid sequence by virtue of which it interacts only with the antigen that induced its synthesis in cells of the lymphoid series (especially plasma cells), or with antigen closely related to it. Antibodies are classified according to their ode of action as agglutinins, bacteriolysins, haemolysins, opsonins, precipitins, etc. [EU]
234 Muscular Dystrophy
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] Aromatic: Having a spicy odour. [EU] Ataxia: Failure of muscular coordination; irregularity of muscular action. [EU]
Atrophy: A wasting away; a diminution in the size of a cell, tissue, organ, or part. [EU] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Benign: Not malignant; not recurrent; favourable for recovery. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Blindness: The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, poly- and heterosaccharides. [EU]
Glossary 235
Cardiac: Pertaining to the heart. [EU] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiovascular: Pertaining to the heart and blood vessels. [EU] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Chemotherapy: The treatment of disease by means of chemicals that have a specific toxic effect upon the disease - producing microorganisms or that selectively destroy cancerous tissue. [EU] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chronic: Persisting over a long period of time. [EU] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Collagen: The protein substance of the white fibres (collagenous fibres) of skin, tendon, bone, cartilage, and all other connective tissue; composed of molecules of tropocollagen (q.v.), it is converted into gelatin by boiling. collagenous pertaining to collagen; forming or producing collagen. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confusion: Disturbed orientation in regard to time, place, or person, sometimes accompanied by disordered consciousness. [EU] Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibres. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is
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excreted as creatinine in the urine. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Pertaining to or exhibiting cytotoxicity. [EU] Dantrolene: Skeletal muscle relaxant that acts by interfering with excitationcontraction coupling in the muscle fiber. It is used in spasticity and other neuromuscular abnormalities. Although the mechanism of action is probably not central, dantrolene is usually grouped with the central muscle relaxants. [NIH]
Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dysphagia: Difficulty in swallowing. [EU] Dystonia: Disordered tonicity of muscle. [EU] Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-
Glossary 237
actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Electrodiagnosis: Diagnosis of disease states by recording the spontaneous electrical activity of tissues or organs or by the response to stimulation of electrically excitable tissue. [NIH] Electromyography: Recording of the changes in electric potential of muscle by means of surface or needle electrodes. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Enterovirus: A genus of the family picornaviridae whose members preferentially inhabit the intestinal tract of a variety of hosts. The genus contains many species. Newly described members of human enteroviruses are assigned continuous numbers with the species designated "human enterovirus". [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] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Fatal: Causing death, deadly; mortal; lethal. [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]
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Femoral: Pertaining to the femur, or to the thigh. [EU] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrosis: The formation of fibrous tissue; fibroid or fibrous degeneration [EU] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluoroscopy: screen. [NIH]
Production of an image when x-rays strike a fluorescent
Gait: Manner or style of walking. [NIH] Gestures: Movement of a part of the body for the purpose of communication. [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] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hemidesmosomes: An anchoring junction of the cell to a non-cellular substrate, similar in morphology to halves of desmosomes. They are composed of specialized areas of the plasma membrane where intermediate filaments bind on the cytoplasmic face to the transmembrane linkers, integrins, via intracellular attachment proteins, while the extracellular domain of the integrins binds to extracellular matrix proteins. [NIH] Heredity: 1. the genetic transmission of a particular quality or trait from parent to offspring. 2. the genetic constitution of an individual. [EU] 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]
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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] Hyperphagia: Ingestion of a greater than optimal quantity of food. [NIH] Hyperthermia: Abnormally high body temperature, especially that induced for therapeutic purposes. [EU] Hypertrophy: Nutrition) the enlargement or overgrowth of an organ or part due to an increase in size of its constituent cells. [EU] Hypogonadism: A condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [EU] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypotonia: A condition of diminished tone of the skeletal muscles; diminished resistance of muscles to passive stretching. [EU] Immunization: The induction of immunity. [EU] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulindependent diabetes mellitus. [NIH] Intercostal: Situated between the ribs. [EU] Intravascular: Within a vessel or vessels. [EU] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone
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synthesis. In solution, it has anti-infective properties and is used topically. [NIH]
Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU] Lipid: Any of a heterogeneous group of flats and fatlike substances characterized by being water-insoluble and being extractable by nonpolar (or fat) solvents such as alcohol, ether, chloroform, benzene, etc. All contain as a major constituent aliphatic hydrocarbons. The lipids, which are easily stored in the body, serve as a source of fuel, are an important constituent of cell structure, and serve other biological functions. Lipids may be considered to include fatty acids, neutral fats, waxes, and steroids. Compound lipids comprise the glycolipids, lipoproteins, and phospholipids. [EU] Lithium: Lithium. An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH] Localization: 1. the determination of the site or place of any process or lesion. 2. restriction to a circumscribed or limited area. 3. prelocalization. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]
Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Masticatory:
1. subserving or pertaining to mastication; affecting the
Glossary 241
muscles of mastication. 2. a remedy to be chewed but not swallowed. [EU] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Membrane: A thin layer of tissue which covers a surface, lines a cavity or divides a space or organ. [EU] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Metabolite: process. [EU]
Any substance produced by metabolism or by a metabolic
Midwifery: The practice of assisting women in childbirth. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Motility: The ability to move spontaneously. [EU] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Myopathy: Any disease of a muscle. [EU] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [NIH] Necrosis: The sum of the morphological changes indicative of cell death and caused by the progressive degradative action of enzymes; it may affect groups of cells or part of a structure or an organ. [EU] Neonatal: Pertaining to the first four weeks after birth. [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Neuralgia: Paroxysmal pain which extends along the course of one or more nerves. Many varieties of neuralgia are distinguished according to the part affected or to the cause, as brachial, facial, occipital, supraorbital, etc., or anaemic, diabetic, gouty, malarial, syphilitic, etc. [EU] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and
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transmit impulses in the nervous system. [NIH] Neuropathy: A general term denoting functional disturbances and/or pathological changes in the peripheral nervous system. The etiology may be known e.g. arsenical n., diabetic n., ischemic n., traumatic n.) or unknown. Encephalopathy and myelopathy are corresponding terms relating to involvement of the brain and spinal cord, respectively. The term is also used to designate noninflammatory lesions in the peripheral nervous system, in contrast to inflammatory lesions (neuritis). [EU] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Oral: Pertaining to the mouth, taken through or applied in the mouth, as an oral medication or an oral thermometer. [EU] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteoporosis: Reduction in the amount of bone mass, leading to fractures after minimal trauma. [EU] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH] Overdose: 1. to administer an excessive dose. 2. an excessive dose. [EU] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations
Glossary 243
must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Paralysis: Loss or impairment of motor function in a part due to lesion of the neural or muscular mechanism; also by analogy, impairment of sensory function (sensory paralysis). In addition to the types named below, paralysis is further distinguished as traumatic, syphilitic, toxic, etc., according to its cause; or as obturator, ulnar, etc., according to the nerve part, or muscle specially affected. [EU] Paraplegia: Paralysis of the legs and lower part of the body. [EU] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [NIH] Perivascular: Situated around a vessel. [EU] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Pharmacokinetics: The action of drugs in the body over a period of time, including the processes of absorption, distribution, localization in tissues, biotransformation, and excretion. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Physostigmine: A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross
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the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Podiatry: A specialty concerned with the diagnosis and treatment of foot disorders and injuries and anatomic defects of the foot. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH]
Prenatal: Existing or occurring before birth, with reference to the fetus. [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] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Prophylaxis: The prevention of disease; preventive treatment. [EU] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]
Proximal: Nearest; closer to any point of reference; opposed to distal. [EU]
Glossary 245
Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Pulmonary: Pertaining to the lungs. [EU] Quadriplegia: Severe or complete loss of motor function in all four limbs which may result from brain diseases; spinal cord diseases; peripheral nervous system diseases; neuromuscular diseases; or rarely muscular diseases. The locked-in syndrome is characterized by quadriplegia in combination with cranial muscle paralysis. Consciousness is spared and the only retained voluntary motor activity may be limited eye movements. This condition is usually caused by a lesion in the upper brain stem which injures the descending cortico-spinal and cortico-bulbar tracts. [NIH] Radiotherapy: The treatment of disease by ionizing radiation. [EU] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Recombinant: 1. a cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU]
Respiratory: Pertaining to respiration. [EU] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Riluzole: A glutamate antagonist that has reported anticonvulsant activity. It has been shown to prolong the survival of patients with amyotrophic lateral sclerosis and has been approved in the United States to treat patients with ALS. [NIH] Saline: Salty; of the nature of a salt; containing a salt or salts. [EU] Sclerosis: A induration, or hardening; especially hardening of a part from inflammation and in diseases of the interstitial substance. The term is used chiefly for such a hardening of the nervous system due to hyperplasia of the connective tissue or to designate hardening of the blood vessels. [EU] Secretion: 1. the process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. any substance produced by secretion. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU]
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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] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU]
Systemic: Pertaining to or affecting the body as a whole. [EU] Testicular: Pertaining to a testis. [EU] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thanatology: The study of the theory, philosophy, and doctrine of death. [NIH]
Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Transgenes: Genes that are introduced into an organism using gene transfer
Glossary 247
techniques. [NIH] Transplantation: The grafting of tissues taken from the patient's own body or from another. [EU] Ubiquinone: A lipid-soluble benzoquinone which is involved in electron transport in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and 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] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Ventilation: 1. in respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. in psychiatry, verbalization of one's emotional problems. [EU] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viruses: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. [NIH] 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]
General Dictionaries and Glossaries While the above glossary is essentially complete, the dictionaries listed here cover virtually all aspects of medicine, from basic words and phrases to more advanced terms (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·
Dictionary of Medical Acronymns & Abbreviations by Stanley Jablonski (Editor), Paperback, 4th edition (2001), Lippincott Williams & Wilkins Publishers, ISBN: 1560534605, http://www.amazon.com/exec/obidos/ASIN/1560534605/icongroupinterna
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·
Dictionary of Medical Terms : For the Nonmedical Person (Dictionary of Medical Terms for the Nonmedical Person, Ed 4) by Mikel A. Rothenberg, M.D, et al, Paperback - 544 pages, 4th edition (2000), Barrons Educational Series, ISBN: 0764112015, http://www.amazon.com/exec/obidos/ASIN/0764112015/icongroupinterna
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A Dictionary of the History of Medicine by A. Sebastian, CD-Rom edition (2001), CRC Press-Parthenon Publishers, ISBN: 185070368X, http://www.amazon.com/exec/obidos/ASIN/185070368X/icongroupinterna
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Dorland's Illustrated Medical Dictionary (Standard Version) by Dorland, et al, Hardcover - 2088 pages, 29th edition (2000), W B Saunders Co, ISBN: 0721662544, http://www.amazon.com/exec/obidos/ASIN/0721662544/icongroupinterna
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Dorland's Electronic Medical Dictionary by Dorland, et al, Software, 29th Book & CD-Rom edition (2000), Harcourt Health Sciences, ISBN: 0721694934, http://www.amazon.com/exec/obidos/ASIN/0721694934/icongroupinterna
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Dorland's Pocket Medical Dictionary (Dorland's Pocket Medical Dictionary, 26th Ed) Hardcover - 912 pages, 26th edition (2001), W B Saunders Co, ISBN: 0721682812, http://www.amazon.com/exec/obidos/ASIN/0721682812/icongroupinterna /103-4193558-7304618
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Melloni's Illustrated Medical Dictionary (Melloni's Illustrated Medical Dictionary, 4th Ed) by Melloni, Hardcover, 4th edition (2001), CRC PressParthenon Publishers, ISBN: 85070094X, http://www.amazon.com/exec/obidos/ASIN/85070094X/icongroupinterna
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Stedman's Electronic Medical Dictionary Version 5.0 (CD-ROM for Windows and Macintosh, Individual) by Stedmans, CD-ROM edition (2000), Lippincott Williams & Wilkins Publishers, ISBN: 0781726328, http://www.amazon.com/exec/obidos/ASIN/0781726328/icongroupinterna
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Stedman's Medical Dictionary by Thomas Lathrop Stedman, Hardcover 2098 pages, 27th edition (2000), Lippincott, Williams & Wilkins, ISBN: 068340007X, http://www.amazon.com/exec/obidos/ASIN/068340007X/icongroupinterna
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Tabers Cyclopedic Medical Dictionary (Thumb Index) by Donald Venes (Editor), et al, Hardcover - 2439 pages, 19th edition (2001), F A Davis Co, ISBN: 0803606540, http://www.amazon.com/exec/obidos/ASIN/0803606540/icongroupinterna
Index 249
INDEX A Acuity...................................................179 Adolescence ..............14, 18, 20, 233, 243 Adverse .........................................20, 243 Alleles ....................................95, 105, 239 Alopecia...............................................118 Analogous..............................................67 Anemia ........................................118, 149 Anesthesia.............................................16 Antibody ......88, 89, 95, 98, 99, 100, 105, 234 Antigen ..................................98, 105, 233 Ataxia.......................................14, 28, 148 Atrophy ......................30, 60, 96, 103, 148 B Bacteria .84, 105, 106, 192, 234, 246, 247 Benign ...........................................97, 101 Biochemical .........................104, 200, 233 Biopsy..................60, 71, 90, 92, 125, 231 Blindness .....................................105, 235 C Calpain ....................................69, 71, 200 Capsules..............................................195 Carbohydrate...............105, 194, 205, 238 Cardiac ..... 11, 15, 20, 64, 76, 80, 84, 87, 95, 182, 234, 243, 246 Cardiomyopathy ....................75, 132, 198 Cardiovascular.........................61, 75, 118 Carnitine ........................................60, 198 Cataract .......................................105, 235 Cerebral.......................15, 17, 23, 61, 118 Chemotherapy .......................16, 101, 102 Cholesterol ....................84, 192, 194, 246 Chronic ....................................30, 60, 216 Collagen ............................79, 80, 90, 235 Conduction ............................................60 Confusion ......................................38, 236 Cranial .....................................39, 61, 245 Creatine ....60, 81, 90, 100, 101, 177, 180, 199, 235 Curative .................................65, 206, 242 Cysteine.................................................87 Cytoskeleton................66, 76, 87, 93, 100 Cytotoxic ................................................68 D Dantrolene ...................................169, 236 Degenerative .................................72, 193 Deprivation ....................................78, 199 Dermatology ........................................118 Diarrhea...............................................192 Distal........................................10, 83, 244
Dysphagia ............................................. 61 Dystonia ................................................ 15 E Electromyography................................. 60 Electrophoresis ............................... 95, 98 Endemic ................................................ 94 Enterovirus.............................. 75, 81, 237 Enzyme .... 80, 81, 83, 130, 235, 237, 243, 244 Eosinophils............................................ 68 Erythrocytes ... 80, 81, 120, 177, 182, 233, 234, 237 Extracellular . 66, 74, 76, 87, 89, 100, 120, 178, 205, 238 F Fatigue .................................................. 60 Femoral................................................. 65 Fibrillation............................................ 176 Fluorescence ........................ 95, 105, 238 Fluoroscopy .......................................... 61 G Gait ..................................................... 125 Gestures ............................................... 15 Glucose....................... 199, 205, 238, 239 Glycoproteins .......... 87, 89, 100, 105, 238 H Heredity................................................. 14 Holidays ................................................ 29 Homeostasis ............................... 197, 198 Homozygote........................................ 102 Hybridization ......................................... 95 Hypertrophy ........................................ 100 Hypogonadism ...................................... 95 Hypothyroidism ....................... 60, 82, 239 Hypotonia.............................................. 90 I Immunization ................................ 84, 246 Implantation .......................................... 15 Indicative........................... 82, 92, 96, 241 Infantile ........................................... 14, 95 Insulin.................................. 205, 238, 239 Intercostal ........................................... 125 Interstitial................................. 20, 60, 245 Intestinal........................ 81, 118, 192, 237 Intravascular ......................................... 65 Ischemia................................................ 78 K Keratin......................................... 120, 240 L Laminin ................... 72, 74, 87, 88, 89, 93 Larynx ................................................. 124
250 Muscular Dystrophy
Lesion ..............39, 91, 106, 240, 243, 245 Lethal .......................................68, 70, 237 Lipid .......................84, 199, 205, 239, 247 Lithium .........................................169, 240 Localization..............................83, 93, 243 Lupus ...................................................118 M Mandible ................................................62 Manifest ...........................................62, 95 Masticatory ............................................62 Maxillary ................................................62 Membrane ..20, 64, 66, 67, 76, 81, 82, 87, 92, 93, 97, 120, 127, 179, 199, 237, 238, 240, 243 Mental ...15, 22, 28, 38, 81, 82, 91, 94, 95, 118, 171, 174, 218, 236, 237, 239, 245 Metabolite ............................................195 Midwifery .............................................108 Mobility ............................................23, 28 Molecular ....71, 72, 73, 87, 88, 90, 94, 95, 97, 98, 106, 112, 114, 142, 145, 147, 246 Motility .................................................124 Musculature ...........................................62 Myasthenia ..............................16, 60, 117 Myopathy .........................75, 91, 101, 102 Myotonia ..................................11, 95, 101 N Nasal ...........................................120, 240 Necrosis.......................60, 67, 69, 97, 199 Neonatal ....................................61, 70, 90 Neuralgia .................................62, 83, 241 Neuromuscular ..... 15, 23, 24, 25, 26, 27, 29, 32, 66, 89, 114, 117, 126, 127, 169, 181, 236 Neuronal ..........................................78, 94 Neurons .........................................32, 241 Neuropathy ......................................60, 72 Neurophysiology....................................61 Neurotransmitter..........................139, 242 Niacin...................................................193 O Ocular ....................................................24 Oral ..........................39, 62, 205, 234, 242 Osteogenesis.........................32, 108, 118 Overdose .............................................193 Oxidation .............................................199 P Pacemaker ..............................11, 20, 243 Paralysis ..........................23, 39, 243, 245 Paraplegia .............................................23 Pelvic ...............................87, 97, 120, 244 Penicillamine .......................................198 Perivascular...........................................60 Peroxidase...........................................182 Pharmacokinetics ..................................61
Phenotype...... 64, 66, 70, 78, 83, 94, 101, 243 Phenytoin .............................................. 11 Placenta ................................................ 93 Podiatry............................................... 118 Polypeptide ............. 88, 89, 101, 105, 239 Posterior................................................ 62 Potassium ........................................... 194 Prenatal......................................... 93, 127 Prevalence ................................ 61, 62, 95 Progressive .. 4, 10, 11, 14, 17, 24, 27, 28, 29, 30, 31, 32, 38, 60, 82, 87, 92, 94, 96, 99, 116, 198, 236, 241 Prophylaxis ......................................... 181 Prostate............................................... 118 Proteins ..... 64, 66, 70, 80, 81, 87, 90, 91, 96, 97, 98, 100, 105, 120, 192, 194, 199, 234, 236, 238, 239, 240 Proximal ............................ 19, 60, 96, 236 Psychiatry ..................................... 39, 247 Q Quadriplegia ........................... 23, 39, 245 R Radiotherapy ........................................ 16 Reagent .......................................... 88, 90 Recombinant............................. 64, 66, 74 Regeneration ................ 60, 69, 70, 72, 92 Respiratory...................... 11, 39, 118, 247 Riboflavin ............................................ 192 Riluzole ................................................. 16 S Saline .................................................... 74 Sclerosis .... 15, 16, 20, 23, 111, 113, 118, 148, 245 Secretion ...... 82, 84, 197, 206, 239, 245, 247 Sedimentation ....................................... 60 Serum ..... 60, 84, 100, 101, 182, 231, 246 Spasticity..................................... 169, 236 Species ................... 81, 86, 106, 237, 246 Suicide ................................................ 118 T Testicular ............................................ 118 Tetracycline........................................... 70 Thermoregulation................................ 192 Thyroxine ............................................ 194 Toxicity.................................. 61, 157, 244 Toxin ............................................... 91, 92 Transgenes ........................................... 65 Transplantation ......... 79, 91, 92, 133, 177 Tremor ................................................ 148 U Ubiquinone............................................ 61 V Vacuoles ............................................... 60
Index 251
Ventilation...... 23, 39, 181, 183, 205, 238, 247 Viral .....................................60, 66, 70, 74
Viruses .................................................. 70 W Withdrawal .......................................... 118
252 Muscular Dystrophy
Index 253
254 Muscular Dystrophy
