Duchenne Muscular Dystrophy - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

DUCHENNE MUSCULAR DYSTROPHY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FE...

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DUCHENNE MUSCULAR DYSTROPHY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1 Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Duchenne Muscular Dystrophy: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84397-X 1. Duchenne 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. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on Duchenne muscular dystrophy. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON DUCHENNE MUSCULAR DYSTROPHY ...................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Duchenne Muscular Dystrophy ................................................... 4 E-Journals: PubMed Central ....................................................................................................... 26 The National Library of Medicine: PubMed ................................................................................ 29 CHAPTER 2. NUTRITION AND DUCHENNE MUSCULAR DYSTROPHY ............................................ 75 Overview...................................................................................................................................... 75 Finding Nutrition Studies on Duchenne Muscular Dystrophy.................................................. 75 Federal Resources on Nutrition ................................................................................................... 79 Additional Web Resources ........................................................................................................... 80 CHAPTER 3. ALTERNATIVE MEDICINE AND DUCHENNE MUSCULAR DYSTROPHY ...................... 81 Overview...................................................................................................................................... 81 National Center for Complementary and Alternative Medicine.................................................. 81 Additional Web Resources ........................................................................................................... 88 General References ....................................................................................................................... 89 CHAPTER 4. DISSERTATIONS ON DUCHENNE MUSCULAR DYSTROPHY ........................................ 91 Overview...................................................................................................................................... 91 Dissertations on Duchenne Muscular Dystrophy....................................................................... 91 Keeping Current .......................................................................................................................... 92 CHAPTER 5. CLINICAL TRIALS AND DUCHENNE MUSCULAR DYSTROPHY ................................... 93 Overview...................................................................................................................................... 93 Recent Trials on Duchenne Muscular Dystrophy....................................................................... 93 Keeping Current on Clinical Trials ............................................................................................. 96 CHAPTER 6. PATENTS ON DUCHENNE MUSCULAR DYSTROPHY ................................................... 99 Overview...................................................................................................................................... 99 Patents on Duchenne Muscular Dystrophy ................................................................................ 99 Patent Applications on Duchenne Muscular Dystrophy .......................................................... 102 Keeping Current ........................................................................................................................ 108 CHAPTER 7. BOOKS ON DUCHENNE MUSCULAR DYSTROPHY .................................................... 109 Overview.................................................................................................................................... 109 Book Summaries: Federal Agencies............................................................................................ 109 Book Summaries: Online Booksellers......................................................................................... 110 Chapters on Duchenne Muscular Dystrophy ............................................................................ 111 CHAPTER 8. PERIODICALS AND NEWS ON DUCHENNE MUSCULAR DYSTROPHY ....................... 113 Overview.................................................................................................................................... 113 News Services and Press Releases.............................................................................................. 113 Academic Periodicals covering Duchenne Muscular Dystrophy .............................................. 115 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 119 Overview.................................................................................................................................... 119 NIH Guidelines.......................................................................................................................... 119 NIH Databases........................................................................................................................... 121 Other Commercial Databases..................................................................................................... 123 APPENDIX B. PATIENT RESOURCES ............................................................................................... 125 Overview.................................................................................................................................... 125 Patient Guideline Sources.......................................................................................................... 125 Finding Associations.................................................................................................................. 130 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 133 Overview.................................................................................................................................... 133 Preparation................................................................................................................................. 133

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Finding a Local Medical Library................................................................................................ 133 Medical Libraries in the U.S. and Canada ................................................................................. 133 ONLINE GLOSSARIES................................................................................................................ 139 Online Dictionary Directories ................................................................................................... 141 DUCHENNE MUSCULAR DYSTROPHY DICTIONARY .................................................... 143 INDEX .............................................................................................................................................. 193

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with Duchenne muscular dystrophy is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about Duchenne muscular dystrophy, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to Duchenne muscular dystrophy, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on Duchenne muscular dystrophy. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to Duchenne muscular dystrophy, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on Duchenne muscular dystrophy. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. DYSTROPHY

STUDIES

ON

DUCHENNE

MUSCULAR

Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Duchenne muscular dystrophy.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and Duchenne 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 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 “Duchenne 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 what you can expect from this type of search: •

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 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

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Duchenne Muscular Dystrophy

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.

Federally Funded Research on Duchenne Muscular Dystrophy The U.S. Government supports a variety of research studies relating to Duchenne muscular dystrophy. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to Duchenne muscular dystrophy. 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 Duchenne muscular dystrophy. The following is typical of the type of information found when searching the CRISP database for Duchenne muscular dystrophy: •

Project Title: ADENO-ASSOCIATED VIRUS (AAV) VECTORS TO IMPROVE MATURE MUSCLE FUNCTION Principal Investigator & Institution: Xiao, Xiao; Associate Professor; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: Muscular dystrophies are a relatively common group of inherited degenerative muscle disease. Most types are caused by mutations in genes coding for membrance associated proteins in muscle. Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophy (LGMD) often manifest themselves in young ages and lead to early morbidity with no currently available effective treatment. These diseases are recessive, loss-of- function of the corresponding gene product, which makes them

2 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).

Studies

5

suitable for gene replacement therapy. Recombinant adeno-associate virus (rAAV) is one promising gene replacement vector based on defective human parvoviruses. The rAAV system has attracted attention due to its non- pathogenicity, genomic integration, transduction of quiescent cells, and apparent lack of cellular immune reactions. In contrast to other viral vectors, rAAV is capable of efficiently bypassing the myofiber basal lamina and transducing mature muscle cells. We have demonstrated that rAAV vectors harboring a foreign gene can achieve highly efficient and sustained gene expression in mature muscle of immunocompetent animals for more than 1.5 years without detectable toxicity. Recently, significant improvement in vector production methodology has made it possible to generate high titer and high quality rAAV vectors completely free of helper adenovirus contamination. However, no experiments using rAAV vectors to restore the functional deficits in muscle tissue itself have been reported to date. Here, we propose to take advantage of rAAV vector system, to test two therapeutic genes (delta-sarcoglycan and a highly truncated dystrophin), under the control of two different promoter systems (viral/CMV or muscle- specific/MCK), in two relevant animal models of muscular dystrophies (Bio14.6 hamster for LGMD and mdx mouse for DMD). Two distinct vector delivery methods, local intramuscular infection versus systemic delivery will be utilized. We have the following three hypotheses to be tested. 1): muscle deficient in delta-sarcoglycan can be functionally rescued by genetic complementation using intramuscular AAV vector injection in the LGMD hamster model. 2) systemic delivery of the delta-sarcoglycan gene can be mediated by rAAV vectors through intra-artery or intra-ventricle injection. 3) a dystrophin mini-gene lacking the central rod domain will improve the function of dystrophin-deficient muscle when delivered into dystrophic mdx mice by AAV vectors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTISENSE OLIGONUCLEOTIDE SUPPRESSION OF DMD Principal Investigator & Institution: Wilton, Stephen D.; University of Western Australia Crawley, Wa, 6009 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): The ultimate goal of this project is to develop an antisense oligonucleotide (AO) therapy for Duchenne muscular dystrophy (DMD). Antisense oligonucleotides (AOs) can be used to reduce the severity of DMD by removing specific exons during pre-mRNA splicing, to either by-pass nonsense mutations or restore the reading frame around dystrophin genomic deletions. As a result of the treatment, dystrophin expression would be restored in dystrophic tissue and DMD patients would theoretically manifest only the milder phenotype of Becker Muscular Dystrophy (BMD). This project will explore the design and delivery of AOs to minimize the consequences of disease-causing dystrophin gene mutations. (1) Animal models of muscular dystrophy will be used to develop treatment regimens and assess therapeutic benefits in vivo. (2) AOs will be designed to target the most amenable splicing motifs at relevant exons in the human dystrophin gene transcript and will be evaluated in cultured human muscle cells. Although this approach cannot permanently correct the primary genetic lesion, we propose that repeated administration, preferably through systemic delivery, should be feasible. AO chemistries or modifications to increase stability and/or uptake, optimized for in vivo induction of exon skipping, will be developed and evaluated. Only periodic administration of AOs should be required to maintain therapeutic levels of induced dystrophin in dystrophic muscle. DMD is a serious disorder for which there is no effective treatment. AOs will not cure this devastating condition, however, AO-based splicing intervention has the potential to

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reduce the severity of DMD so that treated boys should be able to produce some functional dystrophin. This would be expected to moderate the severity of DMD and improve the quality of life for patients and their families. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DYSTROPHY

BIOENGINEERING

RESEARCH

PARTNERSHIP--MUSCULAR

Principal Investigator & Institution: Sweeney, Hugh Lee.; Professor and Chairman; Physiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 20-SEP-2000; Project End 31-AUG-2005 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 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://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL AND MOLECULAR ANALYSIS OF OREGON EYE DISEASE Principal Investigator & Institution: Pillers, De-Ann M.; Associate Professor; Pediatrics; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 30-SEP-1994; Project End 31-MAY-2004 Summary: (Verbatim from applicant's abstract): The title of the application is "Clinical and molecular analysis of Oregon Eye Disease." A more current title would be "Dystrophin and the retina." During the initial application period, it was shown that dystrophin, the product of the Duchenne muscular dystrophy (DMD) gene, is involved in retinal electrophysiology. Three lines of evidence support this. The position of a mutation in the DMD gene predicts the ERG phenotype, and abnormal ERGs were correlated in large part with mutations of a specific isoform of dystrophin, Dp260, which was identified and cloned from retina. New data suggests that other muscular dystrophies are associated with defects in retinal electrophysiology. Specifically, mouse models with defects in laminin-2 have abnormal ERGs. Dystrophin is part of a cellular continuum from the actin cytoskeleton to laminin and the extracellular matrix via a transmembrane group of proteins known as dystrophin-associated glycoproteins (DGC). It is hypothesized that defects in the interaction between retina-specific isoforms of dystrophin and the DGC result in altered retinal electrophysiology and an abnormal

Studies

7

ERG. It is proposed that the retinal isoform Dp260 plays an important role in retinal electrophysiology by interfacing with the DGC at the photoreceptor to bipolar synapse. It is further proposed that dystrophin isoforms with non-overlapping cellular distributions have distinct roles in retinal function. Three specific aims will be performed to test these hypotheses, involving: (1) defining genotype-phenotype correlations for the DGC performing ERGs on both mutant mice and patients with defects in these proteins; (2) defining the specific cell synapse responsible for the ERG abnormalities demonstrated in the mdxCV3 mouse by in vitro cell-specific electrophysiology; and (3) delineating the diversity of dystrophin isoform expression in retina and to determining unique aspects of isoform structure and expression that may contribute to retinal electrophysiology. The long-term goals are to delineate the pathway by which dystrophin contributes to the normal ERG. By so doing, proteins will be identified, which when mutated, will be candidate genes for inherited retinal disorders associated with abnormal electrophysiology. Dystrophin and other proteins including members of the DGC will be targets for future gene therapy approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COGNITIVE GENETIC ASPECTS OF DUCHENNE MUSCULAR DYSTROPHY Principal Investigator & Institution: Hinton, Veronica J.; Gertrude H Sergievsky Center; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-MAY-1996; Project End 30-JUN-2007 Summary: (provided by investigator): The objective of this study is to investigate neuropsychological function in individuals diagnosed with Duchenne muscular dystrophy (DMD) as a model for developmental neuroscience. DMD is a single-gene disorder that interferes with the expression of the protein dystrophin and its isoforms. The consequences of lack of dystrophin in muscle are well known; boys have progressive muscular weakness that results in death generally by their third decade of life. Dystrophin isoforms are also missing from the central nervous system, yet what functional consequences that may have is unclear. Interdisciplinary study of the cognitive profile, the behavioral attributes, and the molecular genetics of DMD will examine genotype/phenotype associations. The study will build on work that ascertained neuropsychological function in a group of 136 boys diagnosed with DMD and was completed during the tenure of an R29 award. Those data confirmed that boys with DMD who are of average intelligence have selective deficits in verbal working memory with intact declarative memory and visuospatial skills, poor social skills and delayed language developmental milestones. Selected subjects from the established cohort will be examined more thoroughly in focused paradigms to tease apart their language and short-term memory skills using a battery of tests designed to examine the hypothetical "phonological loop." Additionally, subjects will be tested on measures of social function and awareness. New subjects will also be enrolled to increase our sample size for genetic analyses. Subjects with more mild manifestations of the disorder (boys with Becker's muscular dystrophy and carrier females) will be tested on neuropsychological measures to determine whether they present with cognitive phenotypes. An ongoing longitudinal study of a sample of 26 boys will be continued with neuropsychological testing every other year. And newly characterized preschool boys with DMD will be followed to track their language and emotional development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--BIOLOGIC IMAGING Principal Investigator & Institution: Watkins, Simon C.; Professor; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Description (provided by applicant): Visualization and localization of message, protein, or structural change resulting from gene expression is an essential step in evaluating the efficacy of successful gene transfer into cells and tissues. The goals of this program are to extend our understanding of the cellular pathology of Duchenne Muscular Dystrophy and to develop vector systems for dystrophin delivery using a variety of possible delivery systems, including AAV, Herpes, and stem cells. It is expected that these vectors will be used to use these vectors to generate clinically useful therapeutic regimens. In each case there is a fundamental need to define the level of incorporation of the delivered dystrophin into muscle, and to assess the effectiveness of the therapy. This identification varies from the low-resolution studies of whole tissues, defining correction of pathological phenotype, to high-resolution observations of successful subcellular passaging and presentation of protein. The Center for Biologic Imaging, in which this core service will be performed, is designed with this function in mind. It is equipped to perform a continuum of optical methods including all types of light and electron microscopy essential to this program project. Within the scope of this project at the light microscopic level these include: histological, immuno-histological and possibly live cell technologies. At the electron microscopic level we will provide fine structural and immuno-electron microscopic evaluation of specimens as a natural extension of the light microscopic analyses when needed. Furthermore, our considerable experience in computerized image processing and morphometry will allow quantitative analysis of observed phenomena to corroborate earlier, possibly quite subtle qualitative changes. This core will be used extensively by all projects, though the imaging tools used will vary from project to project. Preliminary data have shown the validity of these approaches, and we expect a very significant increase in the use of optical techniques within the formal setting of this program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: DUAL AAV VECTORS FOR DUCHENNE MUSCULAR DYSTROPHY THERAPY Principal Investigator & Institution: Duan, Dongsheng; Assistant Prof. of Microbio & Immunology; Molecular Microbiol and Immun; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2003; Project Start 14-JUL-2003; Project End 30-APR-2008 Summary: (provided by applicant): Duchenne muscular dystrophy (DMD) is the most common form of inherited muscle disease. It usually leads to death from respiratory or cardiac failure by age 20. Currently, no effective treatment is available for this fatal disease. DMD is an X-linked genetic disease caused by dystrophin gene mutation. Gene therapy represents a very promising avenue to cure DMD. Recombinant adenoassociated virus (rAAV) mediates high-level persistent transgene expression in muscle. Recent clinical trials have further confirmed the efficiency and the safety of rAAV vectors in muscle. However, rAAVmediated DMD gene therapy has been significantly limited by the small viral packaging capacity. Only the highly truncated C-terminaldeleted versions of "micro-dystrophin" genes have been attempted. Both clinical and transgenic studies show that the C-terminal-inclusive larger genes (such as the 6.0-6.3kb "mini-dystrophin" genes and the approximately 4.7kb "C-terminal-inclusive micro-

Studies

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dystrophin" genes) are therapeutically superior. Unfortunately the strong therapeutic expression cassettes derived from these genes are too large to be packaged in a single AAV virion. We have recently developed several dual vector approaches to expand AAV packaging capacity. Among these, the concatamerization-based "trans-splicing" and "cis-activation" strategies hold great promise for delivering the C-terminal-inclusive larger dystrophin genes. However, the expression level achieved so far is not sufficient for DMD gene therapy. In this proposal, we plan to extend our previous findings and further explore the molecular mechanisms underlying these methods, in the hope of improving the transduction efficiency for DMD gene therapy. In particular, we will try to identify and overcome the rate-limiting barriers to transgene expression. These include problems associated with dual vector co-infection, concatamerization of AAV genome inside cell, and transcription, splicing, and stability of AAV concatamers. More important, we will apply this newly obtained information to generate the most effective trans-splicing and cis-activation AAV vectors for the C-terminal-inclusive larger dystrophin genes. Therapeutic potentials of these newly developed AAV vectors will be rigorously tested in the limb muscle, diaphragm, and heart of the murine DMD model (mdx mouse). A comprehensive array of assays will be used to examine the level of gene expression and the functional improvement in muscle histology and contraction. To address safety concerns, we also plan to evaluate the potential deleterious effects from putative truncated protein production in the trans-splicing method. Taken together, our findings will lead to the eventual application of these very promising dual AAV vector strategies to the human DMD gene therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENHANCEMENT OF MYOBLAST CHEMOTACTIC MIGRATION Principal Investigator & Institution: Dominov, Janice A.; Boston Biomedical Research Institute 64 Grove St Watertown, Ma 02472 Timing: Fiscal Year 2002; Project Start 26-SEP-2002; Project End 30-JUN-2004 Summary: (provided by applicant): Genetic defects underlying several degenerative muscle diseases such as Duchenne muscular dystrophy (DMD) are known, yet effective therapies for these disorders have not been found. One approach has been cell-based therapy in which normal myoblasts or genetically modified patient myoblasts are injected into diseased muscle with the intent that engraftment would be sufficient to compensate for protein deficiencies. Little success has been achieved with this approach however due to problems such as poor graft survival and impractical requirements for numerous muscle injections. Recently, systemic delivery of muscle precursor cells via tail vein or arterial injection in mice has been demonstrated resulting in low-level donor cell engraftment of regenerating muscle tissue. Vascular migration and extravasation of precursor cells thus occurs and could provide a useful route for improved cell-based therapy for these devastating diseases. The specific aims of the proposed work are to 1) Identify molecules expressed in myoblasts that are involved in the attachment to activated endothelial cells and promote trans-endothelial cell migration, 2) Improve the efficiency of myoblast trans-endothelial migration, if possible, by cytokine-induced expression of molecules known to regulate attachment and extravasation of immune system cells. Methods: Murine skeletal muscle myoblasts will be studied to determine expression levels of proteins known to function in leukocyte extravasation. Inflammatory cytokines will be used to induce myoblast expression of proteins relevant to chemotactic movement. In vitro trans-endothelial cell migration assays will be used to assess the role of specific chemokines, receptors and cell adhesion molecules in this process and the influence of inflammatory cytokine stimulation on myoblast migration.

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Normal myoblasts and those induced by cytokines will be injected into tail veins of mdx mice (model for DMD) undergoing muscle regeneration and extravasation into tissues assessed. Results will further our understanding of the mechanisms that promote systemic engraftment of donor myoblasts into diseased muscle could significantly advance the therapeutic use of myogenic precursor cells for the treatment of muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUSCLE

EXCITATION-CONTRACTION COUPLING IN

DYSTROPHIC

Principal Investigator & Institution: Vergara, Julio L.; Professor; Physiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Abnormalities in the mechanisms of calcium regulation and excitation-contraction (EC) coupling that may be linked to the degeneration of skeletal muscle fibers in Becker Muscular Dystrophy (BMD) and in Duchenne Muscular Dystrophy (DMD) will be investigated using isolated muscle fibers from mdx mice. Cells from this animal model, like those of dystrophic patients, have deficiencies in the expression of the protein dystrophin. Although there is substantial biochemical evidence demonstrating the association of the dystrophinglycoprotein complex with transmembrane- and membrane-bound muscle proteins, little is known about its specific role in the physiological aspects of a muscle fiber. The main goal of this proposal is to obtain critical experimental evidence linking the absence of dystrophin with specific alterations in the electrical propagation in the transverse tubular system and calcium signaling machinery. Several possibilities that may explain these observations will be explored experimentally. Changes in intracellular calcium concentration triggered by electrical activity of the muscle fibers will be recorded with the aid of low affinity calcium sensitive fluorescent indicators and membrane potential changes in the transverse tubules will be monitored with potentiometric indicators. The investigations will be carried out using high-resolution optical methods that permit to assess the functional state of these critical steps of the EC coupling process, not only at the cellular level, but also within sub-regions of the muscle fiber and even within a single sarcomere. We will perform these measurements across three different age groups of the mdx mouse in order to understand the progression of the disease with time. We will also test if muscle fibers from a utrophin/dystrophin-lacking double mutant mouse, which exhibits a harsher pathology (similar to DMD), show signs of more pronounced defects in EC coupling. These types of experiments are necessary to unravel the mysterious role that dystrophin may play in the normal regulation of calcium metabolism in skeletal muscle. The knowledge gained in the proposed studies will help to elucidate the functional role of dystrophin in mammalian skeletal muscle, to this date the most fundamental and elusive problem in muscular dystrophy research. The enhanced methods proposed to detect defective steps in the EC coupling mechanisms within localized submicroscopic regions of mammalian muscle fibers may become the optimal choice for the future evaluation of genetic therapeutic procedures in sub-regions of a single muscle cell. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE AND CELL THERAPY OF DUCHENNE MUSCULAR DYSTROPHY Principal Investigator & Institution: Glorioso, Joseph C.; Professor and Chairman; Molecular Genetics & Biochem; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: Muscular dystrophy is a common genetic disease that affects 1 in 3500 male births annually. The disease is characterized by early muscle hypertrophy followed by muscle degeneration and early death in adolescence resulting from failure of heart and diaphragm muscle. The disease results from mutations that affect expression or function of dystrophin, an important structural component of the subplasma membrane. Currently no treatment is available. The overall goal of the proposed research is to develop gene and cell therapeutic methods for treatment of muscular dystrophy. Clinical, pre-clinical and basic muscle cell development studies are described in which experts in gene transfer, muscle cell biology, animal models of muscular dystrophy and clinical applications are brought together in a manner to achieve the highest level of data sharing, synergy and creative solution finding will be possible. Project 1 (J Mendell) will define clinical end-points and identify cohorts of patient that would participate in a phase I dose escalation safety clinical trial using an AAV gene vector carrying the functional dystrophin minigene delivered to a single skeletal muscle and continue gene therapy clinical trials for limb girdle MD. In Project 2 (X Xiao and J Kornegay), will explore methods for improved AAV-dys gene delivery using the dog model. In Project 3 (J Huard), experiments using muscle stem cells will be carried out using dystrophic mouse models in attempts to achieve muscle delivery of normal muscle derived stem cells to engraft into diseased heart. In Project 4 (J Glorioso), a novel functional genomics approach to identify genes that participate in differentiation of mouse embryonic stem cells toward muscle cell lineages is proposed using HSV gene vector cDNA libraries obtained from muscle derived stem cells. The core programs are designed to directly support the projects in the form of Administration (Core A: J Glorioso and P Robbins), Clinical Vector Production (Core B: J Barranger), a muscular dystrophy dog colony (Core C: J Kornegey) and Imaging (Core D: S Watkins) to provide information on the results of gene transfer in animals and patients. Finally, our center includes a training program for residents interested in gene therapy for muscle disease. We believe this to be a timely and highly innovative proposal which is likely to provide new armroaches to the treatment of muscular dvstrophv. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE THERAPY FOR DUCHENNE MUSCULAR DYSTROPHY Principal Investigator & Institution: Wolff, Jon A.; Professor; Pediatrics; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 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

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

Project Title: GENTAMICIN TRIAL IN DUCHENNE AND LIMB GIRDLE DYSTROPHIES Principal Investigator & Institution: Mendell, Jerry R.; Neurology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): The study will determine if the aminoglycoside, gentamicin, has potential as a therapeutic medication for Duchenne muscular dystrophy (DMD). To fulfill this potential, long-term administration of gentamicin must be safe and improve muscle strength. Ideally, it will also increase dystrophin expression with binding at the muscle membrane. The testing paradigm will be a three-arm, sixmonth, double blind, randomized controlled trial of intravenous (IV) 7.5 mg/kg of gentamicin. Groups 1, 2, and 3 will each have 12 subjects. Group 1 will receive gentamicin every three days, while group 2 will receive drug every seven days. Group 3 subjects receive an IV placebo of 5% dextrose and saline; six subjects infused every three days and six others every seven days. In addition, gentamicin will be used in two shortterm, 14-day studies. If either of these groups responds to the 14-day administration by decreasing serum creative kinase (CK), then they become potential candidates for sixmonth administration. One group of 14-day subjects will have DMD with frameshift mutations. Despite commonly held dogma that aminoglycosides have no effect on this mutation-type, it is important to establish as effect by testing to see if CK drops. A positive outcome potentially reaches more patients, since this is the most common type of DMD gene mutation. Gentamicin will also be used to treat limb girdle muscular dystrophy subjects with stop codon mutations. If the serum CK is lowered, the potential for long-term treatment will be established for these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTEGRIN REGULATION OF VASCULAR SMOOTH MUSCLE Principal Investigator & Institution: Burkin, Dean; University of Nevada Reno 204 Ross Hall Mailstop 325 Reno, Nv 89557 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2008 Summary: This proposal seeks to understand the functional roles of the alpha7beta1 integrin in regulating vascular smooth muscle plasticity and in vascular disease. The alpha7beta1 integrin and the dystrophin glycoprotein complex connect muscle cells to

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their surrounding matrix. Duchenne Muscular Dystrophy (DMD) patients and mdx mice (a model for the human disease) have genetic mutations that result in an absence of dystrophin. DMD is characterized by progressive muscle weakness leading to early death from cardiopulmonary failure. DMD patients exhibit vascular abnormalities caused by weak smooth muscle cell attachment, poor contractile responses and excessive bleeding after surgery. In skeletal muscle of DMD patients and mdx mice, the alpha7beta1 integrin is increased and may partially compensate for the absence of the dystrophin complex. Enhanced transgenic expression of the alpha7beta1 integrin in skeletal muscle increases the longevity and decreases the pathology of severely dystrophic mice, supporting the hypothesis that alpha7beta1 and the dystrophin complex functionally overlap. Both dystrophin and the alpha7beta1 integrin are expressed in vascular smooth muscle where they mediate cell attachment to laminin. The dystrophin complex is involved in vascular smooth muscle plasticity and Ca 2+ homeostasis. This proposal will test the hypothesis that the alpha7beta1 integrin has a complementary role in regulating vascular smooth muscle cell plasticity. We will use mdx mice to determine if alpha7beta1 levels are increased in vascular smooth muscle in the absence of dystrophin. We will further determine if altered levels of the alpha7beta1 integrin result in alterations of Ca 2+ homeostasis, cell contractility, vascular tone, and cell differentiation. Molecules downstream of the integrin will be analyzed to determine the mechanisms by which increased alpha7beta1 compensates for the absence of dystrophin. The alpha7beta1 integrin may play a critical role in vascular plasticity and disease and these studies may shed light on the underlying molecular basis of vascular function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ION CHANNELS AND CHEMICALS CONTROLLING SYNAPSE STABILITY Principal Investigator & Institution: Mcardle, Joseph J.; Professor; Pharmacology and Physiology; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Synapses are the major locus of information transfer within our brain as well as the target of numerous pathologies which can afflict humans from development in utero to death. Therefore, major research effort is given to understanding synapse formation and stabilization throughout life. The scientific literature concerning synapses is rich with discovery of fundamental principles derived from study of the neuromuscular junction (NMJ). In particular, proteins responsible for NMJ function, formation, and stability are relatively well understood. Nevertheless, fundamental questions remain concerning interactions between these proteins. An important experimental model suggests that heterogeneous activity of AChRs influences stability of the adult NMJ. This proposal modifies and extends that model to the developing NMJ where co-expression of immature gamma and mature epsilon AChRs during the critical phase of NMJ maturation produces heterogeneity of end-plate activity. Our model suggests that end-plate areas rich in epsilon AChR mediate Ca 2+ influx which activates co-localized nitric oxide synthase (nNOS). The nitric oxide (NO) produced diffuses to nerve terminals competing for the motor end-plate. New preliminary data suggest that NO enhances Ca2+ currents and transmitter release at adult motor nerve terminals. Thus, developing nerve terminals activating end-plate loci containing the epsilon AChR may be functionally enhanced and nurtured via NO activation of presynaptic guanylyl cyclase. In contrast, NO may repress function and stability of competing nerve terminals activating epsilon AChR poor end-plate foci. The

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mouse Triangularis sterni (TS) preparation facilitates exact testing of our model. Our preliminary data show that the TS preparation isolated from neonatal mice allows simultaneous recording of nerve terminal currents and post-synaptic events at endplates receiving innervation from terminals originating in distinct nerve trunks. This allows unprecedented study of the function of, and NO-mediated cross talk between, mammalian nerve terminals competing for a postsynaptic target. The availability of epsilon subunit and nNOS knock out mice, as well as the epsilon AChR selective ligand Waglerin- 1 further strengthen experiments proposed to test our model. Additional novel preliminary data suggest that insulin, an activator of the neuronal K-ATP channel, suppresses quantal release of Ach at the adult NMJ. Therefore, a second goal of this proposal is to discover if insulin, as well as glucose, effects the function, and eventual stability, of nerve terminals competing at the developing NMJ. This will be explored in a non-obese mouse model of type I diabetes. Overall, this research is clinically relevant since NO signaling cascades are significantly altered in Duchenne muscular dystrophy as well as animal models of stroke. In addition, altered function of the epsilon AChR is responsible for NMJ pathology associated with slow channel congenital myasthenic syndrome. The proposed evaluation of insulin effects is novel and will enhance understanding of the neurologic consequence of adult and juvenile forms of diabetes. The knowledge gained from this research will enlighten future molecular approaches to treating pathologies which afflict children and adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MODIFIED ADENOVIRAL VECTORS FOR GENE TRANSFER TO MUSCLE Principal Investigator & Institution: Chamberlain, Jeffrey S.; Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: The long range goal of this project is to develop viral vectors of gene therapy of muscle diseases. In transgenic mdx mice, a model for Duchenne muscular dystrophy (DMD), low-level expression of dystrophin mini-genes prevents dystrophy through at least years of age. Modified adenoviral vectors are being developed to test whether gene transfer can treat, rather than prevent, dystrophy in young and aging animals. Adenoviruses (Ad) efficiently infect muscle but they display a number of disadvantages preventing use in clinical trials for DMD. Ad vectors trigger a host immune response that prevents long term gene expression in vivo. Ad vectors have a cloning capacity of only approximately 8 kb, smaller than the 14 kb dystrophin cDNA. Finally. strong viral promoters typically used to driven transgene expression from Ad vectors are often shutoff in vivo. A new Ad vector is being developed that could overcome each of these problems. Our hypothesis is that Ad vector systems lacking all viral genes can support long-term gene expression. in muscle. Critical to this 'gutted' vector strategy is the development of a self-limiting helper virus system. Vector lacking viral genes can only be propagated in the presence of a helper virus that produces proteins needed for Ad replication and packaging. However, it the preparations of gutted vector contain significant levels of the helper virus, then the contaminating helper virus will trigger the same immune response that the gutted system is designed to avoid. Our strategy for perfecting the gutted vector system relies heavily on improvements to the helper viruses used for gutted vector propagation. The Cre-LoxP system will be used to disable packaging of helper DNA into virions. Modified Ad packaging cell lines will also be used to grow helper viruses lacking a subset of genes required for propagation and gene expression in vivo. Muscle specific promoters are also being developed to limit virally-

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delivered transgene expression to muscle tissues. Finally, a functional homologue of dystrophin [utrophin] will be tested for the ability to prevent an immune response against dystrophin. This gutted vector/helper virus system will be tested in vivo to identify any residual host immune responses that might be generated, and if needed a variety of vector modifications will be tested to attenuate this response. If successful, these studies could lead to a treatment for DMD and other muscle diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR DYSTROPHINOPATHIES

IDENTIFICATION

OF

CANINE

Principal Investigator & Institution: Smith, Bruce F.; Associate Professor; Scott-Ritchey Research Center; Auburn University at Auburn Auburn University, Al 36849 Timing: Fiscal Year 2002; Project Start 05-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Duchenne muscular dystrophy is a common inherited disease, affecting approximately 1 in 3000 live male births. Currently, there is no effective therapy for this disease, however, new therapies are being proposed that offer hope to patients and their families. These therapies must be evaluated for their efficacy in the most stringent manner possible, and in the case of DMD, that requires an appropriate animal model. The long term GOAL of this project is to characterize the molecular defects present in 3 new canine models of dystrophin deficiency. It is hypothesized that these models accurately reflect the depth and breadth of mutations and their effects that is seen in the human population. Current murine models require that multiple genes be knocked out to show the same disease that the loss of dystrophin causes in boys. The canine model system is the only model which appropriately reflects the relentlessly progressive and ultimately fatal disease of boys. However, the complexity of the dystrophin gene and thus the variety of mutations possible, require the availability of multiple models in which to test therapies. The best source of these models continues to be spontaneously occurring canine disease. This severely handicaps the utility of these models in evaluating new therapies. This project will not only elucidate the mutation in these three new canine models, but it will also create a set of tools that will allow investigators worldwide to rapidly evaluate further spontaneous cases of canine muscular dystrophy for their usefulness, both in exploring new therapies and in gaining new insight into the mechanism behind Duchenne muscular dystrophy. Specifically, we propose to use panels of monoclonal antibodies with known specificity to dystrophin, simultaneously with PCR amplification of the coding sequence to rapidly scan for mutations. Suspicious areas will be sequenced to determine if the mutation is contained within. Once the mutations are identified, their effect on transcription, translation and the presence of dystrophin will be evaluated and compared to similar human mutations to determine if there is a pathophysiological correlation between species and their mutations. Successful completion of this project will result in the addition of three models of human dystrophin deficiency to the tools available to investigators seeking novel treatments. The correlation of these mutations with the clinical course of the disease will allow therapies to be evaluated under a variety of clinical circumstances. These mutations will provide new and different genetic backgrounds upon which various therapies, and in particular genetic therapies, may be examined in a large, outbred animal species. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR PATHOPHYSIOLOGY OF FACIOSCAPULOHUMERAL MUSCUL* Principal Investigator & Institution: Chen, Yi-Wen; Children's Research Institute Washington, D.C., Dc 20010 Timing: Fiscal Year 2002; Project Start 28-SEP-2001; Project End 31-MAY-2004 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 clinically-affected 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 custom-produced 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 FSHD, as well as identification of functional SNPs in the refined gene list that correlate with disease severity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MUSCLE RESPONSE TO STRESS IN CANINE MUSCULAR DYSTROPHY Principal Investigator & Institution: Childers, Martin K.; Associate Professor; Phys Med and Rehabilitation; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2002; Project Start 01-MAR-1999; Project End 28-FEB-2004 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

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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 determine if a lower threshold to stressinduced 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://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUSCLE CARDIOMYOPATHY

STEM

CELL-BASED

THERAPIES

FOR

Principal Investigator & Institution: Huard, Johnny; Henry J. Mankin Associate Professor of o; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: Cardiomyopathy is a serious heart disease that often leads to congestive heart failure, a condition in which the heart muscle can no longer effectively pump blood. Patients that suffer from various muscle diseases, including Duchenne muscular dystrophy (DMD), develop progressive cardiomyopathy. Cellular cardiomyoplasty (CCM), a procedure that involves the transplantation of exogenous cells into damaged myocardium, has been proposed as a possible therapy to regenerate diseased myocardium and deliver therapeutic genes. Although a wide variety of cell types has been used for CCM, various limitations (including ethical, biological, or technical challenges) have impeded their suitability for use in human patients. We recently have used the modified preplate technique to isolate a novel population of muscle-derived stem cells (MDSCs) that display improved transplantation capacity in skeletal muscle when compared to satellite cells. The MDSCs' ability to proliferate in vivo for an extended period of time-- combined with their strong capacity for serf-renewal, multipotent differentiation, and immune-privileged behavior--reveals, at least in part, a basis for the benefits associated with their use in cell transplantation in skeletal muscle. The proposed project will investigate the use of MDSCs as a novel cell source for cardiac cell transplantation in a cardiomyopathic murine model of muscular dystrophy. We already have observed that MDSCs delivered by intra-cardiac injection display good cell survival and can deliver dystrophin within the dystrophic myocardium. In this project we will investigate whether MDSCs implanted in the hearts of dystrophic mdx mice display an improved transplantation capacity when compared to conventional satellite cell implantation (Aim #1). We then will explore the relative contribution of the MDSCs' capacity for long-term proliferation and self-renewal (Aim #2) to the increased regenerative capacity of these cells after transplantation in heart muscle. Finally, we will

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determine the degree to which development of approaches to prevent fibrosis (Aim #3) and improve angiogenesis (Aim #4) would further enhance the regenerative capacity of muscle-derived cells in the heart. This project will increase our understanding of the basic biology of myogenic cell populations that display stem cell characteristics. This information may, in turn, unveil new techniques to improve heart regeneration and repair via the transplantation of muscle-derived stem cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MYELOID CELL FUNCTION IN MUSCULAR DYSTROPHY Principal Investigator & Institution: Tidball, James G.; Professor; Physiological Sciences; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 24-SEP-2001; Project End 31-AUG-2006 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 dystrophin-deficiency in the mdx mouse model of the disease. The long-term goal of our studies of the pathology of dystrophindeficiency 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 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://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MYOSIN GENE DIVERSITY AND FUNCTION Principal Investigator & Institution: Leinwand, Leslie A.; Professor and Chair; Molecular, Cellular & Dev Biol; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2003; Project Start 01-SEP-1981; Project End 31-JAN-2007 Summary: (provided by applicant): The formation of skeletal muscle and its adaptation to the environment requires precise temporal and spatial regulation of a host of proteins, including the molecular motor protein, myosin. The precise adaptation of myosin heavy chain (MyHC) genes requires coordinate regulation, yet, little is known

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about its molecular biology. We propose to define the molecular aspects of fiber type specificity and the pathways that regulate these genes. In mammals, there are 6 characterized skeletal muscle MyHC genes. Although muscle fibers expressing each of them have unique contractile velocities, the enzymatic properties of the individual motors remain elusive. We will express the 6 human skeletal MyHC head domains in an inducible mammalian system and characterize their biochemical and biophysical properties. Despite the perception that the sarcomeric MyHC gene family had been defined, examination of the human genome revealed a novel striated MyHC that we propose to characterize. We have found that it is expressed in cardiac and skeletal muscle and that phylogenetically, it appears most closely related to the alpha and beta MyHC genes. We will compare the sequence features of the coding, regulatory regions and the intron/exon organization of this gene in mouse and human. We will also determine its expression in development and in the adult and test whether wellcharacterized muscle adaptations alter its pattern of expression. Until recently, there had been no diseases associated with mutations in skeletal MyHC. However, a mutation in the MyHC IIa gene has been reported which we propose to model in transgenic mice. We are also characterizing the IId gene of a childhood myopathy patient who appears to be null for its expression. An interesting feature of the MyHC gene family that may have relevance to Duchenne muscular dystrophy (DMD) is that the most abundant MyHC protein in rodents, IIb, is barely detectable in normal adults. However, we find its expression is induced in DMD. Because of the potential functional consequences of expression of this fast myosin motor, we will define the molecular basis for this species difference and its induction. Finally, we will extend our studies of an unusual cell type, the myofibroblast, which has properties of both muscle and nonmuscle cells, including expression of adult fast skeletal MyHCs, to understand the pathways that define these cells and distinguish them from skeletal muscle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENESIS OF EMERY-DREIFUSS MUSCULAR DYSTROPHY Principal Investigator & Institution: Worman, Howard J.; Associate Professor; Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): Emery-Dreifuss muscular dystrophy (EDMD) is characterized by region muscle contractures, slow progressive muscle wasting and cardiomyopathy with atrioventricular conduction block. Indistinguishable forms of EDMD are inherited in autosomal dominant and X-linked manners. Mutations in emerin, an integral protein of the nuclear envelope inner membrane, cause X-linked EDMD. Autosomal dominant EDMD is caused by mutations in the LMNA gene, which encodes the nuclear envelope intermediate filament proteins lamins A and C. It is not known how mutations in nuclear envelope proteins cause muscular dystrophy. We hypothesize that mutations in these chromatin-associated proteins cause changes in the expression of genes responsible for muscle cell differentiation or survival. Our goal is to test this hypothesis using a combination of studies in transfected cells, patients' cells and tissues and animals models. In the first specific aim, we will use fluorescence microscopy and photobleaching methods to investigate how lamin A and C mutants from patients with autosomal dominant EDMD influence the mobility of emerin in the inner nuclear membrane. We will determine if mutant lamins A and C cause emerin to "escape" from the inner nuclear membrane into the continuous endoplasmic reticulum. As patients with X-linked EDMD do not have emerin in the inner nuclear membrane, this finding would demonstrate a connection between the X-linked and autosomal

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dominant forms of the disease. In the second aim, we will use microarrays to compare gene expression in cells from patients with autosomal dominant EDMD to X-linked EDMD and Dunnigan-type partial lipodystrophy, a disease caused by mutations in different regions of lamins A and C. This will establish if emerin and lamin mutations responsible for EDMD alter expression of the same genes. We will also use microarrays to determine gene expression profiles in muscles from lamin A/C "knockout" mice that develop muscular dystrophy and compare the results to what is known about pathologic alterations in gene expression in Duchenne muscular dystrophy. The results will be confirmed in tissues from human subjects with EDMD. In Aim 3, we will generate transgenic mice expressing human lamin A mutants and determine if they develop pathological abnormalities of EDMD and similar gene expression changes. This work will help establish how abnormalities in the nuclear envelope cause muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF SKELETAL MUSCLE REGENERATION Principal Investigator & Institution: Li, Yi-Ping; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Tumor necrosis factor-alpha (TNF-alpha) is traditionally recognized as a circulating mediator that stimulates muscle catabolism in inflammatory diseases. However, recent discoveries indicate that TNF-alpha plays a more complex and more fundamental role in skeletal muscle. It is now clear that skeletal myocytes constitutively express TNF-alpha. Biological processes that demand myofiber regeneration - degenerative muscle diseases (inflammatory myopathies and Duchenne muscular dystrophy), injury and exercise -- accelerate TNF-alpha expression by myocytes. Further, it is increasingly evident that TNF-alpha is critical for muscle regeneration because it accelerates myogenic gene expression. Based on growing evidence from our and other laboratories, we propose that TNF-alpha functions as an autocrine/paracrine modulator of muscle regeneration by promoting the expression of adult-type muscle proteins during early differentiation via activating MADS-box myogenic factors, MEF2 and SRF, and a muscle hypertrophy mediator GATA-2. Three specific aims will be pursued to test this model. Aim 1. To evaluate upregulation of TNF-alpha as an autocrine modulator of primary myoblast differentiation. TNF-alpha expression during differentiation induced by distinct stimuli (serum restriction, cell confluence and cyclic stretch), and effects of TNF-alpha on adult-type muscle protein expression during differentiation will be determined in rat and mouse primary myoblasts. Aim 2. To determine whether TNF-alpha promotes muscle regeneration in vivo. Effects of TNF-alpha deficiency on muscle regeneration evoked by cardiotoxininduced muscle injury will be evaluated in mice with genetic or immunological blockade of TNF-alpha receptors. Muscle histology, contractile force generation, and myogenic gene expression will be determined to evaluate regeneration. Aim 3. To determine signaling events by which TNF-alpha stimulates myogenic differentiation. TNF-alpha stimulation of MEF2, SRF, and GATA-2, and the underlying signaling mechanisms will be evaluated. Our long-term objectives are to understand the role of cytokines as an emerging group of muscle regeneration modulators, and to improve the treatment of degenerative muscle diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RESCUE ANALYSIS OF UTROPHIN & NMJ SUPPORT BY SYNTROPHIN Principal Investigator & Institution: Sealock, Robert W.; Associate Professor; Cellular/Molecular Physiology; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): The syntrophins are a family of peripheral membrane adapter proteins that function in association with dystrophin, utrophin, and the dystrobrevins, all of which are proteins of the surface membrane of skeletal muscle and implicated in the important human disease, Duchenne muscular dystrophy (DMD). Alpha-syntrophin is the major syntrophin in muscle. In the alpha-syntrophin knockout mouse, the postsynaptic membrane at the neuromuscular junction shows major biochemical and morphological defects including low amounts of acetylcholine receptors and acetylcholinesterase, a complete absence of utrophin, immature appearing contacts, junctional folds that are disorganized and few in number, and altered distribution of AChR. Thus, there is a utrophin and NMJ support function of alphasyntrophin. The first two aims of the project are to intended to extend current understanding that the other syntrophins of muscle (beta1, beta2, and probably gamma2) are not redundant with alpha-syntrophin. They are: 1) Test the hypothesis that transgenically expressed beta 1-syntrophin will restore utrophin to adult alphasyntrophin 4- junctions but will not rescue other, or all other, aspects of the phenotype. 2) Test the hypothesis that transgenically expressed beta 2-syntrophin will restore no aspects of the alpha-syntrophin -/- phenotype. The results will provide a solid framework for molecular analysis of the mechanisms of the support function. Aim 3) Identify the critical functional domains of the alpha-syntrophin molecule by transgenic expression in alpha-syntrophin -/- mice of a) chimeric proteins containing domains of beta substituted into alpha-syntrophin (or the converse, alpha into beta) and/or b) alpha-syntrophin specifically mutagenized at selected sites. The results will identify domains and implicate syntrophin-dependent pathways. Aim 4) Determine whether low levels of utrophin mRNA, inability of the membrane to accept utrophin incorporation, or both contribute to the lack of utrophin at alpha-syntrophin -/- NMJs. If applicable, use these tools to analyze the transgenic mice. 5) Seek to identify determinants in the AChR accumulation pathway-- AChR mRNA levels, total AChR expression, cell surface AChR expression, AChR clustering response to agrin, stability of agrin-induced clusters--that may contribute to the low AChR content of alphasyntrophin 4- NMJs. If applicable, use the understanding so generated to analyze the transgenic mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RNA/PROTEIN REGULATION

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Principal Investigator & Institution: Singh, Ravinder; Molecular, Cellular & Dev Biol; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Sex determination is a fundamental decision that essentially all metazoans encounter during their development. Sex determination in Drosophila melanogaster involves a hierarchy of alternative splicing decisions, and is also the best understood example of splicing regulation. Splicing is a process by which non-coding sequences (introns) are removed from the precursor messenger RNA. In higher eukaryotes,

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constitutive and alternative splicing are important aspects of gene regulation in many important cellular processes. Approximately 15 percent of the mutations that have been linked to human diseases affect RNA splicing signals, including cellular transformation, Duchenne muscular dystrophy, and tumor metastasis. Our goal is to understand how RNA-binding proteins recognize target RNAs and regulate constitutive and alternative pre-mRNA splicing. The Drosophila protein Sex-lethal (SXL) acts as a key binary switch between the male and female cell fates. In the past, we defined the mechanism by which SXL regulates alternative splicing by antagonizing the known splicing factor U2AF65. Specificity is an underlying theme in biological regulation. U2AF65 and SXL offer excellent models for specific RNA-protein interactions in the context of splicing regulation. For example, while the general splicing factor U2AF65 recognizes a wide variety of polypyrimidine-tract/3' splice sites, the highly specific splicing repressor SXL recognizes a specific sequence. Although both proteins contain a ribonucleoproteinconsensus motif, they have distinct RNA-binding specificity. However, it is not understood how these seemingly similar proteins achieve unique RNA-binding specificities. To define the structural basis for the RNA-binding specificities of U2AF65 and SXL, we will extend our analysis of the RNA and the proteins by using a combination of biochemical, molecular, and genetic approaches. Our findings will also be directly applicable to other members of this largest family that likely regulate different aspects of RNA biogenesis. In addition, SXL controls many female-specific functions. However, some of the relevant genes that are regulated by SXL remain to be identified. To identify these targets, we will use a combination of recently developed molecular approaches - genomic SELEX and subtractive hybridization/differential display. These approaches should complement genetic analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SKELETAL MUSCLE STRUCTURE AND FUNCTION IN AGING MDX MICE Principal Investigator & Institution: Brooks, Susan V.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: The purpose is to investigate the function of dystrophin and the dystrophinassociated proteins (DAPs) in skeletal muscle fibers and how defects in the dystrophinDAP complex contribute to the pathological changes in muscle over the life span of mdx mice. The absence of dystrophin from the muscles of patients with Duchenne muscular dystrophy leads to ongoing muscle fiber degeneration, progressive necrosis, and fibrosis. Dystrophin is also absent from the muscles of mdx mice. The mechanisms underlying the degenerative process in dystrophic muscle are unknown, but replacement of dystrophin in transgenic-mdx mice prevents many of the dystrophic symptoms. In control animals, degeneration of myofibers may result from contractioninduced injury and susceptibility to contraction-induced injury than those in agematched control mice, but for muscles in transgenic-mdx mice the susceptibility to injury is not known, nor has the effect of age on contraction-induced injury been studied in mdx or transgenic mdx-mice. The working hypothesis are that (i) the dystrophin-DAP complex shunts contractile forces laterally from the myofibrils through the plasma membrane to the extracellular matrix, and a lack of dystrophin results in stress concentrations on the sarcolemma which damage the membrane, and a mechanically compromised cytoskeleton which increases sarcomere heterogeneity and damage; and (ii) the increased susceptibility to both sarcolemma and sarcomere damage is aggravated as animals age. Specific hypotheses have been formulated regarding the mechanical

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function of dystrophin and the effects of age on contraction- induced injury of dystrophic muscle fibers. Structure/function relationships of the dystrophin-DAP complex will be studied in single intact fibers from muscles of control, mdx, and transgenic-mdx mice, and contraction-induced injury will be studied using single fibers in vitro and whole muscles in situ from adult and old mice. Determining the function of dystrophin and why its absence is so devastating will contribute significantly to out understanding of the mechanisms underlying the wasting and weakness that occurs with dystrophy and with normal aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SPIRITUALITY OF CHILDREN WITH DMD Principal Investigator & Institution: Pehler, Shelley-Rae; None; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 01-JAN-2004; Project End 31-DEC-2006 Summary: (provided by applicant): This application proposes research to explore the spirituality of an 8 -12 year old child with Duchenne Muscular Dystrophy. Duchenne Muscular Dystrophy (DMD) is a progressive, genetically inherited, chronic disease with a life-threatening prognosis. Early confirmation of the type of genetic disease a child has allows interventions to be initiated that may affect the quality and longevity of life. What is not known is the spirituality of children with a genetically inherited, life threatening disease, even though the literature is clear that there is a heightened spirituality in the adult and adolescent populations with similar diseases. This heightened spirituality has provided meaning to the adult and adolescents' life to promote healing. Healing does not mean cure in the usual use of the word, but instead a sense of health and well-being as experienced by hope, love, sense of control, relatedness with others, finding meaning and purpose in life and disease, and a sense that there is something greater than the self (Fryback, 1993; Mytko & Knight, 1999). The purpose of this study is to explore spirituality in children who are 8 -12 years of age and who have been diagnosed with the genetic, life-threatening disease of Duchenne Muscular Dystrophy. Giorgi's (1985) qualitative design will be used for this phenomenological study. Children 8 -12 years old with DMD will be recruited from a large, mid-western genetics clinic. Children will be invited to participate in the research until no new themes or meaning units are identified during the interviews. Interviews using open-ended questions and descriptions by the children of drawings they have made will elicit the data. Interview data will be transcribed to sheets of paper verbatim. Demographic information will be used to generate descriptive statistics for the sample population and to determine any religious belief systems that would help in the understanding of the child's responses to the questions. Analysis of the data will follow Giorgi's (1985) method of analysis. Rigor will be addressed through bracketing prior to interviewing and data analysis, using two different data collection strategies, development of a detailed Interview Schedule, using a peer debriefed, and developing an audit process for field notes and data analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SURGICAL APPROACHES TO SYSTEMIC GENE TRANSFER Principal Investigator & Institution: Stedman, Hansell H.; Assistant Professor; Surgery; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007

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Summary: (provided by applicant): The overall aim of the proposed research is to improve the prospects for therapeutic gene transfer in Duchenne muscular dystrophy by addressing two essential rate-limiting issues: immunity to the transgene product and vector delivery. Using a newly described canine animal model for Duchenne muscular dystrophy, the German Short Haired Pointer, the experimental design takes advantage of a deletion of the dystrophin gene to evaluate the comparative immunogenicity of dystrophin and utrophin. We make exclusive use of rAAV vectors. The experimental design tests the hypothesis that in the context of the deletion, recombinant (canine) mini-dystrophin will elicit a deleterious cellular immune response. It further tests the hypothesis that substitution of a similarly designed canine mini-utrophin transgene will circumvent this immune response. Based on extensive preliminary data, the proposal also addresses the hypothesis that the endothelial barrier to systemic gene delivery can be bypassed by temporarily infusing histamine during a period of mechanical circulatory support. We propose a graded series of experiments to address the latter hypothesis, starting with isolated limb perfusion and culminating in systemic gene delivery. These studies will also make extensive use of another naturally occurring animal model, the hamster model for limb-girdle muscular dystrophy. Successful completion of the experimental plan will provide general information relevant to the immunological response to somatic gene delivery and the preservation of organ function during profound but rapidly reversible alterations in endothelial integrity. It will also provide specific information about the rational design of strategies for systemic gene therapy in one of the most common single-gene lethal diseases in man, Duchenne Muscular Dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TEST OF AAV VECTORS IN K9 DMD MODEL Principal Investigator & Institution: Little, Marie-Terese E.; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-JUL-2008 Summary: Duchenne Muscular Dystrophy (DMD) in both humans and dogs is a fatal, Xlinked, recessive muscle disease caused by a lack of dystrophin due to deletions or mutations in the dystrophin gene. The disease is inherited in a recessive pattern suggesting that gene therapy could offer an effective treatment if methods can be found to replace the defective gene in muscle. Studies in the mouse model ofDMD (mdx) have shown that delivery of mini-dystrophin adeno-associated viral (AAV) vectors, which display a remarkable ability to transduce skeletal muscle vectors to adult mdx muscle results in correction of most, but not all, features of dystrophy. Prior to launching into clinical trials with this vector system, data in a large animal model, which more closely reflects the disease phenotype in humans, are needed to assess the safety and effectiveness of this approach. Three specific hypotheses will be tested: 1) that an increase in muscle fiber integrity and function can be achieved by targeted direct injection of AAV vectors containing truncated canine dystrophin genes; 2) that wild type satellite cell transfer and vascularized muscle transplants will result in successful transfer and persistence of wild type satellite cells for the correction of the DMD phenotype; and 3) that seeding of wild type satellite cells will occur from normal to diseased muscle. Aims 1 and 2 will be conducted in recipients of marrow grafts to avoid potential rejection of wild type cells by the immune system. The canine model of DMD that is clinically and pathologically similar to human DMD will be used. These studies will provide baseline data for the development of a phase I clinical AAV gene therapy trial for DMD (Project 1). The long-term obiectives of the proposed research are to

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determine if direct AAV-dystrophin gene and cellular itransplant delivery ameliorates and reverses dystrophic pathology in xmd muscle and if this leads to normal myofiber morphology, histology, cell membrane integrity and function. The development of new therapies in the canine model could have immediate impact on the treatment of DMD patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THERAPEUTIC APPROACHES FOR MUSCULAR DYSTROPHY Principal Investigator & Institution: Spencer, Melissa J.; Assistant Professor; Duchenne Muscular Dystrophy Res Ctr; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 05-MAY-2000; Project End 30-APR-2007 Summary: (appended verbatim from investigator's abstract): Duchenne muscular dystrophy (DMD) is the most common, inherited, lethal disease of childhood. Despite its high frequency of occurrence and the extensive knowledge of the molecular genetics of DMD, the lifespan or quality of life of DMD children has not improved over that which existed before the mutant gene was discovered approximately 13 years ago. Recently, our laboratories have shown that the histologically discernible pathology of the muscles of mdx mice, the most widely used animal model of the disease, could be reduced by more than half through interventions that inhibit cytotoxic T lymphocytes (CTLs). This is the greatest systemic improvement in the pathology of dystrophic muscle attained by any intervention, and it indicates that important new avenues for approaching DMD therapeutics may exist. The general goal of the investigation proposed here is to obtain more specific information concerning the role of T Iymphocytes in the death of dystrophic muscle, so that more specific therapeutic interventions with applicability to humans can be developed in future work. This will be done by: 1) determining whether distinct populations of T lymphocytes function through independent mechanisms in the autoreactive killing of mdx muscle, 2) testing whether binding of costimulatory molecules that are involved in Tcell activation is important for activation of autoreactive Tcells in mdx mice, and whether simultaneous blockade of these molecules is maximally effective for treatment, 3) testing whether the blockade of costimulating molecu1es of Tcells in mdx mice is most effective at reducing muscle pathology when applied early in the disease process, and 4) testing whether treatment of utrophin deficient mdx mice through Tcell depletions or with blockers of Tcell costimulation is effective in reducing muscle pathology and extending lifespan. Collectively, these findings can provide the basis for design of immune interventions to reduce the pathology of dystrophin deficient muscle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSLATIONAL RESEARCH IN THE DYSTROPHINOPATHIES Principal Investigator & Institution: Flanigan, Kevin M.; Associate Professor; Neurology; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD) are devastating disorders. Both are associated with mutations in the dystrophin gene, a huge gene with 79 exons spread over 2.4 million bases of genomic sequence. Deletions of large portions of the gene account for around 60% of all dystrophin mutations. The remainder consist of point mutations (primarily premature stop codon mutations), small deletions resulting in shift of the reading frame,

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and (in less than 5%) duplications. Dystrophin gene deletion testing is commercially and readily available, but point mutation testing is not. Recent studies in the mdx mouse, a model for DMD due to a premature stop codon mutation, have demonstrated the ability of aminoglycosides to increase the expression of dystrophin protein via induction of increased read-through. Recently, we and others have demonstrated some rules for the specificity of this effect, and a growing body of data suggests that aminoglycoside therapy may prove beneficial in some patients. We have developed the methodology to rapidly, robustly, and economically perform direct sequence analysis of the entire coding and regulatory regions of the dystrophin gene, greatly expediting the characterization of mutations in non-deleted dystrophinopathy patients. Using this methodology, we propose to characterize the mutations responsible for DMD and BMD in a large cohort of patients, from whom a standardized and thorough phenotypic characterization, will be obtained. Phenotype/genotype information will be compiled in a pilot dystrophinopathy registry database. Correlation of the phenotype to the sequence context of specific individual mutations will generate hypotheses of aminoglycoside-induced read-through efficiency in specific sequence contexts, which will be tested in an in vitro dual-luciferase transfection assay. This same assay will be used to systematically study other pharmaceutical compounds, which may cause readthrough of premature stop codon or frameshift mutations, and to study other potential mechanisms for modifying intrinsic frame shifting and read-through. Finally, we propose to develop a dual-GFP transgenic mouse, which will allow in vivo characterization of tissue-specific variation in aminoglycoside-induced read-through. Although we do not propose to perform an aminoglycoside treatment trial at present, this proposed study will identify a cohort of patients who may be candidates for any future trials here or at other institutions, and may provide a rationale to suggest that individual compounds or dosages may need to be tailored to specific sequence variations in all future trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “Duchenne 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 Duchenne muscular dystrophy in the PubMed Central database:

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

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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A 230kb cosmid walk in the Duchenne muscular dystrophy gene: detection of a conserved sequence and of a possible deletion prone region. by Heilig R, Lemaire C, Mandel JL.; 1987 Nov 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=306457

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A 71-Kilodalton Protein is a Major Product of the Duchenne Muscular Dystrophy Gene in Brain and Other Nonmuscle Tissues. by Lederfein D, Levy Z, Augier N, Mornet D, Morris G, Fuchs O, Yaffe D, Nudel U.; 1992 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49288

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A second promoter provides an alternative target for therapeutic up-regulation of utrophin in Duchenne muscular dystrophy. by Burton EA, Tinsley JM, Holzfeind PJ, Rodrigues NR, Davies KE.; 1999 Nov 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24184

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Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. by Chamberlain JS, Gibbs RA, Ranier JE, Nguyen PN, Caskey CT.; 1988 Dec 9; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=339001

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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 Kim T, Wu K, Xu J, Black IB.; 1992 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50609

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Direct analysis of amniotic fluid cells by multiplex PCR provides rapid prenatal diagnosis for Duchenne muscular dystrophy. by Simard LR, Gingras F, Labuda D.; 1991 May 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329469

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Direct PCR from CVS and blood lysates for detection of cystic fibrosis and Duchenne muscular dystrophy deletions. by Balnaves ME, Nasioulas S, Dahl HH, Forrest S.; 1991 Mar 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=333801

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DNA amplification of a further exon of Duchenne muscular dystrophy locus increase possibilities for deletion screening. by Speer A, Rosenthal A, Billwitz H, Hanke R, Forrest SM, Love D, Davies KE, Coutelle C.; 1989 Jun 26; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=318056

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Duchenne muscular dystrophy (DMD) gene cDNA 8 PstI and TaqI polymorphisms involve exon 51 of the HindIII map. by Laing NG, Akkari PA, Chandler DC, Thomas HE, Layton MG, Mears ME, Kakulas BA.; 1990 Jul 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=331223

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Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy. by Sander M, Chavoshan B, Harris SA, Iannaccone ST, Stull JT, Thomas GD, Victor RG.; 2000 Dec 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17659

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Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscle. by Haslett JN, Sanoudou D, Kho AT, Bennett RR, Greenberg SA, Kohane IS, Beggs AH, Kunkel LM.; 2002 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137534

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Gene for OTC: characterisation and linkage to Duchenne muscular dystrophy. by Davies KE, Briand P, Ionasescu V, Ionasescu G, Williamson R, Brown C, Cavard C, Cathelineau L.; 1985 Jan 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=340981

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Human X chromosome markers and Duchenne muscular dystrophy. by Davies KE, Speer A, Herrmann F, Spiegler AW, McGlade S, Hofker MH, Briand P, Hanke R, Schwartz M, Steinbicker V, et al.; 1985 May 24; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=341249

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Immunological identification of a high molecular weight protein as a candidate for the product of the Duchenne muscular dystrophy gene. by Kao L, Krstenansky J, Mendell J, Rammohan KW, Gruenstein E.; 1988 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280456

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Isolation of a conserved sequence deleted in Duchenne muscular dystrophy patients. by Smith TJ, Wilson L, Kenwrick SJ, Forrest SM, Speer A, Coutelle C, Davies KE.; 1987 Mar 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=340624

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Linkage analysis of two cloned DNA sequences flanking the Duchenne muscular dystrophy locus on the short arm of the human X chromosome. by Davies KE, Pearson PL, Harper PS, Murray JM, O'Brien T, Sarfarazi M, Williamson R.; 1983 Apr 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=325885

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Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation. by Gussoni E, Bennett RR, Muskiewicz KR, Meyerrose T, Nolta JA, Gilgoff I, Stein J, Chan YM, Lidov HG, Bonnemann CG, von Moers A, Morris GE, den Dunnen JT, Chamberlain JS, Kunkel LM, Weinberg K.; 2002 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151133

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Modulation of Myoblast Fusion by Caveolin-3 in Dystrophic Skeletal Muscle Cells: Implications for Duchenne Muscular Dystrophy and Limb-Girdle Muscular Dystrophy-1C. by Volonte D, Peoples AJ, Galbiati F.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=207001

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MspI RFLP for Duchenne muscular dystrophy cDNA subclone 9. by Wagner M, Reiss J, Hentemann M, Thies U.; 1989 Apr 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=317767

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NO skeletal muscle derived relaxing factor in Duchenne muscular dystrophy. by Bredt DS.; 1998 Dec 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33925

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Non-operative treatment for perforated gastro-duodenal peptic ulcer in Duchenne Muscular Dystrophy: a case report. by Brinkman JM, Oddens JR, Van Royen BJ, Wever J, Olsman JG.; 2004; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=324410

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RFLP for Duchenne muscular dystrophy cDNA clone 30-2. by Walker AP, Bartlett RJ, Laing NG, Siddique T, Yamaoka LH, Chen JC, Hung WY, Roses AD.; 1988 Sep 26; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=338682

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RFLP for Duchenne muscular dystrophy cDNA clone 44-1. by Laing NG, Siddique T, Bartlett RJ, Yamaoka LH, Chen JC, Walker AP, Hung WY, Roses AD.; 1988 Jul 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=338389

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RFLP for HindIII at the Duchenne muscular dystrophy gene. by Prior TW, Friedman KJ, Silverman LM.; 1989 Mar 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=317618

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Social deprivation in Duchenne muscular dystrophy: population based study. by Bushby K, Raybould S, O'Donnell S, Steele JG.; 2001 Nov 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&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 Perkins KJ, Burton EA, Davies KE.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96689

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Two human cDNA molecules coding for the Duchenne muscular dystrophy (DMD) locus are highly homologous. by Rosenthal A, Speer A, Billwitz H, Cross GS, Forrest SM, Davies KE.; 1989 Jul 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=318130

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

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

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following is the type of output you can expect from PubMed for Duchenne muscular dystrophy (hyperlinks lead to article summaries): •

A comparison of the stress and coping strategies between the parents of children with Duchenne muscular dystrophy and children with a fever. Author(s): Chen JY, Chen SS, Jong YJ, Yang YH, Chang YY. Source: Journal of Pediatric Nursing. 2002 October; 17(5): 369-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12395305&dopt=Abstract

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A descriptive epidemiological study of Duchenne muscular dystrophy in childhood in Estonia. Author(s): Talkop UA, Kahre T, Napa A, Talvik I, Soot A, Piirsoo A, Sander V, Talvik T. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 2003; 7(5): 221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14511626&dopt=Abstract

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A new approach to the therapy of Duchenne muscular dystrophy with early precursors of myogenesis. Author(s): Sukhikh GT, Malaitsev VV, Bogdanova IM, Dubrovina IV, Sitnikov VF. Source: Bulletin of Experimental Biology and Medicine. 2001 December; 132(6): 1131-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12152867&dopt=Abstract

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A noninvasive means of detecting preclinical cardiomyopathy in Duchenne muscular dystrophy? Author(s): Towbin JA. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 317-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875770&dopt=Abstract

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Activation of nuclear factor-kappaB in inflammatory myopathies and Duchenne muscular dystrophy. Author(s): Monici MC, Aguennouz M, Mazzeo A, Messina C, Vita G. Source: Neurology. 2003 March 25; 60(6): 993-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654966&dopt=Abstract

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Acute heart failure during spinal surgery in a boy with Duchenne muscular dystrophy. Author(s): Hayes JA, Ames WA. Source: British Journal of Anaesthesia. 2004 January; 92(1): 149; Author Reply 149-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14714277&dopt=Abstract

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Acute heart failure during spinal surgery in a boy with Duchenne muscular dystrophy. Author(s): Schummer W, Schummer C. Source: British Journal of Anaesthesia. 2004 January; 92(1): 149; Author Reply 149-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14665570&dopt=Abstract

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Acute heart failure during spinal surgery in a boy with Duchenne muscular dystrophy. Author(s): Schmidt GN, Burmeister MA, Lilje C, Wappler F, Bischoff P. Source: British Journal of Anaesthesia. 2003 June; 90(6): 800-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765898&dopt=Abstract

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Adequate tidal volume with row-a-boat phenomenon in advanced Duchenne muscular dystrophy. Author(s): Yasuma F, Kato T, Naya M. Source: Chest. 2002 May; 121(5): 1726. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006480&dopt=Abstract

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Advances in Duchenne muscular dystrophy gene therapy. Author(s): van Deutekom JC, van Ommen GJ. Source: Nature Reviews. Genetics. 2003 October; 4(10): 774-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14526374&dopt=Abstract

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Airway nitric oxide in Duchenne muscular dystrophy. Author(s): Straub V, Ratjen F, Amthor H, Voit T, Grasemann H. Source: The Journal of Pediatrics. 2002 July; 141(1): 132-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091865&dopt=Abstract

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Alpha-sarcoglycanopathy previously misdiagnosed as Duchenne muscular dystrophy: implications for current diagnostics and patient care. Author(s): Schara U, Gencik M, Mortier J, Langen M, Gencikova A, Epplen JT, Mortier W. Source: European Journal of Pediatrics. 2001 July; 160(7): 452-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11475588&dopt=Abstract

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Altered regional brain glucose metabolism in Duchenne muscular dystrophy: a pet study. Author(s): Lee JS, Pfund Z, Juhasz C, Behen ME, Muzik O, Chugani DC, Nigro MA, Chugani HT. Source: Muscle & Nerve. 2002 October; 26(4): 506-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362416&dopt=Abstract

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Analysis of dystrophin mRNA from skeletal muscle but not from lymphocytes led to identification of a novel nonsense mutation in a carrier of Duchenne muscular dystrophy. Author(s): Ito T, Takeshima Y, Yagi M, Kamei S, Wada H, Nakamura H, Matsuo M. Source: Journal of Neurology. 2003 May; 250(5): 581-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736738&dopt=Abstract

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Analysis of RFLPs and DNA deletions in the Chinese Duchenne muscular dystrophy gene. Author(s): Zeng YT, Chen MJ, Ren ZR, Qui XK, Huang SZ. Source: Journal of Medical Genetics. 1991 March; 28(3): 167-70. Erratum In: J Med Genet 1991 July; 28(7): 501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1675685&dopt=Abstract

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Antisense-induced multiexon skipping for Duchenne muscular dystrophy makes more sense. Author(s): Aartsma-Rus A, Janson AA, Kaman WE, Bremmer-Bout M, van Ommen GJ, den Dunnen JT, van Deutekom JC. Source: American Journal of Human Genetics. 2004 January; 74(1): 83-92. Epub 2003 December 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14681829&dopt=Abstract

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Are clinical trials of cell transplantation for Duchenne muscular dystrophy ethical? Author(s): Cho MK. Source: Irb. 1994 January-April; 16(1-2): 12-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11652321&dopt=Abstract

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Assessment of cardiac function in adolescents with Duchenne muscular dystrophy: importance of neurohormones. Author(s): Ramaciotti C, Scott WA, Lemler MS, Haverland C, Iannaccone ST. Source: Journal of Child Neurology. 2002 March; 17(3): 191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12026234&dopt=Abstract

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Assessment of locomotor function in young boys with Duchenne muscular dystrophy. Author(s): Smith RA, Newcombe RG, Sibert JR, Harper PS. Source: Muscle & Nerve. 1991 May; 14(5): 462-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1870637&dopt=Abstract

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Augmented synthesis and differential localization of heparan sulfate proteoglycans in Duchenne muscular dystrophy. Author(s): Alvarez K, Fadic R, Brandan E. Source: Journal of Cellular Biochemistry. 2002; 85(4): 703-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11968010&dopt=Abstract

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Basilar artery occlusion in a case of Duchenne muscular dystrophy. Author(s): Matsuishi T, Yano E, Terasawa K, Nonaka I, Ishihara O, Yamaguchi Y, Okudera T. Source: Brain & Development. 1982; 4(5): 379-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7137515&dopt=Abstract

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Becker and Duchenne muscular dystrophy: a comparative morphological study. Author(s): Dennett X, Shield LK, Clingan LJ, Woolley DA. Source: Aust Paediatr J. 1988; 24 Suppl 1: 15-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3202735&dopt=Abstract

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Benign Duchenne muscular dystrophy in a patient with growth hormone deficiency: a five years follow-up. Author(s): Zatz M, Betti RT. Source: American Journal of Medical Genetics. 1986 July; 24(3): 567-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3728575&dopt=Abstract

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Birth and population prevalence of Duchenne muscular dystrophy in The Netherlands. Author(s): van Essen AJ, Busch HF, te Meerman GJ, ten Kate LP. Source: Human Genetics. 1992 January; 88(3): 258-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1733827&dopt=Abstract

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Bladder dysfunction in Duchenne muscular dystrophy. Author(s): MacLeod M, Kelly R, Robb SA, Borzyskowski M. Source: Archives of Disease in Childhood. 2003 April; 88(4): 347-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651768&dopt=Abstract

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Blind evaluation of lymphocyte capping in Duchenne muscular dystrophy. Author(s): Goldsmith BM, Drachman DB, Gruemer HD, Miller WG, Self SS. Source: Neurology. 1984 June; 34(6): 821-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6374498&dopt=Abstract

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Blood loss in Duchenne muscular dystrophy: vascular smooth muscle dysfunction? Author(s): Noordeen MH, Haddad FS, Muntoni F, Gobbi P, Hollyer JS, Bentley G. Source: Journal of Pediatric Orthopaedics. Part B / European Paediatric Orthopaedic Society, Pediatric Orthopaedic Society of North America. 1999 July; 8(3): 212-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10399127&dopt=Abstract

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Body composition and energy expenditure in Duchenne muscular dystrophy. Author(s): Zanardi MC, Tagliabue A, Orcesi S, Berardinelli A, Uggetti C, Pichiecchio A. Source: European Journal of Clinical Nutrition. 2003 February; 57(2): 273-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571659&dopt=Abstract

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Body composition determined with MR in patients with Duchenne muscular dystrophy, spinal muscular atrophy, and normal subjects. Author(s): Leroy-Willig A, Willig TN, Henry-Feugeas MC, Frouin V, Marinier E, Boulier A, Barzic F, Schouman-Claeys E, Syrota A. Source: Magnetic Resonance Imaging. 1997; 15(7): 737-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9309604&dopt=Abstract

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Bone mineral density and bone metabolism in Duchenne muscular dystrophy. Author(s): Bianchi ML, Mazzanti A, Galbiati E, Saraifoger S, Dubini A, Cornelio F, Morandi L. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 September; 14(9): 761-7. Epub 2003 July 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897980&dopt=Abstract

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Bone mineral density and fractures in boys with Duchenne muscular dystrophy. Author(s): Larson CM, Henderson RC. Source: Journal of Pediatric Orthopedics. 2000 January-February; 20(1): 71-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10641693&dopt=Abstract

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Botulinum toxin for amelioration of knee contracture in Duchenne muscular dystrophy. Author(s): von Wendt LO, Autti-Ramo IS. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 1999; 3(4): 175-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10476367&dopt=Abstract

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Brain abnormalities in Duchenne muscular dystrophy: phosphorus-31 magnetic resonance spectroscopy and neuropsychological study. Author(s): Tracey I, Scott RB, Thompson CH, Dunn JF, Barnes PR, Styles P, Kemp GJ, Rae CD, Pike M, Radda GK. Source: Lancet. 1995 May 20; 345(8960): 1260-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7746055&dopt=Abstract

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Brain biochemistry in Duchenne muscular dystrophy: a 1H magnetic resonance and neuropsychological study. Author(s): Rae C, Scott RB, Thompson CH, Dixon RM, Dumughn I, Kemp GJ, Male A, Pike M, Styles P, Radda GK. Source: Journal of the Neurological Sciences. 1998 October 8; 160(2): 148-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9849797&dopt=Abstract

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Brain function in Duchenne muscular dystrophy. Author(s): Anderson JL, Head SI, Rae C, Morley JW. Source: Brain; a Journal of Neurology. 2002 January; 125(Pt 1): 4-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834588&dopt=Abstract

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Brain morphology in Duchenne muscular dystrophy: a Golgi study. Author(s): Jagadha V, Becker LE. Source: Pediatric Neurology. 1988 March-April; 4(2): 87-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3242516&dopt=Abstract

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Branched-chain ketoacids reduce muscle protein degradation in Duchenne muscular dystrophy. Author(s): Stewart PM, Walser M, Drachman DB. Source: Muscle & Nerve. 1982 March; 5(3): 197-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7088016&dopt=Abstract

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Breathing patterns and HbSaO2 changes during nocturnal sleep in patients with Duchenne muscular dystrophy. Author(s): Manni R, Ottolini A, Cerveri I, Bruschi C, Zoia MC, Lanzi G, Tartara A. Source: Journal of Neurology. 1989 October; 236(7): 391-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2809640&dopt=Abstract

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Calcium currents and transients in co-cultured contracting normal and Duchenne muscular dystrophy human myotubes. Author(s): Imbert N, Vandebrouck C, Duport G, Raymond G, Hassoni AA, Constantin B, Cullen MJ, Cognard C. Source: The Journal of Physiology. 2001 July 15; 534(Pt. 2): 343-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454955&dopt=Abstract

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Cardiac involvement of female carrier of Duchenne muscular dystrophy. Author(s): Kamakura K. Source: Intern Med. 2000 January; 39(1): 2-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10674837&dopt=Abstract

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Cardiac transplantation in a Duchenne muscular dystrophy carrier. Author(s): Melacini P, Fanin M, Angelini A, Pegoraro E, Livi U, Danieli GA, Hoffman EP, Thiene G, Dalla Volta S, Angelini C. Source: Neuromuscular Disorders : Nmd. 1998 December; 8(8): 585-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10093066&dopt=Abstract

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Carrier detection and prenatal molecular diagnosis in a Duchenne muscular dystrophy family without any affected relative available. Author(s): Alcantara MA, Garcia-Cavazos R, Hernandez-U E, Gonzalez-del Angel A, Carnevale A, Orozco L. Source: Annales De Genetique. 2001 July-September; 44(3): 149-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694228&dopt=Abstract

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Cause of progression in Duchenne muscular dystrophy: impaired differentiation more probable than replicative aging. Author(s): Oexle K, Kohlschutter A. Source: Neuropediatrics. 2001 June; 32(3): 123-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11521207&dopt=Abstract

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cDNA microarray analysis of individual Duchenne muscular dystrophy patients. Author(s): Noguchi S, Tsukahara T, Fujita M, Kurokawa R, Tachikawa M, Toda T, Tsujimoto A, Arahata K, Nishino I. Source: Human Molecular Genetics. 2003 March 15; 12(6): 595-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620965&dopt=Abstract

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Changes in spirometry over time as a prognostic marker in patients with Duchenne muscular dystrophy. Author(s): Phillips MF, Quinlivan RC, Edwards RH, Calverley PM. Source: American Journal of Respiratory and Critical Care Medicine. 2001 December 15; 164(12): 2191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751186&dopt=Abstract

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Characterisation of dystrophin in carriers of Duchenne muscular dystrophy. Author(s): Clerk A, Rodillo E, Heckmatt JZ, Dubowitz V, Strong PN, Sewry CA. Source: Journal of the Neurological Sciences. 1991 April; 102(2): 197-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2072119&dopt=Abstract

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Clinical and experimental results on cardiac troponin expression in Duchenne muscular dystrophy. Author(s): Hammerer-Lercher A, Erlacher P, Bittner R, Korinthenberg R, Skladal D, Sorichter S, Sperl W, Puschendorf B, Mair J. Source: Clinical Chemistry. 2001 March; 47(3): 451-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11238296&dopt=Abstract

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Clinical implications of maximal respiratory pressure determinations for individuals with Duchenne muscular dystrophy. Author(s): Hahn A, Bach JR, Delaubier A, Renardel-Irani A, Guillou C, Rideau Y. Source: Archives of Physical Medicine and Rehabilitation. 1997 January; 78(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9014949&dopt=Abstract

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Coats' disease and Duchenne muscular dystrophy. Author(s): Bobart A, Brosnahan D. Source: Eye (London, England). 2001 August; 15(Pt 4): 563-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11767047&dopt=Abstract

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Collaborative translational research leading to multicenter clinical trials in Duchenne muscular dystrophy: the Cooperative International Neuromuscular Research Group (CINRG). Author(s): Escolar DM, Henricson EK, Pasquali L, Gorni K, Hoffman EP. Source: Neuromuscular Disorders : Nmd. 2002 October; 12 Suppl 1: S147-154. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206809&dopt=Abstract

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Complete skipping of exon 66 due to novel mutations of the dystrophin gene was identified in two Japanese families of Duchenne muscular dystrophy with severe mental retardation. Author(s): Wibawa T, Takeshima Y, Mitsuyoshi I, Wada H, Surono A, Nakamura H, Matsuo M. Source: Brain & Development. 2000 March; 22(2): 107-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10722962&dopt=Abstract

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Contiguous gene deletion syndrome involving glycerol kinase and Duchenne muscular dystrophy loci. Author(s): Asghar M, Nevin NC, Beattie ED, McManus D, Roberts GM, Phillips JA. Source: Journal of Inherited Metabolic Disease. 1999 December; 22(8): 933-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10604146&dopt=Abstract

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Contrasting evolutionary histories of two introns of the duchenne muscular dystrophy gene, Dmd, in humans. Author(s): Nachman MW, Crowell SL. Source: Genetics. 2000 August; 155(4): 1855-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10924480&dopt=Abstract

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Correlation between progression of spinal deformity and pulmonary function in Duchenne muscular dystrophy. Author(s): Yamashita T, Kanaya K, Yokogushi K, Ishikawa Y, Minami R. Source: Journal of Pediatric Orthopedics. 2001 January-February; 21(1): 113-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11176364&dopt=Abstract

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Correlation of laboratory and clinical findings with the location of Xp21 deletion in Duchenne muscular dystrophy. Author(s): Tasdemir HA, Topaloglu H, Dincer P, Gogus S, Kotiloglu E, Ozdirim E, Yalaz K. Source: Turk J Pediatr. 1997 July-September; 39(3): 317-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9339110&dopt=Abstract

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Correlation of muscle fiber type measurements with clinical and molecular genetic data in Duchenne muscular dystrophy. Author(s): Wang JF, Forst J, Schroder S, Schroder JM. Source: Neuromuscular Disorders : Nmd. 1999 May; 9(3): 150-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382908&dopt=Abstract

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Corticosteroids in Duchenne muscular dystrophy: a reappraisal. Author(s): Wong BL, Christopher C. Source: Journal of Child Neurology. 2002 March; 17(3): 183-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12026233&dopt=Abstract

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Creatine kinase, cell membrane and Duchenne muscular dystrophy. Author(s): Ozawa E, Hagiwara Y, Yoshida M. Source: Molecular and Cellular Biochemistry. 1999 January; 190(1-2): 143-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10098981&dopt=Abstract

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De novo mutations in sporadic deletional Duchenne muscular dystrophy (DMD) cases. Author(s): Mukherjee M, Chaturvedi LS, Srivastava S, Mittal RD, Mittal B. Source: Experimental & Molecular Medicine. 2003 April 30; 35(2): 113-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754415&dopt=Abstract

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Denaturing gradient gel electrophoresis (DGGE) for mutation detection in Duchenne muscular dystrophy (DMD). Author(s): Dolinsky LC. Source: Methods in Molecular Biology (Clifton, N.J.). 2003; 217: 165-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12491931&dopt=Abstract

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Dental characteristics of patients with Duchenne muscular dystrophy. Author(s): Symons AL, Townsend GC, Hughes TE. Source: Asdc J Dent Child. 2002 September-December; 69(3): 277-83, 234. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613312&dopt=Abstract

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Detection of glucocorticoid-like activity in traditional Chinese medicine used for the treatment of Duchenne muscular dystrophy. Author(s): Courdier-Fruh I, Barman L, Wettstein P, Meier T. Source: Neuromuscular Disorders : Nmd. 2003 November; 13(9): 699-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14561491&dopt=Abstract

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Detection of point mutation in dystrophin gene reveals somatic and germline mosaicism in the mother of a patient with Duchenne muscular dystrophy. Author(s): van Essen AJ, Mulder IM, van der Vlies P, van der Hout AH, Buys CH, Hofstra RM, den Dunnen JT. Source: American Journal of Medical Genetics. 2003 April 30; 118A(3): 296-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673664&dopt=Abstract

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Diaphragm kinetics during pneumatic belt respiratory assistance: a sonographic study in Duchenne muscular dystrophy. Author(s): Ayoub J, Milane J, Targhetta R, Prioux J, Chamari K, Arbeille P, Jonquet O, Bourgeois JM, Prefaut C. Source: Neuromuscular Disorders : Nmd. 2002 August; 12(6): 569-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117482&dopt=Abstract

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Direct analysis of amniotic fluid cells by multiplex PCR provides rapid prenatal diagnosis for Duchenne muscular dystrophy. Author(s): Simard LR, Gingras F, Labuda D. Source: Nucleic Acids Research. 1991 May 11; 19(9): 2501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2041789&dopt=Abstract

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Direct deletion analysis in two Duchenne muscular dystrophy symptomatic females using polymorphic dinucleotide (CA)n loci within the dystrophin gene. Author(s): Giliberto F, Ferreiro V, Dalamon V, Surace E, Cotignola J, Esperante S, Borelina D, Baranzini S, Szijan I. Source: J Biochem Mol Biol. 2003 March 31; 36(2): 179-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12689516&dopt=Abstract

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Direct PCR from CVS and blood lysates for detection of cystic fibrosis and Duchenne muscular dystrophy deletions. Author(s): Balnaves ME, Nasioulas S, Dahl HH, Forrest S. Source: Nucleic Acids Research. 1991 March 11; 19(5): 1155. Erratum In: Nucleic Acids Res 1991 May 11; 19(9): 2537. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2020553&dopt=Abstract

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Domiciliary investigation of sleep-related hypoxaemia in Duchenne muscular dystrophy. Author(s): Carroll N, Bain RJ, Smith PE, Saltissi S, Edwards RH, Calverley PM. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1991 April; 4(4): 434-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1855572&dopt=Abstract

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Dose-dependent effect of individualized respiratory muscle training in children with Duchenne muscular dystrophy. Author(s): Topin N, Matecki S, Le Bris S, Rivier F, Echenne B, Prefaut C, Ramonatxo M. Source: Neuromuscular Disorders : Nmd. 2002 August; 12(6): 576-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117483&dopt=Abstract

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Duchenne muscular dystrophy in a female child. Author(s): Viswanathan V. Source: Indian Pediatrics. 2002 October; 39(10): 980-1; Author Reply 981. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428052&dopt=Abstract

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Duchenne muscular dystrophy. Author(s): Metules T. Source: Rn. 2002 October; 65(10): 39-44, 47; Quiz 48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432710&dopt=Abstract

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Duchenne muscular dystrophy: current knowledge, treatment, and future prospects. Author(s): Biggar WD, Klamut HJ, Demacio PC, Stevens DJ, Ray PN. Source: Clinical Orthopaedics and Related Research. 2002 August; (401): 88-106. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151886&dopt=Abstract

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Duchenne muscular dystrophy: hopes for the sesquicentenary. Author(s): Byrne E, Kornberg AJ, Kapsa R. Source: The Medical Journal of Australia. 2003 November 3; 179(9): 463-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14583075&dopt=Abstract

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Duchenne muscular dystrophy: prolongation of life by noninvasive ventilation and mechanically assisted coughing. Author(s): Gomez-Merino E, Bach JR. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2002 June; 81(6): 411-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12023596&dopt=Abstract

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Duchenne muscular dystrophy--a molecular service. Author(s): Ballo R, Hitzeroth HW, Beighton PH. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1991 February 16; 79(4): 209-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1671720&dopt=Abstract

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Duchenne muscular dystrophy--parental perceptions. Author(s): Bothwell JE, Dooley JM, Gordon KE, MacAuley A, Camfield PR, MacSween J. Source: Clinical Pediatrics. 2002 March; 41(2): 105-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11931326&dopt=Abstract

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Duchenne muscular dystrophy-rhabdomyosarcoma, ichthyosis vulgaris/acute monoblastic leukemia: association of rare genetic disorders and childhood malignant diseases. Author(s): Jakab Z, Szegedi I, Balogh E, Kiss C, Olah E. Source: Medical and Pediatric Oncology. 2002 July; 39(1): 66-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116087&dopt=Abstract

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Dystrophin gene deletions in South Indian Duchenne muscular dystrophy patients. Author(s): Mallikarjuna Rao GN, Hussain T, Geetha Devi N, Jain S, Chandak GR, Ananda Raj MP. Source: Indian Journal of Medical Sciences. 2003 January; 57(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14514278&dopt=Abstract

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Early decrease of IIx myosin heavy chain transcripts in Duchenne muscular dystrophy. Author(s): Pedemonte M, Sandri C, Schiaffino S, Minetti C. Source: Biochemical and Biophysical Research Communications. 1999 February 16; 255(2): 466-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10049732&dopt=Abstract

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Early diagnosis in Duchenne muscular dystrophy. Author(s): Zalaudek I, Bonelli RM, Koltringer P, Reisecker F, Wagner K. Source: Lancet. 1999 June 5; 353(9168): 1975. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10371601&dopt=Abstract

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Early diagnosis of Duchenne muscular dystrophy with high level of transaminases. Author(s): Kurul S, Ulgenalp A, Dirik E, Ercal D. Source: Indian Pediatrics. 2002 February; 39(2): 210-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11867860&dopt=Abstract

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Early diagnosis of Duchenne muscular dystrophy. Author(s): Appleton RE, Nicolaides P. Source: Lancet. 1995 May 13; 345(8959): 1243-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7739330&dopt=Abstract

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Early prednisone treatment in Duchenne muscular dystrophy. Author(s): Merlini L, Cicognani A, Malaspina E, Gennari M, Gnudi S, Talim B, Franzoni E. Source: Muscle & Nerve. 2003 February; 27(2): 222-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548530&dopt=Abstract

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Early symptoms of Duchenne muscular dystrophy--description of cases of an 18month-old and an 8-year-old patient. Author(s): Iwanczak F, Stawarski A, Potyrala M, Siedlecka-Dawidko J, Agrawal GS. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2000 May-June; 6(3): 592-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11208376&dopt=Abstract

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Early treatment to preserve quality of locomotion for children with Duchenne muscular dystrophy. Author(s): Rideau Y, Duport G, Delaubier A, Guillou C, Renardel-Irani A, Bach JR. Source: Seminars in Neurology. 1995 March; 15(1): 9-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7638464&dopt=Abstract

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Effect of spinal surgery on lung function in Duchenne muscular dystrophy. Author(s): Kennedy JD, Staples AJ, Brook PD, Parsons DW, Sutherland AD, Martin AJ, Stern LM, Foster BK. Source: Thorax. 1995 November; 50(11): 1173-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8553273&dopt=Abstract

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Effects of deflazacort on left ventricular function in patients with Duchenne muscular dystrophy. Author(s): Silversides CK, Webb GD, Harris VA, Biggar DW. Source: The American Journal of Cardiology. 2003 March 15; 91(6): 769-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633823&dopt=Abstract

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Elevated basic fibroblast growth factor in the serum of patients with Duchenne muscular dystrophy. Author(s): D'Amore PA, Brown RH Jr, Ku PT, Hoffman EP, Watanabe H, Arahata K, Ishihara T, Folkman J. Source: Annals of Neurology. 1994 March; 35(3): 362-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8122890&dopt=Abstract

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Enhanced urinary spontaneous luminescence in Duchenne muscular dystrophy. Author(s): Reyes J, Salim-Hanna M, Lissi EA, Videla LA, Holmgren J. Source: Free Radical Biology & Medicine. 1994 June; 16(6): 851-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8070691&dopt=Abstract

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ERG phenotype of a dystrophin mutation in heterozygous female carriers of Duchenne muscular dystrophy. Author(s): Fitzgerald KM, Cibis GW, Gettel AH, Rinaldi R, Harris DJ, White RA. Source: Journal of Medical Genetics. 1999 April; 36(4): 316-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10227401&dopt=Abstract

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Establishment of long-term myogenic cultures from patients with Duchenne muscular dystrophy by retroviral transduction of a temperature-sensitive SV40 large T antigen. Author(s): Simon LV, Beauchamp JR, O'Hare M, Olsen I. Source: Experimental Cell Research. 1996 May 1; 224(2): 264-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8612703&dopt=Abstract

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Evaluation of a program for long-term treatment of Duchenne muscular dystrophy. Experience at the University Hospitals of Cleveland. Author(s): Vignos PJ, Wagner MB, Karlinchak B, Katirji B. Source: The Journal of Bone and Joint Surgery. American Volume. 1996 December; 78(12): 1844-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8986661&dopt=Abstract

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Evaluation of microchip electrophoresis as a molecular diagnostic method for Duchenne muscular dystrophy. Author(s): Ferrance J, Snow K, Landers JP. Source: Clinical Chemistry. 2002 February; 48(2): 380-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11805028&dopt=Abstract

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Examination of telomere lengths in muscle tissue casts doubt on replicative aging as cause of progression in Duchenne muscular dystrophy. Author(s): Oexle K, Zwirner A, Freudenberg K, Kohlschutter A, Speer A. Source: Pediatric Research. 1997 August; 42(2): 226-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9262227&dopt=Abstract

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Expression and localization of protein inhibitor of neuronal nitric oxide synthase in Duchenne muscular dystrophy. Author(s): Guo Y, Petrof BJ, Hussain SN. Source: Muscle & Nerve. 2001 November; 24(11): 1468-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745948&dopt=Abstract

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Expression of dystrophin-associated glycoproteins and utrophin in carriers of Duchenne muscular dystrophy. Author(s): Sewry CA, Matsumura K, Campbell KP, Dubowitz V. Source: Neuromuscular Disorders : Nmd. 1994 September-November; 4(5-6): 401-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7881285&dopt=Abstract

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Expression of heat-shock/stress proteins in Duchenne muscular dystrophy. Author(s): Bornman L, Polla BS, Lotz BP, Gericke GS. Source: Muscle & Nerve. 1995 January; 18(1): 23-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7799995&dopt=Abstract

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Expression of human full-length and minidystrophin in transgenic mdx mice: implications for gene therapy of Duchenne muscular dystrophy. Author(s): Wells DJ, Wells KE, Asante EA, Turner G, Sunada Y, Campbell KP, Walsh FS, Dickson G. Source: Human Molecular Genetics. 1995 August; 4(8): 1245-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7581360&dopt=Abstract

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Failure of early diagnosis in symptomatic Duchenne muscular dystrophy. Author(s): Bushby KM, Hill A, Steele JG. Source: Lancet. 1999 February 13; 353(9152): 557-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10028989&dopt=Abstract

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Failure to thrive in Duchenne muscular dystrophy. Author(s): Call G, Ziter FA. Source: The Journal of Pediatrics. 1985 June; 106(6): 939-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3998951&dopt=Abstract

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Fast muscle fibers are preferentially affected in Duchenne muscular dystrophy. Author(s): Webster C, Silberstein L, Hays AP, Blau HM. Source: Cell. 1988 February 26; 52(4): 503-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3342447&dopt=Abstract

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Fatal air embolism in an adolescent with Duchenne muscular dystrophy during Harrington instrumentation. Author(s): Lang SA, Duncan PG, Dupuis PR. Source: Anesthesia and Analgesia. 1989 July; 69(1): 132-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2742178&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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Female carriers of Duchenne muscular dystrophy: a dilemma. Author(s): Isaacs H, Badenhorst M. Source: Clinical Genetics. 1987 May; 31(5): 288-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3608214&dopt=Abstract

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Fetal muscle biopsy as a diagnostic tool in Duchenne muscular dystrophy. Author(s): Nevo Y, Shomrat R, Yaron Y, Orr-Urtreger A, Harel S, Legum C. Source: Prenatal Diagnosis. 1999 October; 19(10): 921-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10521816&dopt=Abstract

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First meeting of the Duchenne Parent Project in Europe: Treatment of Duchenne Muscular Dystrophy. 7-8 November 1997, Rotterdam, The Netherlands. Author(s): Scheuerbrandt G. Source: Neuromuscular Disorders : Nmd. 1998 May; 8(3-4): 213-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9631405&dopt=Abstract

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Force plate studies of Duchenne muscular dystrophy. Author(s): Khodadadeh S, McClelland M, Patrick JH. Source: Eng Med. 1987 July; 16(3): 177-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3678573&dopt=Abstract

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Four novel dystrophin point mutations: detection by protein truncation test and transcript analysis in lymphocytes from Duchenne muscular dystrophy patients. Author(s): Tuffery S, Bareil C, Demaille J, Claustres M. Source: European Journal of Human Genetics : Ejhg. 1996; 4(3): 143-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8840114&dopt=Abstract

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Fracture prevalence in Duchenne muscular dystrophy. Author(s): McDonald DG, Kinali M, Gallagher AC, Mercuri E, Muntoni F, Roper H, Jardine P, Jones DH, Pike MG. Source: Developmental Medicine and Child Neurology. 2002 October; 44(10): 695-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418795&dopt=Abstract

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Fractures in Duchenne muscular dystrophy--chiefly about their causes. Author(s): Hatano E, Masuda K, Kameo H. Source: Hiroshima J Med Sci. 1986 December; 35(4): 429-33. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3570852&dopt=Abstract

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Frameshift deletions of exons 3-7 and revertant fibers in Duchenne muscular dystrophy: mechanisms of dystrophin production. Author(s): Winnard AV, Mendell JR, Prior TW, Florence J, Burghes AH. Source: American Journal of Human Genetics. 1995 January; 56(1): 158-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7825572&dopt=Abstract

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Frameshift duplication resulting in truncated dystrophin in a patient with Duchenne muscular dystrophy. Author(s): Hu X, Bulman DE, Ray PN, Worton RG. Source: Human Mutation. 1992; 1(2): 172-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1301205&dopt=Abstract

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Free cytoplasmic Ca++ at rest and after cholinergic stimulus is increased in cultured muscle cells from Duchenne muscular dystrophy patients. Author(s): Mongini T, Ghigo D, Doriguzzi C, Bussolino F, Pescarmona G, Pollo B, Schiffer D, Bosia A. Source: Neurology. 1988 March; 38(3): 476-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3347352&dopt=Abstract

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Freeze-fracture analysis of plasma membranes in Duchenne muscular dystrophy. A study using cultured skin fibroblasts. Author(s): Jones GE, Severs NJ, Witkowski JA. Source: Journal of the Neurological Sciences. 1983 February; 58(2): 185-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6300339&dopt=Abstract

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Frequency and distribution of deletions in dystrophin gene in Duchenne muscular dystrophy patients from an east-European Slavonic population. Author(s): Kadasi L, Gecz J, Saksova L. Source: Gene Geogr. 1991 December; 5(3): 137-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1841599&dopt=Abstract

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Functional involvement of cerebral cortex in Duchenne muscular dystrophy. Author(s): Di Lazzaro V, Restuccia D, Servidei S, Nardone R, Oliviero A, Profice P, Mangiola F, Tonali P, Rothwell JC. Source: Muscle & Nerve. 1998 May; 21(5): 662-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9572251&dopt=Abstract

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Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy. Author(s): Sander M, Chavoshan B, Harris SA, Iannaccone ST, Stull JT, Thomas GD, Victor RG. Source: Proceedings of the National Academy of Sciences of the United States of America. 2000 December 5; 97(25): 13818-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11087833&dopt=Abstract

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Functional significance of dystrophin positive fibres in Duchenne muscular dystrophy. Author(s): Nicholson LV, Johnson MA, Bushby KM, Gardner-Medwin D. Source: Archives of Disease in Childhood. 1993 May; 68(5): 632-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8323331&dopt=Abstract

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Gait and posture changes in the Duchenne muscular dystrophy child. Author(s): Hsu JD, Furumasu J. Source: Clinical Orthopaedics and Related Research. 1993 March; (288): 122-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8458124&dopt=Abstract

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Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscle. Author(s): Haslett JN, Sanoudou D, Kho AT, Bennett RR, Greenberg SA, Kohane IS, Beggs AH, Kunkel LM. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 November 12; 99(23): 15000-5. Epub 2002 Nov 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415109&dopt=Abstract

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Gene expression profiling of Duchenne muscular dystrophy skeletal muscle. Author(s): Haslett JN, Sanoudou D, Kho AT, Han M, Bennett RR, Kohane IS, Beggs AH, Kunkel LM. Source: Neurogenetics. 2003 August; 4(4): 163-71. Epub 2003 April 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698323&dopt=Abstract

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Gene therapy in Duchenne muscular dystrophy. Author(s): Inui K, Okada S, Dickson G. Source: Brain & Development. 1996 September-October; 18(5): 357-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8891229&dopt=Abstract

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Gene therapy in man and mice: adenosine deaminase deficiency, ornithine transcarbamylase deficiency, and Duchenne muscular dystrophy. Author(s): Grompe M, Mitani K, Lee CC, Jones SN, Caskey CT. Source: Advances in Experimental Medicine and Biology. 1991; 309B: 51-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1781405&dopt=Abstract

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Gene therapy of Duchenne muscular dystrophy. Author(s): Fassati A, Murphy S, Dickson G. Source: Adv Genet. 1997; 35: 117-53. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9348647&dopt=Abstract

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Gene therapy prospects for Duchenne muscular dystrophy. Author(s): Clemens PR, Caskey CT. Source: European Neurology. 1994; 34(4): 181-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8082675&dopt=Abstract

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Gene-deletion and carrier detections, and prenatal diagnosis of Duchenne muscular dystrophy by analysis of the dystrophin gene amplified by polymerase chain reaction. Author(s): Fujishita S, Shibuya N, Niikawa N, Nagataki S. Source: Jinrui Idengaku Zasshi. 1991 December; 36(4): 317-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1811098&dopt=Abstract

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Genetic and biochemical normalization in female carriers of Duchenne muscular dystrophy: evidence for failure of dystrophin production in dystrophin-competent myonuclei. Author(s): Pegoraro E, Schimke RN, Garcia C, Stern H, Cadaldini M, Angelini C, Barbosa E, Carroll J, Marks WA, Neville HE. Source: Neurology. 1995 April; 45(4): 677-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7723955&dopt=Abstract

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Genetic counseling for childless women at risk for Duchenne muscular dystrophy. Author(s): Eggers S, Pavanello RC, Passos-Bueno MR, Zatz M. Source: American Journal of Medical Genetics. 1999 October 29; 86(5): 447-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10508987&dopt=Abstract

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Genetic counseling of isolated carriers of Duchenne muscular dystrophy. Author(s): Hoffman EP, Pegoraro E, Scacheri P, Burns RG, Taber JW, Weiss L, Spiro A, Blattner P. Source: American Journal of Medical Genetics. 1996 June 28; 63(4): 573-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8826437&dopt=Abstract

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Genetic risk: women's understanding of carrier risks in Duchenne muscular dystrophy. Author(s): Parsons EP, Clarke AJ. Source: Journal of Medical Genetics. 1993 July; 30(7): 562-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8411028&dopt=Abstract

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Genotype and electroretinal heterogeneity in Duchenne muscular dystrophy. Author(s): Ino-ue M, Honda S, Nishio H, Matsuo M, Nakamura H, Yamamoto M. Source: Experimental Eye Research. 1997 December; 65(6): 861-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9441711&dopt=Abstract

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Germinal mosaicism from grand-paternal origin in a family with Duchenne muscular dystrophy. Author(s): Claustres M, Kjellberg P, Desgeorges M, Bellet H, Demaille J. Source: Human Genetics. 1990 December; 86(2): 241-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1979959&dopt=Abstract

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Germinal mosaicism in a Duchenne muscular dystrophy family: implications for genetic counselling. Author(s): Melis MA, Cau M, Congiu R, Puddu R, Muntoni F, Cao A. Source: Clinical Genetics. 1993 May; 43(5): 247-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8375105&dopt=Abstract

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Germinal mosaicism in Duchenne muscular dystrophy. Author(s): Wood S, McGillivray BC. Source: Human Genetics. 1988 March; 78(3): 282-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3346017&dopt=Abstract

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Germinal mosaicism increases the recurrence risk for 'new' Duchenne muscular dystrophy mutations. Author(s): Bakker E, Veenema H, Den Dunnen JT, van Broeckhoven C, Grootscholten PM, Bonten EJ, van Ommen GJ, Pearson PL. Source: Journal of Medical Genetics. 1989 September; 26(9): 553-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2810338&dopt=Abstract

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Germline and somatic mosaicism in a female carrier of Duchenne muscular dystrophy. Author(s): Bunyan DJ, Robinson DO, Collins AL, Cockwell AE, Bullman HM, Whittaker PA. Source: Human Genetics. 1994 May; 93(5): 541-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8168831&dopt=Abstract

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Glucose, free fatty acid and ketone body metabolism in Duchenne muscular dystrophy. Author(s): Nishio H, Wada H, Matsuo T, Horikawa H, Takahashi K, Nakajima T, Matsuo M, Nakamura H. Source: Brain & Development. 1990; 12(4): 390-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2240459&dopt=Abstract

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Glutathione depletion during experimental damage to rat skeletal muscle and its relevance to Duchenne muscular dystrophy. Author(s): Jackson MJ, Brooke MH, Kaiser K, Edwards RH. Source: Clinical Science (London, England : 1979). 1991 June; 80(6): 559-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1647917&dopt=Abstract

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Head circumference and intellectual performance of patients with Duchenne muscular dystrophy. Author(s): Appleton RE, Bushby K, Gardner-Medwin D, Welch J, Kelly PJ. Source: Developmental Medicine and Child Neurology. 1991 October; 33(10): 884-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1743411&dopt=Abstract

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Height and clinical course of Duchenne muscular dystrophy. Author(s): Coakley JH, Griffiths RD, Edwards RH. Source: American Journal of Medical Genetics. 1989 April; 32(4): 552-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2774003&dopt=Abstract

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High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy. Author(s): Connolly AM, Schierbecker J, Renna R, Florence J. Source: Neuromuscular Disorders : Nmd. 2002 December; 12(10): 917-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467746&dopt=Abstract

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High-resolution banding study of an X/4 translocation in a female with Duchenne muscular dystrophy. Author(s): Saito F, Tonomura A, Kimura S, Misugi N, Sugita H. Source: Human Genetics. 1985; 71(4): 370-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4077054&dopt=Abstract

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Hip subluxation and dislocation in Duchenne muscular dystrophy. Author(s): Chan KG, Galasko CS, Delaney C. Source: Journal of Pediatric Orthopaedics. Part B / European Paediatric Orthopaedic Society, Pediatric Orthopaedic Society of North America. 2001 July; 10(3): 219-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11497366&dopt=Abstract

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Histochemical fibre typing and ultrastructure of the small fibres in Duchenne muscular dystrophy. Author(s): Watkins SC, Cullen MJ. Source: Neuropathology and Applied Neurobiology. 1985 November-December; 11(6): 447-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2936970&dopt=Abstract

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HLA phenotypes in children with Duchenne muscular dystrophy and their gene carrier mothers. Author(s): Laszlo A, Kaiser G. Source: Acta Paediatr Hung. 1983; 24(4): 323-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6608950&dopt=Abstract

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HLA-A & HLA-B antigens in multiple sclerosis, motor neuron disease & Duchenne muscular dystrophy. Author(s): Mehta MM, Chablani UA, Contractor NM, Bhatia HM, Singhal BS, Mondkar VP, Desai AD. Source: The Indian Journal of Medical Research. 1986 May; 83: 519-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3733208&dopt=Abstract

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Hot spot of recombination within DXS164 in the Duchenne muscular dystrophy gene. Author(s): Grimm T, Muller B, Dreier M, Kind E, Bettecken T, Meng G, Muller CR. Source: American Journal of Human Genetics. 1989 September; 45(3): 368-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2570527&dopt=Abstract

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Human molecular genetics and the elucidation of the primary biochemical defect in Duchenne muscular dystrophy. Author(s): Hoffman EP. Source: Cell Motility and the Cytoskeleton. 1989; 14(1): 163-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2684423&dopt=Abstract

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Human ornithine transcarbamylase locus mapped to band Xp21.1 near the Duchenne muscular dystrophy locus. Author(s): Lindgren V, de Martinville B, Horwich AL, Rosenberg LE, Francke U. Source: Science. 1984 November 9; 226(4675): 698-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6494904&dopt=Abstract

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Human X chromosome markers and Duchenne muscular dystrophy. Author(s): Davies KE, Speer A, Herrmann F, Spiegler AW, McGlade S, Hofker MH, Briand P, Hanke R, Schwartz M, Steinbicker V, et al. Source: Nucleic Acids Research. 1985 May 24; 13(10): 3419-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3859837&dopt=Abstract

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Hypercapnia in relation to pulmonary function in Duchenne muscular dystrophy. Author(s): Canny GJ, Szeinberg A, Koreska J, Levison H. Source: Pediatric Pulmonology. 1989; 6(3): 169-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2497432&dopt=Abstract

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Hyperkalaemic cardiac arrest in a manifesting carrier of Duchenne muscular dystrophy following general anaesthesia. Author(s): Kerr TP, Duward A, Hodgson SV, Hughes E, Robb SA. Source: European Journal of Pediatrics. 2001 September; 160(9): 579-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585084&dopt=Abstract

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Hyperproliferation of synapses on spinal motor neurons of Duchenne muscular dystrophy and myotonic dystrophy patients. Author(s): Nagao M, Kato S, Hayashi H, Misawa H. Source: Acta Neuropathologica. 2003 December; 106(6): 557-60. Epub 2003 August 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12920538&dopt=Abstract

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Hypersensitivity to DNA-damaging agents in abiotrophies: a new explanation for degeneration of neurons, photoreceptors, and muscle in Alzheimer, Parkinson and Huntington diseases, retinitis pigmentosa, and Duchenne muscular dystrophy. Author(s): Robbins JH, Brumback RA, Polinsky RJ, Wirtschafter JD, Tarone RE, Scudiero DA, Otsuka F. Source: Basic Life Sci. 1985; 35: 315-44. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2933027&dopt=Abstract

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Hypersensitivity to DNA-damaging agents in cultured cells from patients with Usher's syndrome and Duchenne muscular dystrophy. Author(s): Robbins JH, Scudiero DA, Otsuka F, Tarone RE, Brumback RA, Wirtschafter JD, Polinsky RJ, Barrett SF, Moshell AN, Scarpinato RG, et al. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1984 April; 47(4): 391-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6726265&dopt=Abstract

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Hypokalemia complicating Duchenne muscular dystrophy. Author(s): McDonald B, Rosenthal SA. Source: Yale J Biol Med. 1987 September-October; 60(5): 405-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3424874&dopt=Abstract

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Hypoosmotic shocks induce elevation of resting calcium level in Duchenne muscular dystrophy myotubes contracting in vitro. Author(s): Imbert N, Vandebrouck C, Constantin B, Duport G, Guillou C, Cognard C, Raymond G. Source: Neuromuscular Disorders : Nmd. 1996 October; 6(5): 351-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8938699&dopt=Abstract

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Hypoxemia during sleep in Duchenne muscular dystrophy. Author(s): Smith PE, Calverley PM, Edwards RH. Source: Am Rev Respir Dis. 1988 April; 137(4): 884-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3354996&dopt=Abstract

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Identification and quantification of somatic mosaicism for a point mutation in a Duchenne muscular dystrophy family. Author(s): Smith TA, Yau SC, Bobrow M, Abbs SJ. Source: Journal of Medical Genetics. 1999 April; 36(4): 313-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10227400&dopt=Abstract

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Identification of altered gene expression in skeletal muscles from Duchenne muscular dystrophy patients. Author(s): Tkatchenko AV, Pietu G, Cros N, Gannoun-Zaki L, Auffray C, Leger JJ, Dechesne CA. Source: Neuromuscular Disorders : Nmd. 2001 April; 11(3): 269-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11297942&dopt=Abstract

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Immune responses to dystropin: implications for gene therapy of Duchenne muscular dystrophy. Author(s): Ferrer A, Wells KE, Wells DJ. Source: Gene Therapy. 2000 September; 7(17): 1439-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11001363&dopt=Abstract

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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): Hoshino S, Ohkoshi N, Watanabe M, Shoji S. Source: Neuromuscular Disorders : Nmd. 2000 August; 10(6): 425-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10899449&dopt=Abstract

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Immunological hurdles in the path to gene therapy for Duchenne muscular dystrophy. Author(s): Wells DJ, Ferrer A, Wells KE. Source: Expert Reviews in Molecular Medicine [electronic Resource]. 2002 November 4; 2002: 1-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14585159&dopt=Abstract

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Impact of nasal ventilation on survival in hypercapnic Duchenne muscular dystrophy. Author(s): Simonds AK, Muntoni F, Heather S, Fielding S. Source: Thorax. 1998 November; 53(11): 949-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10193393&dopt=Abstract

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Impairment of cardiac autonomic function in patients with Duchenne muscular dystrophy: relationship to myocardial and respiratory function. Author(s): Lanza GA, Dello Russo A, Giglio V, De Luca L, Messano L, Santini C, Ricci E, Damiani A, Fumagalli G, De Martino G, Mangiola F, Bellocci F. Source: American Heart Journal. 2001 May; 141(5): 808-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11320370&dopt=Abstract

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In situ measurements of muscle fiber conduction velocity in Duchenne muscular dystrophy. Author(s): Al-Ani FS, Hamdan FB, Shaikhly KI. Source: Saudi Med J. 2001 March; 22(3): 259-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11307114&dopt=Abstract

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In utero fetal muscle biopsy in the diagnosis of Duchenne muscular dystrophy. Author(s): Ladwig D, Mowat D, Tobias V, Taylor PJ, Buckley MF, McNally G, Challis D. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2002 February; 42(1): 79-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926646&dopt=Abstract

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In utero fetal muscle biopsy: a precious aid for the prenatal diagnosis of Duchenne muscular dystrophy. Author(s): Heckel S, Favre R, Flori J, Koenig M, Mandel J, Gasser B, Chaigne D. Source: Fetal Diagnosis and Therapy. 1999 May-June; 14(3): 127-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10364661&dopt=Abstract

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Incidence of cerebral infarction in Duchenne muscular dystrophy. Author(s): Hanajima R, Kawai M. Source: Muscle & Nerve. 1996 July; 19(7): 928. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8965857&dopt=Abstract

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Increase in fetal breech presentation in female carriers of Duchenne muscular dystrophy. Author(s): Geifman-Holtzman O, Bernstein IM, Capeless EL, Hawley P, Specht LA, Bianchi DW. Source: American Journal of Medical Genetics. 1997 December 19; 73(3): 276-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9415684&dopt=Abstract

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Increased acetylcholine sensitivity in Duchenne muscular dystrophy myotubes. Author(s): Meola G, Mancinelli E, Geremia L, Scarlato G. Source: Italian Journal of Neurological Sciences. 1991 April; 12(2): 181-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2071364&dopt=Abstract

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Increased cerebral choline-compounds in Duchenne muscular dystrophy. Author(s): Kato T, Nishina M, Matsushita K, Hori E, Akaboshi S, Takashima S. Source: Neuroreport. 1997 April 14; 8(6): 1435-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9172149&dopt=Abstract

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Increased expression of IGF-binding protein-5 in Duchenne muscular dystrophy (DMD) fibroblasts correlates with the fibroblast-induced downregulation of DMD myoblast growth: an in vitro analysis. Author(s): Melone MA, Peluso G, Galderisi U, Petillo O, Cotrufo R. Source: Journal of Cellular Physiology. 2000 October; 185(1): 143-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10942528&dopt=Abstract

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Increased number of caveolae and caveolin-3 overexpression in Duchenne muscular dystrophy. Author(s): Repetto S, Bado M, Broda P, Lucania G, Masetti E, Sotgia F, Carbone I, Pavan A, Bonilla E, Cordone G, Lisanti MP, Minetti C. Source: Biochemical and Biophysical Research Communications. 1999 August 11; 261(3): 547-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10441463&dopt=Abstract

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Indicators of need for mechanical ventilation in Duchenne muscular dystrophy and spinal muscular atrophy. Author(s): Lyager S, Steffensen B, Juhl B. Source: Chest. 1995 September; 108(3): 779-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7656633&dopt=Abstract

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Inspiratory flow reserve in boys with Duchenne muscular dystrophy. Author(s): De Bruin PF, Ueki J, Bush A, Y Manzur A, Watson A, Pride NB. Source: Pediatric Pulmonology. 2001 June; 31(6): 451-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11389578&dopt=Abstract

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Intelligence and Duchenne muscular dystrophy: full-scale, verbal, and performance intelligence quotients. Author(s): Cotton S, Voudouris NJ, Greenwood KM. Source: Developmental Medicine and Child Neurology. 2001 July; 43(7): 497-501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11463183&dopt=Abstract

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Is glutamine a 'conditionally essential' amino acid in Duchenne muscular dystrophy? Author(s): Hankard R, Mauras N, Hammond D, Haymond M, Darmaun D. Source: Clinical Nutrition (Edinburgh, Lothian). 1999 December; 18(6): 365-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10634922&dopt=Abstract

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Knee moments in Duchenne muscular dystrophy. Author(s): Siegel IM. Source: Lancet. 1986 October 25; 2(8513): 977-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2877155&dopt=Abstract

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Knee moments in Duchenne muscular dystrophy. Author(s): Khodadadeh S, McClelland MR, Patrick JH, Edwards RH, Evans GA. Source: Lancet. 1986 September 6; 2(8506): 544-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2875283&dopt=Abstract

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Learning and transfer in two perceptual-motor skills in Duchenne muscular dystrophy. Author(s): Nakafuji A, Tsuji K. Source: Percept Mot Skills. 2001 October; 93(2): 339-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11769887&dopt=Abstract

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Lightweight, modular knee-ankle-foot orthosis for Duchenne muscular dystrophy: design, development, and evaluation. Author(s): Taktak DM, Bowker P. Source: Archives of Physical Medicine and Rehabilitation. 1995 December; 76(12): 115662. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8540794&dopt=Abstract

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Localisation and characterisation of dystrophin in the central nervous system of controls and patients with Duchenne muscular dystrophy. Author(s): Uchino M, Teramoto H, Naoe H, Yoshioka K, Miike T, Ando M. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1994 April; 57(4): 426-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8163990&dopt=Abstract

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Longitudinal data analysis: an application to construction of a natural history profile of Duchenne muscular dystrophy. Author(s): Hyde SA, Steffensen BF, Floytrup I, Glent S, Kroksmark AK, Salling B, Werlauff U, Erlandsen M. Source: Neuromuscular Disorders : Nmd. 2001 March; 11(2): 165-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11257473&dopt=Abstract

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Longitudinal study of spinal deformity in Duchenne muscular dystrophy. Author(s): Oda T, Shimizu N, Yonenobu K, Ono K, Nabeshima T, Kyoh S. Source: Journal of Pediatric Orthopedics. 1993 July-August; 13(4): 478-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8370781&dopt=Abstract

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Long-term follow-up of patients with Duchenne muscular dystrophy receiving ventilatory support. Author(s): Fukunaga H, Okubo R, Moritoyo T, Kawashima N, Osame M. Source: Muscle & Nerve. 1993 May; 16(5): 554-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8515763&dopt=Abstract

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Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation. Author(s): Gussoni E, Bennett RR, Muskiewicz KR, Meyerrose T, Nolta JA, Gilgoff I, Stein J, Chan YM, Lidov HG, Bonnemann CG, Von Moers A, Morris GE, Den Dunnen JT, Chamberlain JS, Kunkel LM, Weinberg K. Source: The Journal of Clinical Investigation. 2002 September; 110(6): 807-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12235112&dopt=Abstract

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Long-term results of spine surgery in Duchenne muscular dystrophy. Author(s): Granata C, Merlini L, Cervellati S, Ballestrazzi A, Giannini S, Corbascio M, Lari S. Source: Neuromuscular Disorders : Nmd. 1996 January; 6(1): 61-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8845720&dopt=Abstract

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Long-term ventilation for patients with Duchenne muscular dystrophy : physicians' beliefs and practices. Author(s): Gibson B. Source: Chest. 2001 March; 119(3): 940-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11243978&dopt=Abstract

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Looking under every rock: Duchenne muscular dystrophy and traditional Chinese medicine. Author(s): Urtizberea JA, Fan QS, Vroom E, Recan D, Kaplan JC. Source: Neuromuscular Disorders : Nmd. 2003 November; 13(9): 705-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14561492&dopt=Abstract

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Loss of a single amino acid from dystrophin resulting in Duchenne muscular dystrophy with retention of dystrophin protein. Author(s): Becker K, Robb SA, Hatton Z, Yau SC, Abbs S, Roberts RG. Source: Human Mutation. 2003 June; 21(6): 651. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14961551&dopt=Abstract

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Lower limb surgery in Duchenne muscular dystrophy. Author(s): Forst J, Forst R. Source: Neuromuscular Disorders : Nmd. 1999 May; 9(3): 176-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382913&dopt=Abstract

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Lung clearance in children with Duchenne muscular dystrophy or spinal muscular atrophy with and without CPAP (continuous positive airway pressure). Author(s): Klefbeck B, Svartengren K, Camner P, Philipson K, Svartengren M, Sejersen T, Mattsson E. Source: Experimental Lung Research. 2001 September; 27(6): 469-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11558965&dopt=Abstract

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Lung function in Duchenne muscular dystrophy. Author(s): Galasko CS, Williamson JB, Delaney CM. Source: European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 1995; 4(5): 263-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8581525&dopt=Abstract

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Macroemg in manifesting carriers of Duchenne muscular dystrophy. Author(s): Szmidt-Salkowska E, Rowinska-Marcinska K, Fidzianska A, HausmanowaPetrusewicz I. Source: Electromyogr Clin Neurophysiol. 1999 March; 39(2): 87-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10207677&dopt=Abstract

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Mivacurium administration in children with Duchenne muscular dystrophy. Author(s): Tobias JD, Uslu M. Source: Anesthesia and Analgesia. 2000 February; 90(2): 498-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10648347&dopt=Abstract

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Mode of death in Duchenne muscular dystrophy. Author(s): Patterson V, Morrison O, Hicks E. Source: Lancet. 1991 March 30; 337(8744): 801-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1672433&dopt=Abstract

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Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy. Author(s): Harper SQ, Hauser MA, DelloRusso C, Duan D, Crawford RW, Phelps SF, Harper HA, Robinson AS, Engelhardt JF, Brooks SV, Chamberlain JS. Source: Nature Medicine. 2002 March; 8(3): 253-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11875496&dopt=Abstract

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Mononuclear cell analysis of muscle biopsies in prednisone-treated and untreated Duchenne muscular dystrophy. CIDD Study Group. Author(s): Kissel JT, Burrow KL, Rammohan KW, Mendell JR. Source: Neurology. 1991 May; 41(5): 667-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2027481&dopt=Abstract

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Multiple regulatory events controlling the expression and localization of utrophin in skeletal muscle fibers: insights into a therapeutic strategy for Duchenne muscular dystrophy. Author(s): Jasmin BJ, Angus LM, Belanger G, Chakkalakal JV, Gramolini AO, Lunde JA, Stocksley MA, Thompson J. Source: Journal of Physiology, Paris. 2002 January-March; 96(1-2): 31-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11755781&dopt=Abstract

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Multiplex PCR excludes Duchenne muscular dystrophy in a twin pregnancy. Author(s): Wadelius C, Anneran G, Dahl N, Holmgren G, Gustavson KH. Source: Clinical Genetics. 1991 April; 39(4): 314-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2070552&dopt=Abstract

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Muscle and joint elastic properties during elbow flexion in Duchenne muscular dystrophy. Author(s): Cornu C, Goubel F, Fardeau M. Source: The Journal of Physiology. 2001 June 1; 533(Pt 2): 605-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11389216&dopt=Abstract

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Myoblast transfer therapy for Duchenne muscular dystrophy. Author(s): Law PK, Goodwin TG, Fang QW, Chen M, Li HJ, Florendo JA, Kirby DS. Source: Acta Paediatr Jpn. 1991 April; 33(2): 206-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1957647&dopt=Abstract

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Myocardial cell damage in Duchenne muscular dystrophy. Author(s): Ramaciotti C, Iannaccone ST, Scott WA. Source: Pediatric Cardiology. 2003 September-October; 24(5): 503-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14627325&dopt=Abstract

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Neonatal screening for Duchenne muscular dystrophy: a novel semiquantitative application of the bioluminescence test for creatine kinase in a pilot national program in Cyprus. Author(s): Drousiotou A, Ioannou P, Georgiou T, Mavrikiou E, Christopoulos G, Kyriakides T, Voyasianos M, Argyriou A, Middleton L. Source: Genetic Testing. 1998; 2(1): 55-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10464597&dopt=Abstract

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New aspects of calcium signaling in skeletal muscle cells: implications in Duchenne muscular dystrophy. Author(s): Gailly P. Source: Biochimica Et Biophysica Acta. 2002 November 4; 1600(1-2): 38-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445457&dopt=Abstract

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Newborn screening for Duchenne muscular dystrophy. Author(s): Parsons EP, Bradley DM, Clarke AJ. Source: Archives of Disease in Childhood. 2003 January; 88(1): 91-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495984&dopt=Abstract

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Newborn screening for Duchenne muscular dystrophy: a psychosocial study. Author(s): Parsons EP, Clarke AJ, Hood K, Lycett E, Bradley DM. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2002 March; 86(2): F91-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882550&dopt=Abstract

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Newly recognized exons induced by a splicing abnormality from an intronic mutation of the dystrophin gene resulting in Duchenne muscular dystrophy. Mutations in brief no. 213. Online. Author(s): Ikezawa M, Nishino I, Goto Y, Miike T, Nonaka I. Source: Human Mutation. 1999; 13(2): 170. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10094556&dopt=Abstract

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NO vascular control in Duchenne muscular dystrophy. Author(s): Crosbie RH. Source: Nature Medicine. 2001 January; 7(1): 27-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11135610&dopt=Abstract

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Nocturnal oxygenation and prognosis in Duchenne muscular dystrophy. Author(s): Ishikawa Y, Bach JR. Source: American Journal of Respiratory and Critical Care Medicine. 2000 February; 161(2 Pt 1): 675-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10673215&dopt=Abstract

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Nocturnal oxygenation and prognosis in Duchenne muscular dystrophy. Author(s): Phillips MF, Smith PE, Carroll N, Edwards RH, Calverley PM. Source: American Journal of Respiratory and Critical Care Medicine. 1999 July; 160(1): 198-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10390400&dopt=Abstract

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Novel deletion at the M and P promoters of the human dystrophin gene associated with a Duchenne muscular dystrophy. Author(s): Frisso G, Sampaolo S, Pastore L, Carlomagno A, Calise RM, Di Iorio G, Salvatore F. Source: Neuromuscular Disorders : Nmd. 2002 June; 12(5): 494-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031623&dopt=Abstract

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Novel therapies for Duchenne muscular dystrophy. Author(s): Kapsa R, Kornberg AJ, Byrne E. Source: Lancet. Neurology. 2003 May; 2(5): 299-310. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849184&dopt=Abstract

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Occurrence of two different intragenic deletions in two male relatives affected with Duchenne muscular dystrophy. Author(s): Mostacciuolo ML, Miorin M, Vitiello L, Rampazzo A, Fanin M, Angelini C, Danieli GA. Source: American Journal of Medical Genetics. 1994 March 1; 50(1): 84-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8160758&dopt=Abstract

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Octreotide enhances positive calcium balance in Duchenne muscular dystrophy. Author(s): Nutting DF, Schriock EA, Palmieri GM, Bittle JB, Elmendorf BJ, Horner LH, Edwards MC, Griffin JW, Sacks HS, Bertorini TE. Source: The American Journal of the Medical Sciences. 1995 September; 310(3): 91-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7668311&dopt=Abstract

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Oligonucleotides against a splicing enhancer sequence led to dystrophin production in muscle cells from a Duchenne muscular dystrophy patient. Author(s): Takeshima Y, Wada H, Yagi M, Ishikawa Y, Ishikawa Y, Minami R, Nakamura H, Matsuo M. Source: Brain & Development. 2001 December; 23(8): 788-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11720794&dopt=Abstract

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On the origin of deletions and point mutations in Duchenne muscular dystrophy: most deletions arise in oogenesis and most point mutations result from events in spermatogenesis. Author(s): Grimm T, Meng G, Liechti-Gallati S, Bettecken T, Muller CR, Muller B. Source: Journal of Medical Genetics. 1994 March; 31(3): 183-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8014964&dopt=Abstract

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One base deletion in the cysteine-rich domain of the dystrophin gene in Duchenne muscular dystrophy patients. Author(s): Tsukamoto H, Inui K, Matsuoka T, Yanagihara I, Fukushima H, Okada S. Source: Human Molecular Genetics. 1994 June; 3(6): 995-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7951251&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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Oral glutamine slows down whole body protein breakdown in Duchenne muscular dystrophy. Author(s): Hankard RG, Hammond D, Haymond MW, Darmaun D. Source: Pediatric Research. 1998 February; 43(2): 222-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9475288&dopt=Abstract

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Origins and early descriptions of “Duchenne muscular dystrophy”. Author(s): Tyler KL. Source: Muscle & Nerve. 2003 October; 28(4): 402-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506712&dopt=Abstract

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Orthopedic approaches for the treatment of lower extremity contractures in the Duchenne muscular dystrophy patient in the United States and Canada. Author(s): Hsu JD. Source: Seminars in Neurology. 1995 March; 15(1): 6-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7638460&dopt=Abstract

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Oxidative damage to muscle protein in Duchenne muscular dystrophy. Author(s): Haycock JW, MacNeil S, Jones P, Harris JB, Mantle D. Source: Neuroreport. 1996 December 20; 8(1): 357-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9051810&dopt=Abstract

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Parental stress in mothers of boys with duchenne muscular dystrophy. Author(s): Nereo NE, Fee RJ, Hinton VJ. Source: Journal of Pediatric Psychology. 2003 October-November; 28(7): 473-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968039&dopt=Abstract

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Pelvic or lumbar fixation for the surgical management of scoliosis in duchenne muscular dystrophy. Author(s): Sengupta DK, Mehdian SH, McConnell JR, Eisenstein SM, Webb JK. Source: Spine. 2002 September 15; 27(18): 2072-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634572&dopt=Abstract

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Physical capacity in non-ambulatory people with Duchenne muscular dystrophy or spinal muscular atrophy: a longitudinal study. Author(s): Steffensen BF, Lyager S, Werge B, Rahbek J, Mattsson E. Source: Developmental Medicine and Child Neurology. 2002 September; 44(9): 623-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12227617&dopt=Abstract

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Postoperative malnutrition in Duchenne muscular dystrophy. Author(s): Iannaccone ST, Owens H, Scott J, Teitell B. Source: Journal of Child Neurology. 2003 January; 18(1): 17-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661933&dopt=Abstract

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Predictive factors of cessation of ambulation in patients with Duchenne muscular dystrophy. Author(s): Bakker JP, De Groot IJ, Beelen A, Lankhorst GJ. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2002 December; 81(12): 906-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447089&dopt=Abstract

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Prednisolone in Duchenne muscular dystrophy. Author(s): Rahman MM, Hannan MA, Mondol BA, Bhoumick NB, Haque A. Source: Bangladesh Med Res Counc Bull. 2001 April; 27(1): 38-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11692899&dopt=Abstract

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Prenatal deletion detection in a sporadic case of Duchenne muscular dystrophy without genotype information from the affected individual. Author(s): Peinemann F, Wagner M, Franke U, Kulle M, Reiss J. Source: European Journal of Pediatrics. 1991 February; 150(4): 256-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1851486&dopt=Abstract

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Prognostic value of electrocardiograms, ventricular late potentials, ventricular arrhythmias, and left ventricular systolic dysfunction in patients with Duchenne muscular dystrophy. Author(s): Corrado G, Lissoni A, Beretta S, Terenghi L, Tadeo G, Foglia-Manzillo G, Tagliagambe LM, Spata M, Santarone M. Source: The American Journal of Cardiology. 2002 April 1; 89(7): 838-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11909570&dopt=Abstract

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Progress in gene therapy for Duchenne muscular dystrophy. Author(s): Clemens PR, Duncan FJ. Source: Curr Neurol Neurosci Rep. 2001 January; 1(1): 89-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898504&dopt=Abstract

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Progress toward gene therapy of Duchenne muscular dystrophy. Author(s): Hartigan-O'Connor D, Chamberlain JS. Source: Seminars in Neurology. 1999; 19(3): 323-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194388&dopt=Abstract

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Quadriceps femoris muscle assist orthosis in Duchenne muscular dystrophy. Author(s): Siegel IM, Silverman O, Silverman M. Source: Physical Therapy. 1982 September; 62(9): 1296. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7111403&dopt=Abstract

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Quantitation of muscle function in children: a prospective study in Duchenne muscular dystrophy. Author(s): Scott OM, Hyde SA, Goddard C, Dubowitz V. Source: Muscle & Nerve. 1982 April; 5(4): 291-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7099196&dopt=Abstract

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Quantitative analysis of quadriceps muscle biopsy. Results in 7 definite and 45 possible carriers of Duchenne muscular dystrophy. Author(s): Doriguzzi C, Palmucci L, Mongini T, Leone M, Gagnor E, Gagliano A, Schiffer D. Source: Journal of the Neurological Sciences. 1986 February; 72(2-3): 201-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3711934&dopt=Abstract

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Quantitative assessment of calf circumference in Duchenne muscular dystrophy patients. Author(s): Beenakker EA, de Vries J, Fock JM, van Tol M, Brouwer OF, Maurits NM, van der Hoeven JH. Source: Neuromuscular Disorders : Nmd. 2002 October; 12(7-8): 639-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12207931&dopt=Abstract

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Quantitative ELISA for platelet m-calpain: a phenotypic index for detection of carriers of Duchenne muscular dystrophy. Author(s): Hussain T, Kumar DV, Sundaram C, Mohandas S, Anandaraj MP. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1998 January 12; 269(1): 13-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9498100&dopt=Abstract

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Quantitative MR evaluation of body composition in patients with Duchenne muscular dystrophy. Author(s): Pichiecchio A, Uggetti C, Egitto MG, Berardinelli A, Orcesi S, Gorni KO, Zanardi C, Tagliabue A. Source: European Radiology. 2002 November; 12(11): 2704-9. Epub 2002 May 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386760&dopt=Abstract

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Quantitative MR relaxometry study of muscle composition and function in Duchenne muscular dystrophy. Author(s): Huang Y, Majumdar S, Genant HK, Chan WP, Sharma KR, Yu P, Mynhier M, Miller RG. Source: Journal of Magnetic Resonance Imaging : Jmri. 1994 January-February; 4(1): 5964. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8148557&dopt=Abstract

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Reading ability and processing in Duchenne muscular dystrophy and spinal muscular atrophy. Author(s): Billard C, Gillet P, Barthez M, Hommet C, Bertrand P. Source: Developmental Medicine and Child Neurology. 1998 January; 40(1): 12-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9459212&dopt=Abstract

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Reduced aquaporin 4 expression in the muscle plasma membrane of patients with Duchenne muscular dystrophy. Author(s): Wakayama Y, Jimi T, Inoue M, Kojima H, Murahashi M, Kumagai T, Yamashita S, Hara H, Shibuya S. Source: Archives of Neurology. 2002 March; 59(3): 431-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11890849&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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Relationship between utrophin and regenerating muscle fibers in duchenne muscular dystrophy. Author(s): Shim JY, Kim TS. Source: Yonsei Medical Journal. 2003 February; 44(1): 15-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619170&dopt=Abstract

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Remission of clinical signs in early duchenne muscular dystrophy on intermittent low-dosage prednisolone therapy. Author(s): Dubowitz V, Kinali M, Main M, Mercuri E, Muntoni F. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 2002; 6(3): 153-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363102&dopt=Abstract

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Respiratory concerns in Duchenne muscular dystrophy (DMD). Author(s): Leger P, Leger SS. Source: Pediatr Pulmonol Suppl. 1997; 16: 137-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9443242&dopt=Abstract

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Resting energy expenditure and energy substrate utilization in children with Duchenne muscular dystrophy. Author(s): Hankard R, Gottrand F, Turck D, Carpentier A, Romon M, Farriaux JP. Source: Pediatric Research. 1996 July; 40(1): 29-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8798242&dopt=Abstract

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Retroviral vectors for gene therapy of Duchenne muscular dystrophy. Author(s): Fassati A, Bresolin N. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2000; 21(5 Suppl): S925-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11382191&dopt=Abstract

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Revertant fibres: a possible genetic therapy for Duchenne muscular dystrophy? Author(s): Wilton SD, Dye DE, Blechynden LM, Laing NG. Source: Neuromuscular Disorders : Nmd. 1997 July; 7(5): 329-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9267847&dopt=Abstract

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Row-a-boat phenomenon: respiratory compensation in advanced Duchenne muscular dystrophy. Author(s): Yasuma F, Kato T, Matsuoka Y, Konagaya M. Source: Chest. 2001 June; 119(6): 1836-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11399712&dopt=Abstract

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Screening of gene deletions by polymerase chain reaction in Japanese patients with Duchenne muscular dystrophy. Author(s): Nakajima T, Matsuo M, Kitoh Y, Takumi T, Nishio H, Masumura T, Koga J, Nakamura H. Source: Journal of Neurology. 1991 February; 238(1): 6-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2030378&dopt=Abstract

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Short stature in Duchenne muscular dystrophy. Author(s): Rapaport D, Colletto GM, Vainzof M, Duaik MC, Zatz M. Source: Growth Regul. 1991 March; 1(1): 11-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1842555&dopt=Abstract

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Skeletal muscle metabolism in Duchenne muscular dystrophy (DMD): an in-vitro proton NMR spectroscopy study. Author(s): Sharma U, Atri S, Sharma MC, Sarkar C, Jagannathan NR. Source: Magnetic Resonance Imaging. 2003 February; 21(2): 145-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670601&dopt=Abstract

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Special Centennial Workshop-- 101st ENMC International Workshop: Therapeutic Possibilities in Duchenne Muscular Dystrophy, 30th November-2nd December 2001, Naarden, The Netherlands. Author(s): Dubowitz V. Source: Neuromuscular Disorders : Nmd. 2002 May; 12(4): 421-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062262&dopt=Abstract

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S-protein is expressed in necrotic fibers in Duchenne muscular dystrophy and polymyositis. Author(s): Louboutin JP, Navenot JM, Rouger K, Blanchard D. Source: Muscle & Nerve. 2003 May; 27(5): 575-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707977&dopt=Abstract

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ST-segment displacement in Duchenne muscular dystrophy: myocardial necrosis or apoptosis? Author(s): Politano L, Palladino A, Petretta VR, Mansi L, Passamano L, Nigro G, Comi LI, Nigro G. Source: Acta Myol. 2003 May; 22(1): 5-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677325&dopt=Abstract

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Surgical prevention of foot deformity in patients with Duchenne muscular dystrophy. Author(s): Wright JG. Source: Journal of Pediatric Orthopedics. 2003 July-August; 23(4): 564-5; Author Reply 565. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826961&dopt=Abstract

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Surgical prevention of foot deformity in patients with Duchenne muscular dystrophy. Author(s): Wright JG. Source: Journal of Pediatric Orthopedics. 2003 May-June; 23(3): 419. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724613&dopt=Abstract

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Surgical prevention of foot deformity in patients with Duchenne muscular dystrophy. Author(s): Scher DM, Mubarak SJ. Source: Journal of Pediatric Orthopedics. 2002 May-June; 22(3): 384-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961461&dopt=Abstract

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Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Author(s): Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Source: Neuromuscular Disorders : Nmd. 2002 December; 12(10): 926-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467747&dopt=Abstract

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The Duchenne muscular dystrophy population in Denmark, 1977-2001: prevalence, incidence and survival in relation to the introduction of ventilator use. Author(s): Jeppesen J, Green A, Steffensen BF, Rahbek J. Source: Neuromuscular Disorders : Nmd. 2003 December; 13(10): 804-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14678803&dopt=Abstract

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The future of Duchenne muscular dystrophy gene therapy: shrinking the dystrophin gene. Author(s): Roberts M, Dickson G. Source: Curr Opin Mol Ther. 2002 August; 4(4): 343-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222872&dopt=Abstract

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The Golden Freeway: a preliminary evaluation of a pilot study advancing information technology as a social intervention for boys with Duchenne muscular dystrophy and their families. Author(s): Soutter J, Hamilton N, Russell P, Russell C, Bushby K, Sloper P, Bartlett K. Source: Health & Social Care in the Community. 2004 January; 12(1): 25-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14675362&dopt=Abstract

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The mechanism of cerebral evoked potentials by repetitive magnetic stimulation of gastrocnemius muscle in Duchenne muscular dystrophy. Author(s): Guan Y, Cui L, Tang X, Li B, Du H. Source: Chinese Medical Sciences Journal = Chung-Kuo I Hsueh K'o Hsueh Tsa Chih / Chinese Academy of Medical Sciences. 2001 June; 16(2): 115-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901502&dopt=Abstract

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The role of utrophin in the potential therapy of Duchenne muscular dystrophy. Author(s): Perkins KJ, Davies KE. Source: Neuromuscular Disorders : Nmd. 2002 October; 12 Suppl 1: S78-89. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206801&dopt=Abstract

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The value of deletion analysis for carrier detection in Duchenne muscular dystrophy (DMD). Author(s): Bejjani B, Finn P, Milunsky A, Amos J. Source: Clinical Genetics. 1991 April; 39(4): 245-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2070545&dopt=Abstract

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Three wishes and psychological functioning in boys with duchenne muscular dystrophy. Author(s): Nereo NE, Hinton VJ. Source: Journal of Developmental and Behavioral Pediatrics : Jdbp. 2003 April; 24(2): 96103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692454&dopt=Abstract

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Time dependent changes of variables associated with malocclusion in patients with Duchenne muscular dystrophy. Author(s): Matsumoto S, Morinushi T, Ogura T. Source: J Clin Pediatr Dent. 2002 Fall; 27(1): 53-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413173&dopt=Abstract

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Tracheobronchomalacia and tracheal hemorrhage in patients with Duchenne muscular dystrophy receiving long-term ventilation with uncuffed tracheostomies. Author(s): Baydur A, Kanel G. Source: Chest. 2003 April; 123(4): 1307-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684330&dopt=Abstract

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Tracheocoele in a Duchenne muscular dystrophy patient. Case report. Author(s): Piazza C, Bolzoni A, Cavaliere S, Peretti G. Source: Acta Otorhinolaryngol Ital. 2003 June; 23(3): 194-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14677314&dopt=Abstract

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Ultrasound tissue characterization detects preclinical myocardial structural changes in children affected by Duchenne muscular dystrophy. Author(s): Giglio V, Pasceri V, Messano L, Mangiola F, Pasquini L, Dello Russo A, Damiani A, Mirabella M, Galluzzi G, Tonali P, Ricci E. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 309-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875769&dopt=Abstract

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Uniparental disomy of the entire X chromosome in a female with Duchenne muscular dystrophy. Author(s): Quan F, Janas J, Toth-Fejel S, Johnson DB, Wolford JK, Popovich BW. Source: American Journal of Human Genetics. 1997 January; 60(1): 160-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8981959&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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Upper extremity functional assessment scales in children with Duchenne muscular dystrophy: a comparison. Author(s): Hiller LB, Wade CK. Source: Archives of Physical Medicine and Rehabilitation. 1992 June; 73(6): 527-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1622300&dopt=Abstract

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Upregulation of utrophin in the myocardium of a carrier of Duchenne muscular dystrophy. Author(s): Behr TM, Fischer P, Mudra H, Theisen K, Spes C, Uberfuhr P, Muller-Felber W, Pongratz DE, Angermann C. Source: European Heart Journal. 1997 April; 18(4): 699-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9129907&dopt=Abstract

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Urinary dysfunction in Duchenne muscular dystrophy. Author(s): Caress JB, Kothari MJ, Bauer SB, Shefner JM. Source: Muscle & Nerve. 1996 July; 19(7): 819-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8965833&dopt=Abstract

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Urinary excretion of acid-soluble peptides in children with Duchenne muscular dystrophy. Author(s): Hirano K, Sakamoto Y. Source: Acta Paediatr Jpn. 1994 December; 36(6): 627-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7871971&dopt=Abstract

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Use of DNA probes in detecting carriers of Duchenne muscular dystrophy: selected case studies. Author(s): Prior TW, Blasco PA, Dove JL, Leshner RT, Gruemer HD. Source: Clinical Chemistry. 1989 April; 35(4): 679-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2564818&dopt=Abstract

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Use of dystrophin genomic and cDNA probes for solving difficulties in carrier detection and prenatal diagnosis of Duchenne muscular dystrophy. Author(s): Shomrat R, Driks N, Legum C, Shiloh Y. Source: American Journal of Medical Genetics. 1992 February 1; 42(3): 281-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1536162&dopt=Abstract

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Usefulness of test: manual muscle testing, goniometry, and daily activities for differential diagnosis of Duchenne muscular dystrophy, Becker's mild muscular dystrophy and Becker's severe muscular dystrophy. Author(s): Alvarez M, Rodriguez I, Zuniga-Charles MA. Source: International Journal of Rehabilitation Research. Internationale Zeitschrift Fur Rehabilitationsforschung. Revue Internationale De Recherches De Readaptation. 1998 March; 21(1): 79-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9924669&dopt=Abstract

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Valley sign in duchenne muscular dystrophy: importance in patients with inconspicuous calves. Author(s): Pradhan S. Source: Neurology India. 2002 June; 50(2): 184-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12134184&dopt=Abstract

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Value of myofibrillar protein catabolic rate in Duchenne muscular dystrophy. A study after lower limb surgery. Author(s): Forst J, Kruger P, Forst R. Source: Archives of Orthopaedic and Trauma Surgery. 2000; 120(1-2): 38-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10653102&dopt=Abstract

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Variable dystrophin expression in different muscles of a Duchenne muscular dystrophy carrier. Author(s): Muntoni F, Mateddu A, Marrosu MG, Cau M, Congiu R, Melis MA, Cao A, Cianchetti C. Source: Clinical Genetics. 1992 July; 42(1): 35-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1355417&dopt=Abstract

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Variations of gait parameters in Duchenne muscular dystrophy. Author(s): Khodadadeh S, McClelland MR, Patrick JH. Source: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of Engineering in Medicine. 1990; 204(4): 241-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2090127&dopt=Abstract

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Ventilation and breathing pattern during sleep in Duchenne muscular dystrophy. Author(s): Smith PE, Edwards RH, Calverley PM. Source: Chest. 1989 December; 96(6): 1346-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2582842&dopt=Abstract

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Ventilator dependency: decision-making, daily functioning and quality of life for patients with Duchenne muscular dystrophy. Author(s): Miller JR, Colbert AP, Osberg JS. Source: Developmental Medicine and Child Neurology. 1990 December; 32(12): 1078-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2286307&dopt=Abstract

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Ventilator management in Duchenne muscular dystrophy and postpoliomyelitis syndrome: twelve years' experience. Author(s): Curran FJ, Colbert AP. Source: Archives of Physical Medicine and Rehabilitation. 1989 March; 70(3): 180-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2647055&dopt=Abstract

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Ventricular arrhythmia in Duchenne muscular dystrophy: prevalence, significance and prognosis. Author(s): Chenard AA, Becane HM, Tertrain F, de Kermadec JM, Weiss YA. Source: Neuromuscular Disorders : Nmd. 1993 May; 3(3): 201-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7691292&dopt=Abstract

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Vertebral compression in Duchenne muscular dystrophy following deflazacort. Author(s): Talim B, Malaguti C, Gnudi S, Politano L, Merlini L. Source: Neuromuscular Disorders : Nmd. 2002 March; 12(3): 294-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11801403&dopt=Abstract

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Vertebral fractures in boys with Duchenne muscular dystrophy. Author(s): Bothwell JE, Gordon KE, Dooley JM, MacSween J, Cummings EA, Salisbury S. Source: Clinical Pediatrics. 2003 May; 42(4): 353-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800730&dopt=Abstract

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Wheelchair-mounted robot manipulators. Long term use by patients with Duchenne muscular dystrophy. Author(s): Bach JR, Zeelenberg AP, Winter C. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 1990 April; 69(2): 55-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2331340&dopt=Abstract

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X chromosome in Duchenne muscular dystrophy. Author(s): Spowart G, Buckton KE, Skinner R, Emery AE. Source: Lancet. 1982 May 29; 1(8283): 1251. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6123008&dopt=Abstract

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X inactivation and dystrophin studies in a t(X;12) female: evidence for biochemical normalization in Duchenne muscular dystrophy carriers. Author(s): Wenger SL, Steele MW, Hoffman EP, Barmada MA, Wessel HB. Source: American Journal of Medical Genetics. 1992 August 1; 43(6): 1012-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1415326&dopt=Abstract

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Xanthine oxidase inhibitor in Duchenne muscular dystrophy. Author(s): Tamari H, Ohtani Y, Higashi A, Miyoshino S, Matsuda I. Source: Brain & Development. 1982; 4(2): 137-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6896406&dopt=Abstract

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X-chromosome-coded antigens in Duchenne muscular dystrophy. Author(s): Walsh FS. Source: Biochemical Society Transactions. 1984 June; 12(3): 368-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6376203&dopt=Abstract

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X-chromosome-specific polymorphisms in Duchenne muscular dystrophy: clinical applications. Author(s): O'Brien T. Source: Biochemical Society Transactions. 1984 June; 12(3): 371-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6734896&dopt=Abstract

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X-linked dilated cardiomyopathy. Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus. Author(s): Towbin JA, Hejtmancik JF, Brink P, Gelb B, Zhu XM, Chamberlain JS, McCabe ER, Swift M. Source: Circulation. 1993 June; 87(6): 1854-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8504498&dopt=Abstract

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X-linked Duchenne muscular dystrophy in an unusual family with manifesting carriers. Author(s): Kaladhar Reddy B, Anandavalli TE, Reddi OS. Source: Human Genetics. 1984; 67(4): 460-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6490012&dopt=Abstract

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X-linked Duchenne muscular dystrophy. Motor functions and prognosis. Author(s): Hinge HH, Hein-Sorensen O, Reske-Nielsen E. Source: Scandinavian Journal of Rehabilitation Medicine. 1989; 21(1): 27-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2711136&dopt=Abstract

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CHAPTER 2. NUTRITION AND DUCHENNE MUSCULAR DYSTROPHY Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Duchenne muscular dystrophy.

Finding Nutrition Studies on Duchenne Muscular Dystrophy The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “Duchenne muscular dystrophy” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “Duchenne muscular dystrophy” (or a synonym): •

A double blind cross over trial of theophylline prophylaxis for sleep hypoxaemia in Duchenne muscular dystrophy. Author(s): Department of Paediatrics, Hammersmith Hospital, London, UK. Source: Khan, Y Heckmatt, J Z Neuromuscul-Disord. 1997 March; 7(2): 75-80 0960-8966

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A pilot trial of plasma infusions in Duchenne muscular dystrophy. Author(s): Department of Biochemistry, Monash University, Clayton, Melbourne, Australia. Source: Arthur, H Austin, L Roberts, L J Aust-Paediatr-J. 1988; 24 Suppl 124-30 0004993X

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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 Cell-Calcium. 1995 September; 18(3): 177-86 0143-4160

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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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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 00435325

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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 CellCalcium. 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. 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

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Corticosteroid therapy in Duchenne muscular dystrophy. Author(s): Department of Anatomy & Cell Biology, State University of New York, Health Science Center at Brooklyn 11203. Source: Khan, M A J-Neurol-Sci. 1993 December 1; 120(1): 8-14 0022-510X

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Corticosteroids in Duchenne muscular dystrophy: a reappraisal. Author(s): Division of Child Neurology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. [email protected] Source: Wong, B L Christopher, C J-Child-Neurol. 2002 March; 17(3): 183-90 0883-0738

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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-Pediatr-Hematol-Oncol. 1999 Nov-December; 21(6): 528-30 1077-4114

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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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Effect of mazindol on growth hormone levels in patients with Duchenne muscular dystrophy. Author(s): Departamento de Biologia, Universidade de Sao Paulo, Brazil. Source: Zatz, M Rapaport, D Vainzof, M Pavanello, R de C Rocha, J M Betti, R T Otto, P A Am-J-Med-Genet. 1988 December; 31(4): 821-33 0148-7299

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Electrocardiographic findings in mdx mice: a cardiac phenotype of Duchenne muscular dystrophy. Author(s): Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA. Source: Chu, V Otero, J M Lopez, O Sullivan, M F Morgan, J P Amende, I Hampton, T G Muscle-Nerve. 2002 October; 26(4): 513-9 0148-639X

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Hypoosmotic shocks induce elevation of resting calcium level in Duchenne muscular dystrophy myotubes contracting in vitro. Author(s): Laboratoire de Physiologie Generale, CNRS 1869, Universite de Poitiers, France. Source: Imbert, N Vandebrouck, C Constantin, B Duport, G Guillou, C Cognard, C Raymond, G Neuromuscul-Disord. 1996 October; 6(5): 351-60 0960-8966

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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 Neuromuscul-Disord. 2000 August; 10(6): 425-9 0960-8966

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Is glutamine a 'conditionally essential' amino acid in Duchenne muscular dystrophy? Author(s): Nemours Children's Clinic, Jacksonville, Florida, USA. Source: Hankard, R Mauras, N Hammond, D Haymond, M Darmaun, D Clin-Nutr. 1999 December; 18(6): 365-9 0261-5614

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Myoplasmic (Ca2+) in Duchenne muscular dystrophy patients. Source: Lopez, J R Briceno, L E Sanchez, V Horvart, D Acta-Cient-Venez. 1987; 38(4): 503-4 0001-5504

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Octreotide enhances positive calcium balance in Duchenne muscular dystrophy. Author(s): Department of Physiology, College of Medicine, University of Tennessee, Memphis 38163, USA. Source: Nutting, D F Schriock, E A Palmieri, G M Bittle, J B Elmendorf, B J Horner, L H Edwards, M C Griffin, J W Sacks, H S Bertorini, T E Am-J-Med-Sci. 1995 September; 310(3): 91-8 0002-9629

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Oral creatine supplementation in Duchenne muscular dystrophy: a clinical and 31P magnetic resonance spectroscopy study. Author(s): Department of Radiology II and Magnetic Resonance, University of Innsbruck, Children's Hospital, LKH Salzburg, Austria. Source: Felber, S Skladal, D Wyss, M Kremser, C Koller, A Sperl, W Neurol-Res. 2000 March; 22(2): 145-50 0161-6412

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Oral glutamine slows down whole body protein breakdown in Duchenne muscular dystrophy. Author(s): Nemours Children's Clinic, Jacksonville, Florida 32247, USA. Source: Hankard, R G Hammond, D Haymond, M W Darmaun, D Pediatr-Res. 1998 February; 43(2): 222-6 0031-3998

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Predictions of energy intake and energy allowance of patients with Duchenne muscular dystrophy and their validity. Author(s): Department of Nutrition, School of Medicine, University of Tokushima, Japan. Source: Okada, K Manabe, S Sakamoto, S Ohnaka, M Niiyama, Y J-Nutr-Sci-Vitaminol(Tokyo). 1992 April; 38(2): 155-61 0301-4800

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Prednisolone in Duchenne muscular dystrophy. Author(s): Deptt. of Neuromedicine, SOMC, Sylhet. Source: Rahman, M M Hannan, M A Mondol, B A Bhoumick, N B Haque, A Bangladesh-Med-Res-Counc-Bull. 2001 April; 27(1): 38-42 0377-9238

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Purine and carnitine metabolism in muscle of patients with Duchenne muscular dystrophy. Author(s): Departamento de Bioquimica, Hospital General de Galicia, Spain. Source: Camina, F Novo Rodriguez, M I Rodriguez Segade, S Castro Gago, M ClinChim-Acta. 1995 December 29; 243(2): 151-64 0009-8981

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Resting energy expenditure and energy substrate utilization in children with Duchenne muscular dystrophy. Author(s): Service de Pediatrie, Gastroenterologie Pediatrique et Genetique Medicale, CHRU Lille, France. Source: Hankard, R Gottrand, F Turck, D Carpentier, A Romon, M Farriaux, J P PediatrRes. 1996 July; 40(1): 29-33 0031-3998

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Selenium and vitamin E treatment of Duchenne muscular dystrophy: no effect on muscle function. Author(s): Department of Neurophysiology, University Hospital, Linkoping, Sweden.

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Source: Backman, E Nylander, E Johansson, I Henriksson, K G Tagesson, C Acta-NeurolScand. 1988 November; 78(5): 429-35 0001-6314 •

Steroids in Duchenne muscular dystrophy--deflazacort trial. Author(s): Seccion de Enfermedades Neuromusculares, Hospital Frances, Buenos Aires, Argentina. Source: Mesa, L E Dubrovsky, A L Corderi, J Marco, P Flores, D Neuromuscul-Disord. 1991; 1(4): 261-6 0960-8966

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The effect of mazindol on growth hormone secretion in boys with Duchenne muscular dystrophy. Author(s): University Department of Medicine, Royal Liverpool Hospital, UK. Source: Coakley, J H Moorcraft, J Hipkin, L J Smith, C S Griffiths, R D Edwards, R H JNeurol-Neurosurg-Psychiatry. 1988 December; 51(12): 1551-7 0022-3050

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Urinary excretion of selenium and other minerals in patients with Duchenne muscular dystrophy (M.D.) and Werdnig-Hoffman (W-H) spinal atrophy. Source: Ahlrot Westerlund, B. Carlmark, B. Nutr-Res. Elmsford, N.Y. : Pergamon Press. 1985. (suppl. 1) page 406-409. ill. 0271-5317

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Wheat kernel ingestion protects from progression of muscle weakness in mdx mice, an animal model of Duchenne muscular dystrophy. Author(s): Department of Neuropediatrics, Virchow Medical Center, Humboldt University, Berlin, Germany. Source: Hubner, C Lehr, H A Bodlaj, R Finckh, B Oexle, K Marklund, S L Freudenberg, K Kontush, A Speer, A Terwolbeck, K Voit, T Kohlschutter, A Pediatr-Res. 1996 September; 40(3): 444-9 0031-3998

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to Duchenne 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: •

Minerals Creatine Monohydrate Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND DUCHENNE MUSCULAR DYSTROPHY Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Duchenne muscular dystrophy. At the conclusion of this chapter, we will provide additional sources.

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

2 Years' experience with inspiratory muscle training in patients with neuromuscular disorders. Author(s): Koessler W, Wanke T, Winkler G, Nader A, Toifl K, Kurz H, Zwick H. Source: Chest. 2001 September; 120(3): 765-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11555507&dopt=Abstract

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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.

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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 •

Actomyosin alterations in Duchenne muscular dystrophy. Author(s): Samaha FJ. Source: Archives of Neurology. 1973 June; 28(6): 405-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4267103&dopt=Abstract

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Administration of chinese herbal medicines facilitates the locomotor activity in dystrophin-deficient mice. Author(s): Chen SS, Wang DC, Chen TJ, Yang SL. Source: The American Journal of Chinese Medicine. 2001; 29(2): 281-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11527070&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. 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

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Clinical pharmacology of the dietary supplement creatine monohydrate. Author(s): Persky AM, Brazeau GA. Source: Pharmacological Reviews. 2001 June; 53(2): 161-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11356982&dopt=Abstract

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Complement and myoblast transfer therapy: donor myoblast survival is enhanced following depletion of host complement C3 using cobra venom factor, but not in the absence of C5. Author(s): Hodgetts SI, Grounds MD. Source: Immunology and Cell Biology. 2001 June; 79(3): 231-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11380675&dopt=Abstract

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Corticosteroids in Duchenne muscular dystrophy: a reappraisal. Author(s): Wong BL, Christopher C.

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Source: Journal of Child Neurology. 2002 March; 17(3): 183-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12026233&dopt=Abstract •

Creatine supplementation improves intracellular Ca2+ handling and survival in mdx skeletal muscle cells. Author(s): Pulido SM, Passaquin AC, Leijendekker WJ, Challet C, Wallimann T, Ruegg UT. Source: Febs Letters. 1998 November 20; 439(3): 357-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9845353&dopt=Abstract

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Creatine supplementation reduces skeletal muscle degeneration and enhances mitochondrial function in mdx mice. Author(s): Passaquin AC, Renard M, Kay L, Challet C, Mokhtarian A, Wallimann T, Ruegg UT. Source: Neuromuscular Disorders : Nmd. 2002 February; 12(2): 174-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11738360&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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Detection of glucocorticoid-like activity in traditional Chinese medicine used for the treatment of Duchenne muscular dystrophy. Author(s): Courdier-Fruh I, Barman L, Wettstein P, Meier T. Source: Neuromuscular Disorders : Nmd. 2003 November; 13(9): 699-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14561491&dopt=Abstract

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Dose-dependent effect of individualized respiratory muscle training in children with Duchenne muscular dystrophy. Author(s): Topin N, Matecki S, Le Bris S, Rivier F, Echenne B, Prefaut C, Ramonatxo M. Source: Neuromuscular Disorders : Nmd. 2002 August; 12(6): 576-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117483&dopt=Abstract

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Dose-dependent effects of inspiratory muscle training in neuromuscular disorders. Author(s): Winkler G, Zifko U, Nader A, Frank W, Zwick H, Toifl K, Wanke T.

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Source: Muscle & Nerve. 2000 August; 23(8): 1257-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10918264&dopt=Abstract •

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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Duchenne muscular dystrophy--parental perceptions. Author(s): Bothwell JE, Dooley JM, Gordon KE, MacAuley A, Camfield PR, MacSween J. Source: Clinical Pediatrics. 2002 March; 41(2): 105-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11931326&dopt=Abstract

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Effects of iron deprivation on the pathology and stress protein expression in murine X-linked muscular dystrophy. Author(s): Bornman L, Rossouw H, Gericke GS, Polla BS. Source: Biochemical Pharmacology. 1998 September 15; 56(6): 751-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9751080&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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Evidence for the association of dystrophin with the transverse tubular system in skeletal muscle. Author(s): Knudson CM, Hoffman EP, Kahl SD, Kunkel LM, Campbell KP. Source: The Journal of Biological Chemistry. 1988 June 15; 263(17): 8480-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3286650&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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Gene therapy and tissue engineering based on muscle-derived stem cells. Author(s): Deasy BM, Huard J.


Source: Curr Opin Mol Ther. 2002 August; 4(4): 382-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222876&dopt=Abstract •

Green tea extract decreases muscle necrosis in mdx mice and protects against reactive oxygen species. Author(s): Buetler TM, Renard M, Offord EA, Schneider H, Ruegg UT. Source: The American Journal of Clinical Nutrition. 2002 April; 75(4): 749-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11916763&dopt=Abstract

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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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Intrauterine stem cell therapy. Author(s): Fisk NM, Chan J, O'Donoghue K. Source: Ann Acad Med Singapore. 2003 September; 32(5 Suppl): S8-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14968717&dopt=Abstract

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Long-term noninvasive ventilation in children and adolescents with neuromuscular disorders. Author(s): Mellies U, Ragette R, Dohna Schwake C, Boehm H, Voit T, Teschler H. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 October; 22(4): 631-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14582916&dopt=Abstract

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Looking under every rock: Duchenne muscular dystrophy and traditional Chinese medicine. Author(s): Urtizberea JA, Fan QS, Vroom E, Recan D, Kaplan JC. Source: Neuromuscular Disorders : Nmd. 2003 November; 13(9): 705-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14561492&dopt=Abstract

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Maximum insufflation capacity. Author(s): Kang SW, Bach JR. Source: Chest. 2000 July; 118(1): 61-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10893360&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.

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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 •

Neuromuscular reaction to paired stimuli. Author(s): Reitter BF, Johannsen S. Source: Muscle & Nerve. 1982 October; 5(8): 593-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7155172&dopt=Abstract

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Novel therapies for Duchenne muscular dystrophy. Author(s): Kapsa R, Kornberg AJ, Byrne E. Source: Lancet. Neurology. 2003 May; 2(5): 299-310. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849184&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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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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Pyruvate kinase: diagnostic value in neuromuscular disease. Author(s): Weinstock IM, Behrendt J, Wittshire HE Jr, Keleman J, Louis S. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1977 November 1; 80(3): 415-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=912912&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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Report on the muscular dystrophy campaign workshop: exercise in neuromuscular diseases Newcastle, January 2002. Author(s): Eagle M.


Source: Neuromuscular Disorders : Nmd. 2002 December; 12(10): 975-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467755&dopt=Abstract •

Respiratory muscle training in Duchenne muscular dystrophy. Author(s): Rodillo E, Noble-Jamieson CM, Aber V, Heckmatt JZ, Muntoni F, Dubowitz V. 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

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Respiratory muscle training in Duchenne muscular dystrophy. Author(s): Smith PE, Coakley JH, Edwards RH. Source: Muscle & Nerve. 1988 July; 11(7): 784-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3405245&dopt=Abstract

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Respiratory muscle training in neuromuscular disease: long-term effects on strength and load perception. Author(s): Gozal D, Thiriet P. Source: Medicine and Science in Sports and Exercise. 1999 November; 31(11): 1522-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10589852&dopt=Abstract

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Restoration of dystrophin expression in cultured hybrid myotubes. Author(s): Radojevic V, Oppliger C, Gaschen F, Burgunder JM. Source: Neuropathology and Applied Neurobiology. 2002 October; 28(5): 397-409. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366821&dopt=Abstract

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Routine suxamethonium in children. A regional survey of current usage. Author(s): Robinson AL, Jerwood DC, Stokes MA. Source: Anaesthesia. 1996 September; 51(9): 874-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8882256&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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Spectrin extractability from erythrocyte in Duchenne muscular dystrophies and the effect of proteases on erythrocyte ghosts. Author(s): Tsuchiya Y, Sugita H, Ishiura S, Imahori K. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1981 February 5; 109(3): 285-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6452973&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. 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

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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to Duchenne 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.drkoop.com


•

Herbs and Supplements Allopurinol Source: Healthnotes, Inc.; www.healthnotes.com BCAAs Source: Prima Communications, Inc.www.personalhealthzone.com

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

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CHAPTER 4. DISSERTATIONS ON DUCHENNE MUSCULAR DYSTROPHY Overview In this chapter, we will give you a bibliography on recent dissertations relating to Duchenne muscular dystrophy. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “Duchenne muscular dystrophy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Duchenne muscular dystrophy, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Duchenne Muscular Dystrophy ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to Duchenne muscular dystrophy. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Adenoviral Vectors for Treatment of Duchenne Muscular Dystrophy by HartiganO'Connor, Dennis Joseph; PhD from University of Michigan, 2003, 158 pages http://wwwlib.umi.com/dissertations/fullcit/3079456

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Duchenne Muscular Dystrophy Genetic and Biochemical Studies of the Female Carriers and Their Families by Hutton, Elaine M. Edwards; AdvDeg from University of Toronto (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK09148

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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

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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

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Ultrastructure of Muscle in Typical and Atypical Duchenne Muscular Dystrophy: a Comparative Study by Oteruelo, Felix Teodoro; PhD from The University of Western Ontario (Canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK12009

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

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CHAPTER 5. CLINICAL MUSCULAR DYSTROPHY

TRIALS

AND

DUCHENNE

Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Duchenne muscular dystrophy.

Recent Trials on Duchenne Muscular Dystrophy The following is a list of recent trials dedicated to Duchenne muscular dystrophy.8 Further information on a trial is available at the Web site indicated. •

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): see Web site below

8

These are listed at www.ClinicalTrials.gov.

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Web Site: http://clinicaltrials.gov/ct/show/NCT00033189 •

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): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033813

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Creatine and Glutamine in Steroid-Naive Duchenne Muscular Dystrophy Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is no longer 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/show/NCT00016653

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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 completed.

Clinical Trials 95

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): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018109 •

Gentamicin Treatment of Muscular Dystrophy Condition(s): Becker muscular dystrophy; Duchenne muscular dystrophy Study Status: This study is completed. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study will evaluate the antibiotic gentamicin for treating patients with muscular dystrophy caused by a specific genetic abnormality known as a nonsense mutation. In studies of mice with this type of muscular dystrophy, gentamicin treatment produced positive changes in muscle tissue. Patients with Duchenne or Becker muscular dystrophy caused by nonsense mutations by may be eligible for this 2week study. Before starting treatment, patients will have evaluations of muscle strength and general well being. Two muscle tissue samples will be taken by needle biopsy, under local anesthetic and sedation. Because of potential risks of hearing loss and kidney toxicity associated with gentamicin, patients will also have a hearing test and blood and urine tests for kidney function before starting treatment. (Currently, gentamicin is commonly prescribed for serious infections of the lungs, heart, and digestive and urinary tracts; adverse effects of hearing loss and kidney toxicity can occur with excessively high drug doses.) Patients will be hospitalized during drug treatment. Gentamicin will be given intravenously (through a vein) once a day for 14 days. Blood samples will be collected daily to monitor drug levels and determine dosage adjustments, if necessary. Urine samples will be collected to assess kidney function. Hearing tests will be done on days 7 and 10. On the last day of the study, hearing, kidney function, and muscle strength will be tested and the results compared with pretreatment levels. Blood and muscle samples will also be taken again for pre-treatment comparison. Hearing, blood, urine, and muscle strength tests will be repeated one month after treatment ends for comparison with previous results. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005574

•

Phase III Randomized, Double-Blind Study of Prednisone for Duchenne Muscular Dystrophy Condition(s): Duchenne Muscular Dystrophy

96


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 insulin-like 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/show/NCT00004646

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “Duchenne 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/

•

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

•

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

•

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

•

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

•

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

Clinical Trials 97

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

99

CHAPTER 6. DYSTROPHY

PATENTS

ON

DUCHENNE

MUSCULAR

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

Patents on Duchenne Muscular Dystrophy By performing a patent search focusing on Duchenne 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 9Adapted

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

100


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 Duchenne muscular dystrophy: •

Medicament for treatment of Duchenne muscular dystrophy Inventor(s): Matsuo; Masafumi (3-31, Kitaochiai 5-chome, Suma-ku, Kobe-shi, Hyogo 654-0151, JP), Takeshima; Yasuhiro (Kobe, JP) Assignee(s): Jcr Pharmaceutical Co., Ltd. (hyogo, Jp), Matsuo; Masafumi (hyogo, Jp) Patent Number: 6,653,467 Date filed: September 22, 2000 Abstract: Antisense oligonucleotides comprising a nucleotide sequence complementary to the nucleotide sequence of SEQ ID NO:1 or NO:2 are disclosed. The antisense oligonucleotides are used for treatment of specific types of Duchenne muscular dystrophy which is attributed to a change in number of the nucleotides composing one or more exons adjacent to exon 43 or 53, respectively, in human dystrophin mRNA, wherein the change is due to deletion of one or more nucleotides from the normal nucleotide sequence for the exons, wherein the net of the change in number of the nucleotides is expressed as a reduction of (3.times.N+1) nucleotides, wherein N is zero or a natural number. Excerpt(s): The present invention relates to medicaments for treatment of Duchenne muscular dystrophy, which medicaments are designed to correct an existing shift of the amino acid reading frame in dystrophin pre-mRNA by inducing in a predetermined manner an exon skipping in the pre-mRNA having the reading frame shift resulting from abnormalities in dystrophin gene. More specifically, the present invention relates to splicing enhancer sequences (SES's) in dystrophin gene which can be used for the preparation of medicaments for treatment of certain types of Duchenne muscular dystrophy, as well as to antisense oligonucleotides against the splicing enhancer sequences, and medicaments comprising thereof. Today, it has become possible to diagnose some hereditary diseases caused by abnormal splicing of corresponding premRNA molecules. An intractable disease, muscular dystrophy, has come to draw particular attention. Muscular dystrophy is divided into Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DMD is a hereditary muscular disease of highest incidence, occurring in one in 3,500 live male births. Patients of DMD at first exhibit lowered muscular power in their infancy, suffer from progressive muscular atrophy since then on, and eventually die in their age of around 20. No effective medicament is so far available for DMD, and development of a medicament for it has been longed for by the patients around the world. In 1987, dystrophin gene, which is the causative gene of DMD, was found using retrospective genetics, and BMD also was found to result from abnormality of the same dystrophin gene [Koenig, M. et al., Cell, 50:509-517(1987)]. As for BMD, its onset is relatively late, observed in the adulthood, and nearly normal survival is allowed, although a mild loss of muscular power is observed after the onset of the disease. Dystrophin gene is located in the subregion 21 of the short arm of the X-chromosome. The size of dystrophin gene is 3,0 Mb, the largest known human gene. Despite that large size, it is regions of only 14 kb in total of the dystrophin gene that encodes dystrophin protein, and the encoding regions are divided into no less than 79 exons which are distributed within the gene [Roberts, R G., et al., Genomics, 16:536-538(1993)]. Its pre-mRNA, the transcript of dystrophin gene, undergoes splicing

Patents 101

into the mature mRNA of 14 kb. The gene includes eight distinct promoter regions, which are also distributed within the gene and responsible for production of respective distinct mRNAs [Nishio, H., et al., J. Clin. Invest., 94:1073-1042(1994), Ann, A H. and Kunkel, L M., Nature Genet., 3:283-291(1993), D'Souza, V N. et al., Hum. Mol. Genet., 4:837-842(1995)]. Thus, dystrophin gene and its transcript are very complex in structure. Web site: http://www.delphion.com/details?pn=US06653467__ •

Method for assaying a human muscular dystrophy protein Inventor(s): Eguchi; Chikahiko (Kawasaki, JP), Ishiguro; Tsuneo (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 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,

102


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 antigenantibody reaction between a substance to be tested and the antiserum or antibody fraction. Web site: http://www.delphion.com/details?pn=US05340718__

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

DNA sequences encoding dystrophin minigenes and methods of use thereof Inventor(s): Xiao, Xiao; (Wexford, PA) Correspondence: David A. Einhorn, ESQ.; Anderson Kill & Olick, P.C.; 1251 Avenue OF The Americas; New York; NY; 10020; US Patent Application Number: 20030171312 Date filed: April 30, 2001 Abstract: The present invention provides a series of novel dystrophin minigenes that retain the essential biological functions. The expression of the dystrophin minigenes may be controlled by a regulatory element along with a small polyadenylation signal. The entire gene expression cassettes may be readily packaged into a viral vector, preferably an AAV vector. The present invention further defines the minimal functional domains of dystrophin and provides ways to optimize and create new versions of dystrophin minigenes. Finally, the present invention provides a method of treatment for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Excerpt(s): The present invention relates to novel dystrophin minigenes that retain the essential biological functions of a full length dystrophin gene, and methods of treatment for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) in a mammalian subject using the dystrophin minigenes. Duchenne muscular dystrophy (DMD) is an X-linked genetic muscle disease affecting 1 of every 3,500 newborn males (Kunkel et al. Nature (London) 322,73-77 [1986]). The progressive muscle degeneration and weakness usually confine the patients to wheelchairs by their early teens, and lead to death by their early twenties. DMD is caused by recessive mutations in the dystrophin gene, the largest gene known to date, which spans nearly 3 million basepairs on the X-chromosome with 79 exons, a coding sequence of about 11 kb, and a high rate of de novo mutations. (Koenig et al. Cell 50, 509-517 [1987]). Dystrophin is an enormous rod-like protein of 3,685 amino acids (aa) localized beneath the inner surface of muscle cell membrane (Watkins, S. C. et al. Nature 333, 863-866 [1988]). It functions through four major structural domains: a N-terminal domain (1-756 aa), a central rod domain (757-3122 aa), a cysteine rich (CR) domain (3123-3409aa), and a distal C-terminal domain (3410-3685 aa). The N-terminal domain binds to the F-actin of cytoskeletal structures, while the CR domain along with the distal C-terminal domain anchors to the

10

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

Patents 103

cell membrane via dystrophin-associated protein (DAP) complexes, thus, dystrophin crosslinks and stabilizes the muscle cell membrane and cytoskeleton. The central rod domain contains 24 triple-helix rod repeats (R1-R24) and 4 hinges (H1-H4). Each repeat is approximately 109 aa long. (Koenig et al. J Biol Chem 265, 4560-4566 [1990]). The central rod domain presumably functions as a "shock absorber" during muscle contraction. Dystrophin crosslinks and stabilizes the muscle cell membrane and cytoskeleton. The absence of a functional dystrophin results in the loss of DAP complexes and causes instability of myofiber plasma membrane. These deficiencies in turn lead to chronic muscle damage and degenerative pathology. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of early detection of duchenne muscular dystrophy and other neuromuscular disease Inventor(s): Hampton, Thomas G.; (Framingham, MA) Correspondence: Lahive & Cockfield; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20030003052 Date filed: June 19, 2002 Abstract: The mdx mouse is a model of Duchenne muscular dystrophy. The present invention describes that mdx mice exhibited clinically relevant cardiac phenotypes. A non-invasive method of recording electrocardiograms (ECGs) was used to a study mdx mice (n=15) and control mice (n=15). The mdx mice had significant tachycardia, consistent with observations in patients with muscular dystrophy. Heart-rate was nearly 15% faster in mdx mice than control mice (P

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