MUSCLE WEAKNESS 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., 1960Muscle Weakness: 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: 0-497-00730-4 1. Muscle Weakness-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:
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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 muscle weakness. 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 MUSCLE WEAKNESS ................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Muscle Weakness .......................................................................... 8 E-Journals: PubMed Central ....................................................................................................... 57 The National Library of Medicine: PubMed ................................................................................ 57 CHAPTER 2. NUTRITION AND MUSCLE WEAKNESS ....................................................................... 97 Overview...................................................................................................................................... 97 Finding Nutrition Studies on Muscle Weakness......................................................................... 97 Federal Resources on Nutrition ................................................................................................... 98 Additional Web Resources ........................................................................................................... 98 CHAPTER 3. ALTERNATIVE MEDICINE AND MUSCLE WEAKNESS ............................................... 101 Overview.................................................................................................................................... 101 National Center for Complementary and Alternative Medicine................................................ 101 Additional Web Resources ......................................................................................................... 105 General References ..................................................................................................................... 107 CHAPTER 4. PATENTS ON MUSCLE WEAKNESS ............................................................................ 109 Overview.................................................................................................................................... 109 Patents on Muscle Weakness ..................................................................................................... 109 Patent Applications on Muscle Weakness ................................................................................. 111 Keeping Current ........................................................................................................................ 112 CHAPTER 5. BOOKS ON MUSCLE WEAKNESS ............................................................................... 113 Overview.................................................................................................................................... 113 Book Summaries: Federal Agencies............................................................................................ 113 Chapters on Muscle Weakness................................................................................................... 114 CHAPTER 6. MULTIMEDIA ON MUSCLE WEAKNESS ..................................................................... 119 Overview.................................................................................................................................... 119 Video Recordings ....................................................................................................................... 119 CHAPTER 7. PERIODICALS AND NEWS ON MUSCLE WEAKNESS .................................................. 121 Overview.................................................................................................................................... 121 News Services and Press Releases.............................................................................................. 121 Newsletter Articles .................................................................................................................... 123 Academic Periodicals covering Muscle Weakness ..................................................................... 125 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 127 Overview.................................................................................................................................... 127 U.S. Pharmacopeia..................................................................................................................... 127 Commercial Databases ............................................................................................................... 128 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 133 Overview.................................................................................................................................... 133 NIH Guidelines.......................................................................................................................... 133 NIH Databases........................................................................................................................... 135 Other Commercial Databases..................................................................................................... 137 APPENDIX B. PATIENT RESOURCES ............................................................................................... 139 Overview.................................................................................................................................... 139 Patient Guideline Sources.......................................................................................................... 139 Finding Associations.................................................................................................................. 144 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 147 Overview.................................................................................................................................... 147 Preparation................................................................................................................................. 147 Finding a Local Medical Library................................................................................................ 147
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Medical Libraries in the U.S. and Canada ................................................................................. 147 ONLINE GLOSSARIES................................................................................................................ 153 Online Dictionary Directories ................................................................................................... 153 MUSCLE WEAKNESS DICTIONARY ...................................................................................... 155 INDEX .............................................................................................................................................. 231
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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 muscle weakness 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 muscle weakness, 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 muscle weakness, 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 muscle weakness. 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 muscle weakness, 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 muscle weakness. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON MUSCLE WEAKNESS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on muscle weakness.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and muscle weakness, 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 “muscle weakness” (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: •
Exercise Guidelines for Patients with Inflammatory Bowel Disease Source: Gastroenterology Nursing. Society of Gastroenterology Nurses and Associates. 21(3): 108-111. May-June 1998. Contact: Available from Williams and Wilkins, 351 West Camden Street, Baltimore, MD 21201-2436. Summary: Aerobic exercise can be beneficial for people with inflammatory bowel disease (IBD), because it tends to reverse muscle weakness and wasting and prevents the loss of calcium and protein that may commonly occur with IBD. Exercise is especially beneficial for people taking glucocorticoid medications; steroids may cause muscle atrophy and weakness, osteoporosis, and bone loss, which increases the risk for fracture. This article discusses five components that need to be included in an exercise
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program: mode of activity, intensity of exercise, frequency and duration of training, and progression. The signs and symptoms of potential complications are reviewed. The article emphasizes that people with IBD can benefit from a well-rounded exercise program that includes aerobic activities, such as brisk walking, jogging, swimming, cycling, or step aerobics, and resistance training with free weights, bands, or pulleys. To derive maximum benefit, aerobic activities must be performed 20 to 60 minutes a day, 3 to 5 days a week. 2 tables. 17 references. •
Importance of Regular Exercise for the Dialysis Patient Source: For Patients Only. 14(2): 16-18. March-April 2001. Contact: Available from For Patients Only. 18 East 41st Street, New York, NY 10017. (818) 704-5555. Fax (818) 704-6500. Summary: In this article, the author emphasizes the importance of regular exercise for the dialysis patient. The article is adapted from a book entitled Exercise: A Guide for People on Dialysis (Life Options Rehabilitation Advisory Council Resource Center,
[email protected] ). The benefits of regular exercise can be striking for dialysis patients, including improved energy levels, less depression and anxiety, reduced need for blood pressure medication, increased flexibility and muscle strength, and reduced risk of heart disease. The author emphasizes the importance of maintaining even a reduced level of activity, in order to prevent muscle weakness. The author outlines the three components of a good and complete fitness program: flexibility, strengthening, and cardiovascular. Readers are advised to consult with their nephrology team before beginning any exercise program. A commitment to a regular exercise program is needed, since regular exercise over an extended period of time is important. The article concludes with a list of simple safety rules to follow during exercise, particularly important for those persons just beginning to exercise after a long period of inactivity. A sidebar lists suggested information resources for exercise programs. 1 figure.
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Pelvic Muscle Exercises: Physiotherapy for the Pelvic Floor Source: Urologic Nursing. 14(3): 136-140. September 1994. Summary: In this article, the author provides a rationale for utilizing pelvic floor reeducation when deciding on appropriate management of all incontinent patients, because many have mixed symptoms. The author discusses the factors associated with pelvic muscle weakness; the muscles in the pelvic floor group; the principles of muscle training; assessment of the pelvic muscles; the use of the mnemonic PERFECT (Power, Endurance, Repetition, Fast contractions; Every Contraction Timed); the perineometer; pelvic muscle reeducation; pelvic muscle exercises; the use of vaginal cones; the role of biofeedback; and the use of neuromuscular electrical stimulation. For each treatment technique, the author cites research studies that support its efficacy. 3 figures. 29 references.
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Clinical Management of Diabetes in the Elderly Source: Clinical Diabetes. 19(4): 172-175. 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Managing type 2 diabetes in the elderly population is difficult because of complex comorbid (other illnesses present at the same time) medical issues and the
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generally lower functional status of elderly patients. Nationally published guidelines often do not apply to geriatric care, and practitioners' individualized approaches to therapy are highly variable. This article reviews the clinical management of diabetes in the elderly. Clinicians should be aware of and primed to recognize the syndromes more commonly occurring in elderly patients with diabetes: diabetic neuropathic cachexia (painful peripheral neuropathy or nerve disease, anorexia, depression and weight loss), diabetic neuropathy, amyotrophy (muscle weakness and muscle wasting), malignant otitis externa (external ear infection), and osteoporosis (low levels of bone density). Goals of therapy for elderly patients with diabetes should include an evaluation of their functional status, life expectancy, social and financial support, and their own desires for treatment. Coexisting health problems, such as dementia or psychiatric illnesses, may require a simplified approach to diabetes care. Overall goals should aim at reduction of all cardiovascular risk factors, smoking cessation, improvement in exercise, elimination of obesity, and optimal control of hypertension (high blood pressure). The authors review five different types of medications and their use in elderly patients: alpha glucosidase inhibitors (Precose and Glyset); biguanides such as metformin (Glucophage); sulfonylureas (e.g., Glucotrol, Micronase, Glynase, Diabeta); thiazolidinediones (Avandia, Actos); and insulin. Complicating aspects of the physiology of aging include changes in the pharmacokinetics (how a drug works) of both insulin and oral medications. Changes in drug absorption, distribution, metabolism, and clearance must be considered when treating any condition in elderly patients. The authors conclude that ideal geriatric care requires a multidisciplinary approach. Successful diabetes care in the aging population requires an understanding of the physiology of aging, recognition of the special issues facing the elderly, and interaction with geriatricians, diabetologists, pharmacists, social workers, diabetes educators, and dietitians to ensure the most effective treatment. 1 table. 22 references. •
Maternally Inherited Diabetes and Deafness: A Multicenter Study Source: Annals of Internal Medicine. 134(9 Part 1): 721-728. May 1, 2001. Contact: Available from American College of Physicians-American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Summary: Maternally inherited diabetes and deafness (MIDD), which is seen in 0.5 percent to 2.8 percent of patients with type 2 diabetes mellitus, is related to a point mutation at position 3243 of mitochondrial (mt) DNA. The clinical description of MIDD is incomplete. This article reports on a study of the clinical presentation and complications of diabetes in patients with MIDD, undertaken to identify clinical characteristics that may help select patients with diabetes for mtDNA mutation screening. The study included 54 patients with type 2 diabetes mellitus and the mtDNA 3243 mutation, from 16 French departments of internal medicine, diabetes, and metabolic diseases. On average, patients with MIDD were young at diabetes onset and presented with a normal or low body mass index. None were obese; 73 percent of subjects had a maternal family history of diabetes. Diabetes was non insulin dependent at onset in 87 percent of patients; however, 46 percent of patients had non insulin dependent disease at onset but progressed to insulin therapy after a mean duration of approximately 10 years. Neurosensory hearing loss was present in almost all patients. Of the patients who received an ophthalmologic examination, 86 percent had macular pattern dystrophy (a specific retinal lesion). Myopathy (muscle weakness and wasting) was found in 43 percent of patients, 15 percent had cardiomyopathy (wasting and weakness of the heart muscles), and 18 percent (9 of 51 patients) had neuropsychiatric symptoms. The prevalence of diabetic retinopathy (eye disease) was 8 percent among
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patients who received an ophthalmologic examination, lower than expected after a mean 12 year duration of diabetes; prevalence of kidney disease was 28 percent. This suggests that a specific renal involvement was the result of mitochondrial disease. The authors conclude that MIDD has a specific clinical profile that may help identify patients with diabetes who should undergo mtDNA testing. 2 figures. 1 table. 46 references. •
Dental Findings in Morquio Syndrome (Mucopolysaccharidoses Type IVa) Source: Journal of Dentistry for Children. 67(6): 431-433. November-December 2000. Contact: Available from American Society of Dentistry for Children. John Hancock Center, 875 North Michigan Avenue, Suite 4040, Chicago, IL 60611-1901. (312) 943-1244. Summary: Morquio syndrome is a genetic disorder of mucopolysaccharide metabolism characterized by skeletal deformities (including dwarfism and general osteoporosis), neurological symptoms, facial features of short nose and broad mouth, muscle weakness and hyperextensible joints, corneal opacities, progressive deafness, normal intelligence, and dental manifestations. This article reports the case of dental findings in a 2 year old male with suspected Morquio syndrome. The authors report how the dental findings helped with the diagnosis of Morquio syndrome and then discuss the child's dental follow up over the next 10 years. Dental treatment has been confined to preventive regimens involving dietary analysis and advice, tooth brush instruction, systemic and topical fluorides, and fissure sealants. The authors discuss the dental manifestations of Morquio syndrome, which are usually confined to enamel defects (the enamel is described as thin, with a tendency to fracture and flake off); tooth discoloration can be greyish or yellowish which probably reflects normal color variation in the dentin which underlies the thin translucent enamel. The authors note that the dental findings are similar to those found in hypoplastic amelogenesis imperfecta. 3 figures. 15 references.
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Myasthenia Gravis: Dental Treatment Considerations Source: SCD. Special Care in Dentistry. 17(1): 25-32. January-February 1997. Summary: Myasthenia gravis (MG) is an autoimmune neuromuscular disorder that presents challenges for the dental practitioner. Facial and masticatory muscles may be involved and complicate dental treatment. Exacerbation of the skeletal muscle weakness and fatigability that characterize this disorder can be precipitated by certain medications used in dentistry. In this article, the authors review the epidemiology, clinical features, diagnosis, and treatment of MG; describe the dental treatment experience of patients with MG seen in a hospital-based dental clinic; and discuss special considerations, including drug precautions, for the effective management of patients with MG in dental practice. A review of 47 dental treatment episodes in 16 patients with MG was undertaken to identify neuromuscular responses to dental treatment and post-dental treatment medical therapy required for control of resultant exacerbations of muscular weakness. Neuromuscular sequalae occurred in 5 treatment episodes for four different patients. 4 figures. 3 tables. 25 references. (AA-M).
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Understanding Strategies for the Treatment of Ischemic Steal Syndrome After Hemodialysis Access Source: Journal of the American College of Surgeons. 191(3): 301-310. September 2000. Contact: Available from Journal of the American College of Surgeons. P.O. Box 2127, Marion, OH 43306-8227. (800) 214-8489 or (740) 382-3322. Fax (740) 382-5866.
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Summary: The recently published guidelines of the National Kidney Foundation Dialysis Outcome Quality Initiative (NKF DOQI) have focused on improving patient outcomes and survival by providing recommendations for optimal clinical practice. These guidelines firmly endorse the establishment of autogenous hemodialysis access and recommend a 40 to 50 percent prevalence of autogenous fistulas among all hemodialysis patients. As surgeons strive to meet these guidelines, it will be necessary to extend autogenous reconstruction to older individuals, people with diabetes, and patients with suitable vein only in the upper arm. These individuals are at increased risk of developing ischemic steal syndrome. This article offers strategies for the treatment of ischemic steal syndrome after hemodialysis access. Ischemic (deficiency of blood in a certain body part) steal syndrome is characterized by extremity coolness and vague neurosensory changes; in more severe cases, patients report ischemic rest pain, ischemic ulceration of the fingers, or intrinsic muscle weakness. The authors stress that surgeons who perform vascular access procedures must have a firm understanding of the symptoms, diagnostic maneuvers, and treatment options for ischemic steal syndrome. The authors explain the distal revascularization, interval ligation (DRIL) procedure in some detail, recommending it as offering substantial benefits for treating patients with ischemic steal syndrome. 6 figures. 1 table. 20 references. •
Subacute Diabetic Proximal Neuropathy Source: Mayo Clinic Proceedings. 72(12): 1123-1132. December 1997. Summary: This article describes a study that evaluated the clinical, electrophysiologic, autonomic, and neuropathologic characteristics and natural history of subacute diabetic proximal neuropathy, as well as its response to immunotherapy. A retrospective review of medical records of patients at the Mayo Clinic who had diabetes with subacute onset and progression of proximal weakness was conducted from 1983 to 1995. The responses of treated versus untreated patients were compared statistically. Results reveal that there were 44 patients with subacute diabetic proximal neuropathy during the study period. Most were middle-aged or elderly, and no sex preponderance was noted. The proximal muscle weakness was often associated with reduced or absent lower extremity reflexes. Associated weight loss was a common finding. Patients frequently had some evidence of demyelination on nerve conduction studies, but it was invariably accompanied by concomitant axonal degeneration. Also, the cerebrospinal fluid protein concentration was usually increased, and diffuse, substantial autonomic failure was generally present. In most cases, a sural nerve biopsy specimen suggested demyelination, although evidence of an inflammatory infiltrate was less common. Of 12 patients who received treatment with prednisone, intravenous immune globulin, or plasma exchange, 9 saw their conditions improve, but 17 of 29 untreated patients with followup also eventually improved, but at a much slower rate. Improvement was usually incomplete. The article concludes that subacute diabetic proximal neuropathy is a severe, extensive variant of bilateral lumbosacral radiculoplexopathy, with some features suggesting an immune-mediated cause. It recommends that, because treatment is unproven, it be restricted to those patients who have severe, bilateral, progressive deficits. 5 tables. 21 references. (AA-M).
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Myopathy Source: STEP Perspective; Vol. 5, No. 3. Contact: Seattle Treatment Education Project, 1123 E John St, Seattle, WA, 98102, (206) 329-4857, http://www.thebody.com/step/steppage.html.
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Summary: This journal article reviews the two most common causes of myopathy in HIV-infected people, primary HIV infection and a reaction to zidovudine (AZT). The article states that the diagnosis is based on clinical symptoms of muscle weakness and pain, can be confirmed by a blood test, and rarely requires biopsy of the muscles. It describes the causes and treatments for myopathy and stresses differential diagnosis for myopathy and AIDS wasting syndrome because although the symptoms are similar, the treatments are different.
Federally Funded Research on Muscle Weakness The U.S. Government supports a variety of research studies relating to muscle weakness. 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 muscle weakness. 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 muscle weakness. The following is typical of the type of information found when searching the CRISP database for muscle weakness: •
Project Title: A SYSTEM FOR MEASURING PELVIC MUSCLE STRENGTH IN WOMEN Principal Investigator & Institution: Cole, Neil Martin.; President; Bio Logic Engineering, Inc. 1675 N Lima Center Rd Dexter, Mi 48130 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2004 Summary: (provided by applicant): One in nine women suffer from pelvic floor dysfunction, including urinary incontinence and vaginal wall or uterine prolapse (VUP). Stress urinary incontinence (SUI) affects 38% of women over the age of 65 years and over 13 million women in the United States. Pelvic muscle strength is commonly assessed in these patients. However, current measurement techniques are either subjective or produce artifact, due to their non-isometric nature or contamination by intraabdominal pressure. During Phase I, we developed a second generation system that measures the isometric strength and contractile properties of female pelvic floor muscles. The system centerpiece is a novel intravaginal transducer that differentiates between intraabdominal pressure and levator ani force. During Phase II, system mechanics, electronics and software will be refined to improve system sensitivity, accuracy, and ease-of-use. Laptop- and Personal Data Assistant-based systems will be developed and validated. Clinical device performance will be confirmed by testing the null hypothesis in 120 women (40 healthy continent, 40 with VUP, 40 with SUI) that localized pelvic floor muscle defects visible on MR scans will correlate with pelvic
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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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muscle weakness. The system allows assessment of pelvic floor function and exercise intervention efficacy, and can provide biofeedback and adherence data during training. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALTERATIONS IN NEUROMUSCULAR FUNCTION FOLLOWING BURNS Principal Investigator & Institution: Martyn, J A.; Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-DEC-1983; Project End 31-MAR-2007 Summary: (provided by applicant): Muscle weakness accompanies all forms of critical illnesses including burns, resulting in hypoventilation, dependence on respirators, and decreased mobilization, all of which lead to increased morbidity and mortality. The loss of muscle strength is out of proportion to loss of muscle mass. It is hypothesized (a) since prolonged open channel time of acetylcholine receptors (AChRs) due to congenital mutations of AChRs results in muscle weakness, the weakness of muscles in close proximity to bums is related to the expression of gamma subunits containing an "immature" isoform of AChRs, which also have a longer mean open-channel time; (b) that akin to that seen in many congenital muscular dystrophies (CMDs), the weakness in muscles at sites distant from burn occurs as a result of changes in muscle membrane structural components termed dystrophin associated complexes (DACs). It is postulated that the pathophysiological bases for the neuromuscular changes following burns are related to (a) decreased signaling via agrin, important for clustering, expression, and maturation of the AChRs, and (b) decreased growth factor signaling via Akt/PKB, important for stabilization and maintenance of DACs, respectively. Related to the above: Specific Aim 1 tests the hypotheses (1) that muscles in close proximity to burn injury express an immature isoform of AChRs at the neuromuscular junction (NMJ), resulting in aberrant neurotransmission, (2) that these AChR changes are related to increased expression of iNOS, resulting in decreased signaling of agrin, and (3) that iNOS inhibitors and/or exogenous agrin will reverse the AChR changes and enhance muscle function. Specific Aim 2 tests the hypothesis that the diminished contractility of skeletal muscle at sites distant from bum is due to changes in muscle membrane DAC, independent of AChRs, since AChRs are unaltered at sites distant from burn. Muscle membrane costamere integrity will be determined by confocal microscope. Biochemical fractionation techniques (velocity gradients) will be utilized to detect molecular localization of each DAC component (dystrophin, dystroglycan, caveolin-3, and integrin), since abnormal localization of these membranes will result in disruption of costamere integrity. Specific Aim 3 using the rat in vivo model and the in vitro cell culture model, tests the hypothesis that bum injury-induced malformation of DAC is due to decreased pro-anabolic signaling via Akt/PKB. Specific Aim 4 tests the hypothesis that the attenuated Akt/PKB activity at sites distant from burn can be rectified by parenteral IGF-I or adenovirus transfer of Akt/PKB, both of which will restore the DAC integrity and function to normal. Delineation of the pathophysiology of burn-induced muscle dysfunction will provide a scientific rationale for therapeutic approaches to prevent muscular complications of burns. These mechanistic studies will also help to understand the molecular etiology of other acquired and congenital diseases of muscle, which affect muscle function in a vast number of adult and pediatric patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANABOLIC STEROIDS AND EXERCISE IN HEMODIALYSIS Principal Investigator & Institution: Johansen, Kirsten L.; Assistant Professor; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: The federally-funded End Stage Renal Disease program was initiated in 1972 with the goal of extending the lives of individuals with kidney disease and allowing them to return to the work force. Though dialysis has prolonged the lives of patients with ESRD, it has not produced the expected degree of occupational and physical rehabilitation. A recent study showed that more than one third of hemodialysis patients had a Karnofsky score below 70, meaning that they were unable to perform the normal activities of daily living without assistance. Investigation into the causes of this striking debility has been limited, but muscle atrophy and concomitant weakness probably contribute. Reduced lean body mass (LBM) and muscle weakness have been demonstrated in this population. Since muscle strength correlates with performance measures such as gait speed in elderly subjects, the reduction in LBM in dialysis patients may affect functional status, and treatments designed to increase muscle size and strength could be of benefit to such individuals. Both anabolic steroid treatment and resistance exercise training (RE) increase strength and muscle mass in healthy subjects. RE also resulted in improved functional status in frail elderly subjects. While there have been no reports of the effects of RE in patients on dialysis, we recently showed that nandrolone decanoate (ND), a 19-nortestosterone derivative, increased LBM and improved walking and stair-climbing time in patients on dialysis. Furthermore, ND was safe in this population and resulted in only occasional mild side effects. In the current application, we propose to perform two studies concurrently. In one, to elucidate the mechanisms of the muscle defects of dialysis patients, healthy control subjects and patients on dialysis will undergo measurement of physical activity levels, and of muscle size, strength, and oxidative capacity. In the second, we will determine whether RE and/or anabolic steroids can increase muscle size and improve muscle strength and physical performance in patients on hemodialysis. In a 12-week study, 80 hemodialysis patients will be randomly assigned to one of 4 groups as follows: ND, weekly ND injections; EX, resistance exercise training plus placebo injections; ND-EX, ND injections plus RE; and PL, placebo injections only. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANKLE STRENGTHENING TO IMPROVE GAIT AND FUNCTION IN CP Principal Investigator & Institution: Engsberg, Jack R.; Associate Professor; Neurological Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2005 Summary: (provided by the applicant): Many treatments exist to improve the gait and function of persons with Cerebral Palsy (CP). Despite recognizing that muscle weakness is a major impairment in CP, none of the treatments have the direct aim of strengthening muscles. Our results from an NIH investigation (R01-NS035830) indicated high correlations between ankle strength and function, with greater strength correlated with higher function. The idea of strengthening muscles has been controversial for safety issues. The purposes of this pilot investigation are to: 1) establish sample sizes for a future randomized clinical trial determining if intensive ankle strength training programs can improve strength, gait, and function without increasing spasticity; and 2)
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investigate potential safety issues arising from the training programs. Aim 1: Establish sample sizes for a future randomized clinical trial determining if intensive ankle strength training programs can improve ankle strength, gait, and function without increasing spasticity. Twenty ambulatory subjects with spastic diplegia CP will be randomly assigned to one of 4 groups: 1) Dorsi-flexor strength training group; 2) Plantar-flexor strength training group; 3) Dorsi-plantarflexor strength training group; and 4) the group undergoing no intensive strength training program. Subjects in the strength training groups will participate in a 12-week progressive, resistance strengthtraining program. Prior to, and at the end of the training program, all subjects will be objectively assessed for ankle Plantar-flexor spasticity, ankle strength, gait, and GMFM. The data will be used in a repeated measures power analysis to establish sample sizes for the clinical trial. Aim 2: Investigate potential safety issues arising from the training programs. The aim has 2 components. The first is the weekly measurement of Plantarflexor spasticity and tightness. The data will permit continuous monitoring of spasticity and tightness, and alert investigators to potential problems during each subject's participation. In the second component, both the pre- and post-intervention measures, and the weekly monitoring of spasticity and tightness, will determine if potential changes could be a concern for the future clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ARGINASE AND REGULATION OF NITRIC OXIDE SYNTHASE IN ALS Principal Investigator & Institution: Ratan, Rajiv R.; Director; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 15-AUG-2001; Project End 31-JUL-2005 Summary: (Adapted from applicant's abstract): Amyotrophic lateral sclerosis is a prevalent neurological disorder characterized by inexorable muscle weakness leading to death. The principal pathological finding in amyotrophic lateral sclerosis is loss of nerve cells in the anterior horns of the spinal cord, the motor nuclei of the brainstem, and the upper motor neurons of the cerebral cortex. Investigations aimed at preventing or limiting progression of amyotrophic lateral sclerosis have thus focused on the mechanisms by which neurons degenerate. A transgenic mouse model has been developed that possesses many of the pathological and clinical features of human familial and sporadic amyotrophic lateral sclerosis. As nitric oxide (NO) has been shown to mediate neuronal loss in other neurodegenerative conditions, several groups have investigated the role that NO may play in disease progression | in the transgenic model. The results have been conflicting likely because currently available inhibitors of nitric oxide synthase do not permit optimal control of NO generation within particular cell types and subcellular compartments. A novel potential strategy for regulating nitric oxide synthesis involves the enzyme arginase that can | regulate availability of arginine in the cytoplasm or mitochondria. In preliminary studies, we have shown that: 1) extracellular arginase blocks neuronal apoptosis and 2) arginase immunoreactivity is, upregulated in the spinal cord of ALS transgenic mice as well as humans with the sporadic and familial forms of amyotrophic lateral sclerosis. These preliminary results lead to the overall hypothesis to be tested in this proposal: about Interventions aimed at promoting arginase activities in microglia, astrocytes and/or motor neurons will limit availability of cell arginine for toxic NO generation and thereby diminish cell death and disease progression in amyotrophic lateral sclerosis but permit NO to, mediate its survival promoting effects in each of these cell types. We propose to test this hypothesis by: 1) determining the cell types and subcellular compartments where arginase is
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Muscle Weakness
expressed in the normal central nervous system of humans and mice, and how the localization and levels of these isoforms change in amyotrophic lateral sclerosis as well as in a transgenic mouse! Model of amyotrophic lateral sclerosis and how this compares to the localization of NOS (all forms) in these tissues; and 2) determining whether increased arginase activity in microglia, astrocytes or neurons from control mice or mice over expressing SOD1 mutant (G93A) will abrogate NO mediated toxicity of motor neurons induced by growth factor deprivation, excitotoxins or LPS/IFN-gamma treatment. These studies promise to enhance our understanding of how arginine about metabolism, including the synthesis of NO, is regulated in the normal and abnormal nervous system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CAUSES AND CONSEQUENCES OF HYPERKYPHOSIS IN OLDER WOMEN Principal Investigator & Institution: Kado, Deborah M.; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2004; Project Start 01-SEP-2004; Project End 30-JUN-2008 Summary: (provided by applicant): Hyperkyphosis refers to an excessive curvature of the thoracic spine, commonly known as the "Dowagers hump." It is frequently observed in the older population, and yet little is known about its causes or consequences. It is generally assumed, but not proven, that hyperkyphosis primarily results from vertebral fractures, although previous small studies suggest that osteoporosis only accounts for less than half of hyperkyphosis. Potential other causes of hyperkyphosis include a genetic predisposition, degenerative disc disease, and muscular weakness. Hyperkyphosis is associated with adverse outcomes including restricted pulmonary function, poor physical function, and an increased risk of mortality that is not accounted for by vertebral fractures. These previous studies suggest that hyperkyphosis is an important clinical indicator of poor health. However, there are no set clinical criteria that define what degree of kyphotic angle constitutes hyperkyphosis. Therefore, defining hyperkyphosis and determining its causes and consequences has important implications for the health of older patients. To define hyperkyphosis, understand its pathogenesis and learn its health outcomes, we propose to conduct a series of analyses using an existing comprehensive data set, the Study of Osteoporotic Fractures (SOF). SOF is the first and largest prospective U.S. study devoted primarily to the study of osteoporotic fractures in older women. Since 1986, participants have attended serial exams of risk factors for fractures and other chronic diseases. In this study, we propose to measure the kyphotic angle from existing baseline radiographs and from repeated radiographs taken an average of 3.5 and 15 years after baseline. We created a digitization program that calculates the most widely used radiological measure of kyphosis, the Cobb angle. Thus, a reliable measure can be made in a large number of subjects with minimal effort. Using existing data from SOF, we will: 1) quantify the kyphotic angle in 1000 older women and determine how much of hyperkyphosis is due to underlying osteoporosis and how much is related to other potential risk factors including a genetic predisposition, muscle weakness, intervertebral disc height loss, and health behaviors; and 2) define what degree of kyphoUc angle constitutes hyperkyphosis by its association with important outcomes including falls, fractures, and functional limitations. This is the first comprehensive study of the causes and consequences of hyperkyphosis. This costeffective and innovative use of an existing data set is likely to produce the first systematic analyses of this common condition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHARACTERIZATION OF MECHANICAL BASED INJURY IN MUSCLE Principal Investigator & Institution: Lutz, Gordon J.; Veterans Medical Research Fdn/San Diego Foundation of San Diego San Diego, Ca 92161 Timing: Fiscal Year 2002; Project Start 07-APR-2000; Project End 31-JUL-2002 Summary: (adapted from Investigator's abstract) When skeletal muscle is forcibly lengthened while activated (eccentric contraction), injury occurs to the muscle that is characterized by a rapid and prolonged loss in force-generating ability followed by delayed onset muscular soreness. Injury to skeletal muscle from eccentric contractions is an extremely common clinical condition that occurs as a result of vigorous exercise or other forms of normal and accidental muscle overuse. Although recent studies have provided some important insights into the cellular and biochemical adaptations that follow eccentric contraction-induced injury, the precise mechanical conditions, at the level of the sarcomere, that result in mechanical injury remain poorly understood. For example, studies from various animal models have reported conflicting results as to whether mechanical stress or strain is the primary determinant of muscle injury. Also, the precise influence of initial sarcomenre length and lengthening velocity on injury remains poorly characterized. Further, only indirect evidence exists as to whether fibers of a particular size and type are selectively predisposed to mechanical injury. Although it has been theorized that non-uniformity in sarcomere length during eccentric contractions leads to mechanical instability, sarcomere popping and subsequent injury, direct tests of this theory have been difficult to achieve. Our understanding on the mechanical basis of muscle injury has been limited because most studies have been performed on whole muscles. The problem with whole muscle preparations is that sarcomeric strain and mechanical stress in individual fibers cannot be measured directly or predicted accurately. In contrast, single isolated fibers allow for accurate measurement of sarcomere strain along the entire length of the cell, and thus permit precise correlations to be made between mechanical events and contractile performance. However, because single intact fibers are extremely difficult to isolate from mammalian muscle, single fiber studies in mammals are restricted to skinned fiber preparations, where the cell membrane is disrupted, drastically altering the fiber's mechanical properties and cell signaling pathways. In contrast to mammalian muscle, single intact fibers can be readily isolated from frog muscle that retain complete mechanical stability, making it possible to study mechanical injury in an intact cellular environment at the single fiber level. Thus, the purpose of this proposal is to study mechanical-based muscle injury during eccentric contractions using intact frog single fibers. The mechanics experiments will be performed while monitoring segment length and sarcomere length transients along the full length of the fiber, providing a very precise and high resolution correlation between mechanical events (fiber stress and sarcomeric strain) and muscle injury. The extent of sarcomere popping will also be evaluated. The mechanical events that result in injury will be related to fiber size and fiber type at the single fiber and individual segment level. The aged population is particularly susceptible to the debilitation effects of eccentric contraction-induced injury because of general muscle weakness and poor regenerative properties. An understanding of the precise mechanical conditions that result in muscle injury could lead to improvements in the development of preventative therapies and rehabilitation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Muscle Weakness
Project Title: NEUROPATHIES
CHARACTERIZATION-NOVEL
SUBTYPES-INHERITED
Principal Investigator & Institution: Lawson, Victoria H.; Neurology; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 21-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): The goal of this project is to clinically characterize and define gene mutations responsible for novel and unusual forms of inherited neuropathies (Charcot-Marie-Tooth) in large Utah families. Charcot-Marie-Tooth (CMT) is one of the most common degenerative neurological disorders with a prevalence of 1 in 2500. It is a clinically heterogeneous group of disorders with distal limb muscle weakness, wasting, and sensory loss usually presenting in childhood or early adulthood and typical skeletal abnormalities. The broad classification of CMT into types 1 and 2 based on electrophysiology and pathology is giving way to genetic classification, reflecting significant genetic heterogeneity. At least 10 CMT gene loci have been defined. The applicant proposes to identify and extensively phenotype novel and unusual forms of CMT by studying large kindreds. Linkage analysis will be performed, then a genome wide screen using polymorphic markers across the genome. Candidate genes in the region of linked loci will be identified from the growing Human Genome Project database and mutation analysis will be performed. One large Utah kindred with an axonal form of CMT has already been studied in detail and no linkage to described loci has been found. Therefore, this represents a completely novel form of axonal CMT. A genome-wide screen for linkage is underway. To date 221 screening markers across the genome have been genotyped, and of these, 1 candidate locus has been identified with a LOD score of nearly 2. Four additional large kindreds have been ascertained: Historical data has been collected on many of these family members and clinical/ electrophysiologic examination is underway. The largest kindred has a maximum simulated LOD score of 9.74. Preliminary data suggest these families may be phenotypically distinct from the family already described and, in at least one kindred, from previously described phenotypes. Therefore, these families may represent additional novel loci. Through an NIH funded K30 award, the University of Utah General Clinical Research Center provides a unique didactic program of training in clinical research focused on the inherited basis of human disease. This program incorporates access to resources such as multiuser core facilities, large research centers at the University, and a designated unit in the University Hospital, with specific, mentored, intensive research experiences for maturing clinical investigators. Thus, the University of Utah provides an ideal environment for maximizing the potential of this project and this project applicant. Molecular characterization of novel and unusual forms of CMT will define basic biologic processes of peripheral nerve function, and may lead to new diagnostic and therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTINUOUS MEASUREMENT OF BREATHLESSNESS Principal Investigator & Institution: Baird, John C.; Psychological Applications, Llc Waterbury, Vt 05676 Timing: Fiscal Year 2003; Project Start 10-SEP-2001; Project End 31-JAN-2005 Summary: (provided by applicant): The objective of this research is to evaluate a computer-assisted, continuous method for measuring breathlessness during exercise. The method represents a new approach to obtain subjective ratings from patients exercising on a cycle ergometer or treadmill. Whereas the "gold standard" Borg scale for
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measuring breathlessness is employed in over one million patients per year, it is limited by the fact that each estimate occurs at a discrete point in time cued or signaled by the health professional, rather than when the patient senses a change in symptom intensity. Moreover, if the patient cannot verbalize a response (e.g., while breathing through a mouthpiece), the rating must be indicated on the scale by finger pointing. During exercise this can lead to uncertainty on the part of the clinician as to exactly where the patient is pointing. The continuous method for obtaining patient-initiated ratings is unencumbered by these limitations, while also providing a direct measure of the absolute threshold and peak of breathlessness. The software to obtain such ratings has been shown to be reliable, valid, and easy to use. Thus far, the method has been successfully applied in patients with chronic obstructive pulmonary disease. The goal of Phase II is to evaluate the new methodology with a wider sample of adult patients afflicted with asthma, interstitial lung disease, respiratory muscle weakness, and pulmonary vascular disease, as well as with a group of children with asthma. Tests will also be conducted to investigate the responsiveness of the continuous method to track the effects of bronchodilator therapy and respiratory load. PROPOSED COMMERCIAL APPLICATION. The commercial goal is to replace the discrete scale with a computeradministered continuous method for measuring breathlessness during exercise. The product marketed in Phase III will be a computer software package that will be purchased by physicians, clinics and hospitals throughout the world. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEPLETION OF MITOCHONDRIAL S-NITROSOTHIOLS IN ALS Principal Investigator & Institution: Mannick, Joan B.; Assistant Professor; Medicine; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): There is increasing evidence that mitochondrial dysfunction contributes to amyotrophic lateral sclerosis (ALS) pathogenesis. However the causes of mitochondrial dysfunction in ALS are not known. We hypothesize that familial ALS-associated SOD1 mutants aberrantly deplete S-nitrosothiols (SNOs) in mitochondria leading to mitochondrial degeneration and motor neuron death. Snitrosothiols are peptides and proteins that have an NO group attached to a cysteine residue. Peptide SNOs are potent antioxidants and neuroprotective. S-nitrosylation of critical cysteine residues on proteins is emerging as a mechanism of signal transduction regulation. Therefore aberrant depletion of mitochondrial SNOs is likely to be a toxic gain-of-function of SOD1 mutants. This is a novel testable working hypothesis in a virtually unexplored area in the ALS field. In support of our hypothesis, our preliminary data indicate that peptide and protein SNOs are located primarily in the mitochondria of cell lines expressing wild-type SOD1. Moreover, SNO levels are significantly decreased in the mitochondria of cells expressing SOD1 mutants. In specific aim 1 of the proposed studies we will extend our preliminary studies in cell lines to an in vivo animal model and determine if mitochondrial SNO levels are decreased in the spinal cord of mutant SOD1 transgenic mice before or at the time of onset of muscle weakness. In specific aim 2 we will determine if restoration of mitochondrial SNO levels improves mitochondrial function and the viability of cells expressing mutant SOD1. If we confirm our hypothesis, then in future studies we will determine if SNO donor compounds improve the survival of mutant SOD1 transgenic mice. Our long term goal is to determine if SNO donor compounds (which have been used for decades in the
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Muscle Weakness
treatment of coronary artery disease with limited toxicity) have therapeutic efficacy in patients with ALS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DISEASE PROGRESSION AND OXIDATIVE STRESS IN ALS Principal Investigator & Institution: Xu, Zuoshang; Associate Professor; Pharmacology; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 01-APR-1996; Project End 31-JAN-2004 Summary: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes degeneration of motor neurons, leading to skeletal muscle atrophy, paralysis and death. Mutations in Cu/Zn superoxide dismutase (SOD1) are one cause of ALS. Transgenic mice that express mutated SOD1 develop ALS similar to human disease. To determine the mechanism by which mutant SOD1 causes motor neuron degeneration, we will test three hypothesis: 1) ALS caused by different SOD1 mutations undergo different clinical and pathological progression; 2) mitochondrial damage precedes the onset of muscle weakness and accumulation of this damage leads to a dysfunction and deletion of normal mitochondria in motor neurons, culminating the onset of ALS; 3) oxidative stress plays a role in triggering the onset of ALS. To test the first hypothesis, we will investigate the pathological evolution in correlation with clinical progression in mice expressing G85R mutation and compare the findings with G37R and G93A mutants. We will delineate and compare the sequence of pathological events leading to motor neuron death in these three lines. By this approach, we will determine the differences and common characteristics of ALS caused by different SOD1 mutations. The outcome of this study will provide guidance to further elucidation of the disease mechanism and help to improve prognosis and design therapies tailored to different mutations. To test the second hypothesis, we will use electron microscopy to characterize the types of mitochondrial abnormality before and after onset of the disease. We will also determine the earliest time when mitochondrial abnormalities emerge and quantify the changes in the number of normal and abnormal mitochondria before and after the onset of the disease. To test the role of mitochondrial abnormality in triggering the onset of the disease, we will test whether energy supplementation by administering creatine delays the onset of the disease. To test the third hypothesis, we will measure the levels of oxidative markers at different disease stages to determine whether oxidative damage precedes or follows the onset of ALS. Further, we will test whether and how anti-oxidant treatment changes the course of disease progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECT OF LEG STRENGTHENING EXERCISE AFTER HIP FRACTURE Principal Investigator & Institution: Mangione, Kathleen K.; Physical Therapy; Arcadia University 450 S Easton Rd Glenside, Pa 19038 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2004 Summary: (provided by applicant): Hip fracture is a common medical problem that can drastically change the quality of life for the elderly person. More than 300,000 older people are expected to fracture a hip each year at an estimated cost of 5 billion dollars. Interventions have not been identified that successfully return a majority of persons to their prefracture level of function following hip fracture. Muscle weakness, loss of balance and decreased physical endurance remain. These impairments are associated
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with slowed gait speed, decreased independence in ambulation, and inability to perform simple activities of daily living. Therefore, despite the improvements in medical care, functional recovery has not occurred. The purpose of this study is to examine the effectiveness of high intensity strengthening exercise used in the home setting for patients who sustain hip fracture. Intervention will begin six months after fracture to ensure healing of bone and soft tissue. Strengthening exercises will be performed twice a week for ten weeks and will be directed to the lower extremity muscles because of their role in gait and transfers. A control group will receive placebo intervention to the same muscle groups. Outcomes will be compared between groups after the intervention and one year after fracture. Effectiveness will be assessed using an impairment measure (quadriceps muscle force production), a functional limitation measure (gait speed), and a disability measure (self-reported physical function). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTIVENESS FIBROMYALGIA
OF
STATIC
MAGNETIC
FIELDS
IN
Principal Investigator & Institution: Boyden, Kathleen M.; None; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-JUN-2002 Summary: Fibromyalgia affects up to an estimate 10 percent of the population, primarily women. The syndrome is characterized as both a musculoskeletal and a subtle neurological disorder, and is associated with widespread muscle pain and tender points, along with fatigue, muscle weakness, and stiffness. Conventional medical approaches have limited success in treating fibromyalgia, leading patients to seek complementary therapies, including the use of magnetic therapies, in the hope of finding more effective pain relief. However, the efficacy and safety of magnetic therapy has not been definitively established through rigorously controlled trials. This double-blind randomized placebo-controlled study is the second in a series investigating the efficacy of static magnetic field (SMF) therapies in alleviating symptoms associated with fibromyalgia. Chronic conditions are frequently associated with poor quality of life; and fibromyalgia is associated with even poorer quality of life than a variety of other chronic conditions such as rheumatoid arthritis, osteoarthritis, permanent ostomies, chronic obstructive pulmonary disease, and insulin dependent diabetes. Successful management of pain, the primary symptom of fibromyalgia, may result in improved quality of life. The study tests the primary hypotheses that locally applied quadripolar SMF devices, which have been shown to suppress the firing of action potentials of sensory neurons, will provide pain reduction and other therapeutic benefits. It is further proposed that treatment with SMF devices will lead to improved functional status and improved quality of life. The specific aims of the research are to compare the effects of quadripolar SMF devices externally applied to tender points and the effects of magnetic placebo devices. The proposed study will include a 6-month treatment period and a 9 month follow-up assessment to determine long-term effectiveness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF BACLOFEN ON MUSCLE STRENGTH IN CEREBRAL PALSY Principal Investigator & Institution: Damiano, Diane L.; Associate Professor; Neurology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 15-JUL-2001; Project End 30-JUN-2005
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Muscle Weakness
Summary: Cerebral palsy (CP) is the most prevalent physical disability originating in childhood of which spasticity and weakness are primary clinical signs. Spasticity management in this population has changed dramatically in the past two decades, first with the introduction of selective dorsal rhizotomy (SDR) and most recently with the introduction of intrathecal baclofen (ITB) pump implantation. ITB is efficacious for persons with spasticity of spinal origin; however, the clinical results in CP, while generally positive, are less well-established, reduction in spasticity is typically less marked, and functional gains are less impressive or even equivocal. Reported positive effects of ITB include a relaxation in spasms and spasticity which may reduce associated discomfort and improve ease of movement. A major unresolved question is whether muscle weakness is a direct effect of ITB or whether only an apparent weakness occurs due to elimination of spasticity, as seen after SDR. Exacerbation of weakness could prove problematic in these patients who are already significantly weak. The Specific Aims of this project are to:(1) quantify the changes in voluntary torque production, spasticity and selective control as a result of ITB; and (2) determine the interplay of these clinical changes on functional motor outcomes so as to improve clinical application of this therapy in CP. The following hypotheses will be tested: a) ITB will have a negative effect on isometric and eccentric peak torque production of eight (8) major lower extremity and two (2) representative upper extremity muscle groups in a dosedependent manner; b) Isolated control of muscles opposing spastic agonists during movement tasks and gait will be conversely improved in a dose-dependent manner; c) Functional gains, including changes in gait temporal-spatial parameters and the Global Function Scale of the PODCI, will not be dose-related. Alternatively, these will depend on the individual's underlying motor capabilities, the amount of change in spasticity and strength produced by ITB, and how these changes interact to alter functional performance. Our long term goal is to improve spasticity management in CP by more precise patient selection and dosage adjustment, and greater consideration of adjunct therapies such as strength training post-operatively. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF TRAINING ON BALANCE BETWEEN OXYGEN DELIVERY & UTILIZATION IN MUSCLE Principal Investigator & Institution: Richardson, Russell S.; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002 Summary: Since their return from the Persian Gulf region, a large number of veterans have reported health problems. Among the most frequent complaints are fatigue, muscle pain, and muscle weakness. In an effort to investigate the etiology responsible for the ongoing chronic fatigue and muscle weakness, we are performing a comprehensive evaluation of skeletal muscle in PG veterans afflicted with chronic fatigue and muscular weakness and in a control group of healthy veterans. To date, 40 Persian Gulf Veterans have been studied 25 suffering from chronic fatigue and muscle weakness (age 33$3yrs; weight 181$11lbs) and 15 controls (age 28$2yrs; weight 180$6lbs). There was only an 8% difference in the rate of PCr resynthesis, a measure of in vivo oxidative capacity, between the veterans with muscular complaints and the healthy veterans. The PCr resynthesis rate constant was 2.19$0.10 s-1 (Mean$SEM) in the sick Persian Gulf veterans and 2.36$0.11 s-1 in the healthy control veterans. Additionally, MRI measurements of subjects from both populations revealed no difference in the cross-sectional area of the calf muscles. Resting spectra from both populations showed little difference. The Pi/PCr of the healthy veterans was 0.13$0.01
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[mM] compared with 0.14$0.01 [mM] in sick veterans. In order to verify the subjective reports of muscle weakness and fatigue, we measured muscular strength and endurance in both populations. The right calf was monitored during isometric and isokinetic contractions. Isometric strength differed between the populations by 50%, with an average peak torque of 86.6$10.8 in the sick veterans and 128.7$11.3 in the healthy ve terans. The relative fatiguability, in contrast, was the same in both groups. However, the sick group performed half as much total absolute work during the same number of maximal contractions (412.1$74.6J versus 795.1$124.3J for the healthy group).Further examination of skeletal muscle using a combination of electrical stimulation, muscle biopsies and EMG will be performed to confirm the myopathic origin of chronic fatigue and muscle weakness in PG illness. In addition, DNA samples will be screened for genetic defects, or polymorphisms, which may have predisposed individuals to develop Persian Gulf illness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CARCINOMA
ELINAFIDE--SALVAGE
THERAPY
RECURRENT
OVARIAN
Principal Investigator & Institution: Rose, Peter G.; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002 Summary: This was a multi-center, non-randomized, open-labeled, uncontrolled, Phase II study of Elinafide in ovarian cancer patients. Patients must have had histologically confirmed ovarian cancer and must have received fewer than four different chemotherapy regimens. The objectives of this study were primarily to determine the efficacy and safety of Elinafide as salvage therapy for patients with recurrent/persistent epithelial ovarian carcinoma. The secondary endpoint was to determine the objective response rate, time to progression, duration of response, and CA-125 levels after treatment with Elinafide. The Elinafide was given at the Clinical Research Center (CRC) for the first three courses. The Elinafide was given IV over 1 hour every week for three consecutive weeks, with a one week rest. Pharmacokinetic blood samples were obtained weekly before and after each treatment. Patients were examined every week for muscle weakness and a Quality of Life Questionnaire was performed before each new 4 week course. Tumor and cardiac evaluations were performed every 2 courses. Blood levels for Creatinine Kinase (CK) were obtained weekly to assess for the primary toxicity of muscle weakness. Laboratory values were obtained weekly to monitor for any other toxicities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FACTORS OSTEOARTHRITIS
INFLUENCING
THE
EVOLUTION
OF
KNEE
Principal Investigator & Institution: Shakoor, Najia; None; Rush University Medical Center Chicago, Il 60612 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2009 Summary: (provided by applicant): The goals of this career development award are to expand the candidate's fundamental knowledge in clinical research through a formal course work program, help integrate the candidate into the academic research community, and to provide the experience and knowledge she will need to successfully develop future independent clinical investigations. This study's purpose is to evaluate early factors involved in the etiopathogenesis of idiopathic osteoarthritis (OA).
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Muscle Weakness
Abnormal dynamic joint loading, muscle weakness, and proprioception deficits have been independently studied and linked to OA. The literature suggests that these factors may be interrelated; however, no single study has looked at these factors together in the pathogenesis of OA. The study population is chosen based upon the candidate's recent investigational findings: that subjects with advanced unilateral hip OA more commonly develop OA of the contralateral knee rather than the ipsilateral knee and that these subjects have higher dynamic joint loads at the contralateral knee relative to the ipsilateral knee before and after hip replacement. This is a cross-sectional evaluation of the knees of 45 subjects with symptomatic early unilateral hip OA and 45 subjects with endstage unilateral hip OA. The specific aims are to investigate relationships between loading, muscle strength, and proprioception of the knees, to identify asymmetries in these factors between the ipsilateral and contralateral knees, and to evaluate these factors in both early and endstages of unilateral hip OA. Subjects will undergo interview, physical exam, and radiography. Specialized testing will include dual x-ray absorptiometry, gait analysis, proprioception evaluation and muscle strength testing of both knees. The data will be evaluated to assess specific associations between the factors, to assess asymmetries in the factors between the subjects' knees, and to demonstrate whether similar asymmetries are present in both early and endstages of unilateral hip OA. The results from this investigation can significantly impact our understanding of neuromechanical mechanisms in the pathogenesis of OA and may provide new avenues for therapeutic and perhaps primary prevention intervention in OA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FREE RADICALS AND MUSCLE DYSFUNCTION IN HEART FAILURE Principal Investigator & Institution: Supinski, Gerald S.; Professor; Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 02-AUG-2002 Summary: Recent work indicates that the intrinsic force-generating capacity and metabolic function of skeletal muscles are altered in patients with heart failure, and that skeletal muscle dysfunction contributes to fatigue and breathlessness in these patients. The underlying mechanism by which these myopathic changes occur in heart failure, however, is currently unknown. The purpose of the studies in this proposal is to test the hypothesis that some or all of the myopathic changes that develop in this condition are due to excessive myocyte generation of free radicals. We postulate that heart failure elicits an increase in myocyte phospholipase A2 (PLA2) activity levels, and that arachidonic acid generated by PLA2 interacts with the electron transport chain to augment free radical formation in resting and contracting muscle. We further propose that the radicals so produced react with and modify protein and lipid components of muscle which, in turn, alters muscle force generation and fatiguability. These hypotheses will be tested in three groups of experiments; in all studies a coronary ligation model will be used to produce heart failure in rats. The purpose of Objective I studies is to find evidence of heightened free radical formation by skeletal muscle in heart failure; experiments will measure both indices of free radical reaction with cellular constituents (i.e. lipid and protein oxidation products) and directly measure free radical formation by muscle using novel fluorescent techniques. Objective II studies will determine the cellular pathways responsible for free radical generation by skeletal myocytes in heart failure and, more specifically, determine if and by what process phospholipase A2 modulates muscle free radical generation in this condition. In
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Objective III, we will examine the role of free radicals in inducing muscle weakness and excessive fatiguability by determining if administration of free radical scavengers to heart failure animals preserves normal muscle function. Our preliminary studies provide the first evidence that excessive skeletal muscle free radical generation in heart failure is linked to reductions in muscle force-generating capacity in this condition. These data suggest that the proposed experiments should provide important information regarding the pathogenesis of heart failure-related skeletal muscle dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FRIEDREICH ATAXIA HIGH THROUGHPUT DRUG SCREENING ASSAYS Principal Investigator & Institution: Wilson, Robert B.; Associate Professor; Pathology and Lab Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2005 Summary: (provided by applicant): Friedreich's ataxia (FRDA) is an autosomal recessive, inherited neurodegenerative disorder. The signs and symptoms of FRDA are reminiscent of the mitochondrial encephalomyopathies and include progressive ataxia of all four limbs, dysarthria, areflexia, sensory loss, and muscle weakness. Skeletal deformities and cardiomyopathy are found in most patients, impaired glucose tolerance and diabetes mellitus are found in -30% of patients, and reduced visual acuity and hearing loss are occasionally seen. Onset of symptoms usually occurs around puberty and most patients are confined to a wheelchair by their late 20s. Myocardial failure is the most common cause of premature death. FRDA is the most common hereditary ataxia, with a prevalence of approximately 1 in 40,000 in European populations, and there is currently no proven effective treatment. FRDA is caused by mutations in the FRDA gene, which encodes the protein frataxin. Although encoded in the nucleus, frataxin is imported into the mitochondrial matrix. Studies of yeast and murine frataxin homologues, and of patient material, indicate that mitochondrial dysfunction, caused by oxidative damage and concomitant mitochondrial iron accumulation, underlies the signs and symptoms of FRDA. Preliminary studies using simple measures of mitochondrial function in the yeast model system, and in primary FRDA cells, support the feasibility of using a cell-based approach to high-throughput drug screening for FRDA. Hit compounds from such a screen could then be tested in the recently developed mouse models of the disease. The protein targets of hit compounds could be identified using a chemical genetic approach in yeast, allowing further drug development. The overall goal of the proposed research is to identify potential treatments for FRDA. The Specific Aims are: 1) To develop high-throughput, cell-based drug screening assays for FRDA. Because mitochondrial dysfunction underlies the signs and symptoms of FRDA, our assays will be designed to screen for compounds that improve mitochondrial function. We will use measures of mitochondrial function suitable for a 96-well format, in the yeast model system, and in primary FRDA cells. 2) To develop a chemical genetic screening assay for the identification of drug targets. We will use a colony-color screening technique in the yeast model system to identify the target proteins of hit compounds from our high-throughput drug screening assays for FRDA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE CAUSING PAGET & LIMB-GIRDLE MUSCULAR DYSTROPHY Principal Investigator & Institution: Kimonis, Virginia E.; Associate Professor; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 31-JAN-2004 Summary: (Taken from the application): Limb-Girdle Muscular Dystrophy (LGMD) encompasses a clinically diverse group of disorders characterized by proximal muscle weakness first affecting the hip and shoulder girdle elevated creatinine kinase values, and non-specific changes in the muscle biopsy. In addition to clinical heterogeneity within the LGMD category, genetic heterogeneity is indicated by the existence of dominant and recessive forms. We have identified a large family with autosomal dominant LGMD and early onset Paget disease of bone (PDB). These individuals have bone pain in the hips, shoulders and back from the Paget disease. Individuals eventually become bed bound and die prematurely from progressive muscle weakness +/cardiomyopathy in their forties to sixties. Laboratory investigation indicates elevated alkaline phosphatase levels in affected individuals. CPK is normal to mildly elevated. Muscle biopsy of the oldest affected male revealed non-specific changes and vacuolated fibers. Preliminary molecular analysis excluded linkage to the known loci for the autosomal dominant and recessive forms as well as 2 loci for autosomal dominant PDB and 6 loci for cardiomyopathy. Exclusion of the candidate loci prompted a genome-wide scan of 39 family members (9 affected, 24 unaffected, 6 spouses} with 402 polymorphic microsatellite markers (Marshfield Genotyping Services). The disease locus was linked to chromosome 9p21-q21 with marker D9S301 (max LOD=3.64), thus supporting our hypothesis that this family displays a genetically distinct form of Limb-GirdleMuscular-Dystrophy associated with Paget disease of bone and cardiomyopathy. Subsequent haplotype analysis with a high density of microsatellite markers flanking D9S301 refined the disease locus to a 3.76 cM region on chromosome 9p21-13.2. This region excludes the IBM2 locus for autosomal recessive vacuolar myopathy. Two candidate genes mapped to the critical region, NDUFB6 and IL-11RA, are being examined for disease-associated mutations. NDUFB6 encodes a subunit of Complex I of the mitochondrial respiratory chain and the IL11RA gene product influences proliferation and differentiation of skeletogenic progenitor cells. Identification of the genes involved in the LGMDs has led to the elucidation of an entire family of proteins that function in the dystrophin-glycoprotein complex. and a basis for understanding the pathophysiology of this complex. Delineation of the genetic component responsible for the LGMD/PDB phenotype should promise similar insight and facilitate in the design of novel treatment protocols for the two disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE EXPRESSION % MUSCLE DEVELOPMENT IN MYOTUBULAR MYOPATHY Principal Investigator & Institution: Beggs, Alan H.; Associate Professor of Pediatrics; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002 Summary: (provided by applicant): The long term goals of this project are to understand the molecular basis for myotubular myopathy (MTM) and its defect in muscle differentiation and to use this information to develop therapies for patients with this neuromuscular disease. X-linked MTM (XLMTM), and its milder variant, centronuclear myopathy (CTNM), are a clinically and genetically heterogeneous group of disorders characterized by congenital skeletal muscle weakness that varies from rapidly fatal in
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the infantile period (XLMTM) to relatively nonprogressive and compatible with normal life span (CTNM). The unifying features are skeletal muscle weakness and myopathic findings on muscle biopsy, including the presence of undifferentiated-appearing small myofibers with characteristic central nuclei or a central clear zone corresponding to the internuclear space ("myotubes"). XLMTM is caused by mutations of myotubularin, a novel dual specificity protein phosphatase whose role in muscle differentiation is unknown. To better understand myotubularin function and muscle development in general, we propose to 1) characterize SP stem cells in XLMTM muscle, 2) develop gene expression profiles for XLMTM myoblasts and muscle at various stages of differentiation, and 3) use this information to identify and characterize new proteins and pathways involved in muscle differentiation. Comparison of XLMTM-associated changes in gene expression with changes in CTNM and other congenital myopathies and dystrophies will allow identification of disease-specific changes. Correlation with data on various muscular dystrophies studied by other components of this Program Project will allow determination of non-dystrophic and dystrophy-specific pathogenic pathways. Knowledge of XLMTM-specific gene expression abnormalities will help in identifying downstream consequences of myotubularin dysfunction providing potential specific targets for therapeutic interventions to treat this disease. Furthermore, better knowledge of myotubularin's role in muscle differentiation will help in identifying candidate genes for the milder related disease CTNM as well as shed light on normal muscle differentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE EXPRESSION IN LIMB GIRDLE MUSCULAR DYSTROPHY Principal Investigator & Institution: Mcnally, Elizabeth M.; Associate Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The muscular dystrophies are a genetically diverse group of disorders that lead to progressive muscle weakness and disability. In recent years, a number of genes have been discovered that, when mutated, lead to muscular dystrophy. In humans, mutations in the genes encoding sarcoglycan proteins produce Limb Girdle Muscular Dystrophy (LGMD). The sarcoglycan genes encode proteins each with a single transmembrane domain. Together, the sarcoglycan subunits form a subcomplex within the dystrophin glycoprotein complex (DGC). The DGC is important for stabilizing the cytoskeleton, the plasma membrane and the extracellular matrix. The loss of sarcoglycan from the plasma membrane causes degeneration to occur in both skeletal and cardiac muscle. Loss of function mutations in sarcoglycan genes causes muscle degeneration and abnormal muscle membrane permeability. Mouse models, engineered with sarcoglycan gene mutations, were found to target different aspects of sarcoglycan function. Mice lacking delta-sarcoglycan develop increased myocyte damage in response to the force of muscle contraction. In contrast, mice lacking gammasarcoglycan do not display increased myocyte damage in response to muscle contraction suggesting that gamma-sarcoglycan deficiency may cause membrane damage by a nonmechanical, or signaling, defect. Interestingly, skeletal and cardiac muscle degeneration is identical between mice lacking either gamma-sarcoglycan or delta-sarcoglycan. Therefore, these two different mouse models modify specific mechano signaling aspects of sarcoglycan function. We propose to conduct a microarray analysis of gene expression using gamma-sarcoglycan and delta-sarcoglycan mutant muscle to compare the changes in gene expression between these two forms of LGMD. The changes in gene expression in sarcoglycan mutant muscle will be compared to those found in dystrophin
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deficient muscle. Finally, we propose to analyze gene expression in cardiac tissue from gamma- and delta-sarcoglycan mutant mice. Together, these experiments will outline the temporal profile of gene expression changes that arise in these disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE EXPRESSION PROFILING IN AGING HUMAN SKELETAL MUSCLE Principal Investigator & Institution: Kandarian, Susan C.; Professor; Health Sciences; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-MAY-2004 Summary: The age-related loss in skeletal muscle mass (sarcopenia) is associated with functional deficits and physical disability. Decreases in fiber size, and in contractile and metabolic capacity underlie the muscle weakness associated with senescence. Changes in gene expression with age represent a significant contribution to the functional defects. Newly developed oligonucleotide arrays are a powerful tool ideally suited for describing global changes in gene expression patterns with advance age. In the present application, we propose to examine in parallel the expression of thousands of genes in human skeletal muscle in response to aging using muscle biopsy samples and oligonucleotide-based DNA arrays. We propose to test the hypothesis that compared to young adult men, skeletal muscle from older healthy men will exhibit an upregulation of the stress response genes (heat shock response, DNA damage-inducible, oxidative stress-inducible), upregulation of genes associated with neuronal injury, and downregulation of the genes associated with energy metabolism (glycolysis, mitochondrial, and biosynthetic enzymes). In future work we will delineate the reversibility of age-associated changes by testing whether 12 weeks of progressive resistance training exercise will reverse the age-associated alterations in skeletal muscle gene expression. Alternatively, there may be age-related changes that are recalcitrant to "correction" or, new patterns of gene expression may result from training that counteract the functional deficits associated with aging. Differential gene expression with age and exercise will be analyzed by known gene functional category, and by similarity of gene expression change (i.e., cluster analysis). Genome- wide experiments will improve our understanding of biological processes by providing a comprehensive view of the molecular landscape in control vs. experimental tissue. The combined skills and expertise of Dr. Kandarian's and Fielding's laboratories lend themselves ideally to the study of the relationship between muscle function and genome-wide phenotypic changes. These investigators are invested in, and uniquely well suited to embark on this exciting collaboration using the expert application of molecular biological tools to the clinical problem of sarcopenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE THERAPY FOR A SEVERE DMD ANIMAL MODEL Principal Investigator & Institution: Xiao, Xiao; Associate Professor; Molecular Genetics & Biochem; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2004; Project Start 15-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is the most common, disabling and lethal muscle disease, afflicting one of every 3500 males. Recently, we have generated a series of highly truncated mini-dystrophin genes that had large deletions in the "non-essential"
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regions including part of the central rod domain and the very C-terminus domain. These minigenes were small enough to be packaged into adeno-associated virus (AAV) vectors and large enough to preserve high functionality, when tested in mdx mice after local intramuscular gene delivery. However, the mdx mice are far from an ideal DMD animal model although it is a commonly used one. While manifesting many similar symptoms of the human patients such as the muscle pathology, the mdx mice do not suffer shortened lifespan and do not show overall muscle weakness and skeletal contractures as do the human patients. This phenomenon is due to the up-regulation of utrophin gene (a dystrophin analogue) that partially compensates the defects of dystrophin in the mdx mice. By knocking out both dystrophin and utrophin genes (double-KO), two teams have recently developed a severe DMD mouse model that closely reflects every major deficiency seen in the human patients including much shortened life-span, severe muscle weakness and skeletal contractures, offering a more truthful small animal model for more stringent tests of new therapeutics. In this grant proposal, we will use the newly available double-KO mice to vigorously test the hypothesis whether the novel mini-dystrophin genes are able to rescue the muscle functions locally and systemically, and more importantly, to improve the overall health and prolong the life-span of the severe DMD animal, which is key to the development of a clinically efficacious gene therapy strategy. In this proposal, we will investigate 1) biological/therapeutic functions of mini-dystrophin genes in the double-KO mice using the transgenic mouse technology; 2) therapeutic effects of mini-dystrophin genes in both young and adult double-KO mice after local intramuscular injection of AAV vectors; 3) systemic gene delivery and its therapeutic effects in large groups of muscles and the entire body; 4) alternative therapeutic genes that may offer synergistic effects along with the minigenes to benefit the dystrophic muscles. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC EPIDEMIOLOGY OF MUSCULOSKELETAL AGING Principal Investigator & Institution: Ferrell, Robert E.; Professor; Human Genetics; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Age related declines in lean body mass become pathologically significant as osteoporosis, leading to fractures and sarcopenia, leading to muscle weakness and loss of function. These changes in body composition are ultimately associated with declines in physical function and the ability to perform tasks of daily living. The Health ABC study is a longitudinal study of 3,075 men and women aged 70-79 (52 percent women and 42 percent African American) with state of the art measures of body composition, strength and function. In Health ABC cohort, we will estimate the contribution of variation at 50 physiological candidate genes on bone (bone mineral density and bone quality) and muscle (muscle mass, strength and quality) phenotypes and performance. We will: (1) evaluate the association of muscle and bone phenotypes with variation in loci involved in six steroid metabolism and action and in growth factor and cytokine structure and action; (2) evaluate the association between candidate gene variation and annualized changes in quantitative measures of muscle and bone phenotypes; (3) evaluate the interaction between genes and between genes and environments in influencing muscle and bone phenotypes; and (4) examine the association between variation at candidate genes and measures of performance. High throughput genotyping will use the recently developed fluorescence polarization technique. To examine the relationship between musculoskeletal phenotypes and genetic polymorphisms, we will use statistical models appropriate for cross-sectional
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and longitudinal data. For cross-sectional analyses, our major tools will be general linear model (regression, ANOVA, and MANOVA). Main effects, interactions and planned contrasts will be assessed. Residuals, outliers and influential points will be examined and sensitivity analyses performed. For longitudinal data analysis of continuous outcomes, will employ standards random effects models. The models account for heterogeneity between subjects and consequently increase the precision with which genetic effects are measured. We will employ a general analytic method for association studies, genomic control, to make our conclusions robust against the impact of population substructure. These studies will contribute to our knowledge of the mechanisms of age related loss of lean body mass and may identify individuals at elevated risk for preventive intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC MECHANISMS OF MUSCULAR DYSTROPHY IN MICE Principal Investigator & Institution: Cox, Gregory A.; Associate Staff Scientist; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The broad long term goals of this research are to better understand the molecular genetic mechanisms underlying neuromuscular disease using a novel mouse mutation as an experimental model. Muscular dystrophies include a diverse group of genetically heterogeneous disorders characterized by progressive muscle weakness and wasting that leads to severe disability and often premature death. There is a need to learn more about pathogenesis of the diseases and translate this knowledge into effective treatments. Toward this goal, we propose to study the mechanism of pathogenesis in the mdm mutant mouse, a novel model of progressive muscular dystrophy that functionally links the enormous Titin (Ttn) gene to the limbgirdle muscular dystrophy type 2A (LGMD2A) cysteine protease calpain 3 (Capn3). We have genetically mapped and identified the mdm mutation as a complex rearrangement that results in a small in-frame deletion within a putative CAPN3-interacting domain of TTN. The mdm mouse may also serve as a genetic model for human tibial muscular dystrophy (TMD) which maps to the TTN locus at 2q31. This is the first demonstration that mutations in Ttn are associated with muscular dystrophy and provides a novel animal model to test for functional interactions between these two disease genes. The steps we will take to elucidate the roles of titin and calpain 3 in muscle cell degeneration will be to 1) test the hypothesis that calpain 3 interactions with titin are disrupted by the mdm mutation, 2) test the alternate hypotheses that the progressive mdm muscular dystrophy is due to either reduced CAPN3 levels or aberrant activation of the CAPN3 protease, and 3) generate a Ttn-null allele by gene targeting and an allelic series of muscular dystrophy mutations at the Ttn locus using a sensitized ENU mutagenesis screen. Thus, the mdm mutant mouse provides a unique tool for understanding molecular pathways causing muscular dystrophy and may reveal entry points in which to intervene in the disease process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GUIDED FIBROMYALGIA
IMAGERY:
A
NURSING
INTERVENTION
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Principal Investigator & Institution: Menzies, Victoria S.; None; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 15-SEP-2002
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Summary: (provided by applicant) Fibromyalgia affects up to an estimated 11 percent of the population, primarily women. The syndrome is characterized as both a musculoskeletal and a subtle neurological disorder, and is associated with widespread muscle pain and tender points, along with fatigue, muscle weakness, and stiffness. Conventional medical approaches have limited success in treating fibromyalgia, leading patients to seek complementary modalities, including the use of cognitive behavioral approaches such as relaxation and imagery, in the hope of finding more effective symptom management. The purpose of the proposed study will be to investigate the effects of guided imagery on selected outcomes in persons with fibromyalgia. The primary aim will be to investigate the effects of an eight-week intervention of guided imagery on self-efficacy and functional status. Two secondary aims will include: (1) to examine the relationship between absorption, a personality trait, and guided imagery effectiveness to identify patients who may benefit most from this modality; and (2) to explore the dose-response effect of imagery use (number of practices) on outcomes. The proposed project is a quasi-experimental study that will use a repeated measures single group design to examine the effectiveness of guided imagery, as an adjunctive modality, to enhance self-efficacy and function a status in persons diagnosed with fibromyalgia. If it can be demonstrated that self-efficacy can be increased and functional status can be improved in this population using a guided imagery intervention, then a future randomized controlled study will explore the effectiveness of guided imagery, as an adjunctive modality, on these outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IGF-1 GENE TRANSFER TO ACCELERATE MUSCLE RECOVERY Principal Investigator & Institution: Vandenborne, Krista H.; Chair and Associate Professor; Physical Therapy; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2006 Summary: Muscle weakness is a common clinical phenomina observed following bed rest, surgery, cast immobilization and injury or disease. The consequences of loss of muscle strength are far reaching and include decrease of motor control and overall fitness, development of functional limitations and impairment, and long term disability. As such, the objective of this study is to investigate the potential of virus-mediated gene transfer of IGF-1 to guard skeletal muscle from the deleterious impact of disuse or forced inactivity and to accelerate the subsequent recovery in muscle size and strength. For this purpose the left or right hindlimb (randomized) muscles of young adult mice will be injected with a recombinant adeno-associated virus vector for IGF-1. 3 months post-injection, both hindlimbs (injected and control) of the animals will be immobilized in a plaster cast for a period of 2 weeks. After removal of the cast the animals are allowed to reambulate and resume their normal cage activity. Cage restricted levels of weight-bearing activity have been shown to be sufficient to induce muscle regeneration and hypertrophy. Morphometric and functional measurements will be performed bilaterally (injected and control limb) at baseline, 3 months post-injection, following 2 weeks of cast immobilization, during reloading and at several time points during reambulation (2, 4 and 10 weeks). Morphological measures will include fiber crosssectional area and fiber number, wet weight and protein content. Functional measures (twitch and tetanic force) will be performed in vitro on superfused muscles. The secondary objective of this study is to elucidate the mechanisms by which IGF-1 overexpression modulates muscle size and function under varying loading/activity conditions. For this purpose we will measure IGF-1 peptide levels, in vivo protein synthesis and degradation rates, and markers of muscle regeneration and satellite cell
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proliferation. We anticipate that the ability to locally manipulate muscle regeneration and hypertrophy during disuse and subsequent rehabilitation will be of great clinical importance. In addition, we anticipate that this study will help elucidate the role of IGF1 in the regulation of muscle size under varying loading/activation conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IGF-I/ALS TRIAL Principal Investigator & Institution: Sorenson, Eric J.; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2007 Summary: (provided by the applicant): The objective of this trial is to determine whether IGF-1 slows progression of weakness in ALS. 300 patients with ALS will be enrolled for 2 years of treatment with a study drug or Placebo. The study will be double-blind, with equal randomization of patients to Placebo or drug. The primary end-point will be the rate of change in Manual Muscle Testing score (MMT). Secondary end-points will be tracheotomy-free survival and change in the ALSFRS score over the 2-year study period. Enrollment will be limited to those with a disease duration of less than 24 months, and a Manual Muscle Testing score of less than 8. The study is designed to detect a 30% difference in survival over the two-year treatment period. Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder that causes progressive muscle weakness and death within 4 years of onset. Its overall incidence is about 2 cases/100,000 in the United States. Except for a very small minority of cases, the cause is unknown. The disease is incurable and only Riluzole has been proven to be effective in slowing the disease. Riluzole effects are modest and more effective treatments for ALS are desirable. IGF-1 had demonstrated neurotropic effects in animal and tissue culture models of motor neuron disease. These findings have led to an interest in its potential use in ALS patients. Clinical trials have been completed in the United States, Europe, and Japan with conflicting conclusions. Previous Clinical Trials in ALS have utilized global measures of function, electrophysiological measures of muscle function, mechanical measurement of maximum force generated by Voluntary Isometric Contraction of Muscle (MVIC) or Manual Muscle Testing (MMT). Loss-of-function and death in ALS is primarily due to loss of muscle strength. Muscle strength is directly related to the underlying pathology (loss-of-motor neurons). To obtain a definitive answer as to the beneficial effects of IGF-1 in ALS, we will assess the most direct and objective effects of the disease, directly, by assessing muscle strength testing, survival and functional performance. The preliminary data from our prior trial allows design of a Phase III treatment trial that will yield a definitive result about the treatment effect of IGF-1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMPACT OF HYPERTHYROIDISM ON SKELETON, MUSCLE STRUCTURE AND FUNCTION Principal Investigator & Institution: Brennan, Michael; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002 Summary: Clinically apparent muscle weakness and wasting occur commonly in hyperthyroidism. In order to assess the independent contributions to skeletal muscle weakness of both muscle wasting and qualitative changes in muscle contraction, we studied muscle strength and volume in a cohort of hyperthyroid patients. Data regarding the response of these paremters to normalization of serum thyroid hormone
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levels is currently available in 10 female patients (median age 39 yrs; range 17-92 yrs). Initial measurements were performed prior to treatment of hyperthyroidism. Repeat measurements were made within 6-9 months of the patients achieving a euthyroid state. Muscle strength was determined by Cybex II dynamometric assessment of knee flexion and extension. Lower extremity total muscle volume was measured by dual photon xray absorptiometry (Lunar DPX-L) and mid-thigh muscle cross sectional area was quantitated by computerized axial tomography. Treatment of hyperthyroidism and restoration of a euthyroid state resulted in mean increases of 10% in thigh muscle cross sectional area (range 1-32%) and 12% in total lower extremity muscle volume (range 131%). Mean thigh muscle strength increased by 57% (range 5-197%). Mean muscle efficiency, defined as the force of muscle contraction per unit of muscle volume (Nm/cm2) is increased by 48% (range 4-183%). This finding suggests that qualitative changes in the force of contraction result in decreased muscle efficiency. Responsible mechanisms remain to be fully elucidated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPROVING RESPIRATORY OUTCOMES IN ALS Principal Investigator & Institution: Lechtzin, Noah; Environmental Health Sciences; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The Principal Investigator, Dr. Noah Lechtzin, is a promising young investigator who has made a substantial commitment to an academic career in clinical research. His commitment is evident in his pursuit of advanced clinical and research training, including completion of a residency in internal medicine, a fellowship in pulmonary and critical care medicine, and a Master's in Health Science degree in clinical epidemiology. This background provides a solid foundation for him to address challenging questions related to respiratory impairment in amyotrophic lateral sclerosis (ALS). ALS is a devastating fatal neurodegenerative illness in which most patients die from respiratory muscle weakness and associated complications. Despite major efforts, the cause of ALS remains elusive and there is no known cure. While it is recognized that evaluation and management of respiratory failure is critical to the care of ALS patients, there has been relatively little research directed at these problems. The proposed research in this application builds on Dr. Lechtzin's previous research and addresses questions of fundamental importance for the management of respiratory illness in ALS. Non-invasive positive pressure ventilation (NIPPV) is a method to augment alveolar ventilation without the use of an endotracheal airway. Because it has limited risks, NIPPV has rapidly become the standard of care for treating respiratory failure in ALS. However, there is relatively limited data on its use and effectiveness in ALS. The primary objective of this proposal is to understand how NIPPV works, how it is being used, and whether it alters pulmonary function, respiratory symptoms, and quality of life. To this end, we propose three related studies: a) an investigation of the immediate effect of NIPPV on lung compliance; b) a randomized trial of NIPPV in patients with mild respiratory muscle weakness; and c) a cohort study evaluating the effect of NIPPV on quality of life and survival. The principal investigator will be strengthening his knowledge base in the methodology of clinical investigation in a supervised environment guided by exceptionally talented mentors.By combining the resources of the Johns Hopkins Medical Institutions toward the completionof the outlined aims, the Mentored Patient-Oriented Research Career Development Award will provide Dr. Lechtzin the opportunity to expand the skills required for development into an independent clinical investigator.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INSTABILITY AND MUSCULAR DEMAND DURING OBSTACLE CROSSING Principal Investigator & Institution: Chou, Li-Shan; Exercise & Movement Science; University of Oregon Eugene, or 97403 Timing: Fiscal Year 2003; Project Start 04-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Falls are among the most serious problems facing the aging population and have become the largest single cause of accidental death. Moreover, the total direct cost of fall injuries in 1994 among people 65 and older was $20.2 billion. Most falls in the elderly stem from interactions between environmental hazards and increased individual susceptibility to hazards from accumulated effects of age and intrinsic factors. Research on biomechanics of selected physical tasks, that take both environmental and intrinsic factors into account, is needed to quantify impairment magnitudes, to determine what elements are critical to the impairment, and ultimately to design more effective interventions for preventing falls in the elderly. The long-term goals of this proposed project are to advance the understanding of the mechanisms underlying the increased incidence of falls in the elderly, to determine a more effective method of identifying aged persons at risk of falling, and eventually to design more effective exercise/strengthening programs for the prevention of falls in the elderly. Specific aims of this project are to (1) demonstrate that motion of the whole body center of mass (COM) during obstacle crossing could better distinguish fallers from non-fallers when compared to individual segmental motion, (2) examine the relationship between ability to accommodate to environmental hazards during locomotion and muscle weakness, and (3) to identify quantitative, biomechanical indices (muscular demand-tocapacity ratios) that can better indicate the level of mechanical challenge imposed on selected muscles. Motion analysis and muscle strength testing will be performed on 24 elderly non-fallers and 24 elderly fallers (65 years or older). Body segment motion, ground reaction forces, and electromyography will be collected during unobstructed walking and stepping over obstacles of heights corresponding to 2.5% and 10% of each subject's height. Isometric strength of selected lower extremity muscles will be measured bilaterally. A thirteen-link biomechanical model, with kinematic inputs of each body segment and ground reaction forces will be used to compute the three-dimensional motion of the whole body COM and three-dimensional joint moments (torques) of the lower limbs. Data analysis will be performed on both mechanical and neuromuscular levels, including the isometric muscle strength, electromyography, motion of the COM, and it's interaction with the center of pressure (COP) of the stance foot derived from ground reaction forces and moments. Finally, correlation between muscle strength and dynamic balance control (indicated by the motion of the whole body COM) will be examined. This proposed project is expected to identify/define more sensitive biomechanical measures (both intrinsic and extrinsic) for better quantification of agerelated mobility impairment and functional challenges imposed on our musculoskeletal system. 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
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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 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: INTRATHYMIC PATHOGENESIS OF MYASTHENIA GRAVIS Principal Investigator & Institution: Levinson, Arnold I.; Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2005 Summary: (provided by applicant): The thymus has been considered to play an important role in the pathogenesis of myasthenia gravis (MG), a prototypic autoimmune disease characterized by skeletal muscle weakness. However, its role still remains a mystery. The expression of the autoantigen, acetylcholine receptor (AChR), in the thymus has raised the hypothesis that immunity to this self-protein may be initiated or perhaps perpetuated in this organ. The overall objective of this proposal is to enhance our understanding of mechanisms by which an immune response to this self-antigen might be engendered in the thymus. The hypothesis to be tested is that an inflammatory reaction to an irrelevant antigen in the thymic medulla leads to augmented entry into the thymus of peripheral T cells. Included amongst these thymic immigrants are T cells with low affinity receptors for AChR. Such T cells become activated in the local milieu of the inflamed thymus where they engage upregulated expression of AChR, MHC antigens and co-stimulatory molecules on thymic stromal cells. The Specific Aims of this project are to 1) further characterize our murine model of thymic inflammation, 2) determine if peripheral T cell immigration to an inflamed thymus is enhanced relative to a normal thymus, 3) determine if thymic T cell immigrants are activated by a neo-selfantigen expressed in an inflamed thymus, and 4) determine if AChR specific T cells migrate to an inflamed thymus, become activated by locally expressed autoantigen and
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initiate a myasthenic syndrome. A retroviral based vector system will be used to induce thymic inflammation by targeting the expression of an irrelevant antigen, betagalactosidase, in the thymic medullary epithelium of mice immunized to this protein. These studies provide a novel approach to elucidate the role of the thymus in the pathogenesis of MG. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LOCAL ENVIRONMENTAL FACTORS IN PROGRESSION OF KNEE OSTEOARTHRITIS Principal Investigator & Institution: Sharma, Leena; Associate Professor; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-DEC-2006 Summary: (provided by applicant): Knee osteoarthritis (OA) is a leading cause of chronic disability in the elderly. The natural rate of progression or worsening of knee OA varies; the reasons for this are poorly understood. The influence of impairments in the local, joint-organ-level environment on CA progression rate or on patient-centered physical functioning has received little attention. Whether such impairments develop before or after CA onset, they may contribute to subsequent CIA progression and/or functional decline. Meniscal tears and malalignment are local impairments which are present in a subset of patients with mild-moderate CA and adversely affect load distribution. The effect of medial meniscal tears may be greatest when coupled with various malalignment, which further stresses the medial compartment. Another key element of the local environment is the functional capacity of the cartilage itself, i.e. its ability to withstand and transmit load. At present, there is no established method to assess this suitable for application in large studies. Our primary goal is to examine the relationship of meniscal tears and malalignment with tibiofemoral progression and with functional status decline in a cohort of 300 patients with knee CIA. Secondarily, we will examine the impact of malalignment, laxity, muscle weakness and proprioception impairment on long-term (0-7 year) outcome. We also propose to measure cartilage deformation after exercise (which may be an in vivo measure of the functional capacity of cartilage) in a pilot study involving a subset of the cohort. An MAMDC-funded, longitudinal, natural history study of knee OA with radiographic and functional status outcomes is ongoing at our institution, the study of Mechanical Factors in Arthritis of the Knee (MAK), in which time 0, 1.5 (completed) and 3 year (ongoing) evaluations of alignment, laxity, proprioception and strength in 300 subjects are funded. The project proposed here builds upon the infrastructure and results of this study. Support to evaluate the MAK cohort at 5 and 7 years (on the MAK timeline) is sought. The proposed study will provide much needed information regarding potential determinants of the natural outcome of knee OA and will help to identify the local, organ-level factors which should ultimately become the target of intervention, based upon their link to disease progression and/or their link to declining functional status. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LOCALIZED BIOIMPEDANCE IN NEUROMUSCULAR DISEASE Principal Investigator & Institution: Rutkove, Seward B.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2007 Summary: (provided by applicant): This proposal introduces a novel, non-invasive and painless method for the evaluation of skeletal muscle, using a recently developed
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technique called electrical impedance myography (EIM). The ultimate goal of this research is to refine ElM as a clinical test that can assist in the diagnosis and treatment of neuromuscular disease and in evaluation of muscle change due to disuse. In addition to complementing and potentially replacing the painful test of needle electromyography, ElM will have unique application in the evaluation of muscle weakness in clinical trials research, rehabilitation, and space flight. Our first aim is to establish normal values and confirm the reproducibility of this technique by performing studies on healthy subjects of varying age and fluid status. Second, patients with different disease and disuse states will be evaluated to determine ElM patterns associated with myopathy vs. neurogenic disease and compare the specificity and sensitivity of these patterns to well-established diagnostic methods. Finally, ElM's use as a tool in evaluating neuromuscular disease progression/remission will be assessed and refined. As part of this aim, a prototype device for easy use will be developed and tested in the clinical setting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANICAL VENTILATION AND RESPIRATORY MUSCLES Principal Investigator & Institution: Powers, Scott K.; Professor and Chair; Exercise and Sport Sciences; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2005 Summary: (Applicant's abstract): Mechanical ventilation (MV) is used clinically to sustain ventilation in patients who are incapable of independently maintaining adequate alveolar ventilation. Unfortunately, the withdrawal of MV, or weaning, can be difficult in a large number of cases. Strong evidence exists that MV-induced respiratory muscle weakness contributes significantly to these difficulties in weaning. Indeed, we have recently demonstrated that prolonged MV results in diaphragmatic atrophy and a significant reduction in diaphragmatic maximal force production. Further, we have observed that prolonged MV results in oxidative injury (i.e. protein oxidation) to the diaphragm; this is significant because oxidized proteins become targets for proteases. The mechanisms responsible for this MV-induced atrophy and protein oxidation are unknown and comprise the focus of our proposed experiments. To determine the factors that contribute to diaphragmatic atrophy during prolonged MV, we will test the following hypotheses: 1a) MV-induced diaphragmatic atrophy occurs due to a decrease in synthesis of muscle proteins as well as an increased rate of proteolysis; 1b) proteolysis is the major contributor to diaphragmatic protein loss during prolonged MV; 2a) The increased activity of calpain, lysosomal, and ATP ubiquitin-dependent proteases are collectively responsible for the protein degradation observed in diaphragms from MV animals; and 2b) Although calpain, lysosomal, and ATP-ubiquitin-dependent proteases all contribute to diaphragmatic protein loss during MV, the ATP-ubiquitin-dependent and calpain proteolytic pathways are dominant. To resolve which chemical pathways are responsible for diaphragmatic protein oxidation during MV we will test the hypothesis that MV-induced protein oxidation in the diaphragm is caused by several reactive chemical species including hypochlorous acid, tyrosyl radicals and hydroxyl radicals. To test these postulates, we will perform both in vitro and in vivo studies using an animal model and utilize the tools of molecular biology, biochemistry, and physiology. These experiments will improve our understanding of the mechanisms associated with MV-induced diaphragmatic atrophy. The long-term goal of our experiments is to provide the knowledge required to develop clinical strategies to oppose the deleterious effects of MV on respiratory muscles. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISM OF BOTULINUM TOXIN ACTION Principal Investigator & Institution: Simpson, Lance L.; Professor; Medicine; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2003; Project Start 01-SEP-1984; Project End 31-MAY-2007 Summary: (provided by applicant): Botulinum toxin is the etiologic agent responsible for the disease botulism. This toxin, which is generally regarded as the most poisonous of all poisons, is known to exist in seven serotypes designated A, B, C, D, E, F and G. Of these seven serotypes, three (A, B and E) account for virtually all cases of human botulism. For botulinum toxin to produce clinical poisoning, it must ordinarily cross at least two membrane barriers. Initially, the toxin binds and undergoes transcytosis across gut or airway epithelial cells. This is the mechanism by which the toxin escapes the lumen of the gut or airway to reach the general circulation. Subsequently, the toxin binds to peripheral cholinergic nerve cells, undergoes receptor-mediated endocytosis and pH-induced translocation, then acts in the cytosol as a zinc-dependent endoprotease to cleave polypeptides that are essential for exocytosis. This is the mechanism by which the toxin produces muscle weakness or flaccid paralysis, which is the characteristic outcome in botulinum toxin poisoning. The goal of the proposed work will be to select botulinum toxin type A as a prototype, to select a human gut epithelial cell line (T-84) as a prototype, and then use these two as models to gain insight into the subcellular and molecular events that account for the ability of the toxin to penetrate membrane barriers. More precisely, two approaches will be used to help elucidate the structural features of the toxin that mediate binding and transcytosis: 1.) a series of truncation mutants will be generated in an attempt to identify the minimal domain that retains the ability to cross gut epithelial cells, and 2.) a series of site-directed mutations will be generated in an attempt to localize critical amino acids within the minimal domain that are needed for binding and transcytosis. In addition, two approaches will be used to help identify subcellular components in human gut cells that transport the toxin from the apical (viz., mucosal) to the basolateral (viz., serosal) surfaces: 1.) pharmacologic techniques will be used to discriminate clathrin-coated vesicles from lipid raft vesicles, and 2.) immunologic techniques will be used to identify membrane polypeptides that are in or near the binding site for the toxin. It is anticipated that the combined products of this proposed research will provide a clear understanding of botulinum toxin penetration of human cell membranes, with the added benefit of generating a potential vaccine against the toxin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR PATHOGENESIS OF MYOTONIC DYSTROPHY Principal Investigator & Institution: Cooper, Thomas; Associate Professor; Pathology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 08-FEB-1999; Project End 31-JAN-2004 Summary: The goal of this project is to determine the molecular basis for myotonic dystrophy (DM), a dominantly inherited disease caused by an expanded CTG trinucleotide repeat in the 3' untranslated region of the DMPK. DM is a multi-systemic disorder characterized by progressive skeletal muscle weakness, cardiomyopathy and arrhythmias, cataracts, and abnormalities in brain and endocrine function. Despite identification of the genetic defect six years ago, the molecular basis of the disease is unknown. DMPK transcripts containing the expanded repeat accumulate in nuclear foci. One hypothesis is that the expanded repeat creates a grain-of-function in the DMPK RNA which has a trans-dominant effect on the expression of other genes. A proposed
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mediator of the nucleus of DM cells. Our preliminary results establish the previously hypothesized link between the nuclear accumulation of expanded-CUG transcripts, nuclear accumulation of CUG-BP, and alteration of tissue-specific RNA processing in DM cells. We demonstrate that CUG-BP positively regulates splicing of the cardiac troponin T (cTNT) alternative exon 5 by binding to a previously characterize musclespecific splicing element. cTNT exon 5 is aberrantly included in DM striated muscle, consistent with nuclear accumulation of a positive splicing regulator. The transdominant effect on cTNT splicing was reproduced in normal muscle cells by cotransfection of cTNT minigenes with expanded DMPK minigenes containing up to 1440 CTG repeats. Wild-type cTNT minigenes but not minigenes with a mutated CUG-BP binding site expressed enhanced levels of exon 5 inclusion demonstrating the role of CUG-BP in the trans-dominant effect. The goals of this proposal are to: (i) characterize expression of a novel protein closely related to CUG-BP (etr-3) recently identified in an EST library (ii) determine the mechanism of etr-3 and CUG-BP nuclear accumulation in DM cells; (iii) identify genes that are regulated post-transcriptionally by etr-3 and CUGBP which are likely to directly mediate DM pathogenesis; (iv) establish stable fibroblast and muscle cell lines that inducible express expanded-CUG RNA; (v) establish lines of transgenic mice that express expanded-CUG RNA. This proposal will directly test the hypothesis that the expanded trinucleotide creates a gain-of-function mutation in the RNA. It will also establish experimental systems to investigate the basis of a novel pathogenic mechanism and ultimately, test means of therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOTOR COMMAND SIGNALS AND THE CORTICO-CEREBELLAR NETWORK Principal Investigator & Institution: Miller, Lee E.; Associate Professor; Physiology; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2006 Summary: (provided by applicant): It has been recognized for hundreds of years, that motor deficits following injury to the brain occur on the same side as a cerebellar lesion, but opposite the side of an injury to the cerebrum. The nature of the deficit also differs. Cerebral cortical injury causes muscle weakness or paralysis, while cerebellar lesions cause uncoordinated movements that are typically of the wrong size. Recognition of these specific motor signs caused great advances in the diagnosis and surgical treatment of such injury, but the personal and societal costs of treatment and rehabilitation following stroke or other injury remain tremendous.There are extensive interconnections between the cerebellum and the cerebral cortex. In fact, the primary motor cortex sends many more fibers to the cerebellum than it does to the spinal cord. Both structures have been studied extensively by means of recordings in behaving animals. Even so, conflicting ideas remain about the relation between these two areas, and the way in which they interact to produce and refine motor command signals. We propose to examine these relations by recording simultaneously in both the cerebellar nuclei (CN) and primary motor cortex (M1) in the awake, behaving monkey. In addition to paired recordings, we propose to use electrical micro-stimulation and averaging methods to examine the interconnections, and to micro-inject drugs during recording in order to distinguish convergent inputs. These measurements will be made during normal movement, and during motor learning, as the monkey adapts to novel forces imposed bya robotic device, that affect the trajectory of its movements.Simultaneous recordings provide far more than the ability to do two experiments at once. Recording simultaneously from select pairs of cells under literally identical experimental
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conditions provides a level of spatial and temporal precision with which to compare response properties that is not possible with single site recordings. More importantly, we will be able to associate these properties with the underlying functional connections between particular pairs of recording sites. This approach should greatly enhance our ability to understand the relation between M 1 and CN during the generation of motor command signals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTICENTER KNEE OSTEOARTHRITIS STUDY Principal Investigator & Institution: Torner, James C.; Professor and Head; Epidemiology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 30-JUN-2008 Summary: (provided by applicant): Osteoarthritis (OA) is the most common form of arthritis and disease in the knee is a leading cause of disability. Most epidemiologic studies of knee OA have focused on radiographic disease, but symptomatic OA should be a major focus of studies on preventing OA, because symptomatic disease causes disability and has formidable societal and public health impacts. OA is potentially preventable, but only a limited number of mostly nonmodifiable risk factors has been identified, even though modifiable risk factors such as particular activities, muscle weakness, proprioceptive deficits, micronutrient deficiencies and structural factors have been proposed and may affect substantially the risk of disease. Prevention opportunities are most relevant and are most likely to be used by those who already have disease or who are at highest risk of getting it. This proposal introduces four new approaches into the epidemiologic study of knee osteoarthritis: l.a focus on symptomatic disease, 2. a comprehensive evaluation of risk factors including modifiable ones, 3. a focus on those who would really benefit from prevention opportunities, those who already have disease or those who are at high risk of getting it and 4. the incorporation of more comprehensive and reproducible imaging than has previously been used including, state of the art radiographic techniques and MRI. MRI provides rich information on structural factors in which abnormalities may affect the risk of disease. The overall objective of this study is to evaluate longitudinally the effects of three groups of factors: biomechanical factors (squatting,kneeling, stair climbing, quadriceps weakness and proprioceptive deficits), bone and structural factors (bone density,bone marrow and meniscal lesions on MRI) and micronutrient deficiencies (vitamin C, E and D) on the occurrence and progression of symptomatic and radiographic knee OA in a populationbased sample of men and women aged 50 to 79. We propose to recruit a communitybased sample of 3,000 men and women likely to either have knee OA or be at high risk of OA. High-risk groups will include those who are overweight, those with knee symptoms or those with a history of knee injuries or operations. Subjects will be evaluated with symptom questionnaires, radiographs and MRI?s and will be followed 36 months for the development or progression of symptomatic or radiographic OA. Analyses will focus on the relation of these important risk factors and OA outcomes. This large, multifaceted and comprehensive study of persons with knee OA, or at high risk of disease, offers to address definitively the relation of potentially important risk factors to the development or progression of a major disabling disease and to provide new insights into disease biology and potential opportunities for prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MULTI-CENTER OSTEOARTHRITIS STUDY Principal Investigator & Institution: Nevitt, Michael C.; Professor; Epidemiology and Biostatistics; University of California San Francisco 3333 California Street, Suite 315 San Francisco, Ca 941430962 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 30-JUN-2008 Summary: (provided by applicant): Osteoarthritis (OA) is the most common form of arthritis, and disease in the knee or hip are leading causes of disability. Most epidemiologic studies of knee and hip OA have focused on radiographic disease, but symptomatic OA should be a major focus of studies on preventing OA, because symptomatic disease causes disability and has formidable societal and public health impacts. OA is potentially preventable, but only a limited number of mostly nonmodifiable risk factors has been identified, even though modifiable risk factors such as particular activities, muscle weakness, proprioceptive deficits, micronutrient deficiencies and structural factors have been proposed and may affect substantially the risk of disease. Prevention opportunities are most relevant and are most likely to be used by those who already have disease or who are at highest risk of getting it. This proposal introduces four new approaches into the epidemiologic study of knee osteoarthritis: l.a focus on symptomatic disease, 2. a comprehensive evaluation of risk factors including modifiable ones, 3. a focus on those who would really benefit from prevention opportunities, those who already have disease or those who are at high risk of getting it and 4. the incorporation of more comprehensive and reproducible imaging than has previously been used including, state of the art radiographic techniques and MRI. MRI provides rich information on structural factors in which abnormalities may affect the risk of disease. The overall objective of this study is to evaluate longitudinally the effects of three groups of factors: biomechanical factors (squatting, kneeling, stair climbing, wearing high heeled shoes, quadriceps weakness and proprioceptive deficits), bone and structural factors (bone density, bone marrow and meniscal lesions on MRI) and micronutrient deficiencies (vitamin C, E and D) on the occurrence and progression of symptomatic and radiographic knee OA in a population-based sample of men and women aged 50 to 79. Although the focus of this project is knee OA, we also incorporate a study of hip OA. We propose to recruit a community-based sample of 3,000 men and women likely to either have knee OA or be at high risk of OA. High risk groups will include those who are overweight, those with knee symptoms and those with a history of knee injuries or operations. Subjects will be evaluated with symptom questionnaires, radiographs and MRI?s and will be followed 36 months for the development or progression of symptomatic or radiographic OA. Analyses will focus on the relation of these important risk factors and OA outcomes. This large, multifaceted study offers to address definitively the relation of potentially important risk factors to the development or progression of a major disabling disease and to provide new insights into disease biology and potential opportunities for disease prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MULTICENTER OSTEOARTHRITIS STUDY (MOST) Principal Investigator & Institution: Lewis, Cora E.; Professor of Medicine; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2008 Summary: (provided by applicant): Osteoarthritis (OA) is the most common form of arthritis and disease in the knee is a leading cause of disability. Most epidemiologic studies of knee OA have focused on radiographic disease, but symptomatic OA should
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be a major focus of studies on preventing OA, because symptomatic disease causes disability and has formidable societal and public health impacts. OA is potentially preventable, but only a limited number of mostly nonmodifiable risk factors has been identified, even though modifiable risk factors such as particular activities, muscle weakness, proprioceptive deficits, micronutrient deficiencies and structural factors have been proposed and may affect substantially the risk of disease. Prevention opportunities are most relevant and are most likely to be used by those who already have disease or who are at highest risk of getting it. This proposal introduces four new approaches into the epidemiologic study of knee osteoarthritis: l.a focus on symptomatic disease, 2. a comprehensive evaluation of risk factors including modifiable ones, 3. a focus on those who would really benefit from prevention opportunities, those who already have disease or those who are at high risk of getting it and 4. the incorporation of more comprehensive and reproducible imaging than has previously been used including, state of the art radiographic techniques and MRI. MRI provides rich information on structural factors in which abnormalities may affect the risk of disease. The overall objective of this study is to evaluate longitudinally the effects of three groups of factors: biomechanical factors (squatting,kneeling, stair climbing, quadriceps weakness and proprioceptive deficits), boneand structural factors (bone density,bone marrow and meniscal lesions on MRI) and micronutrient deficiencies (vitamin C, E and D) on the occurrence and progression of symptomatic and radiographic knee OA in a populationbased sample of men and women aged 50 to 79. We propose to recruit a communitybased sample of 3,000 men and women likely to either have knee OA or be at high risk of OA. High risk groups will include those who are overweight, those with knee symptoms or those with a history of knee injuries or operations. Subjects will be evaluated with symptom questionnaires, radiographs and MRI?s and will be followed 36 months for the development or progression of symptomatic or radiographic OA. Analyses will focus on the relation of these important risk factors and OA outcomes. This large, multifaceted and comprehensive study of persons with knee OA, or at high risk of disease, offers to address definitively the relation of potentially important risk factors to the development or progression of a major disabling disease and to provide new insights into disease biology and potential opportunities for prevention Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MYELOID CELL FUNCTION IN MUSCLE INJURY AND REPAIR 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 01-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Muscle weakness, injury and inflammation are important obstacles to normal locomotory function in individuals subjected to periods of muscle unloading followed by normal loading. These defects are expected to acquire increased importance in health care of an aging population, in which periods of convalescence can entail prolonged bed rest followed by attempts to regain normal ambulation. The design of optimal preventative or therapeutic treatments to minimize the muscle defects that arise upon reloading will rely upon identifying the factors that contribute to muscle damage during this reloading period. Our findings support the view that myeloid cells contribute to promoting injury and repair during muscle reloading. We hypothesize that neutrophils promote injury to reloaded muscle via free radical mediated events. Furthermore, we propose that the reduction in the expression of nitric oxide synthase (NOS) during muscle unloading renders muscle susceptible to
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neutrophil-mediated damage, because NO can normally protect muscle from damage by free radicals. Finally, we hypothesize that macrophages participate in muscle repair, so that interventions that affect their presence or activity in muscle can influence the repair process. In the study proposed here, we will test our hypothetical model of myeloid cell function in muscle injury and repair following modified muscle use. We will use mouse hindlimb suspension followed by reloading to induce injury and repair caused by modified muscle use, and assess the effects of depleting neutrophils or macrophages from the animals prior to reloading. We will also examine muscle injury and repair during reloading in transgenic mice that are null mutants or over-expressers of enzymes that generate specific molecules that are implicated in promoting muscle injury or protecting muscle from injury by myeloid cells. The results of the investigation proposed here will provide the first experimental data on the role of myeloid cells in muscle injury and repair following modified use. Those findings can indicate new therapeutic approaches to improving muscle function during muscle reloading following periods of reduced loading. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MYOCARDIAL MYOTONIC DYSTOPHY PROTEIN KINASE FUNCTION Principal Investigator & Institution: Perryman, M Benjamin.; Director; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (the applicant's description verbatim): The overall goal of this research project is to identify the functional role of human myotonic dystrophy protein kinase (DMPK) in myocardium. DMPK was the first identified member of a novel family of multi-domain serine-theronine protein kinases defined by a unique kinase core and common non-catalytic domains. Physiological substrates and functions for most members of this kinase family are unknown. DMPK was originally identified when a CTG triplet repeat sequence located in the 3' untranslated region of the DMPK gene was identified and shown to be expanded in patients with myotonic dystrophy (DM). DM is an autosomal dominant myopathy with pleiotropic effects including skeletal muscle weakness and wasting, a cardiomyopathy with cardiac conduction abnormalities and myocardial dysfunction, frontal baldness, and cataracts. The pathophysiology of DM is not understood, and a number of mechanisms-including reduced DMPK expression, RNA splicing defects, and reduced expression of a homeobox gene-have been postulated to explain this complex phenotype. DMPK mRNA and protein expression is greater in myocardium than in any other tissue type implying the presence of a previously unknown protein kinase mediated signal transduction pathway in myocardium. We hypothesize that DMPK is a multifunctional protein kinase and is a component of a previously uncharacterized myocardial and skeletal muscle signal transduction pathway. Alterations in the DMPK signaling pathway are likely to be responsible for at least a portion if not all of the pathophysiology of myotonic dystrophy. This hypothesis cannot be directly tested without a better understanding of fundamental properties of the kinase including DMPK enzymatic activity, domain structure and interacting proteins. We will use biochemical analysis and molecular biology techniques to characterize DMPK enzymatic activity and autophosphorylation, identify potential physiologic substrates, define DMPK domain function, determine the effect of DMPK proteolytic processing on enzyme function and localization, and determine the functional relationship of DMPK to other members of this kinase family.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NERVE TERMINAL AS A SITE OF ACRYLAMIDE ACTION Principal Investigator & Institution: Lopachin, Richard M.; Professor of Anesthesiology; Montefiore Medical Center (Bronx, Ny) Bronx, Ny 104672490 Timing: Fiscal Year 2002; Project Start 01-AUG-1988; Project End 31-AUG-2003 Summary: Exposure to acrylamide (ACR) causes nerve damage characterized by distal axon swelling and degeneration. We investigated (years 08-11) the possibility that degeneration is caused by reverse Na+/Ca2+ exchanger- mediated Ca/2+ entry secondary to reduced Na+/K+ ATPase activity. Subchronic oral ACR intoxication of rats produced distal tibial nerve axon degeneration and decreased Na/+ pump activity whereas neither enzymatic nor structural perturbation of PNS axons was associated with subacute i.p. treatment despite development of classic neurotoxicity. To determine whether route-specific differences in biotransformation might be involved in differential expression of axonopathy, Specific Aim #1 studies of this competitive renewal application will characterize ACR disposition and kinetics following i.p. and oral exposure. To provide conclusive evidence that axon degenerations does not occur during subacute i.p. intoxication, Specific Aim #2 studies will assess axon morphology in nervous tissue (CNS, intramuscular nerves) not examined during years 08-11. Overall, our results (years 08-11) suggest other non-axonal sites might mediate the neurotoxic actions of ACR. Nerve terminals are rationale sites for mediation of ACRinduce dysfunction (skeletal muscle weakness, sensory ataxia) and have been found to be damaged as an early consequence of exposure. We hypothesize ACR acts at presynaptic sites in CNS and PNS to reduce quantal release of neurotransmitter. Therefore, research proposed in Specific Aims #3-#5 will evaluate the role of nerve terminal injury in ACR-induced neurotoxicity and identify corresponding molecular mechanisms. Specific Aim #3 studies will define the onset and magnitude of synaptic damage in ACR-treated rats. In Specific Aim #4 experiments, the rat hindlimb neuromuscular junction will be used a model system to investigate potential pre- and post-junctional sites of ACR action. Specific Aim #5 studies are proposed to quantitate ACR-induced changes in binding of synaptic vesicles with presynaptic plasma membrane. In addition, ACR adduction of cysteine string protein and SNAP-25 will be determined in brain synaptosomes from intoxicated rats. Exploring compromised nerve terminal function during ACR intoxication and identifying corresponding molecular mechanism of action represents a new area of investigation in toxic axonopathies. Results could lead to a better understanding of acquired and inherited human neuropathies and the development of efficacious pharmacotherapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEURAL CONTROL OF NONINVASIVE VENTILATION IN THE PRETERM Principal Investigator & Institution: Sinderby, Christer; St. Michael's Hospital 30 Bond St Toronto, on M5b 1W8 Timing: Fiscal Year 2003; Project Start 29-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): There is an abundance of evidence in the literature suggesting that maintenance of spontaneous breathing with a synchronized mode of ventilatory assist, and the use of non-invasive interface to deliver the assist, has the potential to significantly improve neonatal respiratory care. Conventional modes of mechanical ventilation use pneumatic signals such as airway pressure, flow, or volume,
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which are dampened by respiratory muscle weakness, increased load, and leaks. In order to improve patient ventilator synchrony, further development over current technology is required. The present research application deals with the implementation and clinical evaluation of neural control of mechanical ventilation in the neonatal intensive care unit. The goal is to demonstrate, in pre-term newborns with extremely low birth weight, that neural control of mechanical ventilation, using the electrical activity of the diaphragm (EAdi), can synchronize delivery of assist to the patient's inspiratory drive, and that synchrony is maintained regardless of the interface used to deliver assist. This application will introduce for the first time technology for neural triggering and cycling-off as well as neurally adjusted ventilatory assist (NAVA) in the treatment of pre-term infants. This will be achieved in two short-term clinical evaluations with the following aims: 1) To demonstrate that neural triggering and cycling-off (i.e. initiation and termination of ventilatory assist using EAdi) improve infant ventilator synchrony, compared to conventional pneumatic trigger systems in pre-term infants with extremely low birth weight. 2) To demonstrate that administration of NAVA with invasive (endotracheal intubation) or non-invasive interface (nasal prongs) is equally efficient in terms of triggering and cycling-off. By overcoming the problems associated with the current technology for ventilator triggering, neural triggering and cycling-off should improve patient-ventilator interaction and patient comfort during assisted mechanical ventilation, regardless of patient-ventilator interface. By improving patient-ventilator interaction and allowing use of a non-invasive patient-ventilator interface, neural control of mechanical ventilators has the potential to significantly reduce ventilator-related complications, reduce the incidence of lung injury, facilitate weaning from mechanical ventilation, and decrease the duration of stay in the intensive care unit and overall hospitalization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROMECHANICAL CHANGES CAUSED BY STROKE & STRETCHING Principal Investigator & Institution: Zhang, Li-Qun; Rehabilitation Institute of Chicago Chicago, Il 60645 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Spasticity, contracture, and muscle weakness are major sources of disability following brain damage, and their development and recovery are closely interrelated. Increased resistance to passive movement in spastic hypertonia can be due to reflex (with both tonic and phasic components) and/or non-reflex (with both viscous damping and elastic stiffness components) changes. The various components contributing to spastic hypertonia and functional deficits following stroke, and the outcome of an intelligent stretching treatment in changing these components and functional performance will be investigated over 7 months for each patient. The first specific aim is to treat/stretch spastic ankle joints in stroke patients safely and repeatedly to joint extreme positions until a pre-specified peak resistance torque is reached with the stretching velocity adjusted constantly and inversely proportional to the resistance torque. The second specific aim is to evaluate pathophysiological changes in spastic hypertonia and to assess outcome of the stretching treatment in terms of both reflex (dynamic and static stretch-reflex gains corresponding to phasic and tonic reflex actions, respectively) and non-reflex (joint elastic stiffness and viscous damping characterizing displacement- and velocity- dependent resistances, respectively) changes in spastic ankles of stroke patients through in vivo experiments under both passive (muscle relaxed) and active muscle contracting) conditions over a period of 4 months.
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The third specific aim is to investigate stretching-induced changes in functional performance and the underlying mechanisms in terms of muscle force-generating capacity, maximum voluntary contraction (MVC), mechanical properties of the Achilles tendon and aponeurosis investigated using ultrasonography, torque-angle relationship of the triceps surae muscles, plantar and dorsi flexor co-contraction, and active ROM before and after stretching and over the period of 4 months. The long-term goals are to provide effective, convenient, and low-cost treatments of spastic limbs in neurologically impaired patients with quantitative outcome evaluation in multiple aspects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NMES FOR OLDER INDIVIDUALS AFTER TOTAL KNEE ARTHROPLASTY Principal Investigator & Institution: Snyder-Mackler, Lynn; Professor; Physical Therapy; University of Delaware Newark, De 19716 Timing: Fiscal Year 2002; Project Start 15-MAR-2002; Project End 28-FEB-2007 Summary: Reduced muscle strength from illness or injuries often leads to loss of function and independence in the elderly. The recovery of muscle strength and function in disabled elderly individuals is a major challenge in rehabilitation. The etiology of the muscle weakness with injury or age is fully elucidated. Training programs designed to maximize strength gains in young individuals may not be optimal in the elderly because the cause of the weakness and the morphology of the muscle may be different for young vs. old people. The overall goal of this work is to determine if physiologically and morphologically based rehabilitation programs are more effective than traditional rehabilitation to counter changes in muscle strength and function in older individuals. Neuromuscular electrical stimulation (NMES) may be used to improve strength and function following injury or surgery. This study provides motivation for exploring the use of NMES with the elderly. We posit that using NMES to augment a traditional rehabilitation program for elderly patients with osteoarthritis following total knee arthroplasties (TKA) will result in greater strength and functional gains than using only traditional rehabilitation. Elderly patients with osteoarthritis who undergo TKAs serve as ideal subjects for testing the effectiveness of rehabilitation programs become those patients almost always exhibit marked quadriceps weakness that is resistant to traditional physical rehabilitation. More than 300,000 TKAs are performed each year in the United States to treat osteoarthritis of the knee in older individuals. Neuromuscular electrical stimulation (NMES) may be used to improve strength and function following injury or surgery. This study provides motivation for exploring the use of NMES with the elderly, We posit that using NMES to augment a traditional rehabilitation program for elderly patients with osteoarthritis following total knee arthroplasties (TKA) will result in greater strength and functional gains than using only traditional rehabilitation. Elderly patients with osteoarthritis who undergo TKAs serve as ideal subjects for testing the effectiveness of rehabilitation programs become those patients almost always exhibit marked quadriceps weakness that is resistant to traditional physical rehabilitation. More than 300,000 TKAs are performed each year in the United States to treat osteoarthritis of the knee in older individuals. So, the successful rehabilitation of elder patients following TKA is an important and challenging problem. The specific aims of this proposal are: 1) To assess the effectiveness of high-level neuromuscular electrical stimulation is an adjunct to ongoing intensive, early rehabilitation in restoring quadriceps strength and improving the functional outcome after primary TKA, and 2) To identify the physiological and morphological bases for improvements in quadriceps strength and functional outcome.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL IMMUNOTOXIN AND IGF THERAPY FOR STRABISMUS Principal Investigator & Institution: Mcloon, Linda K.; Associate Professor; Ophthalmology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 30-NOV-2006 Summary: (provided by applicant): Strabismus is a common ophthalmologic problem, affecting between 2-5% of the population of preschool aged children in the U.S. It is manifested by a misalignment of the eyes and untreated results in amblyopia and permanent visual deficits. Many of these children require a surgical procedure for correction of their binocular alignment. The goal of this study is to develop pharmacologic treatments that will result in both muscle strengthening and muscle weakening. Current options include incisional surgery and botulinum toxin. Incisional surgery may be limited by induced scarring, altered muscle-globe dynamics, and disruption of extraocular muscle relationships with soft-tissue pulleys. These changes affect extraocular muscle function and may influence surgical outcomes. Botulinum toxin injection avoids most of these complications and has been used effectively for both childhood and adult strabismus. However, the treatment of congenital strabismus with botulinum toxin often yields inconsistent results, particularly where the initial deviation is large. The principle limitation of botulinum toxin injection is its relatively short duration of action. Ideally, injected agents should allow titratable adjustment of extraocular muscle force generation so that, in the presence of abnormal efferent motor signals, binocular alignment can be achieved. These effects must last sufficiently long so that sensory and motor adaptation can occur to create a permanent change in the rotational position of the globe. Immunotoxins are biological toxins, such as ricin, conjugated to antibodies that target the toxin against specific cells and tissues that express the selected antigen. This study is designed to test the primary hypothesis that immunotoxins, targeted against extraocular muscle, can be used in the treatment of strabismus by producing long-term muscle weakness. We will continue to test ricinmAb 35 and a new immunotoxin we are developing, DR-iTox, a fusion protein composed of the ricin A chain and the diphtheria A chain conjugated to a monoclonal antibody to the nicotinic acetylcholine receptor. Both immunotoxins are myotoxic and targeted to mature myofibers; they spare satellite cells and myoblasts, permitting muscle regeneration. We will determine if the increased myotoxicity of the DR-iTox will extend the duration of muscle weakening compared to treatment with ricin-mAb35. We will also attempt to strengthen selected extraocular muscles by direct injection of insulin growth factor I or II. Increasing the motive force of the antagonist could augment the long-term weakening effect of an immunotoxin in an extraocular muscle, and this represents a unique approach to strabismus treatment. These novel treatments may allow titratable and sustained changes in the rotational position of the globe, the goal of strabismus surgery, without requiring an incisional procedure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OSTEOBLAST AND ADIPOCYTE DIFFERENTIATION BY FOSB Principal Investigator & Institution: Baron, Roland E.; Orthopedics and Rehabilitation; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007
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Summary: Anterior cruciate ligament (ACL) injury is prevalent and often leads to instability, quadriceps muscle weakness and osteoarthritis. (OA) Many of those with chronic ACL deficiency have evidence of knee OA years after ACL rupture. Weakness and instability experienced by those who do not compensate well for ACL deficiency (non-copers) independently lead to compensation strategies that could precipitate or worsen knee OA. These poor compensation strategies do not uniformly resolve after surgical reconstruction and those who undergo reconstruction also have an increased risk of developing knee OA. The overall goal of this work is to determine whether effective rehabilitation programs to dynamically stabilize the knee reduce the adaptations that lead to osteoarthritis in a population at great risk for the development of knee OA. Eighty individuals with ACL rupture who are scheduled for surgery will be randomly assigned to a group that includes a form of neuromuscular training called perturbation training, or a standard group. They will be evaluated before and after surgery using motion analysis and radiography. In vivo measures of kinematics, kinetics, tibial translation and EMG based models of joint compression will be used for comparison. This randomized trial is designed to demonstrate that, after preoperative rehabilitation that includes perturbation training, movement patterns adopted by noncopers: 1) demonstrate improve joint stability and reduced muscle cocontraction, 2) persist after reconstruction and 3) result in better functional outcomes after reconstruction and 4) lead to the development of less knee pain and OA over time than standard preoperative treatment strategies. The information derived from this project will provide valuable insight into the management of the approximately 100,000 Americans who rupture their ACLs each year and undergo reconstructive surgery. More importantly, if the perturbation training program's ability to induce dynamic knee stability actually results in joint protection, its application to others at risk for the development knee OA may help reduce the incidence of this disabling clinical condition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHOGENESIS OF SARCOPENIA AND METABOLIC CHANGE IN AGING Principal Investigator & Institution: Nair, K. Sreekumaran.; Professor of Medicine; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 31-MAY-2004 Summary: Sarcopenia is a major public health problem among the rapidly elderly population expanding elderly population in our society. Disabilities directly related to muscle weakness, and indirectly related to changes in body composition and metabolic dysfunctions, are causing a staggering toll in disability and health care costs. Osteopenia occurs almost simultaneously with sarcopenia in the elderly population and muscle weakness increases the risk for falls and, therefore, fractures. Although these issues have been separately addressed in several studies, an integrated investigational approach to better understand the pathogenesis of sarcopenia and other age-related metabolic abnormalities and to investigate the potential role of androgens have not been undertaken in a comprehensive manner. The program contains four independent research programs, each representing different research disciplines, and four separate cores supporting the four projects. The main focus on the project is to determine the effect of the replacement of testosterone in elderly men and DHEA in elderly men and women and to compare these effects with placebo treatment over a two-year period. Project 1, "Effect of Androgen Replacement on Muscle Metabolism" will specifically determine whether these interventions have a different effect on size and quality of muscle in terms of strength and metabolic functions. Project 2, "Effect of Androgen
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Replacement on Bone Metabolism," will determine the effects of this intervention on bone mineral density and markers of bone turnover. Project 3, "The Effect of Androgen Replacement on Carbohydrate Metabolism," will determine whether the age-associated decrease in circulating androgens contributes to the alterations in carbohydrate metabolism that are commonly observed in the elderly and on insulin action, insulin secretion, and glucose effectiveness. Project 4, "Effect of Androgen Replacement on Fat Metabolism" will determine whether changes in fat distribution that occur with aging could result from differences in regional fatty acid uptake and systemic fatty acid kinetics, and whether these determinants of fat distribution are altered by the interventions. The data emerging from these studies will be integrated to determine the intervention of sarcopenia with other metabolic change and hopefully will contribute to a better understanding of the relationship between sarcopenia, hormonal changes, and many associated metabolic dysfunctions of muscle, bone, carbohydrate and fat metabolism. This study will hopefully form the scientific basis for future trials of androgen replacement in the elderly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHASE II DEVELOPMENTAL STUDY ON FATIGUE IN CANCER Principal Investigator & Institution: Cruciani, Ricardo; Director of Clinical Studies; Beth Israel Medical Ctr (New York) 1St Ave at 16Th St New York, Ny 10003 Timing: Fiscal Year 2002; Project Start 27-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): Fatigue is the most frequently reported symptom in patients with cancer. The causes of fatigue are multifactorial and include the disease itself, antineoplastic therapies, anemia, depression, and malnutrition. Our preliminary data suggest that micronutrient deficiencies, specifically carnitine deficiency, may be an important factor in fatigue. Carnitine plays a major role in energy metabolism. Systemic depletion is characterized by weight loss, fatigue, muscle weakness, decreased tolerance to metabolic stress, andcardiomyopathy. We found deficiency of the micronutrient carnitine in 17/27 patients with cancer. Symptoms of fatigue and functional status improved significantly in those patients who received oral L-carnitine supplementation. In addition, we observed similar results in 6/10 patients with end stage AIDS presenting with carnitine deficiency. Objectives: a) To determine the effect of L-carnitine therapy on symptoms of fatigue in patients with terminal cancer and serum carnitine deficiency, and b) to determine the effect of L-carnitine therapy on performance status, cognitive function, mood, quality of life, and motor activity in these patients. Study Design: We propose to conduct a Phase Il developmental randomized double-blind placebocontrolled study to determine the effect of the micronutrient L-carnitine on fatigue and other outcomes in patients with terminal cancer. A sample of 130 patients with terminal cancer, fatigue and serum carnitine deficiency will be recruited into the intervention study. At the first visit, the patients will receive a baseline assessment of fatigue, performance status, cognitive function, mood, and quality of life and motor activity. a) During weeks 1-4, patients will be randomized to receive L-carnitine, 2 g/day, placebo. b) During weeks 5-8, all patients will receive L-carnitine at a dose of 2 g/day, for a period of 4 weeks. Measures will be repeated at 48 hs, 2 weeks, 4 weeks and 8 weeks. The primary endpoint will be change in fatigue at 4 weeks. Analysis will evaluate group differences in the primary endpoint and other outcomes. An interim analysis will be done once 15 patients have been observed in each group at 4 weeks. Paired and unpaired data analyses between groups will be conducted with the assistance of a statistician. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHYSIOLOGY OF RESPIRATORY MUSCLE MIRCO MECHANICS Principal Investigator & Institution: Boriek, Aladin; Associate Professor of Medicine and Phys; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 28-FEB-2005 Summary: We propose to investigate the mechanisms of force transmission in skeletal muscles. In particular, we will investigate the contribution of desmin and dystrophin, intracellular components of the membrane cytoskeleton, the membrane receptor alpha7-integrin, and the extracellular molecular merosin to force transmission in diaphragm muscle. Desmin deficiency leads to desminopathy, a rare disease. Deficiencies of dystrophin, merosin, or alpha-7-integrin lead to various form of muscular dystrophy, which are more common diseases. Lack of any of these proteins causes skeletal muscle degeneration, chronic inspiratory muscle weakness, and ultimately respiratory insufficiency that leads to respiratory failure and eventually death. The diaphragm, unlike most other skeletal muscles, is loaded biaxially in vivo. That is the diaphragm experiences loads along muscle fibers and transverse to fibers during contractile activity. This application is an initial first step towards understanding the mechanical behavior of diaphragm muscle at the cellular level. Our central hypothesis is that force transmission in the diaphragm is modulated by transverse fiber loading and mediated by the linkage of specific intra- and extracellular members of the transmembrane protein network. This hypothesis will be tested by studying spontaneous and engineered mutant mouse strains; using strains missing key elements of the transmembrane protein network, we will test the response of the biaxial mechanical properties of the diaphragm and hindlimb muscles to the absence of these proteins. The long term goals of this research program are to understand muscle force transmission in skeletal muscles at the protein level and build a detailed model of mechanical coupling in normal skeletal muscles that explains the mechanism(s) by which force is transmitted from cytoskeleton to extracellular matrix. The specific aims of this project are to determine passive mechanical properties of the mouse diaphragm and their influence on contractile function and to evaluate the role of intracellular, transmembrane, and extracellular elements on the biaxial transmission of force in the diaphragm. Using a electron microscopy and biaxial loading technique applied to whole diaphragm and limb skeletal muscles in vitro, we will test the following hypotheses at both tissue and sarcomere levels: (1) transverse stress mediates force transmission in the normal diaphragm at both tissue and at sarcomere levels, and both passive and contractile properties of the diaphragm are altered by the presence of transverse stress; (2) intracellular members of the transmembrane protein network, desmin and dystrophin, are essential in integrating transverse and longitudinal mechanical properties of the diaphragm, and the strength of the mechanical linkage between myofibrils and the plasma membrane is determined primarily by these proteins; and (3) the mechanical coupling between myofibrils and extracellular matrix is crucial to force transmission along and transverse to the fibers in normal skeletal muscles, and force transmission is compromised by loss of either alpha7-integrin or merosin. These aims address the mechanism(s) by which force transmission is mediated by specific cytoskeletal and extracellular proteins in skeletal muscles. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: POSTTRANSLATIONAL PROCESSING BY ZMPSTE24 AND LAMINOPATHY Principal Investigator & Institution: Ng, Jennifer K.; J. David Gladstone Institutes Box 419100, 365 Vermont St San Francisco, Ca 94103
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Timing: Fiscal Year 2003; Project Start 16-MAR-2004; Project End 15-MAR-2006 Summary: (provided by applicant): The proteins of the nuclear lamina have generated enormous interest because missense mutations in LMNA (the gene for prelamin A, which encodes both lamin A and lamin C) cause a host of diseases, including EmeryDreifuss muscular dystrophy, limb-girdle muscular dystrophy, Charcot-Marie-Tooth type II peripheral neuropathy, and Hutchinson-Gilford progeria syndrome. Prelamin A, the precursor to mature lamin A, undergoes a series of posttranslational modifications, including the covalent attachment of a lipid to the protein, proteolytic clipping of the protein, and methylation of the protein. These post-translational modifications are important both to the targeting of the lamins to the nuclear envelope and to their function. The laboratory of my mentor, Dr. Stephen G. Young, recently identified an endoprotease, Zmpste24, that is required for the maturation of prelamin A to lamin A. Interestingly, Zmpste24-deficient mice develop a muscle weakness phenotype I strikingly similar to that observed in mice lacking lamin A/C. A key objective of my application is to define the pathological and molecular underpinnings of the possible muscular dystrophy, peripheral neuropathy and progeria phenotype in Zmpste24deficient mice, as well as compare them to mice harboring mutant Lmna alleles. Finally, I will investigate the consequences of defective posttranslational processing of lamin A on a cellular level in order to elucidate the biochemical role of Zmpste24 in prelamin A processing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREDNISONE OCULAR MYASTHENIA GRAVIS TRIAL PLANNING GRANT Principal Investigator & Institution: Kupersmith, Mark J.; Beth Israel Medical Ctr (New York) 1St Ave at 16Th St New York, Ny 10003 Timing: Fiscal Year 2004; Project Start 23-JUL-2004; Project End 30-JUN-2005 Summary: (provided by applicant): Myasthenia gravis, a chronic autoimmune neuromuscular disease, is characterized by muscle weakness that increases during periods of activity and improves after periods of rest and can result in life-threatening complications such as respiratory failure. Often patients present with weakness confined to the ocular muscles, Ocular Myasthenia Gravis but within 1 to 2 years, approximately two-thirds of patients develop generalized disease. This application is for funding to support the final planning of a clinical trial for patients with Ocular Myasthenia Gravis. A double masked, placebo-controlled, randomized clinical trial of 240 patients will be designed to test the hypothesis that corticosteroid therapy with prednisone, in doses that do not cause major adverse events or side effects, will reduce the incidence of systemic muscle involvement and improve disease-related visual disability at one year. Reducing the risk of Generalized Myasthenia Gravis will decrease the risk of overall disability, Myasthenic crises, hospitalizations, and costly invasive therapies such as thymectomy and plasmaphoresis. In addition, if the proposed therapy reduces double vision and restores binocular function, patients may be better able to perform activities of daily living such as reading, driving an automobile, handling machinery, and work. If chronic low dose corticosteroids are beneficial in decreasing the incidence of generalized disease as well as reducing visual disability, it will replace the moderate to high dose therapy used by many neurologists; there by avoiding the significant complications of hypertension, infections, hyperglycemia, and osteoporosis. Our activities during the one year award period will be directed towards developing a Manual of Procedures, finalizing Study protocol, recruiting clinic sites, outlining data management systems, detailing Study drug distribution and tracking, creating clinic and patient brochures,
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and preparing and submitting the grant applications for the Study trial, via executive committee meetings and teleconferences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF THE SYNAPTIC LOCALIZATION OF THE NACHR Principal Investigator & Institution: Ferns, Michael J.; Physiology & Membrane Biology; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 956165200 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2008 Summary: (provided by applicant): Synapses are highly specialized for efficient synaptic transmission, with the transmitter release sites in the presynaptic nerve terminal being aligned with postsynaptic concentrations of the neurotransmitter receptor. At the developing neuromuscular junction, a nerve-derived factor called agrin directs the postsynaptic localization of the acetylcholine receptor, and our goal is to understand the molecular mechanisms that underlie agrin's action. Specifically, we will test the hypothesis that agrin regulates AChR localization by inducing phosphorylation of the AChR and altering its association with the intracellular scaffolding protein, rapsyn. We have the following specific aims: (1) To define the role of agrin-induced phosphoryation of the beta subunit in AChR localization. We will generate transgenic mice with a beta subunit lacking the phosphorylation site, and then determine whether this mutation impairs the synaptic localization of the AChR. We will also determine whether phosphorylation specifically regulates the anchoring, clustering, and/or stabilization of the receptor in the postsynaptic membrane. (2) To define the molecular mechanism of rapsyn-mediated AChR localization. Here, we will define rapsyn's binding site(s) on the AChR and determine whether binding is regulated by agrin. Moreover, we will investigate how agrin-induced changes in rapsyn/AChR association mediate receptor localization. This work is directly relevant to neuromuscular disorders such as congenital and autoimmune myasthenic syndromes, where there are severe deficiencies in AChR levels at the synapse, leading to impaired synaptic function and debilitating muscle weakness. Our work will help define the mechanisms involved in receptor localization and may suggest strategies to stabilize its localization in patients with myasthenic syndromes or other forms of neuromuscular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RESPIRATORY MUSCLE TRAINING IN VENTILATOR DEPENDENT PTS. Principal Investigator & Institution: Martin, Anatole D.; Physical Therapy; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2004; Project Start 15-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): Failure to wean patients from mechanical ventilation (MV) is a medical, economic and social problem. Approximately 40% of the time patients spend in ICU on MV is devoted to weaning. Numerous algorithms to predict weaning outcome have been published, but few studies have examined the specific treatment of weaning failure. The traditional approach to MV weaning has focused on optimizing medical care and the patient-ventilator interface, but there is growing evidence that MV use leads to inspiratory muscle weakness and this weakness is a major contributor to MV dependence. We have developed a practical rehabilitation approach to improving inspiratory muscle strength in MV dependent patients to facilitate weaning. We have assembled a team of physicians, a rehabilitation specialist, a
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respiratory physiologist, a communication specialist and developed a systematic rehabilitation approach to treating MV dependence due to inspiratory muscle weakness. We propose to study the effectiveness of threshold inspiratory muscle strength training (IMST) to improve weaning outcome in MV dependent patients. We will test the hypothesis that threshold IMST will increase the inspiratory pressure generating capacity of MV dependent patients, decrease the time required to wean these patients from MV and increase the proportion of patients weaned. MV dependent patients in ICUs will be divided into 2 groups: a SHAM group and an IMST group. Both groups will receive an identical MV management strategy with progressively lengthening spontaneous breathing trials as tolerated. The IMST group will receive up to 6 weeks of high intensity, low repetition training using a threshold inspiratory muscle trainer. The SHAM group will receive a training program for an equal period of time. The personnel providing the IMST and SHAM treatments and the subjects will be blinded to the treatments. Groups will be compared on the number of subjects weaned, the duration of time needed to wean following protocol completion and changes in breathing pattern. The results of this work will provide new information on an inspiratory muscle strengthening rehabilitation approach to weaning for MV dependent patients. This study will illuminate the mechanisms mediating MV dependence in these patients and lead to effective treatment strategies for patients dependent upon MV due to respiratory muscle weakness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF NITIRC OXIDE IN EXPERIMENTAL MYASTHENIA GRAVIS Principal Investigator & Institution: Krolick, Keith A.; Professor; Microbiology and Immunology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Experimental Autoimmune Myasthenia Gravis (EAMG) is a neuromuscular disease that can be induced in rodents such as rats and mice by immunization with purified acetylcholine receptor (AChR). Neuromuscular dysfunction is associated with the production of autoantibodies directed at the AChR on the post-synaptic muscle membrane. The resulting abnormal function of the AChR leads to inefficient contractile function, muscle weakness and rapid fatigue characteristic of human MG. it is clear from both human and animal studies that antibody with reactivity against the AChR, although the most prominent disease determining factor, is not the only disease-determining factor. In addition, cytokines associated with the balance of TH1 vs TH2 activities may play an important role in the severity of disease symptoms in EAMG. In light of pilot studies presented below, it is likely that nitric oxide (NO), a potent immunomodulator capable of both beneficial and deleterious effects, may be a muscle-derived factor that could influence disease severity and progression. Therefore, it is the primary goal of this project to evaluate the potential of muscle-derived NO to influence disease progression in the rat model of EAMG. The general strategy to be used in this investigation is to seek links between iNOS/NO production and EAMG by monitoring skeletal muscle following in vivo exposures to immune mediators of EAMG (i.e., antibodies reactive with the acetylcholine receptor (AChR) and particular subsets of cytokine-producing cells). The Specific Aims of this project are as follows: Specific Aim 1. Evaluate INOS/NO-inducing activity associated with individual clonotypic ACHRreactive antibody species of Lewis and WF rats. Specific Aim 2. Evaluate the ability of ACHR-reactive T cells to influence the expression of INOS/NO by rat skeletal muscle.
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Specific Aim 3. Determine influences of NO production on immune activities associated with EAMG. Specific Aim 4. Determine influences of NO production on the diseasesusceptibility of the AChR-immune Lewis rat and the disease-resistance of the AChRimmune Wistar Furth rat. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF TROPONIN T ISOFORMS IN AMISH NEMALINE MYOPATHY Principal Investigator & Institution: Jin, Jian-Ping; Physiology and Biophysics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: (provided by applicant): The nemaline myopathies are neuromuscular disorders characterized by muscle weakness and rod-shaped "nemaline" inclusions in skeletal muscle fibers. Recent studies have identified a recessively inherited form of nemaline myopathy, the Amish nemaline myopathy (ANM), among the Old Order Amish at the rate of 1 of 500 births. The molecular cause of ANM is a nonsense mutation in the gene encoding slow skeletal muscle troponin T (TnT), a muscle- specific Ca2+ regulatory protein, truncating the protein at amino acid 179. We have shown that the truncated slow TnT is degraded and not incorporated into the myofibrils, consistent with the recessive inheritance of the disease. The ANM phenotypes include tremors, contractures and hypotonia. A rapid postnatal progress results in death from respiratory insufficiency, usually in the second year. No effective treatment is available. The discovery of ANM gene has given the affected families the first hope for a cure of this fatal disease. Three homologous genes are present in the vertebrate genome encoding the slow, fast and cardiac TnT isoforms. Despite the loss of slow TnT in ANM muscle, only mild phenotypes are shown at birth. The postnatal worsening of myopathy is concurrent with the developmental down-regulation of cardiac TnT in skeletal muscle and the embryonic to adult isoform transition of fast skeletal muscle TnT. Therefore, cardiac and embryonic fast TnT, but not adult fast TnT, may compensate for the lost function of slow TnT. To understand the pathology of ANM in which the loss of only one isoform of TnT causes severe myopathy, we shall investigate the functional relationship between TnT isoforms. In addition to a better understanding of the Ca2+regulation of muscle contraction, this study aims at the development of therapies for ANM. Four specific aims are proposed to bridge the basic studies of TnT isoform gene regulation and structure-function relationships to the clinical management of this lethal disease.I. Biochemical characterization of TnT isoforms to investigate their functional difference and whether the cardiac TnT and embryonic fast TnT, both of which are acidic isoforms, are functionally similar to slow TnT which is also acidic.II. Functional characterization of the truncated slow TnT to determine whether it may have a dominant negative effect in ANM.III. Protein interaction and transgenic expression experiments to investigate whether disorganization of muscle thin filament due to change in one regulatory protein forms the basis of nemaline myopathy.IV. Production and characterization of the slow TnT mutation in an animal model of ANM to study muscle pathophysiology, fatigue tolerance, and therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RXR ALPHA: SCREENING A CANDIDATE FOR LATE LIFE DISEASE Principal Investigator & Institution: Beamer, Brock A.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218
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Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2003 Summary: While changes in body composition-and often disastrous sequelae thereofuniversally accompany old age, there is tremendous variability in their onset, pattern and severity. The long term objective of this project is to better understand the molecular basis for this heterogeneity, and thereby the pathways which underlie such changes. The immediate focus is whether some variability is due to genetic heterogeneity in the nuclear receptor RXRalpha (9-cis retinoic acid receptor). RXRalpha is essential for the action of many nuclear receptors (e.g. PPAR, THR, RAR) and lays significant roles in development and maintenance of bone, muscle and skin tissue (among other tissues). Ligand and artificial mutation suggest that alterations in RXRalpha activity or interactivity could have a variety of phenotypic consequences. We hypothesize that mutations in genes such as RXRalpha could contribute to (or protect against) severe or early onset declines in bone, muscle or skin. Specific aim #1 is to recruit small cohorts of well-characterized older individuals free of confounding conditions (e.g. glucocorticoid use) selected for severe and/or early onset: (i) osteoporosis, (ii) muscle weakness, (iii) decreased skin integrity, or (iv) absence of these at extreme old age. Specific Aim #2 is to perform SSCP analysis of RXRalpha on genomic DNA from 15 individuals of each cohort, and begin characterization of any variants identified. Beyond the scope of this pilot project is (i) screening these cohorts for variation in other genes that may influence musculoskeletal or dermatologic changes with age; (ii) performing functional analyses of large definitive association studies with any variants found from this screen; or (iii) assessing other conditions potentially influenced by variation in RXRalpha (e.g. thyroid function, vision). However, this project should form bases from which such questions could be explored. Within its scope, it may help to elucidate general pathways underlying age-related changes in body composition/function, which ultimately will lead to improved means of preventing and treating their sequelae (perhaps with the RXRalpha agonists/antagonists now being developed). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SARCOPENIA--UNDERLYING MECHANISMS Principal Investigator & Institution: Larsson, Lars G.; Noll Physiological Res Ctr; Pennsylvania State University-Univ Park 110 Technology Center University Park, Pa 16802 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: The demographic evolution in the US, with an increasing number of elderly citizens, is probably the single most important socio- economic challenge to the American health care system, both today and in the future perspective. A number of diseases associated with aging have received intense scientific attention, such as Alzheimer's disease, diabetes mellitus, Parkinson's disease, osteoporosis, and others. The aging-related motor handicap and the impaired neuromuscular function in old age, on the other hand, have received relatively less scientific interest, especially studies bridging the gap between basic science and clinical practice. This is surprising, since slowing of movements and muscle weakness are prominent features of old age in most mammals, and by far the most commonly encountered type of muscle atrophy in man is that associated with senility. Thus, improving functional independence has become an important goal as the elderly population increases, and it is well accepted that while individuals may live longer, they do not necessarily live active, happy and independent lives. This project is the first of its kind where state-of-the-art techniques are used to study the mechanisms underlying aging- related impairments in muscle function from
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the whole muscle to the cellular and molecular levels in humans, and how they are affected by gender. Specific interest is focused on aging- related post-translational modifications of the motor protein myosin by oxidative stress and non-enzymatic glycosylation (glycation), and the consequences of these modifications on regulation of muscle contraction. This is of significant interest since antioxidant defense system and other intracellular factors which affect glycation may become less efficient in the aged organism. The use of whole muscle, cellular- and molecular physiological methods in combination with ultrasensitive electrophoretic protein separation, imaging and immuno/enzyme- histochemical techniques offers a unique possibility to explore the regulatory and modulatory influence of the molecular motor protein myosin on contractile speed and how this regulation is affected by aging in humans. This research project will elucidate basic mechanisms underlying the motor handicap in the elderly at the skeletal muscle level and apply this knowledge to clinical research/practice, aiming to improve the quality of life and to decrease the dependency of the increasing population of elderly US citizens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SMN ASSOCIATED PROTEINS AND COMPOUNDS FOR SMA THERAPY Principal Investigator & Institution: Zhou, Jianhua; Medicine; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: (provided by applicant): The autosomal recessive spinal muscular atrophy (SMA) is one of the most common genetic causes of infant death. In SMA, there is anterior horn cell death and muscle weakness. Deletions or mutations in the survival motor neuron gene, SMN, are responsible for the disease. There are two SMN genes. However, only telomeric copy (SMNt or SMNI) causes disease. Due to a single nucleotide difference, T in the second gene SMN2 from C in SMNI, the majority of SMN2 mRNA or protein skips exon7, resulting in an unstable SMNA7 protein and reduction of its oligomerization ability. Therefore, the presence of the SMN2 gene in SMA patients can not compensate for the loss of the SMNI gene. To understand the pathogenesis of SMA, the first goal of this proposal is to use the yeast two-hybrid screens to identify SMN interacting proteins, particularly those from motor neurons. The interactions will be further characterized by other complementary methods including mammalian two hybrid assays, in vitro binding assays and in vivo coimmunoprecipitation assays. The biological significance of interactions between SMN and its interactors will be investigated in cell lines, and as long-term goals, in animal models. The second goal of this proposal is to develop cell-based systems for therapeutic studies of SMA based on the hypothesis that increasing of total or full-length SMN protein from SMN2 would reduce the severity of SMA. Stable cell lines and transgenic mice expressing exon 7 splicing cassettes with reporters such as GFP, luciferase or Plactamase will be established. Both high and low throughput screening (HTS, LTS) will be used to identify small molecules to promote inclusion of exon 7 in SMN2 mRNA and protein. These compounds will be tested in SMA mouse models. Signal pathways and other mechanisms that regulate RNA splicing of SMN genes will be investigated. 1 ZNS1 SRB R(01) 3 1 R01 NS41665-01 DECEMBER 13-14, 2000 ZHOU, DR. JIANHUA Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRENGTH TRAINING FOR THERAPY-INDUCED MUSCLE WEAKNESS Principal Investigator & Institution: Visovsky, Constance G.; None; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2004; Project Start 07-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): Treatments for cancer can have deleterious effects. Both chemotherapy and biotherapy have documented ill effects on skeletal muscle. Cancer and treatment-related side effects such as decreased energy level, muscle weakness and declines in functional status and body mass have been well documented. Early detection methods and novel therapies have increased the life span of individuals living with cancer, and thus, individuals with cancer are living longer lives with the effects of disease and treatment. The purpose of this study is to test the effectiveness of adherence to a strength training exercise program in individuals undergoing chemotherapy for Stage I-IIIa non-metastatic breast cancer. The primary specific aim of this study is to determine the effect of a strength training exercise program on changes in muscle strength, fatigue, body composition and quality of life over time, controlling for age, total drug dose, research site, and baseline muscle strength. A secondary specific aim is to determine the feasibility and acceptability of a home-based strength training exercise program to patients and clinicians. A two group randomized clinical trial will be used for this study, a convenience sample of 128 (64 per group) subjects receiving treatment with chemotherapy will be recruited and data on muscle strength, body composition, fatigue levels and quality of life will be collected at baseline, and 4, 8 and 12 weeks of treatment. Following baseline data collection, subjects will be randomly assigned to the tailored strength training intervention or to the control group. Subjects in the intervention group will be given usual care plus a home strength training exercise program. Participants in the comparison group will receive an attentional intervention in addition to the usual care. Data analysis will compare group differences using ANCOVA and regression slopes calculated as scores of change over time for the dependent variables. Questions regarding the feasibility and acceptability of a homebased strength training exercise program will be collected from the intervention group at protocol completion. Content analysis and quantitative data will be used to determine the feasibility and acceptability of a home-based strength training exercise program to patients and clinicians. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TESTOSTERONE THERAPY AFTER HIP FRACTURE IN ELDERLY WOMEN Principal Investigator & Institution: Binder, Ellen F.; Associate Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2004; Project Start 01-JUN-2004; Project End 31-MAY-2006 Summary: provided by applicant): Hip fractures are common among elderly women and can have a devastating impact on their ability to remain independent. A significant functional decline following a hip fracture has been documented, and many patients have persistent strength and mobility deficits that impair their capacity for independent function. Such individuals are at high risk for continued supportive services, recurrent injury, and institutionalization. High-risk patients include those with deficits in skeletal muscle strength during the post fracture period. Age-associated androgen deficiency contributes to deficits in muscle mass and strength that are common in this patient population. The role of testosterone therapy for improving deficits in muscle mass,
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strength, and functional capacity in the frail elderly is unclear, particularly for elderly women. There is insufficient information regarding tolerability of testosterone therapy, and the appropriate medication dosage and target serum testosterone levels necessary to induces changes in skeletal muscle mass and functional measures in elderly women with physical frailty due to muscle weakness. The goals of this project are to conduct a randomized, double-blinded, placebo-controlled prospective study to determine the feasibility, tolerability, and safety of 6 months of testosterone therapy in community dwelling, physically frail, elderly female hip fracture patients. Twenty-seven female hip fracture patients will be enrolled, using objective criteria for testosterone deficiency and frailty. We plan to evaluate two dosages of testosterone, administered as a 0.5% topical gel: a physiologic replacement dosage, and a supraphysiologic dosage. We plan to carefully monitor testosterone levels, side effects, biochemical parameters, and factors related to compliance with therapy. We plan to obtain preliminary information regarding the changes in measurements of muscle strength, total score on an Objective Physical Performance Test, total lean body mass by dual energy x-ray absorptiometry (DEXA), thigh cross-sectional areas by magnetic resonance imaging (MRI), and selfreported performance of activities of daily living, and quality of life. These data will be used to develop a full-scale proposal to test the long-term hypothesis that testosterone therapy combined with exercise training can improve physical function after a hip fracture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TH1 AND TH2 RESPONSES AND MYASTHENIA GRAVIS Principal Investigator & Institution: Infante, Anthony J.; Professor; Pediatrics; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: (Adapted from Investigator's abstract): Experimental autoimmune myasthenia gravis (EAMG) is induced in susceptible strains of mice by immunization with acetylcholine receptor (AchR). Muscle weakness is thought to be entirely mediated by high-affinity IgG autoantibodies, with little participation from cell-mediated effector mechanisms. Recently, strong evidence has been provided that EAMG depends on the production of Th1 cytokines, especially IL-12 and interferon-gamma (IFN-gamma). IFNgamma has been shown to have powerful direct influences on muscle cells in culture, among them upregulation of MHC class II and cell adhesion molecules. The applicant proposes that Th1 cytokines, predominantly IFN-gamma, have a direct action on muscle in vivo, causing increased susceptibility to immune-mediated damage and interference with muscle function, regeneration and repair. Three specific aims are proposed to test this hypothesis. In Aim 1, the investigator will define the role of key Th1 and Th2 cytokines in EAMG, by administration of recombinant cytokines, neutralization of cytokine activity by monoclonal antibodies (mAbs) and studies in cytokine gene knockout mice. The investigator will be particularly interested in whether Th1 and Th2 cytokines are antagonistic or synergistic. In Aim 2, the applicant will purify antibodies made under the influence of various cytokines and assess their pathogenicity by adoptive transfer. The direct effect of cytokines will be measured, individually and in combinations, with and without co-application of autoantibodies to muscle cells grown in culture. These changes in cultured muscle cells will then be correlated with muscle tissue findings in vivo. In Aim 3, a dominant-negative IFN-gamma receptor transgene under the control of tissue specific promoters will be used to confer specific tissue resistance to the actions of IFN-gamma. This hypothesis may show that muscle unresponsiveness to IFN-gamma may confer resistance to EAMG. In addition to
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providing significant advances in understanding the immunopathogenic basis of MG, such a result could also lead to novel therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ELECTROPHYSIOLOGY OF MOTOR NEURON DISEASES Principal Investigator & Institution: Bromberg, Mark B.; Professor; Neurology; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2003 Summary: (provided by applicant): Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders of unknown etiology. They have in common death of lower motor neurons (LMN) causing muscle weakness, and both disorders are fatal. Mechanisms of LMN death differ for SMA and ALS. In SMA, LMN death may occur over a limited period of time. Unanswered is whether there is late or continued LMN loss. Recent genetic studies in SMA indicate a relationship between survival motor neuron gene (SMN2) copy number and SMA type. Unanswered is the relationship between copy number and LMN number. In ALS, no single mechanism of LMN death explains known features, and a cascade of events ultimately leading to LMN death is likely. Unanswered in ALS is the natural pattern of progression of LMN loss from muscle to muscle. Although muscle weakness is the clinical manifestation of LMN loss for both disorders, the rate of loss of strength does not accurately reflect the rate of loss of LMNs. The discrepancy is due to the compensatory effects of reinnervation of denervated fibers by collateral sprouting from surviving motor nerve terminals. Similarly, routine electrophysiologic tests do not accurately measure LMN loss. Unanswered for both disorders is the dynamics of the compensatory process that determines the clinical state and level of function. Motor unit number estimation (MUNE) is a special electrophysiologic test that can directly assess the number of LMNs innervating a muscle. There are no data on the natural course of LMN loss for SMA, and little data for ALS. We propose to develop and refine MUNE and other electrophysiologic techniques to study, and follow the course of LMN loss and associated compensatory changes. For SMA, we will adapt MUNE techniques to study infants and children. For older SMA and ALS, we will refine MUNE techniques to optimize data collection. For SMA, we will correlate LMN loss with clinical type and SMN2 copy number. We will begin, in the two years of the grant-performing serial studies, to assess whether there is continued LMN loss. For ALS, we will determine and compare the rate and pattern of LMN loss in distal and proximal muscles. In older SMA and ALS, we will assess relationships between LMN loss and measures of collateral reinnervation and strength. We anticipate that MUNE and other electrophysiologic techniques will have direct applicability to the design of clinical trials for SMA and ALS, because these techniques can be used as informative end-point measures. To facilitate the use of MUNE in clinical trials, we will develop and refine the techniques in a form that can be used in any clinical center participating in trials. Currently, most MUNE techniques rely on proprietary software. We will develop software for use on PC-based computer systems, making them available to all laboratories. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE SARCOLEMMA IN FSHD AND IN THE MYD MOUSE Principal Investigator & Institution: Bloch, Robert J.; Professor; Physiology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004
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Summary: (provided by applicant): Facioscapulohumeral Muscular Dystrophy (FSHD) affects 1 of every 20,000 adults in this country. FSHD has been linked to deletions at the telomeric region of chromosome 4 (4q35-4q35ter), and is inherited as a dominant trait. Although we have learned a great deal about the genetic defects that lead to FSHD, we still know very little about the effects these defects have at the level of individual muscle fibers. Indeed, the cell biological changes that result in muscle weakness and myofiber degeneration have never been studied. Here we propose to address this issue by examining human biopsied materials using ultrastructural techniques and immunofluorescence coupled with confocal laser scanning microscopy. We postulate that, like other human dystrophies, such as Duchennes, Beckers, and some limb girdle muscular dystrophies, the sarcolemma of FHSD muscle is altered in ways that lead to muscle weakness and ultimately to muscle degeneration. In support of this hypothesis, our preliminary studies show that the sarcolemma of FSHD muscle has frequent interruptions in its membrane skeleton, is separated from the nearest myofibrils by a considerable gap, and is organized irregularly, and most closely resembles the sarcolemma of slow twitch muscle fibers although the myoplasm is rich in fast twitch myosin. We propose to pursue three aims in our exploratory studies of FSHD muscle that will: (i) test the validity of these observations and to extend them, if possible; (ii) compare them to other human muscular dystrophies; and (iii) study the biomechanical properties of the sarcolemma, to learn if they are compromised by FSHD. Our final aim will: (iv) examine the sarcolemma of the myd mouse, which has been proposed as a possible animal model of FSHD. Our laboratory has developed an unique set of methods and antibodies that permit us to examine the overall organization of the sarcolemma and its relationship to the nearby contractile apparatus. In the past year, we have adapted these methods for use with snap frozen biopsies of human skeletal muscle. We therefore anticipate making significant progress in understanding the cell biological changes that occur in FSHD skeletal muscle, and in determining which, if any, of these changes are related to the pathophysiology of FSHD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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 “muscle weakness” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for muscle weakness in the PubMed Central database: •
Acetylcholine receptor [var epsilon]-subunit deletion causes muscle weakness and atrophy in juvenile and adult mice. by Witzemann V, Schwarz H, Koenen M, Berberich C, Villarroel A, Wernig A, Brenner HR, Sakmann B.; 1996 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24085
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 muscle weakness, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “muscle weakness” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for muscle weakness (hyperlinks lead to article summaries): •
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70-year-old woman with rash and muscle weakness. Author(s): Mehta V, Swaroop VS. Source: Mayo Clinic Proceedings. 2004 July; 79(7): 923-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15244391
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. 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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A 21-year-old woman with muscle weakness and impaired vision. Author(s): Harris-Lawlor P. Source: Journal of Emergency Nursing: Jen : Official Publication of the Emergency Department Nurses Association. 1989 November-December; 15(6): 529-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2687547
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A case of respiratory muscle weakness due to cytochrome c oxidase enzyme deficiency. Author(s): O'Brien A, Blaivas M, Albers J, Wald J, Watts C. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1998 September; 12(3): 742-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9762807
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A low maximum inspiratory pressure is not the same as respiratory muscle weakness. Author(s): Davis MP. Source: Journal of Pain and Symptom Management. 2001 March; 21(3): 175-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11303497
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A novel 7.4 kb mitochondrial deletion in a patient with congenital progressive external ophthalmoplegia, muscle weakness and mental retardation. Author(s): Tabaku M, Legius E, Robberecht W, Sciot R, Fryns JP, Cassiman JJ, Matthijs G. Source: Genet Couns. 1999; 10(3): 285-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10546101
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A novel syndrome of episodic muscle weakness maps to xp22.3. Author(s): Ryan MM, Taylor P, Donald JA, Ouvrier RA, Morgan G, Danta G, Buckley MF, North KN. Source: American Journal of Human Genetics. 1999 October; 65(4): 1104-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10486330
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A second locus for autosomal dominant myopathy with proximal muscle weakness and early respiratory muscle involvement: a likely chromosomal locus on 2q21. Author(s): Xiang F, Nicolao P, Chapon F, Edstrom L, Anvret M, Zhang Z. Source: Neuromuscular Disorders : Nmd. 1999 July; 9(5): 308-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10407851
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A study of thigh muscle weakness in different pathological states of the lower extremity. Author(s): Nicholas JA, Strizak AM, Veras G. Source: The American Journal of Sports Medicine. 1976 November-December; 4(6): 2418. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12667
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A suspected case of proximal diabetic neuropathy predominantly presenting with scapulohumeral muscle weakness and deep aching pain. Author(s): Ogawa K, Sasaki H, Kishi Y, Yamasaki H, Okamoto K, Yamamoto N, Hanabusa T, Nakao T, Nishi M, Nanjo K. Source: Diabetes Research and Clinical Practice. 2001 October; 54(1): 57-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11532331
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A young woman with muscle weakness. Author(s): Singh NP, Anuradha S, Agarwal SK. Source: Postgraduate Medical Journal. 2001 April; 77(906): 273-4; Discussion 284-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11264505
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Acetazolamide-induced muscle weakness in hypokalemic periodic paralysis. Author(s): Ikeda K, Iwasaki Y, Kinoshita M, Yabuki D, Igarashi O, Ichikawa Y, Satoyoshi E. Source: Intern Med. 2002 September; 41(9): 743-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12322805
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Adaptive response to ocular muscle weakness in human pursuit and saccadic eye movements. Author(s): Optican LM, Zee DS, Chu FC. Source: Journal of Neurophysiology. 1985 July; 54(1): 110-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4031979
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Adult Fanconi syndrome with proximal muscle weakness and hypophosphatemic osteomalacia: report of a case. Author(s): Lian LM, Chang YC, Yang CC, Yang JC, Kao KP, Chung MY. Source: J Formos Med Assoc. 1994 August; 93(8): 709-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7858457
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Adult onset lipid storage in gastric mucosa and skeletal muscle fibers associated with gastric pain, progressive muscle weakness and partial deficiency of cytochrome C oxidase. Author(s): Schroder JM, Weber R, Weyhenmeyer S, Lammers-Reissing A, Meurers B, Reichmann H. Source: Pathology, Research and Practice. 1991 January; 187(1): 85-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1851299
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Adult onset supranuclear ophthalmoplegia, cerebellar ataxia, and neurogenic proximal muscle weakness in a brother and sister: another hexosaminidase A deficiency syndrome. Author(s): Harding AE, Young EP, Schon F. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1987 June; 50(6): 687-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2956362
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Adult-onset muscle weakness. How to identify the underlying cause. Author(s): Riggs JE. Source: Postgraduate Medicine. 1985 September 1; 78(3): 217-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4034446
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Alveolar hypoventilation and respiratory muscle weakness. Author(s): Davis JN, Loh L. Source: Bull Eur Physiopathol Respir. 1979; 15 Suppl: 45-53. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=122069
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An episode of malignant hyperthermia followed by a persisting muscle weakness. Author(s): Michalek-Sauberer A, Gilly H. Source: Anesthesiology. 1998 April; 88(4): 1128-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9579529
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An inherited dystrophin deletion without muscle weakness. Author(s): Collins AL, Leyland KG, Kennedy CR, Robinson D, Spratt HC. Source: Journal of Medical Genetics. 1994 June; 31(6): 505. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8071981
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An unusual case of muscle weakness. Author(s): Dunne CA, Molloy MG. Source: Ir Med J. 1991 June; 84(2): 61. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1894498
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An unusual cause of hypokalemic muscle weakness. Author(s): Valeriano J, Tucker P, Kattah J. Source: Neurology. 1983 September; 33(9): 1242-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6684266
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An unusual presentation of polymyalgia rheumatica with severe muscle weakness. Author(s): Radhamanohar M. Source: Br J Clin Pract. 1992 Autumn; 46(3): 213-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1286029
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Analysis of lung volume restriction in patients with respiratory muscle weakness. Author(s): De Troyer A, Borenstein S, Cordier R. Source: Thorax. 1980 August; 35(8): 603-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7444828
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Apnea and muscle weakness in two premature infants: descriptive case reports. Author(s): Thibeault DW. Source: Military Medicine. 1972 August; 137(8): 305-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4626054
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Approach to diagnosis in the child with muscle weakness. Author(s): Spiro AJ. Source: Pediatric Annals. 1977 March; 6(3): 149-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=322047
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Atracurium and prolonged muscle weakness. Author(s): Rosenberg SG. Source: Anesthesia and Analgesia. 1994 December; 79(6): 1211. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7978457
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Benign congenital myopathy. A cause for mild, nonprogressive or slowly progressive muscle weakness. Author(s): Saper JR. Source: The American Journal of Medicine. 1974 August; 57(2): 157-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4276677
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Breathing during sleep in patients with myotonic dystrophy and non-myotonic respiratory muscle weakness. Author(s): Gilmartin JJ, Cooper BG, Griffiths CJ, Walls TJ, Veale D, Stone TN, Osselton JW, Hudgson P, Gibson GJ. Source: The Quarterly Journal of Medicine. 1991 January; 78(285): 21-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1670061
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Breathing patterns during curare-induced muscle weakness. Author(s): Rosenbaum SH, Askanazi J, Hyman AI, Kinney JM. Source: Anesthesia and Analgesia. 1983 September; 62(9): 809-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6881569
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Can low blood pressure over a long period cause dizziness or extreme muscle weakness? Author(s): Goldfinger SE. Source: Harvard Health Letter / from Harvard Medical School. 1998 October; 23(12): 7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9780866
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Carcinoid myopathy. Serotonin-induced muscle weakness in man? Author(s): Swash M, Fox KP, Davidson AR. Source: Archives of Neurology. 1975 August; 32(8): 572-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1156216
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Cardiac abnormalities and skeletal muscle weakness in carriers of Duchenne and Becker muscular dystrophies and controls. Author(s): Grain L, Cortina-Borja M, Forfar C, Hilton-Jones D, Hopkin J, Burch M. Source: Neuromuscular Disorders : Nmd. 2001 March; 11(2): 186-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11257476
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Carnitine deficiency with hyperbilirubinemia, generalized skeletal muscle weakness and reactive hypoglycemia in a patient on long-term total parenteral nutrition: treatment with intravenous L-carnitine. Author(s): Worthley LI, Fishlock RC, Snoswell AM. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1983 March-April; 7(2): 176-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6406707
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Carnitine deficiency with hyperbilirubinemia, generalized skeletal muscle weakness, and reactive hypoglycemia in a patient on long-term total parenteral nutrition. Author(s): Meguid MM, Borum P. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1984 January-February; 8(1): 51-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6422074
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Carnitine palmityltransferase deficiency and fixed muscle weakness. Author(s): Nelson KR, Davis D. Source: Archives of Neurology. 1990 January; 47(1): 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2328044
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Case of the month: February 1999--54 year old man with severe muscle weakness. Author(s): Hill MD, Bilbao JM. Source: Brain Pathology (Zurich, Switzerland). 1999 July; 9(3): 607-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10416996
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Case-of-the-month: autosomal recessive myotonia congenita: marked muscle weakness in a 16-year-old boy. Author(s): Miller RG, Buchthal F. Source: Muscle & Nerve. 1992 January; 15(1): 111-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1732755
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Cerivastatin monotherapy-induced muscle weakness, rhabdomyolysis and acute renal failure. Author(s): Bakri R, Wang J, Wierzbicki AS, Goldsmith D. Source: International Journal of Cardiology. 2003 September; 91(1): 107-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12957739
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Cervical radiculopathy: pain, muscle weakness and sensory loss in patients with cervical radiculopathy treated with surgery, physiotherapy or cervical collar. A prospective, controlled study. Author(s): Persson LC, Moritz U, Brandt L, Carlsson CA. 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. 1997; 6(4): 256-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9294750
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Cervical vertebral osteomyelitis revisited: a case of retropharyngeal abscess and progressive muscle weakness. Author(s): Sakamoto M, Ichimura K, Tayama N, Nakamura M, Inokuchi K. Source: Otolaryngology and Head and Neck Surgery. 1999 November; 121(5): 657-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10547492
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Chest wall stiffness in patients with chronic respiratory muscle weakness. Author(s): Estenne M, Heilporn A, Delhez L, Yernault JC, De Troyer A. Source: Am Rev Respir Dis. 1983 December; 128(6): 1002-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6228174
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Chronic muscle weakness caused by Borrelia burgdorferi meningoradiculitis. Author(s): Wokke JH, de Koning J, Stanek G, Jennekens FG. Source: Annals of Neurology. 1987 September; 22(3): 389-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3674804
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Chronic renal failure presenting as proximal muscle weakness in a child. Author(s): Berretta JS, Holbrook CT 3rd, Haller JS. Source: Journal of Child Neurology. 1986 January; 1(1): 50-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3598108
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Clinical spectrum of muscle weakness in human West Nile virus infection. Author(s): Leis AA, Stokic DS, Webb RM, Slavinski SA, Fratkin J. Source: Muscle & Nerve. 2003 September; 28(3): 302-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12929189
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Clinically significant muscle weakness induced by oral dantrolene sodium prophylaxis for malignant hyperthermia. Author(s): Watson CB, Reierson N, Norfleet EA. Source: Anesthesiology. 1986 September; 65(3): 312-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3752576
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Contributing factors to muscle weakness in children with cerebral palsy. Author(s): Elder GC, Kirk J, Stewart G, Cook K, Weir D, Marshall A, Leahey L. Source: Developmental Medicine and Child Neurology. 2003 August; 45(8): 542-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12882533
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Correlation between tests of muscle involvement and clinical muscle weakness in polymyositis and dermatomyositis. Author(s): Tymms KE, Beller EM, Webb J, Schrieber L, Buchanan WW. Source: Clinical Rheumatology. 1990 December; 9(4): 523-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2088650
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Corticosteroids contribute to muscle weakness in chronic airflow obstruction. Author(s): Decramer M, Lacquet LM, Fagard R, Rogiers P. Source: American Journal of Respiratory and Critical Care Medicine. 1994 July; 150(1): 11-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8025735
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Cough dynamics during progressive expiratory muscle weakness in healthy curarized subjects. Author(s): Arora NS, Gal TJ. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 1981 August; 51(2): 494-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7263456
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Cross-bridge mechanisms of muscle weakness in multiple sclerosis. Author(s): Garner DJ, Widrick JJ. Source: Muscle & Nerve. 2003 April; 27(4): 456-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12661047
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Cutaneous changes of dermatomyositis precede muscle weakness. Author(s): Rockerbie NR, Woo TY, Callen JP, Giustina T. Source: Journal of the American Academy of Dermatology. 1989 April; 20(4): 629-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2715409
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Delayed recovery from muscle weakness due to malignant hyperthermia during sevoflurane anesthesia. Author(s): Maeda H, Iranami H, Hatano Y. Source: Anesthesiology. 1997 August; 87(2): 425-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9286908
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Dermatomyositis without muscle weakness associated with transitional cell carcinoma of the bladder. Author(s): Apaydin R, Gul U, Bahadir S, Siviloglu C, Ofluoglu I. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2002 March; 16(2): 172-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12046828
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Dermatomyositis without muscle weakness. Long-term follow-up of 12 patients without systemic corticosteroids. Author(s): Cosnes A, Amaudric F, Gherardi R, Verroust J, Wechsler J, Revuz J, Roujeau JC. Source: Archives of Dermatology. 1995 December; 131(12): 1381-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7492125
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Determinants of respiratory muscle weakness in stable chronic neuromuscular disorders. Author(s): Vincken W, Elleker MG, Cosio MG. Source: The American Journal of Medicine. 1987 January; 82(1): 53-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3799694
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Diabetes mellitus, deafness, muscle weakness and hypocalcemia in a patient with an A3243G mutation of the mitochondrial DNA. Author(s): Tanaka K, Takada Y, Matsunaka T, Yuyama S, Fujino S, Maguchi M, Yamashita S, Yuba I. Source: Intern Med. 2000 March; 39(3): 249-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10772130
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Dialysis-induced hyperkalaemia presenting as profound muscle weakness. Author(s): Brady HR, Goldberg H, Lunski C, Uldall PR. Source: Int J Artif Organs. 1988 January; 11(1): 43-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3360512
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Difference in distribution of muscle weakness between myasthenia gravis and the Lambert-Eaton myasthenic syndrome. Author(s): Wirtz PW, Sotodeh M, Nijnuis M, Van Doorn PA, Van Engelen BG, Hintzen RQ, De Kort PL, Kuks JB, Twijnstra A, De Visser M, Visser LH, Wokke JH, Wintzen AR, Verschuuren JJ. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 December; 73(6): 7668. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12438488
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Differential diagnosis of muscle weakness. Part I. Material, method, examination. Author(s): Rozhold O, Kos V, Bednarik J. Source: Acta Univ Palacki Olomuc Fac Med. 1987; 117: 137-49. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2963489
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Differential diagnosis of muscle weakness. Part II: Own results, discussion. Author(s): Rozhold O, Bednarik J, Kos V. Source: Acta Univ Palacki Olomuc Fac Med. 1987; 117: 151-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2963490
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Diphenylhydantoin for steroid-induced muscle weakness. Author(s): Stern LZ, Gruener R, Amundsen P. Source: Jama : the Journal of the American Medical Association. 1973 March 12; 223(11): 1287-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4739339
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Distinguishing between extrinsic and intrinsic tongue muscle weakness in unilateral hypoglossal palsy. Author(s): Riggs JE. Source: Neurology. 1984 October; 34(10): 1367-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6541310
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Distribution of extremity muscle weakness in myasthenia gravis: sparing of tibialis anterior muscle. Author(s): Ozturk A, Deymeer F, Serdaroglu P, Parman Y, Ozdemir C. Source: Acta Myol. 2003 September; 22(2): 58-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14959565
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Distribution of muscle weakness in patients with stable chronic obstructive pulmonary disease. Author(s): Gosselink R, Troosters T, Decramer M. Source: Journal of Cardiopulmonary Rehabilitation. 2000 November-December; 20(6): 353-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11144041
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Distribution of muscle weakness of central and peripheral origin. Author(s): Thijs RD, Notermans NC, Wokke JH, van der Graaf Y, van Gijn J. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1998 November; 65(5): 794-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9810962
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Disturbances of neuromuscular interaction may contribute to muscle weakness in spinal muscular atrophy. Author(s): Greensmith L, Vrbova G. Source: Neuromuscular Disorders : Nmd. 1997 September; 7(6-7): 369-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9327400
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Does parkinsonian action tremor contribute to muscle weakness in Parkinson's disease? Author(s): Brown P, Corcos DM, Rothwell JC. Source: Brain; a Journal of Neurology. 1997 March; 120 ( Pt 3): 401-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9126052
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Dominantly inherited megalencephaly, muscle weakness, and myoliposis: a carnitine-deficient myopathy within the spectrum of the Ruvalcaba-Myhre-Smith syndrome. Author(s): Powell BR, Budden SS, Buist NR. Source: The Journal of Pediatrics. 1993 July; 123(1): 70-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8320628
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Dyspnea and muscle weakness in a 65-year-old woman. Author(s): Mahler DA. Source: Chest. 1992 December; 102(6): 1875-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1446505
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Effect of diet on human muscle weakness following prolonged exercise. Author(s): Young K, Davies CT. Source: European Journal of Applied Physiology and Occupational Physiology. 1984; 53(1): 81-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6542506
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Effect of manually assisted cough and mechanical insufflation on cough flow of normal subjects, patients with chronic obstructive pulmonary disease (COPD), and patients with respiratory muscle weakness. Author(s): Sivasothy P, Brown L, Smith IE, Shneerson JM. Source: Thorax. 2001 June; 56(6): 438-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11359958
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Effect of pattern and severity of respiratory muscle weakness on carbon monoxide gas transfer and lung volumes. Author(s): Hart N, Cramer D, Ward SP, Nickol AH, Moxham J, Polkey MI, Pride NB. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 October; 20(4): 996-1002. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12412695
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Effect of respiratory muscle weakness on P0.1 induced by partial curarization. Author(s): Holle RH, Schoene RB, Pavlin EJ. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 1984 October; 57(4): 11507. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6438029
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Effects of 1,25-dihydroxycholecalciferol on calcium absorption, muscle weakness, and bone disease in chronic renal failure. Author(s): Henderson RG, Russell RG, Ledingham JG, Smith R, Oliver DO, Walton RJ, Small DG, Preston C, Warner GT. Source: Lancet. 1974 March 9; 1(7854): 379-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4131033
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Effects of intravenous immunoglobulin on muscle weakness and calcium-channel autoantibodies in the Lambert-Eaton myasthenic syndrome. Author(s): Bain PG, Motomura M, Newsom-Davis J, Misbah SA, Chapel HM, Lee ML, Vincent A, Lang B. Source: Neurology. 1996 September; 47(3): 678-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8797464
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Effects of respiratory muscle weakness on daily living function, quality of life, activity levels, and exercise capacity in mild to moderate Parkinson's disease. Author(s): Haas BM, Trew M, Castle PC. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2004 August; 83(8): 601-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15277961
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Electromyographic assessment of back muscle weakness and muscle composition: reliability and validity issues. Author(s): Lariviere C, Arsenault AB, Gravel D, Gagnon D, Loisel P, Vadeboncoeur R. Source: Archives of Physical Medicine and Rehabilitation. 2002 September; 83(9): 120614. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12235599
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Electromyographic predictors of residual quadriceps muscle weakness after anterior cruciate ligament reconstruction. Author(s): McHugh MP, Tyler TF, Browne MG, Gleim GW, Nicholas SJ. Source: The American Journal of Sports Medicine. 2002 May-June; 30(3): 334-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12016072
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Expiratory muscle weakness and assisted cough in ALS. Author(s): Lahrmann H, Wild M, Zdrahal F, Grisold W. Source: Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases. 2003 April; 4(1): 49-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12745619
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Facial and skeletal malformations, mental retardation, aganglionosis, and neurogenic muscle weakness: a variant of Niikawa-Kuroki syndrome or a new syndrome? Author(s): Greco D, Romano C, Elia M. Source: Journal of Child Neurology. 2001 April; 16(4): 296-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11332467
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Factors related to hip muscle weakness following fixation of acetabular fractures. Author(s): Matta JM, Olson SA. Source: Orthopedics. 2000 March; 23(3): 231-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10741367
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Flow-volume loop changes reflecting respiratory muscle weakness in chronic neuromuscular disorders. Author(s): Vincken WG, Elleker MG, Cosio MG. Source: The American Journal of Medicine. 1987 October; 83(4): 673-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3674055
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Four-month-old male infant with generalized muscle weakness. Author(s): Shirabe T. Source: Neuropathology : Official Journal of the Japanese Society of Neuropathology. 2002 December; 22(4): 365-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12564782
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Functional electrical stimulation treatment of postradiculopathy associated muscle weakness. Author(s): Abdel-Moty E, Fishbain DA, Goldberg M, Cutler R, Zaki AM, Khalil TM, Peppard T, Rosomoff RS, Rosomoff HL. Source: Archives of Physical Medicine and Rehabilitation. 1994 June; 75(6): 680-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8002769
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Genetic deficiency of short-chain acyl-coenzyme A dehydrogenase in cultured fibroblasts from a patient with muscle carnitine deficiency and severe skeletal muscle weakness. Author(s): Coates PM, Hale DE, Finocchiaro G, Tanaka K, Winter SC. Source: The Journal of Clinical Investigation. 1988 January; 81(1): 171-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3335634
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Graves' disease, gastrointestinal dysfunction, and muscle weakness. Author(s): Temple TE Jr, Watts NB. Source: J Med Assoc Ga. 1970 August; 59(8): 313-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5468582
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Hand muscle weakness in long-term vibration exposure. Author(s): Necking LE, Lundborg G, Friden J. Source: Journal of Hand Surgery (Edinburgh, Lothian). 2002 December; 27(6): 520-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12475507
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Hemodialysis encephalopathy with osteomalacic fractures and muscle weakness. Author(s): Pierides AM, Edwards WG Jr, Cullum UX Jr, McCall JT, Ellis HA. Source: Kidney International. 1980 July; 18(1): 115-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7218657
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Hypoglycemia, hepatic dysfunction, muscle weakness, cardiomyopathy, free carnitine deficiency and long-chain acylcarnitine excess responsive to medium chain triglyceride diet. Author(s): Glasgow AM, Engel AG, Bier DM, Perry LW, Dickie M, Todaro J, Brown BI, Utter MF. Source: Pediatric Research. 1983 May; 17(5): 319-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6682967
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Hypokalemic periodic paralysis or hypokalemic muscle weakness? Author(s): Buruma OJ, Schipperheyn JJ. Source: Archives of Neurology. 1981 May; 38(5): 326. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7224928
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Hypophosphatemia with muscle weakness due to antacids and hemodialysis. Author(s): Boelens PA, Norwood W, Kjellstrand C, Brown DM. Source: Am J Dis Child. 1970 October; 120(4): 350-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4924167
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Hypophosphatemia, osteomalacia and proximal muscle weakness treated by surgery. Author(s): Hoogendoorn EH, White KE, Econs MJ, Hermus AR. Source: Clinical Endocrinology. 2003 June; 58(6): 796-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12780759
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Hypophosphatemia-associated respiratory muscle weakness in a general inpatient population. Author(s): Gravelyn TR, Brophy N, Siegert C, Peters-Golden M. Source: The American Journal of Medicine. 1988 May; 84(5): 870-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3364446
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Hypothyroidism presenting with respiratory muscle weakness. Author(s): Laroche CM, Cairns T, Moxham J, Green M. Source: Am Rev Respir Dis. 1988 August; 138(2): 472-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3195839
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Increased muscular fatigue in patients with neurogenic muscle weakness: quantification and pathophysiology. Author(s): Milner-Brown HS, Miller RG. Source: Archives of Physical Medicine and Rehabilitation. 1989 May; 70(5): 361-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2541671
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Inhaled and systemic corticosteroid therapies: Do they contribute to inspiratory muscle weakness in asthma? Author(s): Akkoca O, Mungan D, Karabiyikoglu G, Misirligil Z. Source: Respiration; International Review of Thoracic Diseases. 1999; 66(4): 332-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10461081
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Inspiratory muscle weakness and dyspnea in chronic heart failure. Author(s): McParland C, Krishnan B, Wang Y, Gallagher CG. Source: Am Rev Respir Dis. 1992 August; 146(2): 467-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1489142
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Inspiratory muscle weakness in chronic heart failure: role of nutrition and electrolyte status and systemic myopathy. Author(s): McParland C, Resch EF, Krishnan B, Wang Y, Cujec B, Gallagher CG. Source: American Journal of Respiratory and Critical Care Medicine. 1995 April; 151(4): 1101-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7697238
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Intermittent positive pressure breathing in patients with respiratory muscle weakness. Alterations in total respiratory system compliance. Author(s): McCool FD, Mayewski RF, Shayne DS, Gibson CJ, Griggs RC, Hyde RW. Source: Chest. 1986 October; 90(4): 546-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3530648
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Isolated late-onset cone-rod dystrophy revealing a familial neurogenic muscle weakness, ataxia, and retinitis pigmentosa syndrome with the T8993G mitochondrial mutation. Author(s): Porto FB, Mack G, Sterboul MJ, Lewin P, Flament J, Sahel J, Dollfus H. Source: American Journal of Ophthalmology. 2001 December; 132(6): 935-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11730668
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Isolated progressive muscle weakness with tubular aggregates. Author(s): Alonso-Losada G, Cimas I, Pego R, La Torre P, Teijeira S, Navarro C. Source: Clin Neuropathol. 1998 January-February; 17(1): 50-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9496541
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Isometric strength measurement for muscle weakness in cancer patients: reproducibility of isometric muscle strength measurements with a hand-held pullgauge dynamometer in cancer patients. Author(s): Knols RH, Stappaerts KH, Fransen J, Uebelhart D, Aufdemkampe G. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2002 July; 10(5): 430-8. Epub 2002 February 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12136228
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Late-onset muscle weakness in partial phosphofructokinase deficiency: a unique myopathy with vacuoles, abnormal mitochondria, and absence of the common exon 5/intron 5 junction point mutation. Author(s): Sivakumar K, Vasconcelos O, Goldfarb L, Dalakas MC. Source: Neurology. 1996 May; 46(5): 1337-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8628478
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Lithium: potassium gradient, muscle weakness and the EKG. Author(s): Lippman S. Source: Dis Nerv Syst. 1977 January; 38(1): 53. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=832571
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Low serum creatine kinase activity is associated with muscle weakness in patients with rheumatoid arthritis. Author(s): Stucki G, Bruhlmann P, Stoll T, Stucki S, Willer B, Michel BA. Source: The Journal of Rheumatology. 1996 April; 23(4): 603-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8730112
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Lung function abnormalities and respiratory muscle weakness in children with juvenile chronic arthritis. Author(s): Knook LM, de Kleer IM, van der Ent CK, van der Net JJ, Prakken BJ, Kuis W. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1999 September; 14(3): 529-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10543271
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Lung volume restriction in patients with chronic respiratory muscle weakness: the role of microatelectasis. Author(s): Estenne M, Gevenois PA, Kinnear W, Soudon P, Heilporn A, De Troyer A. Source: Thorax. 1993 July; 48(7): 698-701. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8153916
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Magnesium deficiency promotes muscle weakness, contributing to the risk of sudden infant death (SIDS) in infants sleeping prone. Author(s): Caddell JL. Source: Magnes Res. 2001 March; 14(1-2): 39-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11300621
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Measuring abdominal muscle weakness in patients with low back pain and matched controls: a comparison of 3 devices. Author(s): Helewa A, Goldsmith CH, Smythe HA. Source: The Journal of Rheumatology. 1993 September; 20(9): 1539-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8164211
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Measuring inspiratory muscle weakness in patients with cancer and breathlessness. Author(s): Feathers LS, Wilcock A, Manderson C, Weller R, Tattersfield AE. Source: Journal of Pain and Symptom Management. 2003 April; 25(4): 305-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12691681
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Mechanism of quadriceps femoris muscle weakness in patients with anterior cruciate ligament reconstruction. Author(s): Konishi Y, Fukubayashi T, Takeshita D. Source: Scandinavian Journal of Medicine & Science in Sports. 2002 December; 12(6): 371-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12453165
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Medial rectus muscle weakness imitating a slipped muscle following medial optic nerve sheath decompression. Author(s): Ing EB, Sergott RC, Savino PJ, Bosley TM. Source: Can J Ophthalmol. 1995 August; 30(5): 259-62. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8529161
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Mobility impairment, muscle imbalance, muscle weakness, scapular asymmetry and shoulder injury in elite volleyball athletes. Author(s): Wang HK, Cochrane T. Source: The Journal of Sports Medicine and Physical Fitness. 2001 September; 41(3): 40310. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11533574
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Monitoring muscle weakness in neonatal myasthenia gravis. Author(s): Hutchison AA, Lloyd DJ, Russell G. Source: British Medical Journal. 1975 December 13; 4(5997): 623-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1203704
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Muscle weakness after anterior cruciate ligament reconstruction using patellar and quadriceps tendons. Author(s): Yasuda K, Ohkoshi Y, Tanabe Y, Kaneda K. Source: Bull Hosp Jt Dis Orthop Inst. 1991 Fall; 51(2): 175-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1666006
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Muscle weakness after rest in myotonic disorders; an electrophysiological study. Author(s): Brown JC. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1974 December; 37(12): 1336-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4448998
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Muscle weakness after short course of steroids. Author(s): Shee CD. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 February; 21(2): 377-8; Author Reply 378. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12608456
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Muscle weakness and cocontraction in upper limb hemiparesis: relationship to motor impairment and physical disability. Author(s): Chae J, Yang G, Park BK, Labatia I. Source: Neurorehabilitation and Neural Repair. 2002 September; 16(3): 241-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12234087
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Muscle weakness and congenital contractures in a case of congenital myasthenia. Author(s): Hageman G, Smit LM, Hoogland RA, Jennekens FG, Willemse J. Source: Journal of Pediatric Orthopedics. 1986 March-April; 6(2): 227-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3958180
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Muscle weakness and difficulty in weaning from the ventilator in the critical care unit. Author(s): Bolton CF. Source: Chest. 1994 July; 106(1): 1-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8020252
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Muscle weakness and myalgia. MR imaging investigation. Author(s): Fleckenstein JL. Source: Magn Reson Imaging Clin N Am. 1995 November; 3(4): 773-803. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8564695
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Muscle weakness and neurological disorders in alcoholics. Author(s): Carlsson C, Dencker SJ, Grimby G, Tichy J. Source: Q J Stud Alcohol. 1969 September; 30(3): 585-91. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5809949
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Muscle weakness and paresthesia associated with epidural analgesia in a patient with an intrathecal neurofibrolipoma as part of a tethered cord syndrome. Author(s): Jetzek-Zader M, Peterschulte G, Ludwig U, Lipfert P. Source: Anesthesia and Analgesia. 2004 July; 99(1): 255-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15281540
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Muscle weakness and the power law. Author(s): Gandevia SC. Source: Am Rev Respir Dis. 1986 October; 134(4): 844-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3767136
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Muscle weakness associated with prolonged continuous high flux haemofiltration. Author(s): Davenport A. Source: Intensive Care Medicine. 1989; 15(5): 328-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2768651
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Muscle weakness due to colchicine in a renal transplant recipient. Author(s): Jagose JT, Bailey RR. Source: N Z Med J. 1997 September 12; 110(1051): 343. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9323377
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Muscle weakness due to sarcoid myopathy. Six case reports and an evalation of steroid therapy. Author(s): Gardner-Thorpe C. Source: Neurology. 1972 September; 22(9): 917-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4673377
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Muscle weakness following dynamic exercise in humans. Author(s): Davies CT, White MJ. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 1982 July; 53(1): 236-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7118637
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Muscle weakness following eccentric work in man. Author(s): Davies CT, White MJ. Source: Pflugers Archiv : European Journal of Physiology. 1981 December; 392(2): 16871. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7322843
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Muscle weakness following sustained and rhythmic isometric contractions in man. Author(s): Davies CT, Young K. Source: European Journal of Applied Physiology and Occupational Physiology. 1985; 54(3): 301-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4065114
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Muscle weakness in a 16-year-old girl. Author(s): Macaulay RJ, Sladky JT, Jay V. Source: Pediatric Neurosurgery. 1993 March-April; 19(2): 93-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8443103
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Muscle weakness in a Japanese family of Arg1239His mutation hypokalemic periodic paralysis. Author(s): Kusumi M, Kumada H, Adachi Y, Nakashima K. Source: Psychiatry and Clinical Neurosciences. 2001 October; 55(5): 539-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11555352
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Muscle weakness in an adolescent male. Author(s): Guggenheim MA, Becker LE, Jagadha V. Source: Pediatr Neurosci. 1985-86; 12(6): 320-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3870656
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Muscle weakness in an adult with infantile x-linked hypogammaglobulinemia. Part one. Author(s): Montanaro A, Bardana EJ Jr. Source: Ann Allergy. 1984 March; 52(3 Pt 1): 153-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6703411
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Muscle weakness in an adult with infantile x-linked hypogammaglobulinemia. Part two. Author(s): Montanaro A, Bardana EJ Jr. Source: Ann Allergy. 1984 March; 52(3 Pt 1): 172-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6422801
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Muscle weakness in continuous ambulatory peritoneal dialysis patients. Author(s): Fahal IH, Ahmad R, Edwards RH. Source: Perit Dial Int. 1996; 16 Suppl 1: S419-23. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8728236
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Muscle weakness in critically ill children. Author(s): Banwell BL, Mildner RJ, Hassall AC, Becker LE, Vajsar J, Shemie SD. Source: Neurology. 2003 December 23; 61(12): 1779-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14694046
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Muscle weakness in infants with rickets: distribution, course, and recovery. Author(s): Torres CF, Forbes GB, Decancq GH. Source: Pediatric Neurology. 1986 March-April; 2(2): 95-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3508685
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Muscle weakness in intensive care patients: initial manifestation of vitamin D deficiency. Author(s): Rimaniol JM, Authier FJ, Chariot P. Source: Intensive Care Medicine. 1994 November; 20(8): 591-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7706575
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Muscle weakness in mechanically ventilated patients with severe asthma. Author(s): Leatherman JW, Fluegel WL, David WS, Davies SF, Iber C. Source: American Journal of Respiratory and Critical Care Medicine. 1996 May; 153(5): 1686-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8630621
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Muscle weakness in osteoarthritis. Author(s): O'Reilly S, Jones A, Doherty M. Source: Current Opinion in Rheumatology. 1997 May; 9(3): 259-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9204263
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Muscle weakness in osteomalacia. Author(s): Schott GD, Wills MR. Source: Lancet. 1976 March 20; 1(7960): 626-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=55903
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Muscle weakness in Parkinson's disease: a follow-up study. Author(s): Nogaki H, Kakinuma S, Morimatsu M. Source: Parkinsonism & Related Disorders. 2001 September; 8(1): 57-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11472881
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Muscle weakness in Parkinson's disease: isokinetic study of the lower limbs. Author(s): Kakinuma S, Nogaki H, Pramanik B, Morimatsu M. Source: European Neurology. 1998; 39(4): 218-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9635472
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Muscle weakness in the middle of the night. Author(s): Turck M. Source: Hosp Pract (Off Ed). 1984 July; 19(7): 93-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6429177
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Muscle weakness in West Nile encephalitis is due to destruction of motor neurons. Author(s): Sampson BA, Nields H, Armbrustmacher V, Asnis DS. Source: Human Pathology. 2003 June; 34(6): 628-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827621
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Muscle weakness in women occurs at an earlier age than in men, but strength is preserved by hormone replacement therapy. Author(s): Phillips SK, Rook KM, Siddle NC, Bruce SA, Woledge RC. Source: Clinical Science (London, England : 1979). 1993 January; 84(1): 95-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8382141
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Muscle weakness is leading cause for nurses' lower back injuries, pain. Author(s): Gates SJ. Source: Occup Health Saf. 1988 April; 57(4): 57, 60, 63. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2966910
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Muscle weakness is related to utilization of health care resources in COPD patients. Author(s): Decramer M, Gosselink R, Troosters T, Verschueren M, Evers G. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1997 February; 10(2): 417-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9042643
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Muscle weakness simulating myopathy in metabolic bone disease. Author(s): Singhal BS. Source: Neurology India. 1966 October-December; 14(4): 194-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5977718
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Muscle weakness, fatigue, and joint pain in a 52-year-old woman. Author(s): Hearth-Holmes M, Campbell GD Jr. Source: Chest. 1995 August; 108(2): 563-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7634900
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Muscle weakness, hyperactivity, and impairment in fear conditioning in tau-deficient mice. Author(s): Ikegami S, Harada A, Hirokawa N. Source: Neuroscience Letters. 2000 February 4; 279(3): 129-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10688046
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Muscle weakness, paralysis, and atrophy after human cervical spinal cord injury. Author(s): Thomas CK, Zaidner EY, Calancie B, Broton JG, Bigland-Ritchie BR. Source: Experimental Neurology. 1997 December; 148(2): 414-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9417821
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Muscle weakness. Neuropathic or myopathic? Author(s): Kagen LJ. Source: Hosp Pract (Off Ed). 1985 September 15; 20(9): 82E, 82F, 82G Passim. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3928650
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Mutations causing muscle weakness. Author(s): Lindstrom J. Source: Proceedings of the National Academy of Sciences of the United States of America. 1998 August 4; 95(16): 9070-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9689034
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Myoadenylate deaminase deficiency with progressive muscle weakness and atrophy caused by new missense mutations in AMPD1 gene: case report in a Japanese patient. Author(s): Abe M, Higuchi I, Morisaki H, Morisaki T, Osame M. Source: Neuromuscular Disorders : Nmd. 2000 October; 10(7): 472-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10996775
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Myositis associated graft-versus-host-disease presenting as respiratory muscle weakness. Author(s): Stephenson AL, Mackenzie IR, Levy RD, Road J. Source: Thorax. 2001 January; 56(1): 82-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11120911
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Myotonic dystrophy: quantification of muscle weakness and myotonia and the effect of amitriptyline and exercise. Author(s): Milner-Brown HS, Miller RG. Source: Archives of Physical Medicine and Rehabilitation. 1990 November; 71(12): 983-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2241546
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Natural history of muscle weakness in Friedreich's Ataxia and its relation to loss of ambulation. Author(s): Beauchamp M, Labelle H, Duhaime M, Joncas J. Source: Clinical Orthopaedics and Related Research. 1995 February; (311): 270-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7634585
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Negative affect, pain and disability in osteoarthritis patients: the mediating role of muscle weakness. Author(s): Dekker J, Tola P, Aufdemkampe G, Winckers M. Source: Behaviour Research and Therapy. 1993 February; 31(2): 203-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8442746
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Neurogenic muscle weakness in chronic progressive external ophthalmoplegia (CPEO) Author(s): Schwartzman MJ, Mitsumoto H, Shields RW Jr, Estes ML, Meisler DM, Kosmorsky GS. Source: Muscle & Nerve. 1990 December; 13(12): 1183-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2266992
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New laryngeal muscle weakness in post-polio syndrome. Author(s): Robinson LR, Hillel AD, Waugh PF. Source: The Laryngoscope. 1998 May; 108(5): 732-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9591555
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Nocturnal rocking bed therapy: improvement in sleep fragmentation in patients with respiratory muscle weakness. Author(s): Iber C, Davies SF, Mahowald MW. Source: Sleep. 1989 October; 12(5): 405-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2799214
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Oblique pectoral crease and "scapular hump" in shoulder contour are signs of trapezius muscle weakness. Author(s): Nelson KR, Bicknell JM. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1987 August; 50(8): 1082-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3655826
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Oropharyngeal palsy in Guillain-Barre and Fisher's syndromes is associated with muscle weakness in the neck and arm. Author(s): Koga M, Yuki N, Hirata K. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1999 February; 66(2): 2545. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10071119
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Peak flow and peak cough flow in the evaluation of expiratory muscle weakness and bulbar impairment in patients with neuromuscular disease. Author(s): Suarez AA, Pessolano FA, Monteiro SG, Ferreyra G, Capria ME, Mesa L, Dubrovsky A, De Vito EL. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2002 July; 81(7): 506-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12131177
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Peripheral muscle weakness and exercise capacity in children with cystic fibrosis. Author(s): de Meer K, Gulmans VA, van Der Laag J. Source: American Journal of Respiratory and Critical Care Medicine. 1999 March; 159(3): 748-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10051246
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Peripheral muscle weakness contributes to exercise limitation in COPD. Author(s): Gosselink R, Troosters T, Decramer M. Source: American Journal of Respiratory and Critical Care Medicine. 1996 March; 153(3): 976-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8630582
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Polymyositis with respiratory muscle weakness requiring mechanical ventilation in a patient with metastatic thymoma treated with octreotide. Author(s): Rini BI, Gajewski TF. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 1999 August; 10(8): 973-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10509161
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Postpoliomyelitis muscle weakness: a prospective study of quadriceps strength. Author(s): Munin MC, Jaweed MM, Staas WE Jr, Satinsky AR, Gutierez G, Herbison GJ. Source: Archives of Physical Medicine and Rehabilitation. 1991 September; 72(10): 72933. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1929796
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Predominant infraspinatus muscle weakness in suprascapular nerve compression. Author(s): Spinner RJ, Tiel RL, Kline DG. Source: Journal of Neurosurgery. 2000 September; 93(3): 516. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10969959
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Preseason hamstring muscle weakness associated with hamstring muscle injury in Australian footballers. Author(s): Orchard J, Marsden J, Lord S, Garlick D. Source: The American Journal of Sports Medicine. 1997 January-February; 25(1): 81-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9006698
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Pressure support ventilation and the critically ill patient with muscle weakness. Author(s): Watt JW. Source: British Journal of Anaesthesia. 2002 September; 89(3): 373-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12402713
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Prevalence of diaphragmatic muscle weakness and dyspnoea in Graves' disease and their reversibility with carbimazole therapy. Author(s): Goswami R, Guleria R, Gupta AK, Gupta N, Marwaha RK, Pande JN, Kochupillai N. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 September; 147(3): 299-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12213666
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Profound muscle weakness and hypokalemia due to clay ingestion. Author(s): Severance HW Jr, Holt T, Patrone NA, Chapman L. Source: Southern Medical Journal. 1988 February; 81(2): 272-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3340881
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Profound muscle weakness as the presenting feature of disseminated cryptococcal infection. Author(s): Hurd DD, Staub DB, Roelofs RI, Dehner LP. Source: Reviews of Infectious Diseases. 1989 November-December; 11(6): 970-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2690291
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Profound muscle weakness associated with axis cylinder ballooning. A case report. Author(s): Peress NS, Kim BK. Source: Acta Neuropathologica. 1974 May 31; 28(1): 87-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4853888
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Progressive muscle weakness after high-dose steroids in two children with CIDP. Author(s): Rostasy KM, Diepold K, Buckard J, Brockmann K, Wilken B, Hanefeld F. Source: Pediatric Neurology. 2003 September; 29(3): 236-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14629908
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Progressive muscle weakness in a 4-year-old girl. Author(s): Kim JB, Ballow M. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2004 January; 92(1): 19-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14756460
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Prolonged muscle weakness after neuromuscular blockade in the intensive care unit. Author(s): Raps EC, Bird SJ, Hansen-Flaschen J. Source: Critical Care Clinics. 1994 October; 10(4): 799-813. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8000927
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Prolonged muscle weakness following emergency tonsillectomy in a patient with familial periodic paralysis and infectious mononucleosis. Author(s): Bunting HE, Allen RW. Source: Paediatric Anaesthesia. 1997; 7(2): 171-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9188121
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Prolonged muscle weakness. Author(s): Coakley JH. Source: Critical Care Medicine. 1991 June; 19(6): 842-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2055065
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Pronator muscle weakness in functional instability of the ankle joint. Author(s): Tropp H. Source: International Journal of Sports Medicine. 1986 October; 7(5): 291-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3793339
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Proximal and distal muscle weakness in patients receiving hemodialysis for chronic uremia. Author(s): McElroy A, Silver M, Morrow L, Heafner BK. Source: Physical Therapy. 1970 October; 50(10): 1467-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5472511
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Proximal muscle weakness and pulmonary hilar prominence in a smoker. Author(s): Fred HL, Wu CC. Source: Hosp Pract (Off Ed). 1995 July 15; 30(7): 30L, 30Q. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7601894
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Proximal muscle weakness and selenium deficiency associated with long term parenteral nutrition. Author(s): Brown MR, Cohen HJ, Lyons JM, Curtis TW, Thunberg B, Cochran WJ, Klish WJ. Source: The American Journal of Clinical Nutrition. 1986 April; 43(4): 549-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3083669
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Proximal muscle weakness due to amyloid deposition. Author(s): Vaish AK, Mehrotra S, Kushwaha MR. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1998 March; 64(3): 409-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9527167
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Proximal muscle weakness following snake bite is not rare. Author(s): Mohapatra BN. Source: J Assoc Physicians India. 1991 March; 39(3): 297. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1880115
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Proximal muscle weakness following snake bite. Author(s): Shrivastava MP, Muthalgu P, Dutta TK. Source: J Assoc Physicians India. 1990 March; 38(3): 249-50. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2391317
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Proximal muscle weakness in a patient with hepatocellular carcinoma. Author(s): MacDonald SM, Hagen N, Bruera E. Source: Journal of Pain and Symptom Management. 1994 July; 9(5): 346-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7963787
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Proximal muscle weakness in children. Author(s): Thompson CE. Source: Postgraduate Medicine. 1981 February; 69(2): 143-7, 150-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7454645
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Proximal muscle weakness in uremia. Case reports and review of the literature. Author(s): Lazaro RP, Kirshner HS. Source: Archives of Neurology. 1980 September; 37(9): 555-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7417055
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Proximal muscle weakness--an unusual presentation of celiac disease. Author(s): Jain V, Angitii RR, Singh S, Thapa BR, Kumar L. Source: Journal of Tropical Pediatrics. 2002 December; 48(6): 380-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12521285
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Proximal myotonic myopathy: a new dominant disorder with myotonia, muscle weakness, and cataracts. Author(s): Ricker K, Koch MC, Lehmann-Horn F, Pongratz D, Otto M, Heine R, Moxley RT 3rd. Source: Neurology. 1994 August; 44(8): 1448-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8058147
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Pulmonary mechanics in patients with respiratory muscle weakness. Author(s): Gibson GJ, Pride NB, Davis JN, Loh LC. Source: Am Rev Respir Dis. 1977 March; 115(3): 389-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=842952
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Pulse methylprednisolone therapy for arthritis causing muscle weakness. Author(s): Shanahan EM, Smith MD, Ahern MJ. Source: Annals of the Rheumatic Diseases. 1999 September; 58(9): 521-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10460183
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Quadriceps femoris muscle weakness and activation failure in patients with symptomatic knee osteoarthritis. Author(s): Lewek MD, Rudolph KS, Snyder-Mackler L. Source: Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society. 2004 January; 22(1): 110-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14656668
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Quadriceps muscle weakness following acute hemiplegic stroke. Author(s): Harris ML, Polkey MI, Bath PM, Moxham J. Source: Clinical Rehabilitation. 2001 June; 15(3): 274-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11386397
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Quantitative evaluation of improvement in muscle weakness in a patient receiving extracorporeal photopheresis for scleroderma: magnetic resonance imaging and magnetic resonance spectroscopy. Author(s): Adams LB, Park JH, Olsen NJ, Gardner ES, Hernanz-Schulman M, King LE Jr. Source: Journal of the American Academy of Dermatology. 1995 September; 33(3): 51922. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7657879
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Quantitative evaluation of muscle weakness in scleroderma patients using magnetic resonance imaging and spectroscopy. Author(s): King LE Jr, Olsen NJ, Puett D, Vital TL, Schulman M, Park JH. Source: Archives of Dermatology. 1993 February; 129(2): 246-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8434988
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Reappraisal of alcoholic myopathy. Clinical and biopsy study on chronic alcoholics without muscle weakness or wasting. Author(s): Faris AA, Reyes MG. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1971 February; 34(1): 8692. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4251669
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Recovery following cranial nerve dysfunction and muscle weakness in infancy. Author(s): Grover WD, Peckham GJ, Berman PH. Source: Developmental Medicine and Child Neurology. 1974 April; 16(2): 163-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4365404
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Recurrent hypokalemic muscle weakness as an initial manifestation of Wilson's disease. Author(s): Chu CC, Huang CC, Chu NS. Source: Nephron. 1996; 73(3): 477-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8832611
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Recurrent muscle weakness and ataxia in thiamine-responsive pyruvate dehydrogenase complex deficiency. Author(s): Kinoshita H, Sakuragawa N, Tada H, Naito E, Kuroda Y, Nonaka I. Source: Journal of Child Neurology. 1997 February; 12(2): 141-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9075024
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Resistance versus endurance training in patients with COPD and peripheral muscle weakness. Author(s): Spruit MA, Gosselink R, Troosters T, De Paepe K, Decramer M. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 June; 19(6): 1072-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12108859
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Respiratory effects of respiratory muscle weakness and atrophy. Author(s): Rochester DF. Source: Am Rev Respir Dis. 1986 November; 134(5): 1083-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3777672
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Respiratory failure due to muscle weakness in inflammatory myopathies: maintenance therapy with home mechanical ventilation. Author(s): Selva-O'Callaghan A, Sanchez-Sitjes L, Munoz-Gall X, Mijares-BoeckhBehrens T, Solans-Laque R, Angel Bosch-Gil J, Morell-Brotad F, Vilardell-Tarres M. Source: Rheumatology (Oxford, England). 2000 August; 39(8): 914-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10952749
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Respiratory muscle activity and oxygenation during sleep in patients with muscle weakness. Author(s): White JE, Drinnan MJ, Smithson AJ, Griffiths CJ, Gibson GJ. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1995 May; 8(5): 807-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7656954
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Respiratory muscle weakness and anorexia nervosa. Author(s): Birmingham CL, Tan AO. Source: The International Journal of Eating Disorders. 2003 March; 33(2): 230-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12616590
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Respiratory muscle weakness and dyspnea in thyrotoxic patients. Author(s): McElvaney GN, Wilcox PG, Fairbarn MS, Hilliam C, Wilkins GE, Pare PD, Pardy RL. Source: Am Rev Respir Dis. 1990 May; 141(5 Pt 1): 1221-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2339842
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Respiratory muscle weakness and fatigue. Author(s): Laroche CM, Moxham J, Green M. Source: The Quarterly Journal of Medicine. 1989 May; 71(265): 373-97. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2690176
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Respiratory muscle weakness and normal ventilatory drive in dilative cardiomyopathy. Author(s): Witt C, Borges AC, Haake H, Reindl I, Kleber FX, Baumann G. Source: European Heart Journal. 1997 August; 18(8): 1322-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9458426
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Respiratory muscle weakness and ventilatory failure in AL amyloidosis with muscular pseudohypertrophy. Author(s): Santiago RM, Scharnhorst D, Ratkin G, Crouch EC. Source: The American Journal of Medicine. 1987 July; 83(1): 175-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3111259
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Respiratory muscle weakness associated with cerebellar atrophy. Author(s): Mier-Jedrzejowicz A, Green M. Source: Am Rev Respir Dis. 1988 March; 137(3): 673-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3345046
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Respiratory muscle weakness during upper respiratory tract infections. Author(s): Mier-Jedrzejowicz A, Brophy C, Green M. Source: Am Rev Respir Dis. 1988 July; 138(1): 5-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3202399
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Respiratory muscle weakness in Addison's disease. Author(s): Mier A, Laroche C, Wass J, Green M. Source: Bmj (Clinical Research Ed.). 1988 August 13; 297(6646): 457-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3139145
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Respiratory muscle weakness in Charcot-Marie-Tooth disease. A field study. Author(s): Nathanson BN, Yu DG, Chan CK. Source: Archives of Internal Medicine. 1989 June; 149(6): 1389-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2730255
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Respiratory muscle weakness in primary hyperparathyroidism. Author(s): Sorva A. Source: Journal of the American Geriatrics Society. 1996 January; 44(1): 104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8537583
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Respiratory muscle weakness in the Lambert-Eaton myasthenic syndrome. Author(s): Laroche CM, Mier AK, Spiro SG, Newsom-Davis J, Moxham J, Green M. Source: Thorax. 1989 November; 44(11): 913-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2595631
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Respiratory muscle weakness in uremic patients under continuous ambulatory peritoneal dialysis. Author(s): Gomez-Fernandez P, Sanchez Agudo L, Calatrava JM, Escuin F, Selgas R, Martinez ME, Montero A, Sanchez-Sicilia L. Source: Nephron. 1984; 36(4): 219-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6709114
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Respiratory muscle weakness, pattern of breathing, and CO2 retention in chronic obstructive pulmonary disease. Author(s): Rochester DF. Source: Am Rev Respir Dis. 1991 May; 143(5 Pt 1): 901-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2024840
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Respiratory muscle weakness. Author(s): Mier A. Source: Respiratory Medicine. 1990 September; 84(5): 351-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2247665
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Reversible hypercapnic respiratory insufficiency in scleroderma caused by respiratory muscle weakness. Author(s): Chausow AM, Kane T, Levinson D, Szidon JP. Source: Am Rev Respir Dis. 1984 July; 130(1): 142-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6742599
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Reversible muscle weakness in patients with vitamin D deficiency. Author(s): Ziambaras K, Dagogo-Jack S. Source: The Western Journal of Medicine. 1997 December; 167(6): 435-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9426489
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Reversible respiratory muscle weakness in hyperthyroidism. Author(s): Mier A, Brophy C, Wass JA, Besser GM, Green M. Source: Am Rev Respir Dis. 1989 February; 139(2): 529-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2913898
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Reversible respiratory muscle weakness in hypothyroidism. Author(s): Weiner M, Chausow A, Szidon P. Source: Br J Dis Chest. 1986 October; 80(4): 391-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3620325
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Reversible upper limb muscle weakness with selective loss of thick filaments. Author(s): Vattemi G, Tonin P, Filosto M, Savio C, Rizzuto N, Tomelleri G. Source: Neurology. 2003 September 23; 61(6): 863-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14504344
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Rigid spine syndrome with selective respiratory muscle weakness. Author(s): Akiyama Y, Aimoto Y, Nishimura M, Takai S, Kawakami Y. Source: Respiration; International Review of Thoracic Diseases. 1992; 59(1): 48-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1579718
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Segmental distribution of muscle weakness in SMA III: implications for deterioration in muscle strength with time. Author(s): Deymeer F, Serdaroglu P, Poda M, Gulsen-Parman Y, Ozcelik T, Ozdemir C. Source: Neuromuscular Disorders : Nmd. 1997 December; 7(8): 521-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9447610
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Serum creatine phosphokinase levels and prednisone treated muscle weakness. Author(s): Munsat TL, Bradley WG. Source: Neurology. 1977 January; 27(1): 96-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=556824
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Serum muscle enzymes, muscle pathology and clinical muscle weakness: correlation in Thai patients with polymyositis/dermatomyositis. Author(s): Louthrenoo W, Weerayutwattana N, Lertprasertsuke N, Sukitawut W. Source: J Med Assoc Thai. 2002 January; 85(1): 26-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12075717
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Severe hyperkalaemia in association with diabetic ketoacidosis in a patient presenting with severe generalized muscle weakness. Author(s): Milionis HJ, Dimos G, Elisaf MS. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 January; 18(1): 198-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480984
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Severe muscle weakness and hypokalaemia secondary to renal tubular acidosis. Author(s): So PC, Sun KO. Source: Anaesthesia and Intensive Care. 1994 October; 22(5): 613-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7818072
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Severe muscle weakness secondary to paraneoplastic hypophosphatemia in neuroblastoma. Author(s): Kats S, Markusse HM, Vecht CJ. Source: The Netherlands Journal of Medicine. 1998 November; 53(5): 207-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9852709
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Severe respiratory muscle weakness related to long-term colchicine therapy. Author(s): Tanios MA, El Gamal H, Epstein SK, Hassoun PM. Source: Respiratory Care. 2004 February; 49(2): 189-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14744269
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Skeletal muscle weakness and dysphagia caused by acid maltase deficiency: nutritional consequences of coincident celiac sprue. Author(s): King TS, Anderson JR, Wraight EP, Hunter JO, Cox TM. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1997 January-February; 21(1): 46-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9002085
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Skeletal muscle weakness and fatigue in old age: underlying mechanisms. Author(s): Faulkner JA, Brooks SV, Zerba E. Source: Annu Rev Gerontol Geriatr. 1990; 10: 147-66. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2102709
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Skeletal muscle weakness in old age: underlying mechanisms. Author(s): Brooks SV, Faulkner JA. Source: Medicine and Science in Sports and Exercise. 1994 April; 26(4): 432-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8201898
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Skeletal muscle weakness is associated with wasting of extremity fat-free mass but not with airflow obstruction in patients with chronic obstructive pulmonary disease. Author(s): Engelen MP, Schols AM, Does JD, Wouters EF. Source: The American Journal of Clinical Nutrition. 2000 March; 71(3): 733-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10702166
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Skeletal muscle weakness resulting from quinidine ingestion. Author(s): Hall CD, Malouf N. Source: Southern Medical Journal. 1987 March; 80(3): 403-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3824038
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Somatic mosaicism of a point mutation in the dystrophin gene in a patient presenting with an asymmetrical muscle weakness and contractures. Author(s): Helderman-van den Enden AT, Ginjaar HB, Kneppers AL, Bakker E, Breuning MH, de Visser M. Source: Neuromuscular Disorders : Nmd. 2003 May; 13(4): 317-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12868501
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Steroid myopathy. Insidious cause of muscle weakness. Author(s): Mandel S. Source: Postgraduate Medicine. 1982 November; 72(5): 207-10, 213-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7134072
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Stroke patients have selective muscle weakness in shortened range. Author(s): Ada L, Canning CG, Low SL. Source: Brain; a Journal of Neurology. 2003 March; 126(Pt 3): 724-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12566292
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Studies on joint temperature, joint stiffness and muscle weakness in rheumatoid arthritis. An experimental and clinical investigation. Author(s): Tiselius P. Source: Acta Rheumatol Scand. 1969; 14: Suppl 14: 1+. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5373799
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Subjective muscle weakness and hypotonia during clozapine treatment. Author(s): Galletly C. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 1996 December; 8(4): 189-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8986312
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Sunlight "D"ilemma: risk of skin cancer or bone disease and muscle weakness. Author(s): Holick MF. Source: Lancet. 2001 January 6; 357(9249): 4-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11197362
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Technique tip: modification of a long-leg cast for use in patients with functional impairment or muscle weakness of the upper extremities. Author(s): Claerbout MT, Matricali GA. Source: Foot & Ankle International / American Orthopaedic Foot and Ankle Society [and] Swiss Foot and Ankle Society. 2004 March; 25(3): 176. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15006341
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Temporal relationship of muscle weakness and pain reduction in subjects treated with botulinum toxin A. Author(s): Freund B, Schwartz M. Source: The Journal of Pain : Official Journal of the American Pain Society. 2003 April; 4(3): 159-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14622713
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Temporary muscle weakness in the early phase of distraction during femoral lengthening. Clinical and electromyographical observations. Author(s): Oey PL, Engelbert RH, van Roermond PM, Wieneke GH. Source: Electromyogr Clin Neurophysiol. 1999 June; 39(4): 217-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10394505
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The contribution of reflex inhibition to arthrogenous muscle weakness. Author(s): Stokes M, Young A. Source: Clinical Science (London, England : 1979). 1984 July; 67(1): 7-14. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6375939
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The distribution of muscle weakness in upper motoneuron lesions affecting the lower limb. Author(s): Adams RW, Gandevia SC, Skuse NF. Source: Brain; a Journal of Neurology. 1990 October; 113 ( Pt 5): 1459-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2245306
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The effects of intermittent positive pressure breathing on patients with respiratory muscle weakness. Author(s): De Troyer A, Deisser P. Source: Am Rev Respir Dis. 1981 August; 124(2): 132-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7020511
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The effects of respiratory muscle weakness on the pattern of breathing. Author(s): Davis JN, Loh L, Casson M. Source: Acta Neurol Belg. 1976; 76(5-6): 291-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1007894
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The role of muscle weakness in the pathogenesis of osteoarthritis. Author(s): Hurley MV. Source: Rheumatic Diseases Clinics of North America. 1999 May; 25(2): 283-98, Vi. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10356418
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The role of the orthopedic surgeon in the management of the child with muscle weakness. Author(s): Trott AW. Source: Pediatric Clinics of North America. 1967 May; 14(2): 479-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6023392
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The use of EMG in the differential diagnosis of muscle weakness in post-polio syndrome. Author(s): Feldman RM. Source: Electromyogr Clin Neurophysiol. 1988 June-July; 28(5): 269-72. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3191877
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Three girls with rash and muscle weakness. Author(s): Culbertson CA, Shetty AK. Source: Clinical Pediatrics. 1998 November; 37(11): 685-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9825213
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Three novel electrophysiologic tests for patients with muscle weakness. Author(s): McComas AJ, Garner S, Dantes M, Hall A, Quartly C. Source: Birth Defects Orig Artic Ser. 1987; 23(4): 201-12. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3620617
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Tick paralysis without muscle weakness. Author(s): Lagos JC, Thies RE. Source: Archives of Neurology. 1969 November; 21(5): 471-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5344356
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Treatment of "permanent" muscle weakness in familial Hypokalemic Periodic Paralysis. Author(s): Dalakas MC, Engel WK. Source: Muscle & Nerve. 1983 March-April; 6(3): 182-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6855804
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Trunk muscle weakness as a risk factor for low back pain. A 5-year prospective study. Author(s): Lee JH, Hoshino Y, Nakamura K, Kariya Y, Saita K, Ito K. Source: Spine. 1999 January 1; 24(1): 54-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9921591
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Usefulness of single fiber EMG for distinguishing neuromuscular from other causes of ocular muscle weakness. Author(s): Ukachoke C, Ashby P, Basinski A, Sharpe JA. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 1994 May; 21(2): 125-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8087737
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Vocal cord paralysis and respiratory muscle weakness: an unusual presentation of chronic polyneuropathy. Author(s): Chau LK, Webb KA, Jackson AC, O'Donnell DE. Source: Can Respir J. 1998 March-April; 5(2): 125-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9707455
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Voluntary muscle weakness and co-activation after chronic cervical spinal cord injury. Author(s): Thomas CK, Tucker ME, Bigland-Ritchie B. Source: Journal of Neurotrauma. 1998 February; 15(2): 149-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9512090
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CHAPTER 2. NUTRITION AND MUSCLE WEAKNESS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and muscle weakness.
Finding Nutrition Studies on Muscle Weakness 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 “muscle weakness” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “muscle weakness” (or a synonym): •
Effects of creatine supplementation on muscle weakness in patients with rheumatoid arthritis. Author(s): Department of Rheumatology and Physical Medicine, University Hospital of Zurich, Switzerland. Source: Willer, B Stucki, G Hoppeler, H Bruhlmann, P Krahenbuhl, S Rheumatology(Oxford). 2000 March; 39(3): 293-8 1462-0324
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Severe muscle weakness due to hypokalemia as a manifestation of small-cell carcinoma. Author(s): Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece. Source: Konstantinidis, A Elisaf, M Panteli, K Constantopoulos, S Respiration. 1999; 66(3): 269-72 0025-7931
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
Nutrition
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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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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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The following is a specific Web list relating to muscle weakness; 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: •
Vitamins Niacin Source: Integrative Medicine Communications; www.drkoop.com Vitamin B Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10067,00.html Vitamin B3 (Niacin) Source: Integrative Medicine Communications; www.drkoop.com
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Minerals Calcium Acetate Source: Healthnotes, Inc.; www.healthnotes.com Creatine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10020,00.html Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,890,00.html Potassium Source: Integrative Medicine Communications; www.drkoop.com
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Potassium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10086,00.html Selenium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10055,00.html
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CHAPTER 3. ALTERNATIVE MEDICINE AND MUSCLE WEAKNESS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to muscle weakness. 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 muscle weakness 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 “muscle weakness” (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 muscle weakness: •
A case of dermato-fasciitis: amyopathic dermatomyositis associated with fasciitis. Author(s): Tsuruta Y, Ikezoe K, Nakagaki H, Shigeto H, Kawajiri M, Ohyagi Y, Kira J. Source: Clinical Rheumatology. 2004 April; 23(2): 160-2. Epub 2004 January 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15045632
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A clinical trial of therapeutic electrical stimulation for amyotrophic lateral sclerosis. Author(s): Handa I, Matsushita N, Ihashi K, Yagi R, Mochizuki R, Mochizuki H, Abe Y, Shiga Y, Hoshimiya N, Itoyama Y, et al. Source: The Tohoku Journal of Experimental Medicine. 1995 February; 175(2): 123-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7597693
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A physiotherapeutic approach to craniomandibular disorders: a case report. Author(s): Bevilaqua-Grosso D, Monteiro-Pedro V, Guirro RR, Berzin F.
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Source: Journal of Oral Rehabilitation. 2002 March; 29(3): 268-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11896844 •
A report of hypothyroidism induced by an over-the-counter fat loss supplement (Tiratricol). Author(s): Scally MC, Hodge A. Source: International Journal of Sport Nutrition and Exercise Metabolism. 2003 March; 13(1): 112-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660410
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Accidental poisoning with autumn crocus. Author(s): Gabrscek L, Lesnicar G, Krivec B, Voga G, Sibanc B, Blatnik J, Jagodic B. Source: Journal of Toxicology. Clinical Toxicology. 2004; 42(1): 85-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15083942
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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/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11527070
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Adult onset systemic carnitine deficiency: favorable response to L-carnitine supplementation. Author(s): Levitan MD, Murphy JT, Sherwood WG, Deck J, Sawa GM. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 1987 February; 14(1): 50-4. Erratum In: Can J Neurol Sci 1987 May; 14(2): 189. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3815165
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Aggravation of vincristine-induced neurotoxicity by itraconazole in the treatment of adult ALL. Author(s): Bohme A, Ganser A, Hoelzer D. Source: Annals of Hematology. 1995 December; 71(6): 311-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8534764
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An unusual cause of hypokalemic paralysis: chronic licorice ingestion. Author(s): Lin SH, Yang SS, Chau T, Halperin ML. Source: The American Journal of the Medical Sciences. 2003 March; 325(3): 153-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12640291
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Antagonism of dithiobiuret toxicity in rats. Author(s): Williams KD, Lopachin RM, Atchison WD, Peterson RE.
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Source: Neurotoxicology. 1986 Spring; 7(1): 33-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3012425 •
Approach to generalized weakness and peripheral neuromuscular disease. Author(s): LoVecchio F, Jacobson S. Source: Emergency Medicine Clinics of North America. 1997 August; 15(3): 605-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9255135
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Audiotympanometric findings in myasthenia gravis. Author(s): Morioka WT, Neff PA, Boisseranc TE, Hartman PW, Cantrell RW. Source: Arch Otolaryngol. 1976 April; 102(4): 211-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1267704
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Biofeedback treatment of fecal incontinence: a critical review. Author(s): Heymen S, Jones KR, Ringel Y, Scarlett Y, Whitehead WE. Source: Diseases of the Colon and Rectum. 2001 May; 44(5): 728-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11357037
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Breathing retraining and exercise conditioning in patients with chronic obstructive pulmonary disease (COPD): a physiological approach. Author(s): Gigliotti F, Romagnoli I, Scano G. Source: Respiratory Medicine. 2003 March; 97(3): 197-204. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12645825
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Cannabinoids in the treatment of pain and spasticity in multiple sclerosis. Author(s): Smith PF. Source: Curr Opin Investig Drugs. 2002 June; 3(6): 859-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12137404
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Cardioactive steroid poisoning from an herbal cleansing preparation. Author(s): Barrueto F Jr, Jortani SA, Valdes R Jr, Hoffman RS, Nelson LS. Source: Annals of Emergency Medicine. 2003 March; 41(3): 396-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12605208
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Carnitine and hemodialysis. Author(s): Bellinghieri G, Santoro D, Calvani M, Mallamace A, Savica V. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 March; 41(3 Suppl 1): S116-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12612967
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Carnitine metabolism in uremia. Author(s): Guarnieri G, Situlin R, Biolo G. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2001 October; 38(4 Suppl 1): S63-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11576925
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Carnitine transporter OCTN2 mutations in systemic primary carnitine deficiency: a novel Arg169Gln mutation and a recurrent Arg282ter mutation associated with an unconventional splicing abnormality. Author(s): Burwinkel B, Kreuder J, Schweitzer S, Vorgerd M, Gempel K, Gerbitz KD, Kilimann MW. Source: Biochemical and Biophysical Research Communications. 1999 August 2; 261(2): 484-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10425211
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Charcot-Marie-Tooth disease type I diagnosed in a 5-year-old boy after vincristine neurotoxicity, resulting in maternal diagnosis. Author(s): Olek MJ, Bordeaux B, Leshner RT. Source: J Am Osteopath Assoc. 1999 March; 99(3): 165-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10217912
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Childhood mixed connective tissue disease. Author(s): Yang YH, Tsai MJ, Lin SC, Lin MT, Chiang BL. Source: J Formos Med Assoc. 2000 February; 99(2): 158-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10770031
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Chinese red rice-induced myopathy. Author(s): Smith DJ, Olive KE. Source: Southern Medical Journal. 2003 December; 96(12): 1265-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14696880
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Chiropractic and pilates therapy for the treatment of adult scoliosis. Author(s): Blum CL. Source: Journal of Manipulative and Physiological Therapeutics. 2002 May; 25(4): E3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12021749
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Effects of creatine supplementation on muscle weakness in patients with rheumatoid arthritis. Author(s): Willer B, Stucki G, Hoppeler H, Bruhlmann P, Krahenbuhl S. Source: Rheumatology (Oxford, England). 2000 March; 39(3): 293-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10788538
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Hypokalemia, muscle weakness, and myoglobinuria due to licorice ingestion. Author(s): Tourtellotte CR, Hirst AE. Source: Calif Med. 1970 October; 113(4): 51-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5479351
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Respiratory muscle weakness and respiratory muscle training in severely disabled multiple sclerosis patients. Author(s): Gosselink R, Kovacs L, Ketelaer P, Carton H, Decramer M. Source: Archives of Physical Medicine and Rehabilitation. 2000 June; 81(6): 747-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10857518
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Severe muscle weakness due to hypokalemia as a manifestation of small-cell carcinoma. Author(s): Konstantinidis A, Elisaf M, Panteli K, Constantopoulos S. Source: Respiration; International Review of Thoracic Diseases. 1999; 66(3): 269-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10364746
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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WebMDHealth: 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/
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The following is a specific Web list relating to muscle weakness; 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 Endocarditis Source: Integrative Medicine Communications; www.drkoop.com Hyperparathyroidism Source: Integrative Medicine Communications; www.drkoop.com Low Back Pain Source: Integrative Medicine Communications; www.drkoop.com Multiple Sclerosis Source: Healthnotes, Inc.; www.healthnotes.com Muscular Dystrophy Source: Integrative Medicine Communications; www.drkoop.com Osteoarthritis Source: Integrative Medicine Communications; www.drkoop.com
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Alternative Therapy Applied Kinesiology Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,711,00.html
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Herbs and Supplements Aminoglycosides Source: Integrative Medicine Communications; www.drkoop.com Antituberculosis Agents Source: Integrative Medicine Communications; www.drkoop.com Barbiturates Source: Integrative Medicine Communications; www.drkoop.com Bile Acid Sequestrants Source: Integrative Medicine Communications; www.drkoop.com Bisphosphonate Derivatives Source: Integrative Medicine Communications; www.drkoop.com Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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Histamine H2 Antagonists Source: Integrative Medicine Communications; www.drkoop.com Horsetail Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10105,00.html Hydantoin Derivatives Source: Integrative Medicine Communications; www.drkoop.com Ketoprofen Source: Healthnotes, Inc.; www.healthnotes.com Loop Diuretics Source: Integrative Medicine Communications; www.drkoop.com Lubricant Laxatives Source: Integrative Medicine Communications; www.drkoop.com Piroxicam Source: Healthnotes, Inc.; www.healthnotes.com Thiazide Diuretics Source: Integrative Medicine Communications; www.drkoop.com Uricosuric Agents Source: Integrative Medicine Communications; www.drkoop.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. PATENTS ON MUSCLE WEAKNESS 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.8 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 “muscle weakness” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on muscle weakness, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Muscle Weakness By performing a patent search focusing on muscle weakness, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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The following is an example of the type of information that you can expect to obtain from a patent search on muscle weakness: •
Compositions for and methods of treating muscle degeneration and weakness Inventor(s): Goodwin; Tena G. (4134 Coventry Dr., Memphis, TN 38127), Law; Peter K. (2277 Union Ave. A702, Memphis, TN 38104) Assignee(s): none reported Patent Number: 5,130,141 Date filed: May 30, 1991 Abstract: Compositions for and methods of treating muscle weakness and degeneration are described. Such compositions include myogenic cells which are administered by the described methods to one or more affected muscles. Excerpt(s): The invention described herein was made in the course of or under grants from the National Institute of Health. This invention pretains to compositions for and methods of treating muscle degeneration and weakness. More particularly, the present invention relates to myogenic cells and methods of using such cells in the treatment of muscle degeneration and weakness. Progressive degeneration and weakness of skeletal muscles are hallmarks of the forty human neuromuscular diseases affecting motoneurones, peripheral nerves and/or muscles. Most of these diseases are fatal, and all are crippling. There is no known cure or effective treatment. These diseases include motoneurone disorders, such as Amyotrophic Lateral Sclerosis (ALS) and neuromuscular junction disorders, such as Myasthenia Gravis and Eaton-Lambert Syndrome. Also included are the twelve hereditary muscular dystrophies, predominantly muscle diseases, affecting over 200,000 Americans. In the muscular dystrophies, dystrophic cells degenerate because of the lack of normal genome. Web site: http://www.delphion.com/details?pn=US05130141__
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Method for treating amyotrophic lateral sclerosis and a therapeutic agent therefor Inventor(s): Kaji; Ryuji (19-7, Sen-cho 2-chome, Ootsu-shi, Shiga-ken, 520-0863, JP) Assignee(s): none reported Patent Number: 5,964,224 Date filed: February 6, 1998 Abstract: A method for treating amyotrophic lateral sclerosis (ALS) and a therapeutic agent therefor are provided. The therapeutic agent comprising ultra-high doses of methylcobalamin (for example, from about 15 mg to about 500 mg per day) is administered to a patient with ALS intramuscularly, subcutaneously or intravenously for from about a week to about 2 years to ameliorate or improve both the clinical symptoms and an objective clinical measure in ALS or retard the muscle weakness caused by ALS. Excerpt(s): The present invention relates to a method for treating amyotrophic lateral sclerosis (ALS) and a therapeutic agent therefor. Patients with ALS have no cure or treatment effective in improving clinical signs or parameters, although riluzole has been reported to prolong life without tracheostomy by 1-3 months in a subgroup of ALS. Other agents such as dextromethorphan, superoxide dismutase, vitamin E, ciliary
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neurotrophic factor have not yet convincingly shown their potency in improving the clinical symptoms or prolonging life in patients with ALS. Anecdotal or preliminary observations have also been made on the beneficial effects of cyclophosphamide and IGF-1 (insulin-like growth factor-1). It is an object of the present invention to provide a safe, simple and effective method and therapeutic agent for ameliorating or improving the clinical signs and symptoms of ALS in humans. Web site: http://www.delphion.com/details?pn=US05964224__
Patent Applications on Muscle Weakness As of December 2000, U.S. patent applications are open to public viewing.9 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 muscle weakness: •
Use of vegf and homologues to treat neuron disorders Inventor(s): Carmeliet, Peter; (Landen, BE), Collen, Desire; (Winksele, BE), Oosthuyse, Bert; (Ooigem, BE) Correspondence: Elie H Gendloff; Amster Rothstein & Ebenstein; 90 Park Avenue; New York; NY; 10016; US Patent Application Number: 20030105018 Date filed: October 10, 2002 Abstract: The present invention relates to neurological and physiological dysfunction associated with neuron disorders. In (particular, the invention relates to the involvement of vascular endothelial growth factor (VEGF) and homologues in the aetiology of motor neuron disorders. The invention further concerns a novel, mutant transgenic mouse (VEGF.sup.m/m) with a homozygous deletion in the hypoxia responsive element (HRE) of the VEGF promoter which alters the hypoxic upregulation of VEGF. These mice suffer severe adult onset muscle weakness due to progressive spinal motor neuron degeneration which is reminiscent of amyotrophic lateral sclerosis (ALS)--a fatal disorder with unknown aetiology. Furthermore, the neuropathy of these mice is not caused by vascular defects, but is due to defective VEGF-mediated survival signals to motor neurons. The present invention relates in particular to the isoform VEGF.sub.165 which stimulates survival of motor neurons via binding to neuropilin-1, a receptor known to bind semaphorin-3A which is implicated in axon retraction and neuronal death, and the VEGF Receptor-2. The present invention thus relates to the usage of VEGF, in particular VEGF.sub.165, for the treatment of neuron disorders and relates, in addition, to the usage of polymorphisms in the VEGF promotor for diagnosing the latter disorders. Excerpt(s): The present invention relates to neurological and physiological dysfunction associated with neuron disorders. In particular, the invention relates to the involvement of vascular endothelial growth factor (VEGF) and homologues in the aetiology of motor neuron disorders. The invention further concerns a novel, mutant transgenic mouse (VEGF.sup.m/m) with a homozygous deletion in the hypoxia responsive element (HRE) of the VEGF promoter which alters the hypoxic upregulation of VEGF. These mice
9
This has been a common practice outside the United States prior to December 2000.
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suffer severe adult onset muscle weakness due to progressive spinal motor neuron degeneration which is reminiscent of amyotrophic lateral sclerosis (ALS)--a fatal disorder with unknown aetiology. Furthermore, the neuropathy of these mice is not caused by vascular defects, but is due to defective VEGF-mediated survival signals to motor neurons. The present invention relates in particular to the isoform VEGF.sub.165 which stimulates survival of motor neurons via binding to neuropilin-1, a receptor known to bind semaphorin-3A which is implicated in axon retraction and neuronal death, and the VEGF Receptor-2. The present invention thus relates to the usage of VEGF, in particular VEGF.sub.165, for the treatment of neuron disorders and relates, in addition, to the usage of polymorphisms in the VEGF promotor for diagnosing the latter disorders. VEGF is a key player in the formation of new blood vessels (angiogenesis) during embryonic development as well as in a variety of pathological conditions.sup.1,2. Although VEGF primarily stimulates endothelial cells, it may also act on other cell types. Indeed, VEGF, VEGF receptor-1 (VEGFR-1/Flt1) and VEGF receptor2 (VEGFR-2/KDR/Flk1) have recently been implicated in stroke.sup.3,4, spinal cord ischemia.sup.5, and in ischemic and diabetic neuropathy.sup.6, WO 0062798. However, the latter molecules act predominantly via affecting vascular growth or function and a direct effect of VEGF on for example neuronal cells has not been shown.sup.11,12. Moreover, the in vivo relevance of such a direct effect is not validated. Ischemia plays an essential role in the pathogenesis of neurological disorders, acutely during stroke and chronically during aging and several neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington disease. Neurons are particularly vulnerable to oxidative stress by free radicals (generated during ischemia/reperfusion) because of their high oxygen consumption rate, abundant lipid content, and relative paucity of antioxidant enzymes compared to other organs.sup.16. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with muscle weakness, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “muscle weakness” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on muscle weakness. You can also use this procedure to view pending patent applications concerning muscle weakness. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 5. BOOKS ON MUSCLE WEAKNESS Overview This chapter provides bibliographic book references relating to muscle weakness. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on muscle weakness include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “muscle weakness” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on muscle weakness: •
Source for Oral-Facial Exercises Source: East Moline, IL: LinguiSystems, Inc. 1993. 176 p. Contact: Available from LinguiSystems, Inc. 3100 4th Avenue, East Moline, IL 612449700. Voice (800) 776-4332 or (309) 755-2300; TTY (800) 933-8331; Fax (309) 755-2377; Email:
[email protected]. PRICE: $37.95 plus shipping and handling. ISBN: 1559992654. Summary: This book provides a compilation of therapy strategies to improve oralmotor, facial, and neck strength and tone in clients with swallowing disorders, muscle weakness, or difficulty communicating. Through a combination of approaches that incorporate visual, auditory, tactile-kinesthetic, verbal, and motor modalities, the clinician is taught how to utilize a variety of exercises to improve a client's posture and muscle tone, thereby improving his or her articulation, swallowing, and voice difficulties. The book includes a speech and language evaluation; a case history form; a
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swallowing evaluation; information on food consistencies; client, family, and caregiver goals; nutrition information; oral-facial-neck exercises; and tips to improve communication. The author stresses that individual differences must be considered in establishing a remediation program. The length of the client's therapy and prognosis will be affected by etiology, baseline level of abilities, the client's motivation, regular involvement by support people (physician, therapist, caregiver, and family), funding for therapeutic and medical intervention, frequency of visits, and setting. The handbook concludes with a glossary, a list of resources and associations, a list of videotapes and instruction manuals, and a bibliography. 2 appendices. 20 references. (AA-M). •
Toby Churchill. Lightwriters: Communication Aids for People Who Cannot Speak Source: Cambridge, England: Toby Churchill Ltd. 1995. 16 p. Contact: Available from Zygo Industries, Inc. P.O. Box 1008, Portland, OR 97207-1008. (800) 234-6006 or (503) 684-6006; Fax (503) 684-6011. PRICE: Single copy free. Summary: This catalog depicts and describes products available from Toby Churchill Ltd, a company that designs and develops Lightwriters, small portable text-to-speech communication aids which are specially designed to meet the needs of people with speech impairments. Most Lightwriter users (including the founder of the company) have developed an acquired speech loss following laryngectomy, tracheostomy, head injury, stroke, or with progressive neurological disease, or congenital speech loss after literacy has been gain. Lightwriters require some degree of literacy. Lightwriters are also designed to accommodate the wide range of other disabilities which may accompany loss of speech, such as poor motor control, tremor, muscle weakness, spasticity, slow reactions, cognitive limitations, impaired vision, and deafness. After more details about Lightwriters and their indications, the catalog lists the different styles available and the features of each. Black and white photographs illustrate each product. Also available are accessories and supplies. The catalog lists the United States distributor for the company (based in England).
Chapters on Muscle Weakness In order to find chapters that specifically relate to muscle weakness, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and muscle weakness using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “muscle weakness” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on muscle weakness: •
Cushing's Disease and Syndrome Source: in Graham, S.D., Jr., et al., eds. Glenn's Urologic Surgery. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins. 1998. p. 3-7. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Website: lww.com. PRICE: $199.00 plus shipping and handling. ISBN: 0397587376.
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Summary: Cushing's disease and syndrome are characterized by the association of pituitary lesions in patients with hirsutism, proximal muscle weakness, round plethoric faces, increased supraclavicular and infrascapular fat pads, thin skin, and other less frequent signs such as acne, purple abdominal striae, and psychiatric symptoms. This chapter on Cushing's disease and syndrome is from an exhaustive textbook on urologic surgery. There are numerous etiologies of Cushing's syndrome, most involving the production of excessive ACTH from pituitary adenomas or from ectopic sources, benign adrenal tumors, and adrenal hyperplasia (overgrowth). The criteria for a diagnosis of Cushing's syndrome is excessive ACTH. The diagnosis may also be based on an abnormality of the plasma or urinary cortisol. Indications for surgery of the adrenal gland in patients with Cushing's syndrome include adrenal adenoma, adrenal hyperplasia, and adrenal carcinoma. The author then describes the posterior approach to the adrenal glands. Surgical complications following adrenal surgery for Cushing's syndrome include not only those that pertain to routine retroperitoneal surgery (e.g., blood loss and infection) but also those complications specific to patients with hormonal imbalances. Postoperative wound healing may be impaired, and the infection rate has been described to be between 4 and 21 percent. 6 figures. 6 references. •
Exercise in Diabetic Patients with Disabilities Source: in Devlin, J.T. and Schneider, S.H., eds. Handbook of Exercise in Diabetes. Alexandria, VA: American Diabetes Association. 2002. p.601-611. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $69.95 plus shipping and handling. ISBN: 1580400191. Summary: Disability and diabetes commonly coexist. Diabetes is a risk factor for stroke, amputation, and neuropathy (nerve disease). This chapter on exercise in diabetic patients with disabilities is from a book that provides a practical, comprehensive guide to diabetes and exercise for health care professionals involved in patient care. Stroke is a common disabling condition in people with diabetes. Exercise therapy is a key component of rehabilitation after stroke. Recent studies have provided increasing evidence that exercise can facilitate stroke recovery. The high prevalence of coronary artery disease in people with diabetes who sustain a stroke should be considered when prescribing exercise for these individuals. Both diabetes and stroke may be risk factors for carpal tunnel syndrome (CPS). Treatment of CPS may be complicated by coexisting disability (e.g., hemiparesis, muscle weakness, in the other arm). Leg amputation may occur as a complication of diabetes and imposes increased energy costs for ambulation (walking). The energy requirements of walking with an above-the-knee amputation are substantially higher than with a below-the-knee amputation. Neuropathy is an important cause of disability in individuals with diabetes. Ankle dorsiflexion weakness ('foot drop') may be effectively managed with the use of an ankle foot orthosis. In severe cases of neuropathy, a Charcot arthropathy may develop in the foot or ankle. This has a substantial impact on the ability to exercise and may result in amputation in some cases. Lower extremity braces may be useful as a compensatory tool for individuals with leg weakness from stroke or neuropathy. Either plastic lightweight braces or metal braces attached to shoes may be appropriate in different situations. The least restrictive brace possible should generally be prescribed. 1 figure. 31 references.
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Dysphagia Source: in Edmundowicz, S.A., ed. 20 Common Problems in Gastroenterology. New York, NY: McGraw-Hill, Inc. 2002. p. 33-47. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Website: www.bookstore.mcgraw-hill.com. PRICE: $45.00;plus shipping and handling. ISBN: 0070220557. Summary: Dysphagia is defined as difficulty swallowing, most often described by patients as 'the food gets stuck.' Dysphagia generally is not painful (painful swallowing is termed odynophagia). Symptoms of dysphagia always require a diagnostic evaluation to determine the etiology. This chapter on dysphagia is from a book that focuses on the most common gastroenterological problems encountered in a primary practice setting. The chapter is organized to support rapid access to the information necessary to evaluate and treat most patients with this problems. Topics include definitions and background; principal diagnoses, which can include cerebrovascular accident (stroke), amyotrophic lateral sclerosis (ALS), myasthenia gravis, Parkinson disease, myopathy (muscle weakness), incomplete relaxation of the upper esophageal sphincter, esophageal cancer, peptic stricture, Schatzki ring, achalasia, diffuse esophageal spasm, and aperistalsis of the esophageal body; key points of the patient history; the physical examination; ancillary tests, including videofluoroscopy, barium swallow, endoscopy, and esophageal manometry; treatment options; patient education, including dietary modification and swallowing therapy; common errors in diagnosis and treatment; controversies, including the use of Botox for esophageal motility disorders; and emerging concepts. The chapter includes a chapter outline for quick reference, the text itself, a diagnostic and treatment algorithm, and selected references. 1 figure. 1 table. 15 references.
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Exercise and Aging Source: in Devlin, J.T. and Schneider, S.H., eds. Handbook of Exercise in Diabetes. Alexandria, VA: American Diabetes Association. 2002. p.567-585. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $69.95 plus shipping and handling. ISBN: 1580400191. Summary: The primary aspects of body composition that change with advancing age are decreased skeletal muscle mass, termed sarcopenia, and increased body fatness. This chapter on exercise and aging is from a book that provides a practical, comprehensive guide to diabetes and exercise for health care professionals involved in patient care. Sarcopenia results in muscle weakness, which has been associated with late life disability and risk of falling among elderly people. Muscle weakness may limit activities of daily living in many older individuals. Therefore, strength training should be the primary recommendation for elderly people. Strength training has a number of positive benefits, including increased muscle strength and size, improved bone health, increased energy requirements, and increased levels of physical activity. Strength training is safe for almost all elderly people and has been demonstrated to be highly effective, even into the tenth decade of life. Relatively low intensity aerobic exercise has been demonstrated to improve insulin action in older people. 54 references.
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Rheumatologic Disease Source: in Daugirdas, J.T. and Ing, T.S., eds. Handbook of Dialysis. 2nd ed. Boston, MA: Little, Brown and Company. 1994. p. 662-672. Contact: Available from Lippincott-Raven Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 777-2295. Fax (301) 824-7390. E-mail:
[email protected]. Website: http://www.lrpub.com. PRICE: $37.95. ISBN: 0316173835. Summary: This chapter on rheumatologic disease in dialysis patients is from a handbook that outlines all aspects of dialysis therapy, emphasizing the management of dialysis patients. Topics include dialysis-related amyloidosis, including carpal tunnel syndrome and destructive spondyloarthropathy; crystal-associated arthropathies; viral arthritis; muscle weakness; extensor tendon rupture; connective tissue disorders; and the use of rheumatologic drugs in dialysis patients, including NSAIDs, drugs for gout, and corticosteroids. For each condition, the authors discuss incidence, symptoms, diagnosis, pathophysiology, prevention, and management. The authors present information in outline form, for easy reference. 3 tables. 21 references.
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Renal Failure and Secondary Hyperparathyroidism Source: in Pellitteri, P.; McCaffrey, T.V. Endocrine Surgery of the Head and Neck. Florence, KY: Thomson Learning. 2003. p. 389-400. Contact: Available from Thomson Learning, Attn: Order Fulfillment. P.O. Box 6904 Florence, KY 41022 (800) 347-7707. Fax (800) 487-8488. E-mail:
[email protected]. Website: www.delmar.com. PRICE: $179.95 plus shipping and handling. ISBN: 076930091x. Summary: This chapter, from a textbook on endocrine surgery of the head and neck, covers renal (kidney) failure and secondary hyperparathyroidism (HPTH). The authors note that secondary HPTH is a complex process. Hyperplasia (overgrowth) of the parathyroid glands and increase in the serum PTH (parathyroid hormone) levels appear early in the development of renal disease. Medical treatment of HPTH is aimed at reducing serum phosphatase levels, increasing serum calcium levels, administering vitamin D analogs, and maintaining an appropriate metabolic equilibrium with adequate dialysis. The most common indications for surgical treatment of secondary HPTH are the development of renal osteodystrophy (bone disease), severe pruritus (itching) associated with HPTH, calciphylaxis, and tumoral calcinosis. Less clear indications for surgery are easy fatigability, proximal muscle weakness and anemia. Patients with secondary HPTH treated surgically can expect substantial improvements in bone and joint pain and pruritus in most cases. Amelioration of fatigue and generalized well being are often observed, albeit harder to quantify. Surgical techniques most commonly employed include subtotal parathyroidectomy and total parathyroidectomy with autotransplantation. There may be a role for minimally invasive approaches, such as endoscopic parathyroidectomy and percutaneous ethanol ablation, which are currently still investigational. 3 figures. 95 references.
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CHAPTER 6. MULTIMEDIA ON MUSCLE WEAKNESS Overview In this chapter, we show you how to keep current on multimedia sources of information on muscle weakness. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on muscle weakness is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “muscle weakness” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “muscle weakness” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on muscle weakness: •
Diabetic Foot Source: Bethesda, MD: American Podiatric Medical Association. 1990. (videocassette). Contact: Available from American Podiatric Medical Association, 9312 Old Georgetown Road, Bethesda, MD 20814-1698. (800) 615-0807 or (301) 571-9200. Fax (301) 530-2752. PRICE: $75.00 plus shipping and handling. Summary: This video discusses the foot problems that people with diabetes may experience. They may develop foot problems from restricted circulation, dulled sensation, and muscle weakness. Podiatrists can determine circulation to the foot by measuring the pulse in each foot and the temperature of the skin of each foot. Podiatrists can also diagnose neuropathy by examining reflexes, determining sensation in the lower limbs, and conducting nerve studies. Foot problems can be prevented by maintaining a good diet, measuring blood glucose levels, exercising, wearing loose-fitting hose and stockings, avoiding the use of tobacco products, inspecting the feet once per day for any changes, washing and drying feet daily, using foot powder, caring for dry skin, selecting
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comfortable footwear, and cutting toenails straight across. Other topics include ways of reducing foot pressure to minimize callous and corn formation and methods of preventing and treating fungal infections. This video may be used by diabetes educators and nonphysician health personnel involved with a person with diabetes. It may also be used as a patient education tool.
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CHAPTER 7. PERIODICALS AND NEWS ON MUSCLE WEAKNESS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover muscle weakness.
News Services and Press Releases One of the simplest ways of tracking press releases on muscle weakness is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “muscle weakness” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to muscle weakness. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “muscle weakness” (or synonyms). The following was recently listed in this archive for muscle weakness: •
After ICU stint, muscle weakness may linger Source: Reuters Health eLine Date: February 20, 2003
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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “muscle weakness” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “muscle weakness” (or synonyms). If you know the name of a company that is relevant to muscle weakness, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “muscle weakness” (or synonyms).
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Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “muscle weakness” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on muscle weakness: •
Constipation: How to Find Relief Without Laxatives Source: Environmental Nutrition. 22(9): 2. September 1999. Contact: Available from Environmental Nutrition, Inc. 52 Riverside Drive, New York, NY 10024-6599. (800) 829-5384. Summary: Constipation is defined as infrequent or difficult bowel movements, typically three consecutive days without a movement. This brief article offers strategies for dealing with constipation without resorting to the use of laxatives. The author notes that, most often, constipation is temporary, triggered perhaps by a change in routine (like travel) and requires no real intervention beyond a cup of prune juice or a bowl of bran flakes. The author reviews the causes of constipation, including sedentary habits, diets of processed, low fiber foods, and a tendency to drink too few fluids. Additional contributors to constipation, especially for older people, include muscle weakness, poor dentition (which makes it hard to chew high fiber foods), and certain medications, including antidepressants, antacids, antihistamines, diuretics, opiates, tranquilizers, iron supplements, and calcium supplements. Three sidebars offer practical strategies for coping with constipation, preventing problems, and being cautious with herbal remedies.
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Salivary Gland Tumors Source: News from SPOHNC. News from Support for People with Oral and Head and Neck Cancer. 4(4): 1-3. December 1994. Contact: Available from Support for People with Oral and Head and Neck Cancer, Inc. (SPOHNC). P.O. Box 53, Locust Valley, NY 11560-0053. (516) 759-5333; E-mail:
[email protected]; http://www.spohnc.org. Summary: This article, from a newsletter for people with oral and head and neck cancer, discusses salivary gland tumors. Topics covered include the incidence of salivary gland tumors; the anatomy and physiology of the salivary glands; the clinical presentation of salivary gland problems; the surgical treatment of salivary gland tumors, including postoperative complications; the risk of damaging facial nerve function with any operation on the parotid gland; postoperative facial muscle weakness; surgical techniques for those parotid gland tumors that are sizable and malignant; the role of post-operative radiation therapy; assessing the results of treating salivary gland tumors; recurrence rates; the classification or grading of salivary gland tumors, and prognosis based on that grading; and survival rates. The author stresses that any swelling near the ear, below the mandible, or in the mouth demands attention even if it is painless or has changed little in many months.
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Urinary Incontinence and Sexuality Source: Quality Care. 16(3): 5. Summer 1998. Contact: Available from National Association for Continence. P.O. Box 8310, Spartanburg, SC 29305-8310. (800) 252-3337 or (864) 579-7900. Fax (864) 579-7902. Summary: This brief newsletter article reviews the problem of urinary incontinence and its impact on the patient's sexuality. The impact of incontinence may upset an established love life or create particular difficulties with a new relationship. Intimacy is about being close, and incontinence or the fear of leakage might be an obstacle, both mentally and physically. Problems may be greatest for those who have known continence but have lost it as a result of a difficult childbirth or surgery. This surgery can include hysterectomy or prolapse surgeries for women and prostatectomy for men. Loss of orgasm can also occur after surgery. There is often embarrassment, anger, and frustration with these adverse outcomes. Some causes for leakage include pelvic floor muscle weakness, overactive bladder contractions, or incomplete bladder emptying. The author notes that incontinence episodes with sex can sometimes be cured, often improved, but always managed by optimal care. The author briefly summarizes the principles of successful management: make sure the bladder and bowel are empty before sexual activity, use warmed lubricating gel, avoid a position that may provoke leakage, and share concerns with the sexual partner. The author encourages readers to work with their health care providers to manage urinary incontinence problems.
•
Sexual Function and Urinary Incontinence Source: Quality Care. 19(4): 1,5. Fall 2001. Contact: Available from National Association for Continence. P.O. Box 8310, Spartanburg, SC 29305-8310. (800) 252-3337 or (864) 579-7900. Fax (864) 579-7902. Summary: This newsletter article helps women with urinary incontinence (UI) understand the impact of UI on sexual function. Some women experience loss of urine during sexual activity. Causes of leakage can include pelvic floor muscle weakness, overactive bladder contractions, or incomplete bladder emptying. With minimal arousal, the pelvic muscles can relax and allow drops of leakage. With penetration (intercourse) a woman may experience bladder contractions, or with orgasm, involuntary relaxation may cause a flood. When this happens, women may avoid sexual activity altogether. In addition, constant wetness from UI may lead to irritation in the vulvar area, and this can cause discomfort with sexual activity. This author offers strategies to prevent these problems, focusing on the surgical options. Surgery is an effective treatment option for some women with UI, particularly the stress type of incontinence (leaking provoked by physical stress such as coughing, sneezing, running, or jumping). Stress incontinence can occur in combination with pelvic organ prolapse (when the vagina, uterus, or bladder have lost support and dropped down). The author briefly describes the surgical techniques that are usually used for UI. The article concludes with four suggestions to help manage UI during sexual activity.
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Hows and Whys of Celiac Disease: Presentation to the 21st Annual CSA Conference, Warwick, Rhode Island Source: Lifeline. 17(2): 1. Spring 1999. Contact: Available from Celiac Sprue Association-United States of America, Inc. P.O. Box 31700, Omaha, NE 68131. (402) 558-0600. Website: www.csaceliacs.org.
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Summary: This newsletter article reprints Dr. Z. Myron Falchuk's presentation to the 21st Annual Celiac Sprue Association (CSA) Conference, held in Warwick, Rhode Island, in 1999. Dr. Falchuk reviews the basics of celiac disease and discusses the diagnosis of celiac disease. Celiac disease, or gluten sensitive enteropathy, is an abnormality of the small intestine that interferes with the absorption of food. The diagnosis is relatively easy in patients with severe disease, but in patients with relatively modest symptoms, malabsorption conditions such as celiac disease are very difficult to pin down. The author notes that there are two presentations of celiac disease, one in childhood and one in adulthood. The role of genetics is considered. From celiac disease, the results can include protein malabsorption, muscle weakness, edema (fluid accumulation), malabsorption of vitamin D, hypocalcemia (which can result in thin bones), and vitamin A malabsorption (which can result in night blindness). The author considers other diseases that may present with or as malabsorption and reviews the use of an organ culture model system that can be used for research on celiac disease. This model focuses in on the immune system factors of celiac disease.
Academic Periodicals covering Muscle Weakness Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to muscle weakness. In addition to these sources, you can search for articles covering muscle weakness that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for muscle weakness. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with muscle weakness. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.).
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The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to muscle weakness: Ascorbic Acid (Vitamin C) •
Vitamin C - U.S. Brands: Ascorbicap; Cebid Timecelles; Cecon; Cecore 500; Cee500; Cemill; Cenolate; Cetane; Cevi-Bid; Flavorcee; Mega-C/A Plus; Ortho/CS; Sunkist http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202071.html
Magnesium Supplements •
Systemic - U.S. Brands: Almora; Chloromag; Citroma; Concentrated Phillips' Milk of Magnesia; Mag-200; Mag-L-100; Magonate; Mag-Ox 400; Mag-Tab SR; Magtrate; Maox; MGP; Phillips' Chewable Tablets; Phillips' Milk of Magnesia; Slow-Mag; Uro-Mag http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202644.html
Potassium Supplements •
Systemic - U.S. Brands: Cena-K; Effer-K; Gen-K; Glu-K; K+ 10; K+ Care; K+ Care ET; K-8; Kaochlor 10%; Kaochlor S-F 10%; Kaon; Kaon-Cl; Kaon-Cl 20% Liquid; Kaon-Cl-10; Kato; Kay Ciel; Kaylixir; K-Dur; K-Electrolyte; K-G Elixir; K-Ide; KLease; K-Lor; Klor-Con 10; Klor-Con 8; Klor-Con Powder; Klor-Con/25 Powder; Klor-Con/EF; Klorvess; Klorvess 10% Liquid; Klorvess Effervescent Granules; Klotrix; K-Lyte; K-Lyte DS; K-Lyte/Cl; K-Lyte/Cl 50; K-Lyte/Cl Powder; KNorm; Kolyum; K-Sol; K-Tab; K-Vescent; Micro-K; Micro-K 10; Micro-K LS; Potasalan; Rum-K; Slow-K; Ten-K; Tri-K; Twin-K http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202473.html
Pralidoxime •
Systemic - U.S. Brands: Protopam Chloride http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202779.html
Selenium Supplements •
Systemic - U.S. Brands: Sele-Pak; Selepen http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202633.html
Thiamine (Vitamin B 1) •
Vitamin B 1 - U.S. Brands: Biamine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202560.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
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Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
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These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
11
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “muscle weakness” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 5957 25 987 14 889 7872
HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “muscle weakness” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
13
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
14
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
18 Adapted 19
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on muscle weakness can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to muscle weakness. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to muscle weakness. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “muscle weakness”:
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Chronic Fatigue Syndrome http://www.nlm.nih.gov/medlineplus/chronicfatiguesyndrome.html Muscle Disorders http://www.nlm.nih.gov/medlineplus/muscledisorders.html Muscular Dystrophy http://www.nlm.nih.gov/medlineplus/musculardystrophy.html Myasthenia Gravis http://www.nlm.nih.gov/medlineplus/myastheniagravis.html Neuromuscular Disorders http://www.nlm.nih.gov/medlineplus/neuromusculardisorders.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on muscle weakness. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Dental Treatment Considerations Source: Chicago, IL: Myasthenia Gravis Foundation of America, Inc. 1998. [4 p.]. Contact: Available from Myasthenia Gravis Foundation of America, Inc. 222 South Riverside Plaza, Suite 1540, Chicago, IL 60606. (800) 541-5454 or (312) 258-0522. Fax (312) 258-0461. Website: www.myasthenia.org. PRICE: Single copy free. Summary: Myasthenia gravis is an autoimmune neuromuscular disorder that presents challenges for both the dental practitioner and the patient. Facial and masticatory muscles may be involved and may complicate dental care and treatment. Exacerbations of muscle weakness and fatigability that characterize this disorder can be precipitated by certain medications used in dentistry. This brochure reviews the oral findings and dental management considerations of myasthenia gravis (MG). The brochure also offers suggestions for monitoring for the oral side effects of drug interactions of therapies used to treat MG, and notes strategies to modify dental treatment to accommodate altered muscle strength. The brochure concludes that the dental team should be cognizant of the medication precautions in this population, modify dental care to accommodate existing neuromuscular weakness and drug therapy, and be prepared to manage emergent complications occurring in the dental office.
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Balancing Calcium and Phosphorus Source: San Bruno, CA: Krames Communications. 1997. [2 p.]. Contact: Available from Krames Communications. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 244-4512. Website: www.krames.com. PRICE: $12.50 for a pad of 50. Item number 5549. Summary: This fact sheet helps readers with kidney disease balance calcium and phosphorus. Calcium and phosphorus are minerals found in many foods. With kidney disease, phosphorus may build up in the blood; this can weaken the bones over time. This fact sheet describes the use of phosphate binders, medications that help prevent phosphorus from being absorbed by the body. The fact sheet leaves blank space for the health care provider to individualize the information about the patient's phosphate binder type, and how to take the medication. The fact sheet recommends that foods that are high in phosphorus should be avoided; these include cola drinks, dried or baked beans, nuts and seeds of all kinds, peanut butter, split peas, and whole grain cereals. The fact sheet then describes the complications of high phosphorus levels, including renal bone disease. If this problem is not controlled, the bones become weaker over time. Other effects of high phosphate levels include itchy skin, bone and joint pain, brittle bones, fractures, muscle weakness, and deposits of calcium phosphate appearing in organs, such as the heart, lungs, eyes, skin, and gums. The fact sheet also includes space for special instructions. The fact sheet is illustrated with simple line drawings of patients and everyday foods.
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Immunosuppressants Source: New York, NY: National Kidney Foundation. 1993. [3 p.]. Contact: Available from National Kidney Foundation of Southern California. 5777 West Century Boulevard, Suite 1450, Los Angeles, CA 90045-7404. (310) 641-8152. Fax (310) 641-5246. Website: www.kidneysocal.org. PRICE: Single copy free; bulk copies available. Summary: This fact sheet offers kidney disease patients an overview of immunosuppressants, a group of drugs or medicines that suppress or lower the body's ability to reject a transplanted organ. These drugs are also called antirejection drugs. Examples of immunosuppressants used for kidney transplants are cyclosporine, azathioprine, prednisone, and FK506. The fact sheet, written in question and answer format, explains the use of immunosuppressants, what to do if a scheduled dose is missed, different drugs and dosages used for different patients, signs or symptoms of rejection (even while on immunosuppressants), the problem of increased risk of infection while on these drugs, specific recommendations for different drugs, the possible side effects of these drugs, and how to get additional information. Prednisone should be taken with meals or food because it can be irritating to the stomach. Side effects can include weight gain, muscle weakness, acne, trouble sleeping, stomach ulcers, diabetes, and cataracts. Azathioprine should be taken once a day. Side effects can include low white blood cell count, liver problems, anemia, and nightmares. Cyclosporine comes in liquid and capsule form; it is usually taken twice a day, but the dose can be adjusted based on the amount in the patient's blood. Side effects can include kidney damage (nephrotoxicity), overgrowth of gums (gingival hyperplasia), hair growth, hair darkening, high blood pressure, tremors of the hands, and liver problems. FK506 is a drug whose actions and side effects are similar to cyclosporine. The fact sheet concludes with a brief description of the National Kidney Foundation (NKF) and its activities.
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Motor Neuron Disease Source: Danbury, CT: National Organization for Rare Disorders. 2000. 7 p. Contact: National Organization for Rare Disorders. P.O. Box 1968, Danbury, CT 068131968. (800) 999-NORD; (203) 744- 0100; TDD (203) 797-9590. E-mail:
[email protected]. Website: www.rarediseases.org. PRICE: Free for 1st request, $7.50 per copy thereafter. Summary: This fact sheet summarizes information on motor neuron diseases (MND' s), including a brief definition and synonyms for the disease, symptom progression, possible causes, the population affected, standard and investigational therapies, and related disorders. MND is a group of serious disorders characterized by progressive degeneration of motor neurons (neurons combined to form nerves that control the behavior of muscles). Symptoms are characterized by muscle weakness, atrophy, and normal intellectual functioning. There are several forms of MND, including amyotrophic lateral sclerosis (Lou Gehrig's disease), primary lateral sclerosis, WerdnigHoffmann disease, and Kugelberg- Welander syndrome. The exact etiology of MND is unknown. In general, all forms of the disease are rare, affecting different populations. Standard therapies include the use of drugs symptoms such as baclofen, quinine, and diazepam to control muscle, and pyridostigmine for nerve- to-muscle transmission; various respiratory aids; devices to help the patient continue daily living activities; and genetic counseling for patients and families with a hereditary form of MND. This fact sheet includes a list of resources on MND.
•
Musculoskeletal Problems Contact: National AIDS Treatment Information Project, Beth Israel Deaconess Medical Center, Beth Israel Hospital, 330 Brookline Ave Libby Bldg 317, Boston, MA, 02215, (617) 667-5520, http://www.natip.org. Summary: This fact sheet, written for individuals with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), presents information about HIV/AIDS and musculoskeletal problems. Musculoskeletal problems represent disorders of the muscles (myositis), joints (arthritis), and connective tissues (tendonitis). A variety of rheumatologic conditions such as arthralgia, fibromyalgia syndrome, Reiter's syndrome, and myositis, have been described in HIV-positive individuals. Arthralgia refers to pain in the joints without evidence of inflammation. Fibromyalgia syndrome causes widespread pain in the body and characteristic muscle tenderness. Reiter's syndrome includes some combination of arthritis, conjunctivitis, and urethritis. Myositis presents with muscle weakness of the shoulders and upper legs. The most common overall symptoms of musculoskeletal problems include pain of the joints, muscles, and connective tissues; fever; chills; weakness; and swelling or redness of the affected area(s). Musculoskeletal problems are often diagnosed through an analysis of individuals' medical histories, a physical examination, blood serology, arthrocentesis, electromyography, and a muscle or bone biopsy. Most musculoskeletal problems are managed with nonsteroidal anti-inflammatory agents (NSAIDS's) and/or antibiotics.
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Mitochondrial Toxicity Contact: University of New Mexico School of Medicine, Infectious Diseases Division, New Mexico AIDS Education and Training Center, New Mexico AIDS InfoNet, PO Box 810, Arroyo Seco, NM, 87514-0810, (505) 776-8032, http://www.aidsinfonet.org.
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Summary: This information sheet provides people who have the human immunodeficiency virus (HIV) with an overview of mitochondrial toxicity (MT). Mitochondria are small organs in the cells that serve as power plants for the cells. MT is damage that decreases the number of mitochondria. A common sign of MT is muscle weakness. Some people with MT have very high levels of lactic acid in their blood, a rare condition known as lactic acidosis. The drugs used to inhibit reverse transcriptase in people who have HIV can also inhibit pol gamma, an enzyme that helps mitochondria multiply. However, there is little research on how much mitochondrial damage each antiviral drug causes to different parts of the body. •
Potassium and Renal Diet Source: New York, NY: National Kidney Foundation. 1999. 3 p. Contact: Available from National Kidney Foundation. 30 East 33rd Street, New York, NY 10016. (800) 622-9010. Website: www.kidney.org. PRICE: Single copy free. Summary: This patient education fact sheet reviews the importance of potassium for patients following a renal (kidney) diet. Potassium is a mineral found in many foods; it plays a role in heartbeat regulation and keeping the muscles working right. The kidneys normally keep the right amount of potassium levels in the body. In people with kidney disease, the kidneys may not perform this regulation function very well, and dietary limitation of potassium can be helpful. Symptoms of too much potassium in the blood (hyperkalemia) include muscle weakness, numbness, and tingling; additional complications include irregular heartbeat or even a heart attack. The fact sheet offers strategies for controlling potassium in the diet, recommending that readers work closely with their dietitian to first learn about their diet therapy. The author emphasizes the importance of portion size; a large amount of a low potassium food can turn it into a high potassium food. The fact sheet includes a table that lists foods that are high in potassium (more than 200 milligrams per portion); the portion size is noted at one-half cup for most foods. A second table lists foods that are low in potassium (lower than 200 milligrams per portion). The fact sheet includes a space for readers to note their own recommended blood potassium level (as determined by their health care provider). The fact sheet concludes with a brief description of the activities of the National Kidney Foundation (800-622-9010). The NIH Search Utility
The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to muscle weakness. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.
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Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to muscle weakness. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with muscle weakness. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about muscle weakness. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “muscle weakness” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received
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your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “muscle weakness”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “muscle weakness” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “muscle weakness” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
21
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
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Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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MUSCLE WEAKNESS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 9-cis retinoic acid: A drug being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acrylamide: A colorless, odorless, highly water soluble vinyl monomer formed from the hydration of acrylonitrile. It is primarily used in research laboratories for electrophoresis, chromatography, and electron microscopy and in the sewage and wastewater treatment industries. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Actinin: A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different
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from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adduction: The rotation of an eye toward the midline (nasally). [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among
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simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agrin: A protein component of the synaptic basal lamina. It has been shown to induce clustering of acetylcholine receptors on the surface of muscle fibers and other synaptic molecules in both synapse regeneration and development. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amblyopia: A nonspecific term referring to impaired vision. Major subcategories include stimulus deprivation-induced amblyopia and toxic amblyopia. Stimulus deprivationinduced amblopia is a developmental disorder of the visual cortex. A discrepancy between visual information received by the visual cortex from each eye results in abnormal cortical development. Strabismus and refractive errors may cause this condition. Toxic amblyopia is a disorder of the optic nerve which is associated with alcoholism, tobacco smoking, and other toxins and as an adverse effect of the use of some medications. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH]
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Amelogenesis Imperfecta: Either hereditary enamel hypoplasia or hypocalcification. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antaganize cholinergic and alpha-1 adrenergic responses to bioactive amines. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amputation: Surgery to remove part or all of a limb or appendage. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Amyotrophy: A type of diabetic neuropathy that causes muscle weakness and wasting. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anabolic Steroids: Chemical derivatives of testosterone that are used for anabolic promotion of growth and repair of body tissues and the development of male sexual characteristics. [NIH] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH]
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Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anisotropy: A physical property showing different values in relation to the direction in or along which the measurement is made. The physical property may be with regard to thermal or electric conductivity or light refraction. In crystallography, it describes crystals whose index of refraction varies with the direction of the incident light. It is also called acolotropy and colotropy. The opposite of anisotropy is isotropy wherein the same values characterize the object when measured along axes in all directions. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Ankle Joint: The joint that is formed by the inferior articular and malleolar articular surfaces of the tibia, the malleolar articular surface of the fibula, and the medial malleolar, lateral malleolar, and superior surfaces of the talus. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]
Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior Cruciate Ligament: A strong ligament of the knee that originates from the posteromedial portion of the lateral condyle of the femur, passes anteriorly and inferiorly between the condyles, and attaches to the depression in front of the intercondylar eminence of the tibia. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH]
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Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH]
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Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginase: A ureahydrolase that catalyzes the hydrolysis of arginine or canavanine to yield L-ORNITHINE and urea. Deficiency of this enzyme causes hyperargininemia. EC 3.5.3.1. [NIH]
Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthralgia: Pain in the joint. [NIH] Arthropathy: Any joint disease. [EU] Articular: Of or pertaining to a joint. [EU] Articulation: The relationship of two bodies by means of a moveable joint. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartate: A synthetic amino acid. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes
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have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrial: Pertaining to an atrium. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Babesiosis: A group of tick-borne diseases of mammals including zoonoses in humans. They are caused by protozoans of the genus babesia, which parasitize erythrocytes, producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by the deer tick ixodes scapularis. [NIH] Back Injuries: General or unspecified injuries to the posterior part of the trunk. It includes injuries to the muscles of the back. [NIH] Baclofen: A GABA derivative that is a specific agonist at GABA-B receptors. It is used in the treatment of spasticity, especially that due to spinal cord damage. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most
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important. [NIH] Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous. [NIH] Barium swallow: A series of x-rays of the esophagus. The x-ray pictures are taken after the person drinks a solution that contains barium. The barium coats and outlines the esophagus on the x-ray. Also called an esophagram. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Bed Rest: Confinement of an individual to bed for therapeutic or experimental reasons. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Beta-Galactosidase: A group of enzymes that catalyzes the hydrolysis of terminal, nonreducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause gangliodisosis GM1. EC 3.2.1.23. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biomechanics: The study of the application of mechanical laws and the action of forces to living structures. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological
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system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brace: Any form of splint or appliance used to support the limbs or trunk. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary
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permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bulbar: Pertaining to a bulb; pertaining to or involving the medulla oblongata, as bulbar paralysis. [EU] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Calcinosis: Pathologic deposition of calcium salts in tissues. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [NIH] Carbimazole: An imidazole antithyroid agent. Carbimazole is metabolized to methimazole, which is responsible for the antithyroid activity. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiopulmonary: Having to do with the heart and lungs. [NIH]
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Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carpal Tunnel Syndrome: A median nerve injury inside the carpal tunnel that results in symptoms of pain, numbness, tingling, clumsiness, and a lack of sweating, which can be caused by work with certain hand and wrist postures. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Castor Oil: Oil obtained from seeds of Ricinus communis that is used as a cathartic and as a plasticizer. [NIH] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which
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oxygen is used to provide a source of energy for the cell. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH]
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Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic Progressive External Ophthalmoplegia: Paralysis of the extraocular muscles. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Neurotrophic Factor: A neurotrophic factor that promotes the survival of various neuronal cell types and may play an important role in the injury response in the nervous system. [NIH] Cinchona: A genus of rubiaceous South American trees that yields the toxic cinchona alkaloids from their bark; quinine, quinidine, chinconine, cinchonidine and others are used to treat malaria and cardiac arrhythmias. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] Clathrin-Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles is covered with a lattice-like network of the protein clathrin. Shortly after formation, however, the clathrin coat is removed and the vesicles are referred to as endosomes. [NIH] Clavicle: A long bone of the shoulder girdle. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH]
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Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [NIH] Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with welldefined distribution patterns in relation to time or place or both. [NIH] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH]
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Communis: Common tendon of the rectus group of muscles that surrounds the optic foramen and a portion of the superior orbital fissure, to the anterior margin of which it is attached at the spina recti lateralis. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computer Systems: Systems composed of a computer or computers, peripheral equipment, such as disks, printers, and terminals, and telecommunications capabilities. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body,
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taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concentric: Having a common center of curvature or symmetry. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH]
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Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continence: The ability to hold in a bowel movement or urine. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibres. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Convalescence: The period of recovery following an illness. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniomandibular Disorders: Diseases or disorders of the muscles of the head and neck, with special reference to the masticatory muscles. The most notable examples are temporomandibular joint disorders and temporomandibular joint dysfunction syndrome.
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[NIH]
Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Critical Illness: A disease or state in which death is possible or imminent. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, .
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New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]
Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Dantrolene: Skeletal muscle relaxant that acts by interfering with excitation-contraction coupling in the muscle fiber. It is used in spasticity and other neuromuscular abnormalities. Although the mechanism of action is probably not central, dantrolene is usually grouped with the central muscle relaxants. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Decompression Sickness: A condition occurring as a result of exposure to a rapid fall in ambient pressure. Gases, nitrogen in particular, come out of solution and form bubbles in body fluid and blood. These gas bubbles accumulate in joint spaces and the peripheral circulation impairing tissue oxygenation causing disorientation, severe pain, and potentially death. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH]
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Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dentition: The teeth in the dental arch; ordinarily used to designate the natural teeth in position in their alveoli. [EU] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermatitis: Any inflammation of the skin. [NIH] Dermatitis Herpetiformis: Rare, chronic, papulo-vesicular disease characterized by an intensely pruritic eruption consisting of various combinations of symmetrical, erythematous, papular, vesicular, or bullous lesions. The disease is strongly associated with the presence of HLA-B8 and HLA-DR3 antigens. A variety of different autoantibodies has been detected in small numbers in patients with dermatitis herpetiformis. [NIH] Desmin: An intermediate filament protein found predominantly in smooth, skeletal, and cardiac muscle cells. Localized at the Z line. MW 50,000 to 55,000 is species dependent. [NIH] Dextromethorphan: The d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is a NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is used widely as an antitussive agent, and is also used to study the involvement of glutamate receptors in neurotoxicity. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Ketoacidosis: Complication of diabetes resulting from severe insulin deficiency coupled with an absolute or relative increase in glucagon concentration. The metabolic acidosis is caused by the breakdown of adipose stores and resulting increased levels of free fatty acids. Glucagon accelerates the oxidation of the free fatty acids producing excess ketone bodies (ketosis). [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [NIH]
Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains
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of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH]
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Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dwarfism: The condition of being undersized as a result of premature arrest of skeletal growth. It may be caused by insufficient secretion of growth hormone (pituitary dwarfism). [NIH]
Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dynamometer: An instrument for measuring the force of muscular contraction. [NIH] Dysarthria: Imperfect articulation of speech due to disturbances of muscular control which result from damage to the central or peripheral nervous system. [EU] Dysphagia: Difficulty in swallowing. [EU] Dyspnea: Difficult or labored breathing. [NIH] Dyspnoea: Difficult or laboured breathing. [EU] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electromyography: Recording of the changes in electric potential of muscle by means of surface or needle electrodes. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in
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all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous)
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production. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotracheal intubation: Insertion of an airtube into the windpipe. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH]
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Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Ergometer: An instrument for measuring the force of muscular contraction. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Manometry: A test to measure muscle tone inthe esophagus. [NIH] Esophageal Motility Disorders: Disorders affecting the motor function of the upper or lower esophageal sphincters, the esophageal body, or a combination of these parts. The failure of the sphincters to maintain a tonic pressure may result in the impeding of the passage of food, regurgitation of food, or reflux of gastric acid into the esophagus. [NIH] Esophagram: A series of x-rays of the esophagus. The x-ray pictures are taken after the person drinks a solution that contains barium. The barium coats and outlines the esophagus on the x-ray. Also called a barium swallow. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Esotropia: A form of ocular misalignment characterized by an excessive convergence of the visual axes, resulting in a "cross-eye" appearance. An example of this condition occurs when paralysis of the lateral rectus muscle causes an abnormal inward deviation of one eye on attempted gaze. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excrete: To get rid of waste from the body. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU]
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Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Exotropia: A form of ocular misalignment where the visual axes diverge inappropriately. For example, medial rectus muscle weakness may produce this condition as the affected eye will deviate laterally upon attempted forward gaze. An exotropia occurs due to the relatively unopposed force exerted on the eye by the lateral rectus muscle, which pulls the eye in an outward direction. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extraocular: External to or outside of the eye. [NIH] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fasciculation: A small local contraction of muscles, visible through the skin, representing a spontaneous discharge of a number of fibres innervated by a single motor nerve filament. [EU]
Fasciitis: Inflammation of the fascia. There are three major types: 1) Eosinophilic fasciitis, an inflammatory reaction with eosinophilia, producing hard thickened skin with an orangepeel configuration suggestive of scleroderma and considered by some a variant of scleroderma; 2) Necrotizing fasciitis, a serious fulminating infection (usually by a beta
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hemolytic Streptococcus) causing extensive necrosis of superficial fascia; 3) Nodular/Pseudosarcomatous/Proliferative fasciitis, characterized by a rapid growth of fibroblasts with mononuclear inflammatory cells and proliferating capillaries in soft tissue, often the forearm; it is not malignant but is sometimes mistaken for fibrosarcoma. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Febrile: Pertaining to or characterized by fever. [EU] Fecal Incontinence: Failure of voluntary control of the anal sphincters, with involuntary passage of feces and flatus. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibula: The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flaccid: Weak, lax and soft. [EU] Flatus: Gas passed through the rectum. [NIH]
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Flexor: Muscles which flex a joint. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescence Polarization: Measurement of the polarization of fluorescent light from solutions or microscopic specimens. It is used to provide information concerning molecular size, shape, and conformation, molecular anisotropy, electronic energy transfer, molecular interaction, including dye and coenzyme binding, and the antigen-antibody reaction. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Free Radical Scavengers: Substances that influence the course of a chemical reaction by ready combination with free radicals. Among other effects, this combining activity protects pancreatic islets against damage by cytokines and prevents myocardial and pulmonary perfusion injuries. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Gait: Manner or style of walking. [NIH] Galactosides: Glycosides formed by the reaction of the hydroxyl group on the anomeric carbon atom of galactose with an alcohol to form an acetal. They include both alpha- and beta-galactosides. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH]
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Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]
Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH] Genetic Screening: Searching a population or individuals for persons possessing certain genotypes or karyotypes that: (1) are already associated with disease or predispose to disease; (2) may lead to disease in their descendants; or (3) produce other variations not known to be associated with disease. Genetic screening may be directed toward identifying phenotypic expression of genetic traits. It includes prenatal genetic screening. [NIH] Genetic transcription: The process by which the genetic information encoded in the gene, represented as a linear sequence of deoxyribonucleotides, is copied into an exactly complementary sequence of ribonucleotides known as messenger RNA. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH]
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Geriatric: Pertaining to the treatment of the aged. [EU] Gingival Hyperplasia: A pathological increase in the depth of the gingival crevice surrounding a tooth at the gum margin. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Gluten Sensitive Enteropathy: A general term that refers to celiac disease and dermatitis herpetiformis. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights. [NIH] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH]
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Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Gonadal: Pertaining to a gonad. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]
Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Handicap: A handicap occurs as a result of disability, but disability does not always constitute a handicap. A handicap may be said to exist when a disability causes a substantial and continuing reduction in a person's capacity to function socially and vocationally. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH]
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Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatomegaly: Enlargement of the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
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Heterotropia: One in which the angle of squint remains relatively unaltered on conjugate movement of the eyes. [NIH] Hindlimb Suspension: Technique for limiting use, activity, or movement by immobilizing or restraining animal by suspending from hindlimbs or tails. This immobilization is used to simulate some effects of reduced gravity and study weightlessness physiology. [NIH] Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]
Homeobox: Distinctive sequence of DNA bases. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydration: Combining with water. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperkalaemia: Pathology: an abnormally high concentration of potassium in the blood. [EU]
Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in
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the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertonia: Or hypertony n, pl. hypertonias or hypertonies : hypertonicity. n. Pathology: increased rigidity, tension and spasticity of the muscles. [EU] Hypertrichosis: Localized or generalized excess hair. The concept does not include hirsutism, which is excess hair in females and children with an adult male pattern of distribution. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypochlorous Acid: HClO. An oxyacid of chlorine containing monovalent chlorine that acts as an oxidizing or reducing agent. [NIH] Hypogammaglobulinemia: The most common primary immunodeficiency in which antibody production is deficient. [NIH] Hypoglycemia: Abnormally low blood sugar [NIH] Hypokalaemia: Abnormally low potassium concentration in the blood; it may result from potassium loss by renal secretion or by the gastrointestinal route, as by vomiting or diarrhoea. It may be manifested clinically by neuromuscular disorders ranging from weakness to paralysis, by electrocardiographic abnormalities (depression of the T wave and elevation of the U wave), by renal disease, and by gastrointestinal disorders. [EU] Hypokalemic Periodic Paralysis: Loss or impairment of muscle function or sensation. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypotonia: A condition of diminished tone of the skeletal muscles; diminished resistance of muscles to passive stretching. [EU] Hypoventilation: A reduction in the amount of air entering the pulmonary alveoli. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Hysterectomy: Excision of the uterus. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
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Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunomodulator: New type of drugs mainly using biotechnological methods. Treatment of cancer. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Immunotoxin: An antibody linked to a toxic substance. Some immmunotoxins can bind to cancer cells and kill them. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incisional: The removal of a sample of tissue for examination under a microscope. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU]
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Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infectious Mononucleosis: A common, acute infection usually caused by the Epstein-Barr virus (Human herpesvirus 4). There is an increase in mononuclear white blood cells and other atypical lymphocytes, generalized lymphadenopathy, splenomegaly, and occasionally hepatomegaly with hepatitis. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insufflation: The act of blowing a powder, vapor, or gas into any body cavity for experimental, diagnostic, or therapeutic purposes. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility.
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[NIH]
Intercostal: Situated between the ribs. [EU] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intrinsic Factor: A glycoprotein secreted by the cells of the gastric glands that is required for the absorption of vitamin B 12. Deficiency of intrinsic factor results in pernicious anemia. [NIH]
Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic
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neurotransmitter receptors are not included. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ipsilateral: Having to do with the same side of the body. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isometric Contraction: Muscular contractions characterized by increase in tension without change in length. [NIH] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]
Karyotypes: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetic: Pertaining to or producing motion. [EU] Knee Injuries: Injuries to the knee or the knee joint. [NIH] Kyphosis: A deformity of the spine characterized by extensive flexion. [NIH] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Lacrimal: Pertaining to the tears. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH]
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Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laryngeal: Having to do with the larynx. [NIH] Laryngectomy: Total or partial excision of the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH]
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Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low Back Pain: Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous sprains and strains; intervertebral disk displacement; and other conditions. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]
Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lung volume: The amount of air the lungs hold. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells
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that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Macroglia: A type of neuroglia composed of astrocytes. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malformation: A morphologic developmental process. [EU]
defect
resulting
from
an
intrinsically
abnormal
Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant Hyperthermia: Rapid and excessive rise of temperature accompanied by muscular rigidity following general anesthesia. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Masticatory: 1. subserving or pertaining to mastication; affecting the muscles of mastication. 2. a remedy to be chewed but not swallowed. [EU] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median Nerve: A major nerve of the upper extremity. In humans, the fibers of the median nerve originate in the lower cervical and upper thoracic spinal cord (usually C6 to T1), travel via the brachial plexus, and supply sensory and motor innervation to parts of the forearm and hand. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU]
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Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megalencephaly: A condition in which there is an abnormally large, heavy, and usually malfunctioning brain. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Metabolic acidosis: (met-ah-BOL-ik as-id-O-sis): A condition in which the blood is too acidic. It may be caused by severe illness or sepsis (bacteria in the bloodstream). [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the
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body to another. [NIH] Methoxsalen: A naturally occurring furocoumarin compound found in several species of plants, including Psoralea corylifolia. It is a photoactive substance that forms DNA adducts in the presence of ultraviolet A irradiation. [NIH] Methylprednisolone: (6 alpha,11 beta)-11,17,21-Trihydroxy-6-methylpregna-1,4-diene-3,2dione. A prednisolone derivative which has pharmacological actions similar to prednisolone. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mixed Connective Tissue Disease: A syndrome with overlapping clinical features of systemic lupus erythematosus, scleroderma, polymyositis, and Raynaud's phenomenon. The disease is differentially characterized by high serum titers of antibodies to ribonucleasesensitive extractable (saline soluble) nuclear antigen and a "speckled" epidermal nuclear staining pattern on direct immunofluorescence. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH]
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Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single zygote, as opposed to chimerism in which the different cell populations are derived from more than one zygote. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor Cortex: Area of the frontal lobe concerned with primary motor control. It lies anterior to the central sulcus. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Motor Neurons: Neurons which activate muscle cells. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle Hypertonia: Abnormal increase in skeletal or smooth muscle tone. Skeletal muscle hypertonicity may be associated with pyramidal tract lesions or basal ganglia diseases. [NIH]
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Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSIN. More than a dozen accessary proteins exist including troponin, tropomyosin, and dystrophin. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myositis: Inflammation of a voluntary muscle. [EU] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU]
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Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Blockade: The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. [NIH] Neuromuscular Diseases: A general term encompassing lower motor neuron disease; peripheral nervous system diseases; and certain muscular diseases. Manifestations include muscle weakness; fasciculation; muscle atrophy; spasm; myokymia; muscle hypertonia, myalgias, and musclehypotonia. [NIH] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH]
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Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Night Blindness: Anomaly of vision in which there is a pronounced inadequacy or complete absence of dark-adaptation. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Envelope: The membrane system of the cell nucleus that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (nuclear pore). [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH]
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Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Octreotide: A potent, long-acting somatostatin octapeptide analog which has a wide range of physiological actions. It inhibits growth hormone secretion, is effective in the treatment of hormone-secreting tumors from various organs, and has beneficial effects in the management of many pathological states including diabetes mellitus, orthostatic hypertension, hyperinsulinism, hypergastrinemia, and small bowel fistula. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odynophagia: A painful condition of the esophagus. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmologic: Pertaining to ophthalmology (= the branch of medicine dealing with the eye). [EU] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Ophthalmoplegia: Paralysis of one or more of the ocular muscles due to disorders of the eye muscles, neuromuscular junction, supporting soft tissue, tendons, or innervation to the muscles. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU]
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Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteodystrophy: Defective bone formation. [EU] Osteomalacia: A condition marked by softening of the bones (due to impaired mineralization, with excess accumulation of osteoid), with pain, tenderness, muscular weakness, anorexia, and loss of weight, resulting from deficiency of vitamin D and calcium. [EU]
Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overactive bladder: A condition in which the patient experiences two or all three of the following conditions: [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH]
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Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Paresthesia: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. [NIH] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH]
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Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Performance status: A measure of how well a patient is able to perform ordinary tasks and carry out daily activities. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Perivascular: Situated around a vessel. [EU] Pernicious anemia: A type of anemia (low red blood cell count) caused by the body's inability to absorb vitamin B12. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity
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increases and below it acidity increases. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photopheresis: A process in which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (methoxsalen) and ultraviolet light - a procedure known as PUVA therapy. Photopheresis is at present a standard therapy for advanced cutaneous T-cell lymphoma; it shows promise in the treatment of autoimmune diseases. [NIH] Physical Endurance: The time span between the beginning of physical activity by an individual and the termination because of exhaustion. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Phytotoxin: A substance which is toxic for plants. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]
Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected
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to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymyalgia Rheumatica: A syndrome in the elderly characterized by proximal joint and muscle pain, high erythrocyte sedimentation rate, and a self-limiting course. Pain is usually accompanied by evidence of an inflammatory reaction. Women are affected twice as commonly as men and Caucasians more frequently than other groups. The condition is frequently associated with temporal arteritis and some theories pose the possibility that the two diseases arise from a single etiology or even that they are the same entity. [NIH] Polyneuritis: Inflammation of several peripheral nerves at the same time. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Positive pressure ventilation: Provision of oxygen under pressure by a mechanical respirator. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of
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the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Power Plants: Units that convert some form of energy into electrical energy, such as hydroelectric or steam-generating stations, diesel-electric engines in locomotives, or nuclear power plants. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoperative: Preceding an operation. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the
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treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Progeria: An abnormal congenital condition characterized by premature aging in children, where all the changes of cell senescence occur. It is manifested by premature greying, hair loss, hearing loss, cataracts, arthritis,osteoporosis, diabetes mellitus, atrophy of subcutaneous fat, skeletal hypoplasia, and accelerated atherosclerosis. Many affected individuals develop malignant tumors, especially sarcomas. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolapse: The protrusion of an organ or part of an organ into a natural or artificial orifice. [NIH]
Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proprioception: The mechanism involved in the self-regulation of posture and movement through stimuli originating in the receptors imbedded in the joints, tendons, muscles, and labyrinth. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostatectomy: Complete or partial surgical removal of the prostate. Three primary
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approaches are commonly employed: suprapubic - removal through an incision above the pubis and through the urinary bladder; retropubic - as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Alveoli: Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between
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alveolar air and pulmonary capillary blood takes place. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Pyruvate Dehydrogenase Complex: An organized assembly of three kinds of enzymes; catalyzes the oxidative decarboxylation of pyruvate. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radicular: Having the character of or relating to a radicle or root. [NIH] Radiculopathy: Disease involving a spinal nerve root (see spinal nerve roots) which may
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result from compression related to intervertebral disk displacement; spinal cord injuries; spinal diseases; and other conditions. Clinical manifestations include radicular pain, weakness, and sensory loss referable to structures innervated by the involved nerve root. [NIH]
Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral
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mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractive Errors: Deviations from the average or standard indices of refraction of the eye through its dioptric or refractive apparatus. [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renal tubular acidosis: A rare disorder in which structures in the kidney that filter the blood are impaired, producing using that is more acid than normal. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH]
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Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory Muscles: These include the muscles of the diaphragm and the intercostal muscles. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retraction: 1. The act of drawing back; the condition of being drawn back. 2. Distal movement of teeth, usually accomplished with an orthodontic appliance. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retropubic: A potential space between the urinary bladder and the symphisis and body of the pubis. [NIH]
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Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by myoglobinuria. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Ricin: A protein phytotoxin from the seeds of Ricinus communis, the castor oil plant. It agglutinates cells, is proteolytic, and causes lethal inflammation and hemorrhage if taken internally. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Riluzole: A glutamate antagonist that has reported anticonvulsant activity. It has been shown to prolong the survival of patients with amyotrophic lateral sclerosis and has been approved in the United States to treat patients with ALS. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] S-1: A drug that is being studied for its ability to enhance the effectiveness of fluorouracil and prevent gastrointestinal side effects caused by fluorouracil. It belongs to the family of drugs called anitmetabolites. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salvage Therapy: A therapeutic approach, involving chemotherapy, radiation therapy, or
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surgery, after initial regimens have failed to lead to improvement in a patient's condition. Salvage therapy is most often used for neoplastic diseases. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoid: A cutaneus lesion occurring as a manifestation of sarcoidosis. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcolemma: The plasma membrane of a smooth, striated, or cardiac muscle fiber. [NIH] Sarcomere: The repeating structural unit of a striated muscle fiber. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scoliosis: A lateral curvature of the spine. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a
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gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Senility: Old age; the physical and mental deterioration associated with old age. [EU] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [NIH] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH]
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Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sharpness: The apparent blurring of the border between two adjacent areas of a radiograph having different optical densities. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU]
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Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Space Flight: Travel beyond the earth's atmosphere. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrin: A high molecular weight (220-250 kDa) water-soluble protein which can be extracted from erythrocyte ghosts in low ionic strength buffers. The protein contains no lipids or carbohydrates, is the predominant species of peripheral erythrocyte membrane proteins, and exists as a fibrous coating on the inner, cytoplasmic surface of the membrane. [NIH]
Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Ischemia: Reduced blood flow to the spinal cord which is supplied by the anterior spinal artery and the paired posterior spinal arteries. This condition may be associated with arteriosclerosis, trauma, emboli, diseases of the aorta, and other disorders. Prolonged ischemia may lead to infarction of spinal cord tissue. [NIH] Spinal Nerve Roots: The paired bundles of nerve fibers entering and leaving the spinal cord at each segment. The dorsal and ventral nerve roots join to form the mixed segmental spinal
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nerves. The dorsal roots are generally afferent, formed by the central projections of the spinal (dorsal root) ganglia sensory cells, and the ventral roots efferent, comprising the axons of spinal motor and autonomic preganglionic neurons. There are, however, some exceptions to this afferent/efferent rule. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Splint: A rigid appliance used for the immobilization of a part or for the correction of deformity. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprains and Strains: A collective term for muscle and ligament injuries without dislocation or fracture. A sprain is a joint injury in which some of the fibers of a supporting ligament are ruptured but the continuity of the ligament remains intact. A strain is an overstretching or overexertion of some part of the musculature. [NIH] Sprue: A non febrile tropical disease of uncertain origin. [NIH] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH]
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Strabismus: Deviation of the eye which the patient cannot overcome. The visual axes assume a position relative to each other different from that required by the physiological conditions. The various forms of strabismus are spoken of as tropias, their direction being indicated by the appropriate prefix, as cyclo tropia, esotropia, exotropia, hypertropia, and hypotropia. Called also cast, heterotropia, manifest deviation, and squint. [EU] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supraclavicular: The depression above the clavicle and lateral to the sternomastoid muscle. [NIH]
Supraspinal: Above the spinal column or any spine. [NIH] Sural Nerve: A branch of the tibial nerve which supplies sensory innervation to parts of the lower leg and foot. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH]
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Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. [NIH] Synchrony: The normal physiologic sequencing of atrial and ventricular activation and contraction. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Talus: The second largest of the tarsal bones and occupies the middle and upper part of the tarsus. [NIH] Telecommunications: Transmission of information over distances via electronic means. [NIH]
Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporomandibular Joint Dysfunction Syndrome: A symptom complex consisting of pain, muscle tenderness, clicking in the joint, and limitation or alteration of mandibular movement. The symptoms are subjective and manifested primarily in the masticatory muscles rather than the temporomandibular joint itself. Etiologic factors are uncertain but
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include occlusal dysharmony and psychophysiologic factors. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Tendonitis: Inflammation of tendons attached to the biceps muscle, i. e. the main flexor muscle of the upper arm. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thiamine: 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2methylthiazolium chloride. [NIH]
hydroxyethyl)-4-
Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thoracic: Having to do with the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation,
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contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thymoma: A tumor of the thymus, an organ that is part of the lymphatic system and is located in the chest, behind the breastbone. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Tibia: The second longest bone of the skeleton. It is located on the medial side of the lower leg, articulating with the fibula laterally, the talus distally, and the femur proximally. [NIH] Tibial Nerve: The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory innervation to parts of the calf and foot. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures
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preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Tracheostomy: Surgical formation of an opening into the trachea through the neck, or the opening so created. [NIH] Tracheotomy: Surgical incision of the trachea. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transitional cell carcinoma: A type of cancer that develops in the lining of the bladder, ureter, or renal pelvis. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual,
Dictionary 227
between individuals of the same species, or between individuals of different species. [NIH] Transurethral: Performed through the urethra. [EU] Transurethral resection: Surgery performed with a special instrument inserted through the urethra. Also called TUR. [NIH] Transurethral Resection of Prostate: Resection of the prostate using a cystoscope passed through the urethra. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Univalent: Pertaining to an unpaired chromosome during the zygotene stage of prophase to first metaphase in meiosis. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH]
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Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uterine Prolapse: Downward displacement of the uterus. It is classified in various degrees: in the first degree the cervix is within the vaginal orifice; in the second degree the cervix is outside the orifice; in the third degree the entire uterus is outside the orifice. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]
Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU]
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Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Visual Cortex: Area of the occipital lobe concerned with vision. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Weight-Bearing: The physical state of supporting an applied load. This often refers to the weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to
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treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIVinduced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
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INDEX 9 9-cis retinoic acid, 51, 155 A Abdomen, 155, 164, 192, 194, 205, 206, 215, 221 Abdominal, 73, 115, 155, 175, 205, 206, 215 Aberrant, 9, 15, 26, 155 Ablation, 117, 155 Abscess, 63, 155 Acceptor, 155, 194, 204, 226 Acetylcholine, 9, 31, 43, 48, 49, 54, 57, 155, 157, 168, 202 Acidity, 155, 207 Acidosis, 143, 155 Acne, 115, 141, 155, 215 Acrylamide, 40, 155 Acrylonitrile, 155 Actin, 155, 199, 200, 227 Actinin, 155, 177 Action Potentials, 17, 155 Activities of Daily Living, 10, 17, 47, 54, 116, 155 Acute renal, 63, 155, 187 Acyl, 70, 155 Adaptability, 155, 166 Adaptation, 43, 156, 202, 208 Adduction, 40, 156 Adenocarcinoma, 156, 187 Adenoma, 115, 156 Adenosine, 156, 207 Adenovirus, 9, 156 Adjustment, 18, 43, 156 Adoptive Transfer, 54, 156 Adrenal Cortex, 156, 172, 210 Adrenal Glands, 115, 156, 158 Adrenergic, 156, 158, 160, 176, 180, 212 Adverse Effect, 156, 157, 169, 219 Aerobic, 3, 116, 156, 198 Aerobic Exercise, 116, 156 Aetiology, 111, 156 Afferent, 156, 181, 221 Affinity, 31, 54, 156, 157, 162, 169, 175, 219 Age of Onset, 157, 227 Agonist, 157, 162, 176 Agrin, 9, 48, 157 Airway, 29, 34, 40, 157, 165 Algorithms, 48, 157, 163 Alimentary, 157, 205
Alkaline, 22, 155, 157, 163, 165, 224 Alkaline Phosphatase, 22, 157 Alkaloid, 157, 169, 212 Alleles, 47, 157 Alopecia, 157, 173 Alpha Particles, 157, 212 Alpha-1, 157, 158, 207 Alternative medicine, 122, 157 Alveoli, 157, 175, 228 Amblyopia, 43, 157 Ameliorating, 111, 157 Amelogenesis Imperfecta, 6, 158 Amenorrhea, 158, 159 Amino acid, 34, 50, 158, 159, 161, 173, 181, 185, 206, 208, 211, 216, 218, 222, 224, 226, 227 Amino Acid Sequence, 158, 159, 181 Amitriptyline, 80, 158 Ampulla, 158, 179 Amputation, 115, 158 Amyloid, 85, 158 Amyloidosis, 89, 117, 158 Amyotrophy, 5, 158 Anabolic, 9, 10, 158 Anabolic Steroids, 10, 158 Anal, 26, 158, 179, 182, 195 Analgesic, 158, 169, 194, 212 Analog, 158, 175, 183, 203 Analogous, 158, 226 Anatomical, 158, 167, 178, 190, 198, 217 Androgens, 44, 156, 158, 172 Anemia, 45, 117, 141, 158, 206, 230 Anesthesia, 61, 65, 75, 157, 159, 173, 196, 201 Angiogenesis, 112, 159 Animal model, 13, 15, 25, 26, 33, 50, 52, 56, 159 Anions, 159, 193, 222 Anisotropy, 159, 183 Ankle, 10, 41, 85, 94, 115, 159 Ankle Joint, 41, 85, 159 Anorexia, 5, 88, 159, 204 Anorexia Nervosa, 88, 159 Antagonism, 102, 159, 169 Anterior Cruciate Ligament, 69, 73, 74, 159 Antiallergic, 159, 172 Antibacterial, 159, 220
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Antibiotic, 159, 220 Antibodies, 43, 49, 54, 56, 159, 162, 186, 190, 196, 198, 199, 208 Antibody, 43, 49, 157, 159, 160, 170, 183, 186, 188, 189, 190, 191, 197, 199, 212, 213, 218, 220 Anticholinergic, 158, 160 Anticoagulant, 160, 211 Anticonvulsant, 160, 216 Antifungal, 160, 193 Antigen, 31, 43, 156, 159, 160, 170, 183, 188, 189, 190, 191, 197, 198, 218 Anti-inflammatory, 142, 160, 172, 185, 209 Anti-Inflammatory Agents, 142, 160, 172 Antineoplastic, 45, 160, 172, 173, 183, 229 Antioxidant, 52, 112, 160, 204 Antipsychotic, 160, 169, 201 Antipyretic, 160, 212 Antitussive, 160, 175 Antiviral, 143, 160, 192 Anus, 158, 160, 164, 169 Anxiety, 4, 160 Aorta, 160, 220, 228 Aponeurosis, 42, 160 Apoptosis, 11, 161 Applicability, 55, 161 Aqueous, 161, 174, 178, 188, 194 Arachidonic Acid, 20, 161, 210 Arginase, 11, 161 Arginine, 11, 161, 202 Arterial, 161, 189, 211, 223 Arteries, 160, 161, 164, 172, 198, 220, 225 Arterioles, 161, 164 Arteriosclerosis, 161, 220 Arteritis, 161, 208 Artery, 16, 115, 161, 172, 178, 205, 212, 214, 217, 220 Arthralgia, 142, 161 Arthropathy, 115, 161 Articular, 159, 161, 204 Articulation, 113, 161, 177 Aseptic, 161, 203, 221 Aspartate, 161, 175 Aspergillosis, 161, 193 Assay, 21, 161 Astrocytes, 11, 161, 196, 198 Ataxia, 21, 40, 60, 72, 80, 88, 162, 167, 224 Atrial, 162, 223 Atrophy, 3, 10, 16, 33, 51, 57, 79, 88, 89, 142, 162, 201, 210 Attenuated, 9, 162, 228 Atypical, 162, 169, 191
Auditory, 113, 162 Autoantibodies, 49, 54, 68, 81, 162, 175 Autoantigens, 162 Autoimmune disease, 31, 162, 199, 207 Autonomic, 7, 155, 160, 162, 202, 206, 221 Axonal, 7, 14, 40, 162 Axons, 40, 162, 203, 206, 215, 221 B Babesiosis, 162, 212 Back Injuries, 78, 162 Baclofen, 18, 142, 162 Bacteria, 155, 159, 160, 162, 171, 178, 179, 181, 182, 184, 195, 197, 198, 220, 226, 228 Bacterial Physiology, 156, 162 Bactericidal, 162, 180 Bacteriophage, 162, 226 Barium, 116, 163, 180 Barium swallow, 116, 163, 180 Basal Ganglia, 160, 162, 163, 199 Basal Ganglia Diseases, 162, 163, 199 Basement Membrane, 163, 181, 193 Bed Rest, 27, 38, 163 Benign, 61, 115, 156, 163, 201, 213 Beta-Galactosidase, 32, 163 Beta-pleated, 158, 163 Bilateral, 7, 163, 215 Bile, 106, 163, 183, 193, 194, 221 Bilirubin, 163, 188 Biochemical, 9, 13, 39, 47, 50, 54, 104, 157, 163, 186, 204, 218 Biomechanics, 30, 163 Biopsy, 7, 8, 22, 23, 24, 87, 142, 163, 206 Biopsy specimen, 7, 163 Biosynthesis, 161, 163, 218 Biotechnology, 57, 122, 135, 163 Biotransformation, 40, 163 Bladder, 65, 124, 164, 170, 190, 199, 210, 211, 214, 215, 226, 227, 228 Blastomycosis, 164, 193 Blood Coagulation, 164, 165, 224 Blood Glucose, 119, 164, 187, 191 Blood pressure, 4, 5, 62, 141, 164, 189, 199, 219 Blood vessel, 112, 159, 164, 166, 167, 179, 187, 193, 195, 196, 206, 219, 222, 224, 228 Body Composition, 25, 44, 51, 53, 116, 164 Body Fluids, 164, 177, 219 Body Mass Index, 5, 164, 204 Bone Density, 5, 36, 37, 38, 164 Bone Marrow, 36, 37, 38, 164, 173, 184, 190, 195, 196, 199, 219, 222, 230 Bone scan, 164, 217
233
Bowel, 3, 123, 124, 158, 164, 172, 191, 192, 203, 206, 221 Bowel Movement, 123, 164, 172, 221 Brace, 115, 164 Brachytherapy, 164, 192, 212 Bradykinin, 164, 202 Brain Stem, 165, 167 Bronchitis, 165, 168 Bronchodilator, 15, 165 Bulbar, 81, 165 Burns, 9, 165 Burns, Electric, 165 C Cachexia, 5, 165 Calcinosis, 117, 165 Calcium, 3, 68, 99, 117, 123, 141, 165, 170, 204, 205, 224, 227 Calculi, 165, 186 Calpain, 26, 33, 165 Carbimazole, 83, 165 Carbohydrate, 45, 165, 172, 185, 186, 208 Carbon Dioxide, 165, 174, 182, 184, 214 Carcinogenic, 165, 191, 210, 221 Carcinoma, 19, 98, 105, 115, 165 Cardiac, 19, 23, 35, 39, 50, 62, 165, 168, 175, 180, 184, 200, 212, 217, 221 Cardiomyopathy, 5, 21, 22, 34, 39, 70, 89, 165 Cardiopulmonary, 31, 66, 165 Cardiorespiratory, 156, 166 Cardiovascular, 4, 5, 166, 218 Carnitine, 45, 62, 67, 70, 102, 103, 104, 166 Carotene, 166, 215 Carpal Tunnel Syndrome, 115, 117, 166 Case report, 61, 75, 79, 83, 84, 86, 101, 166 Castor Oil, 166, 216 Catalytic Domain, 39, 166 Cataracts, 34, 39, 86, 141, 166, 210 Caudal, 166, 209 Causal, 166, 179, 218 Celiac Disease, 86, 124, 125, 166, 185 Cell Adhesion, 54, 166 Cell Adhesion Molecules, 54, 166 Cell Death, 11, 52, 161, 166, 200 Cell Differentiation, 31, 166 Cell Division, 162, 166, 174, 186, 197, 198, 208, 210 Cell membrane, 13, 34, 166, 183, 207 Cell proliferation, 28, 161, 166 Cell Respiration, 166, 198, 214 Central Nervous System, 12, 155, 167, 169, 177, 183, 185, 198, 199, 203, 218
Centrifugation, 167, 223 Cerebellar, 35, 60, 89, 162, 167, 214, 227 Cerebellar Diseases, 162, 167, 227 Cerebellum, 35, 167, 214 Cerebral, 10, 11, 18, 35, 64, 162, 163, 165, 167, 180, 182, 183, 220, 223 Cerebral Cortex, 11, 35, 162, 167, 182 Cerebral hemispheres, 163, 165, 167, 223 Cerebral Palsy, 10, 64, 167, 220 Cerebrospinal, 7, 167 Cerebrospinal fluid, 7, 167 Cerebrovascular, 116, 163, 167, 224 Cerebrum, 35, 167, 223 Cervical, 63, 79, 96, 167, 196 Cervix, 167, 228 Character, 167, 174, 185, 212 Chemotherapy, 19, 53, 167, 216 Chin, 167, 197 Chlorine, 167, 189 Cholera, 168, 218 Cholesterol, 163, 168, 221 Cholinergic, 34, 158, 160, 168 Chorioretinitis, 168, 215 Choroid, 168, 215 Chromatin, 161, 168 Chromosomal, 58, 168, 199, 217 Chromosome, 22, 56, 168, 171, 193, 194, 217, 227 Chronic Disease, 12, 165, 168 Chronic Obstructive Pulmonary Disease, 15, 17, 66, 67, 82, 90, 93, 103, 168 Chronic Progressive External Ophthalmoplegia, 80, 168 Chronic renal, 63, 68, 168 Ciliary, 110, 168 Ciliary Neurotrophic Factor, 111, 168 Cinchona, 168, 212 CIS, 168, 215 Clathrin, 34, 168, 169, 179 Clathrin-Coated Vesicles, 34, 168 Clavicle, 168, 222 Cleave, 34, 168 Clinical Medicine, 169, 209 Clinical trial, 8, 11, 28, 33, 47, 55, 101, 135, 169, 172, 173, 176, 205, 211, 213 Cloning, 163, 169 Clozapine, 93, 169 Cluster Analysis, 24, 169 Coated Vesicles, 168, 169, 179 Codeine, 169, 175 Coenzyme, 70, 169, 183 Cofactor, 169, 211, 224
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Cohort Studies, 169, 179 Colchicine, 75, 92, 169 Colitis, 169, 191 Collagen, 158, 163, 169, 182, 208 Colon, 103, 169, 191, 194 Communis, 166, 170, 216 Complement, 170, 193 Complementary and alternative medicine, 101, 107, 170 Complementary medicine, 101, 170 Compliance, 29, 54, 72, 170 Computational Biology, 135, 170 Computed tomography, 164, 170, 171, 217 Computer Systems, 55, 170 Computerized axial tomography, 29, 170, 171, 217 Computerized tomography, 170, 171 Concentric, 171, 202 Concomitant, 7, 10, 21, 171 Conduction, 7, 39, 171, 201 Cone, 72, 171 Confounding, 51, 171 Confusion, 171, 201, 227 Congenita, 63, 171, 212 Conjugated, 43, 171, 173 Conjugation, 164, 171 Conjunctiva, 171 Conjunctivitis, 142, 171 Connective Tissue, 117, 142, 164, 169, 171, 182, 183, 195, 206, 216, 222, 223, 224 Connective Tissue Cells, 171 Consciousness, 158, 171, 174, 176, 211 Constipation, 123, 160, 171 Constitutional, 171, 200, 215 Constriction, 171, 193, 217 Contamination, 8, 172 Continence, 124, 172 Contractility, 9, 31, 172 Contracture, 41, 172 Contraindications, ii, 172 Contralateral, 20, 172, 203, 214 Control group, 17, 18, 53, 172, 210, 213 Controlled study, 17, 27, 45, 63, 172 Convalescence, 38, 172 Coordination, 167, 172, 199 Coronary, 16, 20, 115, 172, 198 Coronary Thrombosis, 172, 198 Cortex, 35, 157, 172, 204 Cortical, 35, 157, 172, 180, 224 Corticosteroid, 47, 71, 172, 209, 221 Cortisol, 115, 172 Cortisone, 172, 209
Cranial, 87, 167, 172, 181, 203, 206 Craniomandibular Disorders, 101, 172 Creatine, 16, 72, 91, 98, 99, 104, 173 Creatine Kinase, 72, 173 Creatinine, 19, 22, 173 Critical Care, 29, 64, 71, 75, 77, 82, 84, 173 Critical Illness, 9, 173 Cross-Sectional Studies, 173, 179 Curare, 61, 173, 200 Curative, 173, 216, 224 Cutaneous, 65, 164, 173, 205, 207 Cyclic, 165, 173, 186, 202 Cyclophosphamide, 111, 173 Cyclosporine, 141, 173 Cysteine, 15, 26, 40, 165, 173 Cystine, 173 Cytochrome, 58, 59, 173 Cytogenetics, 174, 217 Cytokine, 25, 49, 54, 174 Cytoplasm, 11, 161, 166, 174, 186, 199, 200, 202, 216, 223 Cytoskeletal Proteins, 165, 168, 174, 177 Cytoskeleton, 23, 46, 174 D Dantrolene, 64, 174 Data Collection, 53, 55, 174 Decarboxylation, 174, 212 Decompression, 73, 174 Decompression Sickness, 174 Degenerative, 12, 14, 174, 187, 204 Deletion, 16, 26, 57, 58, 60, 111, 161, 174 Delivery of Health Care, 174, 186 Dementia, 5, 160, 174 Dendrites, 174, 201 Density, 22, 25, 45, 164, 167, 175, 203, 220 Dental Care, 140, 175 Dentition, 123, 175 Deprivation, 12, 157, 175 Dermatitis, 175, 185 Dermatitis Herpetiformis, 175, 185 Desmin, 46, 175 Dextromethorphan, 110, 175 Diabetes Mellitus, 5, 21, 51, 175, 185, 187, 203, 210 Diabetic Ketoacidosis, 92, 175 Diabetic Retinopathy, 5, 175 Diagnostic procedure, 109, 122, 175 Dialyzer, 175, 187 Diaphragm, 33, 41, 46, 175, 215 Diarrhoea, 175, 189 Diastolic, 175, 189 Dietitian, 143, 175
235
Digestion, 157, 163, 164, 175, 192, 194, 206, 221, 228 Digestive tract, 175, 219 Diphtheria, 43, 175 Direct, iii, 10, 13, 15, 18, 28, 30, 43, 54, 55, 112, 127, 169, 176, 195, 198, 209, 212, 214, 223 Discrete, 15, 176, 224 Disinfectant, 176, 180 Disposition, 40, 176 Dissociation, 156, 176 Distal, 7, 14, 40, 55, 83, 85, 162, 176, 206, 215 Dizziness, 62, 176, 228 Dopamine, 160, 169, 176, 202 Dorsal, 18, 176, 208, 220, 221 Dorsum, 176 Dose-dependent, 18, 176, 230 Double-blind, 17, 28, 45, 54, 176 Double-blinded, 54, 176 Drive, ii, vi, 41, 89, 97, 123, 176, 194 Drug Interactions, 129, 140, 176 Drug Tolerance, 177, 225 Duct, 158, 177, 216, 221 Duodenum, 163, 177, 179, 221 Dwarfism, 6, 177 Dyes, 158, 177 Dynamometer, 72, 177 Dysarthria, 21, 177 Dysphagia, 92, 116, 177 Dyspnea, 67, 71, 89, 177 Dyspnoea, 83, 177 Dystrophic, 23, 25, 31, 110, 177 Dystrophin, 9, 22, 23, 24, 31, 46, 60, 93, 102, 177, 200 Dystrophy, 5, 22, 23, 24, 26, 31, 39, 46, 47, 56, 72, 80, 106, 140, 177 E Edema, 125, 167, 175, 177 Effector, 54, 155, 170, 177 Efferent, 43, 177, 181, 199, 221 Efficacy, 4, 9, 16, 17, 19, 27, 177 Elastic, 41, 177, 185, 220 Electrolyte, 71, 128, 172, 177, 198, 209, 219 Electromyography, 30, 33, 142, 177 Electrons, 160, 177, 193, 196, 204, 212, 213 Electrophoresis, 155, 178 Electrophysiological, 28, 74, 178 Elementary Particles, 177, 178, 196, 202, 211 Emboli, 178, 220 Embryo, 166, 178, 190
Emphysema, 168, 178 Emulsion, 178, 182 Enamel, 6, 158, 178 Encephalitis, 78, 178 Encephalitis, Viral, 178 Encephalopathy, 70, 178 Endemic, 168, 178, 221 Endocrine Glands, 178, 205 Endocytosis, 34, 178 Endogenous, 162, 165, 176, 178, 179 Endorphins, 179, 202 Endoscope, 179 Endoscopic, 117, 179 Endoscopy, 116, 179 Endosomes, 168, 178, 179 Endothelial cell, 112, 179, 224 Endothelium, 179, 202 Endothelium-derived, 179, 202 Endotoxic, 179, 194 Endotracheal intubation, 41, 179 End-stage renal, 168, 179 Enkephalins, 179, 202 Environmental Health, 29, 134, 136, 179 Enzymatic, 39, 40, 52, 158, 165, 166, 170, 179, 215 Eosinophilia, 179, 181 Epidemic, 179, 221 Epidemiologic Studies, 36, 37, 179 Epidermal, 179, 198 Epidural, 75, 179 Epinephrine, 156, 176, 180, 202 Epithelial, 19, 34, 156, 180, 193 Epithelial Cells, 34, 180, 193 Epithelium, 32, 163, 179, 180, 184, 193 Ergometer, 14, 180 Erythrocytes, 158, 162, 164, 165, 180 Esophageal, 116, 180 Esophageal Manometry, 116, 180 Esophageal Motility Disorders, 116, 180 Esophagram, 163, 180 Esophagus, 163, 175, 180, 195, 203, 214, 221 Esotropia, 180, 222 Ethanol, 117, 180 Eukaryotic Cells, 174, 180, 203, 227 Evacuation, 171, 180 Excitability, 180, 212 Excitation, 174, 180, 202 Excitatory, 162, 180, 185 Excrete, 180, 214 Exhaustion, 159, 180, 207 Exogenous, 9, 163, 178, 180, 184, 227
236
Muscle Weakness
Exon, 35, 52, 72, 181 Exotropia, 181, 222 Expiration, 181, 214 Expiratory, 64, 69, 81, 181 Extensor, 117, 181 External-beam radiation, 181, 212 Extracellular, 11, 23, 46, 158, 161, 171, 178, 181, 182, 219, 224 Extracellular Matrix, 23, 46, 171, 181, 182 Extracellular Space, 181 Extracorporeal, 87, 181, 207 Extraocular, 43, 81, 168, 181 Extremity, 7, 17, 18, 29, 30, 58, 66, 93, 115, 181, 196, 217 Eye Infections, 156, 181 Eye Movements, 59, 181 F Facial, 6, 69, 113, 123, 140, 181, 205 Facial Expression, 181 Facial Nerve, 123, 181, 205 Family Planning, 135, 181 Fasciculation, 181, 201 Fasciitis, 101, 181 Fat, 45, 93, 102, 115, 161, 164, 166, 172, 178, 182, 193, 194, 199, 204, 210, 216, 219, 227 Fatigue, 17, 18, 20, 27, 45, 49, 50, 53, 71, 79, 82, 89, 92, 117, 140, 182, 187 Febrile, 182, 221 Fecal Incontinence, 103, 182, 190 Feces, 171, 182, 221 Femoral, 94, 182 Femur, 159, 182, 225 Fetus, 182, 209, 228 Fibroblasts, 70, 171, 182 Fibrosarcoma, 182 Fibrosis, 82, 172, 182, 217 Fibula, 159, 182, 225 Fissure, 6, 170, 182 Fistula, 182, 203 Fixation, 69, 182 Flaccid, 34, 182 Flatus, 182, 184 Flexor, 11, 42, 181, 183, 224 Fluorescence, 25, 183 Fluorescence Polarization, 25, 183 Fluorouracil, 183, 216 Fold, 182, 183 Forearm, 164, 182, 183, 196 Fossa, 167, 183 Fovea, 182, 183 Fractionation, 9, 183, 223 Free Radical Scavengers, 21, 183
Free Radicals, 20, 39, 112, 160, 176, 183 Frontal Lobe, 183, 199 G Gait, 10, 17, 18, 20, 167, 183 Galactosides, 163, 183 Gallbladder, 155, 183 Gamma Rays, 183, 212, 213 Ganglia, 155, 163, 183, 201, 206, 221 Gangrenous, 183, 218 Gap Junctions, 183, 223 Gas, 68, 165, 167, 174, 182, 184, 188, 191, 202, 211, 212, 215, 228 Gas exchange, 184, 211, 215, 228 Gastric, 59, 166, 180, 184, 192, 206 Gastric Acid, 180, 184 Gastric Juices, 184, 206 Gastric Mucosa, 59, 184 Gastrin, 184, 188 Gastrointestinal, 70, 165, 180, 184, 189, 216, 218, 220, 222 Gastrointestinal tract, 180, 184, 218, 220 Gene Expression, 23, 24, 184 Gene Targeting, 26, 184 Gene Therapy, 25, 156, 184 Genetic Counseling, 142, 184 Genetic Screening, 21, 184 Genetic transcription, 184, 210 Genetics, 24, 25, 58, 60, 125, 171, 174, 184 Genotype, 184, 207 Geriatric, 5, 185 Gingival Hyperplasia, 141, 185 Gland, 115, 123, 156, 172, 185, 195, 196, 205, 207, 210, 218, 221, 225 Glomerular, 185, 214 Glucocorticoid, 3, 51, 185, 209 Glucose, 21, 45, 164, 175, 185, 187, 191, 207, 217 Glucose Intolerance, 175, 185 Glucose tolerance, 21, 185 Glucose Tolerance Test, 185 Glutamate, 175, 185, 216 Glutamic Acid, 185, 202 Glutathione Peroxidase, 185, 218 Gluten, 125, 166, 185 Gluten Sensitive Enteropathy, 125, 185 Glycine, 158, 185, 202, 218 Glycols, 185, 188 Glycolysis, 24, 185 Glycoprotein, 22, 23, 31, 185, 192, 193, 224 Glycosylation, 52, 186 Gonadal, 186, 221 Gout, 117, 169, 186
237
Governing Board, 186, 209 Grade, 186 Grading, 123, 186 Graft, 79, 186, 190 Graft Rejection, 186, 190 Grafting, 186, 190 Granulocytes, 186, 200, 229 Gravis, 6, 31, 47, 49, 54, 66, 74, 81, 103, 110, 116, 140, 186 Growth factors, 186, 198 Guanylate Cyclase, 186, 202 H Handicap, 51, 186 Haptens, 157, 186 Health Behavior, 12, 186 Health Care Costs, 44, 186, 187 Health Expenditures, 186, 187 Health Status, 186, 187 Heart attack, 143, 187 Heart failure, 20, 71, 187 Heartbeat, 143, 187 Heme, 163, 173, 187 Hemiparesis, 74, 115, 187 Hemodialysis, 6, 7, 10, 70, 85, 103, 175, 187 Hemoglobin, 158, 180, 187 Hemoglobinopathies, 184, 187 Hemolytic, 182, 187 Hemorrhage, 187, 216, 222, 229 Hepatic, 70, 185, 187 Hepatitis, 187, 191 Hepatocellular, 86, 187 Hepatocellular carcinoma, 86, 187 Hepatomegaly, 187, 191 Hereditary, 21, 110, 142, 158, 186, 187, 215 Heredity, 184, 187 Heterogeneity, 14, 22, 26, 51, 157, 187 Heterotropia, 188, 222 Hindlimb Suspension, 39, 188 Hirsutism, 115, 188, 189 Homeobox, 39, 188 Homeostasis, 31, 188 Homologous, 50, 157, 184, 188, 223 Hormonal, 45, 115, 162, 172, 188 Hormone, 28, 78, 172, 177, 180, 184, 188, 191, 203, 210, 216, 220, 224, 225 Hormone Replacement Therapy, 78, 188 Hybrid, 52, 188 Hydration, 155, 188 Hydrogen, 155, 165, 185, 188, 194, 199, 202, 204, 206, 211, 222 Hydrogen Peroxide, 185, 188, 194, 222 Hydrolysis, 161, 163, 164, 188, 208, 211
Hydroxides, 188 Hydroxyl Radical, 33, 188 Hydroxyproline, 158, 169, 188 Hyperaemia, 171, 188 Hyperbilirubinemia, 62, 188, 193 Hyperglycemia, 47, 188 Hyperkalaemia, 65, 92, 188 Hyperplasia, 115, 117, 188 Hypersensitivity, 189, 216 Hypertension, 5, 47, 189, 203, 225 Hyperthyroidism, 28, 91, 189 Hypertonia, 41, 189 Hypertrichosis, 188, 189 Hypertrophy, 27, 188, 189 Hyperuricemia, 186, 189 Hypochlorous Acid, 33, 189 Hypogammaglobulinemia, 76, 77, 189 Hypoglycemia, 62, 70, 189 Hypokalaemia, 92, 189 Hypokalemic Periodic Paralysis, 59, 76, 96, 189 Hypoplasia, 158, 189, 210 Hypothyroidism, 71, 91, 102, 189 Hypotonia, 50, 93, 167, 189 Hypoventilation, 9, 60, 189 Hypoxia, 111, 189, 224 Hypoxic, 111, 189 Hysterectomy, 124, 189 I Idiopathic, 19, 189, 217 Imidazole, 165, 189 Immune response, 31, 160, 162, 172, 186, 189, 190, 222, 229 Immune Sera, 190 Immune system, 125, 189, 190, 196, 199, 229 Immunization, 49, 54, 156, 190, 210 Immunodeficiency, 142, 143, 189, 190 Immunofluorescence, 56, 190, 198 Immunogenic, 190, 194 Immunoglobulin, 68, 159, 190, 199 Immunologic, 34, 156, 190, 213, 230 Immunology, 49, 84, 156, 190 Immunomodulator, 49, 190 Immunosuppressive, 173, 185, 190 Immunosuppressive therapy, 190 Immunotherapy, 7, 156, 190 Immunotoxin, 43, 190 Impairment, 10, 17, 27, 29, 30, 32, 74, 79, 81, 94, 162, 181, 189, 190, 197 Implant radiation, 190, 192, 212 Implantation, 18, 190
238
Muscle Weakness
In vitro, 9, 27, 33, 46, 52, 184, 190, 218, 225 In vivo, 9, 15, 18, 27, 32, 33, 41, 44, 46, 49, 52, 54, 112, 184, 190, 224 Incision, 190, 192, 211, 226 Incisional, 43, 190 Incontinence, 8, 124, 190 Induction, 158, 160, 190 Infancy, 87, 191, 216 Infantile, 23, 76, 77, 191 Infarction, 172, 191, 198, 214, 220 Infectious Mononucleosis, 84, 191 Inflammatory bowel disease, 3, 191 Ingestion, 84, 93, 102, 105, 185, 191, 208, 224 Inhalation, 191, 208 Initiation, 41, 191, 210 Innervation, 181, 191, 196, 203, 217, 222, 225 Insight, 22, 34, 44, 191 Insufflation, 67, 191 Insulator, 191, 199 Insulin, 5, 17, 43, 45, 111, 116, 175, 185, 191, 193, 227 Insulin-dependent diabetes mellitus, 191 Insulin-like, 111, 191 Intensive Care, 41, 75, 77, 84, 92, 191 Intercostal, 192, 215 Interferon, 54, 192 Interferon-alpha, 192 Intermittent, 72, 94, 192, 206 Internal radiation, 192, 212 Interstitial, 15, 164, 181, 192, 214 Intervertebral, 12, 192, 195, 213 Intervertebral Disk Displacement, 192, 195, 213 Intestinal, 166, 185, 192, 196 Intestinal Mucosa, 166, 192 Intestine, 164, 192, 194 Intoxication, 40, 192, 229 Intracellular, 46, 48, 52, 168, 191, 192, 202, 209, 218 Intramuscular, 25, 40, 192, 205 Intrathecal, 18, 75, 192 Intravenous, 7, 62, 68, 192, 205 Intrinsic, 7, 20, 30, 66, 157, 163, 192 Intrinsic Factor, 30, 192 Intubation, 192 Invasive, 29, 32, 40, 47, 117, 192, 196 Involuntary, 124, 163, 182, 192, 200, 214, 219, 220 Ion Channels, 162, 192, 223 Ions, 155, 176, 177, 188, 193
Ipsilateral, 20, 193, 214 Iris, 193, 212 Ischemia, 112, 162, 193, 214, 220 Isoenzyme, 173, 193 Isometric Contraction, 28, 76, 193 Itraconazole, 102, 193 J Jaundice, 188, 193 K Karyotypes, 184, 193 Kb, 58, 134, 193 Ketone Bodies, 175, 193 Ketosis, 175, 193 Kidney Disease, 6, 10, 103, 104, 134, 141, 143, 193 Kinetic, 193 Knee Injuries, 36, 37, 38, 193 Kyphosis, 12, 193 L Labyrinth, 193, 210 Lacrimal, 181, 193 Laminin, 31, 163, 193 Large Intestine, 175, 192, 194, 213, 219 Laryngeal, 80, 194 Laryngectomy, 114, 194 Larynx, 194, 226 Latent, 194, 209 Lens, 166, 171, 194 Lesion, 5, 35, 164, 194, 195, 217, 227 Lethal, 24, 50, 162, 194, 216 Lethargy, 189, 194 Leukemia, 184, 194 Leukocytes, 164, 186, 192, 194, 199 Leukopenia, 194, 230 Levorphanol, 175, 194 Libido, 158, 194 Life Expectancy, 5, 194 Ligament, 44, 159, 194, 210, 221 Ligands, 166, 194 Ligation, 7, 20, 194 Linkage, 14, 22, 46, 194 Lipid, 20, 34, 47, 59, 112, 161, 191, 194, 199, 204, 227 Lipid A, 20, 194 Lipid Peroxidation, 194, 204 Lipopolysaccharides, 194 Liver, 141, 155, 158, 161, 163, 165, 166, 173, 178, 182, 183, 185, 187, 194, 195, 209, 217, 227 Liver scan, 195, 217 Localization, 9, 12, 39, 48, 195
239
Localized, 8, 155, 158, 175, 177, 182, 188, 189, 191, 193, 195, 204, 208, 217, 224, 227 Locomotion, 30, 195, 208 Locomotor, 102, 195 Longitudinal study, 25, 195 Loop, 69, 107, 195 Low Back Pain, 73, 96, 106, 195 Lower Esophageal Sphincter, 180, 195 Lucida, 193, 195 Luciferase, 52, 195 Lumbar, 192, 195, 217, 225 Lung volume, 61, 68, 73, 195 Lymph, 167, 179, 191, 195, 196, 217 Lymph node, 167, 195, 196, 217 Lymphadenopathy, 191, 195 Lymphatic, 179, 191, 195, 219, 221, 225 Lymphatic system, 195, 219, 221, 225 Lymphocyte, 160, 196, 197 Lymphoid, 159, 196 Lymphoma, 196, 207 M Macroglia, 196, 198 Magnetic Resonance Imaging, 54, 87, 196, 217 Magnetic Resonance Spectroscopy, 87, 196 Maintenance therapy, 88, 196 Malabsorption, 125, 166, 196 Malformation, 9, 196 Malignant, 5, 60, 64, 65, 123, 156, 160, 182, 196, 201, 210, 213 Malignant Hyperthermia, 60, 64, 65, 196 Malignant tumor, 196, 210 Malnutrition, 45, 162, 165, 196, 200 Mandible, 123, 167, 196 Manifest, 162, 196, 222 Mastication, 196 Masticatory, 6, 140, 172, 196, 223 Mastitis, 196, 218 Mechanical ventilation, 33, 40, 48, 83, 88, 196 Medial, 32, 73, 159, 161, 181, 196, 203, 225 Median Nerve, 166, 196 Mediate, 11, 31, 34, 35, 40, 48, 166, 176, 196 Mediator, 35, 197, 218 Medical Records, 7, 197 Medical Staff, 176, 197 MEDLINE, 135, 197 Medullary, 32, 175, 197 Megalencephaly, 67, 197 Meiosis, 197, 223, 227 Memory, 159, 174, 197
Meninges, 167, 197 Meningitis, 193, 197 Mental, iv, 8, 58, 69, 134, 136, 167, 171, 174, 176, 182, 189, 197, 210, 211, 217, 218, 227 Mental Disorders, 197, 210, 211 Mental Health, iv, 8, 134, 136, 197, 210, 211 Mental Retardation, 58, 69, 197 Mentors, 29, 197 Metabolic acidosis, 175, 197 Metabolic disorder, 186, 197 Metabolite, 164, 197 Metastasis, 166, 197, 201 Metastatic, 53, 83, 197 Methoxsalen, 198, 207 Methylprednisolone, 86, 198 MI, 68, 82, 87, 153, 198 Microbe, 198, 226 Microbiology, 49, 156, 162, 198 Microglia, 11, 161, 198 Milliliter, 164, 198 Mineralization, 198, 204 Mineralocorticoids, 156, 172, 198 Mitochondria, 11, 15, 16, 72, 143, 198, 203 Mitosis, 161, 198 Mixed Connective Tissue Disease, 104, 198 Mobility, 30, 53, 74, 198 Mobilization, 9, 198 Modification, 94, 116, 158, 198, 212, 230 Molecule, 160, 169, 170, 176, 177, 179, 180, 187, 188, 199, 204, 207, 208, 213, 226, 228 Monitor, 19, 54, 173, 199, 202 Monoclonal, 43, 54, 199, 212 Monoclonal antibodies, 54, 199 Monocytes, 194, 199, 200 Mononuclear, 182, 191, 199 Monotherapy, 63, 199 Morphological, 27, 42, 178, 199 Morphology, 40, 42, 199 Mosaicism, 93, 199 Motor Activity, 45, 199 Motor Cortex, 35, 199, 214 Motor nerve, 55, 181, 199, 200, 206 Motor Neurons, 11, 16, 28, 52, 55, 78, 111, 112, 142, 199 Mucosa, 184, 199, 222 Multiple sclerosis, 64, 103, 105, 199 Muscle Contraction, 23, 28, 50, 52, 177, 199 Muscle Fibers, 46, 50, 56, 59, 81, 157, 199, 200, 227
240
Muscle Weakness
Muscle Hypertonia, 199, 201 Muscle Proteins, 33, 200 Muscle relaxant, 174, 200 Muscle Relaxation, 200, 201 Muscular Atrophy, 52, 55, 67, 200 Muscular Dystrophies, 9, 23, 56, 62, 110, 177, 200 Mutagenesis, 26, 200 Mutagens, 200 Myalgia, 75, 200 Myasthenia, 6, 31, 47, 49, 54, 66, 74, 81, 103, 110, 116, 140, 200 Myelin, 199, 200, 218 Myeloid Cells, 38, 200 Myocarditis, 176, 200 Myocardium, 39, 198, 200 Myofibrils, 46, 50, 56, 165, 177, 200 Myopathy, 5, 7, 8, 22, 33, 39, 50, 58, 61, 62, 67, 71, 72, 75, 78, 86, 87, 93, 104, 116, 200 Myosin, 52, 56, 199, 200, 227 Myositis, 79, 142, 200 Myotonia, 63, 80, 86, 200, 212 Myotonic Dystrophy, 34, 39, 61, 200 N Nausea, 160, 193, 200, 227 Necrosis, 161, 182, 191, 198, 200, 214, 216, 217, 218 Neonatal, 40, 74, 200 Neoplasms, 156, 160, 201, 213, 224 Neoplastic, 196, 201, 217 Nephrology, 4, 92, 201 Nephropathy, 193, 201 Nerve Endings, 201, 223 Nervous System, 12, 156, 167, 168, 197, 201, 202, 206, 223 Neural, 41, 74, 156, 158, 198, 201 Neuroblastoma, 92, 201 Neuroleptic, 160, 169, 201 Neuromuscular Blockade, 84, 201 Neuromuscular Diseases, 110, 201 Neuromuscular Junction, 9, 40, 48, 110, 155, 201, 203 Neuronal, 11, 24, 111, 112, 168, 201, 206 Neurons, 11, 16, 17, 111, 112, 142, 174, 180, 183, 199, 200, 201, 221, 223 Neuropathy, 5, 7, 47, 59, 111, 112, 115, 119, 158, 201, 206 Neuropeptides, 165, 201 Neuroretinitis, 202, 215 Neurotoxic, 40, 202 Neurotoxicity, 40, 102, 104, 175, 202
Neurotransmitter, 40, 48, 155, 156, 158, 165, 176, 185, 193, 202, 220, 222, 223 Neutralization, 54, 202 Neutrons, 157, 202, 212 Neutrophil, 39, 202 Night Blindness, 125, 202, 215 Nitric Oxide, 11, 38, 49, 202 Nitrogen, 157, 158, 173, 174, 182, 202 Norepinephrine, 156, 158, 176, 202 Nuclear, 34, 47, 51, 163, 171, 178, 180, 183, 198, 200, 202, 209, 215 Nuclear Envelope, 47, 202 Nuclear Pore, 202 Nuclei, 11, 23, 35, 157, 171, 178, 184, 196, 198, 202, 203, 211 Nucleic acid, 200, 202, 203, 212, 230 Nucleus, 21, 35, 161, 163, 168, 173, 174, 178, 180, 183, 192, 197, 199, 202, 203, 210, 211, 224 O Octreotide, 83, 203 Ocular, 47, 59, 96, 180, 181, 203 Odynophagia, 116, 203 Opacity, 166, 175, 203 Operon, 203, 210 Ophthalmologic, 5, 43, 203 Ophthalmology, 43, 72, 81, 182, 203 Ophthalmoplegia, 58, 60, 203 Opsin, 203, 215, 216 Optic Chiasm, 203 Optic Nerve, 73, 157, 202, 203, 215 Organ Culture, 125, 203, 225 Organelles, 167, 168, 174, 199, 203 Orgasm, 124, 203 Orthostatic, 160, 203 Ossification, 204, 216 Osteoarthritis, 17, 19, 32, 36, 37, 42, 44, 77, 80, 87, 95, 106, 204 Osteodystrophy, 117, 204 Osteomalacia, 59, 71, 77, 204 Osteomyelitis, 63, 204 Osteoporosis, 3, 5, 6, 12, 25, 47, 51, 204, 210 Otitis, 5, 204 Ovary, 204, 222 Overactive bladder, 124, 204 Overweight, 36, 37, 38, 98, 204 Oxidation, 20, 33, 155, 160, 164, 173, 175, 185, 194, 204 Oxidation-Reduction, 164, 204 Oxidative Stress, 16, 24, 52, 112, 204 Oxygen Consumption, 112, 204, 214
241
Oxygenation, 88, 174, 204 P Palliative, 204, 224 Palsy, 18, 66, 81, 204 Pancreas, 155, 191, 205, 220 Pancreatic, 166, 183, 205 Paralysis, 16, 34, 35, 70, 79, 82, 84, 95, 96, 102, 165, 168, 173, 180, 187, 189, 203, 205, 220 Parathyroid, 117, 205, 216, 224 Parathyroid Glands, 117, 205, 216 Parathyroid hormone, 117, 205 Parenteral, 9, 62, 85, 92, 205 Parenteral Nutrition, 62, 85, 205 Paresthesia, 75, 205 Parotid, 123, 205, 217 Partial remission, 205, 214 Particle, 205, 220, 226 Pathogenesis, 12, 15, 20, 21, 26, 31, 35, 44, 52, 95, 112, 205 Pathologic, 81, 155, 161, 163, 165, 172, 188, 189, 205, 209 Pathologic Processes, 161, 205 Pathophysiology, 9, 22, 39, 50, 56, 71, 117, 205 Patient Education, 116, 120, 140, 143, 148, 150, 153, 205 Patient Selection, 18, 205 Pelvic, 4, 8, 124, 205, 210 Pelvis, 155, 195, 205, 227, 228 Pepsin, 205, 206 Peptic, 116, 206 Peptide, 15, 27, 158, 206, 208, 211, 225 Perception, 171, 206, 217 Percutaneous, 117, 206 Performance status, 45, 206 Perfusion, 183, 189, 206 Peripheral blood, 192, 206, 207 Peripheral Nerves, 110, 206, 208, 221 Peripheral Nervous System, 177, 179, 201, 202, 204, 206, 220, 222 Peripheral Nervous System Diseases, 201, 206 Peripheral Neuropathy, 5, 47, 206 Peritoneal, 77, 90, 206 Peritoneal Cavity, 206 Peritoneal Dialysis, 77, 90, 206 Peritoneum, 206, 215 Perivascular, 198, 206 Pernicious anemia, 192, 206 PH, 29, 87, 164, 206 Phagocytosis, 198, 207
Phallic, 182, 207 Pharmacists, 5, 207 Pharmacokinetic, 19, 207 Pharmacologic, 34, 43, 159, 207, 226 Phenotype, 14, 22, 39, 47, 207 Phospholipids, 182, 207 Phosphorus, 141, 165, 205, 207 Phosphorylase, 165, 207 Phosphorylated, 169, 207 Phosphorylation, 48, 207 Photopheresis, 87, 207 Physical Endurance, 16, 207 Physical Examination, 116, 142, 207 Physiologic, 39, 54, 157, 163, 207, 213, 223, 227 Physiology, 5, 33, 35, 48, 50, 55, 64, 67, 68, 76, 123, 178, 188, 201, 207 Phytotoxin, 207, 216 Pigments, 166, 193, 207, 215 Pilot study, 32, 207 Pituitary Gland, 172, 207 Plants, 157, 165, 185, 198, 199, 202, 207, 208, 209, 217, 226 Plasma, 7, 23, 40, 46, 115, 159, 166, 177, 185, 187, 198, 208, 217 Plasma cells, 159, 208 Plasticity, 31, 208 Platelet Aggregation, 202, 208, 224 Platelets, 165, 202, 208, 218 Platinum, 195, 208 Pneumonia, 172, 208 Point Mutation, 5, 72, 93, 208 Poisoning, 34, 102, 103, 192, 200, 208 Polymerase, 208, 210 Polymorphic, 14, 22, 208 Polymyalgia Rheumatica, 60, 208 Polyneuritis, 176, 208 Polypeptide, 158, 169, 208, 220, 230 Polysaccharide, 160, 208 Positive pressure ventilation, 29, 208 Posterior, 115, 158, 162, 167, 168, 176, 193, 205, 208, 220 Postmenopausal, 204, 209 Postnatal, 50, 209, 221 Postoperative, 115, 123, 209 Postoperative Complications, 123, 209 Postsynaptic, 48, 209, 223 Post-synaptic, 49 Post-synaptic, 209 Post-synaptic, 223 Post-translational, 47, 52, 209
242
Muscle Weakness
Potassium, 72, 99, 100, 128, 143, 188, 189, 198, 209, 212 Potentiating, 158, 209 Power Plants, 143, 209 Practice Guidelines, 136, 209 Precursor, 47, 161, 173, 176, 177, 179, 202, 209 Predisposition, 12, 209 Prednisolone, 198, 209 Prednisone, 7, 47, 91, 141, 209 Prenatal, 178, 184, 209 Preoperative, 44, 209 Presynaptic, 40, 48, 201, 202, 209, 223 Prevalence, 5, 7, 14, 21, 83, 115, 209 Primary endpoint, 45, 209 Primary Prevention, 20, 210 Progeria, 47, 210 Progesterone, 210, 221 Progression, 4, 7, 11, 16, 19, 28, 32, 33, 36, 37, 38, 49, 55, 142, 159, 210 Projection, 202, 203, 210, 214 Prolapse, 124, 210 Promoter, 111, 210 Promotor, 111, 112, 210 Prone, 73, 210 Prophase, 210, 223, 227 Prophylaxis, 64, 210, 215 Proprioception, 20, 32, 210 Prospective study, 54, 83, 96, 195, 210 Prostaglandins, 161, 210 Prostate, 210, 227 Prostatectomy, 124, 210 Protease, 26, 211 Protein C, 7, 27, 35, 43, 157, 158, 162, 168, 169, 200, 211, 220, 227 Protein Kinases, 39, 211 Protein S, 27, 52, 163, 211, 216 Proteolytic, 33, 39, 47, 157, 170, 211, 216 Protocol, 47, 49, 53, 211 Protons, 157, 188, 196, 211, 212 Pruritus, 117, 211 Psychiatric, 5, 115, 197, 211 Psychiatry, 60, 66, 67, 74, 76, 80, 81, 85, 87, 93, 182, 211, 228 Psychic, 194, 197, 211 Psychoactive, 211, 229 Puberty, 21, 211 Public Health, 36, 37, 38, 44, 136, 211 Public Policy, 135, 211 Publishing, 57, 211 Pulmonary, 12, 15, 29, 85, 86, 164, 167, 183, 189, 211, 212, 215, 228
Pulmonary Alveoli, 189, 211 Pulmonary Artery, 164, 212, 228 Pulmonary Ventilation, 212, 215 Pulse, 86, 119, 199, 212 Pupil, 81, 212 Purines, 212, 218 Pyogenic, 204, 212, 218 Pyrimidines, 212, 218 Pyruvate Dehydrogenase Complex, 88, 212 Q Quality of Life, 16, 17, 19, 29, 45, 52, 53, 54, 68, 212 Quinidine, 93, 168, 212 Quinine, 142, 168, 212 R Radiation, 123, 178, 181, 183, 192, 212, 213, 216, 217, 229 Radiation therapy, 123, 181, 183, 192, 212, 216 Radicular, 212, 213 Radiculopathy, 63, 212 Radioactive, 164, 188, 190, 192, 195, 199, 202, 212, 213, 217 Radiography, 20, 44, 213 Radiolabeled, 212, 213 Radiological, 12, 82, 206, 213 Radiology, 213 Radiotherapy, 164, 212, 213 Random Allocation, 213 Randomization, 28, 213 Randomized, 10, 17, 19, 27, 29, 44, 45, 47, 53, 54, 177, 213 Randomized clinical trial, 10, 47, 53, 213 Reagent, 167, 195, 213 Receptor, 31, 34, 43, 46, 48, 49, 51, 54, 57, 111, 112, 156, 160, 169, 171, 175, 176, 213, 218 Recombinant, 27, 54, 213, 228 Recombination, 171, 184, 213 Rectum, 103, 160, 164, 169, 175, 182, 184, 190, 191, 194, 210, 213 Recurrence, 123, 213 Red Nucleus, 162, 213 Refer, 1, 170, 176, 179, 182, 195, 201, 202, 214, 226 Reflex, 41, 94, 181, 214 Reflux, 180, 214 Refraction, 159, 214, 220 Refractive Errors, 157, 214 Regeneration, 27, 43, 54, 157, 214 Regimen, 177, 214
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Regurgitation, 180, 214 Reliability, 68, 214 Remission, 33, 196, 213, 214 Renal failure, 214 Renal pelvis, 214, 226 Renal tubular, 92, 214 Renal tubular acidosis, 92, 214 Reperfusion, 112, 214 Reperfusion Injury, 214 Respiration, 71, 91, 98, 105, 165, 173, 199, 214 Respirator, 196, 208, 215 Respiratory failure, 29, 46, 47, 88, 215 Respiratory Muscles, 33, 215 Respiratory Physiology, 58, 68, 73, 74, 78, 88, 215, 228 Respiratory System, 72, 215 Response rate, 19, 215 Retina, 168, 175, 194, 202, 203, 215, 216 Retinal, 5, 171, 175, 203, 215, 216, 229 Retinal Ganglion Cells, 203, 215 Retinitis, 72, 215 Retinitis Pigmentosa, 72, 215 Retinoids, 155, 215 Retinol, 215, 216 Retraction, 111, 112, 215 Retroperitoneal, 115, 156, 215 Retropubic, 211, 215 Retrospective, 7, 216 Retroviral vector, 184, 216 Rhabdomyolysis, 63, 216 Rheumatism, 216 Rheumatoid, 17, 72, 93, 98, 104, 216 Rheumatoid arthritis, 17, 72, 93, 98, 104, 216 Rhinitis, 216, 218 Rhodopsin, 203, 215, 216 Ribonuclease, 198, 216 Ribosome, 216, 226 Ricin, 43, 216 Rickets, 77, 216 Riluzole, 28, 110, 216 Risk factor, 5, 12, 36, 37, 38, 96, 115, 179, 210, 216 Risk patient, 53, 216 Rod, 25, 50, 72, 216 S S-1, 18, 216 Saline, 198, 216 Saliva, 216 Salivary, 123, 181, 216 Salivary glands, 123, 181, 216
Salvage Therapy, 19, 216 Saponins, 217, 221 Sarcoid, 75, 217 Sarcoidosis, 217 Sarcolemma, 56, 217 Sarcomere, 13, 46, 217 Satellite, 27, 43, 217 Scans, 8, 217 Schizoid, 217, 229 Schizophrenia, 217, 229 Schizotypal Personality Disorder, 217, 229 Sciatic Nerve, 217, 225 Scleroderma, 87, 90, 181, 198, 217 Sclerosis, 11, 15, 16, 28, 29, 55, 69, 101, 106, 110, 111, 112, 116, 142, 161, 199, 216, 217 Scoliosis, 104, 217 Screening, 5, 14, 21, 51, 52, 169, 184, 217 Secretion, 45, 172, 177, 189, 191, 198, 203, 217, 218, 228 Secretory, 218, 223 Sedative, 158, 169, 218 Sedentary, 123, 218 Sedimentation, 167, 208, 218 Segmental, 30, 91, 218, 220 Segmentation, 218 Selenium, 85, 100, 128, 218 Self Care, 155, 218 Senescence, 24, 210, 218 Senile, 204, 218 Senility, 51, 218 Sensory loss, 14, 21, 63, 213, 218, 224 Septicaemia, 218 Sequencing, 218, 223 Sequester, 218, 223 Serine, 39, 218 Serology, 142, 218 Serotonin, 62, 158, 160, 169, 202, 218 Serotypes, 34, 218 Serum, 28, 45, 54, 72, 91, 117, 156, 170, 173, 190, 198, 218 Sex Characteristics, 158, 211, 219, 224 Sharpness, 219, 229 Shock, 24, 219, 227 Side effect, 10, 47, 53, 54, 127, 140, 141, 156, 160, 173, 189, 216, 219, 226 Signs and Symptoms, 4, 21, 111, 214, 219 Skeleton, 56, 155, 182, 219, 225 Skull, 219, 223 Small intestine, 125, 177, 188, 192, 219 Smoking Cessation, 5, 219 Smooth muscle, 31, 165, 171, 199, 219, 220, 222
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Muscle Weakness
Sneezing, 124, 219 Social Environment, 212, 219 Social Work, 5, 219 Sodium, 64, 186, 198, 212, 219 Soft tissue, 17, 164, 182, 203, 219 Solid tumor, 159, 219 Solvent, 180, 219 Somatic, 93, 197, 198, 206, 220 Somatostatin, 203, 220 Sound wave, 171, 220 Space Flight, 33, 220 Spasm, 116, 201, 220, 224 Spastic, 11, 18, 41, 220 Spatial disorientation, 176, 220 Specialist, 48, 144, 220 Species, 33, 49, 169, 173, 175, 180, 188, 193, 197, 198, 199, 212, 220, 222, 227, 229 Specificity, 23, 33, 157, 220 Spectrin, 177, 220 Spectrum, 64, 67, 198, 220 Sperm, 158, 168, 220 Sphincter, 116, 194, 220 Spinal Cord Ischemia, 112, 220 Spinal Nerve Roots, 212, 220 Spinal Nerves, 206, 221 Spleen, 158, 195, 196, 217, 221 Splenomegaly, 191, 221 Splint, 164, 221 Sporadic, 11, 221 Sprains and Strains, 195, 221 Sprue, 92, 124, 125, 221 Stabilization, 9, 48, 221 Staging, 217, 221 Standard therapy, 207, 221 Stem Cells, 23, 221 Stenosis, 221, 222 Sterile, 161, 205, 221 Sterility, 173, 221 Steroid, 10, 25, 66, 75, 93, 103, 172, 217, 221 Steroid therapy, 75, 221 Stimulus, 157, 172, 176, 180, 191, 192, 214, 221, 224 Stomach, 141, 155, 175, 180, 184, 185, 188, 193, 195, 200, 205, 206, 214, 219, 221 Stool, 169, 190, 194, 221 Strabismus, 43, 157, 222 Stress, 7, 8, 13, 24, 45, 46, 124, 172, 200, 204, 209, 216, 222 Stricture, 116, 221, 222 Stroke, 35, 41, 87, 93, 112, 114, 115, 116, 134, 222 Stromal, 31, 222
Stromal Cells, 31, 222 Subacute, 7, 40, 191, 222 Subclinical, 191, 222 Subcutaneous, 177, 183, 205, 210, 222 Subspecies, 220, 222 Substance P, 197, 218, 222 Substrate, 166, 222 Superoxide, 16, 110, 222 Superoxide Dismutase, 16, 110, 222 Supplementation, 16, 45, 98, 102, 104, 222 Suppression, 172, 222, 230 Supraclavicular, 115, 222 Supraspinal, 162, 222 Sural Nerve, 7, 222 Survival Rate, 123, 222 Symptomatic, 20, 36, 37, 87, 222 Synapse, 48, 156, 157, 201, 209, 223, 226 Synaptic, 40, 48, 157, 202, 223 Synaptic Transmission, 48, 223 Synaptic Vesicles, 40, 223 Synaptosomes, 40, 223 Synchrony, 41, 223 Synergistic, 25, 54, 223 Systemic lupus erythematosus, 198, 223 Systolic, 189, 223 T Talus, 159, 223, 225 Telecommunications, 170, 223 Telencephalon, 163, 167, 223 Temporal, 18, 24, 36, 94, 208, 223 Temporomandibular Joint Dysfunction Syndrome, 172, 223 Tendon, 42, 117, 170, 224 Tendonitis, 142, 224 Testosterone, 44, 53, 158, 224 Tetanic, 27, 224 Tetanus, 224 Tetany, 205, 224 Thalamic, 162, 224 Thalamic Diseases, 162, 224 Therapeutics, 25, 104, 129, 224 Thiamine, 88, 128, 224 Thigh, 29, 54, 58, 182, 224 Thoracic, 12, 71, 91, 105, 175, 196, 224, 229 Threonine, 218, 224 Threshold, 15, 49, 180, 189, 224 Thrombin, 208, 211, 224 Thrombomodulin, 211, 224 Thrombosis, 211, 222, 224 Thromboxanes, 161, 224 Thymoma, 83, 225 Thymus, 31, 190, 195, 196, 225
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Thyroid, 28, 51, 189, 205, 225 Thyroid Gland, 189, 205, 225 Thyrotropin, 189, 225 Tibia, 159, 182, 225 Tibial Nerve, 40, 217, 222, 225 Tinnitus, 204, 225 Tissue Culture, 28, 225 Tolerance, 45, 50, 155, 185, 225 Tomography, 196, 225 Tone, 31, 113, 180, 189, 199, 225 Tonic, 41, 180, 225 Tonus, 225 Tooth Preparation, 156, 225 Topical, 6, 54, 180, 188, 226 Toxic, iv, 11, 15, 40, 157, 168, 171, 173, 176, 177, 190, 201, 207, 218, 226, 230 Toxicity, 12, 16, 19, 102, 142, 143, 176, 226 Toxicokinetics, 226 Toxicology, 102, 136, 226 Toxin, 34, 43, 94, 176, 179, 224, 225, 226 Trachea, 194, 225, 226 Tracheostomy, 110, 114, 226 Tracheotomy, 28, 226 Transcriptase, 143, 226 Transduction, 15, 39, 226 Transfection, 35, 163, 184, 226 Transfer Factor, 190, 226 Transferases, 186, 226 Transitional cell carcinoma, 65, 226 Translation, 44, 158, 226 Translational, 226 Translocation, 34, 226 Transmitter, 48, 155, 162, 176, 192, 197, 202, 223, 226 Transplantation, 92, 168, 190, 226 Transurethral, 211, 227 Transurethral resection, 211, 227 Transurethral Resection of Prostate, 211, 227 Trauma, 163, 200, 220, 224, 225, 227 Tremor, 67, 114, 227 Triglyceride, 70, 227 Tropomyosin, 200, 227 Troponin, 35, 50, 200, 227 Type 2 diabetes, 4, 5, 227 U Ubiquitin, 33, 227 Ulcer, 227 Ulceration, 7, 227 Ultrasonography, 42, 227 Univalent, 188, 204, 227 Urea, 161, 227
Uremia, 85, 86, 104, 214, 227 Ureter, 214, 226, 227 Urethra, 210, 227, 228 Uric, 186, 189, 212, 227 Urinary, 8, 115, 124, 165, 190, 211, 215, 227, 228 Urine, 124, 164, 172, 173, 190, 193, 214, 227, 228 Uterine Prolapse, 8, 228 Uterus, 124, 167, 189, 210, 228 V Vaccines, 228, 229 Vacuoles, 72, 178, 203, 228 Vagina, 124, 167, 228 Vaginal, 4, 8, 228 Valves, 228 Vascular, 7, 15, 31, 111, 168, 179, 191, 202, 225, 228 Vascular endothelial growth factor, 111, 228 Vasodilators, 202, 228 VE, 18, 228 Vector, 27, 32, 226, 228 Vein, 7, 192, 202, 205, 217, 228 Venous, 211, 228 Ventilation, 29, 33, 41, 83, 228 Ventricle, 212, 223, 228 Ventricular, 223, 228 Venules, 164, 228 Vertebrae, 192, 220, 228 Vertebral, 12, 63, 228 Vertigo, 204, 228 Veterinary Medicine, 135, 229 Villous, 166, 229 Vinca Alkaloids, 229 Vincristine, 102, 104, 229 Viral, 117, 178, 226, 229, 230 Virulence, 162, 226, 229 Virus, 25, 27, 64, 142, 143, 162, 191, 192, 216, 226, 229 Visual Acuity, 21, 229 Visual Cortex, 157, 229 Visual field, 203, 215, 229 Vitreous, 168, 175, 194, 215, 229 Vitreous Hemorrhage, 175, 229 Vitro, 229 Vivo, 54, 229 Volition, 192, 229 W Weight-Bearing, 27, 229 White blood cell, 141, 159, 191, 194, 195, 196, 202, 208, 229
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Muscle Weakness
Windpipe, 179, 225, 229 Withdrawal, 33, 229 Womb, 228, 229 Wound Healing, 115, 166, 229 X Xenograft, 159, 229
X-ray, 20, 29, 54, 163, 164, 170, 171, 180, 183, 202, 212, 213, 217, 229 Y Yeasts, 207, 230 Z Zidovudine, 8, 230 Zygote, 171, 199, 230 Zymogen, 211, 230
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Muscle Weakness
