Lou Gehrig's Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

LOU GEHRIG’S DISEASE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES ...

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LOU

GEHRIG’S DISEASE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

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., 1960Lou Gehrig’s Disease: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84014-8 1. Lou Gehrig’s Disease-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on Lou Gehrig’s disease. 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 LOU GEHRIG’S DISEASE ............................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Lou Gehrig’s Disease..................................................................... 5 E-Journals: PubMed Central ....................................................................................................... 12 The National Library of Medicine: PubMed ................................................................................ 16 CHAPTER 2. ALTERNATIVE MEDICINE AND LOU GEHRIG’S DISEASE ............................................ 33 Overview...................................................................................................................................... 33 National Center for Complementary and Alternative Medicine.................................................. 33 Additional Web Resources ........................................................................................................... 40 General References ....................................................................................................................... 41 CHAPTER 3. DISSERTATIONS ON LOU GEHRIG’S DISEASE .............................................................. 43 Overview...................................................................................................................................... 43 Dissertations on Lou Gehrig’s Disease ........................................................................................ 43 Keeping Current .......................................................................................................................... 43 CHAPTER 4. CLINICAL TRIALS AND LOU GEHRIG’S DISEASE ........................................................ 45 Overview...................................................................................................................................... 45 Recent Trials on Lou Gehrig’s Disease ........................................................................................ 45 Keeping Current on Clinical Trials ............................................................................................. 53 CHAPTER 5. PATENTS ON LOU GEHRIG’S DISEASE......................................................................... 55 Overview...................................................................................................................................... 55 Patents on Lou Gehrig’s Disease ................................................................................................. 55 Patent Applications on Lou Gehrig’s Disease.............................................................................. 61 Keeping Current .......................................................................................................................... 65 CHAPTER 6. BOOKS ON LOU GEHRIG’S DISEASE ............................................................................ 67 Overview...................................................................................................................................... 67 Book Summaries: Federal Agencies.............................................................................................. 67 Book Summaries: Online Booksellers........................................................................................... 68 CHAPTER 7. PERIODICALS AND NEWS ON LOU GEHRIG’S DISEASE .............................................. 69 Overview...................................................................................................................................... 69 News Services and Press Releases................................................................................................ 69 Academic Periodicals covering Lou Gehrig’s Disease.................................................................. 72 CHAPTER 8. RESEARCHING MEDICATIONS ..................................................................................... 73 Overview...................................................................................................................................... 73 U.S. Pharmacopeia....................................................................................................................... 73 Commercial Databases ................................................................................................................. 74 Researching Orphan Drugs ......................................................................................................... 74 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 79 Overview...................................................................................................................................... 79 NIH Guidelines............................................................................................................................ 79 NIH Databases............................................................................................................................. 81 Other Commercial Databases....................................................................................................... 83 APPENDIX B. PATIENT RESOURCES ................................................................................................. 85 Overview...................................................................................................................................... 85 Patient Guideline Sources............................................................................................................ 85 Associations and Lou Gehrig’s Disease ....................................................................................... 91 Finding Associations.................................................................................................................... 92 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 95 Overview...................................................................................................................................... 95 Preparation................................................................................................................................... 95

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Finding a Local Medical Library.................................................................................................. 95 Medical Libraries in the U.S. and Canada ................................................................................... 95 ONLINE GLOSSARIES................................................................................................................ 101 Online Dictionary Directories ................................................................................................... 103 LOU GEHRIG’S DISEASE DICTIONARY............................................................................... 105 INDEX .............................................................................................................................................. 145

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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 Lou Gehrig’s disease 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 Lou Gehrig’s disease, 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 Lou Gehrig’s disease, 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 Lou Gehrig’s disease. 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 Lou Gehrig’s disease, 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 Lou Gehrig’s disease. 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 LOU GEHRIG’S DISEASE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Lou Gehrig’s disease.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and Lou Gehrig’s disease, 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 “Lou Gehrig’s disease” (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: •

Dental Management of Long-Term Amyotrophic Lateral Sclerosis: Case Report Source: SCD. Special Care in Dentistry. 13(6): 241-244. November-December 1993. Summary: This article presents a case report on methods of dental treatment in a young male patient with amyotrophic lateral sclerosis (ALS), a progressive motor neuron disease. This case is unusual in several respects: the early age of onset, the long survival time, and the period of time in which the case was followed in the authors' dental clinic. The report presents aspects of ALS which are of concern to dentistry, as related to clinical care and strategies for effective oral health delivery. The most striking physical effect of ALS relates to function of the breathing muscles. Since the patient may be unable to cough or clear his throat, a reclining position for dental treatment is contraindicated due to the increased risk of aspiration. A hyperactive gag reflex is

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another characteristic symptom of ALS. Successful treatment strategies to reduce the chances of aspiration were keeping the patient NPO for 12 hours prior to dental procedures and keeping instruments from touching soft-tissue surfaces. Several changes were noted about the introduction of enteral feeding. First was a profound decrease in the rate of dental decay. Second, there was an increase in marginal plaque, inflammation, and general intraoral debris. 1 figure. 2 tables. 23 references. (AA-M). •

Amyotrophic Lateral Sclerosis: Lou Gehrig's Disease Source: American Family Physician. 59(6): 1489-1496. March 15, 1999. Contact: American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 906-6000. E-mail: [email protected]. Website: www.aafp.org. Summary: This journal article provides health professionals with information on the pathology, epidemiology, etiology, clinical features, diagnosis, and management of amyotrophic lateral sclerosis (ALS). This progressive neuromuscular disease, commonly called Lou Gehrig's disease in memory of the famous baseball player who died of ALS in 1941, is characterized by weakness, muscle wasting, fasciculations, and increased reflexes. Approximately 30,000 Americans currently have the disease. The annual incidence rate is 1 to 2 cases per 100,000 people. The disease is most commonly diagnosed in middle age and affects more men than women. The etiology of the disease in unknown. Current research is focused on abnormalities of neuronal cell metabolism involving glutamate and the role of potential neurotoxins and neurotrophic factors. ALS usually presents with problems in dexterity or gait resulting from muscle weakness. Difficulty in speaking or swallowing is the initial symptom in the bulbar form of the disease. Over a period of months or years, patients who have ALS develop severe, progressive muscular weakness and other symptoms caused by loss of function in both upper and lower motor neurons. Sphincter control, sensory function, intellectual abilities, and skin integrity are preserved. Patients become completely disabled, often requiring ventilatory support and gastrostomy. Death usually occurs within 5 years of diagnosis and is attributed to respiratory failure or cachexia. Diagnosis of ALS is clinical, and is based on the characteristic signs of progressive weakness, atrophy, fasciculations, and hyperreflexia affecting several regions of the body. The management of ALS is a complex and demanding team effort requiring individualized therapy and continual adaptation of medications and therapies. The only agent currently labeled for the treatment of ALS is riluzole. This drug is believed to decrease glutamate release. Various symptomatic treatments may also be helpful. Spasticity may be relieved by use of baclofen, diazepam, or dantrolene. Physical therapy can help relieve many of the painful symptoms of ALS. Nonsteroidal anti-inflammatory drugs and anticonvulsants may also be helpful. Mechanical suction devices are useful in preventing aspiration of excess saliva. Tricyclic antidepressants are widely used in the treatment of ALS because of their multiple effects. Supportive therapies, including physical, occupational, and speech therapy and nutritional support, also have a crucial role in the care of patients who have ALS. The article includes two illustrative cases. 2 tables and 26 references. (AA-M).

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Olfactory Impairment in Motor Neuron Disease: A Pilot Study Source: Journal of Neurology, Neurosurgery, and Psychiatry. 54(10): 927-928. October 1991. Summary: This journal article reports findings from a pilot study to test the ability of individuals with motor neuron disease to identify smells. Similar deficits have been seen

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in patients with Parkinson's disease, Alzheimer's disease, and Parkinson-dementia complex, which is often associated with motor neuron disease. The author suggests that these diseases may cause destruction of the olfactory pathway, that environmental agents related or unrelated to the development of these disorders may also cause destruction of sensory function, or that dysfunction of the olfactory system may facilitate the development of these neural disorders by making individuals more susceptible to certain environmental agents. 12 references.

Federally Funded Research on Lou Gehrig’s Disease The U.S. Government supports a variety of research studies relating to Lou Gehrig’s disease. 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 Lou Gehrig’s disease. 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 Lou Gehrig’s disease. The following is typical of the type of information found when searching the CRISP database for Lou Gehrig’s disease: •

Project Title: BIOCARBONATE ENHANCES PEROXIDATION OF SOD/ALS MUTANTS Principal Investigator & Institution: Kalyanaraman, Balaraman; Professor/Director; Biophysics; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 31-MAY-2004 Summary: (adapted from applicant's abstract): Proposed research has a long-term goal to unravel the molecular mechanisms by which mutations of Sod1 gene encoding Cu, Zn superoxide dismutase (SOD1) produce selective motor neuron degeneration in amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease. The central hypothesis of this proposal is that bicarbonate anion enhances the peroxidative potential of SOD1 and its mutant variants via generation of a highly potent carbonate anion radical (CO3.-). Specific Aims include demonstration of CO3.- radical generation using purified enzymes; studies on the role of carbonate radical in hydroxylation, oxidation and nitration reactions; characterization of bicarbonate effects on oxidation/nitration reaction catalyzed by spinal cord extracts of transgenic ALS mutant mice and wild type animals. Four major analytical techniques to be used include electron spin resonance spectroscopy (ESR) and spin trapping; HPLC; UV-visible spectroscopy and chemiluminescence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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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Project Title: COPPER HOMEOSTASIS IN YEAST Principal Investigator & Institution: Thiele, Dennis J.; Professor; Biological Chemistry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-APR-1989; Project End 31-MAR-2004 Summary: The trace metal copper is essential for all life forms as a co-factor for many critical cellular enzymes such as cytochrome oxidase, Cu,Zn superoxide dismutase, dopamine beta hydroxylase and ceruloplasmin. However, due to its ability to engage in reactions generating reactive oxygen species that damage nucleic acids, proteins and membranes, Cu is also highly toxic. The importance of maintaining Cu balance is underscored by the existence of severe genetic diseases of Cu homeostasis and by the demonstration that Cu binding proteins are involved in diseases as Lou Gehrig's disease and prion diseases, and implicated in cancer and aging. This proposal describes avenues of investigation, using yeast as a model system, aimed at understanding the molecular mechanisms whereby cells appropriately acquire Cu, regulate the Cu transport process and regulate gene expression in response to changes in cellular Cu status. First, experiments are described to elucidate the topological arrangement of high affinity Cu transporters, localized to the plasma membrane, and to determine the mechanisms whereby these molecules specifically capture extracellular Cu ions and move these redox active metals across the plasma membrane in a highly controlled fashion. Second, experiments are described to understand how yeast cells fine tune the levels of the Ctr1 Cu transporter at the plasma membrane, as a function of environmental cu levels, by signaling events that lead to Cu induced endocytosis. Third, the function and mechanism of action of a novel Cu transport protein in facilitating the assembly of an active Cu transport complex at the plasma membrane will be determined. Fourth, the mechanisms whereby a Cu-sensing transcription factor couples intracellular Cu and iron levels by regulating expression of iron transport genes will be determined. The studies described in this proposal will provide fundamentally important information on the mechanisms whereby all cells maintain normal Cu homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ETIOLOGIC STUDIES ON EMND: AN ANIMAL MODEL FOR ALS Principal Investigator & Institution: Mohammed, Hussni O.; Clinical Sciences; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 28-FEB-2005 Summary: (provided by applicant): Equine motor neuron disease (EMND) is a neurodegenerative disorder of the horse characterized by progressive weakness, fasciculations, muscle wasting, and weight loss. Histopathological findings in the brain stem and spinal cord studies reveal that the weakness and muscle wasting result from degeneration of motor neurons in these tissues. The nature and the distribution of the neurodegenerative changes in EMND are strikingly similar to those reported in human progressive muscular atrophy, a form of amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease. As in ALS, the cause(s) of this disease is not known. The long-term objective of our research is to understand the pathogenesis of this disease so that effective control measures can be recommended to prevent its occurrence. We believe that findings on this equine disorder can help to uncover the causative factor(s) for sporadic ALS. Our epidemiologic studies to date have implicated oxidative stress in the risk of EMND and have suggested that some intrinsic factors, e.g. disruption of the

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blood-brain-barrier, may influence the risk. We hypothesize that the blood-brain barrier (BBB), normally innocuous, can be disrupted as a result of the oxidative stress, exposing the central nervous system to exogenous, highly detrimental substances (i.e. neurotoxic). The proposed studies are aimed to test this hypothesis. We are planning to carry out two randomized trials to evaluate this hypothesis in rats. In the first trial two groups of rats will be identified and allocated randomly to either treatment or control group. The treatment group will receive a diet deficient in vitamin E and the control will receive a normal diet. The two groups will be followed up for a period of time and the permeability of the BBB will be assessed and compared in the two groups. In the second trial the impact of neurotoxic drugs on the risk of neurologic disorder in rats fed diet deficient in antioxidants will be assessed. The treatment group will receive ivermectin and the control group will not. The risk of neurologic disorder will then be assessed in the two groups. In the third hypothesis we will investigate whether the permeability of the BBB is disrupted in horses afflicted with EMND. Data obtained from these pilot studies will represent a major breakthrough towards the understanding of the mechanism of the motor neuron disease and lay the foundation for more thorough investigation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HISTIDYL IMIDAZOLE LIGAND IN METALLOPROTEINS Principal Investigator & Institution: Valentine, Joan S.; Professor; Chemistry and Biochemistry; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-JAN-1980; Project End 31-MAR-2002 Summary: (Adapted from applicant's abstract) Copper containing proteins play important roles in organisms ranging from bacteria and yeast to plants and animals. Three different copper-containing proteins are the focus of this research project. The overall objectives are to understand the properties and biological functions of wild type copper-zinc superoxide dismutases (CuZn SOD), to understand why mutant human CuZn SOD proteins cause familial amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), to understand the properties and biological functions of stellacyanins and the copper binding domains of human blood coagulation factor VIII, and to prepare novel synthetic metalloproteins using the genes for CuZn SOD and stellacyanin as starting points. CuZnSOD is an antioxidant enzyme that catalyzes the disproportionation of superoxide. Approximately 50 different single mutations in human CuZn SOD have individually been linked to an inherited form of amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). Results of transgenic mouse studies point to a toxic gain of function for these mutations rather than a loss of their antioxidant function as the cause of the disease. Human ALS mutant CuZn SODs have been prepared in our laboratory and have been found to have lost several of the properties characteristic of wild type CuZn SOD other than its SOD activity. These properties are highly likely to be essential to CuZnSOD in performing its normal biological functions. Moreover, the loss of these properties in the ALS mutant enzymes will likely prove to be linked to the gain of the new toxic property that is involved in the mechanism of causation of the disease. Preparation and characterization of these human mutant ALS CuZn SOD proteins for the purpose of identifying their disease-causing properties is a major objective of this project. Studies of another copper protein, stellacyanin, are designed to test the hypothesis that this blue copper protein is a cell wall protein that is involved in plant defense mechanisms. Another human protein, blood coagulation factor VIII, is involved in causing hemophilia A. It possesses protein sequences characteristic of blue copper

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binding sites, but no structural information nor characteristics of these sites are yet known. The copper-binding domains of this protein will be expressed, purified, and characterized. A major objective of this research is to understand the role of copper in human coagulation factor VIII and how it is related to the overall function of this protein in the blood clotting process. Finally, new metalloproteins will be designed, based on CuZn SOD and stellacyanin. They will be prepared using site-directed mutagenesis, expressed, and purified and their new properties will be characterized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYDROGEN PEROXIDE & SUPEROXIDE DISMUTASE SPIN TRAPPING EXPERIMENTS Principal Investigator & Institution: Gunther, m; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2001 Summary: Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a fatal condition occurring in midlife where motor neurons degenerate in the spinal cord and motor cortex. One genetic defect in familial ALS (FALS) has now been linked to Sod 1, the gene that encodes the cytosolic CuZnSOD enzyme. Postulated mechanisms for onset and progression of FALS include gain-in-function of Sod 1, i.e., increased peroxidase or hydroxyl radical activity. ESR spin-trapping with oxygen-17 hydrogen peroxide was used to investigate the mechanism of hydroxyl radical adduct of DMPO formation from the SOD and SOD mutants. The relative ratios of oxygen-17 hydroxyl radical adduct of DMPO formed in the Fenton reaction were 90% and 10%, respectively. The reaction of the wild type SOD (WT-SOD) with oxygen-17 hydrogen peroxide in bicarbonate/carbon dioxide buffer yielded 56 +/- 0.47% of oxygen-17 hydroxyl radical adduct of DMPO spin adduct and 44 +/- 0.47% oxygen-16 hydroxyl radical adduct of DMPO. Similar results were obtained from the reaction between FALS SOD mutants and oxygen-17 hydrogen peroxide: oxygen-17 hydroxyl radical adduct of DMPO, 57 +/1.41%, and oxygen-16 hydroxyl radical adduct of DMPO, 43 +/- 1.41% from A4V and 55 +/- 0.82% oxygen-17 hydroxyl radical adduct of DMPO and 45 +/- 0.82% oxygen-16 hydroxyl radical adduct of DMPO from G93A. These results indicate that a significant fraction of hydroxyl radical adduct of DMPO formed during the reaction of SOD and FALS SOD mutants with hydrogen peroxide is derived from the incorporation of oxygen atom from water. We found no evidence for increased peroxidase or hydroxyl radical activity in ALS mutant SOD compared with the WT-SOD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISTIC AND STRUCTURAL BASIS OF AMYLOIDOSIS Principal Investigator & Institution: Gillespie, Joel R.; Biological Sciences; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 01-JUL-2001 Summary: The process of protein aggregation is currently very poorly understood despite the increasing public awareness of protein deposition diseases such as Alzheimer's, trans-missible bovine spongiform encephalopathy (mad cow disease), Huntington's disease, and ALS (Lou Gehrig's disease). The purpose of this proposal is to describe the detailed mechanism of protein aggregation specifically leading to the formation of amyloid fibrils. Knowledge of the mechanism of protein aggregation may facilitate the rational design of therapeutic agents to combat or prevent such diseases. A model aggregation system consisting of three recombiant human immunoglobulin light

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chain (VL) domains will be used to assertain the structure of amyloid fibrils and the mechanism by which they are formed. These objectives will be met using a combination of techniques including site directed mutagenesis, ESI-MS and HPLC/MS/MS, NMR, and TEM (among others). The approaches utilized are designed to give complemetary information that can then be combined to give a complete picture of fibril growth. In vitro inhibitors of amyloid formation and/or fibril elongation will be designed using leads from a combinatorial phage display library. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BASIS OF AMYOTROPHIC LATERAL SCLEROSIS Principal Investigator & Institution: Lo, Terrence P.; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001 Summary: Point mutations in human Cu, Zn superoxide dismutase (HSOD) have been linked to the neurodegenerative disease amyotrophic lateral sclerosis (ALS), also know as Lou Gehrig's disease. ALS is a progressive paralytic disorder resulting from the degeneration of large motor neurons in the brain and spinal cord, and is usually fatal within five years of onset. We are probing the structural basis of this disease by determining the three-dimensional structures of several mutant HSOD's. In conjunction with these structural studies, we are investigating the stability and functional properties of these mutant proteins to fully characterize their role in ALS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF SOD INSTABILITY IN ALS MOTOR NEURON TOXICITY Principal Investigator & Institution: Hayward, Lawrence J.; Neurology; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease) is an age-dependent degenerative disorder of motor neurons characterized by progressive weakness and death within five years after the onset of symptoms. A subset of familial ALS is caused by mutations in Cu/Zn superoxide dismutase (SOD1) that render this antioxidant enzyme toxic by an unknown mechanism. Expression of mutant SOD1 in man or mice causes selective degeneration of motor neurons in the brain and spinal cord. The long-term objectives of this study are to understand how mutant SOD1 kills neurons and to identify novel pathways of cell death that may be relevant to ALS. Aim 1 of this project is to define important biophysical and biochemical characteristics that distinguish mutant from wild type SOD1. Recent studies in our lab indicate that mutant SOD1 enzymes all share an increased tendency to unfold or to lose metal ions when stressed by denaturing influences. Experiments will be performed to (1) define conditions that preferentially destabilize mutant but not normal SOD1, (2) identify factors that alter the dynamics of the SOD1 monomer-dimer equilibrium as measured by analytical ultracentrifugation, and (3) map regions of the protein that are susceptible to proteolytic cleavage or partial unfolding. In Aim 2, the affinities and thermodynamics of metal binding to SOD1 as a function of pH or denaturant will be measured using a novel calorimetric approach. Conditions that alter Cu ion reactivity in mutant SOD1 will also be defined. Aim 3 will employ cell culture models to test hypotheses of mutant SOD1 toxicity that are consistent with the physicochemical findings from Aims 1 and 2. Initial investigations will test whether early lysosomal dysfunction occurs in response to specific stresses in mutant SOD1 -bearing neuroblastoma cells or in organotypic spinal

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cord slice cultures. Future results from Aims 1 and 2 may favor alternative hypotheses of mutant SOD1 toxicity to test in these cellular models and may suggest new therapeutic approaches to evaluate in ALS mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF UBIQUITININ LYSOSOME MEDIATED PROTEOLYSIS Principal Investigator & Institution: Bucci, Mirella; Biological Sciences; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-DEC-2001 Summary: Several diseases have been characterized based on the presence of abnormal protein aggregates found within cells, including Parkinson's disease and Lou Gehrig's disease. Ubiquitin is found conjugated to proteins found within these inclusions. Being a signal for proteasome- mediated degradation, the presence of ubiquitin in these aggregates suggests that either the recognition or the degradation machinery is perturbed in these cells, causing an accumulation of undegraded protein. Another type of protein degradation is that which is mediated by the lysosome, an acidic organelle harboring most of the proteolytic enzymes of the cell. Several pathways exist for proteins to be delivered to the lysosome, including the autophagic pathway. Recently, researchers have begun to identify the first molecular players involved in formation of autophagic vesicles, double-membrane bound vesicles which are transported to lysosomes for ultimate degradation. My goal is to begin to characterize the role of these proteins in degradation of protein and protein complexes during the autophagic pathway. In the first specific aim, I propose that these proteins are involved in an early stage of autophagosome formation, perhaps by recognizing such ill-fated proteins. In the second and third aims, I propose to examine the role of a subset of these proteins in signaling the formation of the autophagic vesicles. This work is designed to begin to understand the basis of the inclusion-forming diseases by examining the critical balance between protein synthesis and protein turnover within cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURE AND FUNCTION OF NUCLEIC ACIDS Principal Investigator & Institution: Tinoco, Ignacio; Professor; Chemistry; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2001; Project Start 01-DEC-1976; Project End 30-NOV-2003 Summary: The long term goal is to be able to deduce a three-dimensional structure for an RNA molecule from the sequence of its bases. Messenger RNA molecules transfer and interpret the genetic information in DNA to produce proteins. Ribosomal RNAs and transfer RNAs are part of the machinery necessary to synthesize the proteins. Errors in RNA processing, in control of messenger RNA translation, and in control of messenger RNA lifetimes are linked to many human diseases, including several neurodegenerative diseases such as Lou Gehrig's disease. In RNA viruses the RNA is both the genetic information, and the messenger for protein synthesis. Thus, naturally occurring RNAs and viral RNAs are outstanding targets for drugs to prevent or cure disease. The overwhelming majority of drug targets up to now have been proteins. Knowledge of the three-dimensional structures of RNAs is crucial to understanding RNA function. The RNA molecules are synthesized in the laboratory by RNA polymerase from a DNA template, using 13C and 15N isotope labeling, if needed. Multidimensional nuclear magnetic resonance spectroscopy of the RNA molecules provides distances between protons, and torsion angles around bonds. Standard bond angles and bond lengths, plus

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the NMR experimental distances and angles, are used in molecular dynamics simulations to obtain coordinates for each atom in the RNA molecule. Representative structural motifs that occur in RNAs are being determined. The thermodynamic stabilities of these motifs (secondary and tertiary structures) relative to the singlestranded molecules are assessed from measured equilibrium concentrations of the different species. This information will lead to improved prediction of RNA structure from sequence alone. RNA structures will help in understanding function, and in controlling the RNA role in viral and genetic diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYNCHROTRON--SUPEROXIDE TOXIN, DE NOVO DESIGNED PEPTIDES

DISMUTASE,

DIPHTHERIA

Principal Investigator & Institution: Hart, P J.; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001 Summary: Amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) is neurodegenerative disorder characterized by the progressive destruction of large motor neurons in the spinal cord and brain. Approximately 10% of ALS-afflicted individuals having the inherited (familial) form of the disease (FALS) display tight genetic linkage between the disorder and a gene encoding a cytosolic Cu/Zn-binding superoxide dismutase (SOD1). We desire to correlate ALS misfunction withCu/ZnSOD structure via crystallographic analysis of human SOD mutants found in FALS patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: X RAY CRYSTALLOGRAPHIC STUDIES--COPPER CHAPERONE LYS7 Principal Investigator & Institution: Lamb, Audrey L.; Biochem/Molecular & Cell Biol; Northwestern University 633 Clark St Evanston, Il 60208 Timing: Fiscal Year 2001; Project Start 01-JUN-1999 Summary: Superoxide dismutase catalyzes the disproportionation of superoxide to hydrogen peroxide and dioxygen. For activity, this exzyme requires one dimetallic Cu,Zn center per subunit. In yeast, the insertion of the copper into superoxide dismutase (Sod1) only occurs in the presence of the copper chaperone protein Lys7. The objective of this proposal is to solve the three dimensional structures of Lys7, with and without the metal ions, and Lys7 complexed with Sod1. In humans, Sod1 has been linked to familial amyotrophic lateral sclerosis (Lou Gehrig's Disease), and a detailed understanding of the mechanism of copper insertion should lead to the development of new therapies for this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: X-RAY STUDIES OF SOD IN AMYOTROPHIC LATERAL SCLEROSIS Principal Investigator & Institution: Hart, P. John.; Associate Professor; Biochemistry; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2001; Project Start 05-MAY-2000; Project End 30-APR-2005 Summary: Eucaryotic copper-zinc superoxide dismutases (CuZnSODs) are 32 kDa homodimeric metalloproteins that catalyze the conversion of superoxide radical to molecular oxygen and hydrogen peroxide. The enzyme is particularly abundant in spinal tissue and red blood cells in mammals. Approximately 60 different single site mutations in human CuZnSOD have individually been linked to an inherited (familial)

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form of amyotrophic lateral sclerosis (FALS or Lou Gehrig's disease). The disease is characterized by progressive paralysis resulting from motor neuron degeneration and death. Trangenic mouse, neuronal cell culture, and in-vitro studies suggest strongly that a copper-mediated toxic gain of function instead of a loss of superoxide disproportionation activity is responsible for disease onset in individuals heterozygous for any one of the FALS CuZnSOD mutations. Many of these human FALS mutants have been prepared in the laboratory and have been found to have aberrant metal binding properties relative to wild type CuZnSOD. The new properties of the FALS mutant proteins will likely be linked to the gain of the toxin function involved in FALS causation. A recently discovered class of molecules termed "copper chaperones for SOD" (CCS) are responsible for sequestering reactive copper ion from the cellular environment and inserting it correctly into newly translated SOD apoprotein. Because the toxic gain of function of FALS mutant SODs appears to be copper-mediated, a search for inhibitors of the copper chaperone may represent a novel therapeutic avenue for FALS. The primary objectives of this proposal are to generate three-dimensional, atomic resolution structural information on the human and yeast FALS mutants and mutant protein analogs, their respective copper chaperones, and their complexes via the wellestablished tools of X-ray diffraction and analytical ultracentrifugation. Specifically, we shall: (1) compare and contrast the FALS structures with normal human CuZnSOD and yeast FALS mutant analog structures. (2) use X- radiation from synchroton sources tuned to copper and zinc absorption edges to determine the location and amount of these ions in the metal binding sites of remetallated and as-isolated FALS CuZnSODs, (3) illuminate the postulated interaction of peroxynitrite with normal and FALS mutant CuZnSOD proteins by determining their structures when exposed to peroxynitrite, (4) determine and analyze the structures of several species of CCS molecules alone and in complex with wild type and FALS mutant CuZnSODs, and elucidate the solution properties of these molecules and their complexes under different conditions using contemporary analytical ultracentrifugation methods. These studies will not only promote understanding of the molecular causes of FALS, but also will provide fundamental information on copper ion homeostasis and trafficking at the level of proteinprotein interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “Lou Gehrig’s disease” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for Lou Gehrig’s disease in the PubMed Central database:

3 4

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

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

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A Gain-Of-Function of an Amyotrophic Lateral Sclerosis-Associated Cu,ZnSuperoxide Dismutase Mutant: An Enhancement of Free Radical Formation Due to a decrease in Km for Hydrogen Peroxide. by Yim MB, Kang J, Yim H, Kwak H, Chock PB, Stadtman ER.; 1996 Jun 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39125

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Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutant. by Williamson TL, Bruijn LI, Zhu Q, Anderson KL, Anderson SD, Julien JP, Cleveland DW.; 1998 Aug 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21390

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Amyotrophic lateral sclerosis: A proposed mechanism. by Okado-Matsumoto A, Fridovich I.; 2002 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124414

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Amyotrophic Lateral Sclerosis: Human Challenge for Neuroscience. by Rowland LP.; 1995 Feb 28; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=42496

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Caspase-1 and -3 are sequentially activated in motor neuron death in Cu,Zn superoxide dismutase-mediated familial amyotrophic lateral sclerosis. by Pasinelli P, Houseweart MK, Brown RH Jr, Cleveland DW.; 2000 Dec 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17673

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Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosisassociated mutations in copper-zinc superoxide dismutase. by Pasinelli P, Borchelt DR, Houseweart MK, Cleveland DW, Brown RH Jr.; 1998 Dec 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28118

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Chaperone-facilitated copper binding is a property common to several classes of familial amyotrophic lateral sclerosis-linked superoxide dismutase mutants. by Corson LB, Strain JJ, Culotta VC, Cleveland DW.; 1998 May 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27707

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Characterization of Three Yeast Copper-Zinc Superoxide Dismutase Mutants Analogous to those Coded for in Familial Amyotrophic Lateral Sclerosis. by Nishida CR, Gralla EB, Valentine JS.; 1994 Oct 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44926

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Chromosomal Localization of Glutamate Receptor Genes: Relationship to Familial Amyotrophic Lateral Sclerosis and Other Neurological Disorders of Mice and Humans. by Gregor P, Reeves RH, Jabs EW, Yang X, Dackowski W, Rochelle JM, Brown RH Jr, Haines JL, O'Hara BF, Uhl GR, Seldin MF.; 1993 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46235

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Common denominator of Cu/Zn superoxide dismutase mutants associated with amyotrophic lateral sclerosis: Decreased stability of the apo state. by Lindberg MJ, Tibell L, Oliveberg M.; 2002 Dec 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139191

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Cytotoxicity of Immunoglobulins from Amyotrophic Lateral Sclerosis Patients on a Hybrid Motoneuron Cell Line. by Smith RG, Alexianu ME, Crawford G, Nyormoi O, Stefani E, Appel SH.; 1994 Apr 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43583

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Elevated free nitrotyrosine levels, but not protein-bound nitrotyrosine or hydroxyl radicals, throughout amyotrophic lateral sclerosis (ALS)-like disease implicate tyrosine nitration as an aberrant in vivo property of one familial ALS-linked superoxide dismutase 1 mutant. by Bruijn LI, Beal MF, Becher MW, Schulz JB, Wong PC, Price DL, Cleveland DW.; 1997 Jul 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23869

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Expression of calbindin-D28K in Motoneuron Hybrid Cells after Retroviral Infection with calbindin-D28K cDNA Prevents Amyotrophic Lateral Sclerosis igG-Mediated Cytotoxicity. by Ho B, Alexianu ME, Colom LV, Mohamed AH, Serrano F, Appel SH.; 1996 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39107

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Fragmentation of the Golgi Apparatus of Motor Neurons in Amyotrophic Lateral Sclerosis Revealed by Organelle-Specific Antibodies. by Mourelatos Z, Adler H, Hirano A, Donnenfeld H, Gonatas JO, Gonatas NK.; 1990 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54116

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Human CCS gene: genomic organization and exclusion as a candidate for amyotrophic lateral sclerosis (ALS). by Silahtaroglu AN, Brondum-Nielsen K, Gredal O, Werdelin L, Panas M, Petersen MB, Tommerup N, Tumer Z.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107843

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IgG from Amyotrophic Lateral Sclerosis Patients Increases Current Through P-Type Calcium Channels in Mammalian Cerebellar Purkinje Cells and in Isolated Channel Protein in Lipid Bilayer. by Llinas R, Sugimori M, Cherksey BD, Smith RG, Delbono O, Stefani E, Appel S.; 1993 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48060

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Immunoglobulins from Animal Models of Motor Neuron Disease and from Human Amyotrophic Lateral Sclerosis Patients Passively Transfer Physiological Abnormalities to the Neuromuscular Junction. by Apel SH, Engelhardt JI, Garcia J, Stefani E.; 1991 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50869

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Modeling Lou Gehrig's Disease in the Fruit Fly. by McCabe ER.; 1995 Sep 12; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=41001

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Mutations Associated with Amyotrophic Lateral Sclerosis Convert Superoxide Dismutase from an Antiapoptotic Gene to a Proapoptotic Gene: Studies in Yeast and Neural Cells. by Rabizadeh S, Gralla EB, Borchelt DR, Gwinn R, Valentine JS, Sisodia S, Wong P, Lee M, Hahn H, Bredesen DE.; 1995 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42351

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Mutations in Copper-Zinc Superoxide Dismutase that Cause Amyotrophic Lateral Sclerosis Alter the Zinc Binding Site and the Redox Behavior of the Protein. by Lyons TJ, Liu H, Goto JJ, Nersissian A, Roe JA, Graden JA, Cafe C, Ellerby LM, Bredesen DE, Gralla EB, Valentine JS.; 1996 Oct 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=37974

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Programmed cell death in amyotrophic lateral sclerosis. by Guegan C, Przedborski S.; 2003 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151885

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Protective effect of neurofilament heavy gene overexpression in motor neuron disease induced by mutant superoxide dismutase. by Couillard-Despres S, Zhu Q, Wong PC, Price DL, Cleveland DW, Julien JP.; 1998 Aug 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21389

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Reexamination of the mechanism of hydroxyl radical adducts formed from the reaction between familial amyotrophic lateral sclerosis-associated Cu,Zn superoxide dismutase mutants and H2O2. by Singh RJ, Karoui H, Gunther MR, Beckman JS, Mason RP, Kalyanaraman B.; 1998 Jun 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22595

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Superoxide Dismutase 1 with Mutations Linked to Familial Amyotrophic Lateral Sclerosis Possesses Significant Activity. by Borchelt DR, Lee MK, Slunt HS, Guarnieri M, Xu Z, Wong PC, Brown RH Jr, Price DL, Sisodia SS, Cleveland DW.; 1994 Aug 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44592

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The Gene Encoding the Glutamate Receptor Subunit GluR5 is Located on Human Chromosome 21q21.1-22.1 in the Vicinity of the Gene for Familial Amyotrophic Lateral Sclerosis. by Eubanks JH, Puranam RS, Kleckner NW, Bettler B, Heinemann SF, McNamara JO.; 1993 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45623

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The role of immunophilins in mutant superoxide dismutase-1linked familial amyotrophic lateral sclerosis. by Lee JP, Palfrey HC, Bindokas VP, Ghadge GD, Ma L, Miller RJ, Roos RP.; 1999 Mar 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15928

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Therapeutic vaccine for acute and chronic motor neuron diseases: Implications for amyotrophic lateral sclerosis. by Angelov DN, Waibel S, Guntinas-Lichius O, Lenzen M, Neiss WF, Tomov TL, Yoles E, Kipnis J, Schori H, Reuter A, Ludolph A, Schwartz M.; 2003 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153634

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Transgenic Mice Carrying a Human Mutant Superoxide Dismutase Transgene Develop Neuronal Cytoskeletal Pathology Resembling Human Amyotrophic Lateral Sclerosis Lesions. by Tu P, Raju P, Robinson KA, Gurney ME, Trojanowski JQ, Lee VM.; 1996 Apr 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39778

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Transgenic Mice Expressing an Altered Murine Superoxide Dismutase Gene Provide an Animal Model of Amyotrophic Lateral Sclerosis. by Ripps ME, Huntley GW, Hof PR, Morrison JH, Gordon JW.; 1995 Jan 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42685

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

A clustering of conjugal amyotrophic lateral sclerosis in southeastern France. Author(s): Corcia P, Jafari-Schluep HF, Lardillier D, Mazyad H, Giraud P, Clavelou P, Pouget J, Camu W. Source: Archives of Neurology. 2003 April; 60(4): 553-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707069&dopt=Abstract

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A double-blind randomized clinical trial in amyotrophic lateral sclerosis using lamotrigine: effects on CSF glutamate, aspartate, branched-chain amino acid levels and clinical parameters. Author(s): Ryberg H, Askmark H, Persson LI. Source: Acta Neurologica Scandinavica. 2003 July; 108(1): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807386&dopt=Abstract

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A new familial amyotrophic lateral sclerosis locus on chromosome 16q12.1-16q12.2. Author(s): Abalkhail H, Mitchell J, Habgood J, Orrell R, de Belleroche J. Source: American Journal of Human Genetics. 2003 August; 73(2): 383-9. Epub 2003 June 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830400&dopt=Abstract

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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 randomized sequential trial of creatine in amyotrophic lateral sclerosis. Author(s): Groeneveld GJ, Veldink JH, van der Tweel I, Kalmijn S, Beijer C, de Visser M, Wokke JH, Franssen H, van den Berg LH. Source: Annals of Neurology. 2003 April; 53(4): 437-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12666111&dopt=Abstract

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A screening for superoxide dismutase-1 D90A mutation in Italian patients with sporadic amyotrophic lateral sclerosis. Author(s): Mancuso M, Filosto M, Naini A, Rocchi A, Del Corona A, Sartucci F, Siciliano G, Murri L. Source: Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases. 2002 December; 3(4): 215-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710511&dopt=Abstract

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A study comparing patients with amyotrophic lateral sclerosis and their caregivers on measures of quality of life, depression, and their attitudes toward treatment options. Author(s): Trail M, Nelson ND, Van JN, Appel SH, Lai EC. Source: Journal of the Neurological Sciences. 2003 May 15; 209(1-2): 79-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686407&dopt=Abstract

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A4T mutation in the SOD1 gene causing familial amyotrophic lateral sclerosis. Author(s): Aksoy H, Dean G, Elian M, Deng HX, Deng G, Juneja T, Storey E, McKinlay Gardner RJ, Jacob RL, Laing NG, Siddique T. Source: Neuroepidemiology. 2003 July-August; 22(4): 235-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792143&dopt=Abstract

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Adult Hallervorden-Spatz syndrome simulating amyotrophic lateral sclerosis. Author(s): Vasconcelos OM, Harter DH, Duffy C, McDonough B, Seidman JG, Seidman CE, Campbell WW. Source: Muscle & Nerve. 2003 July; 28(1): 118-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811783&dopt=Abstract

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Altered expression of cardiac ankyrin repeat protein and its homologue, ankyrin repeat protein with PEST and proline-rich region, in atrophic muscles in amyotrophic lateral sclerosis. Author(s): Nakamura K, Nakada C, Takeuchi K, Osaki M, Shomori K, Kato S, Ohama E, Sato K, Fukayama M, Mori S, Ito H, Moriyama M. Source: Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology. 2002-2003; 70(4): 197-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679596&dopt=Abstract

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Amyotrophic lateral sclerosis associated with pregnancy: report of four new cases and review of the literature. Author(s): Chio A, Calvo A, Di Vito N, Vercellino M, Ghiglione P, Terreni A, Mutani R, Mora G. 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): 45-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745618&dopt=Abstract

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Amyotrophic lateral sclerosis with IgM antibody against gangliosides GM2 and GD2. Author(s): Mizutani K, Oka N, Kusunoki S, Kaji R, Kanda M, Akiguchi I, Shibasaki H. Source: Intern Med. 2003 March; 42(3): 277-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705795&dopt=Abstract

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Amyotrophic lateral sclerosis, lead, and genetic susceptibility: polymorphisms in the delta-aminolevulinic acid dehydratase and vitamin D receptor genes. Author(s): Kamel F, Umbach DM, Lehman TA, Park LP, Munsat TL, Shefner JM, Sandler DP, Hu H, Taylor JA. Source: Environmental Health Perspectives. 2003 August; 111(10): 1335-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12896855&dopt=Abstract

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Amyotrophic lateral sclerosis. Author(s): Gordon PH, Mitsumoto H, Hays AP. Source: Science of Aging Knowledge Environment [electronic Resource] : Sage Ke. 2003 September 3; 2003(35): Dn2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954882&dopt=Abstract

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Amyotrophic lateral sclerosis. Helping the patient with Lou Gehrig's disease. Author(s): Bartels EJ. Source: Rn. 1979 December; 42(12): 48-50, 79-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=261458&dopt=Abstract

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Amyotrophic lateral sclerosis: Lou Gehrig's disease. Author(s): Walling AD. Source: American Family Physician. 1999 March 15; 59(6): 1489-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10193591&dopt=Abstract

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An evidence-based medicine approach to the evaluation of the role of exogenous risk factors in sporadic amyotrophic lateral sclerosis. Author(s): Armon C. Source: Neuroepidemiology. 2003 July-August; 22(4): 217-28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792141&dopt=Abstract

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An outcome study of riluzole in amyotrophic lateral sclerosis--a population-based study in Ireland, 1996-2000. Author(s): Traynor BJ, Alexander M, Corr B, Frost E, Hardiman O. Source: Journal of Neurology. 2003 April; 250(4): 473-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700914&dopt=Abstract

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Are amyotrophic lateral sclerosis patients cognitively normal? Author(s): Lomen-Hoerth C, Murphy J, Langmore S, Kramer JH, Olney RK, Miller B. Source: Neurology. 2003 April 8; 60(7): 1094-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682312&dopt=Abstract

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Behavioural and anatomical effects of systemically administered leukemia inhibitory factor in the SOD1(G93A G1H) mouse model of familial amyotrophic lateral sclerosis. Author(s): Azari MF, Lopes EC, Stubna C, Turner BJ, Zang D, Nicola NA, Kurek JB, Cheema SS. Source: Brain Research. 2003 August 22; 982(1): 92-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915243&dopt=Abstract

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Biochemical and therapeutic effects of antioxidants in the treatment of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Author(s): Di Matteo V, Esposito E. Source: Current Drug Targets. Cns and Neurological Disorders. 2003 April; 2(2): 95-107. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769802&dopt=Abstract

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Biochemical and ultrastructural study of neurofibrillary tangles in amyotrophic lateral sclerosis/parkinsonism-dementia complex in the Kii peninsula of Japan. Author(s): Itoh N, Ishiguro K, Arai H, Kokubo Y, Sasaki R, Narita Y, Kuzuhara S. Source: Journal of Neuropathology and Experimental Neurology. 2003 July; 62(7): 791-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901704&dopt=Abstract

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Burden of care in amyotrophic lateral sclerosis. Author(s): Hecht MJ, Graesel E, Tigges S, Hillemacher T, Winterholler M, Hilz MJ, Heuss D, Neundorfer B. Source: Palliative Medicine. 2003 June; 17(4): 327-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822849&dopt=Abstract

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Cell cycle regulators in the neuronal death pathway of amyotrophic lateral sclerosis caused by mutant superoxide dismutase 1. Author(s): Nguyen MD, Boudreau M, Kriz J, Couillard-Despres S, Kaplan DR, Julien JP. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 March 15; 23(6): 2131-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657672&dopt=Abstract

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Cerebral blood flow and oxygen metabolism in patients with progressive dementia and amyotrophic lateral sclerosis. Author(s): Tanaka M, Ichiba T, Kondo S, Hirai S, Okamoto K. Source: Neurological Research. 2003 June; 25(4): 351-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870260&dopt=Abstract

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Ciliary neurotrophic factor genotype does not influence clinical phenotype in amyotrophic lateral sclerosis. Author(s): Al-Chalabi A, Scheffler MD, Smith BN, Parton MJ, Cudkowicz ME, Andersen PM, Hayden DL, Hansen VK, Turner MR, Shaw CE, Leigh PN, Brown RH Jr. Source: Annals of Neurology. 2003 July; 54(1): 130-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838531&dopt=Abstract

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Cognitive processing in completely paralyzed patients with amyotrophic lateral sclerosis. Author(s): Kotchoubey B, Lang S, Winter S, Birbaumer N. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2003 September; 10(5): 551-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12940838&dopt=Abstract

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Conflicts of interest: experiences of close relatives of patients suffering from amyotrophic lateral sclerosis. Author(s): Bolmsjo I, Hermern G. Source: Nursing Ethics. 2003 March; 10(2): 186-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659489&dopt=Abstract

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Cu/Zn superoxide dismutase mutants associated with amyotrophic lateral sclerosis show enhanced formation of aggregates in vitro. Author(s): Stathopulos PB, Rumfeldt JA, Scholz GA, Irani RA, Frey HE, Hallewell RA, Lepock JR, Meiering EM. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 June 10; 100(12): 7021-6. Epub 2003 May 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773627&dopt=Abstract

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Decreased galectin-1 immunoreactivity of the skin in amyotrophic lateral sclerosis. Author(s): Wada M, Ono S, Kadoya T, Kawanami T, Kurita K, Kato T. Source: Journal of the Neurological Sciences. 2003 April 15; 208(1-2): 67-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639727&dopt=Abstract

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Diffusion tensor imaging detects corticospinal tract involvement at multiple levels in amyotrophic lateral sclerosis. Author(s): Toosy AT, Werring DJ, Orrell RW, Howard RS, King MD, Barker GJ, Miller DH, Thompson AJ. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 September; 74(9): 1250-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933929&dopt=Abstract

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Diffusion tensor imaging for long-term follow-up of corticospinal tract degeneration in amyotrophic lateral sclerosis. Author(s): Jacob S, Finsterbusch J, Weishaupt JH, Khorram-Sefat D, Frahm J, Ehrenreich H. Source: Neuroradiology. 2003 September; 45(9): 598-600. Epub 2003 August 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904924&dopt=Abstract

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Dissociation between neurodegeneration and caspase-11-mediated activation of caspase-1 and caspase-3 in a mouse model of amyotrophic lateral sclerosis. Author(s): Kang SJ, Sanchez I, Jing N, Yuan J. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 July 2; 23(13): 5455-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843244&dopt=Abstract

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Dorfin localizes to the ubiquitylated inclusions in Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and amyotrophic lateral sclerosis. Author(s): Hishikawa N, Niwa J, Doyu M, Ito T, Ishigaki S, Hashizume Y, Sobue G. Source: American Journal of Pathology. 2003 August; 163(2): 609-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875980&dopt=Abstract

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Drug therapy for amyotrophic lateral sclerosis: Where are we now? Author(s): Carter GT, Krivickas LS, Weydt P, Weiss MD, Miller RG. Source: Idrugs. 2003 February; 6(2): 147-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789618&dopt=Abstract

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Early or late appearance of “dropped head syndrome” in amyotrophic lateral sclerosis. Author(s): Gourie-Devi M, Nalini A, Sandhya S. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 May; 74(5): 683-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700323&dopt=Abstract

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Effect of a multidisciplinary amyotrophic lateral sclerosis (ALS) clinic on ALS survival: a population based study, 1996-2000. Author(s): Traynor BJ, Alexander M, Corr B, Frost E, Hardiman O. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 September; 74(9): 1258-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933930&dopt=Abstract

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Endogenous protectant kynurenic acid in amyotrophic lateral sclerosis. Author(s): Ilzecka J, Kocki T, Stelmasiak Z, Turski WA. Source: Acta Neurologica Scandinavica. 2003 June; 107(6): 412-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757473&dopt=Abstract

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Epidemiological and clinical patterns of western pacific amyotrophic lateral sclerosis (ALS) in Guam and sporadic ALS in Rochester, Minnesota, U.S.A. and Hokkaido, Japan: a comparative study. Author(s): Okumura H. Source: Hokkaido Igaku Zasshi. 2003 May; 78(3): 187-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795170&dopt=Abstract

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Erythrocyte zinc, copper, and copper/zinc superoxide dismutase and risk of sporadic amyotrophic lateral sclerosis: a population-based case-control study. Author(s): Vinceti M, Bergomi M, Nacci G, Pietrini V, Ferrari A, Fortini K, Guidetti D, Sola P, Rocchi E, Mancia D, Vivoli G. Source: Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases. 2002 December; 3(4): 208-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710510&dopt=Abstract

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Expression of hepatocyte growth factor and c-Met in the anterior horn cells of the spinal cord in the patients with amyotrophic lateral sclerosis (ALS): immunohistochemical studies on sporadic ALS and familial ALS with superoxide dismutase 1 gene mutation. Author(s): Kato S, Funakoshi H, Nakamura T, Kato M, Nakano I, Hirano A, Ohama E. Source: Acta Neuropathologica. 2003 August; 106(2): 112-20. Epub 2003 April 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707786&dopt=Abstract

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Factors which predict physical and mental health status in patients with amyotrophic lateral sclerosis over time. Author(s): Norquist JM, Jenkinson C, Fitzpatrick R, Swash M; ALS-HPS Steering Group. Source: Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases. 2003 June; 4(2): 112-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506943&dopt=Abstract

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Familial amyotrophic lateral sclerosis and parkinsonism-dementia complex-tauopathy without mutations in the tau gene? Author(s): Kowalska A, Konagaya M, Sakai M, Hashizume Y, Tabira T. Source: Folia Neuropathol. 2003; 41(2): 59-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899197&dopt=Abstract

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Familial amyotrophic lateral sclerosis with a point mutation (G37R) of the superoxide dismutase 1 gene: a clinicopathological study. Author(s): Inoue K, Fujimura H, Ogawa Y, Satoh T, Shimada K, Sakoda S. Source: Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases. 2002 December; 3(4): 244-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710516&dopt=Abstract

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Free insulin-like growth factor (IGF)-I and IGF binding proteins 2, 5, and 6 in spinal motor neurons in amyotrophic lateral sclerosis. Author(s): Wilczak N, de Vos RA, De Keyser J. Source: Lancet. 2003 March 22; 361(9362): 1007-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660059&dopt=Abstract

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Gene linked to Lou Gehrig's disease. Author(s): Marx J. Source: Science. 1993 March 5; 259(5100): 1393. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8451634&dopt=Abstract

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Hexosaminidase A deficiency is an uncommon cause of a syndrome mimicking amyotrophic lateral sclerosis. Author(s): Drory VE, Birnbaum M, Peleg L, Goldman B, Korczyn AD. Source: Muscle & Nerve. 2003 July; 28(1): 109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811781&dopt=Abstract

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Identification of two novel loci for dominantly inherited familial amyotrophic lateral sclerosis. Author(s): Sapp PC, Hosler BA, McKenna-Yasek D, Chin W, Gann A, Genise H, Gorenstein J, Huang M, Sailer W, Scheffler M, Valesky M, Haines JL, Pericak-Vance M, Siddique T, Horvitz HR, Brown RH Jr. Source: American Journal of Human Genetics. 2003 August; 73(2): 397-403. Epub 2003 July 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858291&dopt=Abstract

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Impaired coordination between grip force and load force in amyotrophic lateral sclerosis: a case-control study. Author(s): Nowak DA, Hermsdorfer J. Source: Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases. 2002 December; 3(4): 199-207. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710509&dopt=Abstract

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Incidence of amyotrophic lateral sclerosis in the local health district of Ferrara, Italy, 1964-1998. Author(s): Govoni V, Granieri E, Capone J, Manconi M, Casetta I. Source: Neuroepidemiology. 2003 July-August; 22(4): 229-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792142&dopt=Abstract

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Increased creatine kinase and spontaneous activity on electromyography, in amyotrophic lateral sclerosis. Author(s): Lima AF, Evangelista T, de Carvalho M. Source: Electromyogr Clin Neurophysiol. 2003 April-May; 43(3): 189-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712806&dopt=Abstract

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Increased hypoxic blood pressure response in patients with amyotrophic lateral sclerosis. Author(s): Hecht MJ, Brown CM, Mittelhamm F, Werner D, Heuss D, Neundorfer B, Hilz MJ. Source: Journal of the Neurological Sciences. 2003 September 15; 213(1-2): 47-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873754&dopt=Abstract

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Insights into Lou Gehrig's disease from the structure and instability of the A4V mutant of human Cu,Zn superoxide dismutase. Author(s): Cardoso RM, Thayer MM, DiDonato M, Lo TP, Bruns CK, Getzoff ED, Tainer JA. Source: Journal of Molecular Biology. 2002 November 22; 324(2): 247-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441104&dopt=Abstract

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Interpreting change scores on the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40). Author(s): Jenkinson C, Peto V, Jones G, Fitzpatrick R. Source: Clinical Rehabilitation. 2003 July; 17(4): 380-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785246&dopt=Abstract

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Involvement of cathepsin B in the motor neuron degeneration of amyotrophic lateral sclerosis. Author(s): Kikuchi H, Yamada T, Furuya H, Doh-ura K, Ohyagi Y, Iwaki T, Kira J. Source: Acta Neuropathologica. 2003 May; 105(5): 462-8. Epub 2003 January 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12677446&dopt=Abstract

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Is somatosensory function abnormal in amyotrophic lateral sclerosis/parkinsonismdementia complex in Kii Peninsula? Author(s): Shibasaki H. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2003 May; 114(5): 775-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738424&dopt=Abstract

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Is there mitochondrial dysfunction in amyotrophic lateral sclerosis skeletal muscle? Author(s): Vielhaber S, Kudin A, Winkler K, Wiedemann F, Schroder R, Feistner H, Heinze HJ, Elger CE, Kunz WS. Source: Annals of Neurology. 2003 May; 53(5): 686-7; Author Reply 687-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12731009&dopt=Abstract

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Longitudinal effects of noninvasive positive-pressure ventilation in patients with amyotrophic lateral sclerosis. Author(s): Butz M, Wollinsky KH, Wiedemuth-Catrinescu U, Sperfeld A, Winter S, Mehrkens HH, Ludolph AC, Schreiber H. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2003 August; 82(8): 597-604. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12872016&dopt=Abstract

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Mechanical insufflation-exsufflation vs. tracheal suctioning via tracheostomy tubes for patients with amyotrophic lateral sclerosis: a pilot study. Author(s): Sancho J, Servera E, Vergara P, Marin J. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2003 October; 82(10): 750-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14508404&dopt=Abstract

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Misfolded CuZnSOD and amyotrophic lateral sclerosis. Author(s): Valentine JS, Hart PJ. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 April 1; 100(7): 3617-22. Epub 2003 March 24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655070&dopt=Abstract

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Mitochondrial dysfunction due to mutant copper/zinc superoxide dismutase associated with amyotrophic lateral sclerosis is reversed by N-acetylcysteine. Author(s): Beretta S, Sala G, Mattavelli L, Ceresa C, Casciati A, Ferri A, Carri MT, Ferrarese C. Source: Neurobiology of Disease. 2003 August; 13(3): 213-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901835&dopt=Abstract

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Mitochondriopathy as a differential diagnosis of amyotrophic lateral sclerosis. Author(s): Finsterer J. Source: Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases. 2002 December; 3(4): 219-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710512&dopt=Abstract

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Mitochondriopathy mimicking amyotrophic lateral sclerosis. Author(s): Finsterer J. Source: The Neurologist. 2003 January; 9(1): 45-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801431&dopt=Abstract

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Molecular and cellular mechanism of glutamate receptors in relation to amyotrophic lateral sclerosis. Author(s): Iwasaki Y, Ikeda K, Kinoshita M. Source: Current Drug Targets. Cns and Neurological Disorders. 2002 October; 1(5): 5118. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769603&dopt=Abstract

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Motor responses evoked by transcranial magnetic stimulation and peripheral nerve stimulation in the ulnar innervation in amyotrophic lateral sclerosis: the effect of upper and lower motor neuron lesion. Author(s): de Carvalho M, Turkman A, Swash M. Source: Journal of the Neurological Sciences. 2003 June 15; 210(1-2): 83-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736094&dopt=Abstract

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Mutant SOD1 linked to familial amyotrophic lateral sclerosis, but not wild-type SOD1, induces ER stress in COS7 cells and transgenic mice. Author(s): Tobisawa S, Hozumi Y, Arawaka S, Koyama S, Wada M, Nagai M, Aoki M, Itoyama Y, Goto K, Kato T. Source: Biochemical and Biophysical Research Communications. 2003 April 4; 303(2): 496-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659845&dopt=Abstract

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N19S, a new SOD1 mutation in sporadic amyotrophic lateral sclerosis: no evidence for disease causation. Author(s): Mayeux V, Corcia P, Besson G, Jafari-Schluep HF, Briolotti V, Camu W. Source: Annals of Neurology. 2003 June; 53(6): 815-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783432&dopt=Abstract

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Neurodegeneration in amyotrophic lateral sclerosis: the role of oxidative stress and altered homeostasis of metals. Author(s): Carri MT, Ferri A, Cozzolino M, Calabrese L, Rotilio G. Source: Brain Research Bulletin. 2003 August 30; 61(4): 365-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909279&dopt=Abstract

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Neuromuscular accumulation of mutant superoxide dismutase 1 aggregates in a transgenic mouse model of familial amyotrophic lateral sclerosis. Author(s): Turner BJ, Lopes EC, Cheema SS. Source: Neuroscience Letters. 2003 October 23; 350(2): 132-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972170&dopt=Abstract

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Neuroradiological study of patients with amyotrophic lateral sclerosis and parkinsonism-dementia complex on the Kii peninsula of Japan. Author(s): Kokubo Y, Kuzuhara S. Source: Archives of Neurology. 2003 September; 60(9): 1257-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975292&dopt=Abstract

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New hope for treatment of Lou Gehrig's disease. Author(s): Piascik P. Source: Journal of the American Pharmaceutical Association (Washington,D.C. : 1996). 1996 June; Ns36(6): 355-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8697260&dopt=Abstract

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No evidence of linkage to chromosome 9q21-22 in a Swedish family with frontotemporal dementia and amyotrophic lateral sclerosis. Author(s): Ostojic J, Axelman K, Lannfelt L, Froelich-Fabre S. Source: Neuroscience Letters. 2003 April 17; 340(3): 245-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672552&dopt=Abstract

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Patients' health-related quality-of-life and health state values for motor neurone disease/amyotrophic lateral sclerosis. Author(s): Green C, Kiebert G, Murphy C, Mitchell JD, O'Brien M, Burrell A, Leigh PN. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2003 August; 12(5): 565-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677501&dopt=Abstract

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Persistent bitter taste as an initial symptom of amyotrophic lateral sclerosis. Author(s): Petzold GC, Einhaupl KM, Valdueza JM. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 May; 74(5): 687-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700324&dopt=Abstract

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Polymorphisms of toxifying and detoxifying hepatic enzymes in amyotrophic lateral sclerosis. Author(s): Bachus R, Neubert K, Roots I, Prudlo J, Brockmoller J, Ludolph AC. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 August; 74(8): 1161. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876266&dopt=Abstract

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Primary lateral sclerosis: a rare upper-motor-predominant form of amyotrophic lateral sclerosis often accompanied by frontotemporal lobar degeneration with ubiquitinated neuronal inclusions? Report of an autopsy case and a review of the literature. Author(s): Tan CF, Kakita A, Piao YS, Kikugawa K, Endo K, Tanaka M, Okamoto K, Takahashi H. Source: Acta Neuropathologica. 2003 June; 105(6): 615-20. Epub 2003 March 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734667&dopt=Abstract

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Prospects for the pharmacotherapy of amyotrophic lateral sclerosis : old strategies and new paradigms for the third millennium. Author(s): Festoff BW, Suo Z, Citron BA. Source: Cns Drugs. 2003; 17(10): 699-717. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873154&dopt=Abstract

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Prostaglandin E2 is increased in amyotrophic lateral sclerosis patients. Author(s): Ilzecka J. Source: Acta Neurologica Scandinavica. 2003 August; 108(2): 125-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859290&dopt=Abstract

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Protein kinase and protein phosphatase expression in amyotrophic lateral sclerosis spinal cord. Author(s): Hu JH, Zhang H, Wagey R, Krieger C, Pelech SL. Source: Journal of Neurochemistry. 2003 April; 85(2): 432-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675919&dopt=Abstract

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Quality of life in patients with amyotrophic lateral sclerosis: perceptions, coping resources, and illness characteristics. Author(s): Nelson ND, Trail M, Van JN, Appel SH, Lai EC. Source: Journal of Palliative Medicine. 2003 June; 6(3): 417-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509487&dopt=Abstract

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Quantification of hyperreflexia in amyotrophic lateral sclerosis (ALS) by the soleus stretch reflex. Author(s): Christensen PB, Nielsen JF, Sinkjaer T. Source: Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases. 2003 June; 4(2): 106-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506942&dopt=Abstract

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Reduction of oxidative stress in amyotrophic lateral sclerosis following pramipexole treatment. Author(s): Pattee GL, Post GR, Gerber RE, Bennett JP Jr. Source: Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases. 2003 June; 4(2): 90-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506939&dopt=Abstract

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Revised medical criteria for evaluating amyotrophic lateral sclerosis. Final rules. Author(s): Social Security Administration. Source: Federal Register. 2003 August 28; 68(167): 51689-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952014&dopt=Abstract

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Risk of sporadic amyotrophic lateral sclerosis associated with seropositivity for herpesviruses and echovirus-7. Author(s): Cermelli C, Vinceti M, Beretti F, Pietrini V, Nacci G, Pietrosemoli P, Bartoletti A, Guidetti D, Sola P, Bergomi M, Vivoli G, Portolani M. Source: European Journal of Epidemiology. 2003; 18(2): 123-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12733833&dopt=Abstract

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Selective loss of trans-acting instability determinants of neurofilament mRNA in amyotrophic lateral sclerosis spinal cord. Author(s): Ge WW, Leystra-Lantz C, Wen W, Strong MJ. Source: The Journal of Biological Chemistry. 2003 July 18; 278(29): 26558-63. Epub 2003 May 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730211&dopt=Abstract

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Serum bilirubin concentration in patients with amyotrophic lateral sclerosis. Author(s): Ilzecka J, Stelmasiak Z. Source: Clinical Neurology and Neurosurgery. 2003 September; 105(4): 237-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954537&dopt=Abstract

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Single-cell analysis of mtDNA in amyotrophic lateral sclerosis: towards the characterization of individual neurons in neurodegenerative disorders. Author(s): Mawrin C, Kirches E, Dietzmann K. Source: Pathology, Research and Practice. 2003; 199(6): 415-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924443&dopt=Abstract

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Single-nucleotide polymorphisms in uncoding regions of ALS2 gene of Japanese patients with autosomal-recessive amyotrophic lateral sclerosis. Author(s): Nagano I, Murakami T, Shiote M, Manabe Y, Hadano S, Yanagisawa Y, Ikeda JE, Abe K. Source: Neurological Research. 2003 July; 25(5): 505-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866199&dopt=Abstract

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Sixteen novel mutations in the Cu/Zn superoxide dismutase gene in amyotrophic lateral sclerosis: a decade of discoveries, defects and disputes. Author(s): Andersen PM, Sims KB, Xin WW, Kiely R, O'Neill G, Ravits J, Pioro E, Harati Y, Brower RD, Levine JS, Heinicke HU, Seltzer W, Boss M, Brown RH Jr. Source: Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases. 2003 June; 4(2): 62-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506936&dopt=Abstract

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Skeletal muscle properties in a transgenic mouse model for amyotrophic lateral sclerosis: effects of creatine treatment. Author(s): Derave W, Van Den Bosch L, Lemmens G, Eijnde BO, Robberecht W, Hespel P. Source: Neurobiology of Disease. 2003 August; 13(3): 264-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901841&dopt=Abstract

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Somatosensory evoked potential recovery in kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (kii AlS/PDC). Author(s): Machii K, Ugawa Y, Kokubo Y, Sasaki R, Kuzuhara S. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2003 March; 114(3): 564-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705437&dopt=Abstract

Studies

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Spatial clustering of amyotrophic lateral sclerosis in Finland at place of birth and place of death. Author(s): Sabel CE, Boyle PJ, Loytonen M, Gatrell AC, Jokelainen M, Flowerdew R, Maasilta P. Source: American Journal of Epidemiology. 2003 May 15; 157(10): 898-905. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746242&dopt=Abstract

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Stem cells in the treatment of amyotrophic lateral sclerosis (ALS). Author(s): Silani V, Fogh I, Ratti A, Sassone J, Ciammola A, Cova L. Source: Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases. 2002 December; 3(4): 173-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710505&dopt=Abstract

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Tau haplotype frequency in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Author(s): Hughes A, Mann D, Pickering-Brown S. Source: Experimental Neurology. 2003 May; 181(1): 12-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710929&dopt=Abstract

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The densitometric physical fractionator for counting neuronal populations: application to a mouse model of familial amyotrophic lateral sclerosis. Author(s): Ciavarro GL, Calvaresi N, Botturi A, Bendotti C, Andreoni G, Pedotti A. Source: Journal of Neuroscience Methods. 2003 October 15; 129(1): 61-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12951233&dopt=Abstract

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The structure of holo and metal-deficient wild-type human Cu, Zn superoxide dismutase and its relevance to familial amyotrophic lateral sclerosis. Author(s): Strange RW, Antonyuk S, Hough MA, Doucette PA, Rodriguez JA, Hart PJ, Hayward LJ, Valentine JS, Hasnain SS. Source: Journal of Molecular Biology. 2003 May 9; 328(4): 877-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729761&dopt=Abstract

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Therapeutic vaccine for acute and chronic motor neuron diseases: implications for amyotrophic lateral sclerosis. Author(s): Angelov DN, Waibel S, Guntinas-Lichius O, Lenzen M, Neiss WF, Tomov TL, Yoles E, Kipnis J, Schori H, Reuter A, Ludolph A, Schwartz M. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 April 15; 100(8): 4790-5. Epub 2003 March 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668759&dopt=Abstract

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Two families with familial amyotrophic lateral sclerosis are linked to a novel locus on chromosome 16q. Author(s): Ruddy DM, Parton MJ, Al-Chalabi A, Lewis CM, Vance C, Smith BN, Leigh PN, Powell JF, Siddique T, Meyjes EP, Baas F, de Jong V, Shaw CE. Source: American Journal of Human Genetics. 2003 August; 73(2): 390-6. Epub 2003 July 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840784&dopt=Abstract

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Validation of bioelectrical impedance analysis in patients with amyotrophic lateral sclerosis. Author(s): Desport JC, Preux PM, Bouteloup-Demange C, Clavelou P, Beaufrere B, Bonnet C, Couratier PP. Source: The American Journal of Clinical Nutrition. 2003 May; 77(5): 1179-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716669&dopt=Abstract

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VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death. Author(s): Lambrechts D, Storkebaum E, Morimoto M, Del-Favero J, Desmet F, Marklund SL, Wyns S, Thijs V, Andersson J, van Marion I, Al-Chalabi A, Bornes S, Musson R, Hansen V, Beckman L, Adolfsson R, Pall HS, Prats H, Vermeire S, Rutgeerts P, Katayama S, Awata T, Leigh N, Lang-Lazdunski L, Dewerchin M, Shaw C, Moons L, Vlietinck R, Morrison KE, Robberecht W, Van Broeckhoven C, Collen D, Andersen PM, Carmeliet P. Source: Nature Genetics. 2003 August; 34(4): 383-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847526&dopt=Abstract

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When motor execution is selectively impaired: control of manipulative finger forces in amyotrophic lateral sclerosis. Author(s): Nowak DA, Hermsdorfer J, Topka H. Source: Motor Control. 2003 July; 7(3): 304-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893960&dopt=Abstract

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CHAPTER 2. ALTERNATIVE MEDICINE AND LOU GEHRIG’S DISEASE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Lou Gehrig’s disease. 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 Lou Gehrig’s disease 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 “Lou Gehrig’s disease” (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 Lou Gehrig’s disease: •

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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7597693&dopt=Abstract

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A non-invasive communication device for the paralyzed. Author(s): Kaiser J, Kubler A, Hinterberger T, Neumann N, Birbaumer N. Source: Minimally Invasive Neurosurgery : Min. 2002 March; 45(1): 19-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932820&dopt=Abstract

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A sporadic case of juvenile amyotrophic lateral sclerosis; semi-quantitative and histoenzymatical study of the denervated muscles. Author(s): Cognazzo A, Martin L. Source: European Neurology. 1970; 3(4): 211-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4314073&dopt=Abstract

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A therapeutic trial of thymic factor in amyotrophic lateral sclerosis (ALS). Author(s): Provinciali L, Giovagnoli AR, Di Bella P, Baroni M, Dellantonio R. Source: Advances in Experimental Medicine and Biology. 1987; 209: 293-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3577920&dopt=Abstract

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Adenyl cyclase in normal and pathologic human muscle. Author(s): Mawatari S, Takagi A, Rowland LP. Source: Archives of Neurology. 1974 January; 30(1): 96-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4357131&dopt=Abstract

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ALS diagnostic criteria, El Escorial, and Philip II of Spain: a historical perspective. Author(s): Belsh JM. Source: Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases. 1999 December; 1(1): 55-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12365069&dopt=Abstract

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ALS. Support groups can help. Author(s): Ashford W. Source: Rnabc News. 1987 January-February; 19(1): 16. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3644432&dopt=Abstract

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Amyotrophic lateral sclerosis and hopelessness: psychosocial factors. Author(s): Plahuta JM, McCulloch BJ, Kasarskis EJ, Ross MA, Walter RA, McDonald ER. Source: Social Science & Medicine (1982). 2002 December; 55(12): 2131-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409126&dopt=Abstract

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Amyotrophic lateral sclerosis. Clinicopathological studies of a family. Author(s): Metcalf CW, Hirano A. Source: Archives of Neurology. 1971 June; 24(6): 518-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5089897&dopt=Abstract

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Amyotrophic lateral sclerosis: a challenge for constant adaptation. Author(s): Stone N.

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Source: The Journal of Neuroscience Nursing : Journal of the American Association of Neuroscience Nurses. 1987 June; 19(3): 166-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2956338&dopt=Abstract •

Amyotrophic lateral sclerosis: integrating care for patients and their families. Author(s): Thompson B. Source: Am J Hosp Palliat Care. 1990 May-June; 7(3): 29-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2361109&dopt=Abstract

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Aquatic therapy for an ALS patient. Author(s): Johnson CR. Source: Am J Occup Ther. 1988 February; 42(2): 115-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3348337&dopt=Abstract

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Beneficial effect of ginseng root in SOD-1 (G93A) transgenic mice. Author(s): Jiang F, DeSilva S, Turnbull J. Source: Journal of the Neurological Sciences. 2000 November 1; 180(1-2): 52-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11090864&dopt=Abstract

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Bereavement--whose responsibility? Author(s): Oliver D, McMurray N. Source: Palliative Medicine. 1993; 7(4 Suppl): 73-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8269177&dopt=Abstract

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Biological markers in the diagnosis and treatment of ALS. Author(s): Kalra S, Arnold DL, Cashman NR. Source: Journal of the Neurological Sciences. 1999 June; 165 Suppl 1: S27-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10448978&dopt=Abstract

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Brain-computer communication: self-regulation of slow cortical potentials for verbal communication. Author(s): Kubler A, Neumann N, Kaiser J, Kotchoubey B, Hinterberger T, Birbaumer NP. Source: Archives of Physical Medicine and Rehabilitation. 2001 November; 82(11): 15339. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11689972&dopt=Abstract

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Burden of care in amyotrophic lateral sclerosis. Author(s): Hecht MJ, Graesel E, Tigges S, Hillemacher T, Winterholler M, Hilz MJ, Heuss D, Neundorfer B.

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Source: Palliative Medicine. 2003 June; 17(4): 327-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822849&dopt=Abstract •

Calcitonin gene-related peptide immunoreactivity in familial amyotrophic lateral sclerosis. Author(s): Kato T, Hirano A, Manaka H, Sasaki H, Katagiri T, Kawanami T, Shikama Y, Seino T, Sasaki H. Source: Neuroscience Letters. 1991 December 9; 133(2): 163-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1667811&dopt=Abstract

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Characterization of three yeast copper-zinc superoxide dismutase mutants analogous to those coded for in familial amyotrophic lateral sclerosis. Author(s): Nishida CR, Gralla EB, Valentine JS. Source: Proceedings of the National Academy of Sciences of the United States of America. 1994 October 11; 91(21): 9906-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7937915&dopt=Abstract

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Controversies about amyotrophic lateral sclerosis. Author(s): Rowland LP. Source: Neurologia (Barcelona, Spain). 1996 December; 11 Suppl 5: 72-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9011143&dopt=Abstract

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Effects of creatine supplementation on exercise performance and muscular strength in amyotrophic lateral sclerosis: preliminary results. Author(s): Mazzini L, Balzarini C, Colombo R, Mora G, Pastore I, De Ambrogio R, Caligari M. Source: Journal of the Neurological Sciences. 2001 October 15; 191(1-2): 139-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11677005&dopt=Abstract

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Ethical aspects of unproved therapies in multiple sclerosis, amyotrophic lateral sclerosis, and other neurologic diseases. Author(s): van den Noort S. Source: Seminars in Neurology. 1984 March; 4(1): 83-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11649670&dopt=Abstract

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Further evidence for corticomotor hyperexcitability in amyotrophic lateral sclerosis. Author(s): Naka D, Mills KR. Source: Muscle & Nerve. 2000 July; 23(7): 1044-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10882998&dopt=Abstract

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Genistein is neuroprotective in murine models of familial amyotrophic lateral sclerosis and stroke. Author(s): Trieu VN, Uckun FM.


Source: Biochemical and Biophysical Research Communications. 1999 May 19; 258(3): 685-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10329446&dopt=Abstract •

Glutathione peroxidase in amyotrophic lateral sclerosis: the effects of selenium supplementation. Author(s): Apostolski S, Marinkovic Z, Nikolic A, Blagojevic D, Spasic MB, Michelson AM. Source: Journal of Environmental Pathology, Toxicology and Oncology : Official Organ of the International Society for Environmental Toxicology and Cancer. 1998; 17(3-4): 3259. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9726810&dopt=Abstract

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Integrating manual and movement therapy with philosophical counseling for treatment of a patient with amyotrophic lateral sclerosis: a case study that explores the principles of holistic intervention. Author(s): Cottingham JT, Maitland J. Source: Alternative Therapies in Health and Medicine. 2000 March; 6(2): 128, 120-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10710808&dopt=Abstract

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Lead content of neuromuscular tissue in amyotrophic lateral sclerosis: case report and other considerations. Author(s): Petkau A, Sawatzky A, Hillier CR, Hoogstraten J. Source: Br J Ind Med. 1974 October; 31(4): 275-87. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4214550&dopt=Abstract

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Management of amyotrophic lateral sclerosis with riluzole. Author(s): Neatherlin JS. Source: The Journal of Neuroscience Nursing : Journal of the American Association of Neuroscience Nurses. 1998 August; 30(4): 257-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9791781&dopt=Abstract

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Marijuana in the management of amyotrophic lateral sclerosis. Author(s): Carter GT, Rosen BS. Source: Am J Hosp Palliat Care. 2001 July-August; 18(4): 264-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11467101&dopt=Abstract

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Motor neuron disease and toxic metals. Author(s): Conradi S, Ronnevi LO, Norris FH. Source: Adv Neurol. 1982; 36: 201-31. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6817611&dopt=Abstract

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Mutant CuZn superoxide dismutase in motor neuron disease. Author(s): Gurney ME, Liu R, Althaus JS, Hall ED, Becker DA. Source: Journal of Inherited Metabolic Disease. 1998 August; 21(5): 587-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9728338&dopt=Abstract

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My journey with amyotrophic lateral sclerosis. Author(s): Nowotny ML. Source: The Journal of Neuroscience Nursing : Journal of the American Association of Neuroscience Nurses. 1998 February; 30(1): 68-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9604825&dopt=Abstract

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Nutritional issues and supplements in amyotrophic lateral sclerosis and other neurodegenerative disorders. Author(s): Cameron A, Rosenfeld J. Source: Current Opinion in Clinical Nutrition and Metabolic Care. 2002 November; 5(6): 631-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394638&dopt=Abstract

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Nutritional management in amyotrophic lateral sclerosis: a worldwide perspective. Author(s): Silani V, Kasarskis EJ, Yanagisawa N. Source: Journal of Neurology. 1998 August; 245 Suppl 2: S13-9; Discussion S29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9747929&dopt=Abstract

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Psychological function in individuals with amyotrophic lateral sclerosis (ALS). Author(s): Brown WA, Mueller PS. Source: Psychosomatic Medicine. 1970 March-April; 32(2): 141-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4392415&dopt=Abstract

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Reduced creatine kinase activity in transgenic amyotrophic lateral sclerosis mice. Author(s): Wendt S, Dedeoglu A, Speer O, Wallimann T, Beal MF, Andreassen OA. Source: Free Radical Biology & Medicine. 2002 May 1; 32(9): 920-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978494&dopt=Abstract

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Resilience and distress among amyotrophic lateral sclerosis patients and caregivers. Author(s): Rabkin JG, Wagner GJ, Del Bene M. Source: Psychosomatic Medicine. 2000 March-April; 62(2): 271-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10772408&dopt=Abstract

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Stem cells in the treatment of amyotrophic lateral sclerosis (ALS). Author(s): Silani V, Fogh I, Ratti A, Sassone J, Ciammola A, Cova L.


Source: Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases. 2002 December; 3(4): 173-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710505&dopt=Abstract •

Survival in amyotrophic lateral sclerosis. The role of psychological factors. Author(s): McDonald ER, Wiedenfeld SA, Hillel A, Carpenter CL, Walter RA. Source: Archives of Neurology. 1994 January; 51(1): 17-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8274106&dopt=Abstract

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Symptomatic care of patients with amyotrophic lateral sclerosis. Author(s): Smith RA, Norris FH Jr. Source: Jama : the Journal of the American Medical Association. 1975 November 17; 234(7): 715-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=52730&dopt=Abstract

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The amyotrophic lateral sclerosis (ALS) support network of Kentucky: an informational support group using interactive video. Author(s): Kasarkis EJ, Elza TA, Bishop NG, Spears AC. Source: Journal of the Neurological Sciences. 1997 October; 152 Suppl 1: S90-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9419062&dopt=Abstract

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The family support group in the treatment of amyotrophic lateral sclerosis. Author(s): Finger S. Source: Neurologic Clinics. 1987 February; 5(1): 83-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3561383&dopt=Abstract

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The role of the amyotrophic lateral sclerosis and motor neurone disease community in health-care resourcing. Author(s): Levvy G. Source: Int J Clin Pract Suppl. 1998 April; 93: 14-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9691245&dopt=Abstract

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The use of alternative medicine by patients with amyotrophic lateral sclerosis. Author(s): Wasner M, Klier H, Borasio GD. Source: Journal of the Neurological Sciences. 2001 October 15; 191(1-2): 151-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11677007&dopt=Abstract

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Therapeutic efficacy of EGb761 (Gingko biloba extract) in a transgenic mouse model of amyotrophic lateral sclerosis. Author(s): Ferrante RJ, Klein AM, Dedeoglu A, Beal MF.

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Source: Journal of Molecular Neuroscience : Mn. 2001 August; 17(1): 89-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11665866&dopt=Abstract

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to Lou Gehrig’s disease; 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: •

Herbs and Supplements BCAAS Source: Prima Communications, Inc.www.personalhealthzone.com Branched-Chain Amino Acids Source: Healthnotes, Inc.; www.healthnotes.com Glutamic Acid Source: Healthnotes, Inc.; www.healthnotes.com Melatonin Source: Healthnotes, Inc.; www.healthnotes.com


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Minerals Creatine Source: Prima Communications, Inc.www.personalhealthzone.com

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

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CHAPTER 3. DISSERTATIONS ON LOU GEHRIG’S DISEASE Overview In this chapter, we will give you a bibliography on recent dissertations relating to Lou Gehrig’s disease. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “Lou Gehrig’s disease” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Lou Gehrig’s disease, we have not necessarily excluded non-medical dissertations in this bibliography.

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

Biophysical Studies of Human Copper-zinc Superoxide Dismutases: an Examination of Their Role in the Neurodegenerative Disease, Familial Amyotrophic Lateral Sclerosis (fals) by Malek, Kevin N.; PhD from University of California, Los Angeles, 2002, 124 pages http://wwwlib.umi.com/dissertations/fullcit/3063924

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

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CHAPTER 4. CLINICAL TRIALS AND LOU GEHRIG’S DISEASE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Lou Gehrig’s disease.

Recent Trials on Lou Gehrig’s Disease The following is a list of recent trials dedicated to Lou Gehrig’s disease.7 Further information on a trial is available at the Web site indicated. •

Clinical Trial of Creatine in Amyotrophic Lateral Sclerosis Condition(s): Amyotrophic Lateral Sclerosis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: The objective of this study is to determine whether creatine slows disease progression in subjects with amyotrophic lateral sclerosis (ALS). ALS is a progressive uniformly lethal neurodegenerative disorder for which there is no known cure. Recent genetic and biochemical studies implicate free radical toxicity, glutamate excitotoxicity and mitochondrial dysfunction as possible causes of familial ALS (FALS) and sporadic ALS (SALS). It has been hypothesized that in ALS there may be involvement of oxidative free radical damage and impaired mitochondrial energy metabolism that could in turn lead to excitotoxic cell death. Creatine, an agent that improves mitochondrial function, has been shown to be neuroprotective in animal models of ALS and Huntington's disease. This study is a double-blind, randomized, placebo-controlled trial of the safety and efficacy of creatine in patients with ALS enrolled at sites distributed throughout the United States, including Northeast ALS (NEALS) sites. The study will provide preliminary data on the safety and efficacy of creatine in ALS. If creatine slows disease progression in ALS and is well tolerated, a phase 3 study with survival as the primary outcome measure will be initiated. 114 eligible subjects will be randomized to receive treatment for 6 months of (1) active

7

These are listed at www.ClinicalTrials.gov.

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creatine or (2) placebo. After randomization, subjects will be followed prospectively for 6 months. The primary outcome measure for the study is the change in upper extremity motor function after 6 months of experimental therapy as tested with the Tufts Quantitative Neuromuscular Exam. Strength in eight arm muscles will be measured (bilateral shoulder and elbow flexion and extension). Secondary outcome measures include grip strength, motor unit number estimates (MUNE), the ALS functional rating score-revised (ALSFRS-R), and rate of change of a well established biochemical marker of oxidative damage to DNA (8OH2'dG levels in urine), and the safety and tolerability of creatine. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005766 •

Clinical trial of creatine in amyotrophic lateral sclerosis [ALS] Condition(s): Amyotrophic Lateral Sclerosis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Muscular Dystrophy Association Purpose - Excerpt: The purpose of this study is to evaluate the safety and effectiveness of creatine treatment in amyotrophic lateral sclerosis (ALS). There is currently no known effective treatment for ALS. It is known that nerve cells die in the brains and spinal cords of patients with ALS but the cause of the cell death is unknown. It has been shown that there is overactive nerve activity due to increased levels of a chemical called glutamate and that there is abnormal cellular metabolism along with increased production of substance called "free radicals." Improving cellular metabolism and readjusting the activity of glutamate in the brain may be beneficial to ALS patients. Creatine is a naturally occurring compound, which improves energy metabolism in cells. Creatine has been given to patients with energy metabolism defects in their muscles, and to athletes. Creatine improves survival in a mouse model of ALS. Three human subjects with ALS have received creatine for up to six months without any side effects. Overall, creatine has been well tolerated and safe. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005674

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Creatine for the Treatment of Amyotrophic Lateral Sclerosis Condition(s): Amyotrophic Lateral Sclerosis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM); Office of Dietary Supplements (ODS) Purpose - Excerpt: Creatine is a naturally occurring chemical involved in the production of energy in muscle. Abnormalities in creatine have been linked to the progression of degenerative neuromuscular diseases such as amyotrophic lateral sclerosis (ALS, or

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Lou Gehrig's Disease). This study will test whether taking creatine can improve the symptoms of ALS. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070993 •

IGF-1/ALS Trial Condition(s): Amyotrophic Lateral Sclerosis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The purpose of this multicenter study is to determine if insulin-like growth factor-1 (IGF-I) slows the progressive weakness in amyotrophic lateral sclerosis (ALS) patients. Study participants will be followed for 2 years once enrolled. They will receive either placebo or the active IGF-I. Examinations will take place at approximately 6-month intervals. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035815

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Magnetic Stimulation of the Human Nervous System Condition(s): Demyelinating Disease; Healthy; Lysosomal Storage Disease; Motor Neuron Disease; Movement Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: Transcranial Magnetic Stimulation (TMS) is a non-invasive technique to gather information about brain function. It is very useful when studying the areas of the brain related to motor activity (motor cortex, corticospinal tract, spinal cord and nerve roots). The procedure is conducted by transmitting a magnetic signal into the brain to stimulate an area of the body. Electrodes (small pieces of metal taped to areas of the body) are used in order to measure electrical activity. A magnetic signal is sent from a metal instrument held close to the patient's head, to an area of the brain responsible for motor activity of a certain area of the body. The electrodes pick up and record the electrical activity in the muscles. This study will employ the use of TMS to diagnose neurological disorders that affect the motor cortex or the corticospinal tract. Normal subjects are sometimes studied to investigate normal activity of the nervous system and to train doctors in clinical neurophysiology and electrodiagnostic medicine at the National Institutes of Health (NIH). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001780

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Minocycline to Treat Amyotrophic Lateral Sclerosis Condition(s): Amyotrophic Lateral Sclerosis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The purpose of this trial is to test the safety, tolerability, and effectiveness of minocycline compared to placebo in patients with amyotrophic lateral sclerosis (ALS). Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047723

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Safety testing of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Laughter & Crying) Condition(s): Amyotrophic Lateral Sclerosis; Multiple Sclerosis; Alzheimer's Disease; Stroke; Traumatic Brain Injury Study Status: This study is currently recruiting patients. Sponsor(s): Avanir Pharmaceuticals Purpose - Excerpt: The purpose of this study is to evaluate the safety of AVP-923 for the treatment of emotional lability. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056524

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Study evaluating 4 oral doses of TCH346 and placebo administered once daily in patients with Amyotrophic Lateral Sclerosis (ALS) Condition(s): Amyotrophic Lateral Sclerosis Study Status: This study is currently recruiting patients. Sponsor(s): Novartis Pharmaceuticals Purpose - Excerpt: This is a global multicenter study designed to evaluate the safety and clinical effects of 4 oral doses of TCH346 (1.0, 2.5, 7.5, and 15 mg) compared to placebo in patients with mild or mild to moderate stages of ALS. The study consists of 3 phases: screening (up to 2 weeks), run-in (16 weeks), and a double-blind treatment phase of variable duration (at least 24 weeks). Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00072709

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Study of Creatine Monohydrate in Patients with Amyotrophic Lateral Sclerosis Condition(s): Amyotrophic Lateral Sclerosis (ALS)

Clinical Trials 49

Study Status: This study is currently recruiting patients. Sponsor(s): The Avicena Group; National Institutes of Health (NIH) Purpose - Excerpt: The purpose of this study is to determine whether nine months of administation of creatine monohydrate results in an increase in muscle strength in patients with amyotrophic lateral sclerosis (ALS). Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069186 •

Study of Inherited Neurological Disorders Condition(s): Ataxia; Motor Neuron Disease; Muscular Disease; Muscular Dystrophy; Peripheral Nervous System Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study is designed to learn more about the natural history of inherited neurological disorders and the role of heredity in their development. It will examine the genetics, symptoms, disease progression, treatment, and psychological and behavioral impact of diseases in the following categories: hereditary peripheral neuropathies; hereditary myopathies; muscular dystrophies; hereditary motor neuron disorders; mitochondrial myopathies; ataxias; hereditary neurocognitive disorders; inherited neurological disorders without known diagnosis; and others. Many of these diseases, which affect the brain, spinal cord, muscles, and nerves, are rare and poorly understood. Children and adults of all ages with various inherited neurological disorders may be eligible for this study. Participants will undergo a detailed medical and family history, and a family tree will be drawn. They will also have a physical and neurological examination that may include blood test and urine tests, an EEG (brain wave recordings), psychological tests, and speech and language and rehabilitation evaluations. A blood sample or skin biopsy may be taken for genetic testing. Depending on the individual patient's symptoms, imaging tests such as X-rays, CT or MRI scans and muscle and nerve testing may also be done. Information from this study may provide a better understanding of the genetic underpinnings of these disorders, contributing to improved diagnosis, treatment, and genetic counseling, and perhaps leading to additional studies in these areas. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004568

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Ultrasound and Videofluoroscopy for Diagnosing Swallowing Disorders Condition(s): Deglutition Disorder; Motor Neuron Disease Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This study will identify clinical signs and symptoms critical for diagnosing swallowing disorders and will characterize swallowing problems in various patient populations, such as patients with Parkinson's disease, stroke, post-polio

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syndrome, multiple sclerosis and other conditions that cause swallowing abnormalities. Patients with swallowing difficulties who are enrolled in NIH neurology or speech pathology protocols may be eligible for this study. Participants will undergo the following procedures: 1. Oral examination-A neurologist and speech pathologist examine the patient's swallowing function. The patient is interviewed about difficulties with food intake, chewing and swallowing during meals. 2. Ultrasound examinationUltrasound creates image of areas inside the body using sound waves. With the patient in a sitting position, a 3/4-inch transducer (device for transmitting and receiving sound waves) is placed under the chin to visualize tongue movements during swallowing. 3. Modified barium swallow-While standing or sitting, the patient swallows 1/2 teaspoon of flavored barium (a radioactive substance) six times (a total of 3 teaspoons), while the tongue and pharynx (tube leading from the mouth to the esophagus) are scanned and videotaped. The barium is given in three consistencies-thin, medium and thick (pudding-like). 4. Electromyography-A small plastic strip with wires attached is placed under the patient's chin. The patient then swallows 1/2 ounce of barium three times in a row, and the movement of the chin muscles during swallowing is displayed. Patients may also be asked to swallow 5/8 cup of barium twice; once with the head tilted upward and once with the head untilted. Depending on the test results, patients may be asked to return for follow-up study and monitoring. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001220 •

A 12-week, multicenter, safety and dose-ranging study of 3 oral doses of TCH346 in patients with Amyotrophic Lateral Sclerosis Condition(s): Amyotrophic Lateral Sclerosis Study Status: This study is no longer recruiting patients. Sponsor(s): Novartis Pharmaceuticals Purpose - Excerpt: This study is the first to be performed in Amyotrophic Lateral Sclerosis (ALS) patients with the novel compound TCH346. Its purpose is to evaluate the safety and clinical effects of 3 dose levels of TCH 346 compared to placebo in patients with a clinical diagnosis of laboratory-supported probable, probable or definite ALS. The study will require patients to visit the study center a total of at least 7 times over the course of up to 14 weeks. The study consists of 2 phases: A screening phase (up to 2 weeks) when patients will be evaluated for eligibility to participate in the study, and a double-blind treatment phase (12 weeks) when patients will receive daily doses of either TCH346 or placebo and will be evaluated for clinical effects. In addition, patients eligible to participate in this study will be required to have 3 magnetic resonance spectroscopic (MRS) scans. The MRS is a non-invasive, painless, "brain scan". The MRS will require traveling to a designated center in Montreal, Canada, which is very experienced in performing such MRS scans in ALS patients. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00036413

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Determinants of Disease Severity in Amyotrophic Lateral Sclerosis Condition(s): Amyotrophic Lateral Sclerosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS); Massachusetts General Hospital Purpose - Excerpt: Objectives: I. Determine specific clinical features, molecular abnormalities, and laboratory-based biological markers of free radical stress that are associated with amyotrophic lateral sclerosis and influence disease severity. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004457

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Exogenous Toxicants and Genetic Susceptibility in ALS Condition(s): Amyotrophic Lateral Sclerosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Environmental Health Sciences (NIEHS) Purpose - Excerpt: Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a fatal neurodegenerative disease that poses a significant burden for affected individuals and their family members. The principal objective of this epidemiologic study is to identify environmental and genetic risk factors for ALS. Of primary interest is whether environmental chemicals such as heavy metals, pesticides and organic solvents contribute to the cause of ALS. We also aim to identify genetic factors that contribute to the risk of ALS because individuals with certain genetic traits may be unable to protect against the toxic effects of chemical exposure. Other factors that may protect against the development of ALS, such as dietary antioxidants, are also under investigation. If modifiable factors affecting the risk for ALS could be identified, interventions to delay or even prevent the development of ALS could be developed. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00011154

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Is there a higher than expected occurrence of ALS among deployed veterans as compared to non-deployed Gulf War veterans? Condition(s): Amyotrophic Lateral Sclerosis Study Status: This study is completed. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Cooperative Studies Program; Department of Defense; Centers for Disease Control and Prevention; Department of Health and Human Services; ALS Association Purpose - Excerpt: Recently, concern has arisen regarding a possible elevated occurrence of ALS among veterans who served in the Persian Gulf during Operations Desert Shield (August 2, 1990 - January 15, 1991), Desert Storm (January 16, 1991 - February 28, 1991) and Clean-up (March 1, 1991 - July 31, 1991). This study involves an epidemiologic investigation into the occurrence of ALS among veterans of the Gulf War. This study will further define the epidemiology of this neurological disease among younger individuals while determining whether there is a higher than expected occurrence. It

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will also ascertain the etiologic importance of deployment to the Persian Gulf and exposure to specific environmental factors in that geographic area. VA is leading this joint federal government epidemiologic study that also involves DoD, HHS, CDC, and academic centers of excellence in neurology, with advice from the ALS Association. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00007722 •

Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis Condition(s): Primary Lateral Sclerosis; Hereditary Spastic Paraplegia; Amyotrophic Lateral Sclerosis Study Status: This study is completed. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study will use a magnetic resonance imaging technique called nuclear magnetic spectroscopy (H-MRS) to define the pathology and progression of primary lateral sclerosis, hereditary spastic paraplegia and amyotrophic lateral sclerosis and assess the usefulness of this technique in evaluating patients' response to therapy. H-MRS will be used to examine metabolic changes in the parts of the brain and spinal cord (motor cortex and corticospinal tract) involved in movement. Normal volunteers and patients with primary lateral sclerosis, hereditary spastic paraplegia or amyotrophic lateral sclerosis between 21 and 65 years of age may be eligible for this study. Participants will have up to five H-MRS studies, including baseline and followup tests. For this procedure, the subject lies on a stretcher that is moved into a strong magnetic field. Earplugs are worn to muffle the loud knocking noise that occurs during switching of radio frequencies. The subject will be asked to lie still during each scan, for 1 to 8 minutes at a time. Total scanning time varies from 20 minutes to 2 hours, with most examinations lasting between 45 and 90 minutes. Communication with the medical staff is possible at all times during the scan. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023075

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Phase II Study of Leuprolide and Testosterone for Men with Kennedy's Disease or Other Motor Neuron Disease Condition(s): Spinal Muscular Atrophy; Amyotrophic Lateral Sclerosis; Spinobulbar Muscular Atrophy Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Ohio State University Purpose - Excerpt: Objectives: I. Evaluate the effects of androgen suppression with leuprolide and androgen replacement with testosterone enanthate on muscle strength in men with Kennedy's disease or other motor neuron disease. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/show/NCT00004771 •

Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS Condition(s): Amyotrophic Lateral Sclerosis Study Status: This study is completed. Sponsor(s): Avanir Pharmaceuticals Purpose - Excerpt: The purpose of this study is to compare and evaluate the safety of AVP-923 (dextromethorphan/quinidine) for the treatment of emotional lability in ALS patients. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00021697

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “Lou Gehrig’s disease” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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

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

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

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

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

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•

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

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

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

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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

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

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

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

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

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CHAPTER 5. PATENTS ON LOU GEHRIG’S DISEASE 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 “Lou Gehrig’s disease” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Lou Gehrig’s disease, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Lou Gehrig’s Disease By performing a patent search focusing on Lou Gehrig’s disease, 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 Lou Gehrig’s disease: •

Anticonvulsant derivatives useful in treating amyotrophic lateral sclerosis (ALS) Inventor(s): Shank; Richard P. (Blue Bell, PA) Assignee(s): Ortho Pharmaceutical Corporation (Raritan, NJ) Patent Number: 5,753,694 Date filed: June 23, 1997 Abstract: Disclosed herein is a method of treating amyotrophic lateral sclerosis with topiramate and related compounds. Excerpt(s): This application claims priority to provisional application Ser. No. 60/022,006, filed Jun. 28, 1996. Compounds of Formula I were initially found to possess anticonvulsant activity in the traditional maximal electroshock seizure (MES) test in mice (SHANK, R. P., GARDOCKI, J. F., VAUGHT, J. L., DAVIS, C. B., SCHUPSKY, J. J., RAFFA, R. B., DODGSON, S. J., NORTEY, S. O., and MARYANOFF, B. E., Epilepsia 35 450-460, 1994). Subsequent studies revealed that Compounds of Formula I were also highly effective in the MES test in rats. More recently topiramate was found to effectively block seizures in several rodent models of epilepsy (J. NAKAMURA, S. TAMURA, T. KANDA, A. ISHII, K. ISHIHARA, T. SERIKAWA, J. YAMADA, and M. SASA, Eur. J. Pharmacol. 254 83-89,1994), and in an animal model of kindled epilepsy (A. WAUQUIER and S. ZHOU, Epilepsy Res. 24, 73-77, 1996). Recent preclinical studies on topiramate have revealed previously unrecognized pharmacological properties which suggest that topiramate should be effective in treating some other neurological disorders. One of these is amyotrophic lateral sclerosis (ALS). Web site: http://www.delphion.com/details?pn=US05753694__

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Method for diagnosing amyotrophic lateral sclerosis Inventor(s): Appel; Stanley H. (Houston, TX), Smith; R. Glenn (Houston, TX), Stefani; Enrico (Houston, TX) Assignee(s): Baylor College of Medicine (Houston, TX) Patent Number: 5,851,783 Date filed: February 13, 1995 Abstract: A method and kit are described that are useful in the diagnosis of amyotrophic lateral sclerosis or the evaluation of its progression. According to the method, a purified voltage-sensitive calcium channel complex is contacted with a biological fluid obtained from a person suspected of having, or known to have, amyotrophic lateral sclerosis. The voltage-sensitive calcium channel is of a type that ALS sera selectively reacts with. The reaction takes place for a time and under conditions sufficient for the calcium channel complex and anti-calcium channel complex antibodies that may be present in the biological fluid to form an antigen/antibody complex. The presence or absence of the antigen/antibody complex is then determined. Excerpt(s): This invention relates to the diagnosis of amyotrophic lateral sclerosis. Additional evidence for autoimmunity in the animal models is the ability of immunoglobulins from affected guinea pigs to passively transfer physiological

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abnormalities of the neuromuscular junction into mice. Following the globulin injections, there is an increase in miniature end plate potential (MEPP) frequency, with normal MEPP amplitude, decay time constant, and resting membrane potential. Similar passive transfer experiments using human immunoglobulins also demonstrate an increased MEPP frequency. The present invention relates, in one aspect, to an improvement in a procedure for diagnosis of amyotrophic lateral sclerosis, or the evaluation of the progression of that disease. The improvement involves determining, in an immunoassay, the presence in a biological fluid obtained from person having ALS of antibodies that selectively react, or cross-react, with the alpha.sub.1 subunit of L-type skeletal muscle calcium channel. In another aspect of the invention, purified L-type skeletal muscle calcium channel is contacted with a biological fluid obtained from an individual having ALS. The reaction takes place for a time and under conditions sufficient for the channel and anti-channel antibodies to form an antigen/antibody complex. The presence or absence of the complex is then determined in order to aid in ALS diagnosis or prognosis. In another aspect, the invention involves a method for determining ALS specific antibodies from a biological fluid obtained from an individual having ALS. The method comprises the steps of providing the ALS specific antibodies; selectively insolubilizing said ALS specific antibodies by an antibody/antigen reaction; determining the presence or absence of insolubilized ALS specific antibodies by means of a detectable label; and correlating the presence or absence of said detectable label with the presence or absence of the ALS specific antibodies. Web site: http://www.delphion.com/details?pn=US05851783__ •

Method for treating amyotrophic lateral sclerosis Inventor(s): Brooks; Benjamin Rix (4818 Fond Du Lac Trail, Madison, WI 53705) Assignee(s): none reported Patent Number: 5,780,489 Date filed: August 21, 1996 Abstract: The invention provides a method for treating amyotrophic lateral sclerosis in a patient which comprises administering to the patient an effective amount of a noncysteine glutathione precursor or a glutathione derivative so as to increase the intracellular glutathione levels and alleviate a symptom of amyotrophic lateral sclerosis. The non-cysteine substrate may be a thiazolidine-4-carboxylate analog, a thiazolidine-4-carboxylate analogs ester, or a pharmaceutically acceptable salt thereof. Excerpt(s): The present invention relates to a method for the treatment of amyotrophic lateral sclerosis (ALS). In particular, it relates to the use of either glutathione (GSH) derivatives such as glutathione alkyl monoesters or glutathione diesters or non-cysteine glutathione precursors to increase intracellular GSH levels in neurons, particularly motor neurons. GSH derivatives or non-cysteine glutathione precursors protect neurological cells from oxidative damage, thereby preventing, reducing the progression of, alleviating the symptoms of and/or treating ALS. Preferably, the non-cysteine glutathione precursor is a thiazolidine-4-carboxylate analog, such as L-2oxothiazolidine-4-carboxylate. Clinical signs of both lower and upper motor neuron involvement are required for a definitive diagnosis. Symptoms can begin either in bulbar or limb muscles (L P Rowland, 1995). The median age of onset is 55 and the median survival is less than five years. One of the characteristics is the progressive loss of muscle strength. Age and gender are the only risk factors repeatedly documented in epidemiological studies (J F Kurtzke, 1991, "Risk Factors in Amyotrophic Lateral

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Sclerosis," Adv Neurol 56: 245-270). There is a slight male predominance (3:2 male to female ratio) in sporadic ALS. There is no racial or geographic predisposition. The cause of sporadic ALS is unknown. Many causes of ALS have been proposed including atypical poliovirus infection, intoxication by exogenous metal-toxins, autoimmune processes targeting motor neurons, cytoskeletal abnormalities, trophic factor deprivation, mitochondrial dysfunction, and toxicity from excess excitation of the motor neuron by transmitters such as glutamate (L P Rowland, "Ten central themes in a decade of ALS research," in Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases, ed. L P Rowland, Advances in Neurology (Raven Press, 1992), 3-23). Given the clinical and epidemiological similarity between sporadic and FALS, it is a reasonable premise that an understanding of the familial disease will illuminate possible pathophysiological mechanisms in sporadic ALS. Web site: http://www.delphion.com/details?pn=US05780489__ •

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 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__

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Method for treatment of amyotrophic lateral sclerosis comprising administration of DMP Inventor(s): Salazar-Grueso; Edgar F. (Chicago, IL) Assignee(s): Arch Development Corporation (Chicago, IL) Patent Number: 5,229,394 Date filed: July 30, 1990 Abstract: A method for treating ALS (Amyotrophic Lateral Sclerosis) is disclosed. The inventive method comprises the administration of controlled dosages of dextromethorphan in therapeutically effective amounts in a pharmaceutically acceptable vehicle Dextromethorphan (DMP) is a dimethylaminomethyl-substituted phenol, a sigma receptor antagonist known also as d-3-methoxy-N methylmorphinan, a d-isomer of the codeine analog, levorphanol. The inventive method has proven useful in controlling the progression of ALS in afflicted patients. Excerpt(s): This invention relates to a method for treatment of Amyotrophic Lateral Sclerosis and other neurodegenerative disorders. This invention further relates to a method for treatment of Amyotrophic Lateral Sclerosis and other neurodegenerative disorders by administering a medicament in controlled doses of therapeutically effective amounts. Amyotrophic Lateral Sclerosis (ALS) is a progressive degenerative disease of the motor system which is usually relentlessly progressive, leading to death in half the cases within three years of onset. It is related to a group of diverse motor-system diseases which include Huntington's Chorea, Parkinson's disease and Alzheimer's disease. Numerous agents have been tried therapeutically in ALS, but none have been unequivocally demonstrated to benefit the disorder. This suggested to us that the LBMAA might be affecting a neuroreceptor type responsible for the ALS symptoms. It is known that other excitatory amino acids can bind in vitro to neuronal receptors. It has further been demonstrated in recent years that the dextrorotary opioid derivative dextromethorphan (DMP) binds to excitatory amino acid receptors in the brain. DMP has long been known as a highly effective cough suppressant. We, therefore, theorized that since a neuro-excitatory receptor in the brain appears to be adversely affected by LBMAA and may produce the motor degeneration characteristic of ALS, the action of LBMAA with the involved receptors might be antagonized by an agent such as DMP that suppresses central synaptic transmission. Web site: http://www.delphion.com/details?pn=US05229394__

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Method of blocking cytotoxic activity in patients with amyotrophic lateral sclerosis using antibodies to Fc.gamma.RIII Inventor(s): Schubert; Walter (Am Muhlengrund 9, D-39175 Biederitz, DE) Assignee(s): none reported Patent Number: 6,638,506 Date filed: September 7, 1999 Abstract: The present invention is directed to a method of blocking the cytotoxic activity of Fc.gamma.RIII receptor-positive immune cells in a patient with amyotrophic lateral sclerosis using antibodies specific for Fc.gamma.RIII receptor. In one aspect, the antibody may be a monoclonal antibody. In another aspect, the antibody or the monoclonal antibody may be conjugated with a cytotoxic substance. In a further aspect,

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the antibody binds to the Fc.gamma.RIII receptor, inactivates the receptor, and destroys cellular forms containing the receptor. Excerpt(s): This application claims the priority of PCT International: Application No. PCT/DE97/02883 under 35 U.S.C.sctn.371, filed on Dec. 10, 1997, the whole of which is hereby incorporated by reference herein. The invention relates to the use of substances having a well-directed, i.e. selective, effect on a certain receptor family (Fc.gamma.R) or on those immune system cells with defined surface characteristics which express said receptor and whose presence--in examinations performed by the applicant--has been found to be specific, or its number specifically increased, in the case of amyotrophic lateral sclerosis. Amyotrophic lateral sclerosis (in the following referred to as ALS, its abbreviation) is a neurodegenerative disease of the human motoneuron system which usually takes a lethal course within 3 to 5 years, whose causes have not been determined etiologically and for which there is no, or no significant, therapy as yet. The progressive decay of nerve cells of the first and second motor neurons are the cause of an increasing paralysis of the voluntary muscles, eventually leading to a total walking inability and the increasing paralysis of the respiratory musculature. It has largely been proven that cellular and humoral (antibody-mediated) immunological processes play an important role, if yet unexplained in the individual case, in the pathogenesis of ALS. Worldwide, the prevalence of this disease is 4 in 100,000 and its incidence is 1 in 100,000 inhabitants. Web site: http://www.delphion.com/details?pn=US06638506__ •

Use of 2-amino-6-(trifluoromethoxy)benzothiazole for obtaining a medicament for the treatment of amyotrophic lateral sclerosis Inventor(s): Louvel; Erik (Manosque, FR) Assignee(s): Rhone Poulenc Rorer S.A. (FR) Patent Number: 5,527,814 Date filed: October 21, 1994 Abstract: Use of 2-amino-6-(trifluoromethoxy)benzothiazole, or a salt of this compound with a pharmaceutically acceptable acid, for obtaining a medicament intended for the treatment of motor neuron diseases, in particular amyotrophic lateral sclerosis, and especially amyotrophic lateral sclerosis with early bulbar involvement or the bulbar form of the disease. Excerpt(s): The present invention relates to the use of 2-amino-6(trifluoromethoxy)benzothiazole, or a salt of this compound with a pharmaceutically acceptable acid, for obtaining a medicament intended for the treatment of motor neuron diseases, in particular amyotrophic lateral sclerosis commonly known as Lou Gehrig's Disease, and especially amyotrophic lateral sclerosis with early bulbar involvement or the bulbar form of the disease. 2-Amino-6-(trifluoromethoxy)benzothiazole (international non-proprietary name: riluzole) is known to be useful as an anticonvulsant, anxiolytic and hypnotic medicament (Patent EP 50,551), in the treatment of schizophrenia (EP 305,276), in the treatment of sleep disorders and depression (EP 305,277), in the treatment of cerebrovascular disorders and as an anaesthetic (EP 282,971). It has now been found that 2-amino-6-(trifluoromethoxy)benzothiazole, or a salt of this compound with a pharmaceutically acceptable acid, is useful in the treatment of motor neuron diseases, in particular amyotrophic lateral sclerosis, and especially amyotrophic lateral sclerosis with early bulbar involvement. Web site: http://www.delphion.com/details?pn=US05527814__

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Use of ginkgo biloba extracts for preparing a medicine for treating amyotrophic lateral sclerosis Inventor(s): Christen; Yves (Paris, FR) Assignee(s): Societe de Conseils de Recherches et d'Applications Scientifiques (FR) Patent Number: 6,524,629 Date filed: January 23, 2001 Abstract: The invention relates to the use of extracts of Ginkgo biloba, and in particular extracts of Ginkgo biloba comprising 20 to 30% of flavoneglycosides, 2.5 to 4.5% of ginkgolides A, B, C and J, 2 to 4% of bilobalide, less than 10% of proanthocyanidines and less than 10 ppm of compounds of alkylphenol type, for preparing a medicament intended to treat amyotrophic lateral sclerosis. Excerpt(s): The invention relates to the use of extracts of Ginkgo biloba for preparing a medicament intended to treat amyotrophic lateral sclerosis (ALS). It is already known that extracts of Ginkgo biloba have an activity in the cardiovascular field (in particular the reduction of platelet adhesion), in the central nervous field (in particular a neuroprotective activity) or in the neurosensory system (in particular retinal protection); cf. for example DeFeudis et al., Ginkgo Biloba Extract (EGb 761), Pharmaceutical Activities and Clinical Applications (Elsevier, Paris, 1991). Their preparation has been the subject of a certain number of patents, of which there can be mentioned the European Patents EP 431 535 and EP 431 536, and the American Patent U.S. Pat. No. 5,389,370. Certain products can be used in the treatment of ALS. In particular there can be mentioned riluzole, gabapentin, 1-(2-naphth-2-ylethyl)-4-(3-trifluoromethylphenyl)1,2,3,6-tetrahydropyrid ine or vitamin E (cf. Gurney M. E. et al., Ann. Neurol., 39 (1996), 147-157; Patent Application PCT WO 97/15304). Web site: http://www.delphion.com/details?pn=US06524629__

Patent Applications on Lou Gehrig’s Disease 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 Lou Gehrig’s disease: •

Method of treatment of amyotrophic lateral sclerosis with a protein extractable from mammalian organs Inventor(s): Panerai, Albert; (Milano, IT) Correspondence: Nixon & Vanderhye, PC; 1100 N Glebe Road; 8th Floor; Arlington; VA; 22201-4714; US Patent Application Number: 20030162705 Date filed: March 21, 2003 Abstract: A method of treatment of patients affected by amyotrophic lateral sclerosis comprising the administration of an effective amount of a 14 kDa protein extractable from mammalian organs, particularly mammalian liver.

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

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Excerpt(s): The present invention concerns a method of treatment of patients affected by amyotrophic lateral sclerosis comprising the administration of an effective amount of a 14 kDa protein extractable from mammalian organs, particularly mammalian liver. Amyotrophic lateral sclerosis (incidence of 1.4 to 4.7/100.000) also named motor neuron disease, is a degenerative disease characterized by progressive paralysis which affects elderly subjects (65-70 years), developing into complete paralysis and death and in a short time. Several biochemical and genetic factors seem to be involved in the pathogenesis of ALS, which remains however to be still elucidated. An increase in some intracellular proteins (cytoskeleton) which affect cell activity and neurotransmission, seems to be the main cause of amyotrophic lateral sclerosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Naaladase inhibitors for treating amyotrophic lateral sclerosis Inventor(s): Slusher, Barbara S.; (Kingsville, MD), Wozniak, Krystyna; (Bel Air, MD) Correspondence: Lyon & Lyon Llp; 633 West Fifth Street; Suite 4700; Los Angeles; CA; 90071; US Patent Application Number: 20020013295 Date filed: May 30, 2001 Abstract: The present invention relates to pharmaceutical compositions and methods for treating amyotrophic lateral sclerosis using NAALADase inhibitors. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/207,317 filed on May 30, 2000. The present invention relates to pharmaceutical compositions and methods for treating amyotrophic lateral sclerosis ("ALS" ) using NAALADase inhibitors. The NAALADase enzyme, also known as prostate specific membrane antigen ("PSM" or "PSMA" ) and human glutamate carboxypeptidase II ("GCP II" ), catalyzes the hydrolysis of the neuropeptide N-acetyl-aspartyl-glutamate ("NAAG") to N-acetyl-aspartate ("NAA") and glutamate. Based upon amino acid sequence homology, NAALADase has been assigned to the M28 family of peptidases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Remedies for amyotrophic lateral sclerosis Inventor(s): Funakoshi, Hiroshi; (Osaka, JP), Nakamura, Toshikazu; (Osaka, JP), Sun, Woong; (Seoul, KR) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20030176347 Date filed: May 14, 2003 Abstract: The invention presents a therapeutic agent (and progress suppressant) for amyotrophic lateral sclerosis (ALS) containing HGF and/or HGF gene as active ingredient. HGF has an effect of improving the motor function of ALS and life span through two actions, that is, direct neuronutrient factor activity on motoneurons, and indirect improving action of glutamate cytotoxicity on motoneurons by maintaining the level of glutamate transporter in astrocytes. Hence, HGF and/or HGF gene can be used as an effective therapeutic agent not known in the past.

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Excerpt(s): The present invention relates to a remedy for amyotrophic lateral sclerosis (ALS). More particular, the invention relates to a remedy for ALS containing HGF (hepatocyte growth factor) and/or HGF genes as active ingredients. Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by progressive loss of motoneurons and degeneration of motor axons, which results in motor dysfunction and shortening of life span. About 15% of ALS patients are patients with familial ALS (FALS), and about 15% to 25% of FALS patients carry mutations in the gene encoding Cu.sup.2+/Zn.sup.2+ superoxide dismutase (SOD1). Transgenic mice with high levels of mutant SOD1 protein and activity develop diseases similar to both familial and sporadic ALS, and such muted SOD1 overexpressing transgenic mice are used as a model for ALS. In the invention, too, G93A mice (Science, 264, 1772-1775, 1994) were used as muted SOD1 (G93A) overexpressing transgenic mice. Since degeneration of motoneurons is thought to be a first sign of the disease, many approaches had been focused to directly support the survival of motoneurons. However, these attempts were not satisfactory. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of difluoromethylornithine (DFMO) for the treatment of amyotrophic lateral sclerosis Inventor(s): Ramesh, Tennore; (Westwood, MA), Scott, Sean; (San Francisco, CA) Correspondence: Nutter Mcclennen & Fish Llp; World Trade Center West; 155 Seaport Boulevard; Boston; MA; 02210-2604; US Patent Application Number: 20030130350 Date filed: November 1, 2002 Abstract: The present invention provides methods and compositions for modulating polyamine pathway activity as a means for ameliorating neurodegenarative disorders. In particular, for ameliorating the symptoms or onset of amyotrophic lateral sclerosis (ALS) by modulating the gene and protein products involved the polyamine pathway, such as by inhibiting the enzyme, ornithine decarboxylase (ODC), involved in the synthesis of the polyamine, putrescine. Compositions and methods are disclosed for inhibiting the polyamine pathway producing lower polyamine levels resulting in a beneficial effect on ALS. This can be accomplished by using modulating agents such as analogs, or polyamine analogs, and antiproliferative drugs. In particular, the ODC inhibitor difuoromethylornithine (DFMO) is disclosed as a useful pharmacological agent in the modulation and treatment of ALS. Screening assays for pharmacological agents that are capable of decreasing polyamine levels and/or reducing cell proliferation are also disclosed. Excerpt(s): This application claims priority to provisional application U.S. Ser. No. 60/333,263, filed Nov. 16, 2001 entitled "Methods for Monitoring and Treating Amyotrophic Lateral Sclerosis". The technical field of the invention concerns methods and compositions for the treatment of neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS). Neurodegencrative diseases are generally characterized by a degeneration of neurons in either the brain or the nervous system of an individual. In addition to ALS, various other diseases, such as Huntington's disease, Parkinson's disease, Alzheimer's disease and Multiple Sclerosis, fall within this category. These diseases are debilitating and the damage that they cause is often irreversible. Moreover, in the case of a number of these diseases, the outcome is invariably fatal.

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

Use of substances with immunomodulating activity for the treatment of amyotrophic lateral sclerosis Inventor(s): Schubert, Walter; (Biederitz, DE) Correspondence: Weingarten, Schurgin, Gagnebin & Hayes Llp; Ten Post Office Square; Boston; MA; 02109; US Patent Application Number: 20010009898 Date filed: March 8, 2001 Abstract: It has been discovered that, in the case of amyotrophic lateral sclerosis, usually a lethal motoneuron disease, a large number of the immune system cells expressing receptors (Fc receptors) of immunoglobulins (IgC), preferably immunoglobulins of classes 1 and 3 (Fc.gamma.RIII receptors for IgG1 and IgG3) can be found in the blood stream. Selective destruction or functional obstruction of these cells can be achieved in order to treat amyotrophic lateral sclerosis (ALS) with the following substances, or their preparations (in the form of intravenous applications or preparations), individually or in combination: a) antibodies, preferably monoclonal antibodies, which bind to Fc.gamma.RIII receptors, inactivate said receptors or individual species of this receptor family or cause the destruction of cellular forms containing said receptors, and/or are coupled to other cytotoxic substances, b) soluble Fc.gamma. receptors, preferably soluble Fc.gamma.RIII receptors, which bind to immunoglobulins, preferably G immunoglobulins of under-class 1 (IgG1) and/or 3 (IgG3), c) the protein V which binds to immunoglobulin G, obtained from Gardnerella vaginalis, and d) antisense RNA molecules which bind specifically to MRNA sequences of Fc.gamma. receptors, preferably to those of Fc.gamma.RIII receptors. Excerpt(s): The invention relates to the use of substances having a well-directed, i.e. selective, effect on a certain receptor family (Fc.gamma.R) or on those immune system cells with defined surface characteristics which express said receptor and whose presence--in examinations performed by the applicant--has been found to be specific, or its number specifically increased, in the case of amyotrophic lateral sclerosis. Amyotrophic lateral sclerosis (in the following referred to as ALS, its abbreviation) is a neurodegenerative disease of the human motoneuron system which usually takes a lethal course within 3 to 5 years, whose causes have not been determined etiologically and for which there is no, or no significant, therapy as yet. The progressive decay of nerve cells of the first and second motor neurons are the cause of an increasing paralysis of the voluntary muscles, eventually leading to a total walking inability and the increasing paralysis of the respiratory musculature. It has largely been proven that cellular and humoral (antibody-mediated) immunological processes play an important role, if yet unexplained in the individual case, in the pathogenesis of ALS. Worldwide, the prevalence of this disease is 4 in 100,000 and its incidence is 1 in 100,000 inhabitants. Numerous examination results seem to imply that immunological mechanisms are at play in the pathogenesis of amyotrophic lateral sclerosis. The following findings substantiate this assumption: Cytotoxic serum activity of ALS patients in neuronal cell cultures; serum immunoglobulin G (IgG) toxicity against spinal and cortical neurons as well as voltage-dependent calcium channel proteins; cytotoxicity of the cerebrospinal fluid of ALS patients against glutamate receptors; changes of the serum concentration of IgG isotypes; immune response of peripheral blood lymphocytes of ALS patients to isolated cell membranes; detection of invasive immune system cells in the motoneuron

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system of ALS patients Here, these cells seem to be involved in the motoneuron damaging mechanisms (the quotations of the individual above data can be found in: Westarp, M. E. et al., Neurosci. Lett. 173, 124-126, 1994). 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 Lou Gehrig’s disease, 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 “Lou Gehrig’s disease” (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 Lou Gehrig’s disease. You can also use this procedure to view pending patent applications concerning Lou Gehrig’s disease. 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 6. BOOKS ON LOU GEHRIG’S DISEASE Overview This chapter provides bibliographic book references relating to Lou Gehrig’s disease. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Lou Gehrig’s disease 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 “Lou Gehrig’s disease” (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 Lou Gehrig’s disease: •

Dying Well: The Prospect for Growth at the End of Life Source: New York, NY: Riverhead Books. 1997. 299 p. Contact: National Hospice Organization Store. 200 State Road, South Deerfield, MA 01373. PRICE: $24.95. ISBN: 1573220515. Summary: This book chronicles the end-of-life experiences of various people. Each of the 12 chapters deals with a specific aspect of human development or personal growth associated with this phase of life. Anecdotes deal with physical and mental debilitation, including amyotrophic lateral sclerosis (Lou Gehrig's disease), Alzheimer's disease and other dementias, heart disease, and various cancers. The appendix includes questions and answers about difficult situations involving terminally ill loved ones. The topics covered in the Appendix are: beginning to talk about dying, easing symptoms and

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bringing relief, dealing with doctors and the medical system, when you are the one who is dying, assisted suicide, and caring for a dying child. List of resources, index.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “Lou Gehrig’s disease” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “Lou Gehrig’s disease” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “Lou Gehrig’s disease” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

ALS-Lou Gehrig's Disease (Diseases and People) by Mary Dodson Wade (2001); ISBN: 0766015947; http://www.amazon.com/exec/obidos/ASIN/0766015947/icongroupinterna

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Brain Disorders Sourcebook: Basic Consumer Health Information About Strokes, Epilepsy, Amyotrophic Lateral Sclerosis (ALS/Lou Gehrig's Disease) Parkinson's Disease, Brain Tumors by Karen Bellenir (Editor) (1999); ISBN: 0780802292; http://www.amazon.com/exec/obidos/ASIN/0780802292/icongroupinterna

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Lou Gehrig's Disease by Lydia G. Sullivan; ISBN: 0806229993; http://www.amazon.com/exec/obidos/ASIN/0806229993/icongroupinterna

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Six Parts Love: One Family's Battle With Lou Gehrig's Disease by Roni Rabin; ISBN: 0684182815; http://www.amazon.com/exec/obidos/ASIN/0684182815/icongroupinterna

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CHAPTER 7. PERIODICALS AND NEWS ON LOU GEHRIG’S DISEASE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Lou Gehrig’s disease.

News Services and Press Releases One of the simplest ways of tracking press releases on Lou Gehrig’s disease 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 “Lou Gehrig’s disease” (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 Lou Gehrig’s disease. 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 “Lou Gehrig’s disease” (or synonyms). The following was recently listed in this archive for Lou Gehrig’s disease: •

Gulf War service linked to Lou Gehrig's disease Source: Reuters Health eLine Date: September 23, 2003

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Possible gene found for Lou Gehrig's disease Source: Reuters Health eLine Date: July 07, 2003

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Study looks at Gulf War vets, Lou Gehrig's disease Source: Reuters Health eLine Date: October 15, 2002

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Arthritis drug helps mice with Lou Gehrig's disease Source: Reuters Health eLine Date: September 27, 2002

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Mouse study reveals clues to Lou Gehrig's disease Source: Reuters Health eLine Date: August 26, 2002

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Job exposure to lead linked to Lou Gehrig's disease Source: Reuters Health eLine Date: May 09, 2002

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Copper may not be culprit in Lou Gehrig's disease Source: Reuters Health eLine Date: March 11, 2002

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Gulf War linked to risk of Lou Gehrig's disease Source: Reuters Health eLine Date: December 11, 2001

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Cancer drug shows promise for Lou Gehrig's disease Source: Reuters Health eLine Date: November 12, 2001

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Second Lou Gehrig's disease gene found Source: Reuters Health eLine Date: October 03, 2001

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Growth factor linked to Lou Gehrig's disease Source: Reuters Health eLine Date: May 29, 2001

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Lou Gehrig's disease on the rise in Norway Source: Reuters Health eLine Date: November 29, 2000

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Experimental drug slows Lou Gehrig's disease in mice Source: Reuters Health eLine Date: April 14, 2000

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Virus possibly linked to Lou Gehrig's disease Source: Reuters Health eLine Date: January 10, 2000

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Gene Flaws Tied To Lou Gehrig's Disease Source: Reuters Health eLine Date: March 23, 1998

Periodicals and News

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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 “Lou Gehrig’s disease” (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 “Lou Gehrig’s disease” (or synonyms). If you know the name of a company that is relevant to Lou Gehrig’s disease, 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 “Lou Gehrig’s disease” (or synonyms).

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Academic Periodicals covering Lou Gehrig’s Disease Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Lou Gehrig’s disease. In addition to these sources, you can search for articles covering Lou Gehrig’s disease 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 Lou Gehrig’s disease. 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 Lou Gehrig’s disease. 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 Lou Gehrig’s disease: Riluzole •

Systemic - U.S. Brands: Rilutek http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202792.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.

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.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to Lou Gehrig’s disease by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “Lou Gehrig’s disease” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact

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information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for Lou Gehrig’s disease: •

Creatine (Trade Name: Creapure) http://www.rarediseases.org/nord/search/nodd_full?code=1241

•

Creatine (Trade Name: Creapure) http://www.rarediseases.org/nord/search/nodd_full?code=1266

•

L-threonine (trade name: Threostat) http://www.rarediseases.org/nord/search/nodd_full?code=200

•

Neurotrophin-1 http://www.rarediseases.org/nord/search/nodd_full?code=219

•

Riluzole (trade name: Rilutek) http://www.rarediseases.org/nord/search/nodd_full?code=24

•

Orgotein for injection http://www.rarediseases.org/nord/search/nodd_full?code=318

•

Gabapentin (trade name: Neurontin) http://www.rarediseases.org/nord/search/nodd_full?code=713

•

Insulin-like growth factor-1 (trade name: Myotrophin) http://www.rarediseases.org/nord/search/nodd_full?code=72

•

Ciliary neurotrophic factor http://www.rarediseases.org/nord/search/nodd_full?code=641

•

Ciliary neurotrophic factor, recombinant human http://www.rarediseases.org/nord/search/nodd_full?code=643

•

L-2-oxothiazolidine-4-carboxylic acid (trade name: Procysteine) http://www.rarediseases.org/nord/search/nodd_full?code=784

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

•

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

•

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

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

10

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

•

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

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

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

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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 “Lou Gehrig’s disease” (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 5774 112 801 2 1 6690

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 “Lou Gehrig’s disease” (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 Lou Gehrig’s disease 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 Lou Gehrig’s disease. 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 Lou Gehrig’s disease. 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 “Lou Gehrig’s disease”:

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•

Guides on Lou Gehrig's disease Amyotrophic Lateral Sclerosis http://www.nlm.nih.gov/medlineplus/amyotrophiclateralsclerosis.html

•

Other guides Degenerative Nerve Diseases http://www.nlm.nih.gov/medlineplus/degenerativenervediseases.html Neurologic Diseases http://www.nlm.nih.gov/medlineplus/neurologicdiseases.html Neuromuscular Disorders http://www.nlm.nih.gov/medlineplus/neuromusculardisorders.html Parkinson's Disease http://www.nlm.nih.gov/medlineplus/parkinsonsdisease.html Spinal Muscular Atrophy http://www.nlm.nih.gov/medlineplus/spinalmuscularatrophy.html

Within the health topic page dedicated to Lou Gehrig’s disease, the following was listed: •

General/Overviews Amyotrophic Lateral Sclerosis http://www.nlm.nih.gov/medlineplus/tutorials/amyotrophiclateralsclerosisloade r.html Amyotrophic Lateral Sclerosis Source: American Speech-Language-Hearing Association http://www.asha.org/speech/disabilities/Amyotrophic-lateral-sclerosis.cfm Facts about Amyotrophic Lateral Sclerosis (ALS) Source: Muscular Dystrophy Association http://www.mdausa.org/publications/fa-als.html

•

Diagnosis/Symptoms Creatine Kinase Test Source: Muscular Dystrophy Association http://www.mdausa.org/publications/Quest/q71ss-cktest.html Electromyography and Nerve Conduction Velocities Source: Muscular Dystrophy Association http://www.mdausa.org/publications/Quest/q75ss.html

•

Treatment FDA Approves Enbrel to Treat Ankylosing Spondylitis Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01240.html

Patient Resources

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Coping ALS Association's Patient Bill of Rights for People Living with ALS Source: ALS Association http://www.alsa.org/als/rights.cfm For Caregivers Source: ALS Association http://www.alsa.org/als/care.cfm Reasons for Living with ALS Source: ALS Association http://www.alsa.org/als/living.cfm When a Loved One Has ALS: A Caregiver's Guide Source: Muscular Dystrophy Association http://www.mdausa.org/publications/alscare/index.html

•

Specific Conditions/Aspects Ask the Experts: Amyotrophic Lateral Sclerosis (ALS) - Diagnosis, Symptoms and Treatments Source: Muscular Dystrophy Association http://www.mdausa.org/experts/ask_als.html Frequently Asked Questions (FAQ) about the ALS/Virus Connection Source: Muscular Dystrophy Association http://www.mdausa.org/research/alsvirusfaq.html Oral Care for the Patient with ALS: A Guide for the Caregiver Source: ALS Association http://www.alsa.org/als/oralcare.cfm

•

Children Lou Gehrig's Disease (ALS) Source: Nemours Foundation http://kidshealth.org/kid/grownup/conditions/als.html

•

From the National Institutes of Health Amyotrophic Lateral Sclerosis (ALS) Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/pubs/als.htm

•

Journals/Newsletter ALS Newsletter Source: Muscular Dystrophy Association http://www.mdausa.org/publications/als/index.html

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•

Law and Policy Professional's Guide To Assisting Persons with ALS and Their Families with Obtaining Government Benefits Source: ALS Association http://www.alsa.org/als/benefits_ss.cfm

•

Organizations ALS Association http://www.alsa.org/ Muscular Dystrophy Association http://www.mdausa.org/ National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/ Society for Neuroscience http://web.sfn.org/

•

Research Doubling Up: Researchers Combine a Common Dietary Supplement with an Antibiotic to Treat Lou Gehrig's Disease Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/news_article_ALS_Combination_Tr eatment.htm Lipid Abnormalities Linked to Lou Gehrig's Disease Source: National Institute on Aging http://www.nih.gov/news/pr/aug2002/nia-21.htm Minocycline Delays Onset and Slows Progression of ALS in Mice Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/news_article_als_minocycline.htm New Clues to Muscle Atrophy in ALS, SMA, CMT Source: Muscular Dystrophy Association http://www.mdausa.org/research/011026newclues.html Transport Problems Cause Motor Neuron Degeneration Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/news_article_axon_transport_0503.h tm

•

Statistics Understanding ALS: Incidence of ALS Source: ALS Association http://www.alsa.org/als/incidence.cfm

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

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(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 Lou Gehrig’s disease. 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: •

Guide to Support Groups in Washington State, 1990-1991 Source: Olympia, WA: Washington Department of Social and Health Services. 1990. 78 p. Contact: Available from Aging and Adult Services Administration, Washington State Department of Social and Health Services. P.O. Box 45600, Olympia, WA 98504-0095. (800) 422-3263 or (206) 493-2500. PRICE: Free. Summary: This booklet, revised annually, provides a listing of major statewide and local support groups in Washington State designed to assist caregivers and families of patients with various diseases, including Alzheimer's disease. It provides information for caseworkers, physicians, nurses, case managers and other providers so that they can refer caregivers or family and elders to groups for support and assistance. The first section of the guide describes national or state organizations, their goals, and headquarters location. Support groups are then listed alphabetically within each county. Information about the location and the facilitator's name and telephone number is provided. Organizations listed include the Amyotrophic Lateral Sclerosis (or Lou Gehrig's Disease) Health Support Services, Alzheimer's Association, American Cancer Society, American Lung Association of Washington, National Multiple Sclerosis Society, Washington Advocates for the Mentally Ill, Washington Neurological Alliance, Washington State Head Injury Foundation, and Washington State Resources for Parkinson Disease. The National Guideline Clearinghouse™

The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “Lou Gehrig’s disease” (or synonyms). The following was recently posted:

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•

Practice parameter: the care of the patient with amyotrophic lateral sclerosis (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology: ALS Practice Parameters Task Force Source: American Academy of Neurology - Medical Specialty Society; 1999 April; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2819&nbr=2045&a mp;string=Lou+AND+Gehrig''s+AND+disease Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Amyotrophic Lateral Sclerosis Fact Sheet Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7227 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 Lou Gehrig’s disease. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites 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

•

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

•

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

•

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

•

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

•

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

•

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

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Associations and Lou Gehrig’s Disease The following is a list of associations that provide information on and resources relating to Lou Gehrig’s disease: •

Amyotrophic Lateral Sclerosis Association Telephone: (818) 880-9007 Toll-free: (800) 782-4747 Fax: (818) 880-9006 Email: [email protected] Web Site: http://www.alsa.org Background: The Amyotrophic Lateral Sclerosis Association (ALSA) is a national notfor-profit voluntary health organization dedicated to the fight against Amyotrophic Lateral Sclerosis (ALS). Amyotrophic Lateral Sclerosis, also known as 'Lou Gehrig s Disease,' is a rapidly progressive neuromuscular disease characterized by degeneration of the motor neurons responsible for transmitting electrical impulses from the brain to the voluntary muscles throughout the body. ALSA consists of a growing network of over 135 local volunteer chapters and support groups across the United States. The Association seeks to encourage, identify, fund, and monitor cutting-edge research into the cause, prevention, and possible cure of ALS. The organization also offers support on how to cope with the disease, provides referrals, and serves as the national information resource on ALS for medical professionals, affected individuals, and family members. The Information Center provides basic information about ALS and answers specific questions about the disease. ALSA also makes referrals to physicians, clinics, extended care facilities, home health agencies, visiting nurse agencies, transportation assistance, and medical equipment supplies. In addition, ALSA has a patient registry of individuals with the disease and distributes information on the latest research and clinical trials regarding ALS. Relevant area(s) of interest: Amyotrophic Lateral Sclerosis, Lou Gehrig's Disease, Motor Neuron Disease

•

Amyotrophic Lateral Sclerosis Society of Canada Telephone: 416-497-2267 Toll-free: (800) 267-4257 Fax: 416-497-1256 Email: [email protected] Web Site: http://www.als.ca Background: The Amyotrophic Lateral Sclerosis (ALS) Society of Canada is a national not-for-profit organization dedicated to providing information and support to individuals and family members affected by ALS and to promoting research to find a cure for the disorder. Amyotrophic Lateral Sclerosis (ALS), also known as 'Lou Gehrig s Disease,' is a rapidly progressive neuromuscular disease characterized by degeneration of the motor neurons responsible for transmitting electrical impulses from the brain to the voluntary muscles throughout the body. Established in 1977, the ALS Society, which operates in many locations across Canada, provides support and counseling for people with ALS, their families, and caregivers; raises funds to support research into the cause of and a potential cure for ALS; engages in patient advocacy; offers networking services; and provides equipment such as wheelchairs.

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Relevant area(s) of interest: Amyotrophic Lateral Sclerosis, Lou Gehrig's Disease •

Les Turner Amyotrophic Lateral Sclerosis Foundation, Ltd Telephone: (847) 679-3311 Toll-free: (888) 257-1107 Fax: (847) 679-9109 Email: [email protected] Web Site: http://www.lesturnerals.org Background: The Les Turner Amyotrophic Lateral Sclerosis Foundation is a voluntary health organization dedicated to raising funds for ALS research, patient services, and public awareness. Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's Disease, is a progressive neurological disease that causes impaired breathing, speaking, and swallowing, as well as muscle weakness and eventually total paralysis. Intellectual function remains unaffected and there is no known cure. The Les Turner ALS Foundation was established in 1977 and provides educational materials for affected individuals and family members, health care professionals, and the general public. Program services include referrals and counseling, audio-visual aids, and a periodic newsletters entitled 'ALS Today.' Consisting of over 1,000 members, the organization offers support groups and patient networking to affected individuals, family members, and caregivers.

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Lou Gehrig’s disease. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Lou Gehrig’s disease. 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 Lou Gehrig’s disease. 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/.

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Simply type in “Lou Gehrig’s disease” (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 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 “Lou Gehrig’s disease”. 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 “Lou Gehrig’s disease” (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 “Lou Gehrig’s disease” (or a synonym) into the search box, and click “Submit Query.”

95

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/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

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

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

22

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

•

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

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

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

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

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

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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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

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

100 Lou Gehrig’s Disease

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

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

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

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). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on Lou Gehrig’s disease: •

Basic Guidelines for Lou Gehrig’s Disease Amyotrophic lateral sclerosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000688.htm

•

Signs & Symptoms for Lou Gehrig’s Disease Ankle, feet, and leg swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003104.htm Apnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003069.htm Clumsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003198.htm Difficulty breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm


Difficulty swallowing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm Hoarseness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003054.htm Incontinence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003142.htm Loss of bladder control Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003142.htm Muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Muscle atrophy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003188.htm Muscle contractions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Muscle cramps Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Muscle weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm Paralysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003190.htm Spasms Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Spasticity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003297.htm Speech impairment Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003204.htm Urinary frequency/urgency, increased Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003140.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm •

Diagnostics and Tests for Lou Gehrig’s Disease EMG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003929.htm Head CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003786.htm

Online Glossaries 103

MRI of head Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003791.htm •

Background Topics for Lou Gehrig’s Disease ALS - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002189.htm Aspiration Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002216.htm Choking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000047.htm Proximal Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002287.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

105

LOU GEHRIG’S DISEASE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [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] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Actin: Essential component of the cell skeleton. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different 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] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [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] 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 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] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis.


[NIH]

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] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] 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] 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] 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] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] 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] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Aminolevulinic Acid: A compound produced from succinyl-CoA and glycine as an intermediate in heme synthesis. [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] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anaesthetic: 1. Pertaining to, characterized by, or producing anaesthesia. 2. A drug or agent that is used to abolish the sensation of pain. [EU] 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]

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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] Androgen suppression: Treatment to suppress or block the production of male hormones. Androgen suppression is achieved by surgical removal of the testicles, by taking female sex hormones, or by taking other drugs. Also called androgen ablation. [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] Ankyrin Repeat: Protein motif that contains a 33-amino acid long sequence that often occurs in tandem arrays. This repeating sequence of 33-amino acids was discovered in ankyrin where it is involved in interaction with the anion exchanger (band 3 protein). Ankyrin repeats cooperatively fold into structures that mediate molecular recognition via proteinprotein interactions. [NIH] Anterior Horn Cells: Motor neurons in the anterior (ventral) horn of the spinal cord which project to skeletal muscles. [NIH] 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] 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] 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-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing 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] Antiproliferative: Counteracting a process of proliferation. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anxiolytic: An anxiolytic or antianxiety agent. [EU] 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] Aptitude: The ability to acquire general or special types of knowledge or skill. [NIH] Aqueous: Having to do with water. [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] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Aspartate: A synthetic amino acid. [NIH] Aspiration: The act of inhaling. [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 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] 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] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autopsy: Postmortem examination of the body. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [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

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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] 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 important. [NIH] Band 3 Protein: A ubiquitous membrane transport protein found in the plasma membrane of diverse cell types and tissues, and in nuclear, mitochondrial, and Golgi membranes. It is the major integral transmembrane protein of the erythrocyte membrane, comprising 25% of the total membrane protein and occurring at 1 million copies per cell. It exists as a dimer and provides a channel for the transport of anions across the membrane. [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] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] 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] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [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] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [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] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluids: Liquid components of living organisms. [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] Brain Diseases: Pathologic conditions affecting the brain, which is composed of the intracranial components of the central nervous system. This includes (but is not limited to) the cerebral cortex; intracranial white matter; basal ganglia; thalamus; hypothalamus; brain stem; and cerebellum. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [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] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bulbar: Pertaining to a bulb; pertaining to or involving the medulla oblongata, as bulbar paralysis. [EU] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [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

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functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Carbohydrates: The largest class of organic compounds, including starches, glycogens, cellulose, gums, and simple sugars. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. [NIH] 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] Carcinogen: Any substance that causes cancer. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [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] 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] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] 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 Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [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 motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cellular metabolism: The sum of all chemical changes that take place in a cell through which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [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 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 Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [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] Cerebrovascular Disorders: A broad category of disorders characterized by impairment of blood flow in the arteries and veins which supply the brain. These include cerebral infarction; brain ischemia; hypoxia, brain; intracranial embolism and thrombosis; intracranial arteriovenous malformations; and vasculitis, central nervous system. In common usage, the term cerebrovascular disorders is not limited to conditions that affect the cerebrum, but refers to vascular disorders of the entire brain including the diencephalon; brain stem; and cerebellum. [NIH] 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] 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] 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] 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] 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] 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

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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] 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] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] 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] 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] 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] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [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] 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] Computerized axial 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 CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Consciousness: Sense of awareness of self and of the environment. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [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] 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] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [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]

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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] 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] 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] Curative: Tending to overcome disease and promote recovery. [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, . 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] 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] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [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] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexterity: Ability to move the hands easily and skillfully. [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] Diagnostic procedure: A method used to identify a disease. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Difluoromethylornithine: DFMO. An anticancer drug that has been shown to reduce the risk of cancer in animals. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH]

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Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] 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] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [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] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [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] 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] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] 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] Electron Spin Resonance Spectroscopy: A technique applicable to the wide variety of substances which exhibit paramagnetism because of the magnetic moments of unpaired electrons. The spectra are useful for detection and identification, for determination of


electron structure, for study of interactions between molecules, and for measurement of nuclear spins and moments. (From McGraw-Hill Encyclopedia of Science and Technology, 7th edition) Electron nuclear double resonance (ENDOR) spectroscopy is a variant of the technique which can give enhanced resolution. Electron spin resonance analysis can now be used in vivo, including imaging applications such as magnetic resonance imaging. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in 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] Electroshock: Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. [NIH] 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] Enanthate: An oily injectable contraceptive given every 8 weeks. [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] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [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] 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] Epidemiological: Relating to, or involving epidemiology. [EU] 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]

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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] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [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]

Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] 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] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] 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]

Fat: Total lipids including phospholipids. [NIH] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filarioidea: A superfamily of nematodes of the suborder Spirurina. Its organisms possess a filiform body and a mouth surrounded by papillae. [NIH] Flexion: In gynaecology, a displacement of the uterus in which the organ is bent so far forward or backward that an acute angle forms between the fundus and the cervix. [EU]


Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Gait: Manner or style of walking. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangliosides: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [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] 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] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] 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] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [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 testing: Analyzing DNA to look for a genetic alteration that may indicate an

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increased risk for developing a specific disease or disorder. [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] Ginkgo biloba: Exclusive species of the genus Ginkgo, family Ginkgoacea. It produces extracts of medicinal interest. Ginkgo may refer to the genus or species. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] 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] 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] 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]

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] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonadorelin: A decapeptide hormone released by the hypothalamus. It stimulates the synthesis and secretion of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. [NIH] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]

Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [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] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the


prosthetic group in many hemeproteins. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Refers to the liver. [NIH] Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [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]

Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histology: The study of tissues and cells under a microscope. [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] Host: Any animal that receives a transplanted graft. [NIH] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] 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]

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Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [NIH] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hypnotic: A drug that acts to induce sleep. [EU] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] 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] Immunophilins: Members of a family of highly conserved proteins which are all cis-trans peptidyl-prolyl isomerases (peptidylprolyl isomerase). They bind the immunosuppressant drugs cyclosporine; tacrolimus and sirolimus. They possess rotomase activity, which is inhibited by the immunosuppressant drugs that bind to them. EC 5.2.1.- [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] 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] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [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]

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] 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] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [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] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Embolism: The sudden obstruction of a blood vessel by an embolus. [NIH] Intracranial Embolism and Thrombosis: Embolism or thrombosis involving blood vessels which supply intracranial structures. Emboli may originate from extracranial or intracranial sources. Thrombosis may occur in arterial or venous structures. [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]

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] 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] Isomerases: A class of enzymes that catalyze geometric or structural changes within a molecule to form a single product. The reactions do not involve a net change in the concentrations of compounds other than the substrate and the product.(from Dorland, 28th ed) EC 5. [NIH] Isotope Labeling: Techniques for labeling a substance with a stable or radioactive isotope. It is not used for articles involving labeled substances unless the methods of labeling are substantively discussed. Tracers that may be labeled include chemical substances, cells, or microorganisms. [NIH] Ivermectin: A mixture of ivermectin component B1a (RN 71827-03-7) and B1b (RN 70209-813), which is a semisynthetic product from Streptomyces avermitilis. A potent macrocyclic lactone disaccharide antiparasitic agent used to prevent and treat parasite infestations in animals. The compound has activity against internal and external parasites and has been found effective against arthropods, insects, nematodes, filarioidea, platyhelminths, and protozoa. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [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] Kynurenic Acid: A broad-spectrum excitatory amino acid antagonist used as a research tool. [NIH]

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] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [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] Leuprolide: A potent and long acting analog of naturally occurring gonadotropin-releasing hormone (gonadorelin). Its action is similar to gonadorelin, which regulates the synthesis and release of pituitary gonadotropins. [NIH] Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. [NIH] Library Services: Services offered to the library user. They include reference and circulation.


[NIH]

Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] 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 Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] 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] 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] 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] 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] Lysosome: A sac-like compartment inside a cell that has enzymes that can break down cellular components that need to be destroyed. [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] 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] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] 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] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by

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means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [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] 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] 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] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microtubule-Associated Proteins: High molecular weight proteins found in the microtubules of the cytoskeletal system. Under certain conditions they are required for tubulin assembly into the microtubules and stabilize the assembled microtubules. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Minocycline: A semisynthetic staphylococcus infections. [NIH]

antibiotic

effective

against

tetracycline-resistant

Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] 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]


Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [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 Neurons: Neurons which activate muscle cells. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

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 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] 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] 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 Diseases: Acquired, familial, and congenital disorders of skeletal muscle and smooth muscle. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] 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] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United

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States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [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] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] 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] 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] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurologist: A doctor who specializes in the diagnosis and treatment of disorders of the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] 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] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] 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] 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] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] 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] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH]

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Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Opsin: A visual pigment protein found in the retinal rods. It combines with retinaldehyde to form rhodopsin. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Ornithine Decarboxylase: A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated Sadenosylmethionine to form spermidine. EC 4.1.1.17. [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]

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] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paraplegia: Severe or complete loss of motor function in the lower extremities and lower portions of the trunk. This condition is most often associated with spinal cord diseases, although brain diseases; peripheral nervous system diseases; neuromuscular diseases; and muscular diseases may also cause bilateral leg weakness. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] 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] Patient Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]


Pelvic: Pertaining to the pelvis. [EU] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peripheral blood: Blood circulating throughout the body. [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] Pernicious: Tending to a fatal issue. [EU] Pernicious anemia: A type of anemia (low red blood cell count) caused by the body's inability to absorb vitamin B12. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] 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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [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] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [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] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of

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skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [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] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [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] Platyhelminths: A phylum of acoelomate, bilaterally symmetrical flatworms, without a definite anus. It includes three classes: Cestoda, Turbellaria, and Trematoda. [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] 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] 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] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [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] 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] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] 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] Prion: Small proteinaceous infectious particles that resist inactivation by procedures modifying nucleic acids and contain an abnormal isoform of a cellular protein which is a major and necessary component. [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] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [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] 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] 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 Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [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] 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] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [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] Psychological Tests: Standardized tests designed to measure abilities, as in intelligence,

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aptitude, and achievement tests, or to evaluate personality traits. [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 Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [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]

Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [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] Radioactive: Giving off radiation. [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] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] 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] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [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] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [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] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [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] 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]

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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] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Riluzole: A glutamate antagonist that has reported anticonvulsant activity. It has been shown to prolong the survival of patients with amyotrophic lateral sclerosis and has been approved in the United States to treat patients with ALS. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]

Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [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] 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] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [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] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [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] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] 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] 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] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [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] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] 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] 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] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] 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

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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] Speech pathologist: A specialist who evaluates and treats people with communication and swallowing problems. Also called a speech therapist. [NIH] Sperm: The fecundating fluid of the male. [NIH] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [NIH] 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 Diseases: Pathologic conditions which feature spinal cord damage or dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [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]

Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [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] Stimulants: Any drug or agent which causes stimulation. [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] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [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] 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] 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] Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] 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] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supraspinal: Above the spinal column or any spine. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [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] Systemic: Affecting the entire body. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex

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characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [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] 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] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [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] 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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] 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] Tracheostomy tube: A 2-inch- to 3-inch-long curved metal or plastic tube placed in a surgically created opening (tracheostomy) in the windpipe to keep it open. Also called a trach ("trake") tube. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [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] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell


to the other at the synapse. [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] Trophic: Of or pertaining to nutrition. [EU] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [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] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [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] 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] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator. [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] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricles: Fluid-filled cavities in the heart or brain. [NIH]

Dictionary 143

Vertebrae: A bony unit of the segmented spinal column. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [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] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] 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] Wheelchairs: Chairs mounted on wheels and designed to be propelled by the occupant. [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] 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 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] 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]

145

INDEX A Aberrant, 12, 14, 105 Ablation, 105, 107 Acceptor, 105, 126, 131 Acetylcysteine, 26, 105 Actin, 105, 129 Adaptability, 105, 111 Adaptation, 4, 34, 105 Adduct, 8, 105 Adjustment, 105 Adrenergic, 105, 117, 118, 135, 140 Adverse Effect, 105, 138 Affinity, 6, 105, 106, 108, 116, 138 Agar, 105, 133 Age of Onset, 3, 57, 106 Agonist, 106, 108, 117 Algorithms, 106, 110 Alkaline, 106, 109, 110 Alkaloid, 106, 128, 135 Alopecia, 106, 115 Alpha Particles, 106, 135 Alternative medicine, 39, 71, 106 Alveoli, 106, 142 Ameliorating, 58, 63, 106 Amino Acid Sequence, 62, 106, 107, 120 Amino Acids, 40, 106, 107, 119, 120, 130, 132, 133, 134, 137, 141, 142 Aminolevulinic Acid, 18, 106 Amyloid, 8, 106 Anaesthesia, 106 Anaesthetic, 60, 106 Anal, 106, 118 Analgesic, 106, 113, 125, 128, 135 Analog, 12, 57, 59, 107, 116, 125 Analogous, 13, 36, 107, 141 Anatomical, 19, 107, 112, 123, 137 Androgen suppression, 52, 107 Animal model, 45, 56, 107 Anions, 107, 109, 125, 140 Ankyrin Repeat, 17, 107 Anterior Horn Cells, 22, 107 Antibiotic, 88, 107, 110, 127, 141 Antibodies, 14, 56, 57, 59, 64, 107, 121, 126, 127, 133 Antibody, 18, 56, 57, 59, 60, 64, 105, 107, 113, 121, 122, 123, 127, 139 Anticoagulant, 107, 134 Anticonvulsant, 56, 60, 107, 137

Antigen, 56, 57, 62, 105, 107, 113, 122, 123 Anti-infective, 107, 122 Anti-inflammatory, 4, 107 Antineoplastic, 107, 115 Antioxidant, 7, 9, 107, 131 Antiproliferative, 63, 108 Antitussive, 108, 116 Antiviral, 105, 108 Anxiolytic, 60, 108 Apoptosis, 108, 111 Aptitude, 108, 135 Aqueous, 108, 109, 115, 122 Arginine, 108, 131, 135 Arterial, 108, 110, 112, 124, 134 Arteries, 108, 110, 112, 115, 127 Arteriovenous, 108, 112 Aspartate, 16, 62, 108, 116 Aspiration, 3, 4, 103, 108 Assay, 108, 123 Astrocytes, 62, 108 Atrophy, 4, 21, 52, 88, 102, 108, 129 Atypical, 58, 108 Autoimmune disease, 108, 128 Autoimmunity, 56, 108 Autopsy, 28, 108 Axons, 63, 108 B Baclofen, 4, 108 Bacteria, 7, 107, 109, 127, 136, 139, 142 Bacterial Physiology, 105, 109 Bacteriophage, 109, 133 Band 3 Protein, 107, 109 Barium, 50, 109, 119 Barium swallow, 50, 109, 119 Base, 109, 116, 120, 125, 133 Beta-pleated, 106, 109 Bilateral, 46, 109, 131 Bile, 109, 120, 122, 126 Bilirubin, 30, 109 Binding Sites, 8, 12, 109 Biochemical, 9, 19, 27, 37, 45, 62, 109, 138 Biological Markers, 51, 109 Biopsy, 49, 109 Biosynthesis, 109, 131 Biotechnology, 12, 16, 71, 81, 109 Bladder, 102, 110, 120, 128, 134, 142 Blood Coagulation, 7, 110, 111, 141 Blood Coagulation Factors, 110


Blood pressure, 24, 110, 127, 138 Blood vessel, 110, 111, 112, 118, 124, 125, 126, 132, 139, 141, 142 Blood-Brain Barrier, 7, 110 Body Fluids, 110, 120, 130, 138 Bone scan, 110, 137 Bowel, 106, 110, 117 Bowel Movement, 110, 117 Brain Diseases, 110, 131 Brain Ischemia, 110, 112 Brain Stem, 6, 110, 112, 129 Branch, 99, 110, 131, 138, 141 Breakdown, 110, 111, 116, 120 Broad-spectrum, 110, 125 Bulbar, 4, 57, 60, 110 C Cachexia, 4, 110 Calcium, 14, 56, 57, 64, 110, 113 Carbohydrates, 111 Carbon Dioxide, 8, 111, 116, 120, 136 Carcinogen, 105, 111 Cardiac, 17, 111, 118, 119, 128, 135 Cardiovascular, 61, 111, 138 Carotene, 111, 136 Case report, 3, 37, 111 Caspase, 13, 21, 111 Catecholamine, 111, 117, 132 Cations, 111, 125 Causal, 111, 118 Cell Death, 9, 15, 45, 46, 108, 111, 129 Cell Division, 109, 111, 126, 133, 134 Cell membrane, 64, 111, 120 Cell motility, 111, 122 Cell proliferation, 63, 111 Cellular metabolism, 46, 111 Cellulose, 111, 133 Central Nervous System, 7, 110, 111, 112, 120, 121, 128, 133, 138 Cerebellum, 110, 112, 133 Cerebral, 20, 110, 112, 114, 118, 120, 129, 138 Cerebral hemispheres, 110, 112 Cerebral Infarction, 112 Cerebral Palsy, 112, 138 Cerebrospinal, 64, 112 Cerebrospinal fluid, 64, 112 Cerebrovascular, 60, 112 Cerebrovascular Disorders, 60, 112 Cerebrum, 112 Cervix, 112, 119 Character, 112, 116 Chin, 24, 50, 112

Chromosome, 15, 16, 27, 32, 112, 121, 126, 142 Chronic, 15, 31, 110, 112, 117, 124, 139 Chronic Disease, 110, 112 Ciliary, 20, 58, 75, 112 Ciliary Neurotrophic Factor, 58, 112 CIS, 112, 123, 136 Clinical Medicine, 113, 133 Clinical trial, 5, 33, 45, 46, 53, 81, 91, 113, 114, 115, 128, 135 Cloning, 110, 113 Coagulation, 7, 110, 113 Codeine, 59, 113, 116 Cofactor, 113, 134, 141 Cohort Studies, 113, 118 Collagen, 113, 120, 134 Combinatorial, 9, 113 Complement, 113, 114 Complementary and alternative medicine, 33, 41, 114 Complementary medicine, 33, 114 Computational Biology, 81, 114 Computed tomography, 114, 137 Computerized axial tomography, 114, 137 Cones, 114, 136 Conjugated, 10, 59, 114, 115 Consciousness, 106, 114, 116, 117 Contraceptive, 114, 118 Contraindications, ii, 114 Control group, 7, 114, 135 Convulsions, 107, 114 Convulsive, 114, 118 Coordination, 24, 112, 114, 128 Coronary, 115, 127 Coronary Thrombosis, 115, 127 Cortex, 47, 110, 115, 122, 129 Cortical, 35, 64, 115, 119, 137 Creatine, 17, 24, 30, 36, 38, 41, 45, 46, 48, 49, 75, 86, 115 Creatine Kinase, 24, 38, 86, 115 Creatinine, 115 Cross-Sectional Studies, 115, 118 Curative, 115, 141 Cyclophosphamide, 58, 115 Cyclosporine, 115, 123 Cysteine, 57, 105, 115 Cystine, 115 Cytochrome, 6, 115 Cytoplasm, 108, 111, 115, 116, 129, 137 Cytoskeleton, 62, 116, 127 Cytotoxic, 59, 64, 116 Cytotoxicity, 14, 62, 64, 116

Index 147

D Dantrolene, 4, 116 Databases, Bibliographic, 81, 116 Decarboxylation, 116, 131, 135 Defense Mechanisms, 7, 116 Degenerative, 9, 46, 59, 62, 86, 116 Dementia, 5, 19, 20, 21, 23, 25, 27, 30, 116, 129 Dendrites, 116, 130 Density, 116, 138 Deprivation, 58, 116 Deuterium, 116, 122 Dexterity, 4, 116 Dextromethorphan, 53, 58, 59, 116 Diagnostic procedure, 55, 71, 116 Diencephalon, 112, 116, 129 Difluoromethylornithine, 63, 116 Digestion, 109, 110, 116, 126, 139, 142 Digestive system, 54, 117 Diploid, 117, 133 Direct, iii, 62, 73, 113, 117, 135, 136 Disease Progression, 45, 49, 117 Dissociation, 21, 105, 117 Domesticated, 117, 121 Dopamine, 6, 117, 132 Drug Interactions, 74, 117 Dyes, 106, 117 E Efficacy, 39, 45, 53, 117 Elective, 29, 117 Electrocoagulation, 113, 117 Electrolyte, 117, 120, 130, 133, 138 Electromyography, 24, 50, 86, 117 Electron Spin Resonance Spectroscopy, 5, 117 Electrons, 108, 109, 117, 118, 125, 126, 131, 135 Electroshock, 56, 118 Elementary Particles, 118, 126, 130, 134 Enanthate, 52, 118 Encephalopathy, 8, 118 Endemic, 118, 139 Endocytosis, 6, 118 Endothelial cell, 110, 118, 141 Environmental Exposure, 109, 118, 131 Environmental Health, 18, 51, 80, 82, 118 Enzymatic, 111, 114, 118, 136 Enzyme, 7, 8, 9, 11, 62, 63, 109, 111, 118, 121, 125, 132, 133, 134, 140, 141, 143 Epidemic, 118, 139 Epidemiologic Studies, 6, 109, 118 Epidemiological, 22, 57, 118

Epinephrine, 105, 117, 118, 130, 142 Epithelial, 119, 122 Epithelial Cells, 119, 122 Erythrocytes, 119, 136 Esophagram, 109, 119 Esophagus, 50, 109, 117, 119, 132, 139 Eukaryotic Cells, 119, 142 Excitability, 119, 135 Excitation, 58, 116, 119 Excitatory, 59, 109, 119, 121, 125 Excitatory Amino Acids, 59, 119 Excitotoxicity, 45, 119 Exogenous, 7, 18, 51, 58, 119 Extracellular, 6, 106, 108, 118, 119, 138 Extrapyramidal, 117, 119 Extremity, 46, 119 F Family Planning, 81, 119 Fasciculation, 119, 129 Fat, 111, 119, 126, 128 Fibril, 9, 119 Fibrin, 110, 119, 141 Fibrosis, 119, 137 Filarioidea, 119, 125 Flexion, 46, 119 Fluid Therapy, 120, 130 Fold, 107, 120 Foramen, 112, 120 Forearm, 110, 120 Frontal Lobe, 112, 120, 128 Fundus, 119, 120 G Gait, 4, 120 Gallbladder, 117, 120 Ganglia, 110, 120, 123, 128, 129, 132 Gangliosides, 18, 120 Gap Junctions, 120, 140 Gas, 111, 120, 122, 124, 130, 136, 140, 142 Gas exchange, 120, 136, 142 Gastric, 120, 124 Gastrointestinal, 118, 120, 138 Gastrostomy, 4, 120 Gelatin, 120, 121, 141 Gene, 5, 6, 8, 11, 14, 15, 16, 17, 22, 23, 30, 36, 62, 63, 70, 109, 110, 120, 131 Gene Expression, 6, 120 Genetic Code, 120, 130 Genetic Counseling, 49, 120 Genetic testing, 49, 120 Genetics, 16, 24, 32, 49, 121 Genotype, 20, 121, 132 Ginkgo biloba, 61, 121


Ginseng, 35, 121 Gland, 121, 131, 134, 139, 141 Glucose, 111, 121, 124 Glutamate, 4, 13, 15, 16, 26, 45, 46, 58, 62, 64, 116, 119, 121, 137 Glutamic Acid, 40, 121, 134 Glutathione Peroxidase, 121, 137 Glycine, 106, 121 Glycols, 121, 123 Glycoprotein, 121, 124, 128, 141 Gonadorelin, 121, 125 Gonadotropin, 121, 125 Governing Board, 121, 133 Growth, 9, 23, 47, 58, 67, 70, 75, 108, 111, 121, 122, 124, 131, 133, 141 Guinea Pigs, 56, 121 H Haploid, 121, 133 Haptens, 105, 121 Heme, 106, 109, 115, 121 Hemorrhage, 117, 122, 139 Hepatic, 28, 122 Hepatocyte, 22, 63, 122 Hepatocyte Growth Factor, 22, 63, 122 Hereditary, 49, 52, 122, 129, 132 Heredity, 49, 120, 121, 122 Heterogeneity, 105, 122 Hippocampus, 122, 129 Histology, 122, 129 Homeostasis, 6, 12, 27, 122 Homologous, 122, 140 Hormonal, 108, 122 Hormone, 109, 118, 121, 122, 124, 125, 140, 141 Host, 109, 119, 122, 143 Human Development, 67, 80, 122 Humoral, 60, 64, 122 Humour, 122 Hydrogen, 8, 11, 13, 105, 109, 111, 116, 121, 122, 123, 126, 127, 130, 131, 134, 140 Hydrogen Peroxide, 8, 11, 13, 121, 122, 126, 140 Hydrolysis, 62, 122, 133, 134 Hydroxides, 123 Hydroxyl Radical, 8, 14, 15, 123 Hydroxylation, 5, 123 Hypnotic, 60, 123 Hypokinesia, 123, 131 Hypoxia, 110, 112, 123 I Id, 40, 90, 98, 100, 123

Immune response, 64, 107, 108, 121, 123, 143 Immune system, 60, 64, 108, 123, 126, 128, 142, 143 Immunoassay, 57, 123 Immunoglobulin, 8, 64, 107, 123, 127 Immunologic, 123 Immunology, 105, 123 Immunophilins, 15, 123 Immunosuppressant, 123 Immunosuppressive, 115, 123, 140 Impairment, 4, 102, 112, 123, 127 In vitro, 9, 20, 59, 123, 140 In vivo, 14, 118, 123, 140 Incision, 123, 124 Indicative, 68, 123, 131, 142 Infarction, 110, 112, 115, 123, 127 Infection, 14, 58, 112, 123, 126, 139, 143 Inflammation, 4, 107, 112, 119, 124, 142 Innervation, 26, 124 Inotropic, 117, 124 Insecticides, 124, 132 Insufflation, 25, 124 Insulator, 124, 128 Insulin, 23, 47, 58, 75, 124 Insulin-dependent diabetes mellitus, 124 Insulin-like, 23, 47, 58, 75, 124 Intermediate Filaments, 124, 129 Intoxication, 58, 124 Intracellular, 6, 57, 62, 123, 124, 133, 137 Intracranial Embolism, 112, 124 Intracranial Embolism and Thrombosis, 112, 124 Intravenous, 64, 124 Intrinsic, 6, 105, 124 Intrinsic Factor, 6, 124 Invasive, 33, 47, 50, 64, 124, 126 Involuntary, 124, 128, 136, 138 Ion Channels, 108, 124, 130, 140 Ions, 6, 9, 11, 12, 109, 117, 122, 125 Ischemia, 108, 110, 120, 125 Isoenzyme, 115, 125 Isomerases, 123, 125 Isotope Labeling, 10, 125 Ivermectin, 7, 125 J Joint, 52, 125, 140 K Kb, 80, 125 Kynurenic Acid, 22, 125 L Large Intestine, 117, 125, 136

Index 149

Latent, 125, 133 Lesion, 26, 125 Lethal, 45, 60, 64, 125 Leukemia, 19, 125 Leukocytes, 125, 132 Leuprolide, 52, 125 Levorphanol, 59, 116, 125 Library Services, 98, 125 Ligament, 126, 134 Linkage, 11, 27, 126 Lipid, 14, 88, 124, 126, 128, 131 Lipid Peroxidation, 126, 131 Liver, 61, 62, 109, 115, 117, 120, 122, 126, 137, 142 Liver scan, 126, 137 Localized, 6, 110, 123, 126, 133 Locomotion, 126, 133 Lymphatic, 124, 126 Lymphocyte, 107, 126 Lymphoid, 107, 126 Lysosome, 10, 126 M Magnetic Resonance Imaging, 52, 118, 126, 137 Magnetic Resonance Spectroscopy, 10, 126 Malnutrition, 108, 110, 126, 128 Mandible, 112, 126 Mediate, 107, 117, 126 Medical Staff, 52, 126 Medicament, 59, 60, 61, 126 MEDLINE, 81, 126 Medullary, 116, 126 Meiosis, 126, 140, 142 Melanin, 127, 132, 142 Membrane, 6, 10, 57, 62, 108, 109, 111, 114, 118, 119, 124, 127, 135, 136 Memory, 4, 116, 127 Meninges, 111, 127, 139 Mental Disorders, 54, 123, 127, 134 Mental Health, iv, 5, 23, 54, 80, 82, 127 MI, 103, 127 Microbe, 127, 141 Microbiology, 105, 108, 127 Microorganism, 113, 127, 143 Microtubule-Associated Proteins, 127, 129 Microtubules, 124, 127, 129 Minocycline, 48, 88, 127 Modification, 127, 135 Molecular, 5, 6, 10, 11, 17, 24, 26, 31, 40, 51, 81, 83, 107, 110, 114, 121, 127, 129, 140

Molecule, 10, 107, 109, 113, 117, 119, 122, 125, 127, 131, 133, 136 Monitor, 91, 115, 127, 130 Monoclonal, 59, 64, 127 Monoclonal antibodies, 64, 127 Morphine, 113, 128 Motor Activity, 47, 114, 128 Motor Cortex, 8, 47, 52, 128 Motor Neurons, 4, 6, 8, 9, 11, 13, 14, 23, 57, 60, 64, 91, 128 Mucins, 128, 137 Mucolytic, 105, 128 Multicenter study, 47, 48, 128 Multiple sclerosis, 36, 50, 128 Muscle Fibers, 128 Muscle Hypertonia, 128, 129 Muscle relaxant, 116, 128 Muscular Atrophy, 6, 52, 86, 128 Muscular Diseases, 128, 129, 131 Muscular Dystrophies, 49, 128 Musculature, 60, 64, 123, 128 Mutagenesis, 8, 9, 128 Mutagens, 128 Myelin, 128 Myocardium, 127, 128 N Narcotic, 125, 128 NCI, 1, 53, 79, 113, 128 Necrosis, 108, 112, 123, 127, 129 Need, 3, 67, 75, 93, 126, 129 Neocortex, 129 Nervous System, 47, 63, 111, 112, 129, 130, 132, 140 Neural, 5, 13, 14, 106, 122, 129 Neuroblastoma, 9, 129 Neurodegenerative Diseases, 10, 63, 129 Neurofibrillary Tangles, 19, 129 Neurofilaments, 13, 129 Neurologic, 7, 36, 39, 86, 129 Neurologist, 26, 50, 129 Neuromuscular, 4, 14, 27, 37, 46, 57, 86, 91, 116, 129, 131 Neuromuscular Diseases, 46, 129, 131 Neuromuscular Junction, 14, 57, 129 Neuronal, 4, 12, 15, 20, 28, 31, 59, 64, 112, 129 Neurons, 9, 30, 57, 63, 64, 107, 116, 119, 120, 128, 129, 130, 140 Neuropeptide, 62, 130 Neurophysiology, 25, 30, 47, 130 Neurotoxic, 7, 130 Neurotoxicity, 116, 130


Neurotoxins, 4, 130 Neurotransmitters, 119, 130 Neutrons, 106, 130, 135 Nitrogen, 106, 115, 130 Norepinephrine, 105, 117, 130 Nuclear, 10, 52, 109, 118, 119, 129, 130 Nuclei, 106, 118, 126, 130, 134 Nucleic acid, 6, 120, 128, 130, 134, 139 Nucleus, 108, 115, 116, 118, 119, 124, 127, 130, 134, 139 Nutritional Support, 4, 120, 130 O Oncogene, 122, 131 Opsin, 131, 136 Oral Health, 3, 131 Ornithine, 63, 131, 135 Ornithine Decarboxylase, 63, 131 Oxidation, 5, 105, 108, 115, 121, 126, 131 Oxidative Stress, 6, 27, 29, 131 P Palliative, 19, 29, 35, 36, 131, 141 Pancreas, 117, 124, 131 Paralysis, 12, 60, 62, 64, 92, 102, 110, 131, 138 Paraplegia, 52, 131 Parasite, 125, 131 Parkinsonism, 19, 23, 25, 27, 30, 131 Particle, 131, 138 Pathogenesis, 6, 60, 62, 64, 131 Pathologic, 34, 108, 109, 110, 115, 131, 139 Patient Advocacy, 91, 131 Patient Education, 89, 96, 98, 103, 131 Pelvic, 132, 134 Peptide, 36, 132, 133, 134 Peripheral blood, 64, 132 Peripheral Nervous System, 49, 129, 131, 132 Peripheral Nervous System Diseases, 129, 131, 132 Pernicious, 124, 132 Pernicious anemia, 124, 132 Peroxidase, 8, 37, 126, 132 Peroxide, 8, 132 Pesticides, 51, 124, 132 Pharmacologic, 132, 141 Pharmacotherapy, 28, 132 Pharynx, 50, 132 Phenotype, 20, 109, 132 Phenylalanine, 132, 142 Phosphorus, 110, 132 Photocoagulation, 113, 132 Physiologic, 106, 109, 123, 132, 136, 142

Physiology, 109, 130, 132 Pigment, 109, 131, 132 Pilot study, 4, 25, 133 Plants, 7, 106, 111, 121, 130, 133, 141 Plaque, 4, 133 Plasma, 6, 107, 109, 111, 120, 133, 137 Plasma cells, 107, 133 Platyhelminths, 125, 133 Point Mutation, 23, 133 Polymerase, 10, 133 Polypeptide, 106, 113, 133, 134, 143 Polysaccharide, 107, 111, 133 Pons, 110, 133 Postsynaptic, 133, 140 Potassium, 133, 135 Practice Guidelines, 82, 89, 133 Preclinical, 56, 133 Precursor, 57, 115, 117, 118, 130, 132, 133, 139, 142 Predisposition, 58, 133 Presynaptic, 133, 140 Prevalence, 60, 64, 133 Prion, 6, 134 Progression, 8, 45, 46, 52, 56, 57, 59, 88, 107, 134 Progressive, 3, 4, 6, 9, 11, 12, 20, 45, 47, 57, 59, 60, 62, 63, 64, 91, 92, 116, 121, 128, 129, 134 Projection, 116, 130, 134 Proline, 17, 113, 134 Prophase, 134, 140, 142 Prostate, 62, 134 Protein C, 10, 106, 109, 134, 142 Protein Conformation, 106, 134 Protein S, 7, 10, 110, 120, 134, 137, 141 Proteolytic, 9, 10, 113, 134 Protons, 10, 106, 122, 126, 134, 135 Protozoa, 125, 127, 134 Psychiatric, 109, 127, 134 Psychiatry, 4, 21, 22, 28, 134, 142 Psychic, 134, 137 Psychological Tests, 49, 134 Public Policy, 81, 135 Publishing, 12, 135 Pulmonary, 110, 135, 142 Pulmonary Artery, 110, 135 Pulse, 127, 135 Putrefaction, 135 Putrescine, 63, 131, 135, 139 Pyridoxal, 131, 135 Q Quality of Life, 17, 28, 135

Index 151

Quinidine, 53, 135 Quinine, 135 R Radiation, 12, 118, 135, 137, 143 Radioactive, 50, 110, 122, 125, 126, 127, 130, 135, 137 Random Allocation, 135 Randomization, 46, 135 Randomized, 7, 16, 17, 45, 117, 135, 136 Randomized clinical trial, 16, 136 Reactive Oxygen Species, 6, 136 Receptor, 13, 15, 18, 59, 60, 64, 105, 107, 116, 117, 122, 136, 138 Recombinant, 75, 136 Rectum, 110, 117, 120, 125, 134, 136 Red blood cells, 11, 119, 136 Refer, 1, 89, 113, 121, 126, 130, 136 Reflex, 3, 29, 136 Regimen, 117, 132, 136 Respiration, 111, 127, 136 Respiratory failure, 4, 136 Respiratory Physiology, 136, 142 Retina, 114, 136, 137 Retinal, 61, 131, 136 Retinol, 136 Ribosome, 137, 141 Rigidity, 131, 133, 137 Riluzole, 4, 19, 37, 58, 60, 61, 74, 75, 137 Risk factor, 18, 51, 57, 118, 137 Rodenticides, 132, 137 Rods, 131, 136, 137 S Saliva, 4, 137 Salivary, 117, 137 Salivary glands, 117, 137 Scans, 49, 50, 137 Schizophrenia, 60, 137 Screening, 17, 48, 50, 63, 113, 137 Secretory, 137, 140 Sedative, 113, 137 Seizures, 56, 137 Selenium, 37, 137 Semen, 134, 137 Semisynthetic, 125, 127, 137 Serologic, 123, 137 Serotonin, 132, 138 Serum, 30, 64, 113, 115, 121, 137, 138 Sex Characteristics, 138, 141 Shock, 118, 138 Side effect, 46, 73, 75, 105, 115, 138, 141 Signs and Symptoms, 49, 58, 138

Skeletal, 25, 30, 57, 107, 115, 116, 128, 135, 138 Skeleton, 105, 125, 138 Social Environment, 135, 138 Sodium, 135, 138 Somatic, 122, 127, 132, 138 Sound wave, 50, 138 Spasm, 114, 129, 138 Spastic, 52, 138 Spasticity, 4, 102, 108, 116, 138 Specialist, 92, 138, 139 Species, 11, 12, 64, 117, 118, 121, 127, 131, 135, 136, 138, 139, 140, 143 Specificity, 105, 139 Speech pathologist, 50, 139 Sperm, 112, 139, 140 Spermidine, 131, 139 Spinal Cord Diseases, 131, 139 Sporadic, 6, 17, 18, 22, 27, 29, 34, 45, 58, 63, 129, 139 Staging, 137, 139 Staphylococcus, 127, 139 Sterility, 115, 139 Stimulants, 121, 139 Stimulus, 119, 124, 136, 139 Stomach, 117, 119, 120, 122, 132, 139 Strand, 133, 139 Stress, 7, 27, 51, 111, 118, 131, 133, 139 Stroke, 36, 47, 48, 49, 51, 52, 54, 80, 87, 88, 90, 139 Subacute, 124, 139 Subclinical, 123, 137, 139 Subspecies, 139, 140 Substrate, 57, 125, 140 Suction, 4, 140 Superoxide, 5, 6, 7, 9, 11, 13, 14, 15, 16, 17, 20, 22, 23, 24, 26, 27, 30, 31, 36, 38, 43, 58, 63, 140 Supplementation, 36, 37, 140 Support group, 34, 39, 89, 91, 92, 103, 140 Suppression, 107, 140 Supraspinal, 109, 140 Sympathomimetic, 117, 118, 130, 140 Symphysis, 112, 134, 140 Symptomatic, 4, 39, 140 Symptomatic treatment, 4, 140 Synapsis, 140 Synaptic, 59, 140 Synaptic Transmission, 59, 140 Systemic, 74, 110, 118, 124, 129, 140 T Tacrolimus, 123, 140


Testicles, 107, 140 Testosterone, 52, 140 Tetracycline, 127, 141 Therapeutics, 74, 141 Threonine, 75, 141 Thrombin, 119, 134, 141 Thrombomodulin, 134, 141 Thrombosis, 124, 134, 139, 141 Thyroid, 141, 142 Tooth Preparation, 105, 141 Topical, 122, 141 Torsion, 10, 123, 141 Toxic, iv, 6, 7, 9, 12, 37, 51, 116, 118, 130, 135, 137, 141 Toxicity, 9, 45, 58, 64, 117, 141 Toxicology, 37, 82, 141 Toxins, 58, 107, 123, 127, 141, 142 Trachea, 132, 141 Tracheostomy, 25, 58, 141 Tracheostomy tube, 25, 141 Transfection, 110, 141 Translation, 10, 141 Transmitter, 108, 117, 119, 124, 130, 141 Tremor, 131, 142 Trophic, 58, 142 Tyrosine, 14, 117, 142 U Ubiquitin, 10, 129, 142 Unconscious, 116, 123, 142 Univalent, 123, 131, 142 Urea, 131, 142 Urethra, 134, 142 Urine, 46, 49, 110, 115, 142

Uterus, 112, 119, 120, 142 V Vaccine, 15, 31, 142 Vacuoles, 118, 142 Vascular, 112, 123, 124, 139, 142 Vasculitis, 112, 142 Vasodilator, 117, 142 VE, 23, 51, 142 Vein, 108, 124, 130, 142 Venoms, 130, 142 Venous, 108, 112, 124, 134, 142 Ventilation, 25, 142 Ventral, 107, 133, 142 Ventricles, 112, 142 Vertebrae, 139, 143 Veterinary Medicine, 81, 143 Viral, 10, 105, 143 Virulence, 141, 143 Virus, 70, 87, 109, 133, 143 Viscosity, 105, 143 Vitro, 12, 143 Vivo, 143 W Wheelchairs, 91, 143 White blood cell, 107, 125, 126, 133, 143 Windpipe, 132, 141, 143 X Xenograft, 107, 143 X-ray, 12, 49, 109, 114, 119, 130, 137, 143 Y Yeasts, 132, 143 Z Zymogen, 134, 143

Index 153


Index 155


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