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

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

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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Parkinson’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: 0-597-84153-5 1. Parkinson’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 Parkinson’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 PARKINSON’S DISEASE ............................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Parkinson’s Disease ...................................................................... 5 E-Journals: PubMed Central ....................................................................................................... 65 The National Library of Medicine: PubMed ................................................................................ 69 CHAPTER 2. NUTRITION AND PARKINSON’S DISEASE ................................................................. 115 Overview.................................................................................................................................... 115 Finding Nutrition Studies on Parkinson’s Disease ................................................................... 115 Federal Resources on Nutrition ................................................................................................. 125 Additional Web Resources ......................................................................................................... 126 CHAPTER 3. ALTERNATIVE MEDICINE AND PARKINSON’S DISEASE ........................................... 129 Overview.................................................................................................................................... 129 National Center for Complementary and Alternative Medicine................................................ 129 Additional Web Resources ......................................................................................................... 160 General References ..................................................................................................................... 165 CHAPTER 4. DISSERTATIONS ON PARKINSON’S DISEASE ............................................................. 167 Overview.................................................................................................................................... 167 Dissertations on Parkinson’s Disease ........................................................................................ 167 Keeping Current ........................................................................................................................ 172 CHAPTER 5. CLINICAL TRIALS AND PARKINSON’S DISEASE ........................................................ 173 Overview.................................................................................................................................... 173 Recent Trials on Parkinson’s Disease ........................................................................................ 173 Keeping Current on Clinical Trials ........................................................................................... 186 CHAPTER 6. PATENTS ON PARKINSON’S DISEASE ........................................................................ 189 Overview.................................................................................................................................... 189 Patents on Parkinson’s Disease ................................................................................................. 189 Patent Applications on Parkinson’s Disease.............................................................................. 197 Keeping Current ........................................................................................................................ 199 CHAPTER 7. BOOKS ON PARKINSON’S DISEASE............................................................................ 201 Overview.................................................................................................................................... 201 Book Summaries: Federal Agencies............................................................................................ 201 Book Summaries: Online Booksellers......................................................................................... 202 The National Library of Medicine Book Index ........................................................................... 209 Chapters on Parkinson’s Disease ............................................................................................... 211 CHAPTER 8. MULTIMEDIA ON PARKINSON’S DISEASE ................................................................. 213 Overview.................................................................................................................................... 213 Video Recordings ....................................................................................................................... 213 Bibliography: Multimedia on Parkinson’s Disease .................................................................... 214 CHAPTER 9. PERIODICALS AND NEWS ON PARKINSON’S DISEASE .............................................. 217 Overview.................................................................................................................................... 217 News Services and Press Releases.............................................................................................. 217 Academic Periodicals covering Parkinson’s Disease.................................................................. 221 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 223 Overview.................................................................................................................................... 223 U.S. Pharmacopeia..................................................................................................................... 223 Commercial Databases ............................................................................................................... 226 Researching Orphan Drugs ....................................................................................................... 226 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 231 Overview.................................................................................................................................... 231

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NIH Guidelines.......................................................................................................................... 231 NIH Databases........................................................................................................................... 233 Other Commercial Databases..................................................................................................... 235 The Genome Project and Parkinson’s Disease ........................................................................... 235 APPENDIX B. PATIENT RESOURCES ............................................................................................... 239 Overview.................................................................................................................................... 239 Patient Guideline Sources.......................................................................................................... 239 Associations and Parkinson’s Disease ....................................................................................... 248 Finding Associations.................................................................................................................. 248 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 251 Overview.................................................................................................................................... 251 Preparation................................................................................................................................. 251 Finding a Local Medical Library................................................................................................ 251 Medical Libraries in the U.S. and Canada ................................................................................. 251 ONLINE GLOSSARIES................................................................................................................ 257 Online Dictionary Directories ................................................................................................... 260 PARKINSON’S DISEASE DICTIONARY................................................................................ 261 INDEX .............................................................................................................................................. 329

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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 Parkinson’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 Parkinson’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 Parkinson’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 Parkinson’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 Parkinson’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 Parkinson’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 PARKINSON’S DISEASE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Parkinson’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 Parkinson’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 “Parkinson’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: •

Parkinson's Disease and Aided AAC: Some Evidence from Practice Source: International Journal of Language and Communication Disorders. 35(3): 377389. July 2000. Contact: Available from Taylor and Francis Inc. 1900 Frost Road, Suite 101, Bristol, PA 19007. Summary: Clinical observation shows that people with Parkinson's disease (PD) seem to have different training needs from other adult client groups in developing effective use of aided augmentative and alternative communication (AAC). This study was developed in response to these observations. One of the main aims of this preliminary study was to elicit the experiences and attitudes of speech and language therapists in

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this specific area of their practice as the basis for future efficacy research and clinical practice. Thirty speech and language therapists were questioned about their experiences introducing low and high tech AAC devices to this client group. Of particular interest was the discovery of the factors identified by the therapists as influencing their introduction of aided AAC to someone with PD and affecting implementation and successful use. Some of the factors reported were disease specific such as motor problems and physical inability to use the AAC device. Other factors were more general such as caregivers not offering adequate support. These factors are relevant to the process of introducing aided AAC to other adult client groups. The authors conclude with a discussion of the implications for future research and practice; they emphasize the need to include people with PD and their caregivers in practice development. One appendix reprints the questionnaire used in the study. 1 figure. 3 tables. 31 references. •

Discourse Comprehension in Huntington's and Parkinson's Diseases Source: American Journal of Speech-Language Pathology. 8(2): 137-148. May 1999. Contact: Available from American Speech-Language-Hearing Association (ASHA). Product Sales, 10801 Rockville Pike, Rockville, MD 20852. (888) 498-6699. TTY (301) 8970157. Website: www.asha.org. Summary: This article reports on a study comparing the discourse comprehension abilities of patients with Huntington disease (HD) or Parkinson's disease (PD) to those of age matched control participants with no brain damage. Results from the Discourse Comprehension Test indicated that patients with HD and PD, even those with mild or no dementia, are at risk for discourse comprehension difficulties. Although the patients with HD and PD adequately perceived main information, they had problems processing detailed or implied information. Correlational findings suggested a strong relationship between HD and PD patients' general cognitive decline and their discourse comprehension difficulties. The authors present suggestions for assessing and treating the discourse comprehension abilities of patients with HD and PD. 1 figure. 5 tables. 88 references. (AA-M).

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Voice Characteristics in the Progression of Parkinson's Disease Source: International Journal of Language and Communication Disorders. 35(3): 407418. July 2000. Contact: Available from Taylor and Francis Inc. 1900 Frost Road, Suite 101, Bristol, PA 19007. Summary: This article reports on a study that examined the acoustic and perceptual voice characteristics of patients with Parkinson's disease (PD) according to disease severity. The perceptual and acoustic voice characteristics of 30 patients with early stage PD and 30 patients with later stage PD were compared with data from 30 normal control subjects. Voice recordings consisted of prolongation of the vowel 'a', scale singing, and a 1 minute monologue. In comparison with controls and with previously published normative data, both early and later stage PD patients' voices were characterized perceptually by limited pitch and loudness variability, breathiness, harshness, and reduced loudness. High modal pitch levels also characterized the voices of males in both early and later stages of PD. Acoustically, the voices of both groups of PD patients demonstrated lower mean intensity levels and reduced maximum phonational frequency ranges in comparison with normative data. Although less clear, the data from this study also suggested that the PD patients' voices were characterized by excess jitter, a high speaking fundamental frequency for males, and a reduced fundamental

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frequency variability for females. While several of these voice features did not appear to deteriorate with disease progression, some aspects (breathiness, monopitch and monoloudness, low loudness, and reduced maximum phonational frequency range) were worse in the later stages of PD. Tremor was the sole voice feature which was associated only with later stage PD. 4 tables. 33 references. •

Burning Mouth in Parkinson's Disease Sufferers Source: Gerodontology. 15(2): 73-78. 1998. Contact: Available from Gerodontology Association. Department of Prosthetic Dentistry, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Turner Street, London E1 2AD, United Kingdom. Summary: This article reports on a study undertaken to determine the prevalence of burning mouth syndrome (BMS) in a population of patients with Parkinson's disease (PD). The study also assessed the use of pain profiles in identifying the type of burning sensation experienced. Subjects were surveyed by means of a one time mailed questionnaire for which ethical approval had previously been granted. BMS was reported by 24 percent of respondents; the pain profiles were completed by 17 of the patients with BMS. None of the patients reported burning before the onset of PD. The incidence of BMS in patients with Parkinson's disease is 5 times greater than that of the general population. The reason for this is uncertain but the result has implications for the future care of PD patients and indicates the need for increased dental input at PD outpatient clinics. The authors hypothesize that because 96 percent of the sample with BMS were on levodopa medication this may be an influential factor in the cause of the burning sensation. There was no significant difference in the prevalence of BMS between dentate, partially dentate, and edentate subjects, which suggests that Candida may not have been an important factor in this population. 1 figure. 2 tables. 22 references.

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

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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: A MODEL FOR INFLAMMATION AND PD Principal Investigator & Institution: Bolin, Laurel M.; Parkinson's Institute 1170 Morse Ave Sunnyvale, Ca 94089 Timing: Fiscal Year 2001; Project Start 10-APR-2000; Project End 31-MAR-2003 Summary: (adapted from applicant's abstract): The long term goal of this work is to identify inflammatory mechanisms underlying the neurodegeneration of Parkinson's disease so that target-specific therapeutics can be designed. Emerging evidence has led investigators to the hypothesis that inflammatory processes are involved in nigrostriatal degeneration which is the pathological hallmark of Parkinson's disease. They propose to determine the relationship between inflammatory cytokine activation and dopaminergic cell damage in the model of 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP)-induced mouse nigrostriatal degeneration. While there is accumulating post-mortem data suggesting an ongoing immune activation in the parkinsonian substantia nigra, the role of the inflammatory cytokines, the mediators of the immune response, as well as the identity of the immunoeffector cells that produce them remain unclear. These multifunctional cytokines that regulate the inflammatory cascade are interleukin-lBeta (IL-1Beta), tumor necrosis factor alpha (TNFalpha) and IL6. These cytokines may have both immunotoxic and neuroprotective activities in the CNS. This proposal is a first step in determining their role in nigrostriatal degeneration. Specifically the investigators will correlate striatal dopamine depletion with the induction of IL-1Beta, TNFalpha and IL-6 proteins in response to MPTP. Further, they will identify and quantify the immunoeffector cell(s) responsible for specific cytokine production in the striatum where dopaminergic projections are damaged and in the substantia nigra where cytokine production could affect dopaminergic neuron cell bodies. To analyze the mechanisms through which astrogliosis and microglia infiltration occur, they will examine glial growth factors and chemoattractants in primary cultures of astrocytes and microglia treated with MPTP. An understanding of inflammatory induction in the MPTP model will provide important clues as to the role of cytokines in neurodegenerative processes. This knowledge could then be applied to cytokine- and cell-specific strategies for anti-inflammatory therapeutic intervention in Parkinson's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: A VACCINE APPROACH TO PARKINSON'S DISEASE Principal Investigator & Institution: Morgan, David G.; Pharmacology and Therapeutics; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2004 Summary: (provided by applicant) Recent work evaluating gene defects leading to Parkinson's Disease (PD) suggests that accumulation of alpha-synuclein may be a critical step in the pathogenic mechanisms leading to Lewy body Parkinsonism. One of us (RM) has developed a rat model of alpha-synuclein over-expression which results in long term elevations of synuclein production and concomitant degeneration of tyrosine hydroxylase neurons in substantia nigra. Because the model uses intracranial genetransfer with viral vectors, it has considerable versatility compared to transgenic models, where over-expression is constant throughout the lifespan. Vaccines, while traditionally viewed as prophylactic approaches to disease, are increasingly being viewed as therapeutic adjuncts in cancer and cardiovascular disease. Others of us (DM and KU) have found that immunization of transgenic mouse models of amyloid overexpression with the All peptide, is surprisingly effective in reducing the Alzheimer

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phenotype, both pathologically and behaviorally, that develops in this model of the disease. This application will use the new rat model of alpha-synuclein over expression to test the hypothesis that vaccination against alpha-synuclein could diminish the toxicity of this agent towards dopamine producing neurons. We will use immunization with whole recombinant protein and synthetic peptides and immunization with DNA vaccines. Initial studies will verify that these vaccination regimens can indeed produce high antibody titers in rats, and determine the active immunization regimen(s) that leads to high stable titers. We will next test the hypothesis that antibodies against synuclein produced by these vaccines can arrest the neurotoxicity of dopaminergic neurons caused by alpha-synuclein over expression. Additionally, we will examine direct injections of anti-synuclein antibodies into the brain, bypassing the blood-brain barrier, to evaluate the effectiveness of this approach in rescuing dopaminergic neurons. Success will encourage further development of a vaccine as a therapeutic agent in PD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADAPT NEURODEGENERATION

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IN

OXIDANT

STRESS,

AGING

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Principal Investigator & Institution: Davies, Kelvin J.; Gerontology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: We are interested in a possible link between oxidative stress, aging and neurodegenerative diseases. In recent studies of adaptation to oxidative stress we have identified several previously unknown genes (in addition to confirming the overexpression of several known genes) that appear to provide stress protection in isolated hamster cells in culture. These "adapt" genes include: adapt15, adapt33, adapt66, adapt73, adapt78, and adapt 116. Although our studies indicate that full adaptation depends upon both transcription and translation, it is not clear which genes are actually required. Although each of these newly discovered genes is worthy of detailed study, adapt78 whose mRNA levels increase more than 50 fold in adaptation, in particular stands out. In screening studies employing autopsy samples from human brains, we have now found that the human homologue of adapt78 exhibits extremely high levels of expression in brain autopsy samples from Alzheimer's disease patients, and low levels of expression in brain samples encompassing the substantia nigra from patients who died with Parkinson's disease. Recently, it has become clear that our adapt78 is identical to (or at least highly homologous with) the simultaneously independently discovered Down syndrome critical region 1 (DSCR1) gene of chromosome 21. Furthermore, two different isoforms of both adapt78 and DSCR1 are differentially expressed; corresponding to differentially spliced forms of exons 1-5, 6, 7 and exons 4-5, 6, 7. We propose to now carefully study expression of both isoforms of the human adapt78 gene in different brain regions, using the more sensitive techniques of RT-PCR and in situ hybridization. We plan to study adapt78 expression as a function of age, in brain autopsy samples from otherwise healthy individuals, since adapt78 expression may well vary with age. We will perform detailed studies of brain samples from Alzheimer's disease patients, Parkinson's disease patients, and Down syndrome patients in order to carefully determine both qualitative and quantitative differences in expression of both isoforms of adapt78 mRNA. Localization of adapt78 mRNA expression by cell type will also be studied. We also will synthesize and characterize the (1-5, 6, 7 and 4-5, 6, 7) Adapt78 proteins and generate antibodies to them in order to study expression of the actual proteins in all cell and brain samples. In cell culture studies, with PC-12 cells, we will test the hypothesis that inducible overexpression of

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adapt78 may confer an oxidative stress resistance phenotype. We will also test the ability of inducible adapt78 overexpressing cells to overcome the lethal oxidizing effects of glutathione deficiency, caused by expression of antisense message to gamma glutamylcysteine synthetase. These studies will allow us to begin to investigate our hypothesis that aging, and perhaps certain neurodegenerative diseases, involving defects in the expression of adapt78 and other adaptive genes required to cope with the deleterious effects of oxidative stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANALYSIS OF TORSIN PROTEIN FUNCTION IN C. ELEGANS Principal Investigator & Institution: Caldwell, Guy A.; Biological Sciences; University of Alabama in Tuscaloosa Tuscaloosa, Al 35487 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2006 Summary: (provided by applicant): Dystonia is estimated to be six times more prevalent than Huntington's Disease, ALS, or Muscular Dystrophy. However, as few as 5% of the over 350,000 persons in North America estimated to be affected have been correctly diagnosed and are under treatment (NIH Budget Office). The most severe early-onset form of this disorder has been linked to a mutation in a human gene named TOR1A that encodes torsinA, a protein that is also localized to inclusions in the brains of Parkinson's patients termed Lewy bodies. While a causative genetic mutation has been identified, the cellular mechanisms of pathogenesis underlying dystonia remain unknown. We are applying the advantages of the model organism, Caenorhabditis elegans, towards a detailed analysis of two specific torsin-related gene products in this nematode. The chromosomal positioning of these genes suggests that they may represent a functionally co-expressed unit and preliminary studies from our laboratory indicate they act neuronally. Phylogenetic analysis of the torsin family indicates these proteins share distant sequence similarity with the functionally diverse AAA+ family of proteins. We have determined that ectopic overexpression of a C. elegans torsin homolog results in a reduction of polyglutamine repeat-induced protein aggregation in a manner similar to that previously reported for molecular chaperones. The suppressive effects of torsin overexpression quantitatively persisted as animals aged. Antibody staining of transgenic animals using antisera specific to TOR-2 indicated this protein was highly localized to sites of protein aggregation. We propose to extend these preliminary studies through a combination of reverse genetic approaches designed to investigate the cellular role of torsin proteins in the nematode. The specific aims of the proposed project include: 1) to determine what phenotypes are associated with C. elegans torsin homologues; 2) to define sites of C. elegans torsin protein function; and 3) to determine potential effectors of torsin activity. These studies will further our understanding of the molecular mechanisms responsible for early-onset torsion dystonia. Moreover, the aberrant protein deposition associated with diverse neurodegenerative disorders like Parkinson's Disease and those caused by polyglutamine expansion such as Huntington's Disease warrants further investigation of any putative neuroprotective effects of torsins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANTAGONIZING NOS ACTIVITY TO INDUCE NEUROGENESIS IN THE* Principal Investigator & Institution: Enikolopov, Grigori N.; Associate Professor; Cold Spring Harbor Laboratory 1 Bungtown Road Cold Spring Harbor, Ny 11724

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Timing: Fiscal Year 2002; Project Start 11-MAR-2002; Project End 31-DEC-2003 Summary: (provided by applicant) Nitric oxide (NO) acts as an essential antiproliferative signal during tissue differentiation and development. We have recently found that we can inhibit NO production and cause an increase in the number of dividing cells in the adult rodent brain by introducing NO synthase (NOS) inhibitors into brain ventricles. This increase was evident in several areas of the adult brain; significantly, we showed this effect in the areas which have very low levels of neurogenesis, including the cortex and striatum. In this proposal we plan to examine whether introducing NOS inhibitors into brains previously lesioned by neurotoxic agents can induce proliferation of nigrostriatal neurons. We also propose to use a line of transgenic mice, where neural stem cells are marked by GFP expression, to follow the fate of transplanted cells in animal models of Parkinson's disease, and to augment the proliferation of these cells by blocking NOS activity. We further propose to generate a double-transgenic mouse line where neural stem cells and differentiated dopaminergic neurons will be marked by the expression of two different fluorescent proteins. This proposal directly relates to the purpose of this RFA as stated in the guidelines: it proposes a strategy for reversing the pathogenesis of Parkinson's disease and it proposes developing an animal model for the studies of the disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ASSESSMENT OF DISEASE PROGRESSION IN PARKINSONISM Principal Investigator & Institution: Eidelberg, David; Director, Center for Neurosciences; North Shore University Hospital 300 Community Dr Manhasset, Ny 11030 Timing: Fiscal Year 2001; Project Start 06-APR-1999; Project End 31-MAR-2004 Summary: The proposed Midcareer Investigator Award is designed to provide the candidate with salary support to devote more time to patient- oriented research and to facilitate his role in mentoring beginning clinical investigators in the field of functional brain imaging in neurodegenerative disorders. Research plan: Parkinson's disease (PD) is the most common degenerative hypokinetic movement disorder. Great strides have been made in the understanding of the pathophysiological mechanisms underlying the neurodegenerative processes in PD, prompting clinical trials of new therapies aimed at slowing or halting the progression of these diseases. To assess these new therapies, reliable in vivo markers of neuronal loss are needed. Currently available clinical measures of disease progression are relatively insensitive, and may not accurately reflect the extent of neuropathological change. Alternatively, quantitative biologically relevant brain imaging markers now exist which may be suitable as outcome measures for clinical trials. Specifically, we have developed three novel methods of assessing disease progression using positron emission tomography (PET): (1) The quantification of dopaminergic function using a radioligand which binds selectively to the dopamine transporter (DAT); (2) The quantification of metabolic brain networks in the resting state; and (3) The quantification of dynamic changes in brain-behavior relationships using regional blood flow activation and network analysis. The goal of the proposed project is to assess the extent to which neurochemical and functional PET imaging markers are sensitive to change in early stage PD, and to compare these measures to standard clinical indices of disease progression. To this end, we propose a longitudinal five-year study to assess disease progression using neurochemical, metabolic, and functional activation PET markers. We hypothesize that PET measures will be more sensitive to disease progression than clinical measures. If this is the case, clinical trials designed to assess potential neuroprotective therapies could require fewer patients and

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be completed in less time. Mentoring plan: The candidate will recruit promising young physicians who have completed high level clinical training in neurology and ancillary specialties. He will afford these individuals with a stimulating post-graduate experience involving specialized aspects of patient-oriented research in movement disorders. He will also provide structured training in the fundamentals of experimental neurological research in using new functional brain imaging techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CATECHOL THIOETHERS IN PARKINSON'S DISEASE Principal Investigator & Institution: Montine, Thomas J.; Professor; Pathology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: (adapted from applicant's abstract) Parkinson's disease (PD) is a serious public health problem for the United States. Although dramatic advances have been made in the clinical management of Parkinson's disease, understanding of the mechanisms that underlie its neurodegeneration is incomplete. Such knowledge will be necessary for future development of therapeutics that impede or halt the progression of Parkinson's disease. The long-term objectives of this project are to determine the mechanisms by which oxidation products of dopamine and related catechols, catechol thioethers, may be converted to neurotoxins that contribute to nigrostriatal oxidative damage and neurodegeneration. The Specific Aims of this projects are: (1) to determine the potency of endogenous catechol thioether produced in the mercapturic acid pathway and the mechanisms by which they may contribute to dopaminergic neurodegeneration in whole mitochondria, cultured dopaminergic neurons, brain regions of aged control and genetically engineered mice with deficiencies in anti-oxidant defenses, (2) to determine the activities of mercapturic acid pathway enzymes and the concentration of catechol mercapturates in brain regions and CSF from patients with Parkinson's disease, other nigrostriatal neurodegenerative diseases, and aged-matched controls, and (3) to determine the mechanisms by which environmental toxicants epidemiological linked with an increased risk of Parkinson's disease may augment neurotoxicity form catechol thioethers. This new information will determine the extent to which catechol thioethers produced in the mercapturic acid pathway may contribute to Parkinson's disease progression, interact with aging and environmental toxicants implicated in Parkinson's disease, and serve as intra vitam biomarkers of nigrostriatal degeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLINICAL CENTER FOR NEUROPROTECTION IN PARKINSON DISEASE Principal Investigator & Institution: Dewey, Richard B.; Neurology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Parkinson's disease is an inexorably progressive disorder of unknown cause in which neurons of the substantial nigra progressively degenerate resulting in ever-greater degrees of brain dopamine deficiency. While a number of treatments have been developed that improve the neurochemical deficit, no treatment has been demonstrated to ameliorate the neuronal deterioration. Such a neuroprotective effect is highly desirable because if this could be achieved, a significant delay in clinical deterioration of patients could be realized. The proposal outlined here

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aims to establish a Clinical Center for neuroprotective research at UT Southwestern Medical Center which will cooperate with up to 42 other such centers around the country in the development and execution of a large-scale clinical trial to test one or more potentially neuroprotective agents for Parkinson's disease. The Clinical Center for Movement Disorders at UT Southwestern Medical Center in Dallas, TX is well suited to becoming such a Clinical Center. It is the primary academic referral center for North Texas and its two staff neurologists are experienced in the design, conduct, and reporting of clinical trials in Parkinson's disease. Once the Clinical Centers are designated, a series of pilot studies will be conducted first to identify the most promising agent or agents. Subsequently, a large trial involving several thousand patients will be developed and conducted to establish whether the chosen agent is actually capable of slowing down the progression of this disease. By studying such a large number of patients under rigorously blinded and controlled conditions, it should be possible to identify even a small beneficial effect on disease progression which would nevertheless be very important, not only for the implications on retarding disease progression, but also because observing such an effect might yield insights into the underlying pathogenesis of this common and disabling disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL CENTER FOR THE STUDY OF NEUROPROTECTION FROM PD Principal Investigator & Institution: Tintner, Ron; Neurology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Our objective is to participate as a clinical center in a national multi-center trial of neuroprotective agents in Parkinson's disease (PD). Over the course of the next five years, we plan to enroll at least two patients per month into these clinical trials to evaluate the efficacy of (yet to be determined) agents for neuroprotection of patients with Parkinson's disease. These patients will be recruited from the Parkinson's Disease Center and Movement Disorders Clinic at Baylor College of Medicine; movement disorders clinic at Ben Taub General Hospital; and, with recruiting efforts in conjunction with local Parkinson's disease support groups. These patients will be evaluated in depth to ensure they meet the criteria for the studies, carefully evaluated with agreed-upon clinical measures and medically monitored to ensure their safety and well-being during the course of the study. We will perform as much of the evaluation as possible at our campus in the Texas Medical Center, but will cooperate fully and enthusiastically to enable evaluations done at cooperating institutions. We will lend our expertise, experience and time to help develop these clinical protocols. We will record complete and accurate data as agreed upon in the study protocols and ensure timely transmission to the statistical coordinating center. We will participate and cooperate with other members and institutions in data analysis and writing and communicating the results of these trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLINICAL CENTER: PARKINSON'S DISEASE NEUROPROTECTION Principal Investigator & Institution: Schneider, Jay S.; Professor; Pathology, Anat/Cell Biology; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007

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Summary: (provided by applicant): The objective of this project is to perform pilot studies to identify putative neuroprotective agents for Parkinson's disease and to demonstrate convincingly in a randomized, double-blind clinical trial the efficacy of one or more pharmacological agents for slowing the progression of Parkinson's disease and to determine the toxicity and tolerability of these agents.Our Clinical Research Center will be a consortium of three local sites, each with a history and interest in conducting Parkinson's disease clinical trials. The lead site will be Thomas Jefferson University (Parkinson's Disease Research Unit), with satellite sites at Main Line Health Hospitals in Bryn Mawr, PA and Neurology Associates, P.A. in Wilmington, DE. This consortium, spanning the Philadelphia metropolitan area, the heavily populated northwestern suburbs of Philadelphia, Southeast Pennsylvania, Southern New Jersey and the entire state of Delaware will greatly enhance our ability to enroll patients in any research project in which we participate. The strength of this consortium is the collective research expertise of the participants and the resultant enhanced availability of early Parkinson's disease patients. As a result of this consortium, we are confident that we will be able to exceed the minimum number of patients to be recruited into study by approximately 50%. Each component of this Clinical Center is staffed by clinical personnel experienced in the clinical and research assessment of Parkinson's disease patients and by accomplished nurses and clinical coordinators with experience in the recruitment and retention of Parkinson's disease patients and the administration of clinical protocols. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEEP BRAIN STIMULATION IN PARKINSON'S MODELS Principal Investigator & Institution: Anderson, Marjorie E.; Professor; Rehabilitation Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Although high-frequency deep brain stimulation (HF-DBS) in the globus pallidus or subthalamic nucleus has become a common technique used to treat drug-resistant symptoms of Parkinson's disease, the mechanisms by which HF-DBS exerts its effects are unknown. In the proposed studies, the ability of chronic administration of the insecticide rotenone, to produce an animal model of Parkinson's disease will first be tested in monkeys. Using PET imaging now available in the University of Washington Regional Primate Research Center, changes in dopamine innervation after administration of rotenone will be measured using a marker of the monoamine vescicular transporter that is present in dopaminergic nerve terminals. These changes will then be correlated, over time, with changes in behavior and with electrophysiological changes in the rate and pattern of discharge of neurons in basal ganglia-receiving areas of the thalamus. This model will then be used to couple the electrophysiological effects of HF-DBS, which can be recorded from basal gangliareceiving neurons of the thalamus, to the stimulation-induced changes in regional metabolism in the cortex and thalamus. PET imaging with the metabolic marker, [8-F] flurodeoxyglucose (FDG), will be used to measure metabolism. This technique has generally shown a relative hypermetabolism in the globus pallidus and thalamus of humans with Parkinson's disease and a relative hypometabolism in areas of the frontal cortex. Changes reported to be induced by HF-DBS have been mixed however. The combination of electrophysiology and metabolic imaging will allow us to address some of the discrepancies from the human literature. Special attention will be paid to the development of abnormal patterns of bursting behavior in the thalamus of monkeys treated with rotenone, as well as the effect of HF-DBS on burst behavior. This will test the hypothesis that some of the symptomatology of Parkinson's disease, and its relief

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using HF-DBS, is a consequence of abnormal patterns of activity in basal gangliathalamic-cortical circuits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEMENTIA OF PARKINSON TYPE: CLINICOPATHOLOGIC PHENOTYPE Principal Investigator & Institution: Galvin, James E.; Assistant Professor; Neurology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: Parkinson's disease and Dementia with Lewy bodies (DLB) together comprise the second most common form of dementia after Alzheimer's Disease (AD). The signature pathologic lesions in these disorders are Lewy bodies (Lbs) found in cortical (DLB) and nigral (PD) neurons. Furthermore, a significant number of AD patients develop parkinsonian signs during the course of disease and many of these patients also are found to have Lbs on autopsy. Whether previously diagnosed with PDassociated dementia now would be classified as DLB is unknown. It is also unclear that PD alone can cause dementia occurs only in the presence of critical Lbs or AD-related pathology. The goal of this project is to characterize the clinicopathologic phenotypes of Dementia of the Parkinson Type (DPT). We propose to analyze the longitudinal studies of the Alzheimer's Disease Research Center (ADRC) for the clinical, motor, cognitive, behavioral, and pathologic characteristics of autopsy defined case of AD, PD and DLB in order to: 1) determine those clinical features that differentiate pathologically diagnosed DLB and PD from AD and from each other to establish the DPT phenotype; 2) identify differences between groups in pathologic features other than those used in the diagnosis by exploring the neuroanatomical correlates of the unique clinical symptomatology of DPT; and 3) to determine the best short set of clinical features for the diagnosis of pathologically defined DPT groups. The ADRC and the Department of Neurology at Washington University School of Medicine provide the candidate with an outstanding environment to develop his skills as an independent clinician-scientist. This K08 award will make available to the candidate protected time to complete the Specific Aims of the project and complete didactic courses in the ethical conduct of research, biostatistics and epidemiological study design. The research career development plan of the candidate is to use the mentored period to establish in the field of dementia research, specifically examining the role co-existent pathologies play in the onset, progression and unique characteristics of dementing disorders. At the completion of the award period, candidate plans to develop an independent R01 project derived from the data generated by the experiments described in this proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEVELOPMENT OF AN IMAGING MARKER FOR PARKINSON'S DISEASE Principal Investigator & Institution: Jennings, Danna L.; Molecular Neuroimaging, Llc 60 Temple St, Ste 8A New Haven, Ct 06510 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-DEC-2002 Summary: (provided by applicant): The development of disease modifying agents in Parkinson's disease has rapidly expanded the need for in vivo markers for diagnosis and monitoring disease progression. Dopamine transporter (DAT) imaging offers the promise of an objective measure of dopaminergic degeneration allowing for identification of changes in the brain that occur early in the illness, prior to clinical

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diagnosis. The primary goal of this project is to examine the sensitivity and specificity of DAT imaging using (3-CIT and SPECT imaging as a diagnostic marker in subjects with suspected PD or PS. Neurologists will identify subjects in whom they have genuine uncertainty regarding diagnosis of PD or PS. The neurologists will be asked to document their 'best guess' diagnosis on a Diagnostic Accuracy Questionnaire at the time of referral. Subjects with suspected PD or PS will be evaluated clinically and with DAT imaging at MNI. The blinded Parkinson's expert will re-examine the subject in 6 months and make a final clinical diagnosis, which will serve as the gold standard diagnosis for each subject. The DAT imaging diagnosis will be compared to the 'gold standard' clinical diagnosis to determine the sensitivity of (3-CIT and SPECT imaging as a diagnostic marker in PD and PS. This project is a crucial step to begin to establish BCIT and SPECT imaging as an objective diagnostic biomarker prior to definitive diagnosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT OF INTEGRATING HSV AMPLICONS FOR PARKINSON'S DISEASE Principal Investigator & Institution: Bowers, William J.; University of Rochester Orpa Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: Gene transfer methodologies have created the opportunity for developing gene therapy for human neurological diseases such as Parkinson's Disease (PD). Adeno-associated virus (AAV) and lentivirus vectors, both of which integrate into the host cell chromosome, have been shown to provide long-term expression of genes and therapeutic efficacy in animal models of PD. These vectors, however, exhibit a number of disadvantages, among them an inability to harbor large transgene segments. Gene therapy vectors based upon the Herpes Simplex virus (HSV) offer numerous advantages for the development of novel therapeutics for PD. These include broad cellular tropism, large DNA packaging capacity that allows for expression of multiple genes, and high transduction efficiency. We propose to modify HSV-derived amplicon vectors to provide stable nigrostriatal cell-specific gene expression. For this pipeline project, we will initially construct novel integrating forms of the amplicon that will direct expression of a reporter gene product specifically within cells of the striatum and substantia nigra. DNA insulator elements will be introduced to facilitate maintenance of the integrated transcription unit in a euchromatic state. These new vectors will be coadministered with an amplicon expressing the Sleeping Beauty transposase into the striata of unlesioned rats, where gene expression duration and cell-type specificity will be experimentally derived. The vectors will then be used to deliver glial cell line-derived neurotrophic factor (GDNF) prior to 6-OHDA-induced lesioning of rats to assess the capacity of the new vector system to confer protection to the nigrostriatal pathway. The proposed studies will yield a novel HSV vector system, provide a detailed understanding of transgene expression in vivo, and evaluate its therapeutic effectiveness in protecting nigrostriatal neurons in a well-established rodent model of PD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIETARY PARKINSONS

ETIOLOGIES

OF

MULTIPLE

SCLEROSIS

AND

Principal Investigator & Institution: Ascherio, Alberto; Associate Professor; Nutrition; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460

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Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-MAR-2002 Summary: We propose to document the occurrence of multiple sclerosis (MS) and Parkinson's disease (PD) among male and female participants of three large ongoing prospective studies and to examine prospectively the association between several dietary and non-dietary risk factors and the incidence of these diseases. The studies are the Nurses' Health Study I (121,000 women), Nurses' Health Study II (116,000 women), and the Health Professionals Follow-up Study (52,000 men). Diet has been assessed repeatedly by a semiquantitative food frequency questinnaire developed and refined by our group over the last 15 years; detailed studies in subsamples of participants demonstrate that this questionnaire performs well, and that the study populations have substantial various in dietary intakes. Several follow-up cycles have been completed, with responses over 90 percent. Numerous non-dietary variables of potential interest as risk factors for MS and Parkinson's disease or as potential confounders of the associations between diet and these diseases have also already been collected at baseline and during the follow-up. We will evaluate the association between history of childhood infections or exposure to dogs potentially infected with the cannine distemper virus and risk of multiple sclerosis by conducting a nested case-control study. In addition, we will examine the association between selected mutations of CYP-2D6-one of the cytochrome P450 enzymes-and risk of PD, and the potential interaction between CPY-2D6 mutations and cigarette smoking as risk factors for PD. The CYP-2D6 genotype will be determined using blood samples that have already been collected, or buccal smears that will be obtained as part of this grant from cases of PD for whom on blood samples are available. The proposed investigation is a highly cost-effective way for studying diet and MS and PD because it draws on a large amount of information already collected and processed, and because the cost of mailing and processing of the foollow-up questionnaires is provided by other sources (CA 55075, CA 40356, CA 50385). Reported cases of MS and PD will be confirmed by supplementary questionnaires sent to the patients and their physicians. Fatal events are identified by next-of-kin, postal service, or the National Death Index and confirmed by hospital records and other additional information. By the end of the follow-up, we project a total of 461 confirmed cases of MS and 380 confirmed cases of PD. We will have sufficient poser to evaluate a series of specific hypotheses with substantial public health implications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DISABILITY IN PARKINSON'S DISEASE Principal Investigator & Institution: Bassett, Susan S.; Associate Professor; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 07-SEP-2001; Project End 31-JUL-2006 Summary: Disability affects as much as 17 percent of the adult population in the US and the majority of these individuals suffer both chronic medical conditions and psychiatric disorders. In combination, the impairments that accompany these disorders synergistically intensify any disability. Parkinson's disease (PD), a progressive neurodegenerative disorder, produces marked impairments of motor function and significant disability. However, the majority of PD patients also experience emotional and cognitive impairments, yet little is known about the contribution of these impairments to disability. In addition, disability assessment in PD has focused narrowly on self-care, ignoring other important areas such as work performance. It is unknown, for example, whether withdrawal from the workforce among PD patients is more closely tied to emotional and cognitive impairments than to decrements in motor function. The aim of this project is to assess impairments in motor, cognitive and

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emotional function and the accompanying disabilities, longitudinally, in individuals with PD, to understand how the impairments contribute to disability and how psychiatric disorders produce excess disability in these patients. Specifically we will examine performance on quantitative motor tests and cognitive tests of memory, attention and executive function. Psychiatric symptom occurrence and severity, clinical diagnosis, and temperament will also be examined. Disability assessment will include the areas of physical, social and occupational functioning as well as perceived quality of life, utilizing clinical interview, performance evaluation, vocational testing and informant interview. Participants will include 100 non-demented individuals with PD, 65 years of age or younger. Approximately equal numbers of males and females will be enrolled. All participants will be evaluated yearly, four times during the course of the project. Investigation into the full range of disability found in PD, and an understanding of the contribution all impairments play in increasing disability, will enable us to develop strategies to improve the care of these patients. It will also provide information to guide interventions to decrease the level of disability suffered by those with PD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DOPAMINE AND OXIDATIVE STRESS IN PARKINSON'S DISEASE. Principal Investigator & Institution: Sidhu, Anita; Associate Professor; Pediatrics; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2002; Project Start 30-SEP-1995; Project End 31-MAR-2007 Summary: (provided by applicant): Oxidative stress is an important causative factor in the onset and maintenance of several neurodegenerative conditions, such as Alzheimer's disease and Parkinson's Disease (PD). While dopamine (DA)-replacement therapy can control the symptoms of PD, it can also cause severe dyskinesia in patients. Blockage of the D1 DA receptors with Dl-selective antagonists in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-lesioned primates, significantly improves dyskinesia, through unknown mechanisms. Autoxidation of DA is a major source of free radicals; activation of D1 receptors also triggers oxidative stress, and these effects are additive, such that the resulting damage produced in the postsynaptic cell is several fold greater than that elicited by sources of free radicals (hydrogen peroxide (H202)), which does not stimulate the D1 receptor. Several indices of oxidative stress, lipid peroxidation, nitrite production, nitric oxide synthases, neurofilament (NF)-kappaB nuclear translocation, are all elevated two to six fold higher with DA-mediated D1 receptor activation, than H202 alone. We will examine in detail the contribution of D1 receptor stimulation, through the use of agonists and antagonists, in causing oxidative stress in SK-N-MC human neuroblastoma cells, which endogenously express the D1 receptor and is representative of postsynaptic cells. We will examine the mechanism and functional consequences of D1 receptor stimulation on signaling pathways, as well as by selectively blocking parts of the oxidative stress cascade(s). The participation of D1 receptors and oxidative stress in cell death and apoptosis will also be measured. Since blockage of D1 receptors in the MPTP model of PD improves some of the symptoms of PD, we will investigate whether D1 receptors augment MPTP effects in SK-N-MC cells. Conversely, blockage of D1 receptors with antagonists may attenuate MPTP effects on the various indices of oxidative stress. A clear understanding of the effects of dopamine autoxidation and the participation of D1 DA receptors in inducing oxidative stress, is important for understanding patient response to agonist therapy in PD, and may aid in the design of novel therapeutic treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ECONOMIC AND POLICY ANALYSES IN GERIATRIC DISEASE Principal Investigator & Institution: Noyes, Ekaterina I.; Community and Prev Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Dr. Noyes proposes to develop the skills necessary to become an independent researcher in the field of cost-effectiveness analysis and health policy evaluation in geriatric disease. The candidate's undergraduate training in biomedical physics and PhD training in neurophysiology confirm her commitment to research as well as her strong analytical capabilities. To strengthen her knowledge in health care policy, outcomes evaluation, statistical analysis, and data management, the candidate will complete the proposed didactic coursework and participate in a series of clinical skills workshops and seminars. The candidate will spend the main part of the five-year grant period conducting proposed research. The candidate's long-term plan is to improve efficiency of the health care system by incorporating cost-effectiveness analysis into health care policy and decision making, in particular, related to Parkinson's disease (PD) and geriatric depression. The study will address shortcomings of the methods currently used to evaluate outcomes in PD and will use patient's quality of life as the effectiveness measure. It is hypothesized that 1) levodopa is more cost-effective than pramipexole in the treatment of early PD; 2) elderly chronically ill patients use more health services than do general Medicare beneficiaries; and 3) disability and long-term care are the main sources of expenses associated with chronic geriatric disease. The project's specific aims are to conduct a cost-effectiveness analysis of early PD therapy with pramipexole compared to levodopa, to assess the pattern of health care utilization in Medicare beneficiaries with PD, and to develop a Parkinson's disease health policy pilot model. The cost-effectiveness will be assessed based on 4 years of data collected from a clinical-economic trial in PD. The patterns of health services utilization of Medicare patients will de examined using the Medicare Current Beneficiary Survey. Supplemental data on costs will be collected from published literature and Medicare fee schedules. The study design will include costeffectiveness analysis, decision analytical modeling, sensitivity analysis, and Bayesian statistics. The results of this study can serve as a foundation for developing clinical guidelines for PD, provide information for resource allocation with respect to long term institutional and informal care, and to improve public health policy associated with chronic diseases and aging. Supervision for this project will be provided by a multidisciplinary team at the University of Rochester whose members are experienced in fostering the development of clinical researchers. The model and analytical approaches acquired by the candidate during her training will be used later to develop a decision analytical model describing geriatric depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECTS OF STRESS ON PATHOLOGY OF PARKINSON'S DISEASE Principal Investigator & Institution: Metz, Gerlinde A.; University of Lethbridge 4401 University Dr Lethbridge, Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Stress can have beneficial and maladaptive consequences depending on its type and duration. Stress can affect motor function and the course of neurodegenerative diseases of the motor system, however, this relationship has not been characterized yet. The proposed projects focus on a systematic investigation of the effects of stress and glucocorticoids, the major stress hormones, on

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motor function and neurodegeneration in Parkinson's disease (PD). The research proposal has three objectives: 1) Do stress and glucocorticoids affect motor performance? This objective is to characterize how stress or glucocorticoids affect skilled and locomotor movements. Glucocorticoid levels of rats will be manipulated and dosedependent effects determined. It is expected that high levels of stress or glucocorticoids alter motor performance more likely than lower doses and that skilled movement are more susceptible to stress than locomotion. 2) Do glucocorticoids affect the onset and course of PD? This objective is to investigate the role of glucocorticoids in motor function and neurodegeneration in three rat models for PD, an acute and a progressive neurotoxic lesion, and a slow progressive lesion induced by an environmental toxin, used as a pesticide. Glucocorticoid levels will be manipulated and functional abilities assessed accordingly. It is expected that absence of glucocorticoids or chronically elevated levels lead to detrimental effects in the course of PD. 3) Can drug treatments or experience attenuate glucocorticoid-induced behavioral and histological aggravation in PD? This objective is to examine possible therapeutic interventions to protect the motor system and its function from harmful effects induced by elevated glucocorticoid levels. One series of experiments will investigate a pharmacological approach, which reduces glucocorticoid levels. Another series of experiments will assess the influence of environmental enrichment on the pathology of Parkinson's disease. It is expected that both treatments slow the progression of neural degeneration and diminish severity of motor symptoms. These projects will determine (1) the degree to which stress and glucocorticoids can influence motor learning, performance, and anatomy of the motor system, (2) the role of glucocortcoids in the etiology of PD and the progression of neural death and motor symptoms, and (3) which interventions can alter the influence of glucocorticoids on the course of PD. These approaches will provide the opportunity to understand factors involved in the pathology of PD and to develop novel therapeutic strategies for neurodegenerative motor disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EMORY UNIVERSITY PD NEUROPROTECTION CLINICAL TRIAL CENT* Principal Investigator & Institution: Watts, Ray L.; Professor and Vice Chairman of Neurology; Neurology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Emory University has all of the necessary components to become a Parkinson's Disease Neuroprotection Clinical Trial Center. There are an estimated 50,000 persons currently diagnosed with Parkinson's disease and an estimated 5,000 newly diagnosed patients each year in the area served by Emory University. The demographic characteristics of the area served by Emory University allows for the recruitment of an ethnically diverse population of study patients. Emory University is an established Clinical Trials Center with the necessary space to efficiently conduct clinical trials, prepare and process lab specimens and securely and confidentially maintain study medication and documentation. An experienced clinical trial team is currently in place to assure that the studies are conducted in a manner which allows for accurate, efficient and timely collection of data and provides a safe and pleasant environment for the patients. The Clinical Trial Staff have all received training and certification to conduct clinical trials from the Emory University Institutional Review Board and have been trained and currently follow Good Clinical Practice Guidelines to assure the safety and protection of study participants. The Principal

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Investigator, Dr. Ray L. Wafts, has extensive experience in developing, conducting and monitoring clinical trials and an excellent track record in the recruitment of patients. The Center currently works closely with the American Parkinson Disease Association and all of its local chapters and support groups to facilitate patient recruitment through multiple resources provided to the Center by the American Parkinson Disease Association. Emory University's Advanced Center for Parkinson Research/A. Worley Brown Family PD Clinical Research Unit is willing and dedicated to adhering to a common protocol and to cooperate with other centers and NINDS in the conduct of both pilot studies and the main efficacy study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENVIRONMENTAL AND GENETIC RISKS FOR PARKINSON'S DISEASE Principal Investigator & Institution: Nelson, Lorene M.; Associate Professor; Health Research and Policy; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 01-JUN-1994; Project End 31-JUL-2005 Summary: The primary goal of this project is to investigate whether certain environmental exposures and genetic variants, either alone or in combination, affect the risk of developing Parkinson's disease (PD). We will investigate mechanisms that may explain the consistently observed inverse associations of cigarette smoking and caffeine consumption with PD, and the role of residential pesticide exposure on the risk of PD. In addition, existing and newly-identified polymorphisms in the coding and regulatory regions of candidate genes will be investigated, including genes that code for: (1) endogenous enzymes involved in metabolism of tobacco or caffeine, or in the detoxification of putative toxicants for PD, (2) proteins involved in dopamine regulation or metabolism, and (3) proteins that play a role in protein degradation and aggregation in dopaminergic neurons. We propose to expand a recently completed case-control study in a large health maintenance population of more than 500 newly diagnosed PD cases and 500 controls. Because preliminary data show that the strongest associations of genetic variants were observed among PD cases with early age at diagnosis (age less than or equal to 60), we will identify approximately 330 additional such cases along with age- and sex-matched controls. This new sample will be combined with that of the previous study, resulting in approximately 420 young diagnosis cases and 430 older diagnosis (age greater than 60) cases to be compared with 870 age- and gender-matched controls. Detailed information will be collected from all study subjects using in- person and telephone structured interviews including information on cigarette smoking, caffeine intake, and residential exposure to pesticides, along with other putative risk factors. Venous blood samples will be drawn for DNA extraction and genotyping assays for the gene polymorphisms of interest. By examining genetic polymorphisms within a group of carefully chosen candidate genes, in combination with extensive information about common environmental exposures, we hope to advance knowledge regarding both genetic and modifiable environmental risk factors for Parkinson's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENVIRONMENTAL, GENETIC AND CELLULAR DETERMINANTS OF PD Principal Investigator & Institution: Langston, J W.; Parkinson's Institute 1170 Morse Ave Sunnyvale, Ca 94089 Timing: Fiscal Year 2002; Project Start 26-AUG-2002; Project End 31-JUL-2007

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Summary: The long-term goal of our research is to identify the cause(s) of Parkinson's disease. This proposal features an integrative approach to the investigation of (1) cellular mechanisms involved in neurodegeneration, (2) environmental determinants that affect disease risk, and (3) genetic factors that may affect susceptibility. It is composed of four different integrative research projects, and three cores (administrative, research development, and information outreach), which together make up a Coordinated Center for Parkinson's Disease Environment Research. The broad theme underlying this proposal is that Parkinson's disease results from the interaction between environmental toxicants (such as pesticides or metals), protective factors in the environment (such as nicotine, caffeine) and genetic susceptibility factors. Project 1 (entitled "Genes, Environment & PD: Studies in 4 Unique Cohorts") investigates the separate and combined roles of occupational toxicant exposure (pesticides, metals), genetic variants of membrane transporters of these toxicants and putative neuroprotective behaviors (tobacco & caffeine use) in more than 1000 PD cases and over 1500 controls. Shared diagnostic and exposure assessment in 4 cohorts facilitates combined analyses, while the diverse characteristics of each cohort maximize generalizability. The goal of Project 2 (entitled "Neurotoxicants, Oxidative Stress and Alpha-synuclein") is to investigate the role of oxidative stress as a key contributor to the development of alpha-synuclein aggregation, inclusion body formation and ultimately neuronal injury at the experimental level. The effects of metals/pesticides on these pathological processes will also be assessed. Our third project (entitled "Iron, Oxidative Stress, and Pesticides)," will examine (i) the agerelated susceptibility of the mouse nigrostriatal system to combined damage from iron and pesticide exposure, (ii) the effects of oxidative stress in the context of such exposures, and (iii) ways to protect against these effects. Both Projects 2 and 3 will utilize well-established and novel transgenic models to achieve their scientific goals. Our fourth project (entitled," Nicotine and neuroprotection in nonhuman primates") will explore the effects of nicotine as a potential neuroprotective agent against nigrostriatal injury in a primate model of Parkinson's disease. The hypothesis that this action may be achieved through a receptor mediated stimulation of growth factors will also be examined. These integrative research projects should provide important new insights in the environmental, genetic and cellular factors contributing to Parkinson's disease, and could bring us closer to finding the cause of the disease. Success in these endeavors could lead to new strategies for treatment and even disease prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGY AND GENETICS OF PARKINSON'S DISEASE Principal Investigator & Institution: Rocca, Walter A.; Professor of Epidemiology and Neurology; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 01-JUN-1996; Project End 31-MAY-2006 Summary: (Adapted from applicant's abstract): Parkinson's disease (PD) is a common and disabling condition in the expanding elderly population of the US and worldwide. Its etiology remains unknown and both genetic and environmental factors have been suspected. The long-term goal of the proposed studies based in different sampling is to clarify the etiology of PD and to identify means to prevent it. Three independent but related studies based on different sampling and measurement strategies are proposed. The hypotheses tested derive directly from our current work and preliminary findings. A case control study will include 800 cases of PD referred to the Mayo clinic from a 120 mile radius or from a 5 state region and 800 controls free pf PD and parkinsonism matched by age (+ 2 years), sex and region of residence. Controls from the general

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population will be identified from health care financial administration lists for cases aged 65 years or above and through random digit dialing for cases below 65 years. Exposures will be accessed through direct telephone interview, and will include tobacco, coffee, and alcohol use; markers of novelty seeking behavior; and, for women, use of estrogen replacement therapy after menopause and other reproductive and estrogen related factors. A first historical cohort study will test the association between unilateral and bilateral oophorectomy before menopause and PD in an established population based cohort. The study will include 2,533 women who underwent oophorectomy in 1950-1987 while residing in Olmsted County, MN and 2,533 women of the same age and residence who did not undergo oophorectomy. A second historical study will test the association between personality traits measured by the Minnesota Multiphasic Personality Inventory (MMPI) and PD in an established research cohort. This study will include 8,775 persons who underwent MMPI testing in 1962-1965 while residing in Minnesota. The proposed case-control study is strong because it has adequate statistical power to confirm our preliminary findings on the role of estrogen in PD and to explore the link between substance use and novelty seeking behaviors in PD. All interviews with case and controls will be direct, the proposed oophorectomy cohort study is strong because of its cohort design, its population-based sampling, its adequate statistical power, and because of the expected high rate of follow-up through both passive and active strategies. The proposed MMPI cohort study is strong because of its cohort design, its adequate statistical power and because of our extensive experience with tracing and interviewing individuals. These three studies will contribute greatly to understanding the causes and possible prevention of PD by exploring novel hypotheses and by using innovative methods. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGY, PATHOLOGY, AND PARKINSONISM IN AGING Principal Investigator & Institution: Schneider, Julie A.; Rush-Presbyterian-St Lukes Medical Ctr Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: This 5-year clinical scientist development award proposes the use of quantitative epidemiologic principles to relate post-mortem findings to neurologic conditions associated with aging. A spectrum of parkinsonian signs, including bradykinesia, rigidity, tremor, and gait imbalance are common in older persons without Parkinson's disease, and are associated with increased morbidity and mortality. The nigrostriatal system also shows a spectrum of change with age. Preliminary data suggest that nigral neurofibrillary pathology is more common than previously recognized and is related to parkinsonian signs in older persons with and without Alzheimer's disease. The proposed studies will relate nigral neurofibrillary pathology and biochemical nigrostriatal changes to quantitative measures of global and specific parkinsonian signs in older persons with and without Alzheimer's disease. We will test the hypotheses that neurofibrillary pathology, specifically within the pars compacta of the substantia nigra, rather than the ventral tegmental or retrorubral areas, accounts for parkinsonian signs in older persons with and without AD, and that the mechanism by which neurofibrillary pathology produces parkinsonian signs involves decreased gene expression of tyrosine hydroxylase and a reduction in striatal dopamine, but not neuronal loss. We will also determine the role of mitochondrial mutations in the pathogenesis of neurofibrillary pathology and parkinsonian signs. The proposed project will use brain tissue of 80 older persons, without Parkinson's disease, in The Religious Order Study, a longitudinal study of over 650 catholic clergy who have agreed to annual examinations and brain

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donation after death. The proposed study will provide the Candidate in the opportunity to work with senior colleagues and allow the development of a unique research area that integrates the clinical neurology and neuropathology training. Through the course of these studies and analyses, through didactic sessions with her sponsors and consultants, and related course work, the candidate will develop the skills necessary to become an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EVALUATION OF DOPAMINE RECEPTORS FOR PARKINSON'S DISEASE Principal Investigator & Institution: Kopin, Alan S.; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2004 Summary: (provided by applicant): Parkinson's disease (PD) results from the degeneration of nigrostriatal dopaminergic neurons. This process ultimately leads to a progressive decrease in dopamine mediated striatal signaling which manifests as a clinical syndrome characterized by bradykinesia, rigidity, tremor, and gait abnormalities. Traditional therapy for PD has aimed at restoring dopamine levels in the striatum through administration of the dopamine precursor, L-dopa. With advanced disease, L-dopa leads to dyskinesias and periods of marked fluctuation in motor activity ('on-off effect'). Alleviation of these side effects has been a major challenge and has prompted a search for alternative strategies which can provide a more stable level of dopaminergic signaling. A previously unexplored option to restore striatal dopaminergic activity and at the same time to potentially avoid the consequences of long term L-dopa administration, is through the introduction of constitutively active dopamine receptors. The laboratory of the PI has extensive experience in generating receptors with ligand independent (or constitutive) activity through the introduction of activating point mutations. These receptors have the potential to maintain dopaminergic signaling even in the absence of dopamine and/or dopaminergic agonist drugs. The premise of this application is that constitutively active dopamine receptors can be identified using in vitro assays and expressed in the striatum of rats to enhance dopaminergic signaling over an extended time interval. The objective of Specific Aim 1 is to generate and pharmacologically characterize in vitro a series of constitutively active dopamine 1 and dopamine 2 receptors. Using recombinant adeno-associated virus, the functional consequences of striatal overexpression of constitutively active dopamine receptors will be explored in rats (Specific Aim 2). Circling behavior after unilateral viral administration will be used as an index of construct activity. The methodologies utilized will include molecular (generation of constitutively active mutant receptors, expression of recombinant proteins), pharmacologic (radioligand binding, second messenger signaling assays), and behavioral approaches (assessment of circling behavior). These experiments will provide additional insight into the role of dopaminergic receptors in the striatum as well as potentially take the first steps toward the development of a new therapeutic option for Parkinson's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EXERCISE, PHYSICAL FUNCTION, AND PARKINSON'S DISEASE Principal Investigator & Institution: Schenkman, Margaret L.; Phys Med and Rehabilitation; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508

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Timing: Fiscal Year 2003; Project Start 11-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Impairments of spinal and extremity range of motion occur as sequelae to Parkinson's disease (PD) and contribute significantly to difficulties with balance. While subtle impairments of balance may not be obvious on routine clinical examination, they clearly are present early in the disease when appropriately evaluated. If diagnosed early in the disease process, impairments of balance can be remediated with exercise, delaying functional limitations. Coupled with functional retraining, exercise may improve overall physical functional ability and quality of life. Additionally, patients with mild PD have been found to have poor economy of movement during walking. Improvements of economy of movement have not been evaluated with exercise; it is likely that improved range of motion and balance will improve economy of movement. This investigation will examine whether: (1) balance, functional abilities and quality of life improve with improvements of spinal range of motion and balance; (2) physical intervention improves economy of movement, (3) general aerobic conditioning improves functional ability; (4) exercise targeting impairments associated with PD (e.g., range of motion and balance) is more effective than general endurance training and both are more effective than 'standard-of-care' treatments; (5) an ongoing home program, following a supervised exercise program, maintains increased spinal range of motion, balance, and functional ability. The proposed study is a randomized clinical trial, with 3 treatment arms and 4 repeated measures (before and after treatment, with follow-up at 10 and16 months). Specifically we will compare usual care based on a booklet provided by the American Parkinson Foundation, general endurance training, and PD specific flexibility and functional training. The primary outcomes (4 and 10 months) are measures of: (1) overall functional ability (Continuous-Scale Physical Functional Performance test; (2) balance, (Functional Reach); and (3) economy of movement (rate of oxygen consumption at a set walking speed, [(O2 consumption]). We postulate that PD-targeted flexibility and functional training will improve physical functional ability, in part, by improving balance & walking economy. Further, we expect the PD-specific targeted intervention to be more effective than general endurance training or 'standard-of-care' at improving overall physical function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FAS (CD95)-INDUCED REGENERATION OF DOPAMINERGIC NEURONS Principal Investigator & Institution: Desbarats, Julie; Mc Gill University James Admin. Bldg., Room 429 Montreal, Pq H3a 2T5 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2004 Summary: Parkinson's disease is characterized by the degeneration of dopamineproducing neurons in the substantial nigra of the brain. The resulting loss of dopamine leads to the cardinal symptoms of Parkinson's disease (PD), namely tremor, bradykinesia, postural instability, and rigidity. The disease is relentlessly progressive, ultimately resulting in a state of almost complete disability. Although PD can be slowed by current treatment protocols, it cannot be cured nor prevented at present. We have recently found that stimulating the cell surface molecule (Fas (CD95) on peripheral sensory neurons induces rapid, extensive neurite outgrowth in vitro, and can accelerate functional recovery in vivo after sciatic nerve crush injury. Contrary to the traditional view of Fas as a "death receptor", we propose that Fas engagement may induce regeneration of the dopaminergic neurons. In support of this notion, PD patients have elevated levels of soluble Fas in the substantial nigra. Soluble Fas acts as decoy receptor

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to prevent cell surface Fas from being engaged. Furthermore, mice with reduced Fas expression undergo progressive neural degeneration, and exhibit neurological and cognitive deficits. We propose to investigate the causal relationship between Fas expression and PD through the following specific aims: 1. To determine the physiological effects, and the signaling pathway(s) triggered, by Fas engagement on dopaminergic neurons. 2. To determine whether lack of Fas expression predisposes dopaminergic neurons to degeneration and/or MPTP toxicity (a model for PD). 3. To establish if anti-Fas antibody can stimulate dopaminergic neuron recovery in vivo. To accomplish these aims, we will use three models: tyrosine hydroxylase-positive (TH+) cell lines; in vitro cultures of embryonic mouse ventral mesencephalon cells enriched for TH+ neurons by flow cytometric sorting; and MPTP- induced nigrostriatal degeneration in the mouse as an in vivo model of PD. We will design our experiments to test the novel concept that Fas is able to induce regeneration in CNS neurons. The successful completion of these aims would yield a conceptually novel direction in the study of PD and neurodegenerative diseases in general, and a new target for innovative treatment strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL MRI EVALUATION OF PARKINSON'S DISEASE Principal Investigator & Institution: Phillips, Micheal D.; Assistant Professor; Radiology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2001; Project Start 20-APR-2000; Project End 31-MAR-2003 Summary: The objective of this proposal is to develop a broadly available, reliable diagnostic test for early Parkinson's disease (PD) using functional magnetic resonance imaging (fMRI). PD is one of the most common neurodegenerative disorders, affecting over 1 million people in the United States. It causes significant human suffering and has annual cost of approximately 24 billion dollars in health care resources and lost wages. Clinical and research efforts in PD are hampered by the lack of a widely available objective test for this disease. Although PET and SPECT imaging provide the best objective testing currently available, they are limited by lack of widespread availability, high cost, relatively poor resolution and the use of ionizing radiation. Recent advances in fMRI allow for imaging of neuronal activation along the entire brain motor pathway including the brainstem and basal ganglia during the performance of a complex motor task. These techniques have been successfully applied to both normal subjects and PD patients. Normal subjects demonstrate symmetric activation along the entire motor pathway whereas PD patients demonstrate asymmetric activation with decreased neuronal activation along the motor pathway contralateral to their symptomatically more affected side. The degree of asymmetry has been quantitatively studied using a newly developed cluster analysis technique and demonstrates significant differences between normal individuals and early PD patients. The present application seeks to expand and refine these techniques to produce a clinically applicable diagnostic fMRI test for PD. The application is divided into two phases: a development phase (year 1 of the proposal) and trial phase (years 2 and 3 of the proposal). The development phase will study both patients with early PD and normal subjects to address two specific aims: 1) modification of the existing fMRI protocol in order to make it shorter and easier to perform while maintaining the robust activation achieved presently and 2) rigorous quantification of motor task performance to establish minimum performance criteria. The overall goal of the development phase is to produce a well-characterized fMRI protocol that can be applied in the clinical setting to obtain consistent results. The trial

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phase will test the newly developed fMRI protocol on a group of patients with early PD and normal subjects. The specific aim of the trial phase will be to test the hypothesis that early PD patients can be distinguished from normal subjects by quantitative measurement of asymmetric fMRI motor pathway activation. A widely available, reliable diagnostic fMRI test for early PD would be useful in both the clinical and research settings. Potential future applications include the detection of preclinical disease, monitoring disease progression and differentiation of PD from parkinsonian syndromes. A single test that could address all of these potential applications would represent an effective diagnostic gold standard for PD. The present proposal represents a first step toward the development of such a gold standard. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE THERAPHY FOR PARKINSON'S DISEASE Principal Investigator & Institution: Bohn, Martha C.; Director of the Neurobiology Program; Children's Memorial Hospital (Chicago) Chicago, Il 606143394 Timing: Fiscal Year 2001; Project Start 01-SEP-1996; Project End 31-MAR-2005 Summary: (Verbatim from the Applicant's Abstract) The long-term goal of this project is to develop novel gene therapies for neurodegenerative diseases. In the previous support period, we focused on adenoviral (Ad) vectors to deliver the gene encoding GDNF (glial cell line-derived neurotrophic factor). Ad-GDNF injected into either the substantia nigra or striatum of a progressive degeneration model of Parkinson's disease protected dopaminergic (DA) neurons against cell death induced by the neurotoxin 6-OHDA. AdGDNF injected into the striatum also prevented the acquisition of behaviors and molecular changes that occurred in DA deficient young and aged rats. This proposal focuses on the hypothesis that anti-apoptotic gene delivery will also protect DA neurons in vitro and in vivo and have a synergistic effect with delivery of neurotrophic factor genes. Viral vectors harboring genes that block specific apoptotic death pathways, including XIAP, a dominant-negative caspase-9, bcl-2 and bclxl will be studied for effects on survival and function of DA neurons either alone or in combination with neurotrophic factors, GDNF or neurturin. Genes will be delivered to DA neurons in culture and in rat brain using helper free HSV:AAV hybrid amplicon vectors. These vectors will incorporate bidirectional expression cassettes that drive both the therapeutic gene and the cellular marker gene, green fluorescent protein, to permit specific evaluation of transduced cells. Expression will be controlled using the tetracycline responsive element such that transgene expression is "on" in the presence of tetracycline activator (TA) and in the absence of doxcycline (Dox). Vectors will be made in which TA is driven by a viral promoter of the DA cellular promoter, tyrosine hydroxylase (TH). Effects of the 'therapeutic' genes will be studied using non-neuronal cells, the DA cell line, MN9D, and primary fetal DA neurons treated with the neurotoxins, MPP+ or 6OHDA or other cellular insults. In vivo effects of therapeutic genes will be studied in: 1) rats that have received grafts of fetal DA neurons, and 2) rats that have received a progressive 6-OHDA lesion of the nigrostriatal projection. Reversibility of effects will be studied by administration of Dox. Effects on DA neurons will be evaluated using quantitative morphometric and molecular techniques and behavioral evaluations. This project also aims to continue its evaluation of new generation viral vectors, including E2b deleted Ad, totally gutted Ad, and HSV:AAV amplicon, for stability and levels of expression in the nigrostriatal system. The studies involve collaborations among investigators at Children's Memorial Hospital and Northwestern Univ. Med. School and are relevant to the development of novel therapies for neurodegenerative diseases and injuries to the CNS.

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

Project Title: GENE THERAPY FOR NEUROLOGICAL DISEASES Principal Investigator & Institution: Lowenstein, Pedro R.; Director and Professor; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Parkinson's disease (PD) is a chronic neurodegenerative disorder. Although we do not yet understand its cause, there is extensive degeneration of nigro-striatal DA neurons. Powerful neurotrophic factors, which could be used for the treatment of Parkinson's disease, have been described recently. The ultimate goal of this proposal is to develop novel high-capacity adenoviral systems for long term, stable, non-cytotoxic, and non-immunogenic delivery of neuroprotective genes to the brain for both experimental transgene expression in adult animals, and for the future treatment of chronic neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease by gene therapy. Currently used adenoviruses are efficient vectors for gene transfer into the brain. However, their use has been limited by high doses of vectors needed, vector-cytotoxicity, short-term transgene expression, and deleterious effects of anti-adenovirus inflammatory and immune responses. These limitations are due to: (i) low efficiency of transcriptional promoter elements currently used, which directly leads to the need to use higher doses of vectors, and (ii) cytotoxicity and immunogenicity of viral proteins expressed from the genomes of first generation adenoviral vectors. We now wish to initiate the next stage in the design of efficient, safe, long-term expressing vectors for neurological gene therapy. First, high-capacity helper-dependent adenoviral vectors that express no adenoviral genes will be constructed. Second, the amount of protein produced per input virus will be increased by using stronger promoters alone, or combined with enhancer elements. Third, the efficacy of the new vectors will be tested, by expressing selected neuroprotective genes and verify that they are effective in a model of neurodegeneration. The reagents and principles established by this work will be of substantial value to those with interests in the basic and clinical neurosciences, and will lead to the development of novel approaches to the treatment of chronic neurodegenerative diseases. This research will facilitate the development of the tools needed to achieve long-lived, safe, non-cytotoxic transgene expression, and, ultimately, for the treatment of patients suffering from chronic neurodegenerative disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE THERAPY FOR PARKINSON'S DISEASE Principal Investigator & Institution: Sun, Mei; Medicine; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The principal investigator for this proposal, Dr. Mei Sun, is an Instructor at the West Roxbury VA Hospital / Harvard Medical School. The work outlined in this proposal will serve to further the mentored transition of Dr. Sun into gene therapy of aging related neurodegenerative diseases, and from a research associate to an independent academic investigator applying for RO1 level funding. The mentor in this proposal, Dr. Geller is an independent scientist with extensive published experience on neurobiology and gene therapy. A number of scientists and neurologists including Drs. Geller, Goldstein, Maher, Holmes, Cook, and Shiromani will serve as Dr. Sun's advisors. These scientists will provide her both intellectual and technical advice in

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their fields of expertise, and will oversee Dr. Sun's progress throughout the grant period. In this proposal, we will investigate an improved gene therapy for Parkinson's Disease. Parkinson's Disease (PD) is a neurodegenerative disorder that primarily affects the aging brain, and the symptoms of PD are principally due to degeneration of nigrostriatal neurons. Current treatments center around restoring striatal dopamine levels and are effective initially. But these treatments gradually lose efficacy, and they do not alter the progression of the Disease. Thus, improved treatments for PD should first, restore the function of the nigrostriatal system, and second, alter progression of the Disease by protecting the remaining nigrostriatal neurons. Our laboratory has previously shown that expression of tyrosine hydroxylase (TH) in striatal cells supports long-term biochemical and behavioral correction of a rat model of PD. I have recently shown that co-expression of TH and aromatic amino acid decarboxylase (AADC) supports both biochemical and behavioral correction of the rat model of PD. Many investigators have shown that glial cell line-derived neurotrophic factor (GDNF) can protect nigrostrital neurons in rodent and primate medols of PD. We now propose to systematically develop an improved gene therapy for PD by two complementary treatment strategies. Gene transfer is performed using a helper virus-free Herpes Simplex Virus vector system pioneered in this Laboratory. The first specific aim will improve biochemical and behavioral correction by investigating the preferred combination of genes (TH, GTP cyclohyrolase, AADC, a vesicular monoamine transporter) to support production and release of dopamine. The second specific aim will combine the 'preferred combination of genes to restore striatal dopamine levels with GDNF to protect nigrostriatal neurons. The long-term goal is to develop human gene therapy for PD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC LINKAGE STUDY IN PARKINSON'S DISEASE Principal Investigator & Institution: Myers, Richard H.; Professor; Neurology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 30-SEP-1997; Project End 31-JUL-2007 Summary: (provided by applicant): The cause of idiopathic Parkinson's disease (PD), a debilitating disease that afflicts an estimated 1 percent of persons age 60 or older, remains unknown. In this application, we propose genetic epidemiological studies, genetic linkage studies, and candidate gene studies for PD. In the past four years, we have established a ulti-institutional research program that has collected 300 PD affected sibling pairs and extended families. Our linkage analyses to onset age revealed evidence for linkage (LOD 2.1) to chromosome 2pl3 at the 'PARK3' locus (Gasser et al. 1998). Recently, we found association (p85% when transfected in human embryonic kidney cells HEK293 or in human neuroblastoma cells SH-5YSY. In addition, rate-limited DA synthesis enzyme tyrosine hydroxylase mRNA was significantly low in the SH-5YSY cells transfected with two variant genes. These data suggest that the variants in the NURR1 gene might be PD-related mutations. We,

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therefore, hypothesize that diminished expression of the NURR1 gene (loss of function), induced by the mutations in the gene, predisposing to DAergic neuron dysfunction, may represents a potentially important risk factor for Parkinson's disease. To test this hypothesis, we propose to study the relationship between the genotype of the mutations and the phenotype of the disease, and to investigate the underlying mechanisms. First (Aim 1), we will assay for the mutations, genotypes, and phenotypes in the first-degree members of all 10 fPD patients with the identified NURR1 mutations to determine the haplotype linkage, relationship between genotype and phenotype. Second (Aim 2), we will investigate if the mutations in NURR1 gene are specific for Parkinson's disease by analyzing the gene mutations in a total of 400 NC, 300 sPD, and 120 non-PD neurological disorders. Finally (Aim 3), we will determine the mechanisms by which the mutant genes alter NURR1 expression and DAergic neuronal dysfunction. The proposed experiments, which will take approximately four years for completion, will be conducted in parallel with a pilot study to generate a mouse model carrying the NURR1 mutations. The outcomes of the proposed study will improve our understanding of the role of NURR1 gene in the pathogenesis of Parkinson's disease, and may lead to potential therapeutic interventions, as well as means for diagnosing individuals having an increased risk of developing the disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ORGANOCHLORINE EXPOSURE, GENETIC POLYMORPHISM AND PARKINSON'S DISEASE Principal Investigator & Institution: Berkowitz, Gertrud S.; Professor; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 01-MAY-1995; Project End 31-MAR-2006 Summary: (Taken from application) Parkinson?s disease (PD) is a progressive, disabling disorder of the central nervous system characterized by tremors at rest, muscle rigidity, slowness, imbalance and, in later stages, often dementia. It is caused by loss of neurons in the substantial nigra that produce dopamine. Approximately half a million Americans are estimated to be affected by PD. Recent data suggest that environmental exposure, possibly in concert with genetically determined vulnerabilities, contribute to causation of PD; particularly in patients with onset of disease above age 50. The study will examine 300 cases of PD whose diagnoses have been confirmed by strict, standardized criteria and 300 controls with "minor" neurologic disorders not involving the basal ganglia. A blood sample will be obtained and a detailed questionnaire will be administered to each case and control. The groups will be half male, half female. All eligible minority patients will be enrolled. Cases and controls will be matched on age, gender, and race. This proposal has two inter-related biomedically based, epidemiologic objectives. We propose to determine: 1) whether serum organochlorine levels and/or a past history of exposure to pesticides are elevated in patients with Parkinson s disease; 2) whether polymorphisms in specific enzymes related to pesticide metabolism are more common in patients with PD; and 3) whether there is evidence for a gene-environment interaction. A more exploratory objective is to evaluate whether diet, particularly intake of antioxidants, may protect against development of PD. To test the hypothesis that organochlorine levels, the most common type of chemical pesticide used between 1940 and 1970, are increased in PD patients, DDT, DDE, Dieldrin, and oxychlordane will be determined and compared between cases and controls. PCB, its congeners and transnonachlor will also be measured since these are organochlorine compounds as well. The gene polymorphism hypotheses will focus specifically on CYP2D6, GSTP1, and PON1. To evaluate the possible protective role of antioxidants, a detailed dietary history will be

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taken to obtain extensive information on usual antioxidant intake before diagnosis, including Vitamins A, C and E, carotenoids, lycopene, tocopherol and polyphenols (phytoestrogens). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE INJURY IN PARKINSONS DISEASE Principal Investigator & Institution: Ferrante, Robert J.; Professor; Neurology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: Oxidative stress has been proposed as a critical mechanism underlying metabolic dysfunction in diseases and aging and has been implicated in both apoptotic and necrotic cell death. Oxygen-derived free radicals are a normal byproduct of respiration and oxidative metabolism. Normally cells have efficient protective mechanisms which can quench radicals. When there is a compromise in cellular antioxidants or an increase in production of free radical species, neuronal damage occurs. An increasing body of evidence has implicated oxidative damage in the pathogenesis of Parkinson's disease (PD), including evidence of increased lipid peroxidation, protein oxidation, and oxidative damage to both nuclear and mitochondrial DNA directly associated with the known topographic and neuronal distribution of pathology observed within PD. The investigators preliminary studies may provide the strongest evidence yet, and they hypothesize that a connection exists between the pathology observed in PD and oxidative damage leading to metabolic dysfunction in this disorder. Their first Specific Aim is to determine the topographic distribution of markers for oxidative damage to protein, lipid, and DNA fractions in postmortem PD brains, using antibodies to several epitopes associated with oxidative damage. They will provide a direct assessment of markers for oxidative damage to determine if they are altered and subsequently correlate them with the selective neuronal vulnerability and the neuro-pathologic hallmarks associated with PD. Their goal will be to develop biochemical markers which may be useful for diagnostic purposes, monitoring disease progression, and the effectiveness of therapeutic interventions. The second Specific Aim will utilize transgenic animal models and therapeutic interventions to assess the role of oxidative stress in MPTP neurotoxicity. The systemic administration of the toxin MPTP in experimental animals replicates the neuropathological, neurochemical, and clinical features in PD, causing cell death by inducing oxidative stress. They will examine whether transgenic mice with a knockout of the manganese superoxide dismutase gene and neuronal nitric oxide synthase gene, as well as those overexpressing bcl-2 show increased vulnerability or resistance, respectively, to MPTP neurotoxicity. They will investigate the use of novel therapeutic strategies, using free radical spin traps, neuronal nitric oxide synthase inhibitors, and dietary creatine supplementation to block MPTP neurotoxicity. These studies will have direct relevance to understanding the pathogenesis of PD and to developing new therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PARKIN--IN VIVO FUNCTION AND ROLE IN PARKINSON'S DISEASE Principal Investigator & Institution: Feng, Jian; Physiology and Biophysics; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2005

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Summary: Parkinson's Disease (PD) is one of the most frequent neurodegenerative disorders. It is an extrapyramidal movement disorder characterized by the progressive loss of dopamine (DA) neurons in substantia nigra (SN). Recent progress in linkage studies on patients with familial PD has led to the identification of several genes implicated in this disease. One of these genes, parkin, is linked to Autosomal RecessiveJuvenile Parkinson's Disease (AR-JP). Deletions, truncations, and point mutations of parkin in AR-JP patients are correlated with their PD symptoms. However, it is not clear whether the loss of function for this gene directly causes PD, and if so, how does it occur? We propose to answer these questions by generating the parkin knockout mice. They will be used to study whether the deletion of parkin directly leads to selective loss of nigral DA neurons, and PD-like symptoms in mice. Since parkin is widely expressed in many tissues, and yet the progressive cell death is restricted to DA neurons in SN, we hypothesize that parkin may interact with specific proteins in these neurons to sustain their survival. To test this hypothesis, we propose to identify proteins that interact with parkin by using the yeast two-hybrid system. Once these proteins are identified, we will investigate their roles, in association with parkin, in the survival of nigral DA neurons. The specific goal of this project is to understand the in vivo function of parkin and its role in the etiology of AR-JP. As AR-JP and the sporadic form of PD share many similar clinical symptoms and pathological hallmarks (e.g. death of nigral DA neurons), knowledge gained from the study of parkin may shed some light on the potentially common mechanism for PD. It is our long-term objective to use this mouse genetic model to elucidate the molecular and cellular processes that lead to the progressive and selective death of nigral dopaminergic neurons and locomotor dysfunction in PD. This animal model would also be a valuable tool for the development of more effective therapeutic strategies for PD patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PARKINSON DISEASE NEUROPROTECTION CLINICAL TRIAL CENTER Principal Investigator & Institution: Manyam, Bala V.; Professor of Neurology; Scott and White Memorial Hospital 2401 S 31St St Temple, Tx 76508 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This application is in response to the Parkinson agenda for the NIH for the initiation of a randomized controlled clinical trial to test potential neuroprotectants in patients with early Parkinson's disease. The neuroprotectants to be tested in the trial have not yet been chosen and will be selected by an NINDS-appointed oversight committee. It is expected that NIH will fund 42 Parkinson's Disease Neuroprotection Clinical Centers to the institutions who demonstrate the ability to recruit subjects and provide high quality data for the trial(s). This application describes the characteristics of the staff and Parkinson's disease clinical center at Scott & White Clinic/Texas A & M College of Medicine that will be able to fulfill these goals. The following specific aims will be met subject to final common protocol finalized by the NINDS-appointed oversight committee. 1). Recruit 12 or more patients in the early stages of Parkinson's disease for the pilot study. 2). Recruit 72 or more patients for the main study once the final neuroprotectant is chosen from the initial pilot studies. The above patients will be in the early, mild Parkinson's disease, not yet requiring symptomatic treatment and unexposed to prior treatment with levodopa/dopamine agonist/selegiline (within four months). 3). For primary outcome measure to assess the degree of Parkinson's disease, and its progression the Unified Parkinson's Disease Rating Scale (UPDRS) (or one selected by NINDS-appointed

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oversight committee) will be followed for a highly reliable functional outcome or disability scale that is multi-modal in each subject and other protocols that may be implemented with the subject and investigator remaining "blinded" as to treatment assignment through the duration of the study. 4). For secondary outcome measures, monitor any adverse events from medication(s), quality of life measurement, depression, dementia and others by use of appropriate scales included in the final common protocol (such as Adverse Reaction Form, Hamilton Depression Scale and Mini-Mental State Exam) over the duration of the study. The PI has a proven track record in having participated in a large number of clinical trials involving early Parkinson's disease patients, has been involved in drug development for Parkinson's disease and has a team of well qualified staff, with access to large number of early Parkinson's disease patients including women and minority patients, through a network of a large primary care physicians along with a long-term track record of involvement in both laboratory and clinical care in the treatment of Parkinson's disease. Thus, the investigators have adequate experience, resources, and proven ability to recruit suitable early Parkinson's disease subjects and carry out the clinical trial to meet the requirements of RFA-NS-02-010 in a timely manner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PARKINSON DISEASE NEUROPROTECTION TRIAL: CLINICAL CENTER Principal Investigator & Institution: Martin, W W.; University of Alberta Edmonton T6g 2E1, Canada Edmonton, Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The long-term objectives are to develop a neuroprotective strategy that can be applied to patients with Parkinson's disease (PD) in order to alter disease progression, and to evaluate in the setting of a multi-center clinical trial the efficacy of any such strategies. In PD, there is a prolonged course of progressive neuronal loss which is not altered by existing treatments. The development of neuroprotective strategies is therefore important to lessen the medical, societal, and economic impact of PD-related disability Patients will be recruited with early Parkinson's disease who have been symptomatic for fewer than five years, and who have received levodopa or dopamine agonists for no more than six months. Patients will be followed clinically over a period of three years to assess the potential neuroprotective benefit associated with a drug or drugs chosen by the Steering Committee. Although the multi-center trial will be based on clinical rather than surrogate endpoints, at this site, magnetic resonance imaging will be used to obtain a quantitative index of regional brain iron concentration which we hypothesize to correlate with disease progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PARKINSON'S DIS. NEUROPROTECTION:BROOKLYN CLINICAL CTR. Principal Investigator & Institution: Bodis-Wollner, Ivan G.; Professor of Ophthalmology; Neurology; Suny Downstate Medical Center 450 Clarkson Ave New York, Ny 11203 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This is an application to be selected to become one of the centers of an NIH directed research to Brooklyn explore therapeutic agents in the prevention and retardation of neural degeneration in Parkinson's disease. The location

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and patient population of our Parkinson's Disease and Related Disorders Center is unique. We serve a large population of minority Parkinson Disease patients consisting almost entirely of black Afro-Americans and of Caribbean descent in the heaviest populated borough, Brooklyn, New York. We have more than the requested minimum new patients for the study even though the bulk of our patients are not specifically referred but diagnosed in our general neurology clinic. We will implement visiting nurse service to ensure retention.What we will contribute by participation in the neuroprotective study are to:provide scientifically usable data from OUR neurodegenerative study in the minority population enhance the capability of the federal health system to embrace this minority population with forefront treatment possibilities provide the best available care to a large segment of the Brooklyn minority population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PARKINSON'S DISEASE CLINICAL TRIAL GROUP SITE Principal Investigator & Institution: Calabrese, Vincent P.; Mc Guire Research Institute, Inc. 1201 Broad Rock Blvd, Res 151 Richmond, Va 23249 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Researchers at the McGuire Veterans Affairs Medical Center (MVAMC) bring to the Parkinson Disease (PD) Neuroprotection Clinical Trial Group exceptional expertise, outstanding clinical and laboratory resources, and a qualified and motivated patient population from which to recruit subjects. The McGuire Parkinson Disease Research, Education, and Clinical Center (PADRECC) provides PD treatment for military personnel and veterans throughout the southeastern United States, ranging from Pennsylvania down to Florida (including Puerto Rico) and west to the Mississippi River. Veterans with PD from this entire region are referred to MVAMC for treatment. Native Americans in this region seeking treatment for PD and patients referred from private practice are also eligible to attend the MVAMC PADRECC. This combined pool of potential study participants will exceed the enrollment needs for a member site of the proposed PD Neuroprotection Clinical Trial Group. The research mission of the MVAMC PADRECC is to establish a center of excellence for clinical trials, emerging biomolecular strategies, and integrated health services. The MVAMC and its affiliate university, Virginia Commonwealth University/Medical College of Virginia Hospitals (VCU/MCVH), boast a talented group of scientist-practitioners with a broad range of clinical interests and research expertise related to PD. The MVAMC PADRECC personnel, resourc6s, and patient population will be available for the PD Neuroprotection Clinical Trial Group. MVAMC investigators have a long history of excellent recruitment and retention capabilities and a supportive clinical environment in which to conduct studies. Their history of participation in multicenter trials managed by pharmaceutical companies, the Parkinson Study Group, and the NIH demonstrate their commitment to cooperative research projects. MVAMC investigators will cooperate fully with all other centers in the PD Neuroprotection Clinical Trial Group in the conduct of each pilot and main study to test agents approved by the Oversight and Steering Committees. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PARKINSON'S DISEASE GENE THERAPY STUDY GROUP Principal Investigator & Institution: Federoff, Howard J.; Professor of Neurology and Director; Neurology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627

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Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: Parkinson's disease (PD) affects about 1 million people in North America. Medications, such as levodopa, and some surgical approaches are available for PD, but offer only symptomatic therapy. New information contribute to current optimism that gene therapy might correct the molecular disturbances of PD, alleviate the symptoms of the illness and/or in retarding disease progression. Setbacks in gene therapy for other diseases underscore the importance of a purposely deliberate and careful approach that demands substantial assurances of safety and potential efficacy in advance of human testing. It is this philosophy of conservatism that will characterize the activities of our group. A coordinated stepwise progression from basic research through exhaustive preclinical evaluation prior to clinical testing is required. A multicenter, multidisciplinary collaborative group (The PD Gene Therapy Study Group [PDGTSG]) has formed and seeks support for those activities that will lead to a large-scale clinical trial of gene therapy for patients with PD. The PDGTSG consists of three different components: Cores, Principal Projects, and Pipeline Projects. Core A. Administrative Core (PI: Dr. Federoff): Houses a Steering Committee, and Vector (Chair: Dr. Lowenstein), Human Subjects/Clinical Assessment (Chair: Dr. Kurlan), Bioethics (Chair: Ms. Greenlaw), Intellectual Property (Chair: Ms. Hunter) and Biostatistics Modules (Chair: Dr. Oakes). Provides for the coordination of budgeting, committee scheduling, reports, progress preparation, and interface with NINDS staff, the clinical, scientific and lay community. Core B. Biological Measurement Core (PI: Dr. Federoff: Functions in the application shared quantitative measurements. Houses the database and the bank of vector constructs used in all studies. Project I. "Enzymatic Gene Transfer in MPTP Monkeys" (PIs: Bankiewicz and Kordower) Will comprehensively evaluate two vector platforms (rHIV and rAAV), each transducing the identical AADC gene cassette in the standardized non-human primate model. Project II. "Trophic Gene Transfer in MPTP Monkeys" (PIs: Bankiewicz and Kordower) Will comprehensively evaluate two vector platforms (rHIV and rAAV), each transducing the identical regulated GDNF gene cassette in the standardized non-human primate model. PIPELINE PROJECTS 0PPs) Focus 1: 1reproved regulation of gene expression PP I. "Tet-Regulated Vectors for Parkinson's Disease" (PI: Bohn). PP II. "Engineering RNA Switches that Respond to Dopamine and its Analogs" (PI: Breaker). Focus 2: Development of new vector platforms for application in PD disease models. PP III. "High Capacity Gutless Adenovirus" (PI: Lowenstein). PP IV. "Development of Integrating HSV Amplicons for Parkinson's Disease" (PI: Bowers). Focus 3: Development of methods to effectively control and distribute lentiviral and AAV vectors throughout the non-human primate brain. PP V. "Enhanced Delivery Methods for Widespread Distribution of Lentiviral and AAV Vectors" (PI: Bankiewicz). PP VI. "Analysis of Vector and Transgene Product Transport and Distribution" (PI: Bankiewicz) Focus 4: Development of imaging methods to detectgene expression. PP VII. "Design, Construction and Evaluation of PET Imaging Gene Surrogate" (PI: Muhkerjee). Focus 5: Development of a hioethics approach to PD gene therapy. PP VIII. "Measuring and Explaining PD Patients' Participation Preferences Regarding Phase I Studies in Gene Transfer Therapy" (PI: Kim). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PARKINSON'S DISEASE NEUROPROTECTION CLINICAL CENTER Principal Investigator & Institution: Adler, Charles H.; Mayo Clinic Arizona Sc Johnson Research Medical Building Scottsdale, Az 85259 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2007

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Summary: (provided by applicant): Parkinson's disease (PD) is a neurodegenerative disorder affecting approximately one million Americans. All patients develop a gradually progressive combination of signs and symptoms, including tremor, rigidity, slowness of movement, drooling, low volume speech, micrographia, gait and balance difficulty, and difficulty with activities of daily living. It is known that patients with PD have a loss of dopamine containing neurons projecting from the substantia nigra to the striatum, and most clinical signs and symptoms respond to replacement therapy with doparminergic medications (ie. levodopa, dopamine agonists). However, the underlying mechanism of neurodegeneration is unknown and therefore, to date, there is no treatment to cure or slow the progression of the disease. Many treatments have been hypothesized to be neuroprotective based on in vitro studies and animal data, but clinical trials have not found these drugs to be neuroprotective in patients with PD. The lack of a neuroprotective treatment has been a serious problem for patients, caregivers, health professionals, and for the economy. As the disease progresses the cost of care increases, with estimates of annual cost for medical care going from $3,000/yr early in the disease course to $15,000/yr in later stage disease. Finding a medication(s) that will slow or halt the progression of PD is therefore a major goal of PD research. To this end creating a multi-center study group to run clinical trials of potential neuroprotective agents has been set as a goal of the NIH. This application has, as its specific aim, to be one of the NIH Clinical Centers for neuroprotection treatment trials. This application proposes to create a consortium of centers at the Mayo Clinic and Sun Health Research Institute in order to best be able to enroll patients with early PD for neuroprotection treatment trials. With the mandate to enroll two patients/month for 42 months, the proposed consortium expects to meet these recruitment goals. Mayo Clinic Scottsdale, Mayo Clinic Jacksonville, Mayo Clinic Rochester, and Sun Health Research Institute, all have clinical centers that specialize in the care and treatment of patients with PD, and all have well established clinical trials experience. The resources are available to run clinical trials with a dedicated physician staff of 10 neurologists specializing in treatment of Parkinson's Disease at these four sites, along with nursing staff and the physical plant required. The protocols will be developed by the PIs of the various clinical centers along with NIH staff. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CENTERS

PARKINSON'S

DISEASE

NEUROPROTECTION

CLINICAL

Principal Investigator & Institution: Fang, John; Neurology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): As outlined in this RFA (RFA-NS-02-010) announcement, the aims of this project are to create a clinical center for the conduct of future clinical trials of neuroprotection for Parkinson's disease. This site has three board-certified neurologists trained in movement disorders who will participate in this proposed project. Upon implementation of this project these neurologists will collaborate to conduct a pilot trial of an agent to prevent disease progression in PD. Subsequently, additional collaboration with the other clinical center sites will lead to at least one multicenter trial. This project will help to maintain a stable infrastructure for the administration of the clinical trial(s) in neuroprotection related to Parkinson's disease. In addition, the conduct of this type of clinical trial(s) will generate a sample of patients with early PD who may be willing to participate in genetic studies. Similarly, subjects may be willing to participate in studies to identify markers from blood or

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cerebrospinal fluid that may indicate disease presence or severity. This research may lead to a greater understanding of PD and better treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PARKINSON'S DISEASE NEUROPROTECTION CLINICAL TRIAL Principal Investigator & Institution: Sethi, Kapil D.; Professor; Neurology; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Specific Aim: To participate in the clinical trial of neuroprotection in Parkinson's disease (PD) as a clinical center. Summary:The Medical College of Georgia (MCG) Movement Disorders Clinic (MDC) is uniquely qualified to be a clinical center for the proposed neuroprotective trial in Parkinson's Disease (PD) because of the varied patient population. The clinic has been operational since 1985 at the MCG and the Augusta Veterans Affairs Medical Center (VAMC). Over 700 patients with PD who are in both early and advanced stages of the disease are evaluated and treated each year at MCG and the VAMC. Kapil D. Sethi, MD, FRCP (UK) and the entire research team have extensive experience in caring for PD patients and conducting clinical drug and research trials. The existing referral base is strong, consisting of general neurologists in the local area and surrounding Primary Care Providers. The local PD support group was started ten years ago under the guidance of the Dr. Sethi. The support group is actively involved with the MDC and is helpful in the education of newly diagnosed PD patients and their families. Long-Term Objectives:1. To delay the progression of PD through the use of medications while maintaining quality of life.2. Discover indicators of those susceptible to PD and prevent or delay onset of the disease.3. Ultimately, find a cure for PD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PARKINSON'S DISEASE NEUROPROTECTION CLINICAL TRIAL Principal Investigator & Institution: Wooten, G F.; Neurology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This is an application for a Clinical Center for the Parkinson's Disease Neuroprotection Trial from the Department of Neurology at the University of Virginia in response to RFA-NS-02-010. We have a clinical staff of four movement disorder subspeciality neurologists, a nurse coordinator, an administrative coordinator, and an information and referral coordinator. Over the past 10 years, our team has enrolled 445 subjects in clinical trials with 413 subjects completing the protocol. Our diagnostic accuracy and interrater reliability are documented objectively and are excellent. We have been highly productive of scholarly publications with 26-refereed publications on clinical aspects of PD in the past 5 years. Over the past six years we have ascertained 150 patients with a clinical diagnosis of Parkinson's disease (PD) who were receiving no symptomatic therapy. We have excellent alliances with multiple patient support groups and both referring neurologists and primary care physicians throughout the state of Virginia. Our team is experienced, productive, and fully able to meet the requirements to become a Clinical Cente for the Parkinson's Disease Neuroprotection Trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PARKINSON'S DISEASE NEUROPROTECTION CLINICAL TRIAL Principal Investigator & Institution: Nance, Martha A.; Park Nicollet Institute 3800 Park Nicollet Blvd Minneapolis, Mn 55416 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The Neurodegeneration and Clinical Trials Group of the National Institute of Neurological Disorders and Stroke (NINDS) has issued a Request for Applications for Clinical Centers to collaborate in a large, double-blind, randomized trial of two or more potential neuroprotective agents in patients with early Parkinson's disease. The specific aim of this application is to describe the characteristics of the Struthers Parkinson's Center that make it an appropriate and desirable site to participate in a multicenter trial of neuroprotective agents for Parkinson's disease. The Struthers Parkinson's Center, a National Parkinson Foundation Center of Excellence, is dedicated to research related to Parkinson's Disease and other Movement Disorders. This nationally recognized center offers an integrated approach to diagnosis, treatment and management with the most comprehensive clinical, therapeutic and support services available in the Upper Midwest. The Center looks forward to supporting this neuroprotective agent research effort for early stage Parkinson's disease. We have the patient population, institutional support, facilities, professional expertise, and enthusiasm necessary to serve as a Clinical Center in such a trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PARKINSON'S DISEASE NEUROPROTECTION CLINICAL TRIAL Principal Investigator & Institution: Aminoff, Michael J.; Professor; Neurology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Parkinson's disease (PD) is the second most common neurodegenerative disorder. While a number symptomatic therapies have been developed, no treatment has been identified that halts or slows this progressive disorder. For a number of reasons, we believe that it is appropriate to begin a prospective clinical trial of one or more of the more promising agents to determine whether they offer benefit. The aim of this application is to participate as a clinical center in a collaborative study of neuroprotective agents. The agents and protocol will be specified by NINDS. UCSF has a long history in providing subspecialty care for subjects with PD. The UCSF Parkinson's Disease Clinic & Research Center (PDCRQ has been involved in a number of clinical trials to elucidate the neurologic dysfunction underlying PD as well as testing a variety of novel treatments for PD. This research has included a number of industry sponsored treatment trials for subjects with early to advanced PD. A large diverse, local population provides a reliable source of motivated subjects for clinical research. The experience of the UCSF PDCRC in evaluating, selecting and following subjects with PD make it an ideal candidate for a multicenter, prospective trial of a potential neuroprotectant therapy. The ideal neuroprotective treatment should be effective, inexpensive, well tolerated, safe, easy to administer, and have few interactions with common medications. A number of studies over the last decade 'in humans and experimental animals have demonstrated a local immunologic response mediated by microglia and a number of inflammatory cytokines. Moreover, several animal models of PD have demonstrated that anti-inflammatory medications can interfere with the local immunologic response, and that they may preserve function of dopaminergic neurons. Although emerging understanding of the pathogenesis of PD may provide an alternative candidate for a neuroprotectant therapy, we propose that an

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anti-inflammatory medication would be a rational and practical candidate for the Parkinson's disease Neuroprotection Trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PARKINSON'S DISEASE NEUROPROTECTION TRIAL Principal Investigator & Institution: Shill, Holly; Professor; St. Joseph's Hospital and Medical Center 350 W Thomas Rd Phoenix, Az 850134409 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The objective of this application is to be selected by the Neurodegeneration and Clinical Trial Groups of the NINDS to participate in the Parkinson Disease Neuroprotection Clinical Trial. It is our understanding that the study design will include 42 clinical sites, the use of two or more neuroprotective agents, and an initial pilot study followed by a larger trial of approximately 3000 subjects with early Parkinson's Disease. It is also our understanding that the protocol for this study is currently under development by representatives from the coordinating center, statistical center, the NINDS Oversight Committee and others. As a clinical site for the study, Dr. Mark Stacy and the research staff at the Muhammad Ali Parkinson Research Center (MAPRC) at Barrow Neurological Institute agree to recruit and follow the required number of participants for the duration of the study, collect accurate and timely data and strictly adhere to the protocol.As a major referral center for Parkinson's Disease patients in the southwestern United States, approximately 4800 PD patients are examined and treated annually at our site. The MAPRC has extensive experience in the execution of clinical trials in the Parkinson's population, averaging approximately 15 to 20 clinical research studies annually. If given the opportunity to act as a clinical center for the Parkinson Disease Neuroprotection trial we will recruit the appropriate number of eligible subjects, taking special effort to ensure adequate representation of females and minorities. We will take all appropriate measures to protect these subjects and follow the participants for the entire duration of the trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PARKINSON'S DISEASE NEUROPROTECTION TRIAL: HAWAII CENTER Principal Investigator & Institution: Ross, G W.; Associate Clinical Professor; Pacific Health Research Institute 846 S Hotel St, Ste 303 Honolulu, Hi 96813 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Parkinson's disease is one of the most common of the neurodegenerative diseases affecting the elderly with rates increasing dramatically with increasing age. Prevalence estimates range from 0.7% to 3% among individuals aged 65 or older. The cause of Parkinson's disease is unknown although there is evidence for a combination of genetic and environmental factors. There is currently no medication proven to delay or arrest the progression of disease. As the world population shifts towards a higher proportion of elderly people in coming years and the number at risk for developing Parkinson's disease increases, the economic and social impact of the disease will grow significantly. The search for neuroprotective agents is vitally important. Our purpose is to develop a clinical center for The Parkinson's Disease Neuroprotection Trial in Honolulu. The study will be a multicenter, randomized, double blind, placebo controlled, clinical trial to determine whether two or more specific agents (still to be chosen) can provide neuroprotection in early Parkinson's disease (PD). Toxicity and tolerability of the chosen agents will also be

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assessed. Investigators in Honolulu will be active participants in the design of the protocol and development of the manual of operations. The Honolulu Center has the ability to recruit and retain the required number of participants and estimates that 45% will be women and 70% or more will be non-White (mostly Asian/Pacific Islander). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PARKINSON'S DISEASE RESEARCH TRIAL: CLINICAL CENTER Principal Investigator & Institution: Shannon, Kathleen M.; Rush-Presbyterian-St Lukes Medical Ctr Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Idiopathic Parkinson's Disease (IPD) is the second most common neurodegenerative disease, affecting an estimated 500,000 Americans; there are 35,000 new cases of IPD annually in the United States. The disease follows a progressive course, culminating in death or severe disability after about 20 years. Although there are medications that help to alleviate the symptoms of IPD by increasing central levels of the neurotransmitter dopamine, there remains no treatment to slow the relentless progression of the underlying degenerative process. A number of potential mechanisms of cell death have been illuminated by studies of pathology, epidemiology and experimental toxin-induced parkinsonism in animals. These include oxidative stress, protein aggregation, mitochondrial dysfunction, indirect excitotoxicity and apoptosis. A number of putative neuroprotective agents including propargylamines, complex I cofactors, substances affecting the mitochondrial energy potential, amantadine and others are emerging from the laboratory or early clinical trials. The Movement Disorders Group, of the Department of Neurological Sciences, Rush Medical College proposes to serve as one of 42 clinical centers for the Parkinson's Disease Neuroprotection Clinical Trial. The Rush Clinical Center will (1) participate in the design and implementation of pilot studies and the large simple clinical trials of 2 or more potential neuroprotective agents (2) recruit up to 12 subjects with early untreated Parkinson's Disease for pilot studies and 2 subjects per month for 36 months in the large simple trial and (3) collaborate with the Coordination and Statistical Centers in timely and accurate data collection and transmission. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PD NEUROPROTECTION CLINICAL TRIAL: CLINICAL CENTERS Principal Investigator & Institution: Hauser, Robert A.; Neurology; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Specific Aim 1: To participate as a clinical center in the National Institute of Neurological Disorders and Stroke (NINDS) Parkinson Disease Neuroprotection clinical trial.The University of South Florida Parkinson's Disease and Movement Disorders Center and affiliated clinics will enroll at least 84 subjects with early Parkinson's disease over 3 1/2 years as part of the NINDS simple neuroprotection trial. The clinical trial will be conducted at the University of South Florida's Parkinson's disease and Movement Disorders Center, a very active clinical care and clinical research facility located in Harbourside Medical Tower adjacent to Tampa General Hospital. Subjects will be recruited from this center and affiliated clinics. These include 1) James A. Haley VA Parkinson's disease and Movement Disorders Center, 2) The University of South Florida Medical clinics and 3) The University of South Florida/Tampa General Hospital Indigent Care Neurology Clinic. The center has a proven track record and

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Parkinson’s Disease

reputation as a high quality and high enrollment clinical trials site in Parkinson's disease and other movement disorders. Over 54 clinical trials have been conducted at the center since its inception and 43 over the last 5 years. Over the last 5 years, 256 Parkinson's disease patients have been entered in these clinical trials and 104 Parkinson's disease patients with early Parkinson's disease have been entered in the clinical trials.Participating physicians will include Robert A. Hauser, M.D., Thresa A. Zesiewicz, M.D., and Juan Sanchez-Ramos, M.D. Lisa Gauger will serve as administrator and Roberta Henneman will serve as study coordinator.Specific Aim II: To participate in the development of the design of the neuroprotection trial.Specific Aim III: To participate in the selection of possible neuroprotective agents to be studied. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHF-TAU IN NEURODEGENERATIVE DIESEASES OF GUAM Principal Investigator & Institution: Lee, Virginia M.; Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-MAR-1997; Project End 31-MAR-2007 Summary: (provided by applicant): Neurodegenerative diseases that affect Chamorros in the Mariana Islands of the Western Pacific resemble Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic Lateral Sclerosis (ALS) elsewhere, but ALS, PD and dementia frequently co-occur in Chamorros, and this syndrome is known as Guam ALS/Parkinson dementia complex (ALS/PDC). However, unlike AD, PD and ALS in other populations, Guam ALS/PDC is characterized predominantly by abundant neurofibrillary tangles (NFTs) in central nervous system (CNS) neurons that progressively degenerate. ALS/PDC NFTs are indistinguishable from those in classic AD, but about 25% of ALS/PDC brains contain AD-like senile plaque (SP) deposits of Ab, and PD-like Lewy bodies (LBs) were detected recently with antibodies to asynuclein (a-syn) in more ALS/PDC brains than previously recognized indicating that ALS/PDC is not a "pure" tauopathy. However, the NFTs in both ALS/PDC and classic AD are intraneuronal aggregates of paired helical filaments (PHFs) formed by hyperphosphorylated tau (PHF-tau) composed of all 6 brain tau isoforms, while tau isoforms containing 3 or 4 microtubule binding repeats predominate in the tangles found in other tauopathies. Recently, we generated transgenic mice overexpressing 3R tau and surprisingly they developed an ALS/PDC-Iike phenotype to provide the first experimental evidence that NFT-like tau inclusions play a mechanistic role in ALS/PDC. Nonetheless, we also hypothesize that SPs and LBs contribute to the progression of ALS/PDC, and that oxidative/nitrative damage plays a role in the development of NFT which in turn contributes to mechanisms of SP and LB formation in this disorder. Thus, the Specific Aims of this project will test the hypothesis that brain degeneration in ALS/PDC results from accumulations of NFTs, SPs and LBs formed by tau, Ab and a-syn, respectively, that are induced to fibrillize and/or aggregate and oxidative/nitrative stress plays an important role in this process in ALS/PDC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PILOT--PARKINSON'S AND SELF-CARE: IMMIGRANT LATINO DESCRIPTIONS Principal Investigator & Institution: Smolowitz, Janice; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2004

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Summary: (from applicant's Abstract)The purpose of this exploratory ethnomedical study is to describe the gender specific health beliefs and self care practices of immigrant Latino adults receiving treatment for Parkinson's Disease (PD) and to contrast these beliefs with the medical/disease model of PD. Parkinson's Disease, a chronic progressive neurological condition, is the third most common neurologic disorder of the elderly. The prevalence and incidence of PD increases dramatically with age. PD is found in elderly Latinos, one of the fastest growing segments of the United States Latino population. Research has demonstrated that patients and health care practitioners frequently do not share the same beliefs about disease causation and treatment. This can cause faulty communication between patient and provider leading to decreased patient adherence with the prescribed treatment regimen. At present, there is no research describing Latino adults' understanding of their disease. Clinicians who provide care for Latino adults with PD require information to better understand their patients' health care needs to improve communication and to design meaningful health care interventions. The specific aims of this study are to a) describe the health beliefs and self care practices of immigrant Latino adults receiving treatment for PD, b) compare participants' health beliefs and self care practices with the medical model of PD diagnosis and treatment, c) compare men's and women's perceptions of the impact of PD on their lives, and d) develop and prioritize a list of gender-specific health care needs as perceived by participants. Study findings will be used to develop clinical interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PRENATAL ENDOTOXIN AS A MODEL OF PARKINSON'S DISEASE Principal Investigator & Institution: Ling, Zaodung; Assistant Professor; RushPresbyterian-St Lukes Medical Ctr Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): Current animal models of Parkinson's disease (PD) use high-dosages of dopamine (DA) neurotoxins to produce rapidly evolving lesions. We have recently shown that injection of the Gram (-) bacteriotoxin, lipopolysaccharide (LPS), into gravid female rats at embryonic (E) day 10.5 produces offspring born with fewer dopamine (DA) neurons. The 30-40% DA neuron loss routinely seen is still present after 4 months and presumed permanent. This DA neuron loss is similar to that seen in the PD patient since it is more pronounced in the lateral nigra and its ventral tier, spares the ventral tegmental area and calbindin immunoreactive DA neurons in the nigra, and is associated with reduced striatal DA and increased DA activity as well as tumor necrosis factor (TNFalpha). Exposure of these animals to the DA neurotoxin 6hydroxydopamine (6OHDA) after 4 months, produces a greater inflammatory response and further DA cell loss. We hypothesize that the elevated DA activity and TNF seen in adult animals as a result of prenatal LPS treatment will lead to increased production of reactive oxygen species (ROS) that will eventually overwhelm ROS detoxification systems leading to further, progressive DA neuron loss as a result of aging or low dose exposure to 6OHDA. Based on this hypothesis we will study rats exposed to prenatal LPS and determine if further DA cell loss occurs with aging (through 21 months; Aim 1). Aim 2 will examine the combined effects of prenatal LPS and postnatal 6OHDA at various ages and determine if the combined effects of these two treatments is additive or synergistic and if the magnitude of the DA neuron loss as a result of these two neurotoxins increases with age. Whether or not animals exposed to prenatal LPS and 6OHDA at a young age exhibit a greater rate of DA neuron loss as they age compared with animals treated later in life, will be evaluated in Specific Aim 3. The successful

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implementation of these Specific Aims will address the notion that prenatal exposure to bacterial endotoxin is a risk factor for PD. Moreover, they would further demonstrate that prenatal infections such as bacterial vaginosis can interact with postnatal neurotoxin exposure to produce a gradual, protracted DA neuron loss that could be useful as a new animal model of PD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEOMICS OF COMPLEX 1 INHIBITION IN GSH-DEPLETED CELLS Principal Investigator & Institution: Gibson, Bradford; Professor; Buck Institute for Age Research Novato, Ca 94945 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Oxidative stress appears to play an important role in degeneration of dopaminergic neurons of the substantia nigra (SN) associated with Parkinson's disease (PD). The SN of early PD patients have dramatically decreased levels of the thiol tripeptide glutathione (GSH). GSH plays multiple roles in the nervous system both as an antioxidant and a redox modulator. Recently, we generated dopaminergic cell lines in which levels of GSH can be inducibly down-regulated via doxycycline (dox) induction of antisense messages against both the heavy and light subunits of gamma glutamyl cysteine synthetase (gamma-GCS), the rate-limiting enzyme in glutathione synthesis. Down-regulation of GCS results in reduction in mitochondrial GSH levels, increased oxidative stress, and decreased mitochondrial function. Interestingly, decreases in mitochondrial activities in GSH-depleted PC12 cells appears to be due to a selective inhibition of complex I activity similar to that observed in PD. This loss in enzymatic activity appears to be a result of cysteine oxidation which is reversible by the thiol-reducing agent dithiothreitol. These results suggest that early observed GSH losses in PD may be directly responsible for the noted decreases in complex I activity and the subsequent mitochondrial dysfunction which ultimately leads to dopaminergic cell death associated with the disease. The hypothesis we will examine in this proposal is that oxidation of specific cysteines within the protein subunits of mitochondrial complex I are responsible for the selective inhibition of its activity following GSH depletion. To accomplish this goal, we will employ a series of sulfhydryl-specific probes to assess the redox states of cysteine thiol groups in complex I proteins. We will use highly sensitive mass spectrometry-based proteomics methods to identify the cysteine residue(s) that are responsible for this reversible loss of mitochondrial complex I activity. We will also examine complex I proteins for other types of oxidative damage (both reversible and irreversible) that may contribute to this loss of activity. These data should provide valuable insight into the effect of oxidative stress on mitochondrial physiology as it relates to PD, particularly the structural basis for alterations in mitochondrial function. Knowledge of the molecular details of complex I dysfunction and the identification specific subunit(s) that are involved may point us towards novel therapeutic targets for the disease and provide key data on whether thiol replacement therapy is a viable option for treatment of the disease. Once identified, presence of these alterations will be assessed in future years in both an antiGSH transgenic mouse model of Parkinson disease as well as in Parkinsonian brains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RESTORATION OF DOPAMINE FUNCTION IN PARKINSON'S DISEASE Principal Investigator & Institution: Gerhardt, Greg A.; Director, Morris K. Udall Parkinson's Ce; Anatomy and Neurobiology; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: The neuroestorative and neuroprotective tropic actions of GDNF on midbrain dopamine (DA) neurons provide a promising therapeutic approach for the treatment of Parkinson's disease. As with many tropic factors, optimum success of this tropic factor depends on focal and controlled delivery of the protein to affect the function of DA neurons, without producing unwanted side effects. It is our central hypothesis that chronic intracerebroventricular or intraputamenal GDNF willproduce effects on damaged DA neurons with greater efficacy, potency and reduced side effects as compared to other methods of delivery. 1. We propose to use a novel indwelling pump that can deliver GDNF chronically in the freely-moving MPTP-lesioned monkey to evaluate two sites of delivery: the lateral ventricle and the putamen. 2. We will also investigate washout of GDNF and re-instatement of the trophic factor in both infusion paradigms. The different highly integrated Projects and Cores will provide key data regarding the functional effects of chronic GDNF treatments to DA neurons, and form the foundation for a Parkinson's Disease Center of Excellence. Project 1 will use microdialysis, in vivo electrochemistry and postmortem HPLC-EC methods to study the nigrostriatal pathway of unilateral MPTP-lesioned monkeys that have received chronic infusions of GDNF. Project 2 will investigate the behavioral consequences of the GDNF infusions and study potential functional changes to DA neurons using fMRI methods. Project 3 will carryout tract tracing and immunohistochemical measures of DA neurons in the same groups of chronically treated monkeys. The Cores A-D will all provide needed support for the experiments outline in Projects 1-3. These studies will answer key questions regarding the chronic delivery of a trophic factor in freely-moving and behaving rhesus monkeys. Such data could lay the foundation for the use of trophic molecules for the treatment of Parkinson's disease in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE NEURODEGENERATION

OF

SOMATIC

MTDNA

MUTATIONS

IN

Principal Investigator & Institution: Khrapko, Konstantin; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (Adapted from the abstract provided by the applicant): The long-term goal of the proposed research is to study the mechanisms responsible for the slow progression of late-onset neurodegenerative diseases. The understanding of these mechanisms may help to find ways to make these processes even slower, thus moving the onset of these debilitating diseases outside the normal human lifespan. Specifically, we propose to test the hypothesis that accumulation of somatic mutations in mtDNA of critical cell types in the brain is one of the conditions necessary for the progression of at least some neurodegenerative processes. One of the possibilities is that once the fraction of mutated mtDNA in specific cells exceeds a certain threshold, these cells become sensitive to biochemical insults associated with some diseases. This hypothesis has arisen from the preliminary finding that individual pigmented neurons in substantia nigra accumulate very high levels of mtDNA deletions, which are highly likely to compromise cell's

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resistance to various stresses. Moreover, there are indications that cells with a heavy mutational load are the first to die in Parkinson's brain. It is also possible that progression of the disease accelerates accumulation of mutations thus creating a positive feedback. The efforts will be focused first on Parkinson's Disease (PD) patients and pigmented neurons of substantia nigra. Then research will be extended to Alzheimer's Disease (AD), Huntington's Disease (HD) and the various corresponding brain areas and critical cell types. The Specific Aims of the proposal are: 1) To develop and optimize the arsenal of methods necessary for the precise quantification and characterization of mtDNA mutations in single cells of the brain. These methods will include laser capture micro-dissection for single cell isolation, amplification of full-length mitochondrial genomes from single cells, single cell competitive PCR, and single cell limiting dilution PCR. 2) To identify brain areas and cell types in which mtDNA mutations are most likely to contribute to neurodegeneration. This will be done by measuring mutation load in individual cells of substantia nigra, cortex and putamen that are known to be rich in mtDNA deletions and are critical for PD, AD, and HD, respectively. 3) To test the hypothesis that clonal expansions of mtDNA mutations in individual cells contribute to mitochondrial defects and to neurodegeneration and death of neurons. This will be done by comparing the mutational load of cells that stained positive for various markers of mitochondrial dysfunction, cell degeneration and death to non-staining control cells. We will also study the distribution the mutations as a function of age and the presence and severity of the disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SAM-E TREATMENT OF DEPRESSION IN PARKINSON'S DISEASE Principal Investigator & Institution: Dirocco, Alessandro; Beth Israel Medical Ctr (New York) 1St Ave at 16Th St New York, Ny 10003 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-MAY-2005 Summary: (provided by applicant): S-Adenosyl-methionme (SAM-e) is a molecule present in all eukaryotic cells, where it serves as the methyl-group donor for a number of metabolic functions. In the nervous system, SAM-E is essential in the metabolism of cathecholamines and may play an essential role in receptor stabilization and myelin formation and repair. SAM-a is available in the USA as a food supplement and is promoted as a mood enhancer. Parkinson's disease (PD) is commonly associated with depression, but conventional antidepressants have limited efficacy in parkinsonian patients and may exacerbate motor symptoms. SAM-a improves dopamine transmission, may have a beneficial effect on dopamine receptors and may be a good alternative to the currently used antidepressants. We have conducted a ten-week pilot study of SAM-e in thirteen depressed patients with PD. All patients had been previously treated with other anti-depressant agents and had no significant benefit or had intolerable side effects. Eleven patients completed the study, and ten had at least a 50% improvement of the 17point Hamilton Depression Scale (HAMD), while one patient did not improve. The mean HAMD score before SAM-e treatment was 27.09 greater than or equal to 6.04 SD), and was 9.55 +/-7.29 SD) after treatment (p Thr mutant alpha -synuclein protects neuronal cells from apoptotic stimuli. Author(s): da Costa CA, Ancolio K, Checler F. Source: The Journal of Biological Chemistry. 2000 August 4; 275(31): 24065-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10818098&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 Parkinson’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: •

General Overview Depression Source: Integrative Medicine Communications; www.drkoop.com Depression (Mild to Moderate) Source: Prima Communications, Inc.www.personalhealthzone.com Insomnia Source: Integrative Medicine Communications; www.drkoop.com Parkinson's Disease Source: Healthnotes, Inc.; www.healthnotes.com Parkinson's Disease Source: Integrative Medicine Communications; www.drkoop.com Schizophrenia Source: Healthnotes, Inc.; www.healthnotes.com Sleeplessness Source: Integrative Medicine Communications; www.drkoop.com Tardive Dyskinesia Source: Healthnotes, Inc.; www.healthnotes.com

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Alternative Therapy Ayurveda Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,672,00.html Cell Therapy Source: Healthnotes, Inc.; www.healthnotes.com Crystal Healing Alternative names: crystal therapeutics crystal therapy crystal work Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/c.html Trager Approach Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,741,00.html

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Herbs and Supplements 5-htp Alternative names: 5-Hydroxytryptophan (5-HTP) Source: Integrative Medicine Communications; www.drkoop.com 5-hydroxytryptophan Source: Healthnotes, Inc.; www.healthnotes.com 5-hydroxytryptophan (5-htp) Alternative names: 5-HTP Source: Integrative Medicine Communications; www.drkoop.com Amantadine Source: Healthnotes, Inc.; www.healthnotes.com BCAAS Source: Prima Communications, Inc.www.personalhealthzone.com Benztropine Source: Healthnotes, Inc.; www.healthnotes.com Beta-carotene Source: Prima Communications, Inc.www.personalhealthzone.com Brewer's Yeast Alternative names: Nutritional Yeast Source: Integrative Medicine Communications; www.drkoop.com Carbidopa Source: Healthnotes, Inc.; www.healthnotes.com

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Carbidopa/Levodopa Source: Healthnotes, Inc.; www.healthnotes.com Coenzyme Q Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,768,00.html Ethylenediaminetetraacetic Acid (EDTA) Source: Integrative Medicine Communications; www.drkoop.com Glutathione Source: Healthnotes, Inc.; www.healthnotes.com Glutathione Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,854,00.html Hyoscyamine Source: Healthnotes, Inc.; www.healthnotes.com Kava Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,798,00.html Kava Kava Alternative names: Ava Source: Integrative Medicine Communications; www.drkoop.com Levodopa Source: Healthnotes, Inc.; www.healthnotes.com Levodopa/Carbidopa Alternative names: Sinemet Source: Prima Communications, Inc.www.personalhealthzone.com L-tyrosine Source: Healthnotes, Inc.; www.healthnotes.com Methionine Source: Healthnotes, Inc.; www.healthnotes.com NAC (N-AcetylCysteine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,809,00.html NADH Source: Healthnotes, Inc.; www.healthnotes.com

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NADH Source: Prima Communications, Inc.www.personalhealthzone.com NADH Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10047,00.html Phenylalanine Source: Healthnotes, Inc.; www.healthnotes.com Phenylalanine Source: Integrative Medicine Communications; www.drkoop.com Phenylalanine Source: Prima Communications, Inc.www.personalhealthzone.com Phosphatidylserine Source: Healthnotes, Inc.; www.healthnotes.com Phosphatidylserine (PS) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,813,00.html Piper Methysticum Alternative names: Kava Kava Source: Integrative Medicine Communications; www.drkoop.com Pramipexole Source: Healthnotes, Inc.; www.healthnotes.com Pregnenolone Source: Prima Communications, Inc.www.personalhealthzone.com Psyllium Alternative names: Plantago ovata, Plantago ispaghula Source: Healthnotes, Inc.; www.healthnotes.com S-Adenosylmethionine (SAMe) Source: Integrative Medicine Communications; www.drkoop.com SAMe Source: Healthnotes, Inc.; www.healthnotes.com SAMe Source: Integrative Medicine Communications; www.drkoop.com SAMe (S-Adenosylmethionine) Source: Prima Communications, Inc.www.personalhealthzone.com

Alternative Medicine 165

Selegiline Source: Healthnotes, Inc.; www.healthnotes.com St. John's Wort Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,824,00.html Tyrosine Source: Integrative Medicine Communications; www.drkoop.com

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

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CHAPTER 4. DISSERTATIONS ON PARKINSON’S DISEASE Overview In this chapter, we will give you a bibliography on recent dissertations relating to Parkinson’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 “Parkinson’s disease” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Parkinson’s disease, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Parkinson’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 Parkinson’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: •

A Comparative Study of Memory Retrieval and Scanning Speed in Parkinson's Disease and Senile Dementia of the Alzheimer Type Implications for the Concept of Fronto-subcortical Syndrome by Laflèche, Ginette C; PhD from University of Ottawa (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL40714

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A Waitlist Control Group Study of Neurobehavioural Outcome from Unilateral Posteroventral Pallidotomy in Advanced Parkinson's Disease by Carr, Jason Andrew Robert; PhD from The University of British Columbia (Canada), 2003, 152 pages http://wwwlib.umi.com/dissertations/fullcit/NQ79205

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Accuracy and Behavioral Correlates of Health Care Practitioners' Impressions of Personality in Parkinson's Disease by Lyons, Kathleen Doyle; Scd from Boston University, 2003, 152 pages http://wwwlib.umi.com/dissertations/fullcit/3090416

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Activity-dependent Enhancement of Balance in Persons with Parkinson's Disease Following Strength and Balance Training by Hirsch, Mark Alexander, PhD from The Florida State University, 1996, 161 pages http://wwwlib.umi.com/dissertations/fullcit/9622856

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Alpha-synuclein Biology and Pathphysiology in Parkinson's Disease by Golts, Natalie V.; PhD from Loyola University of Chicago, 2002, 127 pages http://wwwlib.umi.com/dissertations/fullcit/3039283

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An Investigation of Syntactic Comprehension Deficits in Parkinson's Disease by Kemmerer, David L., PhD from State University of New York at Buffalo, 1996, 375 pages http://wwwlib.umi.com/dissertations/fullcit/9704897

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Assessment of Cognition and Mood Following Unilateral Deep Brain Stimulation of the Globus Pallidus or Subthalamic Nucleus in Patients with Parkinson's Disease by Van Dillen, Thomas Anthony; PhD from Alliant International University, Fresno, 2002, 147 pages http://wwwlib.umi.com/dissertations/fullcit/3062698

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Assessment of Graft Effects and Function in Cell Replacement Therapy for Parkinson's Disease by Hagell, Peter; PhD from Lunds Universitet (sweden), 2002, 200 pages http://wwwlib.umi.com/dissertations/fullcit/f441153

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Behavioral Alterations in Models of Parkinson's Disease by Tillerson, Jennifer Layne; PhD from The University of Texas at Austin, 2002, 352 pages http://wwwlib.umi.com/dissertations/fullcit/3086717

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Complex Figure Performance in Patients with Parkinson's Disease: the Role of Planning and Strategy in Visuoconstruction and Visuospatial Memory by Rilling, Laurie Michelle; PhD from The University of Utah, 2002, 94 pages http://wwwlib.umi.com/dissertations/fullcit/3067466

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Coping with Parkinson's Disease: the Influence of Personality, Cognitions, and Hope by Trojahn, Carolyn Ivy; PhD from University of Kansas, 2002, 137 pages http://wwwlib.umi.com/dissertations/fullcit/3083202

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Cyp2d6 Polymorphisms and Pesticide Exposure in Parkinson's Disease by Hariri, Susan Harir; PhD from Colorado State University, 2003, 264 pages http://wwwlib.umi.com/dissertations/fullcit/3092674

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Daytime Sleep and Wakefulness in Parkinson's Disease Patients Treated with Dopamine Agonists by Razmy, Ajmal; Msc from University of Toronto (Canada), 2002, 116 pages http://wwwlib.umi.com/dissertations/fullcit/MQ68797

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Depressive Symptoms in Parkinson's Disease by Ehmann, Thomas Stephan; PhD from Queen's University at Kingston (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL45227

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Diet Quality (as Assessed by the Healthy Eating Index) of Patients with Moderate Parkinson's Disease by Andersen, Anne M.; Ms from Rush University, 2002, 119 pages http://wwwlib.umi.com/dissertations/fullcit/1410873

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Effects of Dopaminergic Drugs on an Animal Model for Parkinson's Disease by Robertson, George S; PhD from Dalhousie University (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL56270

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Effects of Visual and Auditory Cues on Mobility and Function in Patients with Parkinson's Disease (pd) by Suteerawattananon, Monthaporn; PhD from Texas Woman's University, 2002, 210 pages http://wwwlib.umi.com/dissertations/fullcit/3046324

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Environmental Risk Factors in the Etiology of Parkinson's Disease: Effects of Combined Exposure to Paraquat and Maneb by Thiruchelvam, Mona; PhD from The University of Rochester, 2002, 249 pages http://wwwlib.umi.com/dissertations/fullcit/3036571

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Epidemiologic Issues in Squamous Cell Skin Cancer, Primary Adult-onset Brain Cancer, and Parkinson's Disease by Efird, Jimmy Thomas; PhD from Stanford University, 2003, 94 pages http://wwwlib.umi.com/dissertations/fullcit/3090582

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Factors Influencing the Efficacy of Delayed Auditory Feedback in Treating Dysarthria Associated with Parkinson's Disease by Blanchet, Paul Gerard; PhD from Louisiana State University and Agricultural & Mechanical College, 2002, 164 pages http://wwwlib.umi.com/dissertations/fullcit/3069698

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Functional Characterization of Familial Parkinson's Disease Gene Product, Parkin by Zhang, Yi; , PhD from The Johns Hopkins University, 2002, 167 pages http://wwwlib.umi.com/dissertations/fullcit/3028357

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Functional Magnetic Resonance Imaging of Repetitive Movement in Healthy Subjects and Patients with Parkinson's Disease by Boyd, Tracy Ann; Msc from University of Alberta (Canada), 2002, 133 pages http://wwwlib.umi.com/dissertations/fullcit/MQ69795

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Hand Preshaping Patterns during Reach-to-grasp Movements in Normal Controls and Parkinson's Disease Patients by Schettino, Luis Felipe; PhD from Rutgers the State University of New Jersey - Newark, 2002, 296 pages http://wwwlib.umi.com/dissertations/fullcit/3043622

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Impairments during Reaching in Parkinson's Disease and the Effect of Antiparkinsons Medications by Kelly, Valerie Elizabeth; PhD from Washington University, 2003, 172 pages http://wwwlib.umi.com/dissertations/fullcit/3095528

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In Vitro Metabolism of Xenobiotics Involved in the Etiology and Treatment of Parkinson's Disease by Smith, Kirsten Seay; PhD from University of Virginia, 2002, 115 pages http://wwwlib.umi.com/dissertations/fullcit/3056861

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Inhibition and Attentional Processes in Parkinson's Disease by Grande, Laura J.; PhD from University of Florida, 2002, 81 pages http://wwwlib.umi.com/dissertations/fullcit/3065939

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Interaction of the Ventral Pallidum and Subthalamic Nucleus in a Rat Model of Parkinson's Disease by Turner, Michael Scott; PhD from Loyola University of Chicago, 2003, 233 pages http://wwwlib.umi.com/dissertations/fullcit/3085105

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Manual Force Modulation and Position Control in Persons with Parkinson's Disease by Ashmore, Amy Frances; PhD from The University of Texas at Austin, 1998, 273 pages http://wwwlib.umi.com/dissertations/fullcit/9936962

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Mechanisms of Environmental Chemical-induced Apoptosis in Dopaminergic Cells: Critical Roles of Protein Kinase C-delta and Relevance to Parkinson's Disease by Kitazawa, Masashi; PhD from Iowa State University, 2003, 341 pages http://wwwlib.umi.com/dissertations/fullcit/3085924

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Modelling Parkinson's Disease in Drosophila: the Protective Role of Molecular Chaperones by Auluck, Pavan Kumar; PhD from University of Pennsylvania, 2003, 187 pages http://wwwlib.umi.com/dissertations/fullcit/3087369

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Moral Boundaries of Medical Research: a Sociological Analysis of Human Fetal Tissue Transplantation (bioethics, Parkinson's Disease) by Kelly, Susan Elizabeth, PhD from University of California, San Francisco, 1994, 395 pages http://wwwlib.umi.com/dissertations/fullcit/9523550

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Neural Transplantation Strategies in the Rodent Model of Parkinson's Disease by Bartlett, Lynsey Erin; Msc from Dalhousie University (Canada), 2002, 108 pages http://wwwlib.umi.com/dissertations/fullcit/MQ75439

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Neurochemical Studies of the Pathogenesis of Four Central Nervous System Disorders Parkinson's Disease, Huntington's Chorea, Dialysis Encephalopathy, and Hallervorden-spatz Syndrome by Yong, Voon Wee; PhD from The University of British Columbia (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL36939

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Nitric Oxide Signaling and Cell Death Mechanisms in the Methylpyridinium Model of Parkinson's Disease by Dennis, Jameel; PhD from University of Virginia, 2002, 187 pages http://wwwlib.umi.com/dissertations/fullcit/3038997

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Parallels between Cognitive and Motor Deficits in Parkinson's Disease: Insights into Basal Ganglia Function by Shook, Sheryl Kay; PhD from University of California, Davis, 2002, 117 pages http://wwwlib.umi.com/dissertations/fullcit/3074609

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Parkinson's Disease: Factors Related to Coping by Dell'aquila, Ralph Daniel; Edd from The George Washington University, 2002, 181 pages http://wwwlib.umi.com/dissertations/fullcit/3062397

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Pharmacotherapy for Parkinson's Disease: Observatons and Innovations by Nyholm, Dag; PhD from Uppsala Universitet (sweden), 2003, 99 pages http://wwwlib.umi.com/dissertations/fullcit/f192881

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Problem-solving Abilities in Parkinson's Disease (frontal Lobe) by Vance, Katherine Therese, PhD from The University of Arizona, 1990, 78 pages http://wwwlib.umi.com/dissertations/fullcit/9100562

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Reaching Movement with Purposeful Activity And/or Visuotemporal Cue in People with Parkinson's Disease by Lai, Chen-ju (jamie); Msc from Queen's University at Kingston (Canada), 2003, 95 pages http://wwwlib.umi.com/dissertations/fullcit/MQ74907

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Reaching Movements and Pursuit Tracking Performance in Patients with Parkinson's Disease by Zackon, Warren T; PhD from Mcgill University (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL57306

Dissertations 171

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Regulation of the Basal Ganglia Circuitry by a 5-ht(1a) Agonist: Relevance to Parkinson's Disease by Schutz-mignon, Laurence; PhD from Loyola University of Chicago, 2002, 200 pages http://wwwlib.umi.com/dissertations/fullcit/3039304

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Repeated Tongue and Hand Strength Measurements in Adult Normal and Parkinson's Disease Males by O'day, Carol P.; PhD from University of South Carolina, 2002, 59 pages http://wwwlib.umi.com/dissertations/fullcit/3076783

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Reproductive History and Pharmacological Agents As Risk Factors for Amyotrophic Lateral Sclerosis and Parkinson's Disease by Popat, Rita Ashok; PhD from Stanford University, 2003, 86 pages http://wwwlib.umi.com/dissertations/fullcit/3090661

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Rhythms of Finger Oscillations in Parkinson's Disease by Saganowich, Lara Agnes; Msc from Queen's University at Kingston (Canada), 2002, 93 pages http://wwwlib.umi.com/dissertations/fullcit/MQ69326

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Roles for Oxidative Stress and the Glutathione System in a Model for Parkinson's Disease by Ehrhart, Juliann; PhD from Rutgers the State U. of N.j. - New Brunswick and U.m.d.n.j., 2003, 164 pages http://wwwlib.umi.com/dissertations/fullcit/3076811

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Self-directed Learning of Lay Caregivers of Parkinson's Disease Patients and the Implications for the Development of Future Educational Programs and Materials by Nolan, Thomas Leonard, Jr.; Edd from Northern Illinois University, 1999, 114 pages http://wwwlib.umi.com/dissertations/fullcit/9955740

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Self-management of Parkinson's Disease: the Effect of a Group Exercise Program on Lifestyle Physical Activity, Self-efficacy, and Function by Peteet, Jean Oulund; PhD from Walden University, 2002, 163 pages http://wwwlib.umi.com/dissertations/fullcit/3081075

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Studies in Applied Computational Chemistry: Meta Model of Photochemical Reactions under Uv under Natural Conditions and an Mcase Approach to the Search of a Cure for Parkinson's Disease by Sedykh, Aleksandr Y.; PhD from Case Western Reserve University, 2003, 176 pages http://wwwlib.umi.com/dissertations/fullcit/3086251

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Testing an Action Selection Model of Basal Ganglia Function in Parkinson's Disease and Huntington's Disease by Wylie, Scott Alan; PhD from Indiana University, 2002, 156 pages http://wwwlib.umi.com/dissertations/fullcit/3076073

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The Effect of Auditory Cues on Gait at Different Stages of Parkinson's Disease: a Preliminary Study by Chester, Emma L.; Msc from Dalhousie University (Canada), 2002, 112 pages http://wwwlib.umi.com/dissertations/fullcit/MQ75453

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The Effects of Right and Left Hemiparkinsonism on Prosody (neuropsychology, Prosody, Nonverbal Communication, Cognition) by Blonder, Lee Xenakis, PhD from University of Pennsylvania, 1986, 167 pages http://wwwlib.umi.com/dissertations/fullcit/8703181

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The Long-term Effect of Using a Verbal Instructional Set to Improve the Gait of People with Parkinson's Disease by Lehman, David Alan; PhD from The Florida State University, 2002, 120 pages http://wwwlib.umi.com/dissertations/fullcit/3043355

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The Management of Parkinson's Disease As It Relates to Marital Quality, Perceived Support, Locus of Control, and Perceived Burden by Edwards, Nancy Elaine, PhD from Purdue University, 1996, 133 pages http://wwwlib.umi.com/dissertations/fullcit/9725539

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The Neuropsychological Profile of Idiopathic Parkinson's Disease Relationship to Severity, Patient Attributes, and Response to Treatment by Taylor, Ann E; PhD from University of Toronto (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL31498

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The Role of the Basal Ganglia in Learning and Memory: Evidence from Parkinson's Disease by Shohamy, Daphna; PhD from Rutgers the State University of New Jersey Newark, 2003, 182 pages http://wwwlib.umi.com/dissertations/fullcit/3080564

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Toward a Restorative Therapy for Parkinson's Disease: Studies on the Functional Efficacy of Intracerebral Fetal Cell Transplants and Gdnf Delivery by Winkler, Christian; PhD from Lunds Universitet (sweden), 2002 http://wwwlib.umi.com/dissertations/fullcit/f441121

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Towards Better Intelligibility Testing of Dysarthria: a Study of Motor Speech Deficits in Native Spanish-speaking Adults with Parkinson's Disease by Fraas, Michael R.; PhD from University of Cincinnati, 2003, 78 pages http://wwwlib.umi.com/dissertations/fullcit/3093366

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Visuospatial Deficits in Parkinson's Disease by Amick, Melissa M.; PhD from Boston University, 2003, 157 pages http://wwwlib.umi.com/dissertations/fullcit/3083816

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Working Memory and Inhibition in Mild Parkinson's Disease by Hollnagel, Caroline Renee; PhD from Washington University, 2003, 94 pages http://wwwlib.umi.com/dissertations/fullcit/3095522

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

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CHAPTER 5. CLINICAL TRIALS AND PARKINSON’S DISEASE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Parkinson’s disease.

Recent Trials on Parkinson’s Disease The following is a list of recent trials dedicated to Parkinson’s disease.8 Further information on a trial is available at the Web site indicated. •

A Clinical Study to Evaluate a New Investigative Drug for the Treatment of Parkinson's Disease Condition(s): Parkinson Disease Study Status: This study is currently recruiting patients. Sponsor(s): (Sponsor Name Pending) Purpose - Excerpt: Double-blind fixed dose study evaluating an investigational drug in early Parkinson's Disease Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00058838

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An Open-Label, Long-Term, Flexible Dose Study of Safety, Tolerability, and Therapeutic Response In Patients with Parkinson's Disease with an Investigational Drug Condition(s): Parkinson Disease Study Status: This study is currently recruiting patients. Sponsor(s): (Sponsor Name Pending) Purpose - Excerpt: Open-label, long-term, flexible dose study of safety, tolerability, and therapeutic response in patients with Parkinson's Disease.

8

These are listed at www.ClinicalTrials.gov.

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00036205 •

Deep Brain Stimulation (DBS) vs. Best Medical Therapy (BMT) Trial Condition(s): Parkinson's Disease Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs; National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The goals of this study are to determine if simultaneous bilateral subthalamic nucleus stimulation or simultaneous bilateral globus pallidus stimulation is more effective in reducing symptoms of Parkinson's disease, and if deep brain stimulation or best medical therapy is more effective in improving Parkinson's disease symptoms. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056563

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Deep Brain Stimulation for Parkinson's Disease Trial Condition(s): Parkinson's Disease; Parkinsonism 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 determine the safety, reliability, and effectiveness of deep brain stimulation for the treatment of Parkinson's disease. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053625

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Diagnosis and Natural History Study of Patients with Neurological Conditions Condition(s): Alzheimer's Disease; Dementia; Movement Disorder; Multiple System Atrophy; Parkinson's Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The purpose of this study is to improve understanding of neurological conditions. Patients participating in this study will continue receiving medical care, routine laboratory tests, and diagnostics tests (X-rays, CT-scans, and nuclear imaging), from their primary care physician. Doctors at the NIH plan to follow these patients and offer advice and assistance to their primary care physicians. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001549

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Donepezil to Treat Dementia in Parkinson's Disease Condition(s): Parkinson Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study will evaluate the safety and effectiveness of donepezil (Aricept) for treating mild dementia in patients with Parkinson's disease. Donepezil is approved for treating patients with Alzheimer's disease, whose memory and cognition problems are similar to those of patients with Parkinson's disease who are affected by dementia. Donepezil prevents the breakdown of a chemical messenger called acetylcholine, which is involved in memory and other cognitive functions, and may improve cognition in patients. Patients 40 years of age and older with Parkinson's disease who have mild to moderate dementia may be eligible for this 6-month study. It involves 6 clinic visits of approximately 2 hours each, described below. Candidates will be screened for participation during Visit 1. - Visit 1 (screening visit): Study candidates will have a medical history, physical and neurological examinations, electrocardiogram (EKG), and possibly blood tests. They will also undergo neuropsychological testing (tests of memory, language, mood and, other brain functions) and fill out a quality of life questionnaire. Those enrolled will be randomly assigned to receive either donepezil (5 mg per day) or placebo-a look-alike pill with no active ingredients. After 4 weeks, the dose of donepezil will be increased to 10 mg per day. Patients who do not tolerate the higher dose will have it reduced to 5 mg. Those who do not tolerate the 5-mg dose will be taken off medication but will continue to be followed and tested. - Visit 2 (week 7): Patients will have a neurological examination and neuropsychological testing and will fill out a quality of life questionnaire. - Visit 3 (week 10): Patients will repeat the evaluations done during visit 2 and will stop taking the study medication. - Visit 4 (week 16): Patients will repeat the evaluations done during visit 2 and will have their study medication switched. That is, patients previously on placebo will be switched to donepezil, and patients who were taking donepezil will be switched to placebo. After 4 weeks, the dose of donepezil will be increased to 10 mg per day. Patients who do not tolerate the higher dose will have it reduced to 5 mg. Those who do not tolerate the 5mg dose will be taken off medication but will continue to be followed and tested. - Visits 5 and 6 (weeks 23 and 26): Patients will repeat the evaluations done during visit 2. This study is being conducted at the National Institutes of Health, the University of Pennsylvania, and Northwestern University Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00030979

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Farming and Movement Evaluation Study (FAME) Condition(s): Parkinson's Disease; Movement Disorders Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Environmental Health Sciences (NIEHS) Purpose - Excerpt: The long term goal of this research is to elucidate the cause(s) of Parkinson's disease, with a focus on environmental determinants. We propose to investigate the relationship between Parkinson's disease and exposure to pesticides and

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other factors by conducting a nested case-control study in the Agricultural Health Study. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042120 •

Genetic Analysis of Parkinson's Disease Condition(s): Parkinson's Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Human Genome Research Institute (NHGRI) Purpose - Excerpt: The purposes of this study are to identify the gene or genes responsible for an inherited form of Parkinson's disease and learn more about how the disease develops. In Parkinson's disease, a deficiency of a brain chemical called dopamine impairs the function of the part of the brain that controls movement. As a result, patients may have difficulty moving or they may have uncontrolled movements of their hands and fingers. Parkinson's disease usually occurs sporadically, with no known cause. In a few families, however, the disease seems to be inherited through a gene mutation (change). There is a 50-50 chance that a parent with the mutated gene will pass it on to a child. Children who do inherit the abnormal gene may or may not go on to actually develop Parkinson's disease-the relative chance of this happening is not known. Individuals 18 years of age and older from families in which Parkinson's disease appears to be inherited may be eligible for this study. Participants will have a brief medical examination, provide a personal and family medical history, and have a small blood sample (2 tablespoons) taken for genetic studies. The total time required for the study is about 1 to 2 hours. Participants are encouraged to meet with a NIH investigator or with a genetics specialist in their local area before testing to talk about the possible implications for themselves and their families of the test results. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001640

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GM1 Ganglioside Effects on Parkinson's Disease Condition(s): Parkinson Disease 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 examine the short term effects (6 months) of GM1 on Parkinson's disease (PD) symptoms, as well as the effects of longterm treatment (2 years) with GM1 on disease progression, and to examine the extent to which GM1 treatment influences the underlying disease process in PD. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00037830

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Investigating the Safety of srTMS in the Treatment of Parkinson's Disease Condition(s): Parkinson Disese Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: Super rapid transcranial magnetic stimulation (srTMS) is a method of brain stimulation that may be able to change the electrical activity of the nerve cells of the brain. It has been proposed and tested as a treatment for brain disorders, including Parkinson's disease. The purpose of this study is to use a device called the magnetic stimulator to investigate the safe limit of srTMS, such as intensity of stimulation and the number of magnetic pulses that may lead to excessive brain stimulation. Ten patients with Parkinson's disease-whose main problems are slowness of movement and difficulty walking-will participate in this study. They will be asked to come to the laboratory for one experiment. Before and after srTMS treatment, investigators will test participants' brain function with a series of psychological tests and an EEG (electroencephalogram). The srTMS treatment is performed by placing an insulated coil of wire on the scalp and passing a very brief electrical current through the wire coil. The experiment will last 2 to 4 hours. Phase(s): Phase I; MEDLINEplus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063284

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JP-1730 to Treat Parkinson's Disease Condition(s): Parkinson Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study will evaluate the effects of an experimental drug called JP1730 on Parkinson's disease symptoms and on dyskinesias (involuntary movements) that develop as a result of long-term treatment with levodopa. JP-1730 affects chemical messengers believed to affect Parkinson's disease symptoms. Patients between 30 and 80 years of age with relatively advanced Parkinson's disease may be eligible for this 3phase study. - Phase 1 - Baseline evaluation Participants will be evaluated with a medical history, physical examination, detailed neurologic evaluation, routine blood tests, urinalysis and an electrocardiogram. They will also have a 24-hour holter monitor (heart monitoring) and cardiology consultation. A chest X-ray and MRI or CT scan of the brain will be done if needed. Patients will, if possible, stop taking all antiparkinsonian medications except levodopa (Sinemet) for one month before the study begins and throughout its duration. (If necessary, patients may use short-acting dopamine agonists, such as Mirapex and Requip.) - Phase 2 - Dose Finding Phase For 2 to 3 days, patients will be admitted to the NIH Clinical Center for a levodopa (a dopamine agonist) dosefinding procedure. For this procedure, patients stop taking Sinemet and instead have levodopa, and subsequently apomorphine, infused through a vein. During the infusions, the drug dose is increased slowly until either 1) parkinsonian symptoms improve, 2) unacceptable side effects occur, or 3) the maximum study dose is reached. Symptoms are monitored frequently to find the optimal dose. (Patients who have had dosing infusions in the last 3 months will not have to undergo this phase of the study.) Phase 3 - Active Study Phase Within 3 months of the dose-finding phase, treatment will

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begin. Patients will receive seven doses of JD-1730 or placebo (an inactive substance) via puffs from an oral spray together with levodopa infusions over a 3-week period. The doses are given on days 1, 2, and 3 of the first week and then approximately twice a week for the next 2 weeks. For these doses, patients are hospitalized 4 days the first week and 2 days each for the next 2 weeks. All participants will receive placebo at some time during the study, and a few patients, selected at random, will receive only placebo the entire 3 weeks. The procedure for the infusions is the same as that for the dosefinding phase, with frequent evaluation of symptoms. Also, small blood samples are drawn up to three times each study day. At the end of the third week, patients will be discharged from the hospital. Their anti-parkinsonian medications may be readjusted, as needed. Patients will be contacted 2 weeks after the end of the study for a check on side effects and, if necessary, will be scheduled for a follow-up evaluation at the clinic. In addition to the above procedures, patients will be asked to have an optional lumbar a puncture (spinal tap) on the first and last days of the study to measure various brain chemicals and drug levels that cannot be measured in blood and urine. For this procedure, a local anesthetic is given and a needle is inserted in the space between the bones (vertebrae) in the lower back. About 2 tablespoons of fluid is collected through the needle. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040209 •

Magnetic Resonance Imaging (MRI) of Neuropsychiatric Patients and Healthy Volunteers Condition(s): Healthy; Mental Disorder; Parkinson's Disease; Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to use brain imaging technology to compare differences in brain structure, chemistry, and functioning in individuals with brain and mental disorders compared to healthy volunteers. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001284

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Magnetic Stimulation for Parkinson Disease Condition(s): Parkinson's Disease; Depression Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: During transcranial magnetic stimulation (TMS), a magnetic coil is placed on the front part of the head. Electric current passes through the coil in brief pulses. Magnetism from the current produces a separate, small electric current inside the brain, which activates brain cells below the coil. This treatment may result in decreased depression and improved Parkinson's disease symptoms. Phase(s): Phase I

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029276 •

Molecular Epidemiology of Parkinson's Disease Condition(s): Parkinson Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Environmental Health Sciences (NIEHS) Purpose - Excerpt: The aim of this research is to discover genes which modify risk for Parkinson's disease. The study includes 800 patients with Parkinson's disease, and their estimated 1,222 available siblings. Common variations of at least 9 genes will be studied, including genes associated with personality, substance use, and anxiety and depression. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042107

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NINDS Parkinson's Disease Neuroprotection Trial Condition(s): Parkinson's Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The goal of this study is to assess the impact of minocycline and creatine on the progression of Parkinson's disease, in order to determine whether it is reasonable to proceed with further study of either of these agents. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063193

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Parkinson's Diseases Susceptibility Genes and Pesticides Condition(s): Parkinson's Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Environmental Health Sciences (NIEHS) Purpose - Excerpt: Parkinson's disease (PD) occurrence is higher in rural than in urban populations of industrialized countries. Epidemiologic and human tissue studies suggest that pesticides may be responsible for causing dopaminergic cell death at increased rates. While many pathophysiologic pathways may be involved in the neurodegeneration responsible for PD, genetic factors are likely to determine a general susceptibility to neurodegeneration. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044590

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PET Scanning in Parkinson's Disease Condition(s): Parkinson Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Human Genome Research Institute (NHGRI) Purpose - Excerpt: This study will compare brain blood flow and the brain's use of dopamine in patients with Parkinson's disease, their family members and normal volunteers. Dopamine is a chemical normally found in the part of the brain involved in controlling movement. This chemical is lacking in people with Parkinson's disease, and patients have difficulty initiating or controlling some body movements. Usually, Parkinson's disease develops in people without any known cause. In a few families, however, three or more people are affected, suggesting these families may have a genetic alteration that makes them more prone to develop the disease. Normal healthy volunteers and members of families in which three or more people have Parkinson's disease may be eligible for this study. Candidates will have a physical examination and provide a personal and family medical history. Volunteers will also have a neurological examination. Participants will undergo PET scanning. One hour before the scan, subjects are given a medication called Carbidopa, which maximizes the usefulness of the scans. For the procedure, the subject lies on a table in the scanner, a catheter (thin plastic tube) is inserted into an arm vein, and a baseline scan is done. Radioactive water is then injected through the catheter and another scan is done. During this scan, the subject is asked questions to stimulate blood flow in certain areas of the brain. Up to 10 injections are given, with different questions asked each time. The total time for the scans is not more than 1 hour. A final scan, which may last up to 2 hours, is then done. Dopamine is injected into the catheter before the scan begins. When it is completed, subjects are instructed to empty their bladder immediately and then every 2 hours for the rest of the day to reduce the exposure to radioactive material. Shortly afterwards, the subject has a magnetic resonance imaging (MRI) scan. This scan is used to help interpret the information obtained from the PET scans. MRI uses radio waves and a magnetic field to image structural and chemical changes in tissues. For this procedure, the subject lies still on a table that is moved into the middle of a narrow circular scanner. An intercom system permits communication with the staff member performing the study at all times during the procedure. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00024622

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Randomized Study of the Effects of Glucose on Cognition in Healthy Young and Elderly People and Parkinson's Disease Patients Condition(s): Parkinson Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH); University of Virginia Purpose - Excerpt: Objectives: I. Determine whether glucose facilitates memory in healthy elderly, but not young, people. II. Determine whether glucose facilitates working memory in people with Parkinson's disease. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004451

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Safety and efficacy study of CEP-1347 in the treatment of Parkinson's disease Condition(s): Parkinson Disease Study Status: This study is currently recruiting patients. Sponsor(s): Cephalon; H. Lundbeck A/S; The Parkinson Study Group Purpose - Excerpt: The purpose of this study is to establish safety for CEP-1347 and to determine an efficacious dose in the treatment of Parkinson's disease. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040404

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SAM-e for the Treatment of Depression in Patients with Parkinson's Disease Condition(s): Parkinson's Disease; Depression 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: This study will test a chemical called s-adenosyl-methionine (SAM-e) for the treatment of depression in patients with Parkinson's disease (PD). Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070941

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Single Photon Emission Computed Tomography to Study Receptors in Parkinson's Disease Condition(s): Parkinson Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study will use single photon emission computed tomography, or SPECT (see below), to examine brain nicotine receptors in evaluating the role of a chemical called acetylcholine in memory and other problems in Parkinson's disease (PD). Acetylcholine acts by binding to these nicotine receptors. Healthy normal volunteers and patients with Parkinson's disease 40 years of age and older, with or without dementia, may be eligible for this study. Candidates will be screened with physical and neurological examinations, a pen and paper test of memory and other mental functions, blood tests, and, for women of childbearing potential, a pregnancy test. Patients with cognition problems will have more intensive mental function tests. All participants will undergo the following procedures: - Magnetic resonance imaging (MRI): This test uses a strong magnetic field and radio waves to show structural and chemical changes in the brain. During the scan, the subject lies on a table in a narrow cylinder (the scanner). The time required in the scanner is about 1 hour, during which the subject is asked to lie very still for 10 to 15 minutes at a time. He or she can speak with a staff member via an intercom system at all times during the procedure. - SPECT: This nuclear medicine test produces a picture of the receptors in the brain. On the night

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before the scan, the day of the scan, and for 4 days after the scan, subjects take an oral dose of potassium iodide to protect the thyroid gland from the radioactive tracer used in the SPECT procedure. (People allergic to potassium iodide will take potassium perchlorate instead.) Before the scan, small radioactive markers containing 99Tc are glued to the subject's head. Two catheters (thin, flexible tubes) are placed in veins in the arms to inject the radioactive tracer [123I]5-I-A-85380 and to draw blood samples. Another catheter is placed in an artery in the wrist to draw arterial blood samples. During the scan, the subject lies on a bed with his or her head held still with a head holder. The scans are taken over a 6-hour period after injection of [123I]5-I-A-85380. An electrocardiogram, respiration, and blood pressure measures are taken before the tracer is injected, then 5 minutes after the injection, and again 30 to 60 minutes after the injection. Blood and urine samples are collected 5 to 6 hours after starting the scan. Participants are asked to urinate at least every 2 hours for 12 hours after injection of [123I]5-I-A-85380 to decrease radiation exposure. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00058721 •

Spheramine(r) in advanced Parkinson's disease (The STEPS Trial) Condition(s): Parkinson Disease Study Status: This study is currently recruiting patients. Sponsor(s): Titan Pharmaceuticals; Schering-Plough Purpose - Excerpt: The purpose of the STEPS clinical research study is to evaluate the effect and safety of Spheramine implantation in patients with Parkinson's disease. Spheramine is a cell therapy that consists of human retinal pigment epithelial (RPE) cells attached to microscopic gelatin beads (microcarriers). The RPE cells produce L-DOPA and are believed to directly enhance brain levels of dopamine. This clinical study will enroll 68 participants with advanced Parkinson's disease. Half of the participants will be randomly (by chance) assigned to receive Spheramine, and half will receive placebo (sham or mock surgical treatment). If Spheramine is proven to be both beneficial and safe in this study, those participants who had the placebo treatment will be offered Spheramine at the end of the trial. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00059007

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Study of Repetitive Transcranial Magnetic Stimulation in Parkinson's Disease Condition(s): Parkinson Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study will examine the effects of repetitive transcranial magnetic stimulation (rTMS) on Parkinson's disease symptoms. rTMS is a way of stimulating the brain that may be able to change the electrical activity of the nerve cells in the brain. It has been proposed as a treatment for brain disorders, including Parkinson's disease. In preliminary studies, some patients' symptoms improved; in some they worsened

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temporarily, and some showed no change. Patients between 40 and 80 years of age with moderately severe Parkinson's disease, whose main problem is slowness of movement and stiffness, may be eligible for this study. Participants will be randomly assigned to one of two treatment groups: one will receive rTMS to parts of the brain involved in controlling movement; the other will receive sham, or placebo, stimulation. Nine treatments will be given over a 4-1/2 week period. Patients will take their Parkinson's disease medications during the study, but will stop taking the medicines for 4 to 5 hours before one of the sessions. For rTMS, an insulated wire coil is placed on the scalp. A brief electrical current is passed through the coil, creating a magnetic pulse that stimulates the brain. The pulses are delivered in trains, or short bursts, lasting 1 second each. There will be 48 trains for a total of 1200 pulses per 24-minute session. The stimulation may cause muscle twitching in the scalp or face and may also cause small movements of the limbs. Just before and after each rTMS session, patients will have a neurologic examination, including an evaluation of walking. Their motor function tests will be recorded on videotape to document possible improvement and to allow physicians to rate the improvement. The physicians will not know which patients are receiving actual rTMS and which are receiving sham treatment. Ratings before the first and after the last rTMS sessions will be more detailed. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029666 •

Studying Automatic Movements in Patients with Parkinson's Disease Condition(s): Parkinson Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: Parkinson's disease patients usually have difficulty making automatic movements. Automatic movements are movements people often make without conscious thought. The purpose of this study is to investigate regions of the brain that affect automatic movements and to understand the movements of Parkinson's patients. Investigators hope this knowledge will lead to better treatment for the disease. Thirty participants will be enrolled in this study. Each will give a medical history and undergo a brief physical exam. Participants will have two MRI scans, each lasting approximately 1.5 hours. During these scans, they may be asked to move their right or left hands or to remember some letters that they have been shown. Before undergoing the second scan, participants will be asked to practice the tasks until they can perform them correctly. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063661

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The Association of Neurotoxin Exposure with Parkinson's Disease and Parkinsonism in World War II Veterans and Other Men Condition(s): Parkinson's Disease Study Status: This study is currently recruiting patients.

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Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: This program aims to investigate factors associated with development of parkinsonism or idiopathic Parkinson's Disease in an ongoing cohort of patients established in 1965 who are currently undergoing their sixth examination. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018577 •

The Role of Dopamine in Motor Learning in Healthy Subjects and Patients with Parkinson's Disease Condition(s): Parkinson Disease; Healthy Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study will examine and compare what happens in the brains of patients with Parkinson's disease with that of healthy normal subjects while they train to react as fast as possible to the appearance of a visual signal. Particularly, we will measure the amount of the chemical dopamine released in the brain as well as the electrical activity during training. Indeed, patients with Parkinson's disease frequently complain of slowness and early fatigue during movements. These symptoms are believed to be related to a decrease of dopamine in the brain which may be associated with abnormalities in cerebral electrical activity. Adult patients with Parkinson's disease who are right-handed, do not have dementia, and are not depressed may be eligible for this study. Healthy volunteers who match patients in age, gender, handedness, and level of education will also be studied. Candidates will be screened with a medical history, physical and neurological examinations, memory test, mood evaluation, and urine toxicology. All participants will be required to stop taking any medications that can influence the central nervous system and to abstain from alcohol consumption for 1 week before the screening examination and during the study training period. Patients with Parkinson's disease will also be required to stop using antiparkinsonian medications for at least 12 hours before the first visit and each training session. Participants will have several 1-hour training sessions. During these sessions, they will sit facing a computer screen at a distance of about 32 inches (80 centimeters) from their eyes. Six permanent position markers will be displayed. A keyboard with six spatially compatible response keys will be within reach of their right hand. Participants will respond as quickly and as accurately as possible to the appearance of a stimulus (e.g., white circle) below one of the markers by pressing the spatially corresponding key. About a second later, the next stimulus will be displayed below one of the other markers, and so on. Reaction times and accuracy will be recorded. After 3 to 10 minutes of practice (one block), there will be a rest period during which the computer will display information about the subject's accuracy of movements and reaction time. Then, a new block will start. There will be about 6 to 20 practice blocks per training session. The number of training session will vary between 3 and 6 depending on accuracy and reaction time during the task. During each training session, subjects will have encephalographic (EEG) recordings to measure the electrical activity of the brain. In addition, they will have one or two positron emission tomography (PET) scans during the first training session, and some will also have one or two PET scans during the last session. For the PET scan, the subject will be injected with a substance called raclopride, which is taken up by the brain. The raclopride is tagged with a radioactive substance so that it can be detected by the PET camera. The amount of raclopride detected in the

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brain will provide an indirect measure of the amount of dopamine released during training. Before or after one of the training sessions, participants will undergo magnetic resonance imaging (MRI) to study brain anatomy. MRI uses a strong magnetic field and radio waves to produce images of the brain. The subject lies on a table in a space enclosed by a metal cylinder (the scanner). The test takes about 45 to 60 minutes, during which the participant must lie very still for 10 to 15 minutes at a time. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00032812 •

Treatment of Agitation/Psychosis in Dementia/Parkinsonism (TAP/DAP) Condition(s): Dementia; Parkinson Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Aging (NIA) Purpose - Excerpt: The aim of this study is to determine the safety and efficacy of quetiapine for the treatment of psychosis and/or agitation in patients with primary dementia complicated by coexistent parkinsonism, or patients with Parkinson's disease with dementia [PDD] who are taking a cholinesterase inhibitor. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00043849

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Treatment of Depression in Parkinson's Disease Trial Condition(s): Parkinson Disease; Depression Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The goal of this study is to evaluate the effectiveness and safety of two antidepressants--nortriptyline and paroxetine, compared to placebo in patients with Parkinson's disease and depression. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00062738

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Valerian to Improve Sleep in Patients with Parkinson's Disease Condition(s): Insomnia; Parkinson's Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The purpose of this trial is to test the short-term effectiveness of valerian, a medicinal herb, to improve sleep in patients with Parkinson's disease (PD). Phase(s): Phase II

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070928 •

Within-Subject, Dose-Escalation Trial of Continuously Infused Intracerebral (IC) Recombinant-Methionyl Human Glial Cell Line-Derived Neurotrophic Factor (rmetHuGDNF) for the Treatment of Subjects with Idiopathic Parkinson's Disease Condition(s): Parkinson Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: Parkinson's disease is characterized by loss of neurons that produce dopamine in a region of the brain called the substantia nigra. In the early stages of the disease, the disease responds to agents that replace dopamine such as levodopa. Patients with more advanced disease have wide fluctuations in their response to levodopa, exhibiting on and off periods. This is due to continued degeneration of neurons. Recombinant-methionyl human glial cell line-derived neurotrophic factor (rmetHuGDNF or GDNF) is a neurotrophic factor that promotes survival of dopaminergic neurons. This is a protein produced by recombinant technology that is almost identical to the naturally produced factor. Results of animal studies indicate that GDNF has the potential to benefit patients with advanced Parkinson's disease. The purpose of this clinical trial is to determine whether GDNF works to relieve symptoms of advanced Parkinson's disease. The study will also test the delivery of GDNF using a catheter implanted into the putamen, the area of the brain associated with Parkinson's disease, and an infusion pump that is implanted under the skin in the abdomen or chest. GDNF will be placed into the pump and delivered through the catheter to the brain. The purposes of this study are to determine the potential benefits and side effects of GDNF. The performance and safety of the catheter/infusion pump system will also be assessed. The study will last for 6 months. Subjects will undergo neurological testing, computerized gait assessment and neurological imaging. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006488

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 “Parkinson’s disease” (or synonyms).

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

Patents on Parkinson’s Disease By performing a patent search focusing on Parkinson’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. 9Adapted 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 Parkinson’s disease: •

3-[4-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)butyl]-5-hydroxy-indole methanesulfonate having sedating and anti-parkinsonism properties Inventor(s): Bergmann; Rolf (Reichelsheim, DE), Bottcher; Henning (Darmstadt, DE), Hausberg; Hans-Heinrich (Ober-Ramstadt, DE), Seyfried; Christoph (SeeheimJugenheim, DE) Assignee(s): Merck Patent Gesellschaft Mit Breschrankter Haftung (Darmstadt, DE) Patent Number: 4,914,114 Date filed: May 16, 1988 Abstract: 3-[4-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)butyl]-5-hydroxy-indole methanesulfonate can be used in the therapy of Parkinsonism and is particularly readily soluble. Excerpt(s): The invention relates to the new compound 3-[4-(4-phenyl-1,2,3,6tetrahydro-1-pyridyl)-butyl]-5-hydroxyindole methanesulfonate (I). The underlying base (II) and the corresponding hydrochloride (III) are described in DE-OS 2,910,367. It has been found that I has considerably more favourable pharmacokinetic properties than III. Thus, for example, 100 mg/kg of I administered orally to Cynomolgus monkeys already lead to a sedating reaction, whilst this effect can be achieved with III only with doses above 500 mg/kg. I also has a considerably better solubility in water (0.921 g in 100 ml) than III (0.035 g in 100 ml). Web site: http://www.delphion.com/details?pn=US04914114__

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Agent for treating Parkinson's disease or Parkinsonism Inventor(s): Hinzen; Dieter (Zornheim, DE), Hornykiewicz; Oleh (Vienna, AT), Schingnitz; Gunter (Bad Kreuznach, DE) Assignee(s): Boehringer Ingelheim KG (Ingelheim am Rhein, DE) Patent Number: 4,645,770 Date filed: February 3, 1986 Abstract: The invention describes the use of 2-amino-6-allyl-5,6,7,8-tetrahydro-4Hthiazolo[4,5-d]azepine and the acid addition salts thereof for the treatment of Parkinson's disease or Parkinsonism. Excerpt(s): The present invention relates to a method of treating Parkinson's disease or Parkinsonism which comprises administering 2-amino-6-allyl-5,6,7,8-tetrahydro-4Hthiazolo [4,5-d]azepine or an acid addition salt thereof. X represents an oxygen or sulphur atom, and the physiologically acceptable acid addition salts thereof with inorganic or organic acids. It is known from Belgian Pat. Nos. 684 415 and 771 330 that the compounds of general formula I and the physiologically acceptable acid addition salts thereof have valuable pharmacological properties. Thus, the compounds described in Belgian Pat. No. 684 415 have, in particular, an analgesic, sedative, antitussive, antipyretic and antiphlogistic activity and the compounds described in Belgian Pat. No. 771 330, depending on their substitution, have a hypotensive, sedative, antitussive and/or antiphlogistic activity.

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Web site: http://www.delphion.com/details?pn=US04645770__ •

Human SDR2 cDNA clone Inventor(s): Albone; Earl Francis (Conshohocken, PA), Kikly; Kristine Kay (Linfield, PA) Assignee(s): SmithKline Beecham Corporation (Philadelphia, PA) Patent Number: 6,090,579 Date filed: December 16, 1997 Abstract: SDR2 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing SDR2 polypeptides and polynucleotides in the design of protocols for the treatment of cancer, inflammation, autoimmunity, allergy, asthma, rheumatoid arthritis, CNS inflamation, cerebellar degeneration, Alzheimer's disease, Parkinsons disease, multiple sclerosis, amylotrophic lateral sclerosis, head injury damage, and other neurological abnormalities, septic shock, sepsis, stroke, osteoporosis, osteoarthritis, ischemia reperfusion injury, cardiovascular disease, kidney disease, liver disease, ischemic injury, myocardial infarction, hypotension, hypertension, AIDS, myelodysplastic syndromes and other hematologic abnormalities, aplastic anemia, male pattern baldness, and bacterial, fungal, protozoan and viral infections, among others, and diagnostic assays for such conditions. Excerpt(s): This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to 6-TM family, hereinafter referred to as SDR2 (stromal-cell derived receptor). The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. Murine SDR2 was cloned from a bone marrow stromal cell line using a signal sequence trap method (Shirozu, M., et al., Genomics 37:273-280, 1996). Murine SDR2 contains a signal sequence and has six putative transmembrane spanning domains. Other six transmembrane spanning proteins function as ion transporters (Becker, D., et al., PNAS 93:8123-8128, 1996), water channel proteins (Misaka, T., et al., FEBS Lett. 381:208-212, 199; Jung, J. S., et al., PNAS 91:1305213056, 1994), iron transporters (Dix, D. R., et al., JBC 269:26092-26099, 1994) or have been linked to cellular activation and division (Gaugitsch, H. W., et al., JBC 267:11267-11273, 1992). This indicates that the 6-TM family has an established, proven history as therapeutic targets. Clearly there is a need for identification and characterization of further members of 6-TM family which can play a role in preventing, ameliorating or correcting dysfunctions or diseases, including, but not limited to, cancer, inflammation, autoimmunity, allergy, asthma, rheumatoid arthritis, CNS inflammation, cerebellar degeneration, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amylotrophic lateral sclerosis, head injury damage, and other neurological abnormalities, septic shock, sepsis, stroke, osteoporosis, osteoarthritis, ischemia reperfusion injury, cardiovascular disease, kidney disease, liver disease, ischemic injury, myocardial infarction, hypotension, hypertension, AIDS, myelodysplastic syndromes and other hematologic abnormalities, aplastic anemia, male pattern baldness, and bacterial, fungal, protozoan and viral infections. In one aspect, the invention relates to SDR2 polypeptides and recombinant materials and methods for their production. Another aspect of the invention relates to methods for using such SDR2 polypeptides and polynucleotides. Such uses include the treatment of cancer, inflammation, autoimmunity, allergy, asthma, rheumatoid arthritis, CNS inflammation, cerebellar

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degeneration, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amylotrophic lateral sclerosis, head injury damage, and other neurological abnormalities, septic shock, sepsis, stroke, osteoporosis, osteoarthritis, ischemia reperfusion injury, cardiovascular disease, kidney disease, liver disease, ischemic injury, myocardial infarction, hypotension, hypertension, AIDS, myelodysplastic syndromes and other hematologic abnormalities, aplastic anemia, male pattern baldness, and bacterial, fungal, protozoan and viral infections, among others. In still another aspect, the invention relates to methods to identify agonists and antagonists using the materials provided by the invention, and treating conditions associated with SDR2 imbalance with the identified compounds. Yet another aspect of the invention relates to diagnostic assays for detecting diseases associated with inappropriate SDR2 activity or levels. Web site: http://www.delphion.com/details?pn=US06090579__ •

Method of treatment of Parkinsons's disease using phytic acid Inventor(s): Sabin; Robert (Goosedown Estate, Box 332, Horseshoe Rd., Mill Neck, Long Island, NY 11765) Assignee(s): none reported Patent Number: 5,206,226 Date filed: December 13, 1991 Abstract: A method is provided for treating Parkinson's Disease by administering to a subject an effective symptom-alleviating amount of a compound selected from the group consisting of phytic acid, phytate salt, an isomer or hydrolysate of phytic acid or phytate salt, or a mixture of any combination thereof. The preferred method of administration is by oral dosages of about 1/8 to 1/2 grams/kilogram bodyweight per day. Excerpt(s): The present invention is directed to a method for treating Parkinson's Disease by use of phytic acid, its salts or hydrolysates. Parkinson's disease is a progressive disorder that affects a small area of cells (called the substantia Nigra) in the middle part of the brain and which occurs slightly more often in men than women. It is also called Shaking palsy or paralysis agitans and is a disorder of the central nervous system primarily attacking people between the ages 50 and 69. Approximately one out of every 1,000 people contact the illness. A cause of Parkinson's disease is that the cells which normally produce dopamine, a chemical necessity for transmitting messages in the brain, degenerate and die causing a deficiency of dopamine and perhaps consequentially the symptoms of Parkinson's disease. The common symptoms include tremor, stiffness (or rigidity) of muscles, slowness of movement (bradykinesia) and loss of balance (postural dysfunction). Parkinson's disease is one of the most prevalent neurological conditions - along with epilepsy, stroke and dementia. The natural history of the disease results in a rate of progression from 10-15 years from onset of the disease, to disability, with some variability from patient to patient. Parkinson's itself, moreover, the disability caused by the disease often leads to fatal infections such as aspiration, pneumonia, and urinary tract infections. Parkinson's disease is usually categorized into three distinct groups. Paralysis agitans usually called Parkinson's disease is the most common form of Parkinsonism, afflicting approximately 75% of the cases and is of unknown origin or cause. The second type of Parkinsonism which is caused by drugs and toxins, which include carbon monoxide, manganese and chemical compound called MPTP (methyl-phenyltetrahydropyridine). The third form of Parkinsonism is called

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Vascular Parkinsonism which may be caused by multiple small strokes which damage the dopamine-producing brain cells. Web site: http://www.delphion.com/details?pn=US05206226__ •

Method to treat Parkinsons disease Inventor(s): Chiesi; Paolo (Parma, IT) Assignee(s): Chiesi Farmaceutici S.p.A. (Parma, IT) Patent Number: 5,017,607 Date filed: June 30, 1989 Abstract: Pharmaceutical compositions for the treatment of Parkinson's disease and neurologic syndromes connected with it, containing as the active principle levodopa methyl ester optionally combined with other active principles selected from dopaminergic, anticholinergic, antidepressive drugs, carboxylase and monoaminoxidase inhibitors. Excerpt(s): The present invention refers to pharmaceutical compositions for the treatment of Parkinson's disease, containing levodopa methyl ester alone or combined with other active principles. Parkinson's disease is characterized by a progressive degeneration of the dopaminergic nigrostriatal pathways in the brain. Biochemical studies carried out in the sixties lead to the discovery of the fundamental role played in the pathogenesis of this disease by the deficit of neurotransmitters, and particularly of dopamine. Web site: http://www.delphion.com/details?pn=US05017607__

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Pharmaceutical compositions and method of producing anti-Parkinsonism activity Inventor(s): Kaiser; Carl (Haddon Heights, NJ), Pendleton; Robert G. (Philadelphia, PA), Setler; Paulette E. (Fort Washington, PA) Assignee(s): SmithKline Corporation (Philadelphia, PA) Patent Number: 4,052,506 Date filed: August 5, 1975 Abstract: Pharmaceutical compositions and method of producing anti-Parkinsonism activity by administering internally a nontoxic effective quantity of a benzazepine derivative to an animal. Excerpt(s): This invention relates to novel pharmaceutical compositions containing as an active ingredient compounds which have anti-parkinsonism activity and to a method of producing anti-parkinsonism activity by administering non-toxic effective quantities of said active ingredients to an animal. Parkinson's disease is a neurological disorder characterized by hypokinesia, akinesia, tremor and rigidity of the limbs. Parkinsonism is believed to be brought about by imbalance in the biochemical systems in the brain between the dopaminergic and cholinergic neural pathways. In patients suffering from parkinsonism, a depletion of dopamine in the brain is observed which is the result of progressive degeneration of nigro-striatal dopaminergic neurons. There is a great need for compounds and compositions which produce anti-parkinsonism activity without having limiting side effects. It is well known that L-dopa, a potential source of brain

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dopamine, has clinical utility in treating parkinsonism. L-Dopa is a precursor of dopamine, being decarboxylated in the brain, and thereby raising the levels of dopamine in patients who are deficient in it. However, L-Dopa does not qualify as an ideal compound in the treatment of parkinsonism due in part to its limiting side effects, such as, for example, nausea, emesis and anorexia. Web site: http://www.delphion.com/details?pn=US04052506__ •

Pharmaceutical preparation and method for treatment of parkinsonism Inventor(s): Nowak; Herbert (Darmstadt, DT), Seyfried; Christoph (Darmstadt, DT) Assignee(s): Merck Patent Gesellschaft mit beschrankter Haftung (Darmstadt, DT) Patent Number: 4,021,555 Date filed: December 16, 1975 Abstract: Administration of mepiprazole during L-dopa therapy for parkinsonism reduces undesired side effects of L-dopa and enhances the desired effects of L-dopa. Excerpt(s): This invention relates to a process for modifying the effects of therapeutic administration of L-dopa, and to pharmaceutical preparations suitable for this purpose. L-Dopa (L-3,4-dihydroxyphenylalanine) is used for the treatment of parkinsonism and Parkinson's disease. The cause of parkinsonism is thought to be a deficiency of the neurotransmitter dopamine, 2-(3,4-dihydroxyphenyl)-ethylamine, in the basal ganglia. Dopamine itself does not pass through the blood-brain barrier; for this reason, this compound is unsuitable for parkinsonism therapy. Consequently, treatment of parkinsonism is carried out by substitute therapy using high doses of L-dopa, a precursor of dopamine, which passes the blood-brain barrier. However, L-dopa is also a precursor of noradrenaline, so that its administration to a patient results in increased formation of noradrenaline. As a result, the metabolic equilibrium of the neurotransmitters noradrenaline and serotonin is disturbed in the brain. Administration of L-dopa also leads to reduction in the activity of serotoninergic neurons. The result is agitation, motoric unrest, increased sexuality, insomnia, hypomanic reactions, and sometimes even hallucinations and delirious conditions, i.e., "L-dopa psychosis". These psychic disturbances normally cannot be overcome by conventional psychopharmacological agents, which simultaneously counteract the effect of the dopamine so that symptoms of the original parkinsonism returns. Web site: http://www.delphion.com/details?pn=US04021555__

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Treating central nervous system diseases Inventor(s): Aroonsakul; Chaovanee (6907 S. Constance, Chicago, IL 60649) Assignee(s): none reported Patent Number: 4,902,680 Date filed: January 3, 1989 Abstract: A method of treating humans suffering from central nervous system diseases, such as Alzheimer's disease, Parkinsons's disease, senile dementia. The treatment consists of inducing into the patient's blood stream at least one from the group consisting of: sex hormones and anabolic hormones. Growth hormone is also be used in those patients in advanced stages of the disease, or in those patients where it has been

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determined that a low level of growth hormone is present. A method of diagnosing Alzheimer's disease, senile dementia, by the determination of the levels of the hormones somatotropin (human growth hormone) and somatomedin-C (IGF-I) after the administration of the Aroonsakul-Allen provocative test is also disclosed. Blood-sera samples are taken at certain time periods after the administration of L-Dopa, and the samples are tested for the levels of these hormones. These levels are then compared against the levels for normal subjects. Excerpt(s): The present invention is directed to a method of treatment for central nervous system diseases. These diseases for which the present inventive method has been found useful are: Alzheimer's disease; Parkinson's disease; senile dementia; essential tremor; senile tremor; and cerebellar atrophy and cerebral atrophy; multiple sclerosis; cerebrovascular accident. Each of these has been found to affect different portions of the brain. Alzheimer's disease affects the portion of the brain vital to memory retention, the cortex. Parkinson's disease is known to affect the nerve cells of the basal ganglia. Cerebellar atrophy is known to affect the nerve cells of the cerebellum. It has also been determined that in each of the above diseases, intrinsic depression develops, which is usually associated with an entirely different portion of the brain than those affected by the above-named diseases. It is also known that in each of these diseases characterized by biochemical lesions in enzymes, membranes, or structure proteins of particular components, cellular atrophy is the result, which is a slow process of cellular deterioration, sometimes deferred bes, but leading to cellular atrophy, and eventually resulting in serious functional loss, causing the symptoms associated with each of the diseases. Such cellular atrophy generally occurs with advancing age, but, owing to these diseases, the processes are somehow speeded up, in a manner not known or understood at the present time. What is certain, however, is that in any cellular breakdown, the enzymes required for protein synthesis are lacking. Further, it is also apparent that this lack of enzyme formation, and concomitant lack of protein synthesis, are caused by some interruption in the neural network through which biochemical signals are generated and transported. Thus, the very problem of each of these diseases runs to the basic structure of life: To wit, RNA and DNA, ribo nucleic acid and deoxyribonucleic acid, which program each cell to provide the necessary enzymes for life-sustaining activity. Heretofore, there has been no effective method of treatment of each of the above-named diseases. In the case of Parkinson's disease, L-Dopa has been employed and has achieved some success. However, the period of efficacy of L-Dopa is limited to a few months. In the case of Alzheimer's disease, and the remainder of the above-named diseases, ergoloid myselates have been used to some small success. The present invention is also directed to a method of diagnosing Alzheimer's Disease in human beings. Presently-used techniques for determining Alzheimer's disease include neuropsychological testing which compares the mental status of the patient relative to a norm, as well as the patient's cognitive dysfunction. Such testing also tests for mood depressions, agitation, irritability, and the like, all of which are symptoms of Alzheimer's disease. Other diagnostic tools and methods are: The use of a brain atlas beam test or EEG (electroencephalogram) which demonstrate increases in delta and theta waves. It is, of course, most important that a correct diagnosis be determined in order to decide upon the best treatment. The present invention is directed towards the incorporation of a novel diagnosis for Alzheimer's disease and senile dementia, that may be used in conjunction with other standard testing methods, or may be used alone for such determination, since this novel diagnosis has been found to be very accurate, especially when used in conjunction with conventional diagnostic tests for other chronic degenerative diseases of the CNS form which similar indications may result. It has been known that the drug levodopa (L-Dopa), a common drug for treating Parkinson's

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disease, causes increased secretion of the growth hormone somatotropin (HGH-human growth hormone). This finding of Aroonsakul and Allen provocative test (AA provocative test) such as L-Dopa's provocative stimulation of the pituitary gland to secrete HGH was used as the basis for viewing the functioning of the peripheral nervous system (PNS) as an aminergic neuronetwork. Furthermore, since the hormone somatomedin-C (often referred to as IGF-I, for insulin-like growth factor) is directly dependent upon the secretion of HGH by the pituitary gland, there has been established a direct linkage between increased secretion of HGH and increased production of the hormone somatomedin-C, which is produced chiefly in the liver and kidneys. The use of L-Dopa to markedly increase the secretions of somatotropin and, consequently, the production of somatomedin-C in the human body has led to what is generally termed the "L-Dopa provocative test". This test is used to determine the normal functioning of the anterior region of the pituitary gland responsible for the HGH production. Generally, the AA provocative test is used by detecting the increase of HGH and IGF-I in a blood serum by the use of radioimmunoassay (RIA), which determines the presence or absence or the amounts of a certain hormone in a serum by the use of a radioactive agent, used in vitro. RIA involves separation of the labelled antigen that is of interest into bound-unbound fractions after the interaction with an antibody in the presence of the unknown quantity of unlabelled antigen to be measured. The radioactive element used in this determination is usually I-125. Web site: http://www.delphion.com/details?pn=US04902680__ •

Treatment of Parkinsons disease Inventor(s): Owen; David A. A. (Welwyn Garden City, GB2) Assignee(s): Smith Kline & French Laboratories Limited (Welwyn Garden City, GB2) Patent Number: 4,824,860 Date filed: May 19, 1988 Abstract: The present invention relates to the use of certain indolone derivatives in particular, 4-(2-di-n-propyl-aminoethyl)-2-(3H)-indolone in a method of treatment of Parkinsons disease. Excerpt(s): The present invention relates to a method of treatment of disorders of the central nervous system, in particular Parkinsons Disease, by the administration of certain indolone derivatives. Parkinsons Disease is a disturbance of voluntary movement in which muscles become stiff and sluggish, movement becomes clumsy and difficult and uncontrollable rhythmic twitching of groups of muscles produces characteristic shaking or tremor. The condition is believed to be caused by a degeneration of pre-synaptic dopaminergic neurones in the brain. The absence of adequate release of the chemical transmitter dopamine during neuronal activity thereby leads to the Parkinsonian symptomatology. Currently, the most widely used treatment for Parkinsonism is administration of L-DOPA, a precursor of dopamine which acts indirectly by replacing the missing dopamine. However, disadvantages are associated with the use of L-DOPA, for example, patients often suffer from side-effects such as dyskinesia and on-off effects, and it is necessary to administer L-DOPA in conjunction with a peripheral dopa-decarboxylase inhibitor such as carbidopa or benzaseride. These inhibitors prevent the peripheral degradation of levodopa to dopamine, thus enabling more drug to enter the brain and limiting peripheral side-effects. Such treatment improves quality of life for patients but does not halt disease progression. Furthermore, such treatment is associated with a number of adverse effects including nausea,

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vomiting, abdominal distension and psychiatric side-effects (for example, toxic confusional states, paranoia and hallucinations). Web site: http://www.delphion.com/details?pn=US04824860__ •

Use of combinations of L-DOPA with trazodone and L-DOPA with etoperidone in Parkinsonism Inventor(s): Silvestrini; Bruno (Rome, IT) Assignee(s): Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.p.A. (Rome, IT) Patent Number: 4,131,675 Date filed: February 9, 1978 Abstract: A combination of trazodone or etoperidone with L-DOPA is used in the treatment of Parkinsonism by oral administration to a patient. Excerpt(s): This invention concerns the use of combinations of L-DOPA with trazodone or L-DOPA with etoperidone in Parkinsonism in order to avoid the side effects of LDOPA resulting from stimulation of the adrenergic system and improve its therapeutic action. L-DOPA is extensively used in the therapy of Parkinsonism. Its use is based on the well known theory that Parkinsons disease and related conditions are produced by an imbalance between dopaminergic and cholinergic mechanisms at the nigrostriatal level. Parkinsonian symptoms appear when the cholinergic mechanism prevails over the dopaminergic one. Since L-DOPA is a precursor of dopamine and potentiates the adrenergic system, it readjusts the above mentioned imbalance thus leading to an improvement in Parkinsonism. See in this respect "The Pharmacological Basis of Therapeutics", L. S. Goodman and A. Gilman, Fourth Edition, The MacMillan Company, 1970, page 423. At the same time its administration produces side effects indicative of activation of the adrenergic system such as stimulation of the central nervous system, blood pressure and ECG changes, etc. Trazodone is the subject of U.S. Pat. No. 3,381,009 and Japanese Pat. No. 555,140 in which the drug's pharmacological and therapeutic properties are attributed to its tranquilizing, hypotensive and analgesic actions. Web site: http://www.delphion.com/details?pn=US04131675__

Patent Applications on Parkinson’s Disease As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to Parkinson’s disease:

10

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

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•

Methods for diagnosing pervasive development disorders, dysautonomia and other neurological conditions Inventor(s): Fallon, Joan M.; (Yonkers, NY) Correspondence: F. Chau & Associates, Llp; Suite 501; 1900 Hempstead Turnpike; East Meadow; NY; 11554; US Patent Application Number: 20020081628 Date filed: November 16, 2001 Abstract: Methods for aiding in the diagnosis of disorders including, but not limited to, PDDs (Pervasive Development Disorders), Dysautonomic disorders, Parkinson's disease and SIDS (Sudden Infant Death Syndrome). In one aspect, a diagnosis method comprises analyzing a stool sample of an individual for the presence of a biological marker (or marker compound) comprising one or more pathogens, which provides an indication of whether the invidual has, or can develop, a disorder including, but not limited to, a PDD, Dysautonomia, Parkinsons disease and SIDS. Preferably, the presence of one or more pathogens is determined using a stool immunoassay to determine the presence of antigens in a stool sample, wherein such antigens are associated with one or more pathogens including, but not limited to, Giardia, Cryptosporidium, E. histolytica, C. difficile, Adenovirus, Rotavirus or H.pylori. Excerpt(s): This application is based on, and claims the benefit of, United States Provisional Application No. 60/249,239, filed on Nov. 16, 2000, which is fully incorporated herein by reference. The present invention generally relates to methods for aiding in the diagnosis of disorders including, but not limited to, PDDs (Pervasive Development Disorders), Dysautonomic disorders, Parkinsons disease and SIDS (Sudden Infant Death Syndrome). More particularly, the invention relates to a diagnosis method comprising analyzing a stool sample of an individual for the presence of a biological marker (or marker compound) comprising one or more pathogens, which provides an indication of whether the invidual has, or can develop, a disorder including, but not limited to, a PDD, a Dysautonomic disorder, Parkinson's disease or SIDS. Currently, extensive research is being conducted to determine associations between gastrointestinal dysfunction and a variety of human disorders that, heretofore, have been of unknown etiology. For example, an association between dysautonomic conditions and gastrointestinal dysfunction has been described in U.S. patent application Ser. No. 09/929,592, filed on Aug. 14, 2001, entitled "Methods For Diagnosing and Treating Dysautonomia and Other Dysautonomic Conditions, which is commonly owned and fully incorporated herein by reference. Further, a relationship between gastrointestinal conditions and PDDs such as Autism, ADD (Attention Deficit Disorder) and ADHD (Attention Deficit Hyperactivity Disorder) has been described in detail in U.S. patent application Ser. No. 09/466,559, filed Dec. 17, 1999, entitled "Methods For Treating Pervasive Development Disorders," and U.S. Ser. No. 09/707,395, filed on Nov. 7, 2000, entitled "Methods For Treating Pervasive Development Disorders", both of which are commonly owned and incorporated herein by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with Parkinson’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 “Parkinson’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 Parkinson’s disease. You can also use this procedure to view pending patent applications concerning Parkinson’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 7. BOOKS ON PARKINSON’S DISEASE Overview This chapter provides bibliographic book references relating to Parkinson’s disease. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Parkinson’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 “Parkinson’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 Parkinson’s disease: •

Augmentative and Alternative Communication for Adults with Acquired Neurologic Disorders Source: Baltimore, MD: Paul H. Brookes Publishing Co. 2000. 425 p. Contact: Available from Paul H. Brookes Publishing Co. P.O. Box 10624, Baltimore, MD 21285. (800) 638-3775. Fax (410) 337-8539. Website: www.brookespublishing.com. PRICE: $42.00 plus shipping and handling. ISBN: 1557664730. Summary: The loss of speech in adulthood due to acquired neurologic disorders causes a person to confront enormous life changes. In this text, speech language professionals, physicians, therapists, service providers, and family members explore the challenges these adults face during their transition, whether gradual or immediate, from speaking to using augmentative and alternative communication (AAC). The chapters of part one focus on issues related to all adults with severe communications disorders caused by

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acquired neurogenic and neuromuscular disabilities. Topics include meaningful communication roles, AAC message management, decision making in AAC intervention, integrating AAC strategies with natural speech in adults, acceptance of AAC by adults with acquired disorders, and rebuilding communicative competence and self determination. The chapters in part two cover issues that pertain to people with specific neurologic and neuromuscular conditions. Topics include AAC for individuals with amyotrophic lateral sclerosis (ALS), AAC for Huntington disease and Parkinson's disease, AAC and traumatic brain injury (the influence of cognitive factors on system design and use), proactive management of primary progressive aphasia, the cognitive and linguistic considerations of AAC and aphasia, and AAC and dementia. Each chapter offers extensive references and the volume concludes with a subject 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 “Parkinson’s disease” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “Parkinson’s disease” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “Parkinson’s disease” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

100 Maxims in Neurology: Parkinson's Disease by Roger J. Porter, et al (1992); ISBN: 0340589477; http://www.amazon.com/exec/obidos/ASIN/0340589477/icongroupinterna

•

2nd Sandoz Symposium on the Treatment of Parkinson's Disease, Tokyo, October 1993 (Journal: Duropean Neurology, Vol. 34, Supplement 3, 1994) by I. Goto (Editor) (1994); ISBN: 3805560583; http://www.amazon.com/exec/obidos/ASIN/3805560583/icongroupinterna

•

A Life Shaken: My Encounter With Parkinson's Disease by Joel Havemann, Stephen G. Reich (2002); ISBN: 0801869285; http://www.amazon.com/exec/obidos/ASIN/0801869285/icongroupinterna

•

A Molecular Biology Approach to Parkinson's Disease by Peter Jenner (Editor), P. Jenner; ISBN: 9051994230; http://www.amazon.com/exec/obidos/ASIN/9051994230/icongroupinterna

•

A Patient's Perspective: Living With Parkinson's Disease: Or Don't Rush Me! I'm Coping As Fast As I Can! by Jon Robert Pierce (1989); ISBN: 0963055909; http://www.amazon.com/exec/obidos/ASIN/0963055909/icongroupinterna

•

Advances in Neurology: Parkinson's Disease by Donald Calne (Editor), Susan Calne (Editor); ISBN: 0781724066; http://www.amazon.com/exec/obidos/ASIN/0781724066/icongroupinterna

•

Alzheimer's and Parkinson's Diseases by H. J. Altman (Editor), B. N. Altman (Editor) (1990); ISBN: 0306834820; http://www.amazon.com/exec/obidos/ASIN/0306834820/icongroupinterna

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•

Alzheimer's and Parkinson's Diseases: Recent Advances in Research and Clinical Management by Harvey J. Altman, Barbara N. Altman (Editor) (1990); ISBN: 9990309639; http://www.amazon.com/exec/obidos/ASIN/9990309639/icongroupinterna

•

Alzheimer's and Parkinson's Diseases: Strategies for Research and Development (Advances in Behavioral Biology, Vol 29) by Abraham Fisher (Editor), et al (1986); ISBN: 0306422328; http://www.amazon.com/exec/obidos/ASIN/0306422328/icongroupinterna

•

An Atlas of Parkinson's Disease and Related Disorders by G. David Perkin; ISBN: 1850709432; http://www.amazon.com/exec/obidos/ASIN/1850709432/icongroupinterna

•

An Illustrated Pocketbook of Parkinson's Disease and Related Disorders by G. David Perkin; ISBN: 1842141422; http://www.amazon.com/exec/obidos/ASIN/1842141422/icongroupinterna

•

Answers to Frequently Asked Questions in Parkinson's Disease: A Resource Book for Patients and Families by David L. Cram (2002); ISBN: 0971098883; http://www.amazon.com/exec/obidos/ASIN/0971098883/icongroupinterna

•

Basic, Clinical, and Therapeutic Aspects of Alzheimer's and Parkinson's Diseases (Advances in Behavioral Biology, Vol 38 A&B) (1991); ISBN: 999028749X; http://www.amazon.com/exec/obidos/ASIN/999028749X/icongroupinterna

•

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

•

Clinical Atlas of Parkinson's Disease by David Nicholl, Adrian Williams (2003); ISBN: 1405107782; http://www.amazon.com/exec/obidos/ASIN/1405107782/icongroupinterna

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Communication in Parkinson's Disease by Sheila Scott; ISBN: 087189078X; http://www.amazon.com/exec/obidos/ASIN/087189078X/icongroupinterna

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Current Concepts in Parkinson's Disease Research by Madi Gupta (Editor), J. S. Schneider (Editor); ISBN: 0920887724; http://www.amazon.com/exec/obidos/ASIN/0920887724/icongroupinterna

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Defending Against the Enemy: Coping With Parkinson's Disease by Eric R. Morgan (1999); ISBN: 0936609362; http://www.amazon.com/exec/obidos/ASIN/0936609362/icongroupinterna

•

Developing and regenerating vertebrate nervous systems : proceedings of the Fourth Tarbox Parkinson's Disease Symposium, September 30-October 2, 1982, Texas Tech University, Lubbock, Texas; ISBN: 0845127055; http://www.amazon.com/exec/obidos/ASIN/0845127055/icongroupinterna

•

Diagnosis & Management of Parkinson's Disease, 2nd ed. by Cheryl H. Waters (1999); ISBN: 1884735533; http://www.amazon.com/exec/obidos/ASIN/1884735533/icongroupinterna

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Dopaminergic Neuron Transplantation in the Weaver Mouse Model of Parkinson's Disease (Advances in Experimental Medicine and Biology, 517) by Lazaros C. Triarhou (2003); ISBN: 0306474352; http://www.amazon.com/exec/obidos/ASIN/0306474352/icongroupinterna

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Early Diagnosis and Preventive Therapy in Parkinson's Disease (Key Topics in Brain Research) by H. Przuntek, P. Riederer (Editor) (1989); ISBN: 0387820809; http://www.amazon.com/exec/obidos/ASIN/0387820809/icongroupinterna

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European Neurology: 3rd Sandoz Symposium on the Treatment of Parkinson's Disease (Journal - European Neurology , Vol 36, Suppl 1) by N. Yanagisawa (Editor) (1996); ISBN: 3805563272; http://www.amazon.com/exec/obidos/ASIN/3805563272/icongroupinterna

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First Sandoz Symposium on the Treatment of Parkinson's Disease, Tokyo, October 1992 by Y. Mizuno (Editor) (1993); ISBN: 3805558295; http://www.amazon.com/exec/obidos/ASIN/3805558295/icongroupinterna

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Flying Lessons: On the Wings of Parkinson's Disease by Joan Grady-Fitchett (1998); ISBN: 0312864906; http://www.amazon.com/exec/obidos/ASIN/0312864906/icongroupinterna

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Handbook of Parkinson's Disease (Neurological Disease and Therapy, Vol 59) by Rajesh Pahwa (Editor), et al (2003); ISBN: 0824742427; http://www.amazon.com/exec/obidos/ASIN/0824742427/icongroupinterna

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L-Dopa and Parkinsonism; ISBN: 0803605951; http://www.amazon.com/exec/obidos/ASIN/0803605951/icongroupinterna

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Long Term Clinical Care of Parkinson's Disease, 5th Symposium, Tokyo, April 1990 by T. Nakanishi (Editor) (1991); ISBN: 380555401X; http://www.amazon.com/exec/obidos/ASIN/380555401X/icongroupinterna

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Mapping the Progress of Alzheimer's and Parkinson's Disease (Advances in Behavioral Biology, 51) by Yoshikuni Mizuno (Editor), et al (2002); ISBN: 0306467631; http://www.amazon.com/exec/obidos/ASIN/0306467631/icongroupinterna

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Molecular Mechanisms of Parkinson's Disease by Philipp Kahle (2004); ISBN: 1587062399; http://www.amazon.com/exec/obidos/ASIN/1587062399/icongroupinterna

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Movement Disorders Sourcebook: Basic Consumer Health Information About Neurological Movement Disorders, Including Essential Tremor, Parkinson's Disease, Dystonia, Ceberal Palsy, by Joyce Brennfleck Shannon (Editor) (2002); ISBN: 078080628X; http://www.amazon.com/exec/obidos/ASIN/078080628X/icongroupinterna

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My Second Life: Living with Parkinson's Disease by William A. Harshaw, Bill Harshaw (2001); ISBN: 0888822367; http://www.amazon.com/exec/obidos/ASIN/0888822367/icongroupinterna

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Neurodegeneration and Neuroprotection in Parkinson's Disease by C. W. Olanow (Editor), et al (1996); ISBN: 0125254458; http://www.amazon.com/exec/obidos/ASIN/0125254458/icongroupinterna

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Neurological Rehabilitation of Parkinson's Disease by Diane Playford (Editor), et al; ISBN: 1841842974; http://www.amazon.com/exec/obidos/ASIN/1841842974/icongroupinterna

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Neurotoxic Factors in Parkinson's Disease and Related Disorders by Michael Storch (Editor), et al (2001); ISBN: 0306465299; http://www.amazon.com/exec/obidos/ASIN/0306465299/icongroupinterna

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New Parkinson's Disease Handbook : Essential Guide for Sifferers and Carers by Dr. Harvey Sagar (Author) (2002); ISBN: 0091883873; http://www.amazon.com/exec/obidos/ASIN/0091883873/icongroupinterna

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New Vistas in Parkinson's Disease (1986); ISBN: 3211819290; http://www.amazon.com/exec/obidos/ASIN/3211819290/icongroupinterna

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Old and New Dopamine Agonists in Parkinson's Disease by U. Bonuccelli (Editor), et al (1996); ISBN: 321182717X; http://www.amazon.com/exec/obidos/ASIN/321182717X/icongroupinterna

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Pallidal Surgery for the Treatment of Parkinson's Disease and Movement Disorders by Joachim K. Krauss (Editor), et al; ISBN: 0781712254; http://www.amazon.com/exec/obidos/ASIN/0781712254/icongroupinterna

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Parenteral Drug Therapy in Spasticity and Parkinson's Disease (New Trends in Clinical Neurology Series) by A.W.F. Rutgers (Editor), et al (1991); ISBN: 1850703590; http://www.amazon.com/exec/obidos/ASIN/1850703590/icongroupinterna

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Parkinson's Disease by J. David Grimes (2003); ISBN: 1552632660; http://www.amazon.com/exec/obidos/ASIN/1552632660/icongroupinterna

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Parkinson's Disease by Ariel Gordin (Editor), et al (2002); ISBN: 0781740843; http://www.amazon.com/exec/obidos/ASIN/0781740843/icongroupinterna

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Parkinson's Disease by Olanow, et al (2002); ISBN: 0195132637; http://www.amazon.com/exec/obidos/ASIN/0195132637/icongroupinterna

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Parkinson's Disease by Dr. Harvey Sagar (Author) (1996); ISBN: 0091813107; http://www.amazon.com/exec/obidos/ASIN/0091813107/icongroupinterna

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Parkinson's Disease by Roger C. Duvoisin (1991); ISBN: 0890041776; http://www.amazon.com/exec/obidos/ASIN/0890041776/icongroupinterna

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Parkinson's Disease - The Facts by Gerald Stern, Andrew Lees (1993); ISBN: 019261293X; http://www.amazon.com/exec/obidos/ASIN/019261293X/icongroupinterna

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Parkinson's Disease (Advances in Neurology, Vol 45) by Melvin D. Yahr (Editor), Kenneth J. Bergmann (Editor); ISBN: 088167205X; http://www.amazon.com/exec/obidos/ASIN/088167205X/icongroupinterna

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Parkinson's Disease (Advances in Neurology, Vol 69) by Leontino Battistin (Editor), et al; ISBN: 0781703417; http://www.amazon.com/exec/obidos/ASIN/0781703417/icongroupinterna

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Parkinson's Disease (Johns Hopkins Series in Contemporary Medicine and Public Health) by Gerald M. Stern (Editor) (1990); ISBN: 0801839750; http://www.amazon.com/exec/obidos/ASIN/0801839750/icongroupinterna

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Parkinson's Disease : The Mystery, the Search and the Promise (1993); ISBN: 9993615722; http://www.amazon.com/exec/obidos/ASIN/9993615722/icongroupinterna

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Parkinson's Disease : The Way Forward! An Integrated Approach including Drugs, Surgery, Nutrition, Bowel and Muscle Function, Self-Esteem, Sexuality, Stress Control and Carers by Geoffrey Leader, et al (2003); ISBN: 0952605686; http://www.amazon.com/exec/obidos/ASIN/0952605686/icongroupinterna

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Parkinson's Disease and Extrapyramidal Disorders by G. Nappi (1994); ISBN: 1854631020; http://www.amazon.com/exec/obidos/ASIN/1854631020/icongroupinterna

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Parkinson's Disease and Its Management (Oxford Medical Publications) by J. M. S. Pearce (1992); ISBN: 0192621777; http://www.amazon.com/exec/obidos/ASIN/0192621777/icongroupinterna

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Parkinson's Disease and Me: Walking the Path by Patricia Lightner (2003); ISBN: 1403397295; http://www.amazon.com/exec/obidos/ASIN/1403397295/icongroupinterna

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Parkinson's Disease and Movement Disorders: Diagnosis and Treatment Guidelines for the Practicing Physician by Charles H. Adler (Editor), J. Eric Ahlskog (Editor) (2000); ISBN: 0896036073; http://www.amazon.com/exec/obidos/ASIN/0896036073/icongroupinterna

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Parkinson's Disease and Parkinsonism in the Elderly by Jolyon Meara (Editor), William C. Koller (Editor); ISBN: 0521628849; http://www.amazon.com/exec/obidos/ASIN/0521628849/icongroupinterna

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Parkinson's Disease and Quality of Life by Lucien J. Cote (Editor), et al (2000); ISBN: 0789007630; http://www.amazon.com/exec/obidos/ASIN/0789007630/icongroupinterna

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Parkinson's Disease and the Problems of Clinical Trials by F. Clifford Rose (1992); ISBN: 1854630903; http://www.amazon.com/exec/obidos/ASIN/1854630903/icongroupinterna

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Parkinson's Disease in the Older Patient by Jeremy R. Playfer (Editor), John V. Hindle (Editor); ISBN: 0340759143; http://www.amazon.com/exec/obidos/ASIN/0340759143/icongroupinterna

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Parkinsons Disease Symposium Review: Proceedings of the Munich Symposium, June 1992: 1992 (Current Trends in the Treatment of Parkinson's Disease) by Merton Sandler (Editor); ISBN: 0861964047; http://www.amazon.com/exec/obidos/ASIN/0861964047/icongroupinterna

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Parkinson's Disease: 100 Maxims (100 Maxims in Neurology, Vol. 2) by John G. Nutt, et al (1992); ISBN: 0801672791; http://www.amazon.com/exec/obidos/ASIN/0801672791/icongroupinterna

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Parkinson's Disease: Anatomy, Pathology, and Therapy (Advances in Neurology, Vol 53) by Max B. Streifler (Editor), et al (1990); ISBN: 0881676349; http://www.amazon.com/exec/obidos/ASIN/0881676349/icongroupinterna

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Parkinson's Disease: Experimental Models and Therapy by Riederer (1996); ISBN: 3211827498; http://www.amazon.com/exec/obidos/ASIN/3211827498/icongroupinterna

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Parkinson's Disease: From Basic Research to Treatment (Advances in Neurology, Vol 60) by T. Nagatsu, et al; ISBN: 0881679674; http://www.amazon.com/exec/obidos/ASIN/0881679674/icongroupinterna

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Parkinson's Disease: Methods & Protocols by Maral M., MD Mouradian (Editor) (2001); ISBN: 0896037614; http://www.amazon.com/exec/obidos/ASIN/0896037614/icongroupinterna

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Parkinson's Disease: Neurobehavioral Aspects by Steven J. Huber, Jeffrey L. Cummings (Editor); ISBN: 0195069692; http://www.amazon.com/exec/obidos/ASIN/0195069692/icongroupinterna

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Parkinson's Disease: Overview and Current Abstracts by Charles S. Mittel (Editor) (2003); ISBN: 1590335058; http://www.amazon.com/exec/obidos/ASIN/1590335058/icongroupinterna

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Parkinson's Disease: Studies in Psychological and Social Care by Ray Percival (1999); ISBN: 1854332996; http://www.amazon.com/exec/obidos/ASIN/1854332996/icongroupinterna

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Parkinson's Disease: The Life Cycle of the Dopamine Neuron (Annals of the New York Academy of Sciences, Vol 991) by Howard Federoff (Editor) (2003); ISBN: 157331448X; http://www.amazon.com/exec/obidos/ASIN/157331448X/icongroupinterna

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Parkinson's Disease: The Mystery, the Search and the Promise [LARGE PRINT] by Sue Dauphin (2000); ISBN: 0962035416; http://www.amazon.com/exec/obidos/ASIN/0962035416/icongroupinterna

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Parkinson's Disease: The New Nutritional Handbook: A Guide for Doctors, Nutritionists, Patients and Carers by Geoffrey Leader (1996); ISBN: 0952605619; http://www.amazon.com/exec/obidos/ASIN/0952605619/icongroupinterna

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Parkinson's Disease: The Role of Dopamine Agonists by A. Lieberman (Editor), X. Lataste (Editor) (1989); ISBN: 1850702721; http://www.amazon.com/exec/obidos/ASIN/1850702721/icongroupinterna

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Parkinson's Disease: The Treatment Options by Peter A. Lewitt (Editor), et al; ISBN: 1853173797; http://www.amazon.com/exec/obidos/ASIN/1853173797/icongroupinterna

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Parkinson's Disease: Your Questions Answered by Thomas Foltynie, et al (2003); ISBN: 0443064172; http://www.amazon.com/exec/obidos/ASIN/0443064172/icongroupinterna

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Patrick Learns About Parkinson's Disease: A Story of a Special Bond Between Friends (Special Family and Friends Series) by Kim Gosselin, Karen Schader (Editor) (2002); ISBN: 1891383183; http://www.amazon.com/exec/obidos/ASIN/1891383183/icongroupinterna

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Progress in Alzheimer's and Parkinson's Diseases (Advances in Behavioral Biology, Vol 49) by Abraham Fisher (Editor), et al (1998); ISBN: 0306459035; http://www.amazon.com/exec/obidos/ASIN/0306459035/icongroupinterna

•

Progress in Parkinson's Disease Research 2 by Franz Hefti, William J. Weiner (Editor) (1992); ISBN: 0879935308; http://www.amazon.com/exec/obidos/ASIN/0879935308/icongroupinterna

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Psychiatric and Cognitive Disorders in Parkinson's Disease by Sergio E. Starkstein (Author), Marcelo Merello (Author); ISBN: 0521663059; http://www.amazon.com/exec/obidos/ASIN/0521663059/icongroupinterna

•

Rehabilitation in Parkinson's Disease by F. I. Caird (1991); ISBN: 1565935616; http://www.amazon.com/exec/obidos/ASIN/1565935616/icongroupinterna

•

Saving Milly : Love, Politics, and Parkinson's Disease by Morton Kondracke (Author) (2002); ISBN: 034545197X; http://www.amazon.com/exec/obidos/ASIN/034545197X/icongroupinterna

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•

Second Canadian-American Conference on Parkinson's Diseases by Fletcher H. McDowell (1974); ISBN: 0911216634; http://www.amazon.com/exec/obidos/ASIN/0911216634/icongroupinterna

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Shadow Over My Brain: A Battle Against Parkinson's Disease by Cecil Todes (2001); ISBN: 1859590497; http://www.amazon.com/exec/obidos/ASIN/1859590497/icongroupinterna

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Sixth Symposium on a Long Term Clinical Care of Parkinson's Disease, Tokyo, October 1991 by T. Nakanishi (Editor) (1992); ISBN: 3805556640; http://www.amazon.com/exec/obidos/ASIN/3805556640/icongroupinterna

•

Symposium on a Long Time Clinical Care of Parkinson's Disease (European Neurology, Vol 26, Suppl 1) by T. Nakanishi (Editor) (1987); ISBN: 3805545908; http://www.amazon.com/exec/obidos/ASIN/3805545908/icongroupinterna

•

The Basal Ganglia and New Surgical Approaches for Parkinson's Disease (Advances in Neurology, Vol 74) by Jose A. Obeso, et al; ISBN: 0397517807; http://www.amazon.com/exec/obidos/ASIN/0397517807/icongroupinterna

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The Comprehensive Management of Parkinson's Disease by Andrea M. Cohen (Editor), et al (1994); ISBN: 0939957744; http://www.amazon.com/exec/obidos/ASIN/0939957744/icongroupinterna

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The Comprehensive Management of Parkinson's Disease by Stern Matthew B., et al; ISBN: 0893353116; http://www.amazon.com/exec/obidos/ASIN/0893353116/icongroupinterna

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The Encyclopedia of Parkinson's Disease by Deborah S. Romaine (2004); ISBN: 0816050325; http://www.amazon.com/exec/obidos/ASIN/0816050325/icongroupinterna

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The Parkinson Predicament & A Spoonful of Sugar: My Life With Parkinson's Disease a Prescription for Living With Parkinson's Disease by Barbara T. Coleman, et al; ISBN: 0964210924; http://www.amazon.com/exec/obidos/ASIN/0964210924/icongroupinterna

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The Parkinson's Disease Handbook by Richard Godwin-Austen (1997); ISBN: 0859697894; http://www.amazon.com/exec/obidos/ASIN/0859697894/icongroupinterna

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The Parkinson's Disease Handbook (1991); ISBN: 9991820442; http://www.amazon.com/exec/obidos/ASIN/9991820442/icongroupinterna

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The Scientific Basis for the Treatment of Parkinson's Disease by Nest Galvez-Jimenez (2004); ISBN: 1842141821; http://www.amazon.com/exec/obidos/ASIN/1842141821/icongroupinterna

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The Scientific Basis for the Treatment of Parkinson's Disease by A.N. Liegerman (Editor), C. W. Olanow (2003); ISBN: 1850703558; http://www.amazon.com/exec/obidos/ASIN/1850703558/icongroupinterna

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Treatment of Parkinson's Disease: 4th Sandoz Symposium Tokyo, October 1995 (European Neurology Ser) by Hisayuki Kowa (Editor) (1997); ISBN: 3805565658; http://www.amazon.com/exec/obidos/ASIN/3805565658/icongroupinterna

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Treatment of Parkinson's Disease: 5th Sandoz Symposium Tokyo, November 1997 (European Neurology Ser) by Ichiro Kanazawa (Editor) (1997); ISBN: 3805566115; http://www.amazon.com/exec/obidos/ASIN/3805566115/icongroupinterna

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Understanding Parkinson's Disease by J. Pearce; ISBN: 1898205868; http://www.amazon.com/exec/obidos/ASIN/1898205868/icongroupinterna

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Understanding Parkinson's Disease : A Scientific American article [DOWNLOAD: PDF] by Moudim B.H. Youssa (Author), Peter Rierder (Author); ISBN: B00006BNMS; http://www.amazon.com/exec/obidos/ASIN/B00006BNMS/icongroupinterna

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Understanding Parkinson's Disease Chart by Anatomical Chart (2003); ISBN: 1587793539; http://www.amazon.com/exec/obidos/ASIN/1587793539/icongroupinterna

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Understanding Parkinson's Disease: A Self-Help Guide by David L. Cram (2001); ISBN: 1886039402; http://www.amazon.com/exec/obidos/ASIN/1886039402/icongroupinterna

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What Your Doctor May Not Tell You About Parkinson's Disease: A Holistic Program for Optimal Wellness by Mary J./Marjama-Lyons Shomon (Author), et al (2003); ISBN: 0446678902; http://www.amazon.com/exec/obidos/ASIN/0446678902/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “Parkinson’s disease” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

Advances in Parkinsonism: biochemistry, physiology, treatment Author: Birkmayer, Walther.; Year: 1978; Basle: Roche, c1976

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Communication in Parkinson's disease Author: Scott, Sheila,; Year: 1983; London: Croom Helm, c1985; ISBN: 0709923929 http://www.amazon.com/exec/obidos/ASIN/0709923929/icongroupinterna

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Depth-electrographic stimulation of the human brain and behavior, from fourteen years of studies and treatment of Parkinson's disease and mental disorders with implanted electrodes. Author: Sem-Jacobsen, Carl Wilhelm.; Year: 1968; Springfield, Ill., Thomas [c1968]

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Dopamine receptor function in Parkinson's disease: a clinical and biochemical study Author: Laihinen, Arto.; Year: 1985; Turku: [s.n.], 1983; ISBN: 951642371X

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Healing the brain: a doctor's controversial quest for a cell therapy to cure Parkinson's disease Author: Freed, Curt.; Year: 2002; New York: Times Books/Henry Holt, 2002; ISBN: 0805070915 http://www.amazon.com/exec/obidos/ASIN/0805070915/icongroupinterna

11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

210 Parkinson’s Disease

•

Hope and help in Parkinson's disease. Author: Button, John C.; Year: 1964; M.P. Norman, Okla., 1964]

•

James Parkinson, 1755-1824; a bicentenary volume of papers dealing with Parkinson's disease, incorporating the original Essay on the shaking palsy. Ed. by Macdonald Critchley, with the collaboration of William H. McMenemey [and others]. Author: Critchley, Macdonald.; Year: 1955; London, Macmillan, 1955

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Parkinson's disease: a guide for patient and family Author: Duvoisin, Roger C.,; Year: 1976; New York: Raven Press, c1978; ISBN: 0890042055 http://www.amazon.com/exec/obidos/ASIN/0890042055/icongroupinterna

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Parkinson's disease: concepts and prospects: proceedings of a symposium held at the University of Groningen, January 28, 1977 Author: Lakke, J. P. W. F.; Year: 1977; Amsterdam: Excerpta medica; New York: sole distributors for the USA, Elsevier/NorthHolland, 1977; ISBN: 0444900063 http://www.amazon.com/exec/obidos/ASIN/0444900063/icongroupinterna

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Parkinson's disease: current progress, problems, and management: proceedings of the Northern European Symposium on Parkinson's Disease, Helsinki, November 6-8, 1979 Author: Klingler, M. (Max); Year: 1980; Amsterdam; New York: Elsevier/NorthHolland Biomedical Press; New York: Sole distributors for the USA, Elsevier NorthHolland, 1980; ISBN: 0444802630 http://www.amazon.com/exec/obidos/ASIN/0444802630/icongroupinterna

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Parkinson's disease: neurophysiological, clinical, and related aspects Author: Messiha, Fathy S.; Year: 1978; New York: Plenum Press, c1977; ISBN: 0306326906 http://www.amazon.com/exec/obidos/ASIN/0306326906/icongroupinterna

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Parkinson's disease and its surgical treatment. Author: Oliver, Leslie C.; Year: 1975; London, Lewis, 1953

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Parkinson's disease. Author: Oliver, Leslie C.; Year: 1977; London, Heinemann [c1967]

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Parkinson's disease; advice and aid for sufferers from Parkinson's disease and other physical disabilities. Author: Buchler, Walter,; Year: 1950; London, [1950]

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Parkinson's disease; present status and research trends, prepared by the staff of the Parkinson's Disease Information Center, College of Physicians and Surgeons, Columbia University. Author: Parkinson Information Center (New York, N.Y.); Year: 1968; Bethesda, Md., National Institute of Neurological Diseases and Blindness; for sale by the Supt. of Docs., U. S. Govt. Print. Off., Washington, 1968

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Parkinson's disease; rigidity, akinesia, behavior. Proceedings. J. Siegfried, editor. Author: Siegfried, J.; Year: 1972; Bern, Huber [1972]-; ISBN: 0345600303

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Parkinson's disease--II: aging and neuroendocrine relationships Author: Finch, Caleb Ellicott.; Year: 1978; New York: Plenum Press, c1978; ISBN: 0306401568 http://www.amazon.com/exec/obidos/ASIN/0306401568/icongroupinterna

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Research progress in Parkinson's disease Author: Rose, F. Clifford (Frank Clifford); Year: 1981; Tunbridge Wells, Kent: Pitman Medical, 1981; ISBN: 0272796018

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Symposium on Parkinson's Disease. [Proceedings of a symposium arranged by the Postgraduate Committee in Medical Education of the University of New South Wales and held in Sydney on 5 December 1970. Author: University of New South Wales. Postgraduate Committee in Medical Education.; Year: 1971; Sydney, 1971]

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The extrapyramidal system and its disorders: VIth International Symposium on Parkinson's Disease Author: Poirier, Louis Joseph,; Year: 1979; New York: Raven Press, 1979; ISBN: 0890043698 http://www.amazon.com/exec/obidos/ASIN/0890043698/icongroupinterna

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The role of peptides and amino acids as neurotransmitters: proceedings of the Third Tarbox Parkinson's Disease Symposium, held on October 16-18, 1980, at Texas Tech University Health Sciences Center, Lubbock, Texas Author: Kenny, Alexander D.; Year: 1981; New York: Liss, c1981

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The shaking palsy (Parkinson's disease) a symposium. Conference editors: Harold Elliot and Blaine Nashold. Author: Elliot, Harold.; Year: 1960; [Montreal, McGill Univ., 1960]

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Third Symposium on Parkinson's Disease held at the Royal College of Surgeons of Edinburgh on 20, 21 and 22 May 1968. [Symposium editors: F. John Gillingham and I. M. L. Donaldson. Associate editors: John Fraser et al.]. Author: Donaldson, I. M. L.; Year: 1969; Edinburgh, Livingstone, 1969

•

Treatment of Parkinson's disease and allied disorders; guest editor: Warren V. Huber. Treatment of acquired hemorrhagic disorders; guest editor: Oscar D. Ratnoff. Author: Huber, Warren V.,; Year: 1968; [New York] Hoeber 1968

Chapters on Parkinson’s Disease In order to find chapters that specifically relate to Parkinson’s disease, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and Parkinson’s disease using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “Parkinson’s disease” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on Parkinson’s disease: •

AAC for Huntington Disease and Parkinson's Disease: Planning for Change Source: in Beukelman, D.R.; Yorkston, K.M.; Reichle, J., eds. Augmentative and Alternative Communication for Adults with Acquired Neurologic Disorders. Baltimore, MD: Paul H. Brookes Publishing Co. 2000. p. 233-270. Contact: Available from Paul H. Brookes Publishing Co. P.O. Box 10624, Baltimore, MD 21285. (800) 638-3775. Fax (410) 337-8539. Website: www.brookespublishing.com. PRICE: $42.00 plus shipping and handling. ISBN: 1557664730. Summary: The loss of speech in adulthood due to acquired neurologic disorders causes a person to confront enormous life changes. This chapter on the use of augmentative and alternative communication (AAC) strategies for people with Huntington disease or Parkinson's disease is from a textbook that explores the challenges these adults face during their transition, whether gradual or immediate, from speaking to using AAC. This chapter focuses on movement disorders and their impact on communication; the daily experiences of people with these diseases and how the diseases can change their lives, their families' lives, and friends in their personal and community networks; and the use of AAC intervention at various stages of these diseases. Huntington disease is characterized by progressive motor disturbances, cognitive impairments, and psychological changes; these manifestations significantly affect the person's ability to communicate. Parkinson's disease is a slowly progressive movement disorder is characterized by an inability to execute learned motor movements; symptoms include resting tremor, rigidity, and slowness of movement. Communication disorders in Parkinson's are common, often beginning with a decrease in facial expression or

212 Parkinson’s Disease

nonverbal gesture, at time progressing to decrease in vocal loudness, and later progressing to severe dysarthria characterized by changes in speaking rate, articulatory precision, and speech intelligibility. The authors conclude the chapter by offering models or frameworks for patient care delivery for these people. 105 references. •

Cognitive Changes Associated With Parkinson's Disease Source: in Hutton, J.T.; Dippel, R. L. Caring for the Parkinson Patient: A Practical Guide. Amherst, NY: Prometheus Books. 1999. p. 175-187. Contact: Available from Prometheus Books. 59 John Glenn Drive, Amherst, NY 142282197. (800)421-0351; (716)691-0133; FAX (716)691-0137. Internet access: www.prometheusbooks.com. PRICE: $19.95. ISBN: 1573926841. Summary: This book chapter discusses what is known about cognitive changes in Parkinson's disease through research and clinical observation, including the relationship between Parkinson's disease and dementia, and offers suggestions for dealing with these problems, including neurorehabilitation. Over 50 percent of Parkinson's disease patients suffer from measurable changes in cognition and there is a direct relationship between severity of the disease and the degree of cognitive dysfunction. Observations and findings are discussed in the areas of patient functioning in familiar versus unfamiliar activities, the ability to think quickly and fluidly, diminished visuospatial abilities, memory capacity, language-related abilities, and the comorbidity of Parkinson's disease with other forms of dementia such as Alzheimer's disease. Besides trying to maintain a sense of humor and a realistic outlook, caregivers are advised to have patience to allow Parkinson's patients time to formulate verbal responses or actions, provide memory aids wherever possible to increase the patient's self-reliance, and exercise caution when allowing patients to retain their driving privileges. Caregivers are further advised to seek more education about the disease, utilize Parkinson's disease support groups, and consider using Parkinson-specific exercise, nutrition, speech, and cognitive rehabilitation therapy programs.

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CHAPTER 8. MULTIMEDIA ON PARKINSON’S DISEASE Overview In this chapter, we show you how to keep current on multimedia sources of information on Parkinson’s disease. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on Parkinson’s disease is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “Parkinson’s disease” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “Parkinson’s disease” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on Parkinson’s disease: •

Pathophysiological Mechanisms Underlying Parkinsonism: Implications for the Speech-Language Pathologist Source: Tucson, AZ: National Center for Neurogenic Communication Disorders. 1993. (videocassette and handout). Contact: Available from National Center for Neurogenic Communication Disorders. Telerounds Coordinator, Building 71, Room 500, University of Arizona, Tucson, AZ 85721. (520) 621-1819 or (520) 621-1472. PRICE: $25.00. Summary: This telerounds program reviews issues related to the pathophysiology of Parkinson's disease and how those issues might explain current treatment limitations and suggest new treatments in the future. Topics covered include the potential impact of Parkinson's disease on the nation's health; how the dysfunction and disabilities caused by Parkinson's disease result from alterations of the normal physiology; and the concept of dynamic modulation of neuronal activity as it relates to physiology, pathophysiology

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of disease, and treatment. The handout provided with the videotape includes an abstract, a list of objectives, a brief outline of the program, a reference list, and an evaluation form for viewers to complete and return. 1 figure 8 references. (AA-M).

Bibliography: Multimedia on Parkinson’s Disease The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in Parkinson’s disease (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on Parkinson’s disease: •

A Question of time [motion picture]: toward earlier diagnosis of Parkinson's disease Source: MSD, Merck Sharp & Dohme; [produced by] SYSTEMA Corporation; Year: 1978; Format: Motion picture; [Rahway, N.J.]: Merck, c1978

•

Advances in the treatment of Parkinson's disease [videorecording] Source: Jean Pintar Hubble. [et al.]; Year: 2001; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c2001

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Caring for people with Parkinson's disease [videorecording] Source: Mosby Lifeline; Samuel Merritt College, Studio Three Productions; Year: 1996; Format: Videorecording; [St. Louis, Mo.]: Mosby-Year Book, c1996

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Current approaches to the management of Parkinson's disease [videorecording] Source: American Academy of Family Physicians; Year: 2000; Format: Videorecording; Leawood, KS: The Academy, c2000

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L-dopa and Parkinson's disease: the treatment is the crisis [motion picture] Source: Maimonides Hospital & Home for the Aged; Year: 1971; Format: Motion picture; [Montreal]: The Hospital; [Atlanta: for loan by National Medical Audiovisual Center; Franklin Lakes, N. J.: for loan and sale by Transit Media], c1971

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Nursing care of the patient with Parkinson's disease [electronic resource] Source: written by Jean Wesley; Year: 1992; Format: Electronic resource; Edwardsville, KS: MediSim; Baltimore, MD: Williams & Wilkins, c1992

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Parkinson's disease [sound recording]: clinical stages and management strategies Source: [Du Pont Pharmaceuticals]; Year: 1983; Format: Sound recording; Wilmington, Del.: Du Pont Pharmaceuticals, c1983

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Parkinson's disease [videorecording] Source: [presented by] Marshfield Medical Foundation and Marshfield Clinic; Year: 1981; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, 1981

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Parkinson's disease [videorecording]: a clinical update on diagnosis and management Source: Matthias C. Kurth; Year: 1995; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1995

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Parkinson's disease [videorecording]: an update Source: a presentation of Films for the Humanities & Sciences; Year: 2000; Format: Videorecording; Princeton, N.J.: Films for the Humanities and Sciences, c2000

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Parkinson's disease [videorecording]: current therapeutic approach Source: [HSTN]; Year: 2003; Format: Videorecording; Carrollton, TX: Primedia Workplace Learning, c2003

Multimedia 215

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Parkinson's disease [videorecording]: current treatment and the prospects for neural transplants Source: with William Langston and James Tetrud; Year: 1989; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1989

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Parkinson's disease [videorecording]: the reality and the promise Source: an AREN production; Year: 1989; Format: Videorecording; Pittsburgh, Pa.: American Rehabilitation Educational Network, c1989

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Parkinson's disease and other movement disorders [slide]. Year: 1987; Format: Slide; [Columbus, Ohio]: Center for Continuing Medical Education, the Ohio State University College of Medicine, [1987]

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Parkinson's disease surgery [videorecording] Source: a presentation of Films for the Humanities & Sciences; produced for the Learning Channel by Advanced Medical Productions, Inc; Year: 2000; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c2000

•

Parkinson's disease, natural and drug-induced causes [videorecording] Source: [presented by] Primark Corporation, HSN, Hospital Satellite Network, produced in cooperation with Office of Clinical Reports and Inquiries, Clinical Center, National Institutes of Hea; Year: 1984; Format: Videorecording; [Los Angeles, Calif.]: HSN, c1984

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Recent research in Parkinson's disease [videorecording] Source: [presented by] Marshfield Clinic, Saint Joseph's Hospital, [and] Marshfield Medical Research Foundation; Year: 1992; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, [1992]

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Recognizing and managing Parkinson's disease [videorecording] Source: Rajesh Pahwa; Year: 1998; Format: Videorecording; Clifton, N.J.: Network for Continuing Medical Education, c1998

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Surgical treatment of Parkinson's disease [videorecording] Source: Marshfield Clinic, Saint Joseph's Hospital; a presentation of the Marshfield Video Network; Year: 1995; Format: Videorecording; Marshfield, WI: The Clinic, [1995]

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The genetic approach to understanding Parkinson's disease [sound recording] Source: [Robert Nussbaum]; Year: 1999; Format: Sound recording; [Bethesda, Md.: National Institutes of Health, 1999]

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Toward a better understanding of Parkinson's disease [motion picture] Source: presented by MSD, Merck Sharp & Dohme; produced by Medi-Cine, ltd; Year: 1980; Format: Motion picture; West Point, PA.: Merck, c1980

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Update and the therapeutical approach to Parkinson's disease [videorecording] Source: [presented by] Marshfield Clinic, Saint Joseph's Hospital [and] Marshfield Medical Research Foundation; Year: 1989; Format: Videorecording; Marshfield, WI: Marshfield Video Network, [1989]

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Voice therapy for patients with Parkinson's disease [videorecording]: it's worth the effort Source: the National Center for Neurogenic Communication Disorders; [with the cooperation of] Veterans Health Administration, Office of Academic Affairs [and] Long Bea; Year: 1993; Format: Videorecording; [Tucson, Ariz.]: Arizona Board of Regents, c1993

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CHAPTER 9. PERIODICALS AND NEWS ON PARKINSON’S DISEASE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Parkinson’s disease.

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

Benefits of deep brain stimulation for Parkinson's disease sustained for years Source: Reuters Medical News Date: November 12, 2003

218 Parkinson’s Disease

•

Overabundant alpha-synuclein may cause Parkinson's disease Source: Reuters Medical News Date: October 30, 2003

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Regulation of dopamine varies in family members with Parkinson's disease Source: Reuters Medical News Date: October 21, 2003

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Studies show Novartis' Stalevo good effective for Parkinson's disease Source: Reuters Industry Breifing Date: September 01, 2003

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NSAID use may protect against Parkinson's disease Source: Reuters Medical News Date: August 18, 2003

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Anti-inflammatories ward off Parkinson's disease Source: Reuters Industry Breifing Date: August 18, 2003

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Antimuscarinic treatment in parkinsonism increases Alzheimer pathology Source: Reuters Industry Breifing Date: July 30, 2003

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Ropinirole slows loss of nerve function in early Parkinson's disease Source: Reuters Industry Breifing Date: July 14, 2003

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Orion gets U.S. approval for combination treatment for Parkinson's disease Source: Reuters Medical News Date: June 13, 2003

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Parkinson's disease linked to high iron intake Source: Reuters Medical News Date: June 09, 2003

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Parkinson's disease more common in Hispanics Source: Reuters Medical News Date: June 05, 2003

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Alcohol use has little, if any, effect on risk of Parkinson's disease Source: Reuters Medical News Date: May 23, 2003

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Predictors of success with surgery for Parkinson's disease identified Source: Reuters Medical News Date: May 20, 2003

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Single severe head injury linked to Parkinson's disease Source: Reuters Medical News Date: May 19, 2003

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Teva to promote Parkinson's disease drug in U.S. with Eisai Source: Reuters Industry Breifing Date: May 15, 2003

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COX-2 inhibitors may offer novel therapy for Parkinson's disease Source: Reuters Medical News Date: April 07, 2003

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Implanted retinal pigment epithelial cells have potential in Parkinson's disease Source: Reuters Medical News Date: April 02, 2003

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Dementia common during second decade after Parkinson's disease onset Source: Reuters Medical News Date: March 20, 2003

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Caffeine-HRT interaction may increase risk of Parkinson's disease Source: Reuters Medical News Date: March 10, 2003

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Parkinson's disease drug may help smokers quit Source: Reuters Medical News Date: January 24, 2003

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Investigational Parkinson's disease drug a disappointment in late studies Source: Reuters Medical News Date: January 06, 2003

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Rasagiline monotherapy curbs early Parkinson's disease symptoms Source: Reuters Industry Breifing Date: December 18, 2002

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Dairy product use linked to Parkinson's disease in me Source: Reuters Medical News Date: December 16, 2002

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Most Parkinson's disease patients do not adhere to drug regimens Source: Reuters Industry Breifing Date: November 13, 2002

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Transdermal rotigotine may reduce symptom fluctuations in Parkinson's disease Source: Reuters Medical News Date: November 12, 2002

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New levodopa formulation may reduce "off-time" in Parkinson's disease Source: Reuters Industry Breifing Date: November 12, 2002

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Foods rich in vitamin E may reduce Parkinson's disease risk Source: Reuters Medical News Date: November 06, 2002

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Fruit fly model for Parkinson's disease developed Source: Reuters Medical News Date: November 04, 2002

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Brain stimulation may treat obsessive-compulsive disorder as well as parkinsonism Source: Reuters Medical News Date: October 25, 2002

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Smoking, coffee drinking again found to lower Parkinson's disease risk Source: Reuters Medical News Date: October 16, 2002

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Parkinson's disease often misdiagnosed at initial presentation Source: Reuters Medical News Date: October 16, 2002

220 Parkinson’s Disease

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Antioxidant may slow functional decline in Parkinson's disease Source: Reuters Medical News Date: October 14, 2002

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Glutamate decarboxylase gene therapy improves experimental parkinsonism Source: Reuters Industry Breifing Date: October 10, 2002

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Genetic and environmental Parkinson's disease factors converge in single pathway Source: Reuters Medical News Date: October 07, 2002

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Inhibitors of p53 may have therapeutic potential in Parkinson's disease Source: Reuters Industry Breifing Date: October 03, 2002

•

Donepezil treatment improves cognition in Parkinson's disease patients Source: Reuters Industry Breifing Date: June 21, 2002 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 “Parkinson’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

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you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “Parkinson’s disease” (or synonyms). If you know the name of a company that is relevant to Parkinson’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 “Parkinson’s disease” (or synonyms).

Academic Periodicals covering Parkinson’s Disease Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Parkinson’s disease. In addition to these sources, you can search for articles covering Parkinson’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 10. 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 Parkinson’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 Parkinson’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.).

224 Parkinson’s Disease

The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to Parkinson’s disease: Amantadine •

Systemic - U.S. Brands: Symmetrel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202024.html

Antihistamines •

Systemic - U.S. Brands: Aller-Chlor; AllerMax Caplets; Aller-med; Atarax; Banophen; Banophen Caplets; Benadryl; Benadryl Allergy; Bromphen; Calm X; Chlo-Amine; Chlorate; Chlor-Trimeton; Chlor-Trimeton Allergy; Chlor-Trimeton Repetabs; Claritin; Claritin Reditabs; Compoz; Conta http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202060.html

Bromocriptine •

Systemic - U.S. Brands: Parlodel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202094.html

Clozapine •

Systemic - U.S. Brands: Clozaril http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202157.html

Droperidol •

Systemic - U.S. Brands: Inapsine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203411.html

Entacapone •

Systemic - U.S. Brands: Comtan http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500103.html

Haloperidol •

Systemic - U.S. Brands: Haldol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202278.html

Levodopa •

Systemic - U.S. Brands: Atamet; Larodopa; Sinemet; Sinemet CR http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202326.html

Methyldopa •

Systemic - U.S. Brands: Aldomet http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202359.html

Orphenadrine •

Systemic - U.S. Brands: Antiflex; Banflex; Flexoject; Mio-Rel; Myolin; Myotrol; Norflex; Orfro; Orphenate http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202426.html

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Pergolide •

Systemic - U.S. Brands: Permax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202451.html

Phenothiazines •

Systemic - U.S. Brands: Chlorpromazine Hydrochloride Intensol; Compazine; Compazine Spansule; Mellaril; Mellaril Concentrate; Mellaril-S; Permitil; Permitil Concentrate; Prolixin; Prolixin Concentrate; Prolixin Decanoate; Prolixin Enanthate; Serentil; Serentil Concentrate; Ste http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202457.html

Pimozide •

Systemic - U.S. Brands: Orap http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202466.html

Pramipexole •

Systemic - U.S. Brands: Mirapex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203739.html

Risperidone •

Systemic - U.S. Brands: Risperdal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202769.html

Ropinirole •

Systemic - U.S. Brands: Requip http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203364.html

Selegiline •

Systemic - U.S. Brands: Carbex; Eldepryl http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202519.html

Tolcapone •

Systemic - U.S. Brands: Tasmar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203115.html

Trimethobenzamide •

Systemic - U.S. Brands: Benzacot; Stemetic; Tebamide; Tigan; Tribenzagan; Trimazide http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202578.html

Vitamin E •

Systemic - U.S. Brands: Amino-Opti-E; E-Complex-600; Liqui-E; Pheryl-E http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202598.html

226 Parkinson’s Disease

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 Parkinson’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 “Parkinson’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 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

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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 Parkinson’s disease: •

Levodopa and carbidopa (trade name: Duodopa) http://www.rarediseases.org/nord/search/nodd_full?code=1014

•

Selegiline HCl (trade name: Eldepryl) http://www.rarediseases.org/nord/search/nodd_full?code=39

•

Apomorphine http://www.rarediseases.org/nord/search/nodd_full?code=669

•

Apomorphine HCI http://www.rarediseases.org/nord/search/nodd_full?code=670

•

Porcine fetal neural dopamiminergic cells and/or p (trade name: anti-MHC-1 Ab for intracerebral implantation TN) http://www.rarediseases.org/nord/search/nodd_full?code=825

•

Porcine fetal neural gabaergic cells and/or precur (trade name: implantation. TN=NeuroCell-PD) http://www.rarediseases.org/nord/search/nodd_full?code=826

•

Human Retinal Pigmented Epithelial Cells on Collag (trade name: Spheramine) http://www.rarediseases.org/nord/search/nodd_full?code=840

•

Apomorphine (trade name: Zydis) http://www.rarediseases.org/nord/search/nodd_full?code=851

•

Porcine Sertoli cells aseptically prepared for int (trade name: N-Graft) http://www.rarediseases.org/nord/search/nodd_full?code=893

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 Institute12: •

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/

12

These publications are typically written by one or more of the various NIH Institutes.

232 Parkinson’s Disease

•

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.13 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:14 •

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

13 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). 14 See http://www.nlm.nih.gov/databases/databases.html.

234 Parkinson’s Disease

•

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 Gateway15 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.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Parkinson’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 28862 590 992 11 4 30459

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 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.19 Simply search by “Parkinson’s disease” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

15

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

16

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). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

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 Biologists20 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.21 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.22 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/.

The Genome Project and Parkinson’s Disease In the following section, we will discuss databases and references which relate to the Genome Project and Parkinson’s disease. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 20 Adapted 21

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. 22 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. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

236 Parkinson’s Disease

To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “Parkinson’s disease” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for Parkinson’s disease: •

Amyotrophic Lateral Sclerosis-parkinsonism/dementia Complex of Guam Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?105500

•

Paralysis Agitans, Juvenile, of Hunt Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?168100 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease,

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Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html •

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

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To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “Parkinson’s disease” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “Parkinson’s disease” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

24 Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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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 Parkinson’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 Internetbased 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 Parkinson’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 Parkinson’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 “Parkinson’s disease”:

240 Parkinson’s Disease

•

Guides on Parkinson’s disease Parkinson's Disease http://www.nlm.nih.gov/medlineplus/parkinsonsdisease.html

•

Other guides Alzheimer's Disease http://www.nlm.nih.gov/medlineplus/alzheimersdisease.html Cerebral Palsy http://www.nlm.nih.gov/medlineplus/cerebralpalsy.html Degenerative Nerve Diseases http://www.nlm.nih.gov/medlineplus/degenerativenervediseases.html Dementia http://www.nlm.nih.gov/medlineplus/dementia.html Huntington's Disease http://www.nlm.nih.gov/medlineplus/huntingtonsdisease.html Movement Disorders http://www.nlm.nih.gov/medlineplus/movementdisorders.html Neurologic Diseases http://www.nlm.nih.gov/medlineplus/neurologicdiseases.html Progressive Supranuclear Palsy http://www.nlm.nih.gov/medlineplus/progressivesupranuclearpalsy.html

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

Diagnosis/Symptoms How is Parkinsons Diagnosed? Source: Parkinson's Disease Foundation http://www.pdf.org/AboutPDF/diagnosing_parkinsons.cfm Primary Symptoms of Parkinson's Disease Source: Parkinson's Disease Foundation http://www.pdf.org/AboutPD/symptoms.cfm Stages of Parkinson Disease Source: National Parkinson Foundation, Inc. http://www.parkinson.org/stages.htm

•

Treatment Commonly Prescribed Medications Source: Parkinson's Disease Foundation http://www.pdf.org/AboutPD/treatment.cfm Deep Brain Stimulation Source: We Move http://www.wemove.org/par_dbs.html

Patient Resources

New Combination Drug for Parkinson's Disease Receives FDA Approval Source: Parkinson's Disease Foundation http://www.pdf.org/news/news.cfm?type=1&selectedItem=109 Pallidotomy http://www.nlm.nih.gov/medlineplus/tutorials/pallidotomyloader.html Parkinson's Disease: Nonpharmacologic Treatments Source: We Move http://www.wemove.org/par_nphm.html Parkinson's Disease: Pharmacologic Treatments Source: We Move http://www.wemove.org/par/par_phm.html Parkinson's Disease: Transplant Surgery Source: We Move http://www.wemove.org/par/par_fnct.html Parkinson's Disease: When Should Treatment Start? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00012 Savings on Drugs Source: Parkinson's Disease Foundation http://www.pdf.org/AboutPDF/savings_on_drugs.cfm Surgery for Parkinson Disease Source: National Parkinson Foundation, Inc. http://www.parkinson.org/surgery.htm Thalamotomy Source: We Move http://www.wemove.org/par_thal.html •

Alternative Therapy Complementary Therapies and Parkinson's Disease Source: National Parkinson Foundation, Inc. http://www.parkinson.org/therapies.htm

•

Nutrition Nutrition and Swallowing In Parkinson's Disease Source: National Parkinson Foundation, Inc. http://www.parkinson.org/nutswa.htm Nutritional Guidelines For Parkinson Patients Source: National Parkinson Foundation, Inc. http://www.parkinson.org/nutrguid.htm Parkinson's Disease: Diet and Exercise Source: We Move http://www.wemove.org/par_ide.html

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242 Parkinson’s Disease

•

Coping Parkinson's Disease: Caring and Coping Source: National Parkinson Foundation, Inc. http://www.parkinson.org/caring.htm Suggestions to Remember Source: National Parkinson Foundation, Inc. http://www.parkinson.org/suggest.htm

•

Specific Conditions/Aspects Bladder Problems in Parkinson Disease Source: National Parkinson Foundation, Inc. http://www.parkinson.org/bladder.htm Difficulty Walking in Parkinson Disease Source: National Parkinson Foundation, Inc. http://www.parkinson.org/walking.htm Drooling in Parkinson Disease: New Treatment, New Hope Source: National Parkinson Foundation, Inc. http://www.parkinson.org/drooling.htm Introduction to Speech and Swallowing Problems Associated With Parkinson's Disease Source: National Parkinson Foundation, Inc. http://www.parkinson.org/swallow.htm Muscle Cramps Source: National Parkinson Foundation, Inc. http://www.parkinson.org/muscramps02.htm Nine Scientific Pathways to Understanding Parkinsons Source: Parkinson's Disease Foundation http://www.pdf.org/AboutPDF/nine_pathways.cfm Parenthood and Parkinsons Disease Source: Parkinson's Disease Foundation http://www.pdf.org/AboutPDF/parenthood.cfm Parkinson Disease at an Early Age Source: National Parkinson Foundation, Inc. http://www.parkinson.org/earlypd.htm Shortness of Breath in Parkinson Disease Source: National Parkinson Foundation, Inc. http://www.parkinson.org/breath.htm Sleep Disturbances in Parkinson's Disease Source: National Parkinson Foundation, Inc. http://www.parkinson.org/SleepDisturbances.htm Visual Disturbances in Parkinson's Disease Source: National Parkinson Foundation, Inc. http://www.parkinson.org/visual.htm

Patient Resources

•

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From the National Institutes of Health Parkinson's Disease Backgrounder Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/pubs/parkinson%27s_disease_ba ckgrounder.htm Parkinson's Disease: Hope Through Research Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/pubs/parkinson_disease_htr.htm

•

Latest News Brain Stimulation Benefit for Parkinson's Lasts Source: 11/12/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14633 .html Investigators Explore Selective Silencing of Disease Genes Source: 10/15/2003, National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/news_article_gene_silencing.htm Major New Finding on Genetics of Parkinson's Disease Zeroes In on Activity of Alpha Synuclein Source: 10/30/2003, National Human Genome Research Institute, National Institute of Neurological Disorders and Stroke, National Institute on Aging http://www.nih.gov/news/pr/oct2003/nia-30.htm Study Links Pesticides with Parkinson's Disease Source: 11/13/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14661 .html Yeast Model Yields Insights into Parkinson's Disease Source: 12/04/2003, National Institute of Neurological Disorders and Stroke http://www.nih.gov/news/pr/dec2003/ninds-04.htm

•

Law and Policy Medicare to Cover Deep Brain Stimulation for Essential Tremor and Parkinson's Disease Source: Social Security Administration http://www.seniors.gov/articles/0203/deep-brain.htm

•

Lists of Print Publication Available Publications Source: National Parkinson Foundation, Inc. http://www.parkinson.org/literatu.htm

•

Organizations National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/

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National Parkinson Foundation Source: National Parkinson Foundation, Inc. http://www.parkinson.org/ Parkinson's Disease Foundation http://www.pdf.org/index.cfm We Move http://www.wemove.org/ •

Research Bone Marrow Generates New Neurons in Human Brains Source: National Institute of Neurological Disorders and Stroke http://www.nih.gov/news/pr/jan2003/ninds-20.htm Brain-Cell Growth Protein Shows Promise For Parkinson's Patients in Early Human Trial Source: Parkinson's Disease Foundation http://www.pdf.org/news/news.cfm?selectedItem=105&type=1&returnURL=new s%252Ecfm%253Ftype%253D1 Combination of Two Widely Used Pesticides Linked to Parkinson's Disease Source: National Institute of Environmental Health Sciences http://www.niehs.nih.gov/centers/2001news/ctrnews5.htm Dystonia Protein Linked to Problem Common in Other Neurological Disorders Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/news_article_torsion_dystonia.htm Engineered Protein Yields Hopeful Results Source: Parkinson's Disease Foundation http://www.pdf.org/AboutPDF/engineeredprotection.cfm Investigators Explore Selective Silencing of Disease Genes Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/news_article_gene_silencing.htm Life and Death of a Neuron Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/pubs/NINDS_Neuron.htm New Drugs Protect Nerve Cells in Parkinson Mice Source: National Institute on Aging http://www.nih.gov/news/pr/sep2002/nia-25.htm New Findings About Parkinson's Disease: Coffee and Hormones Don't Mix Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/news_article_parkinson_caffeine_hr t.htm Research Brief: Cells That Live and Let Die Source: National Institute of General Medical Sciences http://www.nigms.nih.gov/news/releases/brief_steller.html Scientists Pinpoint Gene Influencing Age-at-Onset of Alzheimers, Parkinsons Source: National Institute on Aging http://www.nia.nih.gov/news/pr/2003/1021b.htm

Patient Resources

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Study Suggests Coenzyme Q10 Slows Functional Decline in Parkinson's Disease Source: National Institute of Neurological Disorders and Stroke http://www.nih.gov/news/pr/oct2002/ninds-14.htm What's in a Connection? A Look at Protein Patterns within Synapses Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/news_article_synapses.htm You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on Parkinson’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: •

Oral Health Care and Parkinson's Disease Source: Staten Island, NY: American Parkinson Disease Association, Inc. (APDA). 1996. 4 p. Contact: Available from American Parkinson Disease Association, Inc. (APDA). 1250 Hylan Boulevard, Suite 4B, Staten Island, NY 10305. (718) 981-8001 or (800) 223-2732; Fax (718) 981-4399. PRICE: Single copy free. Summary: This fact sheet provides basic information about the oral health needs of people with Parkinson's disease (PD). The fact sheet first outlines some usual oral health findings in patients with PD. There is an increase in dental caries and in accumulation of dental plaque associated with increased gum inflammation and periodontal disease, overt tooth mobility, and pain. This is due to reduction of hand to mouth mobility in PD and in part the loss of toothbrushing skills. In addition, when patients wear removable partial and complete dentures for a long time, the fit is poor and usually there is a loss of bite stability. The fact sheet then outlines treatment options for these dental and oral health concerns. The remainder of the fact sheet addresses quality of life issues related to the need for dental care. These include disorders of swallowing, disorders of nutrition, disorders of language and speech communication, loss of self esteem, impairment of job and vocational function, and impairment of social and community communication. The fact sheet concludes with a few resource organizations through which readers can locate dentists familiar with PD.

246 Parkinson’s 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 “Parkinson’s disease” (or synonyms). The following was recently posted: •

Evaluation of surgery for Parkinson's disease. A report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. The Task Force on Surgery for Parkinson's Disease Source: American Academy of Neurology - Medical Specialty Society; 1999 December; 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2830&nbr=2056&a mp;string=Parkinson''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: •

Depression and Parkinson's Disease Summary: Depression can strike anyone, but people with Parkinson's disease, a progressive brain disorder affecting more than 500,000 Americans, may be at greater risk. Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6898

•

Facts About Progressive Supranuclear Palsy.PSP Summary: PSP is a rare, degenerative brain disorder related to Parkinson's disease. It strikes middle aged adults and the elderly, slightly more men than women and affects 6.4 in 100,000. Source: Society for Progressive Supranuclear Palsy http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7729

•

Parkinson's Disease Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2898

Patient Resources

•

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Parkinson's Disease (NINDS) Summary: Parkinson's disease belongs to a group of conditions called motor system disorders. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6873

•

Parkinson's Disease Foundation Expert Resource Center Summary: Search by keyword or category here to find answers to questions about Parkinson's disease. Source: Parkinson's Disease Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7771

•

Parkinson's Disease: How Occupational Therapy Can Help Summary: healthfinder® — your guide to reliable health information health library just for you health care organizations search: go help | about healthfinder® Parkinson's Source: American Occupational Therapy Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7345 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 Parkinson’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/

248 Parkinson’s Disease

•

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

•

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

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

Parkinson's Disease Foundation, Inc Telephone: (212) 923-4700 Toll-free: (800) 457-6676 Fax: (212) 923-4778 Email: [email protected] Web Site: http://www.pdf.org Background: Parkinson s Disease Foundation, Inc., is a national not-for-profit organization dedicated to funding medical research to investigate the cause and cure of Parkinson s disease and related disorders. Established in 1957, the Foundation has a post-doctoral training program, offers extramural research grants, and makes referrals to physicians who treat Parkinson s disease. It strives to provide individuals with Parkinson's disease a better quality of life and, ultimately, find the cause and a cure. Other activities of the organization include counseling, supporting advocacy efforts, and providing referrals to self-help groups. In addition, the Foundation has a Research Advisory Board composed of internationally known neurological scientists. The Parkinson s Disease Foundation conducts symposia and distributes a variety of educational materials including brochures, booklets, a manual for health care professionals, and a regular newsletter. Relevant area(s) of interest: Parkinson's Disease

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

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The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “Parkinson’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 “Parkinson’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 “Parkinson’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 “Parkinson’s disease” (or a synonym) into the search box, and click “Submit Query.”

251

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.26

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

26

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

252 Parkinson’s Disease

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)27: •

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/

27

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

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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/

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

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

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

•

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

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

•

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/

Finding Medical Libraries

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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

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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

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

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

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

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

•

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

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

•

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/

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•

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 Parkinson’s disease: •

Basic Guidelines for Parkinson’s Disease Cerebrovascular disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000726.htm Hypoparathyroidism Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000385.htm Parkinson's disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000755.htm Parkinson's disease - resources Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002196.htm

•

Signs & Symptoms for Parkinson’s Disease Anxiety, stress, and tension Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm

258 Parkinson’s Disease

Confusion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003205.htm Constipation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003125.htm Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Difficulty eating Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm Difficulty speaking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003204.htm Difficulty swallowing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm Difficulty with walking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003199.htm Dizziness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003093.htm Drool Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003048.htm Drooling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003048.htm Gait (walking pattern) changes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003199.htm Hallucinations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003258.htm Hypotension Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm Incontinence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003142.htm Loss of balance Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003093.htm Memory loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003257.htm Movement, uncontrolled - slow Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003197.htm

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Muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Muscle aches Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003178.htm Muscle atrophy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003188.htm Muscle rigidity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Myalgia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003178.htm Nausea/vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Sexual dysfunction Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003164.htm Shuffling walk Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003199.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Stria Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003287.htm Tiredness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm •

Diagnostics and Tests for Parkinson’s Disease Dopamine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003561.htm MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm

•

Background Topics for Parkinson’s Disease Exercise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Parkinson's disease - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002196.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm

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Toxins Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002331.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

261

PARKINSON’S DISEASE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acoustic: Having to do with sound or hearing. [NIH] Actin: Essential component of the cell skeleton. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [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] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections.

262 Parkinson’s Disease

Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among 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] Aggravation: An increasing in seriousness or severity; an act or circumstance that intensifies, or makes worse. [EU] 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] AK: Enzyme of the biosynthetic pathway. [NIH] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular

Dictionary 263

quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Akinesia: 1. Absence or poverty of movements. 2. The temporary paralysis of a muscle by the injection of procaine. [EU] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] 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] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of Influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH]

264 Parkinson’s Disease

Aminoethyl: A protease inhibitor. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [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] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analeptic: A drug which acts as a restorative, such as caffeine, amphetamine, pentylenetetrazol, etc. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [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] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Ansa: A turn or bend in a thread or line; a bend in a wire; one of the patterns formed by the dermal ridges on the finger tips. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Dictionary 265

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] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [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] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [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] Antiphlogistic: An agent that counteracts inflammation and fever. [EU] Antiproliferative: Counteracting a process of proliferation. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and

266 Parkinson’s Disease

tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Aphasia: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. [NIH] Aplastic anemia: A condition in which the bone marrow is unable to produce blood cells. [NIH]

Apomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. [NIH] 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] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Articulation: The relationship of two bodies by means of a moveable joint. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the

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biological or pharmacological potency of a drug. [EU] Astringent: Causing contraction, usually locally after topical application. [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] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] 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] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [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] 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

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coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] 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] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] 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] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biomolecular: A scientific field at the interface between advanced computing and biotechnology. [NIH] 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]

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Blood Coagulation Disorders: Hemorrhagic and thrombotic disorders that occur as a consequence of abnormalities in blood coagulation due to a variety of factors sych as coagulation protein disorders, blood platelet disorders, blood protein disorders or nutritional conditions. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [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] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradykinesia: Abnormal slowness of movement; sluggishness of physical and mental responses. [EU] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Bromocriptine: A semisynthetic ergot alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion and is used to treat amenorrhea, galactorrhea, and female infertility, and has been proposed for Parkinson disease. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the

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buccal surface of a tooth. [EU] Burning Mouth Syndrome: A group of painful oral symptoms associated with a burning or similar sensation. There is usually a significant organic component with a degree of functional overlay; it is not limited to the psychophysiologic group of disorders. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calibration: Determination, by measurement or comparison with a standard, of the correct value of each scale reading on a meter or other measuring instrument; or determination of the settings of a control device that correspond to particular values of voltage, current, frequency, or other output. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [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] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [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] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH]

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Carotid Body: A small cluster of chemoreceptive and supporting cells located near the bifurcation of the internal carotid artery. The carotid body, which is richly supplied with fenestrated capillaries, senses the pH, carbon dioxide, and oxygen concentrations in the blood and plays a crucial role in their homeostatic control. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [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] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which

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oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Diseases: Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chaperonins: A class of sequence-related molecular chaperones found in bacteria, mitochondria, and plastids. Chaperonins are abundant constitutive proteins that increase in amount after stresses such as heat shock, bacterial infection of macrophages, and an increase in the cellular content of unfolded proteins. Bacterial chaperonins are major immunogens in human bacterial infections because of their accumulation during the stress of infection. Two members of this class of chaperones are chaperonin 10 and chaperonin 60. [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] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU]

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Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [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] Chiropractic: A system of treating bodily disorders by manipulation of the spine and other parts, based on the belief that the cause is the abnormal functioning of a nerve. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in cartilage. [NIH]

Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by

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calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical Protocols: Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [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] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [NIH] Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with welldefined distribution patterns in relation to time or place or both. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [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] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease

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inhibitor). [NIH] Community Networks: Organizations and individuals cooperating together toward a common goal at the local or grassroots level. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Compacta: Part of substantia nigra. [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] Compulsions: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [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]

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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 tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a

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myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Striatum: Striped gray and white matter consisting of the neostriatum and paleostriatum (globus pallidus). It is located in front of and lateral to the thalamus in each cerebral hemisphere. The gray substance is made up of the caudate nucleus and the lentiform nucleus (the latter consisting of the globus pallidus and putamen). The white matter is the internal capsule. [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] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cranial Nerves: Twelve pairs of nerves that carry general afferent, visceral afferent, special afferent, somatic efferent, and autonomic efferent fibers. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Criterion: A standard by which something may be judged. [EU] Crowns: A prosthetic restoration that reproduces the entire surface anatomy of the visible natural crown of a tooth. It may be partial (covering three or more surfaces of a tooth) or complete (covering all surfaces). It is made of gold or other metal, porcelain, or resin. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] 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] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior

278 Parkinson’s Disease

of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] 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] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [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] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH]

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Dental Abutments: Natural teeth or teeth roots used as anchorage for a fixed or removable denture or other prosthesis (such as an implant) serving the same purpose. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dental Plaque: A film that attaches to teeth, often causing dental caries and gingivitis. It is composed of mucins, secreted from salivary glands, and microorganisms. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Dentures: An appliance used as an artificial or prosthetic replacement for missing teeth and adjacent tissues. It does not include crowns, dental abutments, nor artificial teeth. [NIH] Deoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] 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,

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liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discriminant Analysis: A statistical analytic technique used with discrete dependent variables, concerned with separating sets of observed values and allocating new values. It is sometimes used instead of regression analysis. [NIH] 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] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissection: Cutting up of an organism for study. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Distemper: A name for several highly contagious viral diseases of animals, especially canine distemper. In dogs, it is caused by the canine distemper virus (distemper virus, canine). It is characterized by a diphasic fever, leukopenia, gastrointestinal and respiratory inflammation and sometimes, neurologic complications. In cats it is known as feline panleukopenia. [NIH] Distemper Virus, Canine: A species of morbillivirus causing distemper in dogs, wolves, foxes, raccoons, and ferrets. [NIH] Disulphides: A covalent bridge formed by the oxidation of two cysteine residues to a cystine residue. The-S-S-bond is very strong and its presence confers additional stability. [NIH]

Dithiothreitol: A reagent commonly used in biochemical studies as a protective agent to prevent the oxidation of SH (thiol) groups and for reducing disulphides to dithiols. [NIH] Diuresis: Increased excretion of urine. [EU] Donepezil: A drug used in the treatment of Alzheimer's disease. It belongs to the family of drugs called cholinesterase inhibitors. It is being studied as a treatment for side effects caused by radiation therapy to the brain. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [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] Dopamine Agonists: Drugs that bind to and activate dopamine receptors. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when

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the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Doxycycline: A synthetic tetracycline derivative with a range of antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species. Animal studies suggest that it may cause less tooth staining than other tetracyclines. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] 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] Dysarthria: Imperfect articulation of speech due to disturbances of muscular control which result from damage to the central or peripheral nervous system. [EU] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyspareunia: Painful sexual intercourse. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ectopic: Pertaining to or characterized by ectopia. [EU] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [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] Elastin: The protein that gives flexibility to tissues. [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] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrochemistry: The study of chemical changes resulting from electrical action and electrical activity resulting from chemical changes. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU]

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Electron microscope: A microscope (device used to magnify small objects) that uses electrons (instead of light) to produce an enlarged image. An electron microscopes shows tiny details better than any other type of microscope. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Electroplating: Coating with a metal or alloy by electrolysis. [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] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]

Emetic: An agent that causes vomiting. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH]

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Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Entopeduncular Nucleus: A portion of the nucleus of ansa lenticularis located medial to the posterior limb of the internal capsule, along the course of the ansa lenticularis and the inferior thalamic peduncle or as a separate nucleus within the internal capsule adjacent to the medial globus pallidus. (NeuroNames, http://rprcsgi.rprc. washington.edu/neuronames/ (September 28, 1998)) In non-primates, the entopeduncular nucleus is analogous to both the medial globus pallidus and the entopeduncular nucleus of human. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [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] 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] 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] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone

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deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]

Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [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] 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] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [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] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH]

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Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fee Schedules: A listing of established professional service charges, for specified dental and medical procedures. [NIH] Feline Panleukopenia: A highly contagious DNA virus infection of the cat family and of mink, characterized by fever, enteritis and bone marrow changes. It is also called feline ataxia, feline agranulocytosis, feline infectious enteritis, cat fever, cat plague, show fever. [NIH]

Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [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] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]

Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]

Fungicide: An agent that destroys fungi. [EU] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gait: Manner or style of walking. [NIH]

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Gallate: Antioxidant present in tea. [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] 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] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] 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] Gene Products, rev: Trans-acting nuclear proteins whose functional expression are required for HIV viral replication. Specifically, the rev gene products are required for processing and translation of the HIV gag and env mRNAs, and thus rev regulates the expression of the viral structural proteins. rev can also regulate viral regulatory proteins. A cis-acting antirepression sequence (CAR) in env, also known as the rev-responsive element (RRE), is responsive to the rev gene product. rev is short for regulator of virion. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genes, env: DNA sequences that form the coding region for the viral envelope (env) proteins in retroviruses. The env genes contain a cis-acting RNA target sequence for the rev protein (= gene products, rev), termed the rev-responsive element (RRE). [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]

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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] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is referred to as periodontitis. Called also oulitis and ulitis. [EU] 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] Globus Pallidus: The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] 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]

Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [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] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH]

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Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Haematemesis: The vomiting of blood. [EU] Hallucination: A sense perception without a source in the external world; a perception of an external stimulus object in the absence of such an object. [EU] Handedness: Preference for using right or left hand. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [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] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Policy: Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heat-Shock Proteins: Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions. [NIH] Heat-Shock Proteins 90: A class of molecular chaperones whose members act in the mechanism of signal transduction by steroid receptors. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level

Dictionary 289

may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhagic Disorders: Spontaneous or near spontaneous bleeding caused by a defect in clotting mechanisms (blood coagulation disorders) or another abnormality causing a structural flaw in the blood vessels (vascular hemostatic disorders). [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatotoxic: Toxic to liver cells. [EU] Herbicide: A chemical that kills plants. [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] Heterodimers: Zippered pair of nonidentical proteins. [NIH] 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]

Heterozygote: An individual having different alleles at one or more loci in homologous chromosome segments. [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] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histology: The study of tissues and cells under a microscope. [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] Hospital Records: Compilations of data on hospital activities and programs; excludes patient medical records. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary,

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which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperventilation: A pulmonary ventilation rate faster than is metabolically necessary for the exchange of gases. It is the result of an increased frequency of breathing, an increased tidal volume, or a combination of both. It causes an excess intake of oxygen and the blowing off of carbon dioxide. [NIH] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [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] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [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]

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Idiopathic: Describes a disease of unknown cause. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] 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] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] 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] 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] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [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] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators

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or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [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]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [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] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [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] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] 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] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [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

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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] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] 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 neurotransmitter receptors are not included. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These

294 Parkinson’s Disease

may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [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] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [EU] Jealousy: An irrational reaction compounded of grief, loss of self-esteem, enmity against the rival and self criticism. [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] Keratolytic: An agent that promotes keratolysis. [EU] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinesthesis: The sense by which muscular motion, weight, position, etc., are perceived. [NIH]

Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] 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] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [NIH] Lethal: Deadly, fatal. [EU] Leukemia: Cancer of blood-forming tissue. [NIH]

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Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [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] Ligands: A RNA simulation method developed by the MIT. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lisuride: An ergot derivative that acts as an agonist at dopamine D2 receptors, may also act as an antagonist at dopamine D1 receptors, and as an agonist at some serotonin receptors. It has been used in parkinsonism but it may be hepatotoxic. It is commonly used as a research tool. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

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] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH]

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Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumbar puncture: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a spinal tap. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

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] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Macroglia: A type of neuroglia composed of astrocytes. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes

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which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Maneb: Manganese derivative of ethylenebisdithiocarbamate. It is used in agriculture as a fungicide and has been shown to cause irritation to the eyes, nose, skin, and throat. [NIH] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] 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 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] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the

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layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [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] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabotropic: A glutamate receptor which triggers an increase in production of 2 intracellular messengers: diacylglycerol and inositol 1, 4, 5-triphosphate. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylprednisolone: (6 alpha,11 beta)-11,17,21-Trihydroxy-6-methylpregna-1,4-diene-3,2dione. A prednisolone derivative which has pharmacological actions similar to prednisolone. [NIH] Methyltransferase: A drug-metabolizing enzyme. [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] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis

Dictionary 299

and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] 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] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [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] Microwaves: That portion of the electromagnetic spectrum lying between UHF (ultrahigh frequency) radio waves and heat (infrared) waves. Microwaves are used to generate heat, especially in some types of diathermy. They may cause heat damage to tissues. [NIH] Micturition: The passage of urine; urination. [EU] Minocycline: A semisynthetic staphylococcus infections. [NIH]

antibiotic

effective

against

tetracycline-resistant

Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Chaperones: A family of cellular proteins that mediate the correct assembly or disassembly of other polypeptides, and in some cases their assembly into oligomeric structures, but which are not components of those final structures. It is believed that chaperone proteins assist polypeptides to self-assemble by inhibiting alternative assembly pathways that produce nonfunctional structures. Some classes of molecular chaperones are the nucleoplasmins, the chaperonins, the heat-shock proteins 70, and the heat-shock proteins 90. [NIH] 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,

300 Parkinson’s Disease

pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] 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] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor Skills: Performance of complex motor acts. [NIH] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [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] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Music Therapy: The use of music as an adjunctive therapy in the treatment of neurological, mental, or behavioral disorders. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelodysplastic syndrome: Disease in which the bone marrow does not function normally.

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Also called preleukemia or smoldering leukemia. [NIH] 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] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]

Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoclonus: Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous systems diseases (e.g., epilepsy, myoclonic). Nocturnal myoclonus may represent a normal physiologic event or occur as the principal feature of the nocturnal myoclonus syndrome. (From Adams et al., Principles of Neurology, 6th ed, pp102-3). [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] N-acetyl: Analgesic agent. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United 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] 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] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining

302 Parkinson’s Disease

to neoplasia (= the formation of a neoplasm). [EU] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Nervous System Diseases: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [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] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]

Neuregulins: A family of peptides originally found as factors that stimulate the phosphorylation of the erbB-2 receptor. Multiple variant forms of neuregulins occur due to alternative splicing of their mRNAs. The neuregulins include products from the three known genes (NGR1, NGR2 and NGR3). [NIH] Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]

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] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [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] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of

Dictionary 303

emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or 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 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] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neuropsychology: A branch of psychology which investigates the correlation between experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology. [NIH] Neurosciences: The scientific disciplines concerned with the embryology, anatomy, physiology, biochemistry, pharmacology, etc., of the nervous sytem. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis. [EU]

Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] 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] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It

304 Parkinson’s Disease

is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

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] Nortriptyline: A metabolite of amitryptyline that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [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] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Nursing Staff: Personnel who provide nursing service to patients in an organized facility, institution, or agency. [NIH] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] 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] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oophorectomy: Surgery to remove one or both ovaries. [NIH]

Dictionary 305

Opacity: Degree of density (area most dense taken for reading). [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [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 metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paranoia: A psychotic disorder marked by persistent delusions of persecution or delusional

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jealousy and behaviour like that of the paranoid personality, such as suspiciousness, mistrust, and combativeness. It differs from paranoid schizophrenia, in which hallucinations or formal thought disorder are present, in that the delusions are logically consistent and that there are no other psychotic features. The designation in DSM III-R is delusional (paranoid) disorders, with five types : persecutory, jealous, erotomanic, somatic, and grandiose. [EU] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]

Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partnership Practice: A voluntary contract between two or more doctors who may or may not share responsibility for the care of patients, with proportional sharing of profits and losses. [NIH] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pergolide: A long-acting dopamine agonist which is effective in the treatment of Parkinson's disease and hyperprolactinemia. It has also been observed to have antihypertensive effects. [NIH]

Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periodicity: The tendency of a phenomenon to recur at regular intervals; in biological

Dictionary 307

systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [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] Perivascular: Situated around a vessel. [EU] Peroneal Nerve: The lateral of the two terminal branches of the sciatic nerve. The peroneal (or fibular) nerve provides motor and sensory innervation to parts of the leg and foot. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the

308 Parkinson’s Disease

formation of an ester bond between the compound and a phosphorus moiety. [NIH] Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [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] Phytic Acid: Complexing agent for removal of traces of heavy metal ions. It acts also as a hypocalcemic agent. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]

Pilot study: The initial study examining a new method or treatment. [NIH] Pitch: The subjective awareness of the frequency or spectral distribution of a sound. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placebo Effect: An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion. [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] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH]

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Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [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] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] 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] Postal Service: The functions and activities carried out by the U.S. Postal Service, foreign postal services, and private postal services such as Federal Express. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postherpetic Neuralgia: Variety of neuralgia associated with migraine in which pain is felt in or behind the eye. [NIH] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Postural: Pertaining to posture or position. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH]

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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] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [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] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Preleukemia: Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [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] Private Practice: Practice of a health profession by an individual, offering services on a person-to-person basis, as opposed to group or partnership practice. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [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] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH]

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Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [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] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] 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] Protein Subunits: Single chains of amino acids that are the units of a multimeric protein. They can be identical or non-identical subunits. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] 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]

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Protozoal: Having to do with the simplest organisms in the animal kingdom. Protozoa are single-cell organisms, such as ameba, and are different from bacteria, which are not members of the animal kingdom. Some protozoa can be seen without a microscope. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychological Tests: Standardized tests designed to measure abilities, as in intelligence, aptitude, and achievement tests, or to evaluate personality traits. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]

Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] 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] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Putamen: The largest and most lateral of the basal ganglia lying between the lateral medullary lamina of the globus pallidus and the external capsule. It is part of the neostriatum and forms part of the lentiform nucleus along with the globus pallidus. [NIH] Pyramidal Tracts: Fibers that arise from cells within the cerebral cortex, pass through the medullary pyramid, and descend in the spinal cord. Many authorities say the pyramidal

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tracts include both the corticospinal and corticobulbar tracts. [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] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Raclopride: A substituted benzamide that has antipsychotic properties. It is a dopamine D2 receptor antagonist. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radio Waves: That portion of the electromagnetic spectrum beyond the microwaves, with wavelengths as high as 30 KM. They are used in communications, including television. Short Wave or HF (high frequency), UHF (ultrahigh frequency) and VHF (very high frequency) waves are used in citizen's band communication. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radius: The lateral bone of the forearm. [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] Reaction Time: The time from the onset of a stimulus until the organism responds. [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

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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] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [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] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [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] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH]

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Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Reticulata: Part of substantia nigra. [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] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH]

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Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Rhythmicity: Regular periodicity. [NIH] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] 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]

Rotenone: A botanical insecticide that is an inhibitor of mitochondrial electron transport. [NIH]

Rye: A hardy grain crop, Secale cereale, grown in northern climates. It is the most frequent host to ergot (claviceps), the toxic fungus. Its hybrid with wheat is triticale, another grain. [NIH]

Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to

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characterize schizophrenia. [NIH] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] 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] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sediment: A precipitate, especially one that is formed spontaneously. [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] Selegiline: A selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Self-Help Groups: Organizations which provide an environment encouraging social interactions through group activities or individual relationships especially for the purpose of rehabilitating or supporting patients, individuals with common health problems, or the elderly. They include therapeutic social clubs. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [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] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [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]

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Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [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] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [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] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of

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the body. [NIH] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. [NIH] Somatotropin: A small peptide hormone released by the anterior pituitary under hypothalamic control. Somatotropin, or growth hormone, stimulates mitosis, cell growth, and, for some cell types, differentiation in many tissues of the body. It has profound effects on many aspects of gene expression and metabolism. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Speech Intelligibility: Ability to make speech sounds that are recognizable. [NIH] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spinal tap: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a lumbar puncture. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU]

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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] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stereotactic: Radiotherapy that treats brain tumors by using a special frame affixed directly to the patient's cranium. By aiming the X-ray source with respect to the rigid frame, technicians can position the beam extremely precisely during each treatment. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] 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] Stria: 1. A streak, or line. 2. A narrow bandlike structure; a general term for such longitudinal collections of nerve fibres in the brain. [EU] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Strychnine: An alkaloid found in the seeds of nux vomica. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea, and as a rat poison. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Subthalamus: A transition zone in the anterior part of the diencephalon interposed between the thalamus, hypothalamus, and tegmentum of the mesencephalon. Components of the

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subthalamus include the subthalamic nucleus, zona incerta, nucleus of field H, and the nucleus of ansa lenticularis. The latter contains the entopeduncular nucleus. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [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] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [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] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] 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

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releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temperament: Predisposition to react to one's environment in a certain way; usually refers to mood changes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] 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] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the

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lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Tibial Nerve: The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory innervation to parts of the calf and foot. [NIH] Tidal Volume: The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are TV or V with subscript T. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonicity: The normal state of muscular tension. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures 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

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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] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] 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] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transposase: An enzyme that binds to single-stranded DNA. It is thought to recognize the repetitive ends of a transposon and to participate in the cleavage of the recipient site into which the new transposon copy inserts. EC 2.7.7.-. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Trihexyphenidyl: A centrally acting muscarinic antagonist used in the treatment of parkinsonism and drug-induced extrapyramidal movement disorders and as an antispasmodic. [NIH]

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Trophic: Of or pertaining to nutrition. [EU] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] 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] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urban Population: The inhabitants of a city or town, including metropolitan areas and suburban areas. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract.

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[NIH]

Urinate: To release urine from the bladder to the outside. [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] Urodynamic: Measures of the bladder's ability to hold and release urine. [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] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [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] Valerian: Valeriana officinale, an ancient, sedative herb of the large family Valerianaceae. The roots were formerly used to treat hysterias and other neurotic states and are presently used to treat sleep disorders. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Hemostatic Disorders: Alterations in the mechanical integrity or structure of the blood vessels leading to bleeding disorders. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venter: Belly. [NIH] 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] Ventral Tegmental Area: A region in the mesencephalon which is dorsomedial to the substantia nigra and ventral to the red nucleus. The mesocortical and mesolimbic dopaminergic systems originate here, including an important projection to the nucleus accumbens. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of schizophrenia. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] 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] Viral Proteins: Proteins found in any species of virus. [NIH]

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Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visual Perception: The selecting and organizing of visual stimuli based on the individual's past experience. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Vomica: The profuse and sudden expectoration of pus and putrescent matter. An abnormal cavity in an organ especially in the lung, caused by suppuration and the breaking down of tissue. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to 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] Zebrafish: A species of North American fishes of the family Cyprinidae. They are used in embryological studies and to study the effects of certain chemicals on development. [NIH]

329

INDEX 1 1-Methyl-4-phenyl-1,2,3,6tetrahydropyridine, 68, 123, 147, 150, 261 A Abdomen, 186, 261, 269, 295, 305, 306, 319, 320, 323 Abdominal, 197, 261, 305 Aberrant, 8, 261 Ablation, 34, 66, 261 Acceptor, 261, 295, 305 Acetylcholine, 175, 181, 261, 273, 303, 304 Acidity, 261, 307 Acoustic, 4, 140, 261 Actin, 261, 302 Activities of Daily Living, 47, 261 Adaptability, 261, 271, 272 Adaptation, 7, 35, 82, 140, 261, 308 Adenine, 261 Adenosine, 130, 261, 270, 307 Adenosine Triphosphate, 130, 261, 307 Adenovirus, 26, 46, 67, 198, 261 Adjunctive Therapy, 262, 300 Adjustment, 35, 261, 262 Adjuvant, 262, 286 Adrenergic, 197, 262, 265, 280, 283, 321, 325 Adverse Effect, 196, 262, 266, 274, 318 Aerobic, 23, 262, 299, 305 Aerobic Metabolism, 262, 305 Aerobic Respiration, 262, 305 Afferent, 106, 262, 277, 310 Affinity, 262, 267, 274, 318 Agar, 262, 308 Age of Onset, 31, 262 Aggravation, 18, 262 Agonist, 16, 22, 43, 80, 82, 85, 138, 155, 171, 177, 262, 266, 269, 280, 295, 303, 306 AK, 68, 102, 131, 139, 262 Akathisia, 70, 262, 265 Akinesia, 133, 193, 210, 263 Alertness, 263, 270 Algorithms, 263, 268 Alkaloid, 263, 269, 300, 303, 320 Alleles, 27, 263, 289 Alpha Particles, 263, 313 Alternative medicine, 220, 263 Alternative Splicing, 263, 302

Amantadine, 51, 71, 94, 117, 130, 162, 224, 263 Ameliorating, 191, 263 Amenorrhea, 263, 269 Amino Acid Sequence, 263, 265, 284, 286 Aminoethyl, 196, 264 Amplification, 56, 264 Amygdala, 264, 268, 295, 322 Amyloid, 6, 66, 264 Anabolic, 194, 264 Anaesthesia, 264, 292 Anal, 264, 280, 296 Analeptic, 264, 320 Analgesic, 190, 197, 264, 300, 301 Analog, 61, 264 Anaphylatoxins, 264, 275 Anatomical, 59, 64, 209, 264, 267, 273, 282, 291, 298, 317 Anemia, 192, 237, 264, 285 Animal model, 9, 12, 14, 28, 31, 38, 39, 40, 42, 43, 49, 53, 57, 62, 64, 70, 132, 138, 264 Anions, 264, 294, 318, 321 Anorexia, 194, 264 Ansa, 264, 283, 321 Antagonism, 264, 270, 274 Antibacterial, 264, 319 Antibiotic, 264, 299, 319, 322 Antibodies, 7, 30, 42, 52, 60, 265, 288, 291, 296, 308 Antibody, 7, 8, 24, 30, 196, 262, 265, 275, 283, 288, 289, 291, 292, 297, 313, 319 Anticholinergic, 155, 193, 265 Anticonvulsant, 265, 316 Antidepressant, 105, 265 Antiemetic, 265, 266 Antigen, 196, 262, 265, 275, 289, 290, 291, 292, 293, 297, 299, 313 Antigen-Antibody Complex, 265, 275 Antihypertensive, 265, 306 Anti-infective, 265, 290 Anti-inflammatory, 6, 49, 99, 265, 287 Antimetabolite, 265, 279 Antimicrobial, 265, 281 Antioxidant, 42, 54, 62, 220, 265, 286, 305 Antiphlogistic, 190, 265 Antiproliferative, 9, 265 Antipsychotic, 70, 265, 274, 302, 313 Antipyretic, 190, 266

330 Parkinson’s Disease

Antiseptic, 266, 271 Antispasmodic, 266, 324 Antitussive, 190, 266 Antiviral, 263, 266, 279 Anus, 264, 266, 269, 274, 293 Anxiety, 179, 257, 263, 266, 304 Aorta, 266, 326 Apathy, 266, 302 Aphasia, 202, 266 Aplastic anemia, 76, 191, 266 Apomorphine, 117, 118, 149, 177, 227, 266 Apoptosis, 16, 51, 71, 170, 266, 271 Aptitude, 266, 312 Aqueous, 266, 268, 278, 290 Arginine, 264, 266, 304 Aromatic, 27, 266, 307 Arterial, 182, 266, 290, 311, 322 Arteries, 266, 269, 276, 298, 301 Artery, 92, 182, 266, 271, 276, 282, 301, 312, 315, 316 Articular, 266, 305 Articulation, 266, 281 Aspiration, 192, 266 Assay, 41, 266, 291, 313 Astringent, 267, 271 Astrocytes, 6, 267, 296, 298, 300 Ataxia, 236, 237, 267, 272, 285, 322 Atrium, 267, 326 Atrophy, 80, 122, 123, 137, 174, 195, 236, 237, 259, 267, 302 Atypical, 75, 267, 274, 304 Auditory, 72, 119, 132, 140, 156, 169, 171, 267, 310 Autoimmune disease, 267, 300 Autoimmunity, 191, 267 Autonomic, 32, 261, 266, 267, 277, 302, 304, 307, 321 Autonomic Nervous System, 267, 302, 307, 321 Autopsy, 7, 13, 37, 267 Axons, 267, 279, 293 B Bacterial Physiology, 261, 267 Bacteriophage, 267, 308, 324 Bacteriuria, 268, 325 Basal Ganglia Diseases, 267, 268, 273, 290 Base, 33, 48, 58, 190, 261, 268, 278, 279, 286, 294, 309, 322 Basement Membrane, 268, 284, 294 Beta-pleated, 264, 268 Bilateral, 21, 69, 73, 78, 81, 85, 103, 106, 119, 130, 132, 133, 153, 158, 174, 268

Bile, 268, 286, 295 Biochemical, 21, 27, 28, 42, 55, 74, 133, 139, 193, 195, 209, 263, 265, 268, 280, 305, 317 Biological therapy, 268, 288 Biomarkers, 10, 132, 268 Biomolecular, 45, 268 Biotechnology, 65, 69, 209, 220, 233, 235, 236, 237, 238, 268 Bladder, 32, 180, 242, 268, 273, 291, 300, 302, 311, 325, 326 Blood Coagulation, 268, 269, 270, 289 Blood Coagulation Disorders, 269, 289 Blood Platelets, 269, 317 Blood pressure, 70, 182, 197, 265, 269, 270, 273, 290, 300, 318 Blood vessel, 269, 270, 272, 273, 282, 289, 294, 295, 306, 318, 320, 322, 323, 326 Blood-Brain Barrier, 7, 194, 269, 295 Body Fluids, 268, 269, 318, 325 Body Mass Index, 105, 269 Bone Marrow, 191, 244, 266, 269, 285, 286, 291, 296, 300, 310, 318, 320 Bone scan, 269, 316 Bowel, 205, 264, 269, 279, 320 Bowel Movement, 269, 279, 320 Bradykinesia, 21, 22, 23, 152, 192, 269 Bradykinin, 269, 304 Brain Stem, 119, 140, 269, 272, 302 Branch, 255, 269, 277, 282, 303, 306, 312, 319, 321, 322, 323 Breakdown, 175, 195, 269, 279, 286, 305 Bromocriptine, 75, 104, 116, 118, 123, 224, 269 Buccal, 15, 269 Burning Mouth Syndrome, 5, 270 C Caffeine, 19, 20, 219, 244, 264, 270 Calcium, 270, 275, 301, 318 Calibration, 35, 270 Capsules, 270, 286 Carbohydrates, 262, 270, 271, 305 Carbon Dioxide, 270, 271, 290, 315 Carcinogenesis, 270, 308 Carcinogenic, 270, 292, 304, 311 Carcinogens, 270, 304 Cardiac, 270, 281, 283, 284, 301 Cardiology, 177, 270 Cardiovascular, 6, 191, 270, 317 Cardiovascular disease, 6, 191, 270 Carotene, 162, 270, 315 Carotenoids, 42, 270 Carotid Body, 72, 271, 273

Index 331

Carrier Proteins, 271, 313 Case report, 160, 271, 274 Case series, 271, 274 Caspase, 25, 66, 72, 147, 271 Catechol, 10, 90, 117, 271 Catecholamine, 271, 280 Catheter, 180, 182, 186, 271 Caudate Nucleus, 98, 268, 271, 277, 302, 304 Causal, 24, 271 Causality, 97, 271 Cell Adhesion, 271, 293 Cell Death, 16, 25, 38, 42, 43, 51, 54, 97, 130, 147, 170, 179, 266, 271 Cell Differentiation, 271, 318 Cell Division, 236, 267, 271, 278, 288, 297, 299, 308, 311 Cell membrane, 34, 271, 279, 286, 293, 294, 307, 309 Cell proliferation, 271, 318 Cell Respiration, 262, 271, 299, 305, 315 Cell Survival, 39, 272, 288 Cell Transplantation, 154, 155, 272 Central Nervous System Diseases, 194, 195, 272 Cerebellar, 63, 191, 195, 267, 272, 314, 324 Cerebellar Diseases, 267, 272, 324 Cerebellum, 195, 272, 309, 314 Cerebral, 105, 134, 146, 152, 155, 184, 195, 240, 267, 268, 269, 272, 277, 278, 283, 284, 285, 301, 312, 322, 323 Cerebral Cortex, 267, 272, 284, 285, 301, 312 Cerebral hemispheres, 268, 269, 272, 322 Cerebrospinal, 48, 272, 296, 319 Cerebrospinal fluid, 48, 272, 296, 319 Cerebrovascular, 195, 257, 268, 270, 272, 322 Cerebrum, 272, 322, 325 Cervical, 160, 272 Cervix, 272 Chaperonins, 272, 299 Character, 272, 278 Chelation, 88, 272 Chemoreceptor, 266, 273 Chemotactic Factors, 273, 275 Chin, 119, 131, 139, 140, 273, 298 Chiropractic, 160, 273 Cholesterol, 268, 273, 276, 297 Cholinergic, 107, 193, 197, 265, 273, 303 Cholinesterase Inhibitors, 273, 280 Chondroitin sulfate, 127, 273

Chorea, 170, 265, 273 Chromatin, 266, 273 Chromosomal, 8, 264, 273, 316 Chromosome, 7, 14, 27, 28, 68, 69, 273, 289, 295, 316 Chronic Disease, 17, 273 Chronic renal, 273, 309 Cirrhosis, 273, 288 CIS, 273, 286, 315 Citrus, 158, 274 Clinical Medicine, 40, 274, 310 Clinical Protocols, 11, 12, 274 Clinical study, 182, 274, 276 Clone, 28, 191, 274 Cloning, 268, 274 Clozapine, 76, 104, 117, 224, 274 Cluster Analysis, 24, 274 Cofactor, 274, 311 Cognition, 86, 106, 138, 168, 171, 175, 180, 181, 212, 220, 274, 302 Collagen, 63, 263, 268, 274, 286, 308, 311 Collapse, 269, 274, 318 Colon, 236, 274, 294 Combination Therapy, 274, 284 Community Networks, 211, 275 Comorbidity, 212, 275 Compacta, 21, 31, 125, 275 Complement, 61, 264, 275, 293, 297 Complementary and alternative medicine, 129, 165, 275 Complementary medicine, 129, 275 Compulsions, 275, 304 Computational Biology, 233, 235, 275 Computed tomography, 135, 181, 276, 316 Computerized tomography, 276 Conception, 276, 285, 319 Concomitant, 6, 195, 276 Cones, 276, 315 Confounding, 60, 276 Congestion, 266, 276 Conjugated, 276, 277 Connective Tissue, 269, 274, 276, 279, 285, 286, 296, 315 Consciousness, 264, 276, 278, 312 Constipation, 77, 108, 258, 266, 276 Constriction, 276, 294, 316 Consultation, 177, 276 Consumption, 19, 23, 184, 276, 305 Contraindications, ii, 276 Contralateral, 24, 133, 276, 298, 314 Controlled clinical trial, 31, 43, 87, 276 Controlled study, 116, 276

332 Parkinson’s Disease

Coordination, 31, 46, 51, 58, 133, 147, 272, 276, 300 Coronary, 270, 276, 298, 301 Coronary heart disease, 270, 276 Coronary Thrombosis, 276, 298, 301 Corpus, 277, 287, 302, 322 Corpus Striatum, 277, 287, 302 Cortex, 9, 12, 56, 195, 277, 283, 310, 314 Cortical, 13, 34, 38, 93, 96, 100, 137, 140, 152, 277, 310, 317, 322 Corticosteroids, 277, 287, 310 Cranial, 130, 272, 277, 288, 302, 304, 307 Cranial Nerves, 277, 302 Creatine, 42, 179, 277 Creatinine, 277 Criterion, 116, 277 Crowns, 277, 279 Cues, 72, 169, 171, 277 Curative, 277, 322 Cyclic, 270, 277, 288, 304 Cytochrome, 15, 90, 277 Cytochrome b, 90, 277 Cytogenetics, 277, 316 Cytokine, 6, 278 Cytoplasm, 266, 271, 278, 288, 302, 316, 322 Cytoskeleton, 63, 278, 293, 299 Cytotoxic, 26, 278, 318 Cytotoxicity, 26, 32, 80, 278 D Data Collection, 51, 278 De novo, 29, 58, 120, 278 Deamination, 278, 300 Decision Making, 17, 202, 278 Defense Mechanisms, 278, 293 Degenerative, 9, 51, 195, 240, 246, 278, 300, 305 Deletion, 40, 43, 266, 278 Delirium, 105, 265, 278 Delusions, 278, 305, 312 Dendrites, 278, 279, 303 Density, 28, 269, 278, 305 Dental Abutments, 279 Dental Care, 245, 279 Dental Caries, 245, 279 Dental Plaque, 245, 279 Dentate Gyrus, 279, 289 Dentists, 245, 279 Dentures, 245, 279 Deoxyglucose, 35, 137, 279 Deoxyribonucleic, 195, 279 Deoxyribonucleic acid, 195, 279

Deoxyribonucleotides, 279 Depolarization, 279, 318 Dermis, 279, 324 Detoxification, 19, 53, 279 Deuterium, 279, 290 Diagnostic procedure, 189, 220, 279 Diastolic, 279, 290 Diencephalon, 272, 279, 290, 302, 310, 320, 322 Digestion, 268, 269, 279, 295, 320 Digestive system, 187, 279 Dilatation, 280, 310 Dilution, 56, 280 Direct, iii, 7, 14, 21, 42, 67, 196, 212, 223, 274, 280, 296, 314, 321 Discrete, 280 Discriminant Analysis, 59, 280 Disease Progression, 5, 9, 10, 11, 13, 25, 33, 35, 38, 42, 44, 46, 47, 59, 107, 138, 176, 196, 280 Disorientation, 278, 280 Dissection, 56, 280 Distal, 280, 281, 312 Distemper, 15, 280 Distemper Virus, Canine, 280 Disulphides, 280 Dithiothreitol, 54, 280 Diuresis, 270, 280 Donepezil, 107, 152, 175, 220, 280 Dopa, 22, 95, 116, 117, 123, 129, 130, 134, 154, 193, 194, 195, 196, 204, 214, 280, 295 Dopamine Agonists, 44, 47, 118, 123, 138, 168, 177, 205, 207, 280 Dose-dependent, 18, 157, 280 Double-blind, 12, 30, 49, 56, 69, 82, 116, 120, 130, 173, 281 Doxycycline, 54, 67, 281 Drive, ii, vi, 24, 25, 62, 115, 212, 281, 293 Drug Interactions, 226, 281 Drug Tolerance, 281, 323 Dyes, 264, 281 Dysarthria, 169, 172, 212, 281 Dyskinesia, 16, 71, 74, 93, 100, 117, 119, 121, 124, 141, 161, 196, 266, 281 Dyspareunia, 281, 284 Dysplasia, 237, 281 Dystonia, 8, 28, 35, 67, 100, 204, 244, 265, 281 Dystrophy, 8, 236, 281 E Ectopic, 8, 281 Effector, 66, 81, 261, 275, 281

Index 333

Efficacy, 4, 11, 12, 14, 19, 26, 27, 29, 31, 38, 44, 46, 55, 56, 57, 59, 82, 96, 116, 120, 144, 158, 169, 171, 172, 181, 185, 195, 281 Elastin, 274, 281 Elective, 153, 281 Electrocardiogram, 175, 177, 182, 281 Electrochemistry, 55, 281 Electrode, 78, 281 Electrolyte, 278, 281, 309, 318 Electron microscope, 60, 282 Electrophysiological, 12, 282 Electroplating, 271, 282 Elementary Particles, 282, 296, 303, 311 Embolus, 282, 292 Embryo, 271, 282, 291 Embryology, 282, 303 Emesis, 194, 282 Emetic, 266, 282 Enamel, 279, 282 Endemic, 282, 319 Endocrine System, 282, 302 Endogenous, 10, 19, 82, 83, 280, 282, 283, 308 Endorphins, 282, 303 Endothelial cell, 269, 282 Endothelium, 282, 304 Endothelium-derived, 282, 304 Endotoxin, 54, 83, 282, 325 End-stage renal, 273, 282, 309 Enhancer, 26, 56, 282 Enkephalins, 283, 303 Entopeduncular Nucleus, 283, 321 Entorhinal Cortex, 283, 289 Environmental Exposure, 19, 40, 41, 283, 304 Environmental Health, 175, 179, 232, 234, 244, 283 Enzymatic, 46, 54, 263, 270, 275, 279, 283, 289, 298, 315 Enzyme, 40, 54, 195, 262, 271, 281, 283, 286, 288, 298, 300, 301, 309, 311, 318, 321, 324, 327 Epidemic, 283, 319 Epidemiological, 10, 13, 27, 283 Epinephrine, 262, 280, 283, 303, 304, 325 Epithelial, 106, 154, 182, 219, 227, 283, 294 Epithelial Cells, 219, 227, 283, 294 Epitope, 30, 283 Ergot, 118, 269, 283, 295, 316 Erythrocytes, 264, 269, 283 Esophagus, 279, 283, 320

Essential Tremor, 92, 96, 195, 204, 236, 243, 283 Estrogen, 21, 37, 125, 283, 311 Estrogen Replacement Therapy, 21, 283 Eukaryotic Cells, 56, 284, 291, 325 Evacuation, 276, 284 Evoke, 284, 320 Excitability, 93, 145, 151, 284 Excitation, 273, 284, 303 Excitotoxicity, 51, 284 Exogenous, 65, 282, 284 Exon, 69, 263, 284 Expiration, 284, 315 Extracellular, 62, 71, 155, 264, 267, 276, 284, 293, 298, 318 Extracellular Matrix, 276, 284, 293 Extracellular Space, 284, 298 Extraction, 19, 284 Extrapyramidal, 43, 105, 206, 210, 263, 265, 280, 284, 324 Extremity, 23, 109, 284, 317 Eye Infections, 261, 284 F Facial, 84, 211, 284 Facial Expression, 211, 284 Family Planning, 233, 284 Fat, 79, 269, 270, 276, 282, 284, 295, 300, 315, 318 Fatigue, 81, 184, 284 Fatty acids, 124, 284, 287 Feces, 276, 285, 320 Fee Schedules, 17, 285 Feline Panleukopenia, 280, 285 Fetus, 285, 310, 326 Fibril, 149, 285 Fibrosis, 85, 237, 285, 317 Fissure, 279, 285, 310 Folate, 91, 137, 285 Fold, 7, 16, 61, 285 Folic Acid, 285 Follow-Up Studies, 59, 285 Forearm, 269, 285, 313 Fossa, 272, 285 Free Radicals, 16, 42, 62, 265, 285, 301 Frontal Lobe, 285, 310 Functional magnetic resonance imaging, 24, 285 Fungicide, 285, 297 Fungus, 283, 285, 316 G Gait, 21, 22, 47, 72, 75, 82, 87, 91, 103, 134, 153, 156, 171, 172, 186, 258, 272, 285

334 Parkinson’s Disease

Gallate, 123, 150, 286 Gallbladder, 261, 280, 286 Ganglia, 12, 24, 29, 35, 38, 39, 41, 64, 122, 149, 170, 171, 172, 194, 195, 208, 261, 266, 268, 286, 295, 302, 304, 307, 312, 321 Gap Junctions, 286, 322 Gas, 270, 286, 290, 303, 312, 326 Gastric, 143, 286, 289 Gastrin, 286, 289 Gastrointestinal, 87, 198, 269, 273, 280, 283, 286, 317, 320, 325 Gastrointestinal tract, 273, 286, 317, 325 Gelatin, 106, 154, 182, 286, 287, 321 Gene Expression, 14, 21, 40, 46, 64, 89, 112, 237, 286, 319 Gene Products, rev, 286 Gene Therapy, 14, 26, 30, 32, 46, 66, 88, 220, 262, 286 Genes, env, 157, 286 Genetic Code, 286, 304 Genetics, 28, 40, 61, 62, 67, 89, 176, 243, 277, 287 Genotype, 15, 41, 87, 92, 97, 287, 307 Gestation, 287, 306 Gingivitis, 279, 287 Ginseng, 148, 287 Gland, 196, 287, 296, 305, 308, 311, 317, 320, 323 Globus Pallidus, 12, 29, 78, 96, 121, 133, 168, 174, 268, 277, 283, 287, 312 Glucocorticoid, 18, 287, 310 Glucose, 152, 180, 236, 279, 287, 288, 290, 292, 293 Glutamate, 29, 38, 107, 220, 284, 287, 298, 316 Glutamic Acid, 285, 287, 303, 311 Glycerol, 287, 307 Glycerophospholipids, 287, 307 Glycine, 38, 263, 287, 303, 320 Glycoprotein, 287, 294, 325 Glycosaminoglycan, 273, 287 Governing Board, 287, 310 Graft, 57, 141, 153, 168, 227, 287, 289, 301 Graft Survival, 141, 287 Grafting, 287, 291 Granulocytes, 288, 318, 327 Growth factors, 6, 20, 40, 288, 299 Guanylate Cyclase, 288, 304 H Haematemesis, 282, 288 Hallucination, 146, 288 Handedness, 184, 288

Haplotypes, 88, 288 Haptens, 262, 288, 313 Headache, 270, 288, 290 Health Policy, 17, 288 Health Services, 17, 45, 288 Heart attack, 270, 288 Heat-Shock Proteins, 288, 299 Heat-Shock Proteins 90, 288, 299 Heme, 277, 288 Hemochromatosis, 98, 288 Hemoglobin, 264, 283, 288, 289 Hemoglobinopathies, 286, 289 Hemoglobinuria, 236, 289 Hemorrhage, 288, 289, 301, 320 Hemorrhagic Disorders, 211, 289 Hemostasis, 289, 293, 317 Hepatic, 278, 289, 300 Hepatotoxic, 90, 289, 295 Herbicide, 120, 289 Hereditary, 30, 289, 300, 302, 315 Heredity, 286, 287, 289 Heterodimers, 289, 293 Heterogeneity, 28, 109, 262, 289 Heterozygote, 144, 289 Hippocampus, 66, 279, 289, 295, 302, 320 Histamine, 264, 265, 289 Histology, 289, 302 Homologous, 7, 263, 286, 289, 321 Hormonal, 267, 283, 289, 307 Hormone, 194, 196, 277, 283, 286, 289, 292, 311, 315, 318, 319, 323 Hospital Records, 15, 289 Host, 14, 57, 267, 285, 287, 289, 291, 316, 326, 327 Human growth hormone, 195, 196, 289 Hybrid, 25, 43, 274, 290, 316 Hydrogen, 16, 146, 261, 268, 270, 279, 290, 295, 299, 303, 305, 307, 311, 321 Hydrogen Peroxide, 16, 146, 290, 295, 321 Hydrolysis, 290, 293, 307, 311 Hydroxylysine, 274, 290 Hydroxyproline, 263, 274, 290 Hypersensitivity, 290, 315 Hypertension, 70, 191, 270, 288, 290 Hyperventilation, 105, 290 Hypoglycaemia, 278, 290 Hypokinesia, 193, 290, 306 Hypoplasia, 63, 290 Hypotension, 191, 258, 266, 290 Hypotensive, 190, 197, 290 Hypothalamic, 92, 290, 319

Index 335

Hypothalamus, 267, 279, 290, 295, 308, 320, 322 Hypoxia, 278, 290, 322 I Id, 126, 160, 241, 246, 247, 254, 256, 290 Immune response, 6, 26, 57, 262, 265, 267, 288, 291, 297, 320, 326, 327 Immune Sera, 291 Immune system, 267, 268, 291, 296, 300, 301, 326, 327 Immunity, 291, 324 Immunization, 6, 291 Immunoassay, 198, 291 Immunodeficiency, 236, 291 Immunogenic, 26, 291, 313 Immunologic, 49, 57, 273, 291 Immunosuppressive, 287, 291 Impairment, 37, 66, 93, 97, 100, 131, 245, 267, 278, 281, 284, 291, 298, 312 Implantation, 78, 106, 154, 182, 227, 276, 291 In situ, 7, 30, 36, 291 In Situ Hybridization, 7, 36, 291 In vitro, 22, 23, 25, 29, 36, 38, 47, 57, 131, 196, 286, 291 In vivo, 9, 13, 14, 23, 25, 29, 32, 36, 43, 55, 57, 64, 65, 88, 146, 286, 291, 298 Incision, 291, 293 Incontinence, 32, 258, 291 Incubation, 291, 294 Incubation period, 291, 294 Indicative, 197, 202, 291, 306, 326 Induction, 6, 40, 54, 265, 291, 311 Infarction, 192, 292, 315 Infection, 268, 272, 273, 278, 284, 285, 291, 292, 294, 296, 315, 327 Infertility, 269, 292 Infiltration, 6, 292, 310 Inflammation, 94, 97, 191, 245, 265, 280, 284, 285, 287, 292, 309, 315, 320 Infusion, 34, 36, 55, 123, 140, 186, 292, 301 Ingestion, 292, 309 Inhalation, 292, 309 Initiation, 31, 43, 292 Inlay, 292, 315 Innervation, 12, 28, 292, 307, 317, 323 Inorganic, 190, 292 Inositol, 292, 298 Inotropic, 280, 292 Insecticides, 292, 307 Insight, 22, 31, 34, 54, 61, 63, 292 Insomnia, 161, 185, 194, 292

Insulator, 14, 292, 300 Insulin, 196, 292, 293 Insulin-dependent diabetes mellitus, 293 Insulin-like, 196, 293 Integrins, 63, 293 Intermediate Filaments, 293, 302 Intermittent, 293, 296 Interneurons, 107, 293 Interstitial, 145, 284, 293, 314 Intestinal, 270, 293, 297 Intestines, 261, 285, 286, 293 Intoxication, 278, 293, 327 Intracellular, 30, 34, 60, 270, 292, 293, 297, 298, 304, 309, 314, 318 Intracellular Membranes, 34, 293, 297 Intravenous, 94, 292, 293 Intrinsic, 195, 262, 268, 293 Invasive, 64, 291, 293, 296 Involuntary, 177, 268, 273, 283, 293, 301, 314, 319 Ion Channels, 267, 293, 322 Ion Transport, 191, 293 Ionization, 294 Ionizing, 24, 263, 283, 294, 297 Ions, 261, 268, 281, 290, 293, 294, 308, 309 Ischemia, 191, 267, 294, 301, 315 Isotonic, 35, 294 J Jealousy, 294, 306 Joint, 109, 266, 294, 305, 321 K Kb, 232, 294 Keratolytic, 279, 294 Kidney Disease, 187, 191, 232, 237, 294 Kinesthesis, 81, 294 Kinetic, 91, 294 L Labile, 275, 294 Laminin, 63, 268, 294 Large Intestine, 280, 293, 294, 314, 318 Latency, 106, 294 Lentivirus, 14, 294 Lethal, 8, 294 Leukemia, 236, 286, 294, 310 Leukocytes, 269, 273, 288, 295, 325 Leukopenia, 280, 295 Library Services, 254, 295 Ligament, 295, 311 Ligands, 293, 295 Limbic, 264, 295, 310 Limbic System, 264, 295, 310 Linkage, 27, 28, 40, 43, 66, 70, 89, 196, 295

336 Parkinson’s Disease

Lipid, 16, 34, 42, 287, 293, 295, 300, 305 Lipid Peroxidation, 16, 42, 295, 305 Lipopolysaccharide, 53, 155, 295 Lisuride, 123, 295 Lithium, 265, 295 Liver, 191, 196, 210, 261, 268, 273, 280, 285, 286, 288, 289, 295, 300, 316 Liver scan, 295, 316 Lobe, 170, 264, 289, 295 Localization, 7, 34, 61, 96, 295 Localized, 8, 28, 57, 279, 292, 294, 296, 300, 308 Locomotion, 18, 296, 308 Locomotor, 18, 32, 43, 296 Longitudinal Studies, 13, 296 Longitudinal study, 21, 35, 84, 116, 142, 296 Long-Term Care, 17, 296 Lucida, 294, 296 Lumbar, 178, 296, 317, 319, 323 Lumbar puncture, 296, 319 Lymph, 272, 282, 296 Lymph node, 272, 296 Lymphatic, 145, 282, 292, 296, 309, 319, 323 Lymphocyte, 265, 296, 297 Lymphoid, 265, 277, 296 Lymphoma, 236, 296 M Macroglia, 296, 298 Magnetic Resonance Imaging, 44, 169, 178, 180, 185, 296, 316 Magnetic Resonance Spectroscopy, 61, 103, 296 Major Histocompatibility Complex, 288, 296 Malabsorption, 236, 297 Malignant, 82, 97, 112, 236, 297 Malnutrition, 267, 297, 300 Maneb, 119, 169, 297 Manic, 265, 295, 297, 312 Manic-depressive psychosis, 297, 312 Man-made, 271, 297 Medial, 283, 287, 297, 323 Mediate, 38, 61, 280, 297, 299 Mediator, 280, 297, 317 Medical Records, 289, 297, 315 MEDLINE, 233, 235, 237, 297 Medullary, 297, 312 Meiosis, 297, 321 Melanin, 297, 307, 325 Melanocytes, 297

Melanoma, 97, 236, 297 Membrane, 20, 33, 267, 271, 275, 279, 284, 293, 294, 297, 298, 307, 315, 318, 322 Membrane Glycoproteins, 297 Membrane Lipids, 33, 297, 307 Meninges, 272, 298 Menopause, 21, 298, 309 Menstruation, 263, 298 Mental Disorders, 178, 187, 209, 290, 298, 312 Mental Health, iv, 5, 178, 180, 187, 232, 234, 246, 298, 312 Mesencephalic, 38, 132, 141, 155, 298, 314 Mesolimbic, 265, 298, 326 Meta-Analysis, 101, 298 Metabolite, 298, 304 Metabotropic, 107, 298 Methionine, 163, 181, 298, 321 Methylprednisolone, 82, 298 Methyltransferase, 90, 117, 298 MI, 87, 133, 260, 298 Microbe, 298, 324 Microbiology, 261, 267, 268, 298 Microdialysis, 36, 55, 64, 298 Microglia, 6, 49, 267, 298, 300 Microorganism, 274, 299, 306, 327 Micro-organism, 279, 299, 308 Microtubule-Associated Proteins, 299, 302 Microtubules, 293, 299, 302 Microwaves, 299, 313 Micturition, 32, 299 Minocycline, 68, 179, 299 Mitochondria, 10, 97, 146, 157, 272, 299, 301 Mitosis, 266, 299, 319 Mitotic, 57, 299 Mobility, 82, 169, 245, 299 Modeling, 17, 108, 149, 159, 299 Modification, 24, 28, 34, 146, 263, 299, 313 Modulator, 54, 299 Molecular, 8, 13, 22, 25, 28, 34, 39, 43, 46, 54, 61, 63, 64, 89, 97, 104, 122, 139, 170, 179, 202, 204, 233, 235, 268, 272, 275, 277, 279, 288, 299, 302, 311, 314, 321, 324, 325 Molecular Chaperones, 8, 170, 272, 288, 299 Monitor, 31, 44, 177, 277, 299, 304 Monoamine, 12, 27, 68, 87, 117, 300, 317, 325 Monoamine Oxidase, 87, 117, 300, 317, 325

Index 337

Mononuclear, 300, 325 Monotherapy, 117, 138, 219, 300 Morphine, 266, 300 Morphology, 60, 300 Motility, 143, 300, 317 Motion Sickness, 300, 301 Motor Activity, 22, 300 Motor Skills, 35, 300 Mucins, 279, 300 Multiple sclerosis, 15, 75, 110, 191, 195, 300 Muscle Fibers, 300 Muscular Atrophy, 236, 300 Muscular Dystrophies, 281, 300 Musculature, 290, 300 Music Therapy, 131, 140, 300 Myelin, 56, 300 Myelodysplastic syndrome, 191, 300, 318 Myocardial infarction, 191, 277, 298, 301 Myocardial Reperfusion, 301, 315 Myocardial Reperfusion Injury, 301, 315 Myocardium, 298, 301 Myoclonus, 105, 301 Myotonic Dystrophy, 236, 301 N N-acetyl, 89, 163, 301 Naive, 118, 301 Nausea, 194, 196, 259, 265, 301 NCI, 1, 187, 231, 274, 301 Neocortex, 301, 302 Neoplasia, 236, 301, 302 Neoplastic, 296, 301 Neostriatum, 271, 277, 302, 312 Nephropathy, 294, 302 Nervous System, 32, 41, 52, 54, 56, 59, 116, 170, 184, 192, 196, 197, 203, 236, 261, 262, 267, 270, 272, 273, 274, 286, 287, 288, 295, 297, 299, 300, 301, 302, 303, 307, 309, 317, 321, 322, 325 Nervous System Diseases, 116, 302 Networks, 9, 34, 96, 142, 145, 302 Neural Pathways, 193, 302 Neuregulins, 36, 302 Neuroanatomy, 64, 295, 302 Neuroblastoma, 16, 40, 302 Neurodegenerative Diseases, 7, 10, 17, 24, 25, 26, 31, 50, 55, 57, 61, 62, 268, 302 Neuroendocrine, 210, 302 Neurofibrillary Tangles, 52, 302 Neurofilaments, 302 Neurogenic, 80, 202, 213, 215, 302 Neuroleptic, 82, 263, 265, 274, 302

Neurologic, 21, 41, 49, 53, 124, 177, 183, 193, 201, 211, 240, 280, 303 Neuromuscular, 202, 261, 302, 303 Neuromuscular Junction, 261, 302, 303 Neuropsychological Tests, 59, 303 Neuropsychology, 71, 98, 112, 171, 303 Neurosciences, 9, 26, 99, 118, 122, 149, 157, 303 Neurotic, 303, 326 Neurotoxic, 9, 18, 36, 204, 261, 303 Neurotoxicity, 7, 10, 38, 39, 42, 88, 113, 121, 152, 155, 303 Neurotoxin, 25, 36, 53, 108, 183, 303 Neutrons, 263, 303, 313 Nicotine, 20, 39, 122, 181, 303 Nitric Oxide, 16, 42, 61, 85, 123, 124, 150, 170, 303 Norepinephrine, 262, 280, 303, 304 Nortriptyline, 185, 304 Nuclear Medicine, 103, 106, 130, 135, 154, 181, 304 Nuclei, 263, 264, 286, 295, 296, 299, 303, 304, 311 Nucleic acid, 195, 286, 291, 304 Nucleus Accumbens, 304, 326 Nursing Staff, 47, 304 O Obsessive-Compulsive Disorder, 99, 219, 304 Occult, 58, 304 Oculomotor, 298, 304 Odour, 266, 304 Oncogene, 236, 304 Oncogenic, 293, 294, 304 Oophorectomy, 21, 304 Opacity, 278, 305 Open Reading Frames, 294, 305 Opsin, 305, 315, 316 Oral Health, 245, 305 Orthostatic, 266, 305 Osteoarthritis, 191, 305 Osteoporosis, 191, 284, 305 Outpatient, 5, 305 Ovaries, 304, 305 Oxidation, 10, 42, 54, 63, 101, 261, 265, 277, 280, 295, 305 Oxidative metabolism, 42, 262, 305 Oxidative Stress, 7, 16, 20, 38, 42, 51, 54, 61, 65, 68, 171, 305 Oxygen Consumption, 23, 305, 315 P Palliative, 305, 322

338 Parkinson’s Disease

Palsy, 192, 204, 210, 211, 240, 246, 305 Pancreas, 261, 268, 280, 288, 292, 305, 325 Pancreatic, 236, 305 Pancreatic cancer, 236, 305 Paralysis, 192, 236, 263, 298, 305 Paranoia, 197, 305 Paroxetine, 185, 306 Paroxysmal, 236, 306 Partnership Practice, 306, 310 Patch, 306, 324 Pathogen, 93, 291, 306 Pathogenesis, 8, 9, 11, 21, 41, 42, 49, 61, 62, 66, 116, 120, 123, 170, 193, 306 Pathologic, 13, 42, 266, 276, 290, 306 Pathologic Processes, 266, 306 Pathologies, 13, 306 Pathophysiology, 29, 32, 63, 100, 136, 213, 306 Patient Education, 79, 245, 252, 254, 260, 306 Pedigree, 40, 306 Pelvic, 306, 311 Pelvis, 261, 296, 305, 306, 326 Peptide, 6, 263, 306, 311, 319 Perception, 35, 288, 306, 316 Perfusion, 130, 141, 149, 290, 306 Pergolide, 102, 122, 146, 225, 306 Perinatal, 63, 306 Periodicity, 306, 316 Periodontal disease, 245, 307 Peripheral Nervous System, 196, 281, 283, 302, 303, 305, 307, 320 Perivascular, 298, 307 Peroneal Nerve, 307, 317 Pesticides, 19, 20, 41, 119, 130, 149, 175, 179, 243, 244, 292, 307 PH, 58, 102, 105, 135, 155, 181, 307 Phagocytosis, 298, 307 Pharmaceutical Preparations, 194, 286, 307 Pharmacokinetic, 190, 307 Pharmacologic, 22, 241, 307, 324 Phenotype, 7, 8, 13, 41, 52, 63, 64, 72, 119, 307 Phenyl, 6, 16, 66, 124, 190, 307 Phenylalanine, 164, 307, 325 Phospholipases, 307, 318 Phospholipids, 61, 284, 292, 297, 307 Phosphorus, 270, 307, 308 Phosphorylated, 34, 60, 307 Phosphorylation, 61, 302, 307, 308 Phosphotyrosine, 61, 308

Physical Examination, 177, 180, 308 Physical Therapy, 156, 308 Physiologic, 262, 280, 290, 294, 298, 301, 308, 314, 324 Physiology, 42, 54, 60, 119, 124, 209, 213, 270, 282, 303, 308 Phytic Acid, 192, 308 Pigments, 270, 308, 315 Pilot study, 41, 43, 50, 56, 103, 308 Pitch, 4, 308 Pituitary Gland, 196, 308 Placebo Effect, 141, 308 Plants, 263, 270, 274, 287, 289, 300, 304, 308, 324, 325 Plaque, 52, 308 Plasma, 71, 265, 271, 286, 288, 289, 308, 317, 318 Plasma cells, 265, 308 Plasticity, 33, 308 Platelet Activation, 308, 318 Platelet Aggregation, 264, 304, 308 Platelets, 304, 308, 309, 323 Plexus, 309, 317 Pneumonia, 192, 276, 309 Point Mutation, 22, 43, 309 Poisoning, 155, 266, 278, 283, 293, 301, 309 Polycystic, 237, 309 Polymerase, 68, 309 Polymorphism, 41, 88, 95, 101, 309 Polysaccharide, 265, 287, 309 Pons, 269, 309 Postal Service, 15, 309 Posterior, 264, 267, 272, 283, 305, 309 Postherpetic Neuralgia, 263, 309 Postmenopausal, 283, 305, 309 Postnatal, 53, 309, 320 Postsynaptic, 16, 309, 318, 322 Post-synaptic, 60, 309 Post-traumatic, 300, 309 Postural, 23, 76, 81, 85, 119, 192, 309 Potassium, 130, 182, 309 Potassium Channels, 130, 309 Potentiates, 197, 309 Potentiation, 273, 309, 318 Practice Guidelines, 18, 234, 246, 310 Precipitating Factors, 271, 310 Preclinical, 25, 29, 32, 37, 46, 72, 150, 310 Precursor, 22, 194, 196, 197, 280, 281, 282, 283, 295, 304, 307, 310, 325 Prednisolone, 298, 310 Prefrontal Cortex, 138, 310 Preleukemia, 301, 310, 318

Index 339

Prenatal, 53, 282, 310 Presynaptic, 34, 61, 64, 123, 303, 310, 321, 322 Prevalence, 5, 50, 53, 67, 109, 310 Private Practice, 45, 310 Probe, 34, 298, 310 Procaine, 263, 310 Progressive disease, 38, 310 Projection, 25, 278, 293, 304, 310, 314, 326 Prolactin, 269, 311 Proline, 274, 290, 311 Promoter, 25, 26, 62, 311 Prone, 59, 180, 311 Prophase, 311, 321 Prophylaxis, 311, 326 Prospective Studies, 15, 311 Prospective study, 296, 311 Prostate, 236, 268, 311, 325 Protease, 264, 274, 311 Protein S, 54, 62, 195, 209, 237, 244, 268, 286, 290, 311, 316, 322 Protein Subunits, 54, 311 Proteolytic, 275, 311 Protocol, 19, 24, 31, 43, 48, 49, 50, 51, 59, 140, 311 Protons, 263, 290, 294, 296, 311, 313 Protozoa, 299, 311, 312 Protozoal, 312 Protozoan, 191, 312 Proximal, 280, 310, 312 Psychiatric, 15, 76, 107, 197, 207, 298, 312 Psychic, 133, 194, 298, 312, 317 Psychoactive, 312, 327 Psychological Tests, 177, 312 Psychology, 275, 303, 312 Psychomotor, 278, 303, 312 Psychophysiology, 303, 312 Psychosis, 97, 104, 108, 185, 194, 265, 312 Public Health, 10, 14, 15, 17, 123, 205, 234, 312 Public Policy, 233, 312 Pulmonary, 269, 276, 290, 312, 326 Pulmonary Artery, 269, 312, 326 Pulmonary Ventilation, 290, 312 Pulse, 82, 151, 183, 300, 312 Putamen, 35, 55, 56, 132, 186, 268, 277, 302, 312 Pyramidal Tracts, 284, 312 Q Quality of Life, 16, 17, 23, 31, 32, 44, 48, 79, 87, 134, 175, 196, 206, 245, 248, 313

R Race, 40, 41, 93, 280, 313 Racemic, 280, 313 Raclopride, 130, 154, 184, 313 Radiation, 24, 182, 280, 282, 283, 285, 294, 297, 313, 316, 327 Radiation therapy, 280, 313 Radio Waves, 180, 181, 185, 299, 313 Radioactive, 180, 182, 184, 196, 269, 290, 291, 294, 295, 297, 304, 313, 316, 322, 325 Radioimmunoassay, 196, 313 Radioisotope, 313, 324 Radiology, 24, 58, 59, 304, 313 Radius, 20, 313 Randomized, 12, 23, 30, 43, 49, 50, 57, 58, 82, 102, 104, 120, 123, 145, 151, 180, 281, 313 Randomized clinical trial, 23, 313 Reaction Time, 81, 82, 151, 184, 313 Reactive Oxygen Species, 53, 313 Reagent, 280, 314 Reality Testing, 312, 314 Receptors, Serotonin, 314, 317 Recombinant, 7, 22, 34, 60, 68, 122, 186, 191, 314, 326 Recombinant Proteins, 22, 314 Recombination, 286, 314 Rectum, 266, 269, 274, 280, 286, 291, 294, 311, 314, 321 Red Nucleus, 267, 314, 326 Refer, 1, 269, 275, 282, 293, 295, 296, 301, 302, 303, 312, 314, 324 Reflex, 32, 90, 92, 156, 314 Refraction, 314, 319 Refractory, 117, 157, 314 Regeneration, 23, 314 Regimen, 7, 53, 274, 281, 308, 314 Regression Analysis, 280, 314 Reliability, 48, 78, 174, 314 Renal failure, 278, 314 Reperfusion, 191, 301, 315 Reperfusion Injury, 191, 315 Respiration, 42, 119, 182, 270, 273, 299, 315 Response rate, 78, 315 Restoration, 36, 158, 277, 301, 308, 315, 327 Reticulata, 29, 315 Retina, 276, 315, 316 Retinal, 106, 154, 182, 219, 227, 315, 316 Retinoblastoma, 236, 315 Retinol, 315, 316 Retrospective, 73, 130, 315 Retrospective study, 73, 130, 315

340 Parkinson’s Disease

Retroviral vector, 286, 315 Rheumatism, 315 Rheumatoid, 191, 315 Rheumatoid arthritis, 191, 315 Rhodopsin, 305, 315, 316 Rhythmicity, 132, 316 Riboflavin, 126, 316 Ribose, 68, 261, 316 Ribosome, 316, 324 Rigidity, 21, 22, 23, 41, 47, 64, 155, 192, 193, 210, 211, 259, 306, 308, 316 Riluzole, 116, 316 Risk factor, 15, 19, 27, 31, 41, 54, 83, 96, 112, 120, 271, 311, 316 Rodenticides, 307, 316 Rotenone, 12, 130, 152, 153, 155, 157, 316 Rye, 283, 316 S Salivary, 279, 305, 316 Salivary glands, 279, 316 Satellite, 12, 215, 316 Scans, 174, 180, 182, 183, 184, 316 Schizoid, 316, 327 Schizophrenia, 161, 178, 306, 316, 317, 326, 327 Schizotypal Personality Disorder, 316, 327 Sciatic Nerve, 23, 307, 317, 323 Sclerosis, 15, 52, 74, 80, 171, 191, 202, 203, 236, 300, 316, 317 Screening, 7, 33, 57, 59, 175, 184, 274, 317, 325 Secretion, 196, 269, 289, 293, 299, 300, 317 Secretory, 317, 321 Sedative, 190, 317, 326 Sediment, 317, 325 Seizures, 278, 306, 317 Selegiline, 43, 67, 165, 225, 227, 317 Self Care, 53, 261, 317 Self-Help Groups, 248, 317 Sella, 308, 317 Semen, 311, 317 Semisynthetic, 269, 299, 317 Senile, 52, 167, 194, 195, 305, 317 Sepsis, 191, 317 Septic, 191, 317 Serologic, 291, 317 Serotonin, 56, 105, 106, 194, 265, 274, 295, 300, 303, 306, 314, 317, 325 Serum, 41, 57, 196, 264, 275, 291, 294, 313, 317, 318, 325 Serum Albumin, 313, 318 Sex Determination, 237, 318

Shock, 191, 272, 301, 318, 324 Signal Transduction, 63, 288, 292, 308, 318 Signs and Symptoms, 29, 47, 148, 318 Skull, 318, 322 Sleep apnea, 318, 320 Small intestine, 289, 293, 318 Smoldering leukemia, 301, 318 Smooth muscle, 264, 270, 289, 300, 318, 319, 320 Social Environment, 313, 318 Sodium, 127, 318 Soft tissue, 269, 318 Soma, 319 Somatic, 35, 55, 277, 295, 297, 299, 306, 307, 310, 319 Somatic mutations, 55, 319 Somatotropin, 195, 196, 319 Spasm, 266, 298, 319 Specialist, 176, 248, 319 Specificity, 14, 30, 32, 59, 262, 310, 319 Spectrum, 21, 299, 313, 319 Speech Intelligibility, 140, 212, 319 Sperm, 273, 319 Sphincter, 32, 319 Spinal cord, 267, 269, 272, 273, 298, 302, 303, 307, 312, 314, 317, 319, 321 Spinal Nerves, 307, 319 Spinal tap, 178, 296, 319 Spleen, 296, 319 Sporadic, 30, 40, 43, 75, 84, 302, 315, 319 Stabilization, 56, 319 Staging, 316, 320 Staphylococcus, 299, 320 Stem Cells, 9, 69, 112, 138, 158, 320 Stereotactic, 29, 80, 87, 96, 98, 109, 124, 320 Steroids, 277, 287, 320 Stimulant, 270, 289, 320 Stimulus, 90, 106, 184, 281, 284, 288, 292, 293, 294, 313, 314, 320, 323 Stomach, 261, 279, 283, 286, 289, 293, 301, 318, 319, 320 Stool, 198, 274, 291, 294, 320 Strand, 309, 320 Stress, 7, 16, 17, 20, 42, 52, 54, 61, 120, 141, 205, 257, 259, 267, 271, 272, 301, 305, 315, 320 Stria, 14, 259, 320 Striatum, 6, 9, 14, 22, 25, 36, 39, 47, 62, 302, 304, 320 Stromal, 191, 320 Strychnine, 38, 320 Subiculum, 289, 320

Index 341

Subspecies, 319, 320 Substance P, 298, 317, 320 Subthalamus, 60, 279, 320 Sulfur, 298, 321 Superoxide, 42, 61, 321 Superoxide Dismutase, 42, 62, 321 Supplementation, 42, 135, 321 Support group, 11, 19, 31, 48, 212, 259, 321 Suppositories, 286, 321 Suppression, 57, 321 Suppressive, 8, 321 Sympathetic Nervous System, 267, 303, 321 Sympathomimetic, 280, 283, 304, 321, 325 Symphysis, 273, 311, 321 Symptomatic, 43, 44, 46, 48, 49, 58, 71, 135, 263, 321 Symptomatic treatment, 43, 263, 321 Symptomatology, 12, 13, 196, 321 Synapse, 129, 137, 262, 303, 310, 321, 324 Synapsis, 321 Synaptic, 33, 60, 133, 158, 196, 303, 318, 321, 322 Synaptic Transmission, 303, 321 Synaptic Vesicles, 322 Synergistic, 25, 29, 53, 155, 311, 322 Systemic, 29, 42, 57, 135, 224, 225, 266, 269, 278, 283, 292, 302, 310, 313, 322, 324 Systolic, 290, 322 T Tardive, 161, 266, 322 Technetium, 59, 322 Telangiectasia, 237, 322 Telencephalon, 268, 272, 322 Temperament, 16, 322 Temporal, 34, 264, 289, 322 Tetracycline, 25, 62, 281, 299, 322 Thalamic, 13, 96, 103, 267, 283, 322 Thalamic Diseases, 267, 322 Thalamus, 12, 277, 279, 295, 310, 320, 322 Therapeutics, 6, 10, 14, 57, 62, 63, 155, 160, 162, 197, 226, 246, 300, 322 Third Ventricle, 290, 322 Thorax, 261, 296, 323 Threshold, 55, 90, 153, 284, 290, 323 Thrombosis, 293, 311, 320, 323 Thrombus, 276, 292, 301, 308, 323 Thymus, 291, 296, 323 Thyroid, 182, 323, 325 Thyroid Gland, 182, 323 Thyroid Hormones, 323, 325 Tibial Nerve, 317, 323

Tidal Volume, 290, 323 Tin, 123, 323 Tolerance, 37, 261, 288, 323 Tomography, 9, 33, 58, 105, 148, 151, 181, 184, 276, 296, 316, 323 Tone, 59, 323 Tonicity, 281, 294, 323 Tonus, 323 Tooth Preparation, 261, 323 Topical, 267, 290, 323 Torsion, 8, 35, 244, 292, 323 Toxic, iv, 124, 193, 197, 278, 283, 289, 291, 303, 316, 323, 324 Toxicity, 7, 12, 24, 38, 50, 57, 66, 85, 86, 281, 324 Toxicology, 40, 108, 110, 123, 160, 184, 234, 324 Toxin, 18, 42, 51, 282, 323, 324 Trace element, 323, 324 Tracer, 182, 324 Trachea, 323, 324 Transdermal, 39, 118, 219, 324 Transduction, 14, 63, 318, 324 Transfection, 268, 286, 324 Transfer Factor, 291, 324 Translation, 7, 64, 263, 286, 324 Translocation, 16, 324 Transmitter, 32, 196, 261, 267, 280, 293, 297, 304, 322, 324, 325 Transposase, 14, 324 Trauma, 268, 278, 288, 322, 324 Tremor, 5, 21, 22, 23, 47, 64, 72, 92, 96, 121, 124, 192, 193, 195, 196, 211, 298, 306, 324 Trigger zone, 266, 324 Trihexyphenidyl, 155, 324 Trophic, 31, 36, 46, 55, 57, 325 Tropism, 14, 325 Tryptophan, 274, 317, 325 Tuberous Sclerosis, 237, 325 Tumor marker, 268, 325 Tumor Necrosis Factor, 6, 53, 325 Tumor suppressor gene, 68, 325 Tyramine, 300, 325 Tyrosine, 6, 21, 24, 25, 27, 40, 67, 163, 165, 280, 308, 325 U Ubiquitin, 95, 116, 302, 325 Unconscious, 278, 290, 325 Uranium, 322, 325 Urban Population, 179, 325 Ureters, 325 Urethra, 32, 311, 325, 326

342 Parkinson’s Disease

Urinalysis, 177, 325 Urinary, 32, 80, 109, 192, 268, 273, 291, 325 Urinary tract, 32, 80, 192, 268, 325 Urinary tract infection, 192, 268, 325 Urinate, 182, 326 Urine, 178, 182, 184, 268, 277, 280, 289, 291, 299, 316, 325, 326 Urodynamic, 80, 326 Uterus, 272, 277, 298, 305, 326 V Vaccination, 7, 326 Vaccine, 7, 262, 311, 326 Valerian, 185, 326 Vascular, 193, 279, 282, 289, 292, 304, 323, 326 Vascular Hemostatic Disorders, 289, 326 Vasodilator, 269, 280, 289, 301, 326 Vasomotor, 284, 326 VE, 45, 326 Vector, 14, 26, 27, 32, 46, 324, 326 Vein, 177, 180, 293, 304, 316, 326 Venous, 19, 311, 326 Venter, 326 Ventral, 21, 24, 36, 53, 141, 169, 290, 304, 309, 319, 326 Ventral Tegmental Area, 53, 326 Ventricle, 55, 264, 271, 289, 304, 312, 322, 323, 326 Vertebrae, 178, 319, 326

Vesicular, 27, 68, 326 Veterinary Medicine, 233, 326 Viral, 6, 22, 25, 26, 68, 70, 191, 280, 286, 304, 324, 326, 327 Viral Proteins, 26, 326 Viral vector, 6, 25, 68, 70, 327 Virulence, 324, 327 Virus, 14, 15, 22, 26, 27, 68, 90, 122, 267, 280, 282, 285, 308, 315, 324, 326, 327 Visual Perception, 70, 327 Vitro, 22, 24, 169, 327 Vivo, 24, 25, 32, 64, 327 Volition, 293, 327 Vomica, 320, 327 W Wakefulness, 168, 278, 327 White blood cell, 265, 295, 296, 308, 327 Windpipe, 323, 327 Withdrawal, 15, 104, 112, 117, 123, 278, 327 Wound Healing, 293, 327 X Xenograft, 264, 327 X-ray, 174, 177, 276, 297, 304, 313, 316, 320, 327 Y Yeasts, 285, 307, 327 Z Zebrafish, 65, 327

Index 343

344 Parkinson’s Disease