Brain Damage - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

BRAIN DAMAGE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2003 by ICON Group International, Inc. Copyright ©2003 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., 1960Brain Damage: 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: 0-597-83773-2 1. Brain Damage-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 brain damage. 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 BRAIN DAMAGE ........................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Brain Damage ............................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 60 The National Library of Medicine: PubMed ................................................................................ 60 CHAPTER 2. NUTRITION AND BRAIN DAMAGE ............................................................................ 105 Overview.................................................................................................................................... 105 Finding Nutrition Studies on Brain Damage ............................................................................ 105 Federal Resources on Nutrition ................................................................................................. 107 Additional Web Resources ......................................................................................................... 107 CHAPTER 3. ALTERNATIVE MEDICINE AND BRAIN DAMAGE ...................................................... 109 Overview.................................................................................................................................... 109 National Center for Complementary and Alternative Medicine................................................ 109 Additional Web Resources ......................................................................................................... 111 General References ..................................................................................................................... 113 CHAPTER 4. DISSERTATIONS ON BRAIN DAMAGE ........................................................................ 115 Overview.................................................................................................................................... 115 Dissertations on Brain Damage................................................................................................. 115 Keeping Current ........................................................................................................................ 116 CHAPTER 5. PATENTS ON BRAIN DAMAGE .................................................................................. 117 Overview.................................................................................................................................... 117 Patents on Brain Damage .......................................................................................................... 117 Patent Applications on Brain Damage ...................................................................................... 144 Keeping Current ........................................................................................................................ 155 CHAPTER 6. BOOKS ON BRAIN DAMAGE ...................................................................................... 157 Overview.................................................................................................................................... 157 Book Summaries: Federal Agencies............................................................................................ 157 Book Summaries: Online Booksellers......................................................................................... 159 The National Library of Medicine Book Index ........................................................................... 165 Chapters on Brain Damage ........................................................................................................ 166 CHAPTER 7. MULTIMEDIA ON BRAIN DAMAGE ........................................................................... 167 Overview.................................................................................................................................... 167 Video Recordings ....................................................................................................................... 167 Bibliography: Multimedia on Brain Damage............................................................................. 168 CHAPTER 8. PERIODICALS AND NEWS ON BRAIN DAMAGE ........................................................ 169 Overview.................................................................................................................................... 169 News Services and Press Releases.............................................................................................. 169 Newsletter Articles .................................................................................................................... 172 Academic Periodicals covering Brain Damage .......................................................................... 172 CHAPTER 9. RESEARCHING MEDICATIONS ................................................................................... 175 Overview.................................................................................................................................... 175 U.S. Pharmacopeia..................................................................................................................... 175 Commercial Databases ............................................................................................................... 176 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 181 Overview.................................................................................................................................... 181 NIH Guidelines.......................................................................................................................... 181 NIH Databases........................................................................................................................... 183 Other Commercial Databases..................................................................................................... 187 APPENDIX B. PATIENT RESOURCES ............................................................................................... 189

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Overview.................................................................................................................................... 189 Patient Guideline Sources.......................................................................................................... 189 Finding Associations.................................................................................................................. 195 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 197 Overview.................................................................................................................................... 197 Preparation................................................................................................................................. 197 Finding a Local Medical Library................................................................................................ 197 Medical Libraries in the U.S. and Canada ................................................................................. 197 ONLINE GLOSSARIES................................................................................................................ 203 Online Dictionary Directories ................................................................................................... 203 BRAIN DAMAGE DICTIONARY.............................................................................................. 205 INDEX .............................................................................................................................................. 287

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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 brain damage 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 brain damage, 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 brain damage, 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 brain damage. 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 brain damage, 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 brain damage. The Editors

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

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CHAPTER 1. STUDIES ON BRAIN DAMAGE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on brain damage.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and brain damage, 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 “brain damage” (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: •

Otoacoustic Emissions and Auditory Assessment in Infants at Risk for Early Brain Damage Source: International Journal of Pediatric Otorhinolaryngology. 58(2): 139-145. April 27, 2001. Contact: Available from Elsevier Science. P.O. Box 945, New York, NY 10159-0945. (888) 437-4636. Fax (212) 633-3680. E-mail: [email protected]. Summary: The importance of early hearing screening has long been recognized, as the prognosis for the hearing impaired child is improved when the diagnosis is made as early as possible, and the intervention is begun immediately. For clinical screening of hearing impairment, the recording of otoacoustic emissions (OAE) was recommended. The authors of this article hypothesize that some risk factors for early brain damage are

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at the same time risk factors for dysfunction of the auditory system; hence, infants at risk for brain damage have hearing impairment more frequently than the rest of the population of the same age. The authors report on their study of the role of OAE testing during the assessment of auditory function in 110 infants at risk for brain damage. Spontaneous OAE was detected in 38.2 percent of the infants; evoked OAE was registered in 27.3 percent of the infants. The testing had to be repeated in 32.7 percent of the infants. Up to 32.7 percent of infants at risk for brain damage were found to have hearing loss. Conductive hearing loss was discovered with 25.4 percent of infants, and eight (7.3 percent) had sensorineural hearing impairment (SNHL). In the group of infants with only risk factors, 3.6 percent had SNHL, and in a group with abnormal motor development, there were 18.5 percent with SNHL. The authors conclude that infants at risk for brain damage have more frequently impaired auditory function than their peers. For this reason, it is vital to focus attention on the hearing condition when dealing with this population. 1 table. 37 references. •

Dementia in Left Brain Damage Source: Clinical Gerontologist. 17(4): 13-22. 1997. Summary: This journal article describes a study of the Spatial Location Test (SLT), a nonverbal test on which aphasic patients have been shown to perform as well as nonaphasic controls. It was hypothesized that, in patients without left brain damage, scores on a test involving visual memory would correlate highly with scores on a dementia test involving verbal skills. In patients with left brain damage, the correlation would be weaker. For this study, the SLT was modified for low scorers. The modified SLT and the Mental Status Questionnaire (MSQ), an established dementia test that is primarily verbal, were administered to two groups, each likely to include members with dementia. One group, 14 inpatients (mean age, 70 years) on a geriatric psychiatry unit, had no evidence of left brain lesions. The other group of 15 patients (mean age, 63 years) were known to have left brain lesions. Among the patients without left brain lesions, there was no significant difference between mean scores (percentage of errors) on the SLT and the MSQ, and the scores on the two tests were strongly correlated. Among patients with left brain lesions, mean scores on the MSQ were significantly higher than those on the SLT, and the correlation between the two scores was weak. Clinical observations suggested that the SLT measured some kind of mental ability that remained after the power of speech was lost. The authors conclude that the modified SLT may be useful in identifying dementia in patients with aphasia. Copies of the SLT and MSQ are appended. 1 table, 17 references.

Federally Funded Research on Brain Damage The U.S. Government supports a variety of research studies relating to brain damage. 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.

2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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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 brain damage. 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 brain damage. The following is typical of the type of information found when searching the CRISP database for brain damage: •

Project Title: 3D MR SPECTROSCOPIC IMAGING OF THE NEWBORN BRAIN Principal Investigator & Institution: Vigneron, Daniel B.; Associate Professor; Radiology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 05-FEB-2001; Project End 31-JAN-2006 Summary: (Verbatim from the Applicant's Abstract): Brain injury in term and preterm neonates is a serious problem. Of the approximately 42,000 infants born yearly in the United States with a birth weight less than 1500 g, approximately 85 percent survive and, of these, 5-10 percent exhibit major motor deficits and another 25-50 percent exhibit developmental and visual difficulties. Hypoxia and ischemia frequently occur during the birth process; however, the amount of brain damage in these patients and the longterm neurologic outcome varies considerably from patient to patient. There is a need, particularly in this group, to identify new clinical diagnostic tools that will improve early prediction of neurodevelopmental abnormalities and therefore allow for pharmacological interventions. The goal of this bioengineering research project is to develop and implement advanced Magnetic Resonance spectroscopic imaging techniques to detect the distribution of metabolite levels throughout the brain of neonates. Studies by ourselves and others have indicated an important role for single voxel MRS in the assessment of the neurologic status of neonates, especially premature infants and those with suspected neonatal hypoxia. However, these techniques provide very limited coverage of the brain and at poor spatial resolution. In this study, we propose to develop and optimize MRSI techniques to provide, for the first time, a study of the 3D distribution of metabolite levels in the newborn brain. This information will define the normal variation in metabolite levels with anatomic location and postconceptional age. The database of normal MRSI spectra will improve our understanding of brain development and provide a reference for detecting abnormal metabolism in neonatal patients with neurologic damage. Current methods are inaccurate for assessing the cerebral metabolism of newborns. Through this project, we aim to develop a noninvasive metabolic imaging technique to address this important problem. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ABNORMAL WATER METABOL IN TYPE 1A ANGIOTENSIN RECEPTOR DEFICIENT MICE: MUTANT Principal Investigator & Institution: Oliverio, Michael I.; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001 Summary: The goal of this project is correlative MR and optical histology of a model of brain damage induced by AET. Recent results have demonstrated neuronal damage detected by MRM in brain specimens from animals treated with DOM. Some of the lesions seen in the MRM specimens were not evident in conventional optical sections with H&E and Nissl stain. If these results can be demonstrated in other models of

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disease, the implications are enormous. Simply put, this suggests that MRM can detect lesions not seen in conventional histology. This is consistent with other recent evidence in the Center. A total of 9 specimens will be scanned. These are 1/2 the brains of rats that have been treated with AET. The other half brains have already been sectioned and analyzed with conventional histology. Six of these specimens show significant damage in four different nuclei: Superior Olive, trapezial nucleus, red nucleus, facial nucleus. Damage ranges from 10% of the nucleus to as much as 97% of the nucleus. We will scan the second 1/2 brain with 2 protocols: I FSE -TR=1.5sec; TE=50 ms; Nechos=8; fovz=fovy=10 mm; fovx=20 mm; matrix (z,y,x)=256x256x128; nex=2 (Total time 6.8 hrs) II GRASS TR=100 ms.TE=3 ms, alpha=350 , same fov matrix as I, nex=4 (total time =3.64 hrs) We will section the specimens after MR and compare specific regions of interest with quantitative morphometry to describe % cell damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ACUTE BRAIN INJURY AFTER SUBARACHNOID HEMORRHAGE Principal Investigator & Institution: Bederson, Joshua B.; Neurosurgery; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 01-JAN-1997; Project End 31-DEC-2001 Summary: (Applicant's abstract): The applicant's long-term goal is to develop a program of laboratory research that parallels the clinical problems of patients with cerebrovascular disorders. One of the most important of these is the lack of treatment options for patients who have suffered a severe subarachnoid hemorrhage (SAH). Although progress has been made in our treatment of the delayed consequences of SAH, acute SAH-induced brain injury is the primary cause of morbidity and mortality from SAH, and no effective treatment exists. In this proposal we utilize a multidisciplinary approach to examine the pathophysiology and pharmacological treatment of acute brain injury after experimental SAH. The investigators hypothesize that: 1)acute brian injury after SAH (as opposed to delayed ischemic damage) is caused by constriction of cortical microvessels, 2) acute vasoconstriction in this setting is due to a multifaceted central adrenergic pathways, and 3) SAH-induced alteration of these pathways is pharmacologically treatable within a clinically relevant time frame. The problem will be approached using a novel rat model of SAH developed in this laboratory. The physiological predictors of early mortality after SAH (cortical blood flow and cerebral perfusion pressure) will be compared with the factors known to influence (or be influenced by) vasodilatory and vasoconstrictive tone. These will include: a) the activity of nitric oxide synthase (NOS) measured by a modified citrulline assay, b) the extracellular concentrations of catecholamines and glutamate measured by cerebral microdialysis and high performance liquid chromatography, and c) histological evidence of acute vasoconstriction and ischemic brain damage. We will determine if acute cerebral ischemia, early mortality rate, and ischemic histological damage can be reduced by enhancing vasodilatory tone and inhibiting vasoconstrictive tone with the NO donor sodium nitroprusside or the cGMP-specific phosphodiesterase inhibitor Zaprinast, the nonspecific c-AMP phosphodiesterase (PDE) inhibitor papaverine hydrochloride or the type III cAMP-specific PDE inhibitor Milrinone, and for alpha adrenergic blockade the selective alpha 1 antagonist Benextramine. In addition, we will administer the NOS inhibitor NG-monomehtyl-L-arginine (L-NMMA) which, if our hypotheses are correct, should increase vasoconstriction and worsen outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AFFECTIVE AND CONATIVE CHANGES IN ALCOHOLISM Principal Investigator & Institution: Berman, Marlene O.; Professor of Psychiatry and Neurology; Psychology; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-DEC-1996; Project End 30-NOV-2001 Summary: This is an application for an ADAMHA Senior Scientist Award (SSA). The SSA would permit the PI (a) to devote all of her research efforts to alcoholism; (b)to expand her research and mentoring activities concerned with gender issues in alcoholism; and (c) to gain valuable experience with structural and functional neuroimaging techniques. In conjunction with 2RO1 AA 07112-09, investigations are planned to examine changes in affect (emotion) and conation (intention) in abstinent alcoholics. Secondary aims of the research are to expand studies of age-related changes and gender differences in emotional and intentional functions. The importance of the research is fourfold: (1) Putative sites of alcohol-related brain damage involve separate frontal systems which are tied to different perceptual/cognitive aspects of emotional and intentional behaviors; (2) gender differences in alcohol- related neurobehavioral functions are ripe for experimental exploration; (3) the literature on whether emotional changes have reciprocal effects on perception and cognition in alcoholism is equivocal and controversial; and (4) even though affective and conative abnormalities have been clinically apparent in alcoholic groups, neuropsychological studies have focused primarily on cognitive changes unrelated to emotion and intention. In the proposed experiments we will enlist the participation of right- handed male and female research subjects ranging in age from 20 to 75 years. The experimental groups will include abstinent alcoholics with and without Korsakoff's syndrome. Patterns and levels of performances by the alcoholics will be compared to those of age-matched nonalcoholic subjects, in order to evaluate the ways in which behavioral consequences of aging and alcoholism are parallel, divergent, or interactive. Additionally, patients with rightfrontal or bilateral frontal lobe damage from cerebrovascular accidents will provide the necessary control comparisons for neurobehavioral changes linked directly to focal brain damage. These groups were chosen specifically to clarify frontal system contributions to deficits of Korsakoff and non-Korsakoff alcoholics. We also will be able to evaluate hypotheses about greater right- than left-hemisphere functional decline in the alcoholic and aging groups, and in women compared to men. It is expected that results of the proposed studies will show clear evidence of frontal-mediated affective and conative changes in alcoholics (most notably in the Korsakoff patients), but that these changes will not be conspicuous in aging populations uncomplicated by alcoholism. By contrast, certain aspects of perceptual functioning will be compromised by aging - whether or not a history of alcohol abuse exists. Finally, women will display different performance patterns than men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AGING AND THE CHOLINERGIC SYSTEM ON ATTENTION AND TIMING Principal Investigator & Institution: Pang, Kevin Ch.; Associate Professor; Psychology; Bowling Green State Univ Bowling Green 220 Mcfall Ctr Bowling Green, Oh 43403 Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): The elderly tend to be afflicted with impairments of several cognitive processes, including a decreased ability to pay attention, perform multiple tasks, and to time short intervals. Some models suggest a close interaction of

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timing and attention. The proposed studies hypothesize that attention and timing involve similar brain regions, in particular motor areas in the frontal lobe. In addition, it is predicted that dysfunction of the frontal motor areas is responsible for the age-related impairments in attention and timing. This dysfunction is due, in part, to the loss of cholinergic neurons of the nucleus basalis magnocellularis (NBM). The proposed studies do the following: 1) examine the effects of damage to motor cortex and NBM projections to motor cortex on attention and time estimation, 2) compare age-related changes of attention and timing in rats and humans, 3) examine the relationship between agerelated loss of NBM neurons and impairments in attention and timing, and 4) investigate the effects of aging and brain damage on attention-related neuronal activity in motor cortex. The proposed behavioral studies with rats and humans involve similar versions of a simultaneous temporal processing (STP) task. In the STP task, subjects' learn to associate auditory and visual cues with short and long fixed time intervals, and are then tested on their ability to produce/estimate this time interval under different attentional demands. In a focused attention condition, only one cue is presented to subjects. In a divided attention condition, both cues are presented and must be attended to in order to respond correctly. The focused attention condition serves as a baseline measure of performance. The central empirical question concerns how aging and lesions (in rats) affect timing performance in divided attention conditions, relative to focused attention conditions. Model fits using scalar-expectance theory facilitate comparison between the human and rat behavioral data and potentially provide a functional interpretation of the effects of aging and lesions on focused and divided attention. Overall, the studies in this proposal will enhance our knowledge of the brain systems participating in attention and timing. Importantly, new information will be revealed that will elucidate the neural mechanisms responsible for age-related impairments in attention and timing. This new knowledge will provide directions for the development of treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AGING BRAIN--CEREBROVASCULAR MECHANISM & AMYLOID BETA Principal Investigator & Institution: Zlokovic, Berislav V.; Professor and Director; Neurology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 30-APR-2004 Summary: This proposal represents investigators from the University of Southern California, Columbia University and State University of New York at Stony Brook Schools of Medicine who participate in a multi-disciplinary program on Cerebrovascular Mechanisms in the Aging Brain. The goal of the program is to advance current knowledge regarding the role of vasculature in the aging brain and major CNS disorders in elderly that predispose to cerebrovascular amyloidosis (e.g., Alzheimer's Disease and related amyloid-beta-peptide (Abeta) disorders, such as hereditary cerebral hemorrhage with amyloidosis Dutch type), Abeta-related vascular injury, brain damage and stroke. We will apply concepts and techniques developed in cerebrovascular biology, blood-brain barrier (BBB) and cerebrospinal fluid physiology, molecular biology, molecular genetics, transgene mice with age-dependent vascular risk factors, and tissues and cell cultures from patients diagnosed with AD. The program consists of five Research Projects and three Core resources. Project 1, Dr. Zlokovic will study the role of BBB and brain clearance in regulating Abeta concentrations in cerebral vessel wall and brain. Project the role of BBB and brain clearance in regulating Abeta concentrations in cerebral vessel wall and brain. Project 2, Dr. Van Nostrand will study

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Abeta production by cerebrovascular smooth muscle cells in relation to amyloidosis. Project, Dr. Stern will study the role of receptor for advanced glycation and end products in acute and chronic cerebrovascular perturbation caused by Abeta and strokerisk factors. Project 44, Drs. Schreiber and Zlokovic will delineate the roles of Abeta dn amyloid in vascular hemostasis in relation to ischemic or hemorrhagic stroke. Project 5, Drs. Kalra and Rhodin will study the role of Abeta in migration of monocytes across the BBB and vascular wall. Core A is the administrative facility. Core B, Dr. Mackic and Kim will provide animal and cell culture facility. Core C, Dr. Miller will provide neuropathologic analysis. The integrated and complementary scientific research projects will provide a molecular and therapeutic rationale to prevent accumulation of Abeta and formation of amyloid in cerebral blood vessels and brain, and counteract agedependent mechanisms responsible for abnormal vascular responses, injury and brain damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BEHAVIOR MEDIATED NEURAL PLASTICITY AFTER BRAIN DAMAGE Principal Investigator & Institution: Jones, Theresa A.; Psychology; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 15-APR-1997; Project End 31-AUG-2001 Summary: Research in the last three decades has made enormous progress in demonstrating and elucidating plasticity in the central nervous system of ~adult animals~. Two important types of proof of this plasticity arise from studies of damage to the brain and from studies using manipulations of behavioral experience. Studies of the effects of brain damage have shown that regions connected to the site of damage undergo reactive neuronal growth and reorganization. Studies manipulating behavioral experience have shown that regions involved in those behaviors also undergo neuronal changes. The emphasis of the present proposal is that these two types of plasticity may be interactive following brain damage. It is obvious that brain damage can produce behavioral changes. Based on abundant evidence that changes in behavioral experience can lead to central neuronal structural changes, it seems reasonable that these behavioral changes may influence and interact with plastic neuronal responses that occur after brain damage. Recent research has revealed a novel examples of neural plasticity following brain damage which seems o be mediated by behavioral changes. Unilateral lesions to the forelimb representation area of the sensorimotor cortex (Flsmc) in adult rats leads to impairments in the use of the forelimb contrlateral to the damage. Animals appear to compensate for these impairments, in part, by developing an over-reliance on the forelimb ipsilateral to the damage (the non-impaired forelimb). Examination of neurons and synapses within the forelimb motor cortex opposite the damage and the non-impaired forelimb revealed a marked dendritic growth and synaptogenesis. This neural plasticity appears to be mediated by the post lesion changes in the use of forelimbs and to be facilitated by the presence of a lesion in the opposite cortex. The processes underlying this behaviorally mediated neural plasticity are not understood and are potentially very important for ongoing attempts to understand brain adaptation to brain injury and to identify processes which can be manipulated to facilitate functional recovery. The proposed studies will (1) characterize structural (neuronal and glial) and connectional plasticity of the motor cortex and cerebellum following unilateral Flsmc lesions using quantitative electron microscopy, immunocytochemistry and anatomical tract tracing methods (2) relate these changes to behavioral changes using sensitive behavioral measures and behavioral manipulations, and (3) manipulate, and

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perhaps facilitate, adaptive neuronal and behavioral changes using complex motor skills training as "therapy" after the lesions. These studies may be of relevance to post-injury rehabilitation and neurolgical disorders in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BLOOD PRESSURE, COGNITIVE FUNCTION & MRI IN OLDER ADULTS Principal Investigator & Institution: Goldstein, Iris B.; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 15-APR-1994; Project End 30-NOV-2003 Summary: The present proposal is a longitudinal study of 135 elderly men and women who were first studied years earlier. The initial data indicated that among healthy individuals, aged 55-79 years, with relatively low blood pressures, 24-hour ambulatory blood pressure and heart rate (both level and variability) were significantly related to cognitive tests and signs of subtle brain damage as assessed by magnetic resonance imaging (MRI). The primary goal of this follow-up study is to demonstrate how ambulatory blood pressure technology can be useful in predicting future changes in brain and cognitive function which may be associated with apparent clinical problems but predate stroke and other cerebrovascular pathology. We will look at blood pressure and heart rate level and variability during two entire 24-hour periods, focusing on variability and level during wake and sleep, and the amount of fall from wake to sleep. In order to determine changes that have occurred, many procedures will be repeated, including a complete medical exam, casual blood pressure and heart rate measurement, and neuropsychological testing (sampling such critical areas as memory, attention, abstract reasoning, and cognitive flexibility. From MRI data we will determine both focal (T2 hyperintense lesions) and non focal (atrophic) brain changes. On the basis of our current findings, we expect that with the passage of time those individuals with higher casual and ambulatory blood pressure, greater blood pressure variability, and a smaller drop in blood pressure and heart rate during sleep will be likely to exhibit decrements in neuropsychological test performance and increases in T2 hyperintensities and brain atrophy. The fact that healthy, elderly individuals with normotensive blood pressure levels may be at risk for cognitive deficits and brain damage has clear implications for decisions regarding the appropriate level and variability of blood pressure to treat in elderly. Also, there is a need for future studies to concentrate on drug and behavioral methods which decrease variability of blood pressure and maintain 24-hour blood pressure control, in addition to decreasing casual blood pressure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BRAIN CELL APOPTOSIS AFTER INTRACEREBRAL HEMORRHAGE Principal Investigator & Institution: Lo, Eng H.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 31-JAN-2004 Summary: (Verbatim from the Applicant's Abstract) Intracerebral hemorrhage constitutes up to 15 percent of all strokes. Yet, compared to ischemic strokes, the mechanisms of brain cell damage after hemorrhage remain relatively unexplored. Prognosis after hemorrhage is less favorable compared to ischemia. Furthermore, with the risks of hemorrhage associated with thromblytic therapy, it becomes increasingly important to understand the mechanisms of brain damage after hemorrhage. In this proposal, we will use rat and mouse models of intrastriatal hemorrhage to test the

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overall hypothesis that cell death after hemorrhage is mediated, in large part, by apoptosis. Our preliminary data show that (i) parancymal ischemia accompanying hemorrhage is mild therefore this may favor apoptotic pathways of cell death; (ii) extensive internucleosomal DNA fragmentation occurs in cells surrounding the hemorrhage; (iii) DNA fragmentation post-hemorrhage is reduced by caspase inhibitors; and (iv) pro-apoptotic factors are released into extracellular space after hemorrhage and can be recovered by in vivo microdialysis. Our specific aims are: 1) establish the spatial and temporeal profile of apoptosis after hemorrhage, 2) quantify the levels of parenchymal ischemia adjacent to the hemorrhage and assess the accompanying release of pro-apoptotic factors (Fe2+, thrombin, FasL, TNF) into extracellular space, 3) test the efficacy of caspase inhibitors for reducing brain cell death after hemorrhage, and 4) investigate possible interactions between tissue plasminogen activator (tPA) and hemorrhagic apoptosis. For the 1st aim, we will map morphological, biochemical, and molecular markers of apoptosis after intracerebral hemorrhage. For the 2nd, parenchymal ischemia will be assessed with in vivo MRI methods that measure hemorrhagic progression, blood-brain barrier breakdown, and perfusion deficit. Additionally, we will use in vivo microdialysis to sample extracellular space after hemorrhage and assess the pro-apoptotic activity of Fe2+, thrombin, FasL and TNF with in vitro cultured cells. Experiments will also be performed in TNFR knockout and MnSOD overexpressing transgenic mice. For the third aim, we will characterize the therapeutic window for the caspase inhibitor zVADfmk, compare it with the free radical spin trap alphaPBN, and explore the benefits of combination therapy. Finally, since hemorrhage can be a serious complication of tPA therapy, we will examine as our 4th aim, the effects of tPA on apoptosis in our models. These proposed 3expeiments are expected to synergize with ongoing work in our labs that examine mechanisms that mediate tPA-induced hemorrhage in ischemic stroke (Lo, R01NS37074) and the efficacy of caspase inhibition for cerebral ischemia (Moskowitz, R01NS37141). Results may be used to improve the clinical management and treatment of intracerebral hemorrhage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAIN DAMAGE EFFECTS ON LANGUAGE PROCESSING Principal Investigator & Institution: Swinney, David M.; Professor; Psychology; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 31-DEC-2002 Summary: (adapted from the applicant's abstract): This proposal seeks to investigate the nature and neurological organization of language-based communicative capacities. It continues the investigator's long-standing aim to provide a detailed functional analysis of language processing in real-time. Studies are aimed at discovering how language comprehension is organized in the brain at the lexical, sentential (structural), and discourse levels. Normal and aberrant processing is examined at each level with consideration of effects of aberrant processing at one level on another. Ten series of experiments are proposed, two at the lexical level, five at the sentential level, and three at the discourse level. These studies are designed to provide a window on a wide range of language processes and how they interact and support one another (or fail to). The guiding hypothesis is that focal brain damage can disentangle cognitive subsystems that normally are inextricably intertwined by examining on-line moment by moment changes in activation, usually of lexical items, under manipulation of differing lexical, structural, or discourse factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BRAIN PATHOGENESIS

DEVELOPMENT

&

ETHANOL:

MICROGLIAL

Principal Investigator & Institution: Kane, Cynthia Jm.; Associate Professor; Anatomy; University of Arkansas Med Scis Ltl Rock 4301 W Markham St Little Rock, Ar 72205 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2003 Summary: Intervention in the extensive CNS pathology that underlies fetal alcohol syndrome is a high priority for alcohol researchers and is the long-term goal of this laboratory. There is no treatment for the brain damage associated with fetal ethanol exposure since the cellular and molecular mechanisms by which ethanol causes developmental neuropathogenesis are not yet understood. Although many years of study have focused on the neuronal and macroglial pathology caused by ethanol, the impact of ethanol upon an important, major cell type in the brain - the microolial cell has not been probed until these recent studies. This is surprising since ethanol damage to microglia may produce serious consequences within developing neuronal populations. Microglia communicate directly with neurons and the immune system to influence neuronal survival and function. They are the first line of defense against CNS insults, are the principal immune cells within the brain, and are active in cytokine secretion, reactive oxygen species secretion, antigen presentation and phagocytosis. Pilot studies reveal that damage to microglia occurs at ethanol concentrations far below that required to cause direct neuronal death. Parallel studies in the cerebellum and cultures of microglia have led to the HYPOTHESIS that ethanol pathogenesis in microglia occurs via specific cellular mechanisms: (1) ethanol inhibits microglial genesis and survival, (2) ethanol suppresses microglial maturation to further reduce the population of mature microglia, (3) the activity and functionality of microglia are impaired as a result, and (4) since there is no turnover of microglia, the impaired microglial functionality persists in the adult. This study will define the mechanisms of ethanol pathogenesis within the microglial population. A causal relationship between microglial pathology and neuronal toxicity will be defined. The critical period of microglial sensitivity to the teratogenic effects of ethanol will be determined. The acute, transient or persistent nature of ethanol pathogenesis within the microglial population will be distinguished. The molecular mechanisms of ethanol activity will be identified. The intracellular signaling pathways underlying ethanol activity will be manipulated in order to block ethanol pathogenesis in microglia. Block of ethanol-induced microglial pathology may provide a new opportunity to intervene in the brain damage caused by fetal ethanol exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAIN INJURY DURING CPR PREVENTED BY VASCULAR NITROXIDE Principal Investigator & Institution: Hsia, Carleton Jc.; Synzyme Technology, Inc. 1 Technology Dr, E-309 Irvine, Ca 92618 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 14-JAN-2004 Summary: (provided by applicant): The brain damage that frequently accompanies cardiac arrest and resuscitation is devastating. Fewer than 10% of cardiopulmonary resuscitation (CPR) attempts result in survival without brain damage when treatment occurs in pre-hospital or a non-special care hospital environment (Safar, 1993). We propose that a novel vascular-compartmentalized nitroxide, polynitroxyl albumin (PNA), which is an enzyme-mimic antioxidant, can reduce brain damage after CPR. We present preliminary results in a CPR model showing PNA attenuates CA1 hippocampal cell loss 7 days after cardiac compression and resuscitation in rats. Published results also

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support this premise. In a middle cerebral artery occlusion model of stroke, mice treated with PNA were significantly protected against neural damage. We propose to further establish the cerebral protective activity of PNA in a cardiac compression model of CPR. Our specific aims are: 1) to address quality assurance issues in PNA production and in vitro documentation of efficacy, and 2) to compare the impact of PNA, human serum albumin (HSA) and saline treatment on the structure and function of the hippocampus. The end-points for the second aim will include measures of pyramidal cell viability, NMDA receptor 1 immunoreactivity, and in vitro electrophysiology of hippocampal slices. This combined morphological and electrophysiological approach in a whole body ischemia model should further document the value of PNA as a potent neuroprotectant. Attainment of these goals will fulfill the feasibility requirement for further study of PNA in a Phase II SBIR grant, which will emphasize dose response, extended time course, neurological recovery and the therapeutic index of PNA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAIN TISSUE RESOURCE CENTRE FOR ALCOHOL RESEARCH Principal Investigator & Institution: Harper, Clive G.; University of Sydney Main Quadrangle, Bld A14 Sydney, 2006 Timing: Fiscal Year 2003; Project Start 01-SEP-2000; Project End 31-AUG-2008 Summary: (provided by applicant): Alcohol-related disorders of the nervous system are major public health and socio-economic problems throughout the world. Per capita consumption of alcohol in Australia is extremely high and, as a result, alcohol-related brain damage is common. A resource (brain bank) to provide these tissues to researchers has been developed in the Department of Pathology at the University of Sydney. The aim of this important and innovative facility, the New South Wales Tissue Resource Center (TRC), is to provide fresh-frozen (-80C) and/or formalin fixed tissues to research groups throughout the world who are studying these disorders. The development of new technologies in pathology and molecular biology means that many more questions can be addressed using appropriately stored human brain tissues. Quantitative neuropathological, neurochemical, neuropharmacological and even neuroimaging techniques can be applied to these tissues. It is possible to detect and measure protein and chemical changes in the brain and abnormalities in gene expression can be identified by the detection and analysis of mRNA molecules. Recent international scientific progress in alcohol-related brain damage attest to the success of the use of these techniques using autopsy tissues. Studies might include dependence and tolerance issues, genetic aspects of alcoholism and mechanisms underlying structural changes in the brain. The accuracy and reliability of the case characterization is paramount to the success of the research projects and reliability of data. Detailed protocols are in place to ensure this outcome. To obtain more cases with full life-style and medical histories a brain donor program called "Using our Brains" (donors sign up during life) has been launched to link with the TRC. A brain bank is necessarily a long-term project and maximum benefits will be seen as case numbers increase. Using the same case material and applying different scientific techniques, research groups can generate data that can be related to pre-mortem clinical, laboratory and radiological information. Funding is sought to help further develop this important resource for international researchers with an interest in alcohol-related brain damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CASPASE MEDIATED CELL DEATH AFTER BRAIN TRAUMA Principal Investigator & Institution: Raghupathi, Ramesh; Surgery; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2003 Summary: (provided by applicant): Traumatic brain injury (TBI) is the leading cause of death among individuals under the age of 45 in the United States and survivors are faced with chronic brain damage leading to debilitating behavioral dysfunction. Brain damage and behavioral dysfunction may be, in part, due to neuronal death following TBI. The hypothesis to be tested in this proposal is that post-traumatic neuronal cell death is a result of activation of the pro-apoptotic caspase family of cysteine proteases. The objectives of this proposal are to elucidate (1) the association between neuronal death in experimental TBI and in postmortem tissue from head-injured patients and the activation of the "executor" caspase-3, (2) whether caspase-3 activation occurs directly as a result of activation of the "initiator" caspase-8, and/or indirectly as a result of mitochondrial pathway which requires Bax translocation, cytochrome c release and caspase-9 activation, (3) whether caspase-8 activation occurs as a result of activation of the tumor necrosis factor family of death receptors, (4) the role of Bax in mediating trauma-induced caspase-9 activation and subsequent caspase-3 activation and cell death, and (5) whether post-traumatic inhibition of caspases-3, -8 and -9 will reduce the extent of injury-induced cell death. Immunoblot and immunohistochemical analyses using specific and selective antibodies will be utilized to temporal and regional patterns of activation of caspases-3, -8 and -9, resdistribution of Bax and cytochrome c, and, apoptotic neuronal damage, as indicated by the presence of cellular DNA fragmentation and morphologic analyses. Mice deficient in TNF will be used to determine the role of TNF in mediating activation of caspases-8 and -3, and eventual apoptotic cell death by using immunoblot, immunohistochemical and histological analyses. The role of Bax in trauma-induced activation of caspase-9 and -3, cytochrome c redistribution, apoptotic neuronal death and behavioral dysfunction will be examined using immunoblot and immunohistochemical techniques, and by testing cognitive and motor function in braininjured, Bax-deficient mice, followed by histological analysis of cell death. The effect of post-traumatic treatment with peptide inhibitors selective for caspases-3 (DEVD), -8 (IETD) and -9 (LEHD), on the extent of regional cell death and behavioral dysfunction will provide the mechanistic link between caspase activation and TBI-induced pathology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CEREBRAL OXYGENERATION DURING CARDIOPULMONARY BYPASS Principal Investigator & Institution: Jonas, Richard A.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2001; Project Start 15-JUL-1998; Project End 31-MAY-2005 Summary: (Provided by Applicant): Brain damage including focal and global cerebral injury as well as suboptimal cognitive developmental outcome continue to be important problems after pediatric heart surgery. Previous work in this area has focused on deep hypothermic circulatory arrest (DHCA) which is now used infrequently. As an alternative to DHCA reduced flow hypothermic cardiopulmonary bypass (CPB) is employed. However in the absence of a validated method for real time monitoring of brain oxygenation there are no guidelines for minimal safe flow and pressure under specific CPB conditions of pH, hematocrit and temperature. The proposed study will

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employ the new techniques of near infrared spectroscopy (NIRS) and intravital microscopy (IVM) to defme a minimal safe flow rate for specific perfusion conditions. The study will be conducted using a juvenile piglet model exposed to various degrees of flow reduction with survival for 4 days postoperatively. Survival allows assessment of functional evidence of brain injury through behavioral assessment by a blinded veterinarian observer as well as meaningful histology determined by a blinded neuropathologist. These functional and structural endpoints will be correlated with indices of brain oxygenation measured by NIRS (Tissue Oxygenation Index (TOl), Oxyhemoglobin nadir time (Hb02 nadir time)) as well as indices of microvascular perfusion measured by IVM (functional capillary density (FCD), NADH fluorescence). The second phase of the proposed study will test the hypothesis that critically reduced low flow perfusion causes hypoxic endothelial injury of cerebral blood vessels. This results in reduced constitutive endothelial nitric oxide synthase (eNOS) activity resulting in microvascular regional ischemia previously described as the "no reflow phenomenon." Acute studies will be undertaken in the piglet model using Western immunoblotting and immunocytochemistry as well as resistance vessel myography to measure eNOS activity. eNOS activity will be manipulated by substrate enhancement and inhibition. The role of inducible NOS (iNOS) in causing neurotoxicity in this setting will also be explored. The proposed study has the potential to reduce the risk of brain injury in children undergoing heart surgery by defining the margin of safety achieved with various perfusion conditions. By enhancing understanding of mechanisms of cardiopulmonary bypass-related brain injury it will facilitate development of novel pharmacologic methods to further reduce the risk of brain damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CEREBROVASCULAR EFFECTS OF PRENATAL ALCOHOL Principal Investigator & Institution: Gleason, Christine A.; Professor and Head; Pediatrics; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: (adapted from applicant's abstract) Fetal brain damage resulting from maternal alcohol abuse is one of the leading causes of mental retardation in the United States and yet the mechanisms by which in utero alcohol exposure adversely affects fetal brain development and function are largely unknown. The investigators have recently demonstrated attenuated hypoxic; cerebral vasodilation in newborn sheep which were exposed to chronic maternal alcohol intoxication in the first trimester. Based on these and other supportive findings, they have developed the hypothesis that in utero alcohol exposure affects the development and function of cerebral blood vessels, and that the consequent vascular abnormalities may contribute to the pathogenesis of brain damage associated with fetal alcohol exposure. The objective of this proposal is to further characterize the cerebrovascular and neuropathological effects of chronic fetal alcohol exposure in sheep, and to evaluate potential mechanisms for and consequences of these effects. They will use in vivo and in vitro physiological methods as well as neuropathology and immunocytochemistry to address the following aims: Aim #1: To determine whether chronic maternal alcohol intoxication in the first or second trimester alters fetal cerebrovascular responses to hypoxia in vivo later in pregnancy. Aim #2: To compare the neuropathologic effects of repeated hypoxic insults in fetuses previously exposed to either alcohol or saline in utero. Aim #3: To determine mechanisms whereby prenatal alcohol exposure alters cerebrovascular reactivity by examining the maturation of the cerebral vascular network and by studying the density and expression of cerebral vasodilatory substances. Aim #4: To determine whether prenatal alcohol alters

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cerebrovascular reactivity in vitro by testing the responses of cannulated, pressurized fetal and adult sheep arterioles to vasoactive substances. Aim #5: To determine whether prior prenatal alcohol exposure during pregnancy alters fetal or adult cerebrovascular responses to acute alcohol intoxication. Results from these studies will provide important new information regarding the contribution of fetal cerebrovascular abnormalities to the brain damage associated with fetal alcohol exposure and will lead to the development of perinatal preventive and/or therapeutic strategies for pregnant women who use alcohol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHANGES IN ADDICTIVE BEHAVIORS AFTER BRAIN LESIONS Principal Investigator & Institution: Bechara, Antoine; Assistant Professor; Neurology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): An R21 for CEBRA: The blossoming field of functional neuroimaging studies has pointed to a network of neural structures that subserve the cognitive and behavioral processes of drug addiction, including nicotine. This neural network includes the orbitofrontal cortex, anterior cingulate, insular cortices, the amygdala, and the striatum (dorsal and ventral (nucleus accumbens) striatum). However, no work to date has addressed how damage to different components of this neural network in humans may impact the craving, subjective feeling of drug administration, and active seeking of drugs. Nor any study has asked which, if any, of these components is critically necessary for maintaining the addiction to drugs. This proposal will take advantage of our unique University of Iowa Department of Neurology Patient Registry to begin addressing some of these important issues in patients addicted to cigarette smoking. Our goal is to understand how focal lesions in brain areas hypothesized to be critical neural substrates for addiction affect cigarette smoking behavior, cue-induced craving and smoking urge, as well as the acute subjective effects of smoking. The studies we propose here seek to address 3 specific aims: (1) determining the real-life changes in smoking behavior, cigarette craving, and smoking satisfaction after the onset of brain damage; (2) determining in laboratory experiments the effects of focal brain lesions on (a) the emotional reactivity to smoking cues, (b) the subjective feeling of craving and urge to smoke, and (c) the subjective feeling of smoking a cigarette; and (3) establishing a Registry of neurological patients pre-morbidly known to abuse other substances, including alcohol, stimulants, and opiates, so that they will participate in future research on addiction to drugs. The proposal is promising because (1) it provides a novel perspective for looking at the neurobiological basis of addiction, which compliments and validates the ongoing work with functional neuroimaging techniques; (2) it may help us identify specific brain regions, which damage (or dysfunction) can effectively break the cycle of addiction. The proposed studies are feasible because of (1) our access to the patient population and resources necessary for the conduction of this type research; 2) the guidance of our investigations by an established theoretical framework, the somatic marker hypothesis, and by abundance of background evidence from functional neuroimaging studies. Thus, the proposed research is a beginning of a novel approach with potential for developing more effective therapies for breaking the vicious cycle of addiction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHRONIC CORRELATES

ALCOHOL

17

CONSUMPTION--NEUROBIOLOGICAL

Principal Investigator & Institution: Walker, Don W.; Professor; Neuroscience; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-JUL-1978; Project End 31-OCT-2002 Summary: Chronic ethanol consumption produces brain damage manifested by morphological, physiological, biochemical and cognitive abnormalities. Controlled studies in laboratory animals have provided convincing evidence of the specificity of ethanol in inducing these abnormalities, however neither the mechanism of ethanol toxicity nor the specific morphological or functional basis of ethanol induced cognitive deficits are known. Considerable evidence has demonstrated that chronic ethanol treatment (CET) results in significant loss of hippocampal neurons, altered dendritic structure and function of surviving neurons and loss or rearrangement of synaptic connections. Damage to the septohippocampal pathway is implicated in deficient memory and learning and this has been attributed to cholinergic deafferentation of the hippocampus, although the role of GABAergic projections has not been carefully examined. Recently it has been reported that CET produces a progressive decline in spatial memory, cholinergic function and acetylcholinesterase-positive neurons in the septal area. If confirmed, these findings represent an important link in our understanding of the morphological and functional basis for the memory deficits found in alcoholism. The proposed work will attempt to confirm and extend these results to include studies of cholinergic and GABAergic morphology and function in the septa] area and the hippocampus. We will investigate the hypothesis that the septohippocampal pathway is particularly vulnerable to CET. Since septohippocampal neurons are dependent on trophic factors for survival and maintenance of their function, we will also investigate the hypothesis that their vulnerability to CET is mediated by the suppression of neurotrophic influence. The first series of experiments will use immunohistochemical, biochemical and electrophysiological techniques to examine the effects of CET on the morphology and function of the septohippocampal pathway. Both cholinergic and GABAergic septohippocampal neurons in the septal area and their target neurons (principal cells and interneurons) in the hippocampus will be studied. The second series of experiments will test the hypothesis that the vulnerability of the septohippocampal system to CET is mediated by the suppression of neurotrophic influences. Tissue culture bioassay and ELISA methods will be used to determine if CET produces a decrease in the content or bioactivity of neurotrophic factors in the hippocampus and/or if acute ethanol exposure attenuates or blocks the action of neurotrophic factors. Immunohistochemical methods will be used to determine if CET reduces the number of septohippocampal neurons immunoreactive for neurotrophic factor receptors, thus further limiting the availability of neurotrophic influence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COGNITIVE & BEHAVIORAL CONSEQUENCES OF FOCAL BRAIN LESIONS Principal Investigator & Institution: Anderson, Steven W.; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002 Summary: Little is known regarding the effects of damage to specific regions of the human brain when this damage occurs early in life, although there is reason to believe that certain impairments of cognition and behavior are a consequence of early-onset

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Brain Damage

brain damage. The NINDS has identified as high research priorities the gathering of more precise descriptions of behavior patterns and developmental disorders, and the achievement of greater understanding of the neural basis of cognition, emotion, and their interaction. Lesion method studies of individuals who have sustained early-onset focal brain damage are an important means to fulfill such priorities, and during the current funding period we have conducted pilot studies of adults with early-onset focal brain damage and marked cognitive and behavioral impairments. Conditions causing focal brain damage in childhood are not common, but a sufficient number of patients is now available for systematic studies. Here we propose to establish a registry of patients with damage to circumscribed brain regions acquired during development, namely during the perinatal period, infancy, childhood, or adolescence, and to perform hypothesis-driven studies of these individuals using: (1) precise description of brain lesions using MRI with 3-D reconstruction, (2) comprehensive characterization of cognition and behavior with standardized, age-appropriate neuropsychological measures, (3) standardized indices of functional outcome (academic achievement, employment, quality of life, and family burden), and (4) experimental measures of cognition and behavior, with a focus on emotion, moral reasoning and social competence Delineation of relationships between damage to specific neural systems early in life and the short- and long-term consequences for cognition and behavior should provide fundamental information which will be relevant to the understanding of human development, and permit better evaluation and treatment of treatment of neurobehavioral disorders with onset in childhood. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COGNITIVE NEUROSCIENCE OF DEMENTIA Principal Investigator & Institution: Farah, Martha J.; Professor; Psychology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 15-SEP-1997; Project End 31-AUG-2003 Summary: After 10 years as a PI in research on cognitive impairments following stroke, and some recent preliminary work on cognition in AIzheimer's disease (AD), l have decided to turn my attention more fully towards the dementias. Although cognitive neuroscience has generally concentrated on focal brain damage, I believe that AD and other dementias, including Parkinson's disease, Huntington's disease and semantic dementia, have much to teach us about the functioning of the normal mind and its neural substrates, particularly with respect to semantic memory and visual cognition, my two areas of specialization. In addition, the dementias represent a major public health problem, and the cognitive neuroscience approach may be able to contribute towards solutions to this problem. I am therefore requesting support to undertake five years of study, research, and career development in the cognitive neuroscience of dementia. During this period I will carry out the proposed research on semantic memory and visual cognition in AD while learning more about AD and other dementias. My goal is to become as competent in research on dementia as I am now in research on focal brain damage, and thereby to contribute to our basic-science understanding of the dementias and to advances in the diagnosis and management of these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COMPREHENSION IMPAIRMENT AND RIGHT BRAIN DAMAGE Principal Investigator & Institution: Tompkins, Connie A.; Professor; Communications; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260

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Timing: Fiscal Year 2003; Project Start 01-SEP-1993; Project End 30-NOV-2006 Summary: (provided by applicant): The proposed research aims to improve our understanding of discourse comprehension deficits often incurred by adults with right hemisphere brain damage (RHD) as a result of stroke. Among the most prominent impairments in this population is a difficulty comprehending material that supports or induces multiple, ostensibly competing interpretations. While these deficits can be quite socially handicapping, they are poorly understood, with conflicting explanations the rule. Two groups of adults, 50 with RHD and 45 without brain damage, will complete auditory sentence- and discourse-level comprehension tasks. Tasks will be designed to generate less explicit and more sensitive than usual indices of comprehension. One main goal of the proposed work is to test the Pl's 'suppression deficit' view of typical RHD deficits in comprehending material that supports competing interpretations, against influential theoretical alternatives in the lexical-semantic processing and social cognition domains. The proposal aims to (1) resolve conflicting hypotheses (suppression deficit vs. maintenance deficit) about RHD lexical-semantic deficits when processing sentences that contain words with alternative meanings or features; (2) test the claim of both the suppression and maintenance deficit positions that such word-level deficits will predict typical RHD discourse comprehension deficits; (3) test the hypothesis that RHD suppression deficits also will predict 'presumed' social cognition impairments (i.e., 'theory of mind' (TOM) deficits), as inferred from common discourse assessment tasks; (4) challenge the validity of the TOM-deficit attribution for RHD comprehension impairments, given various confounds in common TOM assessments; (5) test specific hypotheses about neuroanatomic bases of possible RHD lexical-processing and TOM deficits; (6) assess whether competing proposals can be reconciled with reference to within-hemisphere lesion location; and (7) evaluate the within domain generality of results with the same large sample of RHD adults, using multiple measures of word and discourse-level deficits. The results of the proposed investigations will advance theorizing in a nascent area of investigation and, by bolstering theoretical rationales for assessment and treatment, have eventual clinical implications for this understudied population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTRASTING TREATMENT FOR SENTENCE PRODUCTION DEFICITS Principal Investigator & Institution: Maher, Lynn M.; Associate Professor; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001 Summary: The syndrome of agrammatism is a form of language impairment that affects sentence processing and results from acquired brain damage. Treatment studies which have taken the complexity of the underlying system into account have demonstrated improvements in sentence processing. What has not been determined is how the underlying physiology of the recovering system effects or interacts with this type of intervention. Furthermore, while there is a developing body of evidence to suggest that learning environments which encourage accurate responses and prevent error responses (i.e. errorless learning) are more efficacious than traditional models of errorful learning, there has been minimal application of this learning theory towards the rehabilitation of acquired brain damage, except in the area of memory (Wilson et al., 1994). The purpose of this subproject is to apply recent advances in learning theory and cognitive linguistics to the rehabilitation of the sentence production deficits observed in this syndrome. We will test the application of errorless learning, an approach supported by parallel

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distributed models of learning and cognition, to the rehabilitation of sentence production deficits. We will do this by comparing the effectiveness of this approach so that of more traditional, errorful learning. Furthermore, we will compare the impact of vicariative substitutive treatment method (i.e. one designed to encourage alternative processes to assume damaged functions) that is derived from current cognitive linguistic models of sentence production, with a restitutive approach (i.e. designed to restore function) that is more typical of traditional aphasia therapy. In so doing we can address the relative limitations of the underlying physiology of the damaged system since current therapies of brain repair suggest that the potential for recovery of function may be time-dependent. By comparing errorless and errorful learning strategies and their interactions with substitutive versus restitutive treatment approaches in a single subject design, we may identify rehabilitation environments which can maximize the individual's response to rehabilitation. It is also the goal of this project to determine if improvements observed in the controlled rehabilitation environment generalize and have an effect on the individual's functional ability to communicate. Generalized improvement in sentence production would contribute to greater independence and improved quality of life. Finally, we will attempt to associate functional changes in sentence production as a result of rehabilitation with observable changes in neural activity using fMRI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTROLLED REPERFUSION FOR WHOLE BODY ISCHEMIC INJURY Principal Investigator & Institution: Buckberg, Gerald D.; Surgery; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The long-term objective is to develop a new approach to treat cardiac arrest. Currently, despite early, successful defibrillation in half the patients, the overall mortality rate is 95%. Furthermore, approximately 70% of these few survivors of whole body ischemia develop neurologic injury: we may save the heart, but lose the brain. The causative factors are inadequate treatment of the underlying cause of arrest by insufficient a) delivery of brain flow during CPR, b) restoring of heart blood supply to allow it to recover, and c) correction of the underlying cardiac cause. A novel approach will be taken to 1) promptly use the heart lung machine without opening the chest by an approach through leg vessels to mechanically, and temporarily, take over heart function, 2) change its prime pharmacologically to make a metabolic fuel for recovery, and 3) correct the underlying cause. We will use a relevant surgical model of either deep hypothermic circulatory arrest (DHCA) or lethal normothermic ventricular fibrillation for 10 minutes to cause whole body ischemia. Both insults cause high mortality and brain damage. We will present pilot studies showing complete heart and 100% brain recovery by integrating the specific aims of these three interventions. These results were achieved by use of a standard prime of the CPB circuit, and adding either a sodium hydrogen exchange inhibitor or specially filtering the white blood cells that cause reperfusion damage. We will extend the period of ischemia to two hours and show how this cardiac arrest model (that permits regional brain flow through the carotid arteries) can also be used to treat stroke. If this novel method of management is correct, the scheme of diagnosis and management of this almost always fatal cardiac arrest complex will change markedly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEVELOPMENT OF COGNITIVE FUNCTIONS: FRONTAL LOBE Principal Investigator & Institution: Diamond, Adele D.; Director; Eunice Kennedy Shriver Center; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2001; Project Start 10-JUN-1997; Project End 31-MAY-2003 Summary: The goals of the proposed research are three:(1) to test children with brain damage localized to frontal cortex on tests (a) which have been linked specifically to frontal cortex function through neuroanatomical and behavioral studies with infant and adult monkeys and (b) on which we know the normal developmental progression in children. Important aspects of this work will be to look for converging evidence from diverse tests all linked to the same subregion of frontal cortex, and to attempt to dissociate performance on these tests from performance on tests linked to other neural circuits. The goal is to develop non-invasive tests capable of detecting frontal cortex damage in infants and young children. Presently such damage often goes undetected for many years because of the lack of such tests. (2) to investigate the relationship of dopamine levels to performance on these tasks, and to begin to investigate the hypothesis that the fundamental maturational change which underlies the emergence of cognitive abilities dependent on frontal cortex during infancy is increasing levels of frontal cortex dopamine. To do this, children with early-treated PKU, who have no known structural brain damage but who are vulnerable to reduced levels of dopamine will be tested. Because their general cognitive functioning is good, if deficits are found they are likely to be selective. If they are selectively impaired on tests of frontal cortex function, this will be the first demonstration in humans of a cognitive deficit on frontal cortex tasks from dopamine depletion alone. Because L-dopa and the dopamine precursor, tyrosine, can be taken orally, there is an excellent chance that if deficits are found, therapeutic interventions will be possible to alleviate any impairments. (3) to better understand the abilities required for success on tasks that depend on frontal cortex function. Hypotheses will be considered that suggest that memory for space, and/or time, or for relational information in general is dissociable from memory for other information and dependent upon frontal cortex function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEVELOPMENTAL BRAIN DAMAGE BY DRUGS OF ABUSE Principal Investigator & Institution: Olney, John W.; Professor; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-SEP-1994; Project End 31-JAN-2005 Summary: (adapted from applicant's abstract)This is an application for competing renewal of a grant that was funded for five years (1994-1999) and was devoted to an investigation of neurotoxic damage induced in the adult rodent brain by phencyclidine (PCP) and related drugs that block NMDA (N-methyl-D-aspartate) glutamate (Glu) receptors. During the grant period, the applicants developed significant new insight into the mechanism of this adult brain damage syndrome and into the potential relevance of this mechanism to human neuropsychiatric disorders. In the course of this work, it was discovered that the immature brain is not vulnerable to damage by this mechanism, but that NMDA antagonists, including PCP and ketamine (both of which are drugs of abuse), can induce an extensive pattern of permanent damage in the developing rat brain by an entirely different mechanism. As a tool for studying this mechanism we have primarily used MK801, a powerful NMDA antagonist that binds with high affinity to the PCP recognition site in the NMDA receptor ion channel. Our interpretation of the

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mechanism, based primarily on MK801 studies, is that immature neurons during a specific stage in development (the synaptogenesis stage, also known as the brain 'growth spurt' stage) are intrinsically dependent on NMDA receptor stimulation for survival, and they are programmed to commit suicide (die by apoptosis) if deprived of this receptor input for several consecutive hours during this critical period. The objectives of this renewal application are to further characterize the ability of several drugs of abuse to trigger apoptotic neurodegeneration in the developing mammalian brain, and evaluate the potential relevance of this neurodegenerative phenomenon to human neurodevelopmental disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIETARY RESTRICTION, AGING, LEARNING, AND LTP Principal Investigator & Institution: Barea-Rodriguez, Edwin J.; University of Texas San Antonio San Antonio, Tx 78249 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: The oxidative stress theory of aging states that damage to molecules that are important for cellular function increases with age. This increase causes a decline in normal physiological function in a number of organs including the brain. Normal aging may be accompanied by a decline in cognitive function. It is widely believed that learning and memory are mediated by dynamic changes in the brain. Long-term potentiation (LTP) is an activity-dependent form of synaptic plasticity thought to be to be the most plausible mechanism for learning and memory. LTP was first discovered in the hippocampus, a neural structure associated with learning and memory. Interestingly, aging is accompanied by impairments in both hippocampal-dependent learning and LTP. Dietary restriction (DR) is the only environmental manipulation known to extend lifespan in all mammals studied. Many studies report that DR can prevent age-related impairments in hippocampal-dependent learning tasks. Most DR studies implement a life-long DR regimen and the animals used are adults at the time of testing. Few studies investigate the effects of short-term DR in aged rats and its consequences for learning and memory. Also, the relationship between DR and LTP longevity remains largely unexplored and no current studies document the effects of short-term DR on LTP in aged rats. The long-term goal of this research is to investigate age-related increases in oxidative brain damage, age-related deficits in hippocampaldependent learning and medial perforant path (MPP)-CA3 LTP in awake rats, as well as their prevention by short-term (3 months) DR. In Specific Aim 1, experiments will investigate whether short-term DR can improve the performance of aged rats in trace fear conditioning and the Morris Water Maze. In Specific Aim 2, experiments will investigate whether short-term DR can extend LTP longevity in aged rats. In Specific Aim 3, experiments will investigate whether short-term DR decreases levels of oxidative brain damage and increases levels of the neuroprotective brain proteins Heat Shock Protein 70 and Brain Derived Neurotrophic Factor. These studies are expected to increase our understanding of how oxidative damage impairs hippocampal-dependent learning and LTP, how such impairments can be prevented by dietary manipulations, and whether the proposed molecular mechanisms are associated with such improvements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIFFUSE BRAIN ABNORMALITY IN SICKLE CELL DISEASE Principal Investigator & Institution: Steen, R Grant.; St. Jude Children's Research Hospital Memphis, Tn 381052794

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Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 31-MAY-2003 Summary: Sickle cell disease (SCD) is the most common hemoglobin mutation in the US, affecting 60,000 people. SCD is often associated with focal brain abnormalities that worsen as the disease progresses, and conventional MRI (cMRI) can demonstrate focal damage even in infants. At least 1 in 4 SCD patients show cMRI evidence of focal abnormality by age 20. However, we hypothesize that diffuse brain abnormality is actually more common than focal damage, and that it usually precedes focal damage. Because diffuse abnormality cannot be well-visualized by cMRI methods, the prevalence of diffuse abnormality is not known. Our goal is to determine whether new quantitative MRI (qMRI) methods are more sensitive than cMRI methods to diffuse brain damage in SCD patients, and to ascertain whether diffuse brain abnormality correlates with the clinical course of disease. We will use qMRI methods developed in our lab, in a prospective, longitudinal, clinical study of young SCD patients. We will enroll 50 patients and 50 sibling controls, and follow all enrolled subjects prospectively for 5 years. We will use T1 mapping and quantitative MR angiography (qMRA), to characterize the prevalence and to evaluate the significance of diffuse brain abnormality in pediatric SCD patients. Data from cMRI, qMRI and qMRA will be correlated with clinical and psychometric data, to determine which MR imaging data are predictive of clinical severity or development of cognitive deficits. To be specific, we will: characterize the relationship between diffuse T1 reduction and focal brain abnormality detected by cMRI; determine if diffuse T1 reduction is associated with subtle loss of gray or white matter volume measured by cMRI image segmentation; ascertain if diffuse T1 reduction is correlated with psychometric deficit; and establish whether diffuse T1 reduction is associated with vasculopathy, including ectasia or stenosis of the cranial arteries. Because infarctive stroke risk in young SCD patients is 6-fold higher than in healthy adults, SCD patients may provide a clinical model for the most common type of stroke in elderly adults. We will establish whether these novel qMRI methods provide a sensitive and clinically-relevant indicator of diffuse brain injury. Our long- range goal is to determine the mechanisms causing cognitive loss in SCD patients, in an effort to determine a therapeutic strategy to minimize such damage in these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DISCOURSE PERFORMANCE AFTER RIGHT BRAIN DAMAGE Principal Investigator & Institution: Brownell, Hiram; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001 Summary: Naturally occurring communication very often takes the form of discourse such as, for example, a friendly conversation. The success of conversations that serve social as well as informational purposes is largely determined by whether the participants obey the rules governing polite discourse. Inappropriate comments or word choices can divert attention from the literal message and, more importantly, can undermine the social bond between the people speaking. Abiding by these conventions requires understanding what affects the feelings other people, keeping track of what other people know and do not know, and knowing what is appropriate in different discourse settings defined by people's feelings and knowledge. The effects of unilateral brain injury on patients' success with these aspects of discourse. The patients of most interest are those who have sustained right hemisphere brain damage (RHD) due to stroke but who do not have aphasia. Non brain-damaged control subjects will provide the primary comparison group in light o the heavy linguistic demands of most of the proposed tasks, but right and (nonaphasic) left prefrontally damaged patients will be

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tested when possible to provide information on localization of function, as will aphasic LHD patients with middle cerebral artery territory lesions. Results from the planned studies will provide a window onto the mental life of the brain-injured individual and will help. us understand the ways in which brain injury impairs social reasoning which is a major source of difficulty for RHD patients and their families. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF ALCOHOL ABUSE ON THE AGING BRAIN Principal Investigator & Institution: Fein, George; President; Neurobehavioral Research, Inc. Corte Madera, Ca 94925 Timing: Fiscal Year 2001; Project Start 25-SEP-1997; Project End 31-AUG-2005 Summary: (Adapted from the Investigator's Abstract) The primary goal of the proposed research is to test two opposing models of why the CNS morbidity due to alcohol abuse is greatest in the elderly alcoholic. The generally accepted age-related vulnerability model postulates a greater vulnerability of the older brain to the toxic effects of alcohol. An alternative model, the cumulative effects model, postulates the duration and amount of abusive drinking (regardless of when in the lifespan it took place) and the aging process as the only factors underlying the greater CNS morbidity in the older alcoholic. In the cumulative effects model, the younger brain is able to compensate for the damage done by alcohol abuse/dependence until cognitive losses associated with normal aging undermine these compensatory mechanisms and the CNS morbidity due to alcohol abuse/dependence (earlier in life) becomes apparent. There is no data in the literature to test the differential predictions of these models (e.g., data on the CNS status of elderly individuals who were alcoholic into late middle age, but who have been abstinent for 10 years or more) because research to date has focused only on recently abstinent individuals. We will test these two opposing models of how age modulates chronic alcohol abuse effects on CNS structure and function using state-of-the-art methods. Structural brain imaging will be used to assess regional morphological brain changes; electrophysiological and neuropsychological testing will assess functional changes in information processing abilities. The study will use a cross-sectional design with five groups, each group consisting of 30 males and 30 females. The secondary goal of this project is to determine whether there are gender differences in the effects of chronic alcohol abuse on CNS function, and the matter in which age modulates these effects. Our final goal in the project is to examine other factors (e.g., brain "functional reserve," presence of the APOE-epsilon4 allele) that may modulate the effects of chronic alcohol abuse/dependence and age on brain structure and function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENDOTHELIAL PRECONDITIONING AND ISCHEMIC BRAIN INJURY Principal Investigator & Institution: Keep, Richard F.; Associate Professor; Neurosurgery; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 25-JUL-1996; Project End 31-MAY-2008 Summary: (provided by applicant): Ischemic preconditioning (IPC) has proved to be one of the most effective methods of reducing ischemic brain damage in animal models of stroke. Attention has focused on the mechanisms by which neurons may be protected by such preconditioning. However, we have found that IPC also protects the endothelium, which forms the blood-brain barrier, from ischemic damage. 'Ischemic' preconditioning

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also protects cerebral endothelial cells in vitro from oxygen glucose deprivation induced injury indicating that there can be direct preconditioning of the endothelium. Damage to the cerebral endothelium may potentiate ischemic brain injury in a number of ways and determining mechanisms to reduce endothelial damage is particularly pertinent at the moment considering the role of endothelial injury (hemorrhagic transformation) in limiting the use of tissue plasminogen activator for the treatment of ischemic stroke. We will examine the mechanisms involved in cerebral endothelial preconditioning both in vivo (rat middle cerebral artery occlusion) and in vitro (primary cultures of rat cerebral microvessel endothelial cells). The in vitro experiments will facilitate exploration of the mechanisms involved in preconditioning while assuring that the preconditioning acts directly on the endothelium. The in vivo experiments will ensure that the mechanisms elucidated in vitro also occur in the whole animal as well as allowing an assessment of the effects of preconditioning on other parameters (such as blood flow, capillary morphology and infarction). Overall the proposal has three main goals. 1) Determine the time course of preconditioning and the extent of its effects on the endothelium (Specific Aim 1). 2) Determine the events that can trigger endothelial preconditioning (Specific Aim 2). 3) Determine what mechanisms are triggered to protect the endothelium (Specific Aim 3). These experiments should provide information on: A) Endogenous defense mechanisms that protect the cerebral endothelium from ischemic injury and which may be therapeutic targets. B) The role of endothelial preconditioning in the effects of IPC on the brain. C) The role of endothelial injury in the overall effects of ischemia on the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENERGY METABOLISM Principal Investigator & Institution: Smith, Michael B.; Chief, Center for Nmr Research; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2002 Summary: The overall objective of this research component is to investigate the highenergy biochemical mechanisms whereby the perinatal brain is damaged by hypoxiaischemia and how brain injury can be prevented or reduced through specific modalities of therapy. Specific Aims include: 1) to characterize the earliest alterations in highenergy phosphate reserves which occur during perinatal cerebral hypoxia-ischemia and to correlate these changes with perturbations in cerebral energy utilization, cerebral glucose utilization, glutamate and nitric oxide neurotoxicity, and intracellular calcium accumulation; 2) to correlate the concentrations in cerebral high-energy phosphate reserves and the changes which occur during hypoxia-ischemia using 31P magnetic resonance (MR) spectroscopic methods and enzymatic, fluorometric techniques; 3) to characterize the secondary (delayed) energy failure which occurs during recovery from perinatal cerebral hypoxia-ischemia and to correlate the alterations with the presence and severity of hypoxia-ischemic brain damage; 4) to ascertain underlying biochemical mechanisms whereby the glucocorticosteroid, dexamethasone, protects the perinatal brain from hypoxic-ischemic damage; 5) to determine the protective influence of magnesium sulfate on perinatal hypoxic-ischemic brain damage and, if so, to ascertain its mechanism of action; and 6) to investigate further the presence and extend of alterations in diffusion-weighted and T2-weighted imaging during recovery from perinatal cerebral hypoxia-ischemia and to correlate any changes with the nature and extent of cerebral edema and associated neuropathologic alterations. Seven-days postnatal rats will undergo unilateral cerebral hypoxia-ischemia, during and following which the animals will undergo those procedures necessary to obtain sequential 31P and

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1H NMR spectra which will allow for measurements of the alterations in high-energy phosphate reserves and other metabolites which result from the insult. Other animals will undergo MR imaging at specific intervals following cerebral hypoxia-ischemia. Other experiments will elucidate the neuroprotective effect of dexamethasone, magnesium sulfate, and L-NAME on hypoxic-ischemic brain damage in the developing rat. Analytic procedures will include sequential measures with NMR spectroscopy as well as brain tissue analysis of high-energy phosphate reserves and other metabolites using enzymatic, fluorometric techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ETIOLOGY OF CELLULAR DAMAGE AFTER EXPERIMENTAL STROKE Principal Investigator & Institution: Aronowski, Jaroslaw A.; Associate Professor; Neurology; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: The objective of this proposal is to examine the relationship of the transcription factor nuclear factor-kappaB (NF-kappaB), and its activation pathway, to neuronal damage induced by intracerebral hemorrhage. The experiments proposed are largely based upon preliminary data linking cellular death to NF-kappaB activation after cerebral infarction and hemorrhage, and our recent finding of involvement of a novel enzyme in the NF-kappaB regulatory pathway, inhibitor kappaB-kinase (IKK). Our overall hypothesis is that the acute phase response following cerebral hemorrhage is in part a dynamic inflammatory response coordinated at the gene transcription level. We hypothesize that NF-kappaB activation leads to neuronal death that is controlled upstream by the phosphorylation of inhibitor kappaB (IkappaB) by IKK. We propose two specific aims. First using carefully selected pharmacologic (15d-PGJ2, IKK inhibiting peptide and proteasome inhibitor) and molecular (knockout and transgenic mice) probes, affecting important components of the NF-kappaB transduction pathway at different up-stream levels of its activation, we will determine the causal relationship of the NF-kappaB pathway to brain damage (neuronal loss and behavioral dysfunction) after intracerebral hemorrhage. Next using relevant biochemical, microscopic and molecular techniques and brains from animals that benefited from inhibition of upstream components of NF-kappaB activation, we will describe the temporal and spatial characteristics of this inhibition and pin down the exact components of the pathway down-stream from the inhibition site, including IKK activity, IkappaB-phosphorylation, NF-kappaB DNA binding and NF-kappaB gene transactivation that were affected by these inhibitions. Subsequently, using a single cell level analysis we will identify what cell type(s) represent the primary target of anti-NF-kappaB therapy in treatment of ICH. These laboratory studies in animal models of hemorrhage and infarction will provide the framework for developing a possible new approach to therapy for stroke in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EXACERBATION OF ALZHEIMER'S DISEASE BY NITROUS OXIDE Principal Investigator & Institution: Kofke, W Andrew.; Anesthesia; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2004 Summary: Research Topic: 3. Alzheimer's Disease Drug Discovery. Recent clinical reports indicate that the onset of Alzheimer's disease (AD) is earlier with prior mild neurologic insults or with increasing prior anesthetic exposure. The specific

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characteristics of anesthesia history that predispose to this earlier onset of AD are unknown but such observations raise the concern that something about anesthesia may constitute a mild neurologic insult. NMDA antagonists such as nitrous oxide (N20) and MK801 have been demonstrated to have a bimodal dose-related protective and then neurotoxic effect in normal rodents, with congruent regional activation by N20 reported in humans. There is ample data indicating an important role for neuroexcitation with associated oxidative injury in the pathogenesis of AD. It thus becomes reasonable to suggest an interaction between the genesis of AD and prior N20 exposure. Clinically N20 is an extremely common anesthetic with virtually ubiquitousexposure by almost everyone at some point in life. This makes its use a reasonable and potentially immensely important area to explore in the pathogenesis of AD. We hypothesize that N20 exposure has a bimodal dose-related effect to either attenuate or exacerbate subsequently developed AD. We will test the specific hypotheses that: 1. High dose N20 exposure exacerbates cognitive dysfunction and brain damage with AD. In a transgenic model of AD, mice will receive five high-dose exposures to N20 during middle-aged, or elderly ages followed at age 10 months by cognitive assessment, analysis of brain isoprostanes as markers of peroxidation and soluble andinsoluble amyloid, and morphologic assessment for amyloid plaques, apoptosis and neuronal degeneration 2. Low dose repetitive N20 exposure attenuates cognitive dysfunction and brain damage with AD. In a transgenic model of AD, mice will receive low doses of N20 nightly from mid-life to elderly ages, followed at age 10 months by cognitive assessment, analysis of brain isoprostanes and soluble and insoluble amyloid, and morphologic assessment for amyloid plaques, apoptosis and neuronal degeneration. Anesthesia has been implicated in postoperative cognitive dysfunction (POCD) in the elderly and has been impugned in the early onset of AD. The proposed research will explore the potential contribution of a ubiquitous anesthetic with neuroexcitatory side effects in a relevant murine model of AD. This will contribute to a focussed evaluation of the potential causes of POCD the results of which will change the practice of anesthesia and thus significantly attenuate the incidence of POCD in the elderly and possibly impact on the epidemiology of AIzheimer's disease. Moreover, observation of a protective effect may result in discovery of an easily implemented preventative drug therapy for AD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FETAL BRAIN INJURY FROM OXIDANTS FOLLOWING ACUTE HYPOXIA Principal Investigator & Institution: Tan, Sidhartha; Evanston Hospital Evanston, Il 60201 Timing: Fiscal Year 2001; Project Start 01-JAN-1997; Project End 31-DEC-2002 Summary: Irreversible brain damage to the fetus frequently results from prolonged ischemia/hypoxia during pregnancy. Oxidants produced during ischemia- reperfusion can cause significant tissue damage if they overwhelm the body's antioxidant defenses. Pro-oxidant systems, like xanthine oxidase, develop earlier than antioxidant enzyme systems in the developing fetus. The hypothesis of this proposal is that oxidants derived from xanthine oxidase and nitric oxide are responsible for cortical fetal brain damage following acute hypoxia. The hypothesis will be tested using specific inhibitors to xanthine oxidase and nitric oxide generating systems in a preterm gestation rabbit model of acute fetal hypoxia. It is proposed: 1) to determine the involvement of xanthine oxidase in excess oxidant production, depletion of antioxidant defense systems, and brain injury following fetal hypoxia-reoxygenation. It is postulated that xanthine oxidase released into the circulation causes multi-system injury, including brain injury.

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The imbalance between oxidant production and antioxidant systems and the relationship to tissue injury will be investigated following interference with xanthine oxidase activity and administration of antioxidants. 2) to determine the involvement of nitric oxide in excess oxidant production, depletion of antioxidant defense systems, and brain injury following fetal hypoxia-reoxygenation. The interaction of nitric oxide with oxidants, including those derived from xanthine oxidase, will be investigated in fetal rabbits in vivo and in fetal neuronal and astrocyte cultures. The regulation of gene expression of xanthine oxidase, nitric oxide synthase (the enzyme that produces nitric oxide) and superoxide dismutase (a key antioxidant enzyme), and correlation with their enzymatic activity will be determine following acute hypoxia. Completion of the proposed research will broaden the understanding of basic mechanisms of oxidantmediated fetal brain injury, and identify useful biochemical markers and pharmacological ameliorations of brain injury in fetal hypoxia. The laboratories of the sponsors and consultants provide a fertile atmosphere in which to do the proposed studies. The experience and training in neurobiology and molecular biology that the candidate will gain on completion of this proposal will form a solid framework for a successful investigative career. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FREQUENCY DOMAIN CEREBRAL OXIMETER FOR PEDIATRICS Principal Investigator & Institution: Kurth, Dean C.; Attending Anesthesiologist; Near Infrared Monitoring, Inc. (Nim) 3401 Market St, Ste 140F Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 29-SEP-2002 Summary: Brain damage from hypoxia-ischemia represents a major health problem in pediatrics. At present, no method exists in clinical care to diagnose cerebral hypoxiaischemia in real-time at the bedside, thereby limiting prevention and treatment of the brain damage. Near infrared spectroscopy (cerebral oximetry) is an emerging optical technology with the potential to fulfill this role. In previous work, we built a prototype frequency domain near infrared cerebral oximeter and found it measures cerebral O2 saturation accurately. However, before clinicians will use cerebral O2 saturation to diagnose cerebral hypoxia-ischemia, the measure needs to be related to other known measures of hypoxia-ischemia, and the instrument needs to be engineered to the clinical environment. This fast-track proposal will develop a frequency domain near infrared cerebral oximeter to diagnose cerebral hypoxia-ischemia in real-time at the bedside for pediatrics (<8 years). Instrument development includes construction of "user-friendly" hardware and software, evaluation of its performance in a simulated clinical environment, and identification of critical cerebral 02 saturation-in piglets to diagnose hypoxia-ischemia. The instrument will be operable by the nurse caring for the child at the bedside and will display cerebral O2 saturation and messages to facilitate its operation. PROPOSED COMMERCIAL APPLICATION: The cerebral oximeter will be used in children at risk of hypoxic-ischemic brain damage. The population at risk, encompassing about 5% of pediatrics, includes sick premature infant and lull term infants, as well as children with congenital heart disease, sickle cell anemia, seizure disorders, or meningitis. The market is enormous as it consists of all hospitals and freestanding clinics treating this population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTIONAL NEUROGENESIS

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Principal Investigator & Institution: Keith, Julian R.; Psychology; University of North Carolina Wilmington 601 S College Rd Wilmington, Nc 284035973 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The adult mammalian hippocampus contains precursor cells that differentiate into neurons during adulthood. This phenomenon is referred to as adult neurogenesis. The proposed studies address whether neurons that form in the adult hippocampus, a brain region involved in learning and memory, affect behavior. Predictions of four hypotheses will be tested. The learning hypothesis posits that adult hippocampal neurogenesis plays a role in the acquisition of hippocampusdependent behavior. Thus, according to the learning hypothesis, factors that increase neurogenesis should improve learning. The forgetting hypothesis posits that new hippocampal neurons contribute to forgetting and that factors that increase neurogenesis will interfere with the long-term retention of hippocampus-dependent behavior. The self-repair hypothesis holds that newly formed neurons repair damaged hippocampal circuitry and predicts that factors that increase neurogenesis will improve recovery of function after hippocampal injury. The injury process hypothesis, in contrast, posits that new neurons that form in response to hippocampal injury interfere with the functioning of the remaining intact hippocampal tissue. Thus, the injury hypothesis predicts that factors that increase hippocampal neurogenesis will exacerbate the behavioral impairments caused by hippocampus damage. The methods used to test these hypotheses will involve studying learning and memory using rats as experimental subjects. Hippocampal neurogenesis will be controlled using the selective serotonin reuptake inhibitor, fluoxetine, and exercise (wheel running). Neurogenesis will be quantified using immunohistochemical methods including BrdU-, NeuN-, GFAP-, and doublecortin-labeling, confocal laser microscopy, and unbiased stereology methods. The proposed studies will provide important new information about the function of adult hippocampal neurogenesis and assess whether factors that increase the rate of neurogenesis enhance, or disrupt, recovery of hippocampal function after brain damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL MAGNETIC RESONANCE STUDIES OF THE BRAIN Principal Investigator & Institution: Van Zijl, Peter Cm.; Professor of Radiology; Radiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 10-JUN-1992; Project End 30-NOV-2004 Summary: It is believed that early intervention is the key to successful therapeutic outcome in stroke, which is the third most frequent cause of mortality in western society. Thus, the ability to diagnose ischemic brain tissue with a high degree of specificity and sensitivity is critical. Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) hold great promise for noninvasive assessment of brain damage. However, if MR is to become useful for prognosis, it is essential to determine whether reversible or irreversible damage has occured during and after ischemic periods. In addition to assessing large- and small-vessel perfusion using MR angiography (MRA) and dynamic contrast imaging, it is essential to have access to MR parameters that reflect reversible and irreversible tissue damage during and after ischemic periods. SpinDensity/T2-weighted imaging is a good indicator of edema (hyperintensity), but is not sensitive in the acute phase. It is therefore important to develop new functional imaging

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methods that can quantitatively assess tissue status when neurologic recovery is still possible. Diffusion imaging can detect ischemic tissue within minutes post-onset, but contrary to early expectations based on animal studies, clinical results generally show that regions of reduced diffusion proceed to infarction at follow-up. In addition, perfusion images generally show an area of reduced flow larger than the region of compromised diffusion, the so-called perfusion-diffusion mismatch. Because it is essential to assess the risk of infarction in this region, which often evolves to reduced diffusion, there is a need for new functional modalities to diagnose this mismatch area at the time of clinical evaluation. Based on recent results obtained by us, we have designed the following hypotheses: (1) quantification of oxygen extraction ratio (OER) can predict the risk for tissue infarction based on the principle of flow thresholds; (2) changes in protein synthesis are reflected in the proton magnetization transfer rate between proteins and water, which can be imaged through the MRI relaxation rate T1rho; (3) It is possible to measure pH using proton MRS, which will provide an additional tissue parameter for stroke evaluation on a standard clinical scanner (proton only). Our corresponding three aims are to develop new methodologies to measure OER, T1rho, and pH, and to subsequently test our three hypothesis on cat brain models of reduced blood flow and of transient global and focal ischemia. Our fourth and final aim is to implement the new technologies on the clinical scanner and to optimize their use for a fast and specific clinical stroke exam. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE REPAIR IN SIGNAL TRANSDUCTION AFTER CNS INJURY Principal Investigator & Institution: Liu, Philip K.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2007 Summary: (provided by applicant): Brain damage of the ischemia/reperfusion type resulting from cardiac arrest and stroke is a major cause of mortality and disability in the United States, attacking one person every minute, and creating more than 500,000 victims every year. Cerebral ischemia causes oxidative damage to lipids, proteins and nucleic acids, reduces energy source with consequent functional deterioration leading to cell death. Restoration processes normally repair genes with few errors. However, ischemia causes elevated oxidative DNA lesions (ODLs) despite these repair mechanisms. These episodes occur concurrently with Fos expression and critical activation of other late genes in the signal transduction pathway. To date, the effect of ODLs on gene function of the brain is not totally understood. We will investigate whether gene damage could affect the function of the c-fos gene using a forebrain ischemia (30-90 min)/reperfusion (FblR) model in male C57black/6 mice. This model induces neuronal death in the hippocampus, similar to that observed after cardiac arrest and in some neurological disorders. Our hypothesis is that repair of genes in the signal transduction benefits neuronal recovery after oxidative stress. The specific aims are to: 1. Establish whether Fos activity induces gene repair function after FblR, we will determine (a) Fos protein, repair activity and neuronal death in the hippocampus using 3-bromo-7nitroindazole that inhibits brain nitric oxide but enhances the expression of cfos mRNA after FblR. (b) Correlation in Fos activity, repair activity and neuronal death in the hippocampus using antisense technology that specifically abolishes the expression of Fos after FblR. 2. Establish whether repair of gene damage protects the hippocampus, we will determine (c) ODLs and ORLs (base modifications) in the c-fos transcript after FblR. (d) Correlation between repair activity, Fos activity and the expression of late effector genes after FblR. We have shown the feasibility of the studies by developing an

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array of technology to detect Fos expression and DNA repair processes in the brain. We have developed effective means to deliver antisense cDNA that abolishes Fos activity to the brain. Several end-points (FblR-induced Fos/AP-1 activity, nerve growth factor mRNA, gene repair activity and neuronal death) will be measured. Future directions include detections of additional gene activators in animals treated with FblR, and application of additional antisense cDNA to these gene activators to elucidate their roles in repair process of the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HIGH DOSE ERYTHROPOIETIN FOR NEONATES WITH ASPHYXIA Principal Investigator & Institution: Christensen, Robert D.; Professor; Pediatrics; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 30-MAR-2005 Summary: (provided by applicant): Damage to the central nervous system as a result of hypoxic-ischemic injury at birth is a major cause of life-long mental and neurodevelopmental handicap. Unfortunately, no therapeutics have yet been identified which, when administered to neonates following birth asphyxia, significantly lessen the extent of brain damage or improve outcome. Recent studies in the investigators' laboratories, and in many others, indicate that erythropoietin (Epo) is a "natural" neuroprotectant. During hypoxemia Epo is produced rapidly and abundantly by the microglia, and in a paracrine fashion this Epo binds to specific Epo receptors on neurons. This binding has at least three salutary actions; 1) it induces antiapoptotic factors that preserve neurons which would otherwise undergo apoptosis, 2) it reduces perineuronal inflammation, and 3) it has direct antioxidant effects. An improved understanding of the biology of Epo during human neuronal development has led to experiments where recombinant Epo (rEpo) was administered in an attempt to reduce post-hypoxic-ischemic brain damage. Indeed, when rodents were subjected to a variety of experimental brain injuries, rEpo administration, even up to six hour after the event, reduced subsequent brain injury by 50-70%. However, the doses of rEpo required were considerably higher (5,000 U/kg/dose) than those traditionally used by neonatologists to stimulate erythropoiesis and reduce erythrocyte transfusions (100 to 200 U/kg/dose). Before a clinical trial can be designed to test the efficacy of very-high-dose rEpo administration in reducing post-asphyxic brain injury, basic Phase I/II information on pharmacokinetics, biologic effect, and safety must be obtained. Therefore, the investigators designed a multi-centered, open-labeled, dose-escillation trial of veryhigh-dose rEpo administration to neonates who have had birth asphyxia. The study will be performed using the consortium known as the Florida Collaborative Neonatology Trials Group and the follow-up will be accomplished using the State of Florida Early Intervention Program (EIP), in which all study patients will be enrolled. Within three hours of birth, each eligible patient will receive one dose of rEpo intravenously (n=5 will receive 1,000 U/kg; the subsequent n=5 will receive 2,500 U/kg; the final n=5 will receive 5,000 U/kg). The doses will be increased to the next highest group if such is sanctioned after review by the Data Safety Monitoring Board. Any patient who has a lumbar puncture performed during the first week of life will have natural Epo and rEpo in their spinal fluid determined to assess the degree of penetration of rEpo across the blood brain barrier. They will also have free iron and total isoprostanes in the spinal fluid quantified as measures of oxidative stress and oxidative damage. The effect of rEpo on plasma free iron and plasma total Isoprostanes following hypoxia will be assessed at intervals following rEpo treatment. Pharmacokinetics of rEpo in this population will be determined and safety parameters evaluated. To aid the design of a

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subsequent Phase III trial, neurodevelopmental outcome will be measured in the EIP program clinics at six and 12 months or life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HIPPOCAMPAL DENTATE GYRUS INJURY IN NEONATAL BACTERIAL Principal Investigator & Institution: Pleasure, Samuel J.; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 31-AUG-2007 Summary: Bacterial meningitis in newborns leads to brain damage and subsequent neurologic sequelae including learning and memory deficits. In an infant rat model of neonatal bacterial meningitis, damage to the dentate gyrus of the hippocampal formation occurred regularly and showed two fundamentally distinct forms: (1) Scattered apoptotic injury confined to cells in the subgranular zone and (2) injury of the lower blade of the dentate gyrus with clusters of pyknotic appearing cells. Since the hippocampus is critical for learning and memory function, damage to it may be the basis for the learning deficits in survivors of bacterial meningitis. Indeed, damage to the dentate gyrus was associated with learning deficits in experimental meningitis. The dentate gyrus of the hippocampus is unique in two respects. First, the morphogenesis occurs very late in development in both rodents and humans, perhaps making it more vulnerable to pathologic insult at later developmental stages than other brain regions. Second, the dentate gyrus is a continuously developing system throughout life, containing progenitor cells able to multiply and give rise to new neurons. This has been implicated in the ability to form new memories and learn new tasks later in life. In meningitis, the progenitor cells appear to be selectively damaged. We will test the hypothesis that bacterial meningitis in young animals leads to selective damage within the dentate gyrus, including the progenitors or their immediate progeny, giving rise to neuroanatomical and functional abnormalities that underlie some of the permanent neurologic deficits affecting survivors of bacterial meningitis. Specifically, we will determine the nature of cell death in the dentate gyrus (apoptosis or necrosis); we will identify the cells damaged by the meningitic process )progenitor cells, immature or mature granule cell neurons, interneurons, glia); we will identify pathophysiologic factors leading to cell death (e.g., ischemia, excitatory amino acids, oxygen radicals, cytokines); and we will define in adult animals the neuroanatomical and functional consequences of damage to the immature dentate gyrus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HYPOXIC/AGLYCEMIC STRESS TO ENDOTHELIAL CELLS OF THE BLO Principal Investigator & Institution: Davis, Thomas P.; Professor; Pharmacology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2001; Project Start 01-JAN-2000; Project End 31-DEC-2004 Summary: Understanding BBB stroke pathophysiology is critical since stroke is a leading cause of death and disability and increased cerebrovascular permeability is an important factor for the development of ischemic brain damage and edema formation. Vasogenic brain edema, due to a BBB opening is the type of edema that is present in the brain after injury induced by a cerebrovascular accident. Vasogenic brain edema can result from opening of tight junctions at the BBB or an increase in pinocytotic activity. Damage to the BBB from ischemia/stroke can result in poor clinical outcomes during

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stroke recovery, such as vasogenic brain edema and inflammation. In addition, changes in BB transport characteristics may influence the transport of clinically useful medications used to either treat the ischemic episode or medicate other disease stages. Our major hypothesis is that hypoxia/aglycemia and reperfusion (associated with stroke) alters both the expression of BB specific proteins and the permeability and transport of critical solutes across the BBB, thereby contributing to the development and severity of stroke. To investigate this hypothesis, our major objective and specific aims are to investigate and quantify the effect of hypoxia/aglycemia/reoxygenation on the endothelial cells of the BBB by quantifying effects on cell resistance, permeability, tight junctional protein/cytoskeletal protein expression and transcriptional/posttranscriptional expression of specific proteins associated with hypoxia. We will also identify the role in calcium in hypoxia/aglycemia/reoxygenation and determine the role of astrocytes. The techniques we will use are both in vitro and in situ coupling our experience of analytical biochemistry and vascular biology in a focused program to study the effect of hypoxic/aglycemic stress on endothelial cells of the BBB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MICROGLIA

IMMUNOREGULATION

OF

HERPES

ENCEPHALITIS

BY

Principal Investigator & Institution: Lokensgard, James R.; Assistant Professor; Minneapolis Medical Research Fdn, Inc. 600 Hfa Bldg Minneapolis, Mn 55404 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Herpes simplex virus 1 (HSV) is an important opportunistic pathogen in HIV-1-infected patients as well as the cause of a devastating CNS infection in normal hosts. Although immune responses to HSV have been the subject of intense investigation, the role of immune-mediated pathology in HSV-related brain damage is unknown. In this proposal, the central hypothesis to be tested is that chemokines produced by microglial cells in response to HSV infection initiate a cascade of neuroimmune responses that result in the serious brain damage seen during herpes encephalitis. To test this hypothesis, chemokine production in the brains of HSVinfected mice will be compared to that in cultures of highly purified murine glial and neuronal cells, and in murine organotypic brain slices infected with HSV. This approach will allow us to differentiate microglial cell chemokine production from that of cells of the somatic immune system. Additionally, the use of organotypic brain slice cultures will enable us to specifically deplete microglial cells for "loss-of-function" experiments. We will then investigate the neurotoxic effects of microglial cell-produced immune mediators on cultured murine neurons. Microglia-driven leukocyte trafficking into the brain will be investigated by determining if neutralizing antibodies to chemokines inhibit T-cell infiltration. The neuropathogenic role of T-cell infiltration will be studied by determining if depletion of T-cells in vivo will delay encephalitis and whether adoptive transfer of HSV-specific lymphocytes restores the encephalitis phenotype. Comparing neuropathology in brain slice cultures with and without the transfer of HSV-specific CD4 + and CD8 +lymphocytes, will allow us to distinguish between injury generated by viral infection and brain damage provoked by immunopathogenic mechanisms. Downregulation of microglial cell chemokine production through peripheral benzodiazepine (BDZ) receptor-mediated cellular deactivation will then be examined. We will determine if deactivation of microglia with BDZs suppresses the production of neurotoxic factors. Finally, we will study the effects of BDZ ligands on chemokine production, T-cell trafficking, and the development of encephalitis in vivo. These in vivo, in vitro, and ex vivo models will provide us with the ability to investigate

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neuropathogenesis, neuroinflammation, neurotoxicity, and neuroimmune-mediated pathology occurring during herpes encephalitis. Knowledge gained from these studies will increase our understanding of the role of microglial cells and chemokine networks that regulate brain inflammation during herpes encephalitis with the ultimate goal of finding new therapy for this serious brain infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IN SITU LIGATION FOR DETECTION OF SPECIFIC DNA DAMAGE Principal Investigator & Institution: Baskin, David S.; Neurosurgery; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-JUL-2002 Summary: (Applicant's Description) A new approach for visualization and detailed analysis of DNA damage at the level of the single cell will be developed. The approach will be based on in situ ligation of double-stranded and hairpin shaped DNA probes with specific architectures that will bind to the ends of DNA in tissue sections. The probes will be designed to selectively detect various types of double strand breaks in cellular DNA. They will be used to find a specific marker of apoptotic DNA damage in order to distinguish it from DNA damage in necrosis, as well as from potentially reparable DNA damage in cells showing no morphological signs of apoptosis or necrosis. The probes will be tested in different models of apoptosis and nonapoptotic DNA damage. The methodology will also be used to study focal brain ischemia, to determine the percentage of different types of DNA damage in a variety of important brain regions. This determination will permit better assessment of cellular damage after ischemia onset, and will be helpful for development of better therapies for ischemic brain damage, as well as for the other CNS diseases characterized by various types of DNA damage. The proposed technology will allow simultaneous evaluation of several types of alterations in DNA at the level of single cell. It, therefore, can be used in molecular and cell biology research, as well as by clinicians in many fields, including pathology oncology, cardiology and the clinical neurosciences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFLAMMATORY MEDIATORS Principal Investigator & Institution: Palmer, Charles; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001 Summary: The objective of this project is to define the key mechanisms leading to hypoxic-ischemic brain injury in the human newborn. Clinical and experimental studies show that after an initial recovery in brain energy metabolism there is a secondary decline that may extend for months What are the key mechanisms responsible for early and late brain injury and can any aspect of the injury process by reduced by therapeutic intervention are clinical priorities addressed in this proposal. We will continue to study the immature rat model of cerebral hypoxia-ischemia. The central focus is to determine how inflammation before hypoxia-ischemia as well as inflammation induced by the consequences of brain injury contribute to progressive brain damage. As brain injury in the neonate is strongly associated with exposure to infection in utero, we will mimic the neuro- inflammation effects of systemic infection by giving immature rates lipopolysaccharide (LPS). Evaluations will include systemic and cerebral analyses of giving immature rats lipopolysaccharide (LPS). Evaluation will include systemic and cerebral analyses of giving immature rats lipopolysaccharide (LPS). Evaluations will

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include systemic and cerebral analyses of inflammatory cells (neutrophils and microglia), cytokines, nuclear transcription factor NF-kappaB activation, brain lipid peroxidation, and disturbances in brain iron metabolism. Mice lacking the receptor for IL-1 will aid in defining IL-1's role in the response to LPS as will anti-cytokine treatment. Specific Aims include: Aim 1: To establish the systemic and cerebral inflammatory responses of immature rats to infections of LPS. Aim 2: To expose immature rats to a combination of LPS and cerebral hypoxia-ischemia to determine whether or not the combined stress accentuates hypoxic-ischemic brain damage in the immature rat. Aim 3: To investigate how nitric oxide contributes to Poly (ADP-ribose)polymerase (PARP) activation and delayed brain energy failure following hypoxia-ischemia and LPS administration in the immature rat. Aim 4: To characterize the chronic neuropathologic alterations which result from cerebral hypoxia-ischemia in the immature rat. Our investigations also will include in vivo sequential MR imaging ant 31P NMR spectroscopy to measure the progression of cerebral atrophy and energy failure in the same rats over the first year of recovery. We will use pharmacologic agents in vivo to test the contribution of key injury mechanisms, including drugs directed at cytok9ines, free radicals, iron nitric oxide, and PARP. We will use biochemical, histologic, and neuropathologic techniques to determine if LPS primes the brain for greater ischemic injury and if a chronic damaging inflammatory process is induced by the primary insult. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ISCHEMIC BLOOD BRAIN BARRIER: GLIAL AND ENDOTHELIAL CELL INTERACTIONS Principal Investigator & Institution: Giffard, Rona G.; Associate Professor; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 30-JUN-2007 Summary: The blood brain barrier (BBB) is necessary to regulate and limit the transport of solutes and proteins into the brain under normal conditions. Under pathological conditions, the BBB can be altered or damaged to permit transmigration of leukocytes and large molecules leading to edema and in the case of complete breakdown, hemorrhage. Such damage is often observed during cerebral ischemia and may result in significant cerebral hemorrhage, a feared complication of thrombolytic therapy. The BBB consists of endothelial cells surrounded by astrocytes and microglia. Following ischemia, reactive oxygen and nitrogen species are generated in the brain by a variety of cell types. These conditions lead to activation of microglia, the brain's resident immune cell. In response to activating stimuli, microglia are capable of expressing inflammatory cytokines, reactive species including superoxide and nitric oxide, and degradative enzymes including matrix metalloproteinases (MMPs). MMPs, once expressed, lead to direct disruption of the BBB resulting in cerebral edema and hemorrhage. We recently observed that microglia potentiate damage to endothelial cells and astrocytes subjected to simulated ischemia. We plan to characterize the mechanisms underlying this observation by examining the effects of simulated ischemia-induced BBB injury as it pertains to 1) the inflammatory cytokines IL-1 beta and TNF-alpha, 2) reactive oxygen and nitrogen species and 3) MMPs. This proposal plans to study these effects both in coculture models of the BBB and in a whole animal model of hemorrhagic embolic stroke. This work may help identify novel therapeutic targets to reduce brain damage and hemorrhage in the setting of impaired BBB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ISCHEMIC BRAIN INJURY IN NEONATAL MENINGITIS Principal Investigator & Institution: Tauber, Martin G.; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001 Summary: Approximately 15,000 cases of bacterial meningitis occur each year in the United States. Meningitis in newborns has a particularly poor prognosis with mortality rates up to 35% for cases caused by group B streptococci (GBS), a major pathogen of neonatal meningitis. Only 50% of survivors of GBS meningitis are neurologically intact, while 21% have severe neurologic sequelae, including global mental retardation, cerebral palsy, and uncontrolled seizure disorder's. The goal of our research is to identify the mechanisms that lead to brain injury in neonatal meningitis in order to develop new therapies that protect the brain. The hypotheses to be tested in the present grant are (1) meningitis leads to global and focal Cerebral blood flow changes; (2) cerebral blood flow is modulated by the interplay of vasodilative and vasoconstrictive mediators; (3) ischemia resulting from cerebral hypoperfusion is a major factor leading to brain damage; and (4) hallmarks of parenchymal brain damage include the release of excitatory amino acids and activation of glial cells (as evidenced by the expression, of cytokines). These hypotheses will be tested in an infant rat model of neonatal meningitis that closely mimics the human disease and in primary cultures of neurons, astrocytes, and microglia. The project has five specific aims: 1. To analyze cerebral blood flow in a rat model of GBS neonatal meningitis and to correlated blood flow changes with the occurrence of tissue hypoxia and the development of neuronal injury. 2. To identify molecular mediators involved in the modulation of cerebral blood flow in the rat model of GBS neonatal meningitis. Using specific inhibitors/agonists, we will focus on the role of nitric oxide as potentially beneficial vasodilator and on endothelin as potentially harmful vasoconstrictor. 3. To examine the contribution of excitatory amino acids (EAA)to neuronal injury in the infant rat model of GBS meningitis by determining whether animals treated with different EAA antagonists have reduced brain injury compared to control animals. 4. To characterize glial cell activation and the expression of selected cytokines (IL-1beta, TNF-alpha, IL-6, TGF-beta) in the GBS meningitis rat model. We will also examine the contribution of cytokines to the development of brain injury in the model: 5. To analyze in primary cultures in vitro which of the factors that play a role in the pathophysiology of meningitis lead to cytokine expression in glial cells, either by direct stimulation of glia or through thee effect on neurons. We will also examine whether the cytokines induced in glial cells have a beneficial or harmful effect on neuronal injury caused by EAA and ischemic conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LANGUAGE AND MOTOR PLASTICITY: FMRI IN CHILDREN Principal Investigator & Institution: Mueller, Ralph-Axel; Psychology; San Diego State University 5250 Campanile Dr San Diego, Ca 92182 Timing: Fiscal Year 2001; Project Start 25-SEP-2001; Project End 31-AUG-2005 Summary: Even though functional neuroimaging techniques have been available for decades, they have generated only limited evidence of developmental plasticity. In human studies, brain -organizational changes during development have been mostly inferred from structural imaging and behavioral data. Our previous positron emission tomography studies in brain-damaged children and adults suggested pronounced functional reorganization following congenital and early postnatal lesion. We propose to approach the issue of developmental plasticity by means of functional magnetic

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resonance imaging (fMRI). The proposed research will examine (i) developmental changes of normal brain organization and (ii) functional reorganization following brain damage (early versus late). It will be performed in close cooperation with investigators of two existing NIH-funded centers for the study of cognitive and language development and the effects of focal brain damage. We will study 96 healthy subjects, evenly distributed across 4 age groups (6-8, 9-12, 13-17, and 18-50 years), using fMRI with two language paradigms (picture naming, syntactic decoding) and one motor task (finger movement). Studies of healthy subjects will provide reference data for the additional study of 20 pediatric and 20 adult patients with left hemisphere damage. Activation measures will be taken for multiple regions of interest, which will be traced on high-resolution anatomical MRIs of each individual brain. Our hypotheses are based on evidence of an experientially influenced interplay of constructive and regressive events in normal brain development. We expect that regressive events (e.g., synaptic pruning) may be partially suspended in reorganization after brain lesion. We specifically hypothesize that (a) task-related activations become more focal and lateralized during normal development, (b) left hemisphere lesion results in interhemispheric reorganization of language and motor processing, (c) reorganization is more pronounced after early (compared to late) lesion, and (d) regional patterns of reorganization differ between functional domains (language versus motor). Findings are expected to contribute to the understanding of compensatory plasticity in development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF PERCEPTUAL EXTINCTION FOLLOWING STROKE Principal Investigator & Institution: Baylis, Gordon C.; Professor; Psychology; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, Sc 29208 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2007 Summary: (provided by applicant): This project seeks to understand the common deficits of attention that result from unilateral brain damage caused by strokes or other injuries. Deficits of attention can lead to grave consequences during rehabilitation, and predispose patients to falls, with attendant complications and mortality. Despite the seriousness of deficits such as extinction and neglect, and the fact that they have been described for more than a century, they are poorly understood. Extinction refers to an inability to attend to, or perceive, stimuli on the side of space opposite to the site of a lesion (i.e., contralesional stimuli) when a stimulus is present in the unaffected side of space, ipsilateral to the lesion. Extinction can occur in vision, audition, tactile sense, and even gustation, but it is not known whether similar causes underlie it in different modalities. A major problem in understanding extinction is that subtle changes in the method of testing may lead to major differences in the clinical impression of a given patient. Specifically, this project will test a new theory of how brain damage may lead to the phenomenon of extinction, although the results of this study will generalize to other deficits of attention. The present theory proposes that extinction in vision, audition and taction following cortical lesions, arises when the identity and location of stimuli cannot be bound together. This proposal will be tested using behavioral tasks that require patients to bind both these aspects of stimuli together, and tasks that do not. It is predicted that tasks that require binding will lead to much higher error rates than tasks that do not. It is suggested that a major source of inconsistency in clinical testing is that some tests make lower demands on binding than others, leading to great differences in the detected levels of inattention. A novel aspect of the present study is that visual, auditory and tactile extinction will all be tested using analogous tasks so that the general

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principles of our theory can be tested? Inherent in this view of extinction is the proposal that attentional failure arises independently within each perceptual modality, that, for example, visual extinction occurs as a binding failure of visual information. This contrasts with a view that overall unilateral inattention will lead to extinction in all modalities, and predicts that most patients will have extinction in only one or two modalities. The occasional co-existence of, say, visual and auditory extinction will be expected simply because areas crucial for auditory binding may be physically close to those crucial for visual binding, thus be affected by a single large lesion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEMORY FUNCTION IN ALCOHOLISM--PROCESSES & BRAIN SYSTEM Principal Investigator & Institution: Jernigan, Terry L.; Clinical Research Psychologist; Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2002; Project Start 01-JUN-1993; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's Abstract) Priming refers to the fact that the mere processing of an item can facilitate subsequent processing of that same item. Priming effects can occur in the absence of conscious recollection of the prior study episode, and it has, therefore, been suggested that priming and explicit memory disorder patients is critical for this hypothesis, since if it is possible to link the breakdown of explicit memory and priming to damage to different brain regions this would strengthen the independent memory systems hypothesis. Difficulties associated with evaluating priming effects in memory impaired subjects include that priming measures may be less sensitive than explicit memory measures, and that the priming obtained in a given task is related to baseline performance, with poorer baseline performance resulting in greater priming. Therefore, it patients have even mild information processing deficits this may make priming impairments. The proposed project will investigate these issues in normal subjects and alcoholic patients with varying degrees of memory and processing deficits. The proposed project will investigate these issues in normal subjects and alcoholic patients with varying degrees of memory and processing deficits. The proposed experiments are designed to manipulate baseline performance level and sensitivity of the priming measures. Measures of priming, baseline performance, and explicit memory will be obtained. The subjects will be normal controls and chronic alcoholic patients who differ in the severity of their explicit memory defects, ranging from non amnesic patients without noticeable memory impairments through "borderline Korsakoff" patients with only mild memory deficits to severely amnesic patients with Korasoff's syndrome. Measures of volume loss in specific brain structures will be obtained from MRI. These measures will be related to the behavioral indices, using a multiple regression approach, to determine the specific role of each brain region in perceptual. lexical processing, explicit memory and magnitude of priming. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: METABOLIC EFFECTS OF BRAIN RADIATION IN CHILDREN Principal Investigator & Institution: Horska, Alena; Radiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2007

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Summary: (provided by applicant): Brain radiation therapy (RT) has contributed positively to long term disease-free survival from childhood cancer. Despite its therapeutic benefit, RT has been associated with a spectrum of acute, early-delayed, and late-delayed toxicities to the central nervous system. As a consequence, children treated with brain radiation often develop neurological and neurocognitive deficits manifesting as behavioral or learning disabilities. It is unclear whether the neurocognitive deficits are due mainly to damage to the white matter or if cortical areas are also involved. Are there markers that could be measured non-invasively that reflect the degree of brain injury? Could these markers predict early in the course of treatment if brain damage will occur? Could these markers be used to evaluate sensitivity of different brain regions to radiation? Can the temporal course of regional changes due to radiation be mapped in the brain, non-invasively? We intend to answer these questions using non-invasive methods based on magnetic resonance (MR): magnetic resonance spectroscopy, diffusion tensor imaging, and volumetric MRI. Methods using MR have been demonstrated to be promising tools for detection of radiation damage. However, their ability to explain neuropsychological deficits in children remains to be evaluated. We plan to perform a longitudinal MR study with a 30 months follow-up to assess changes in brain metabolism, damage to tissue microstructure, and loss of brain tissue. Concurrent neuropsychological assessments will further enhance our understanding of the relationship between neuropsychological status and parameters measured by the proposed MR methods. The broad objectives of our research are to determine a) how brain function and integrity, as measured by MR techniques, can be correlated with total radiation dose delivered to the brain and b) whether changes in measured parameters (metabolite concentrations, water diffusion characteristics, and lobar gray and white volumes) can be used as surrogate markers to predict the neuropsychological outcome from RT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MODELING NORMAL AND IMPAIRED LEXICAL SEMANTIC PROCESSING Principal Investigator & Institution: Plaut, David C.; Associate Professor; Psychology; Carnegie-Mellon University 5000 Forbes Ave Pittsburgh, Pa 15213 Timing: Fiscal Year 2001; Project Start 01-JAN-1997; Project End 31-DEC-2001 Summary: (Applicant's Abstract): The nature of the semantic representations of words, and how these representations interact with other forms of lexical knowledge, is fundamental to linguistic and cognitive behavior. The proposed research employs computational modeling to provide insight into lexical semantic processing, both in normal individuals and in neurological patients with semantic impairments due to brain damage, and into the nature of recovery after semantic damage. The research is cast within a connectionist/parallel distributed processing (PDP) framework in which groups of simple, neuron-like processing units representing different types of lexical information (e.g., orthographic, phonological, semantic) interact across weighted connections in the process of settling into stable patterns of activity representing the network's interpretation of a given input. This framework provides a rich set of computational principles that provide new ways of thinking about how cognitive processes are implemented in the brain. The computational principles central to the proposed research are that learning and processing, both in the normal system and after damage, are sensitive to the similarity of representations within a domain, to the frequency and consistency of the mappings between domains, and to the temporal contiguity of representations both within and between domains. Three sets of

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simulations are proposed. The first set (1-4) addresses normal lexical semantic processing as reflected by semantic and associative priming in naming and lexical decision. The models encode semantic relatedness by pattern overlap and associative relatedness by temporal contiguity during training, and account for empirical phenomena relating to interactions between types of priming, priming across unrelated items, and lexical ambiguity resolution. The second set (5-8) investigates the degree of specialization within semantics, as evidenced by the occurrence of selective deficits following brain damage, by exploring the effects of damage to a system in which internal representations--corresponding to lexical semantics--must learn to mediate between multiple modalities in performing lexical tasks. The issues addressed include access vs. degraded-store deficits, modality-specific aphasias, category-specific impairments, and abnormal priming in dementing patients. The third set (9-12) investigates generalized recovery via retraining after damage and explores the benefits of retraining strategies employing multiple modalities and tasks. The research provides new insights into normal and impaired lexical semantic processing and should contribute to improved patient therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR PATHOLOGY OF BINGE INDUCED BRAIN DAMAGE Principal Investigator & Institution: Crews, Fulton T.; Director, Bowles Center for Alcohol Stu; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 27-DEC-2002; Project End 30-NOV-2007 Summary: (provided by applicant): Alcoholics suffer from neuroticdeneration and loss of CNS function, which could occur due to hinge drinking. Studies in vivo using a 4-day animal binge model found neurodegeneration in corticolimbic areas, i.e. Binge-Induced Brain Damage (BIBD). BIBD is characterized by significant neuronal damage, longlasting expression of markers of inflammation, and changes in behavior. Although in vitro studies have found glutamate-NMDA excitotoxicity following chronic ethanol treatment, BIBD is not blocked by glutamate-NMDA antagonists, hut BIBD is blocked by antioxidants. This proposal will investigate the role of oxidative stress in BIBD and how it alters signaling pathways involved in neuronal survival. We will also determine the contribution of multiple ethanol exposures and ethanol-induced plasma toxins to alcoholic neurodegeneration as both of these pathological states can lead to oxidative stress. Ethanol-induced plasma toxins may contribute to oxidative stress and multiple ethanol exposures may lead to cumulative stress prompting experiments to determine the contributions of these factors to alcoholic neurodegeneration. The following hypotheses will be tested. Aim 1. BIBD is related to oxidative stress. This hypothesis will be tested by measuring nitro-tyrosine, 4-hydroxynenenol and 8-hydroxyguanosine, indicators of protein, lipid and nucleic acid oxidation respectively. In addition, genes related to oxidative stress, e.g., NADPH oxidase, cytochrome P(450)2E1,TNFalpha and NFkappaB, will be studied as potential components of BIBD. Oxidative stress and TNFalpha can activate NFkappaB, which is known to induce COX-2, iNOS and MnSOD expression. We will also investigate prosurvival signaling molecules such as MAPK/ERK and CREB, which provide resistance to neurotoxic events such as oxidative stress. Preliminary studies comparing the P and NP rat strains indicate that ethanol increases MAPK/ERK activation, atrophic signaling pathway that causes prosurvival gene induction, likely as a protective response to ethanol-induced oxidative stress. MAPK/ERK activation is inversely related to BIBD, that is, P rats have greater BIBD and reduced MAPK/ERK activation compared to NP rats. Thus, a second component of this

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aim will be to investigate aspects of P-MAPK/ERK and P-CREB. The antioxidant butylated hydroxytoluene (BHT) pre-vents BIBD and these studies will be extended using other antioxidants. The effect of antioxidants on induction of oxidative stress markers, enzymes, and the signaling cascades mentioned above will also be determined using immunohistochemistry, EMSA, western and blot analyses. Experiments using transgenic mice strains including NFkappaB reporter gene mice, TNFalpha knockouts, CYP2E1 knockouts and PKC knockouts will test the role of these specific genes in B1BD. Aim 2. Peripheral tissue damage is involved in BIBD. Our 4-day binge elevates plasma ammonia and enzyme levels. Further, intragastric models of liver fibrosis induce CNS inflammation. Thus, models that are known to induce hepatotoxicity will be investigated for brain gene activation and neuropathology as described above. Aim 3. Repeated binge exposure will increase BIBD. Clinical studies have shown that multiple withdrawals lead to a higher incidence of seizures and correlates with memory and learning impairments. Thus, the effects of multiple episodes of alcohol exposure on BIBD, gene induction and oxidative stress will be determined. These in vivo studies will greatly increase our understanding of the factors that cause neurodegeneration in alcoholics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MRI OF BRAIN ISCHEMIA AND REPERFUSION IN A PRIMATE MODEL Principal Investigator & Institution: De Crespigny, Alex; Associate Physicist, Massachusetts Gener; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-DEC-2001; Project End 30-NOV-2005 Summary: (provided by applicant): The focus of this proposal is the application of advanced magnetic resonance imaging techniques, specifically diffusion and perfusion weighted MRI, to study the evolution of ischemic brain injury in a model of stroke in nonhuman primates (macaques). The use of diffusion and perfusion MRI for assessing stroke in animal models is well established and is becoming increasingly popular for diagnosing and monitoring acute stroke in human patients. Their clinical application remains somewhat controversial however, primarily because of an apparent lack of validation of the methodology in humans. This proposal will address this deficiency using clinically applicable MRI techniques in a macaque stroke model that closely resembles human stroke, but with the advantages of a controlled experimental setting and histologically defined endpoints. The overall objective of this proposal is to distinguish reversible from nonreversible brain damage in ischemic stroke using MRI. We will also show that MRI provides a "surrogate endpoint" to supplement or replace neurological testing in the assessment of stroke outcome in humans. We will use an endovascular stroke model in macaques, recently developed at MGH. Under fluoroscopic guidance, animals will receive 10, 20, 40, 60, 120, or 240 minutes of middle cerebral artery occlusion, or permanent occlusion. The specific aims are (1) to measure the natural evolution of the brain lesion using continuous T2-diffusion-and perfusionweighted MRI during and up to 30 days after transient and permanent focal cerebral ischemia and (2) determine the combination of MRI derived parameters that can reliably predict reversible/nonreversible brain damage after transient ischemia using a statistical model that incorporates all the imaging findings. In addition to MRI, we will perform serial neurological testing and finally histological analysis of the brain slices. We hypothesize that (1) injury indicated by diffusion abnormality is reversible beyond a critical ischemia duration and that stroke evolution in macaques is closer to that in humans than rats, and (2) acute MRI scans can predict regional brain tissue status at the

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endpoint and that the statistical model can predict infarct location and neurological outcome from the chronic MRI data. A successful outcome from this study on nonhuman primates will generate data that will be directly relevant to the study and management of stroke in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MRI/S IN CHILDREN WITH PRENATAL ALCOHOLIC EXPOSURE Principal Investigator & Institution: Astley, Susan J.; Epidemiology; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 28-FEB-2005 Summary: (provided by applicant): Fetal alcohol syndrome (FAS) is a permanent birth defect syndrome caused by maternal drinking during pregnancy. FAS is characterized by growth deficiency, a unique facial phenotype and central nervous system (CNS) dysfunction. The cognitive/behavioral problems in this condition stem from prenatal organic brain damage. Not all individuals with prenatal alcohol exposure suffer brain damage and not all who do suffer brain damage have FAS. The degree of brain damage among individuals with prenatal alcohol exposure may vary from microcellular and neurochemical aberrations to gross structural anomalies. Similarly, cognitive/behavioral dysfunction varies considerably. Teratogenic physical findings in individuals with FAS lend credence to the clinical judgment that their cognitive and behavioral dysfunction is due, in part, to organic brain damage. But without the physical features of FAS or at least a severe expression of brain damage, the injury often goes undiagnosed and unserved. This project proposes to use (magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MM), and functional MM (fMRI)) to determine if prenatally alcohol-exposed children, with and without FAS, who present along the full continuum of mild to severe CNS dysfunction, have irrefutable evidence of organic brain damage in the form of chemical and structural alterations. An MRS pilot study of prenatally alcohol-exposed monkeys with moderate CNS dysfunction found that levels of choline/creatine in the brain, a marker of cell membrane breakdown, rose with increasing alcohol exposure and increasing neuropsychological dysfunction. An MRS pilot study in children with FAS also showed that choline/creatine increased with increasing neuropsychological dysfunction. These findings are consistent with MRS outcomes in individuals with organic brain damage associated with other disease states. MRI studies in small numbers of people with FAS and in alcohol-exposed monkeys with moderate CNS dysfunction demonstrate significant size alterations of selected brain regions. Together, these studies demonstrate the utility and sensitivity of MM/S in better understanding alcohol teratogenesis. Neuropsychological dysfunction will be measured using a global index of impairment generated from psychometric measuresand with experimental measures of discrete, clinically meaningful cognitive skills subserved by brain regions that prior literature suggests may be affected by alcohol teratogenesis. A pilot feasibility study will also be conducted to determine if fMRI can be effectively administered to this population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEONATAL BRAIN ISCHEMIA AND REPERFUSION Principal Investigator & Institution: Keller, Richard W.; Ctr/Neuropharmacology/Neurosci; Albany Medical College of Union Univ Union University Albany, Ny 12208 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2004

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Summary: Stroke is among the most common neurological disorders in the US. Most strokes involve a blockage of one of the blood vessels of the brain, thus depriving a region of brain tissue of its much needed oxygen and nutrients. In many cases, at least some blood flow is restored (reperfusion). Whereas restoration of blood flow sounds very positive, unfortunately providing significant levels of oxygen to a compromised tissue can also lead to the generation of reactive oxygen species. Both of the damaging aspects of the two main components of stroke - acute ischemia and reperfusion - have been reproduced in adult rat models, and the pathways and mechanisms of damage are beginning to emerge. Several observations suggest that the neonatal brain is more tolerant to ischemic events than the adult brain. Most current ischemia research in neonates is focused on the hypoxia associated with child birth and these models lack the reperfusion component studied in stroke. Ischemic strokes in infants and children are rare compared to strokes in adults, yet they do occur and are probably under diagnosed. When strokes occur in children they are frequently in the same brain regions as in adults. Our studies will examine important basic mechanisms of brain damage in an infant rat model of transient focal ischemia with reperfusion. We will determine the presence, sources and persistence of several known mediators of ischemic damage, namely: excitatory amino acids, immediate early genes, and hydroxyl radical. Our studies will focus on the mechanisms that regulate the levels of these mediators and the interactions between and among them. We will also investigate the changes that occur in various regions of the infarct - the core, the penumbra and the extra-penumbra areas. Understanding how these mediators are regulated in the infant brain will provide insights into the differences in ischemic responses in the infant and the adult, and will promote rational treatment of both juvenile and adult ischemic events. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURAL BASIS OF LEXICAL DEFICITS IN HYPERACUTE STROKE Principal Investigator & Institution: Hillis, Argye E.; Associate Professor; Neurology and Neurosurgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The question of how and where language is represented in the brain has been an area of intense investigation for more than a century. The various methodologies that have addressed this question each have their own limitations, and the various methodologies have yielded divergent answers. However, some conclusions have been robust across investigations: (1) a given language task (say, naming a picture) requires a number of distinct processes or levels of mental representation; (2) there is some specialization across cortical regions, such that each distinct level of processing may take place in separate brain regions; thus, a whole network of regions might subserve the task; (3) these structure/function relationships are fairly similar across most individuals, but can change in response to brain damage. Yet, there are many unanswered questions. What are the precise areas that are either necessary or sufficient for any given language process? How fine-grained are the structure/function relationships with respect to language in the brain? That is, for any given level of representation, such as a lexical (word form) representation, are there distinct regions for different types of words (e.g., nouns versus verbs) and/or for different output modalities (e.g., spoken versus written) for the same word? The goal of this project is to address these questions with a novel approach utilizing MR perfusion weighted imaging (PWI) and diffusion weighted imaging (DWI), along with testing of language processing at the same time, in subjects <24 hours post onset of stroke. The major hypothesis is that PWI and DWI with concurrent language testing can reveal

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areas of neural dysfunction, with or without structural damage, associated with disruption of each level of representation underlying lexical tasks such as naming, reading, or spelling a word. The imaging and language tests together are expected to show that there are distinct areas of cortex that are essential for the processing of phonological representations (or spoken word forms) versus orthographic representations (or written word forms), and that the regions are specific to a particular grammatical word class (e.g., nouns versus verbs). It is also predicted that still other regions are crucial for representing the meanings of various types of words, or for more peripheral components of speech or written output for all types of words. It is also hypothesized that repeat DWI, PWI, and language tests at 3 days post-onset will reveal mechanisms of early recovery of lexical functions in acute stroke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURAL DAMAGE IN METHAMPHETAMINE USERS: AN MRS STUDY Principal Investigator & Institution: Nordahl, Thomas E.; Associate Professor; Psychiatry; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 28-FEB-2005 Summary: High dose exposure of animals to methamphetamine [MA] causes significant damage to frontostriatal brain regions, which are relatively rich in dopaminergic [DA] and serotonergic [5-HT] innervation. Although animal models of drug addiction are extremely valuable, convergent findings from human studies are critical if one is to understand the impact of long-term MA use on the human brain. The goal of this proposal is to examine the effects of long-term effects of MA use in frontostriatal regions using proton magnetic resonance spectroscopy [MRS] in conjunction with mature neurons (primarily N- acetyl aspartase [NAA], high energy metabolic products (phosphocreatine and creatine [Cr], cell membrane synthesis or degradation (choline [Cho]), and glia (myoInositol [mI). MRS is a safe non-invasive tool that can detect certain proton spectroscopic metabolite patterns associated with brain damage and has been validated as a viable tool in detecting neuronal damage in both animals and humans. The interdisciplinary approach of MRS and cognitive assessment will yield valuable data essential for understanding the cognitive sequelae of neuronal damage resulting from MA abuse. Our preliminary data from methamphetamine dependent (MD) subjects (n=9) reveal likely neuronal damage in the prefrontal cortex [PFC] and anterior cingulate [ACC] as well as deficits on attentional tasks subserved by these regions. The proposed work is essential to confirm these clinically important findings by testing a larger sample of MD subjects and controls, using MRS in conjunction with sensitive computerized tasks of attention and memory. NAA, Choline, myo- Inositol and creatine will be measured in the PFC (dorsal and ventral), ACC, striatum, and control structures (primary visual cortex). Group differences in levels of NAA, Chol, mI, and Cr in the above regions will be determined by repeated measured analysis of variance. A similar analysis approach will be applied to the behavioral data. Correlational analyses between cognitive measures and imaging data from specific hypothesized regions of interest will be conducted. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEURAL ORGANIZATION OF COGNITION Principal Investigator & Institution: Polk, Thad A.; Assistant Professor; Psychology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-MAY-2000; Project End 30-APR-2004 Summary: One of the central tenets of modern cognitive neuroscience is that the neural architecture of cognition is organized into anatomically segregated subsystems (modules) that perform different functions. It is usually plausible to assume that the underlying neural segregation was genetically predetermined, but there are cases that this hypothesis cannot easily accommodate. Furthermore, a growing body of evidence in neuroscience has demonstrated that experience can and does lead to what might be called quantitative changes in brain organization (e.g., changes in the size of an existing functional region). It is therefore natural to ask: Can experience lead to qualitative changes in the brain's modular organization (such as the neural segregation of a function that was not previously localized) or are neural modules always hard-wired by genetics? Previous patient work demonstrating selective impairments in experiencedependent functions (e.g., reading and writing) suggests that experience may indeed be able to produce neural segregation, although the interpretation of those findings can be controversial. We propose to develop converging evidence relevant to the issue by using an independent methodology (neuroimaging) that complements lesion studies. Making progress on this issue could have important implications for our understanding of neural organization, for the interpretation of neurological patients, and ultimately for the rehabilitation of patients with brain damage. The method we propose to use is functional magnetic resonance imaging (fMRI). fMRI has a number of features that make it ideal for addressing the issue of experience-dependent neural segregation: (1) its spatial resolution (1-5mm3) is sufficiently fine to detect anatomic segregation of functional modules, (2) significant results can typically be obtained in individuals making it unnecessary to average across subjects (a critical point because the underlying neural organization under study may differ across individuals), and (3) it can be used with human subjects who are neurologically intact. Our plan is to develop converging evidence regarding experience- dependent neural segregation by investigating three sub- questions: (1) Is letter recognition segregated from digit recognition? (2) Is semantic knowledge about numbers segregated from semantic knowledge about other categories? (3) Are different languages segregated in bilinguals? We chose these domains for four reasons. First, in each case the putatively segregated function can be selectively impaired by brain damage (suggesting that it may be segregated). Second, in each case it is problematic to assume that any underlying neural segregation could be hard-wired. Third, the functions can be relatively well matched with control tasks (making it more difficult to attribute positive results to artifacts). And fourth, the functions can be readily studied using fMRI (e.g., they do not require extensive movement). By studying these three domains in parallel we hope to develop converging evidence that will allow us to draw more general conclusions relevant to the issue of experience-dependent neural segregation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROANATOMIC/PSYCHOLOGIC ANALYSES OF FAS/FAE DEFICITS Principal Investigator & Institution: Streissguth, Ann P.; Psychiatry and Behavioral Scis; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2003; Project Start 01-AUG-1996; Project End 30-APR-2006

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Summary: (provided by applicant): This research proposes to extend the successful work already completed in quantifying the neuroanatomic abnormalities underlying neuropsychological deficits among people with brain damage caused by prenatal alcohol exposure. Although Fetal Alcohol Syndrome (FAS) is a distinct diagnostic entity, it conceals substantial variability of deficits. Many individuals with substantial prenatal alcohol exposure exhibit dysfunctional behaviors that appear to be CNS-based, but do not have facial manifestations of FAS. These features are sometimes referred to as possible fetal alcohol effects (FAE). In prior work, we developed and demonstrated a new method of shape analysis targeting the corpus callosum (CC) that was above 80% accurate in separating FAS/FAE from controls, using a symmetrical four-quadrant data set of male and female adolescents and adults across three diagnostic groups: FAS, FAE, and age/sex matched non-exposed controls. Using newly developed methods, we now propose to reanalyze these magnetic resonance images for additional brain structures, targeting the cerebellum, and to compare these images with the full battery of neuropsychological tests obtained on our 180 subjects. We hypothesize that these new image analyses will reveal significant differences in mean or variance of brain form between FAS/FAE and controls, that FAS and FAE will not differ from each other, and that distinct profiles of association will be observed between neuroanatomy and neuropsychology. Over three years, we will pursue four aims: (1.) To quantify new morphological data from existing magnetic resonance images, to examine additional curves and shapes on and near the cerebellum that will be combined with CC and gray/white matter volumes in detecting FAS/FAE; (2.) To examine the behavioral phenotype of FAS/FAE, using already collected data augmented with new scores from existing data, to study the other three quadrants of subjects for profiles of Executive Function and Motor Function deficits that were related to different CC shape anomalies in adult males; (3.) To conclude the full four-quadrant neuroanatomic/neuropsychologic analysis, using the new data on cerebellar shape and size combined with the augmented behavioral phenotype data; (4.) To develop a datadriven diagnostic protocol based on the principles already demonstrated and utilizing entire data sets from both imaging and behavior. This will be the first systematic study to move directly from state-of-the-art image analysis techniques and neuropsychological testing, to a diagnostic protocol with practical utility, filling a compelling need for diagnosing fetal alcohol brain damage in adolescents and adults and in the absence of the typical facial characteristics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROANATOMICAL/NEUROCHEMICAL REORGANIZATION AFTER EARLY INSULT LIMBIC CIRCUIT Principal Investigator & Institution: Felleman, Daniel J.; Professor; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2001 Summary: Developmental disorders such as autism offer a unique opportunity to identify important brain structures and functional circuits that underlie complex, perceptual, cognitive, and social behaviors. The proposed multi-disciplinary program, utilizing behavioral testing (Project I) and MRI spectroscopy in autistic children (Project II), and behavioral, MRI-spectroscopic, and neuroanatomical studies in monkeys (Projects II and III), offers a comprehensive analysis of testable animal model of human autism. According to this hypothesis, early damage to the amygdala-orbitofrontal circuit causes a developmental impairment characterized by disturbances in social, emotional, and cognitive behavior. Project IV will evaluate the degree to which the infant responds

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to injury to the orbitofrontal-amygdala circuit. In order to evaluate fully the possible mechanisms of functional reorganization following this neonatal brain damage, the normal infant and normal adult patterns of cortico-limbic connections will be evaluated using modern neuroanatomical pathways tracing techniques. These patterns of connections will then be correlated with the immunocytochemical development of this circuit and closely related structures. Next, the patterns of cortico-limbic connections with be evaluated in adult monkeys that received either early or late lesions of the amygdala or orbitofrontal cortex. These results will establish the degree to which the developing nervous system can utilize compensatory mechanisms to stabilize developmentally transient neural pathways, to recruit new pathways between weakly associated structures, or to recruit new target structures into functional cortico-limbic circuits. Overall, this research will make a significant contribution towards our understanding of the neurobiological bases of pervasive developmental disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROBIOLOGICAL BASIS OF DEPRESSION AFTER BRAIN DAMAGE Principal Investigator & Institution: Solodkin, Ana; Neurology; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2001; Project Start 15-SEP-1999; Project End 31-AUG-2004 Summary: Depression is a serious complication of structural brain injury, and can severely impair physical and cognitive recovery. Of the three million stroke survivors living in the US, more than 65 percent of them will suffer clinical symptoms of depression. Many of these cases can be directly attributable to the stroke, making poststroke depression a serious health problem. The specific aim of this proposal is to study the biological bases of depression as revealed through patients recovering from ischemic focal brain injury. These studies of depression will focus on its effects on motor system plasticity after middle cerebral artery infarction. We will test the following hypotheses: Motor cortices in clinically depressed subjects will present neurochemical changes in monoaminergic systems (Serotonin, dopamine and noradrenaline). Recovery of motor skills after frontal ischemic stroke depends on the anatomical reorganization of ipsilateral frontal regions adjacent to the infarcted area, and these anatomical changes will be more pronounced in individuals without depression when compared to cases with post-stroke depression. Functional neuroimaging will corroborate the anatomical findings, demonstrating poorer anatomical recovery in depressed patients than in those without depression. Areas underlying functional recovery as seen with fMRI will show the greatest degree of anatomical reorganization when assessed with direct anatomical methods in non-depressed cases compared to depressed ones. The overriding goal of this research is to investigate the neuroanatomical and neuropharmacological differences between depressed and non-depressed patients following focal ishemic brain damage, and to correlate the findings from studies of autopsy tissue with neuroimaging studies using functional magnetic resonance imaging (fMRI). Since combining both methods will limit the number of cases, in parallel, we will perform the same neuroantomical studies in post-mortem tissue with damage in the equivalent areas (but without fMRI assessment). The detection of the changes in cellular circuitry during recovery in groups with and without post-stroke depression will allow us to understand better the neurobiological substrate of this disorder. In the long run, this information may lead to novel pharmacological treatments in both depression and stroke, but most importantly, in those cases where depression is a concomitant of structural brain injury.

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At the same time, the current research aims to give the principal investigator necessary mentored experience to achieve independence in biological psychiatry research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURO-COGNITIVE OUTCOME AFTER EARLY FOCAL BRAIN DAMAGE Principal Investigator & Institution: Trauner, Doris A.; Professor; Neurosciences; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2008 Summary: (provided by applicant): A great deal can be learned about plasticity in the developing human nervous system by studying children who incur brain insults during critical periods of brain development. Damage to the developing brain may have a very different impact on cognition than would damage to the fully developed brain. The focus of this study will be to evaluate the role of seizures and of epileptiform brain activity on cognitive function in children with early focal brain damage (FL). The study proposes to explore issues of plasticity and reorganization in the developing human brain by studying children who suffered very early unilateral brain damage from stroke or hemorrhage, incurred prior to or at birth. The specific aims of the project are 1) to determine the impact of seizures and of epileptiform brain activity on cognitive outcome in children with early focal brain damage; 2) to determine whether epileptiform electroencephalographic (EEG) abnormalities in the FL population are stable over time, or get worse or better with time, and whether changes in the EEG over time correlate with changes in cognitive function; 3) to identify the extent and limits of plasticity in this population, and the role of seizures or epileptiform brainwave activity in limiting plasticity. Three groups of children between the ages of 8 and 12 years with pre- or perinatal unilateral brain lesions in the middle cerebral artery distribution from stroke or hemorrhage, and matched controls, will receive neuropsychological, behavioral, and adaptive function assessments, including tests of intelligence, language, visual spatial skills, attention, memory, academic achievement, and executive function. Subjects will also have EEGs to assess the effects of epileptiform abnormalities on cognitive function, and brain MRI scans to determine the volume and location of the lesions. The 3 FL groups will consist of 20 children with a history of seizures, 20 children without seizures but with epileptiform EEG abnormalities, and 20 children with no seizures and normal EEGs. The results of these investigations should provide a better understanding of the role of seizures and epileptiform brain activity on cognitive function during brain development, as well as potential limitations on plasticity in the developing human brain. The findings may further serve as a basis from which to design more effective interventions for children at risk for cognitive dysfunction because of early brain damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEURON PLASTICITY AND RECOVERY OF FUNCTION AFTER STROKE Principal Investigator & Institution: Kartje, Gwendolyn L.; Neurology; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2001; Project Start 15-SEP-2001; Project End 14-SEP-2006 Summary: (Verbatim from the Applicant's Abstract) Stroke is a devastating clinical problem which leads to neuronal death and functional loss. Interestingly, similar brain damage in the perinatal period often results in better functional outcome. This improved

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recovery is thought to be due to the inherent "plasticity" of the young brain, with the formation of new neuroanatomical connections from spared neural tissue replacing damaged pathways. The main goal of the present proposal is to promote neuroanatomical plasticity following adult brain damage, and thereby improve functional outcome. We have recently shown that a powerful technique to induce adult plasticity is by blockade of the myelin associated neurite inhibitory protein Nogo-A. We now plan to use a clinically relevant model of focal ischemic stroke to determine if Nogo-A blockade results in neuroanatomical plasticity and functional recovery and Hypothesize that: following focal ischemic brain damage, blockade of the myelin associated neurite inhibitory protein Nogo-A with the monoclonal antibody IN-1 will result in cortico-efferent plasticity from the spared, unlesioned cortex and improved functional outcome. This hypothesis will be tested in the following Specific Aims: Specific aim #1 will determine if blockade of Nogo-A following stroke leads to structural plasticity of corticofugal fibers from the spared, unablated cortex using neuroanatomical tracing techniques. Specific aim #2 will determine if blockade of NogoA following stroke leads to behavioral recovery in forelimb performance affected by the stroke using specific tests for forelimb motor and sensory function. Specific aim #3 will determine if improved recovery in forelimb use is directly related to the new structural plasticity from the spared cortex using electrophysiological methods to define the new neuronal pathways. The results of these studies may lead to new therapeutic approaches to return lost functions to patients suffering from ischemic as well as other causes of brain damage by enhancing the inherent ability of the brain to use undamaged tissue to repair and recover. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OPTICAL MONITORING OF CEREBRAL OXYGENATION IN INFANTS Principal Investigator & Institution: Franceschini, Maria A.; Instructor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-APR-2006 Summary: (provided by applicant): Oxygen deprivation, typically the result of a combination of hypoxia and hypoperfusion, is often the primary event setting off a biochemical cascade that leads to irreversible brain injury in perinatal encephalopathy. The long-term objective of this project is the development of a novel near-infrared spectroscopy (NIRS) device for the continuous monitoring of the regional tissue saturation (St02), arterial saturation (Sa02), and venous saturation (Sv02) in the neonate's brain. Such a device could potentially detect brain tissue compromise before the development of irreversible structural damage, thus allowing for timely and specific intervention. The novelty of our approach relates to the hypothesis that an appropriate temporal analysis of NIRS data can yield three different oxygenation measurements: (1) St02 from the temporal average of the optical signal; (2) Sa02 from the oscillating component of the optical absorption at the pulse frequency; (3) Sv02 from the oscillating component of the optical absorption at the respiratory frequency. The short-term goals of this project are to characterize NIRS measurements of cerebral oxygenation and to identify the most effective practical implementation of NIRS (in terms of instrumentation and data processing) for non-invasive cerebral oximetry. In particular, we aim to 1 ) investigate the relationship between the local measurements of the hemoglobin oxygenation in the cerebral tissue, in the arterial vascular compartment, and in the venous vascular compartment, and 2) perform spatially resolved measurements of cerebral oxygenation to localize areas of brain damage. To achieve our short-term

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goals, we propose to perform measurements on an animal model (piglets) where we can induce changes in the hemoglobin oxygenation levels over a large range, where we can perform hemodilution experiments, where we can induce focal brain injury, and where we have access to invasive readings of Sa02 and Sv02 from the gas analysis of blood samples. Finally we will test our proposed NIRS approach to cerebral oximetry on human neonates. The completion of this study will lead to the characterization of NIRS oximetry of the brain, to the development of multimode optical oximetry (simultaneous local measurement of St02, Sa02, and Sv02), and to the identification of the most effective approach to the non-invasive. continuous monitoring of cerebral oxygenation in neonates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXYGEN THERAPY IN NEONATAL HYPOXIA-ISCHEMIA Principal Investigator & Institution: Zhang, John H.; Schumpert Professor and ViceChair; Neurosurgery; Louisiana State Univ Hsc Shreveport P. O. Box 33932 Shreveport, La 71103 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The long-term goal of this study is to establish an oxygen therapy for neonatal hypoxia-ischemia and to identify the molecular mechanisms of oxygen treatment in brain protection. The Research Plan is based on our preliminary data that ONE treatment of 100% oxygen at normal baric pressure does in fact offer neuroprotection to the brain by reducing the damage to the ipsilateral hemisphere. These findings have given rise to the overall hypothesis that oxygen therapy will be beneficial to patients that have experienced a hypoxia-ischemia insult. To test this hypothesis, we propose the following four Specific Aims. The Specific Aim 1 will determine if long term brain protection can be achieved by using a short oxygen exposure (1 hour) at normal baric pressure applied at one hr after hypoxic/ischemic insult. Our specific hypothesis is that oxygen treatment (only one treatment]) will reduce hypoxic-ischemic brain damage in terms of brain weight, morphology (regional differences will be examined and compared between grey and white matters, ischemic core vs. penumbra, and cortex vs. hippocampus) and neurological and behavior functions. The Specific Aim 2 will examine the possible side effects of oxygen treatment. Our specific hypothesis is that only one oxygen treatment at constant normal baric pressure for short duration (1 hour) will result in no harmful side effects. Lipid peroxidation levels will be examined in the brain and lungs. Inflammatory responses will also be examined in the lungs. The occurrences of retinopathy of prematurity (ROP) will also be examined. The Specific Aim 3 will study the molecular mechanisms of oxygen-induced brain protection, especially the role of hypoxia-inducible factor-lalpha (HIF-1alpha) and its downstream effectors. Our specific hypothesis is that severe HIF1alpha up-regulation after neonatal hypoxia leads to the expression of pro-apoptotic genes and cell death. Oxygen treatment will reduce the hypoxic-induced upregulation of HIF-1alpha to a moderate level above normal level and thereby inhibit apoptotic pathways that are associated with HIF-1alpha and promote cell protective mechanisms through VEGF and erythropoietin. The Specific Aim 4 will continue to study the molecular mechanisms of oxygen-induced brain protection, especially the role of inflammatory cytokines such as interleukin-1beta (IL-1 beta), IL-6, IL-IO, IL-11 and TNFalpha, and the role of inducible nitric oxide synthase (iNOS). Our specific hypothesis is that the level and expression of inflammatory cytokines and iNOS increased in injured brain tissues and lead to cell death. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PERINATAL HYPOXIC ISCHEMIC BRAIN DAMAGE Principal Investigator & Institution: Vannucci, Robert C.; Professor of Pediatrics And; Pediatrics; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001; Project Start 06-SEP-1994; Project End 30-JUN-2004 Summary: The overall objective of the present Program Project proposal is to improve our understanding of the pathophysiologic mechanisms leading to hypoxic-ischemic brain damage in the human fetus and newborn infant and to develop effective strategies to prevent or minimize permanent brain damage which ultimately leads to mental retardation or developmental disability. Our specific aims include: 1) to elucidate underlying cellular and molecular mechanisms responsible for the occurrence of hypoxic-ischemic brain damage in perinatal animals; 2) to investigate mechanisms of hypoxic-ischemic neuroprotection through preconditioning and metabolic and pharmacologic manipulations; 3) to ascertain the contribution of oxidative stress and inflammatory mediators to the production of perinatal hypoxic-ischemic brain damage; 4) to study the effects of perinatal hypoxic-ischemic brain damage on short- and longterm cerebral development; and 5) to investigate the role of status epilepticus in perinatal hypoxic-ischemic brain damage. Included in the Program Project Proposals are 7 basic research projects and 3 Core projects, the latter to include an Administrative and Biostatistics Core, Neuropathology Core, and MR spectroscopy and imaging Core. The individual research project titles are: 1) Oxidative Metabolism; 2) Energy Metabolism; 3) Neuroprotective Mechanisms; 4) Inflammatory Mediators; 5) Oxidative Stress/Glia; 6 Cellular Differentiation; and 7) Status Epilepticus. Scientific disciplines represented in the Program Project include pediatric neurology, perinatology, neuroscience, neuropathology, neuroradiology, computer science and biostatistics. It is anticipated that the findings derived from the described research endeavors will have direct relevance to preventative and therapeutic interventions necessary to reduce substantially the significance and severity of mental retardation and developmental disability in developing human infants and children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PLASTICITY IMPLICATIONS--RECOVERY OF FUNCTION AFTER INJURY TO MOTOR CORTEX Principal Investigator & Institution: Pons, Timothy P.; Professor; Wake Forest University 2240 Reynolda Rd Winston-Salem, Nc 27106 Timing: Fiscal Year 2001 Summary: One of the difficulties associated with evaluating the relationship between cortical damage/reorganization and functional deficit/recovery is the issue of variability in any stroke model. The patient population is heterogeneous with regard to both the amount and location of damaged cortical territory and, accordingly, the severity and type of physical impairment. This is also true in monkey models of stroke where occlusions of the middle cerebral artery at the same point in the brain gives rise to variable functional outcomes as well as variable regions of damage to the brain. Fortunately, we are now able to non-invasively determine the regions of the brain damaged after stroke with magnetic resonance imaging (MRI) techniques in humans and monkeys alike. Additionally, with the advent of the many neuron recording technique, we can use the information gathered from the MRI scans in experimental monkeys to guide placement of recording electrodes adjacent to permanently damaged regions of cortex or into totally healthy regions of cortex. This technique also allows us

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to examine changes on a daily basis. In Project 3 we propose to use these technologies to follow reorganizational changes correlated with functional recovery at the single unit level of analysis. Our goal is to test specific hypotheses of cortical reorganization by recording from cortical regions that are important for motor control and likely to be involved in compensatory reorganization during recovery of function after occlusion of the middle cerebral artery or after striato-capsullary infarcts. These two types of experimental manipulation are chosen because they mimic the most common types of strokes seen in humans and are the types of stroke studied in human patients in projects 1 & 2. The experiments in project 4 will allow us to begin to unravel the location of cortical region that when damaged give rise to behavioral deficits as well as those implicated in the recovery of behavioral function after stroke. The proposed experiments represent initial efforts to explore the relationship between cortical reorganization and recovery of function in this manner. In the short term, the specific approach will begin to unravel the complex relationships between damaged cortical territories, reorganizing cortical domains, and behavioral performance. In the long term such knowledge show allow for more accurate prognoses and the design of rehabilitative strategies that are optimal for any given pattern for cortical damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POTASSIUM CHANNELS AND EPILEPTOGENESIS Principal Investigator & Institution: Rho, Jong M.; Assistant Professor; Pediatrics; University of California Irvine Campus Dr Irvine, Ca 92697 Timing: Fiscal Year 2001; Project Start 23-JUL-1997; Project End 30-JUN-2004 Summary: This application is for a Mentored Clinical Scientist Development Award (K08). The candidate obtained clinical training in Child Neurology at UCLA, and then completed a two-year fellowship in neuropharmacology at the National Institutes of Health (Epilepsy Research Branch, NINDS) prior to taking his current faculty appointment in 1994 at the University of Washington. The long- term career goal of the candidate is to study the relationship between ion channels and epileptogenesis, to identify potentially novel treatments for developmental epilepsies that have a rational molecular basis, and to explore the relationship between genetic susceptibility and environmental influence in the pathogenesis of the developmental epilepsies. The university medical center and Children's Hospital possess complementary strengths in the basic neurosciences and clinical pediatric epileptology, respectively. Laboratory space, equipment, and specialized consultants are available to the candidate on a collaborative basis provided by several academic departments. This environment is ideally suited for supporting and fostering the candidate's long-term professional goals. We have chosen as our experimental model the mKv1.1 potassiumchannel single gene mouse mutant which exhibits spontaneous seizures early in development. First, we hypothesize that loss of a specific potassium channel subunit in the CA 3 region of the hippocampus results in a functional alteration in physiological properties of pyramidal neurons such that they became hyperexcitable and prone to excessive synchronization of discharge. Second, we postulate that pharmacological treatment can alter the natural course of the epilepsy and may protect the animal from neuronal injury as a consequence of repeated seizures. Finally, we will explore whether partial expression of the mKv1.1 gene in plus/minus mice, resulting in an enhanced susceptibility to seizures, can be modified by secondary exposure to kainic acid (a potent convulsant and neurotoxin) early in development. Initial efforts will involve electrophysiological recordings from CA3 pyramidal neurons in hippocampal slices taken from null mutants at different ages; intrinsic and synaptic properties of these cells, as well as whole-cell

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potassium currents, will be measured with extracellular, intracellular and patch-clamp recording techniques. Video-EEG monitoring (with depth electrodes) will be employed to document epileptiform or seizure activity in the hippocampus, and histochemical analysis of neuronal damage and/or plasticity will be made with routine and special (e.g., Timm) stains. The results of these studies may lead to an improved understanding of the role ion channels play in epileptogenesis, may shed light on the controversial issue of whether chronic seizures can cause brain damage, and will provide a framework for further studies examining genetic and environmental interactions in the developing brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROGRESSION OF TEMPORAL LOBE EPILEPSY Principal Investigator & Institution: Dudek, Francis Edward.; Professor; Anatomy and Neurobiology; Colorado State University Fort Collins, Co 80523 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: (provided by applicant): Although epidemiological studies have provided valuable perspectives on temporal lobe epilepsy, the ethical limitations of human research prevent a definitive answer to the important question: is antiepileptic drug (AED) therapy purely symptomatic, or does it affect the natural history of the epilepsy? The proposed experiments use an animal model of temporal lobe epilepsy to determine whether spontaneous epileptic seizures damage the brain and increase the likelihood of more seizures (i.e., promote epileptogenesis), and conversely, whether decreasing the number of seizures with AEDs significantly reduces brain damage and epileptogenesis. The central hypothesis is that prolonged treatment with an AED, which significantly reduces spontaneous epileptic seizures, causes long-term reductions in the frequency and severity of subsequent epileptic seizures after AED withdrawal. The kainate-treated rat, a well-characterized animal model of temporal lobe epilepsy, will be used to determine whether the progressive increase in the frequency ofspontaneous seizures during the months after status epilepticus continues to damage the hippocampus and contributes to epileptogenesis. AEDs (i.e., phenytoin, phenobarbital, and valproate) will be used to block spontaneous epileptic seizures for prolonged periods to determine whether AED therapy reduces epileptogenesis and results in a long-term decrease in spontaneous seizure frequency (i.e., a decrease in frequency that persists after the AED therapy has been withdrawn). A related hypothesis is that prolonged AED treatment reduces neuronal death and other potential markers of hippocampal epileptogenesis. Chronic recording of electrographic seizures, quantitative histopathological studies, and in vitro electrophysiological recording of synaptic and epileptiform events in hippocampal slices will be used to determine if prolonged AED treatment decreases neuronal damage, reorganization of neural circuits, and epileptogenesis. These experiments will provide precise and valuable information regarding the influence of seizure frequency on brain damage and on the propensity for future seizures, which will be important for understanding the mechanisms of epileptogenesis and for making clinical decisions regarding AED therapy and epilepsy surgery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RADIATION DAMAGE REPAIR IN THE BRAIN VIA HUMAN ES CELLS Principal Investigator & Institution: Tabar, Viviane; Sloan-Kettering Institute for Cancer Res New York, Ny 10021

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Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2005 Summary: (provided by applicant): Brain irradiation is a powerful tool in the treatment of cancers including primary and metastatic many tumors, and even leukemias and lymphomas. However its use is restricted by the poor tolerance of the nervous tissue and the development of serious side effects among long-term survivors. These include a decline in IQ and cognitive function. This phenomenon is very frequent and irreversible. Its pathogenesis is not fully elucidated but it involves extensive demyelination occurring in a delayed fashion (months to years). Based on preliminary data obtained in the rat, we hypothesize that radiation exhausts the pool of dividing oligodendrocyte progenitors (OPC) and therefore the brain's ability to replace the myelinating cells. We have developed significant experience in the neural differentiation of human ES (hES) cells and we propose the transplantation of hES-derived neural precursors as an effective strategy for repair of radiation-induced brain damage. We will study the temporal and topographic pattern of cell loss following whole brain irradiation in the rat at five timepoints over the course of one year. The rats will receive BrdU prior to sacrifice and the brains will be processed for BrdU, NG2 (an OPC marker) and other neural markers. We will then graft irradiated rats with two different populations of neural precursors obtained from hES cells: a multipotential neural stem cell-like population, and an oligodendroglial progenitor population. In our preliminary data we have successfully derived such cells from hES cells and established stable eGFPexpressing hES cells via lentiviral gene transfer for reliable in vitro and in vivo identification. Grafted animals will be examined at 6 weeks after transplantation to assess cell survival, migration, and ability to replace the OPC niche, and at 6-8 months after transplantation to evaluate the ability of hES cells to contribute to remyelination of the injured brain. This work addresses a therapeutically important problem in brain cancer treatment and will provide a wealth of information on the behavior of grafted human ES cells within the context of an injured brain. If successful, we plan to initiate future studies addressing the functional impact of hES-derived neural precursor grafts on radiation-induced cognitive decline. This grant will only use the INIH-approved cell line: HI. NIH code WA01. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF COX2 GENE EXPRESSION IN ISCHEMIC BRAIN DAMAGE Principal Investigator & Institution: Iadecola, Costantino; Professor; Neurology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-MAR-1997; Project End 30-APR-2002 Summary: (Adapted from applicant's abstract): The long-term goal of this research program is to elucidate the role of the prostanoid-synthesizing enzyme cyclooxygenase2 (COX-2) in ischemic brain injury. Studies during the previous funding period have provided evidence that COX-2 is one of the factors by which the inflammatory process involving the ischemic brain (post-ischemic inflammation) contributes to the late progression of focal cerebral ischemic damage. These findings have indicated that COX2 participates in the late stages of ischemic brain injury. Other evidence however suggests additional mechanisms by which COX-2 could contribute to ischemic brain injury. In particular, COX-2-derived prostanoids are potent constrictors of cerebral blood vessels and participate in pathogenic processes linked to the activation of glutamate receptors. Considering that cerebral blood flow and activation of glutamate receptors play a critical role in the initiation of ischemic damage, these data raise the possibility that COX-2 could also be involved in early events of the ischemic cascade. Therefore, in this renewal application we will continue to pursue our long-term goal by

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testing the hypothesis that COX-2, in addition to its role in post-ischemic inflammation, is also involved in the mechanisms initiating ischemic brain injury. As a starting point, we will focus on the role of COX-2 in critical hemodynamic changes that occur during ischemia-reperfusion and in glutamate receptor-mediated cytotoxicity. In the proposed experiment, we will use molecular and biochemical approaches, as well as methods to assess hemodynamic, histological, and neurological outcome after cerebral ischemia. Focal cerebral ischemia will be produced by transient occlusion of the middle cerebral artery in mice. The brain damage resulting from focal microinjection of N-methyl-Daspartate or kainate in neocortex will also be investigated. The role of COX-2 will be examined using both pharmacological inhibition of COX-2, and COX-2-deficient mice. The role of COX-2 derived reactive oxygen species will be examined using mice over expressing the antioxidant superoxide dismutase. While the proposed studies will expand our understanding of the involvement of COX-2 in ischemic brain injury, they will also provide the rational basis for new neuroprotective strategies for human stroke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SENTENCE SEMANTICS: NORMAL PROCESSES AND LESION EFFECTS Principal Investigator & Institution: Zurif, Edgar B.; Psychology; Brandeis University 415 South Street Waltham, Ma 024549110 Timing: Fiscal Year 2001; Project Start 29-SEP-1999; Project End 31-AUG-2002 Summary: The broad purpose of the proposed research program is to investigate the nature and neurological organization of the capacity for understanding natural language sentences. The research will focus on the interface between syntactic and conceptual representations. It will examine the real-time operations involved in combining lexical conceptual content into contextualized interpretations; and it will examine the effects of variously sited focal brain damage on these operations. One aim is to determine if combinatorial meaning the combination of word meanings in a sentence is directed not only by the syntactic arrangement of the words in that sentence, but also by non-syntactic, generative lexical operations. A second aim is to determine if these two kinds of combinatorial processes can be dissociated by brain damage. This work will use reaction-time paradigms as an on-line means of studying these sentence comprehension operations. This program of research should yield information of relevance to remediation in aphasia. It should specify the kinds of real-time processing limitations that therapeutic efforts must address. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SERUM C-TAU PRECITION OF BRAIN DAMAGE IN MILD TBI Principal Investigator & Institution: Zemlan, Frank P.; Professor; Phase 2 Discovery, Inc. 3130 Highland Ave, 3Rd Fl Cincinnati, Oh 45219 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2004 Summary: (provided by applicant): The objective of the present Phase 1 feasibility study is to develop a quantitative serum-based biomarker for detecting neuronal damage in mild traumatic brain injury (TBI). Postconcussion Syndrome (PCS) is believed to be the cause for much if not all of the disability suffered by mild TBI patients. Although PCS occurs in about 40% of mild TBI patients, radiologic techniques detect few of these patients. The purpose of the proposed studies is to develop a new serum biomarker of neuronal damage for identifying mild TBI patients who subsequently develop PCS. We have developed a sandwich ELISA that quantifies a neuronally localized protein, MAP-

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tau, that is proteolytically cleaved and released from damaged neurons after brain injury (C-tau). In preliminary studies we demonstrate that serum C-tau levels are significantly elevated in mild TBI patients. The proposed studies will determine if initial serum C-tau levels predict which mild TBI patients subsequently develop PCS. Our Specific Aims are: Specific Aim 1: Determine if initial C-tau levels are a reliable predictor of Postconcussion Syndrome in mild TBI patients (N=80). Initial serum C-tau levels (<12 hrs postinjury), head CT (12). Diagnosis of PCS is made at 3-month follow-up. Patients will be dichotomized by presence or absence of PCS. The serum C-tau cut-off for predicting PCS will be determined by ROC analysis and the sensitivity, specificity and predictive value of initial C-tau levels for predicting PCS determined. Specific Aim 2: Determine if initial C-tau levels predict intracranial injury in mild TBI patients. Similar analysis of Specific Aim 1 patients but patients dichotomized by presence or absence of CT abnormality. Specific Aim 3: Determine if initial C-tau levels are a reliable predictor of Postconcussion Syndrome in mild TBI patients with no CT abnormality. Similar analysis as for Specific Aim 1 but restricted to patients with no CT abnormality which is projected to be about 85% to 90% of all patients (N = approximately 70). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNAL DETECTION THEORY AND SOURCE MEMORY Principal Investigator & Institution: Glanzer, Murray; Emeritus Professor; Psychology; New York University 15 Washington Place New York, Ny 10003 Timing: Fiscal Year 2001; Project Start 15-SEP-1999; Project End 31-MAY-2003 Summary: (Applicant's abstract): Item memory is memory for occurrence of events (e.g., Was this word spoken?). Source memory is memory for the source of an occurrence (e.g., Did A say it?). There is evidence that source memory is particularly vulnerable to aging and that it is differentially affected by different types of brain damage (e.g., frontal versus temporal). Signal Detection Theory has to date been extensively applied to item memory but has not been applied to source memory. When extended to cover source memory, it offers new and interesting predictions concerning the relation between source and item memory. The implications of Signal Detection Theory for performance of normal participants will be tested. The results will be compared with the results predicted by a different approach to memory, the family of threshold theories. The Signal Detection Theory will be applied then to evaluate the effects of aging and specific brain damage on memory. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SLEEP & FRONTAL LOBE FUNCTION IN REHAB FROM STROKE & TRAUMATIC BRAIN INJURY Principal Investigator & Institution: Kuna, Samuel T.; Associate Professor of Medicine; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: Sleep disturbance can be significant after brain damage due to trauma or stroke, but little is known regarding its prevalence and consequences. Patients often complain of symptoms of disturbed sleep and lack of dreaming, and demonstrate inattentiveness, memory difficulties, and easy fatigability, which are commonly associated with sleep disturbance in uninjured populations. In this protocol the sleep of a representative sample of TBI and stroke patients will precisely characterized, and the findings correlated with independent observations of brain function as delineated through formal neuropsychological evaluation. Subjects will be evaluated while

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attending the post-acute rehabilitation program of the Transitional Learning Community in Galveston. The results will increase our understanding of brain behavior relationships, and provide a scientific basis for intervening beneficially in these populations with better behavioral and pharmacological therapies Such interventions may directly improve quality of life in these patients and enable them to better engage in other rehabilitation efforts. Because stroke and trauma are leading causes of brain damage in the U.S., and cause considerable disability as well as expenditure for health care and rehabilitation, these results could have major public health impact. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STATUS EPILEPTICUS Principal Investigator & Institution: Towfighi, Javad; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001 Summary: The overall objective of this research project is to determine whether or not prolonged or repetitive seizures (status epilepticus) occurring in the newborn period lead to permanent brain damage or contribute to the neuronal injury caused by a prior or concurrent insult to the immature brain. In addition, it will be ascertained whether or not seizures occurring prior to a hypoxic-ischemic insult reduces the severity of the ultimate brain damage. Sp3ecific Aims include: 1) to ascertain whether or not status epilepticus causes overt brain damage in developing rabbits; 2) to ascertain whether or not sub-threshold and damaging status epilepticus induced during early recovery following cerebral hypoxia-ischemia accentuates the ultimate brain damage to developing rabbits; 3) to ascertain whether or n not a sub-threshold episode of status epilepticus confers protection against a subsequent episode of status epilepticus and seizure-induced brain damage in developing rabbits; and 4) to ascertain whether or not a sub-threshold episode of status epilepticus occurring prior to cerebral hypoxiaischemia confers protection against the ultimate brain damage in developing rabbits and, if so, by what mechanism. Developing rabbits will be used in all experiments and will be subjected to chemically induced status epilepticus using either kainic acid or flurothyl. Selected animals will undergo electrocorticographic monitoring and measurements of systemic physiologic variables; including blood pressure, heart rate, oxygen and acid-base status, blood glucose, lactate and ketone body concentrations. Rabbits undergoing status epilepticus with or without prior or subsequent cerebral hypoxia-ischemia will undergo neuropathologic processing and analysis to ascertain the distribution of severity of brain damage. Experiments are proposed in both unrestrained developing rabbits and in rabbits in which systemic physiologic variables are controlled to ascertain the contribution of alterations in body temperature, blood pressure, and oxygen and acid- based status to the ultimate brain damage caused either by status epilepticus, cerebral hypoxia-ischemia, or a combination of the two insults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TCDD-INDUCED OXIDATIVE STRESS Principal Investigator & Institution: Hassoun, Ezdihar A.; Pharmacology; University of Toledo 2801 W Bancroft St Toledo, Oh 43606 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 30-MAY-2004 Summary: In this project, we propose that subchronic exposure to 2,3,7,8tetrachlorodibenzo-p-dioxin (TCDD), induces oxidative stress with the production of oxidative tissue damage and changes in the antioxidant defense mechanisms and the

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aminergic systems in various regions of the brain. We also propose that antioxidants, such as vitamin E succinate and ellagic acid provide protection against these effects. To test this hypothesis, groups of female Sprague Dawley rats will be treated p.o., with daily doses of TCDD for 13 weeks and will then be sacrificed at the end of this period. Various regions of the brain will be dissected and assayed for the determination of the biomarkers of oxidative stress, as well as the levels of different monoamines and their metabolites. The formation of reactive oxygen species in brain tissues will be determined using the cytochrome c reduction assay, and the induction of the processes of lipid peroxidation and DNA-single strand breaks (SSB) will be measured using the thiobarbituric acid reactive substances (TBARS) assay and the alkaline elution technique, respectively. The levels of glutathione and the activities of various antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase and catalase will be also determined, using established biochemical assays. The levels of different biogenic amines in the brain regions will be determined using high performance liquid chromatography (HPLC). The protective effects of selected antioxidants, namely vitamin E succinate and ellagic acid against TCDD-induced oxidative stress in the brains of mice, will also be assessed. The results of the study will help future investigations of the body functions that are associated with the affected brain regions, which will provide tools for early detection of TCDD-intoxication. Furthermore, the study will be the first to investigate the protection by antioxidants against TCDD-induced effects on the brain, which may lead to new preventive measures against TODD-induced brain damage in exposed human populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE BIOLOGICAL BASIS OF ALCOHOL INDUCED BRAIN DAMAGE Principal Investigator & Institution: Meyerhoff, Dieter J.; Associate Professor; Northern California Institute Res & Educ San Francisco, Ca 941211545 Timing: Fiscal Year 2001; Project Start 01-AUG-1996; Project End 31-JUL-2006 Summary: (Provided by applicant): Long-term chronic alcohol abuse is associated with structural brain changes and neuro-cognitive impairment. Few studies have shown a convincing correlation between these phenomena and it appears likely that neurosubstrates other than structural alterations underlie the cognitive changes associated with heavy drinking and recovery. The overall goal of this project is to test the hypothesis that axonal/dendritic and membrane phospholipid ( and possibly perfusion) changes in white matter underlie the reversible structural and neurocognitive changes associated with long-term chronic alcohol abuse and recovery. Subjects: 50 light drinkers (LD) and 100 heavy drinkers. LD will be studied at baseline and 9-12 months later, HD will be studied at entry into alcohol abuse treatment (to capture the full extent of brain damage due to heavy drinking), at 2-4 weeks of abstinence, and at 9-12 months after treatment entry during abstinence or relapse. Measurements: Cognition by neuropsychological testing; brain structures by MRI, axonal/dendritic and neuronal viability by 1H MR spectroscopic imaging (N-acetyl aspartate, a putative neuronal/axonal marker); lipids by choline-containing compounds (Cho) and myoinositol (ml) and by phosphorus-31 MRS (via membrane phospholipids and their breakdown products and precursors); regional cerebral blood flow will be measured with exploratory spin-tagged perfusion MRI. The specific focus of the study will be on white matter, but cortical and subcortical gray matter, cerebellum, hippocampus, corpus callosum, and brain stem, intracranial volume and volumes of various brain nuclei will also be assessed. We expect that initially low regional NAA and phospholipid measures

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and initially high Cho and mI measures correlate with specific measures of cognitive impairment and that these outcome measures will recover during abstinence in association with cognitive improvements; relapse will arrest structural, metabolic, and cognitive improvements. The significance of these results is several fold: First, this project will develop non invasive outcome measures which provide objective quantitative measurements of alcohol-induced brain damage. This may be useful in future clinical trials in which drugs or treatments are used to reduce drinking, or to monitor effects of drugs aimed at reducing brain damage, or facilitating recovery. Second, these results may also provide information, which can lead to the development of specific drug treatments, aimed at preventing brain damage at the neuron or membrane or at facilitating recovery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THERAPEUTIC MOTOR TRAINING AND FETAL ALCOHOL EFFECTS Principal Investigator & Institution: Greenough, William T.; Swanlund Professor of Psychology,; Psychology; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2002; Project Start 01-AUG-1994; Project End 31-MAR-2007 Summary: (provided by applicant): Exposure to ethanol during brain development can permanently alter cerebellar and cerebral morphology and produce functional impairments in many aspects of behavior, including cognitive and motor performance. There currently is no known effective rehabilitation treatment for fetal alcohol syndrome (FAS). The long term objectives of this competing renewal are to identify methods to stimulate neuroplasticity that promotes rehabilitation of functional deficits resulting from brain damage induced by prenatal alcohol exposure. The general hypothesis is that complex motor learning, involving intensive training on an obstacle course, promotes structural neuroplasticity and ameliorates functional deficits in rats with brain damage induced by neonatal binge alcohol exposure. This period of brain development, comparable to that of the human 3rd trimester, is a time of heightened vulnerability to alcohol-induced cerebellar damage. Complex motor training in adulthood stimulated synaptic morphological plasticity of parallel fiber synapses in the cerebellar paramedian lobule (PML) and in motor cortex, and concurrently rehabilitated motor performance deficits. The three new aims build on this positive evidence of therapeutic rehabilitation, and now use early intervention initiated just after weaning. Aim 1 will identify other structural correlates of the rehabilitative effects in PML and motor cortex, including evaluation of plasticity of climbing fibers and effects on astrocytes and vasculature. Aim 2 will test whether the training can stimulate synaptogenesis in other regions of the cerebellum and in the hippocampus, and concurrently rehabilitate deficits in cerebellardependent and hippocampal dependent learning. Aim 3 will determine whether rats with alcohol- induced brain damage have the capacity for neurogenesis in the postweaning or adult brain, and whether stimulation of adult neurogenesis (or enhanced survival of newly-generated neurons) by behavioral experience, has merit as a potential mode of rehabilitation. These studies will provide important new data that can guide and inform efforts to develop a rational approach to rehabilitation for children with FAS Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

Matrix Metalloproteinases Contribute to Brain Damage in Experimental Pneumococcal Meningitis. by Leib SL, Leppert D, Clements J, Tauber MG.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97183

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Traumatic Brain Damage Prevented by the Non-N-Methyl-D-Aspartate Antagonist 2,3-Dihydroxy-6-Nitro-7-Sulfamoylbenzo[f]quinoxaline. by Bernert H, Turski L.; 1996 May 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39228

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

A case of brain damage due to a high-energy proton beam. Author(s): Torubarov FS, Zvereva ZF, Prikhod'ko AE. Source: Neuroscience and Behavioral Physiology. 2003 March; 33(3): 227-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769053&dopt=Abstract

3 Adapted 4

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

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A meta-analytic review of the sensitivity of the Wisconsin Card Sorting Test to frontal and lateralized frontal brain damage. Author(s): Demakis GJ. Source: Neuropsychology. 2003 April; 17(2): 255-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12803431&dopt=Abstract

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A neurologist's reflections on boxing. IV. Late and permanent brain damage. Author(s): Unterharnscheidt F. Source: Revista De Neurologia. 1995 September-October; 23(123): 1013-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8556584&dopt=Abstract

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A preliminary study to investigate the empowerment factors of survivors who have experienced brain damage in rehabilitation. Author(s): Man DW. Source: Brain Injury : [bi]. 2001 November; 15(11): 961-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11689094&dopt=Abstract

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A worry for ravers. One night of ecstasy could cause brain damage. Author(s): Carmichael M. Source: Newsweek. 2002 October 7; 140(15): 64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12389311&dopt=Abstract

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Adult stroke and perinatal brain damage: like grandparent, like grandchild? Author(s): Leviton A, Dammann O, O'Shea TM, Paneth N. Source: Neuropediatrics. 2002 December; 33(6): 281-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571781&dopt=Abstract

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Adult versus infant brain damage: behavioral and electrophysiological effects of striatectomy in adult and neonatal rabbits. Author(s): Stewart DL, Riesen AH. Source: Adv Psychobiol. 1972; 1: 171-211. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4199739&dopt=Abstract

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Affective language and humor appreciation after right hemisphere brain damage. Author(s): Lehman Blake M. Source: Seminars in Speech and Language. 2003 May; 24(2): 107-19. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709884&dopt=Abstract

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Age-dependent consequences of seizures: relationship to seizure frequency, brain damage, and circuitry reorganization. Author(s): Lado FA, Sankar R, Lowenstein D, Moshe SL. Source: Mental Retardation and Developmental Disabilities Research Reviews. 2000; 6(4): 242-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11107189&dopt=Abstract

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Alcohol-related brain damage--the concerns of the Mental Welfare Commission. Author(s): Jacques A. Source: Alcohol Alcohol Suppl. 2000 May-June; 35 Suppl 1: 11-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11304068&dopt=Abstract

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Amnesia following cortical brain damage in mice. Author(s): Glick SD, Greenstein S. Source: Behav Biol. 1972 August; 7(4): 573-83. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5065697&dopt=Abstract

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An approach to the study of brain damage. The principles of fetal electroencephalography. Author(s): Rosen MG, Scibetta J, Chik L, Borgstedt AD. Source: American Journal of Obstetrics and Gynecology. 1973 January 1; 115(1): 37-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4681833&dopt=Abstract

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An investigation of the ability to process inferences in language following right hemisphere brain damage. Author(s): McDonald S, Wales R. Source: Brain and Language. 1986 September; 29(1): 68-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3756462&dopt=Abstract

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An ordinate comparison method of calculating brain damage probability. Author(s): Glaister BR. Source: Br J Soc Clin Psychol. 1971 December; 10(4): 367-74. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5151868&dopt=Abstract

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Analysis of ischemic brain damage in cases of acute subdural hematomas. Author(s): Abe M, Udono H, Tabuchi K, Uchino A, Yoshikai T, Taki K. Source: Surgical Neurology. 2003 June; 59(6): 464-72; Discussion 472. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826344&dopt=Abstract

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Are text and tune of familiar songs separable by brain damage? Author(s): Hebert S, Peretz I. Source: Brain and Cognition. 2001 June-July; 46(1-2): 169-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11527321&dopt=Abstract

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Are there sex differences in the brain basis of literacy related skills? Evidence from reading and spelling impairments after early unilateral brain damage. Author(s): Frith U, Vargha-Khadem F. Source: Neuropsychologia. 2001; 39(13): 1485-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585616&dopt=Abstract

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Assessment of early brain damage in carotid endarterectomy: evaluation of S-100B serum levels and somatosensory evoked potentials in a pilot study. Author(s): Mussack T, Biberthaler P, Geisenberger T, Gippner-Steppert C, Steckmeier B, Mutschler W, Jochum M. Source: World Journal of Surgery. 2002 October; 26(10): 1251-5. Epub 2002 September 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12205550&dopt=Abstract

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Association of global brain damage and clinical functioning in neuropsychiatric systemic lupus erythematosus. Author(s): Bosma GP, Middelkoop HA, Rood MJ, Bollen EL, Huizinga TW, van Buchem MA. Source: Arthritis and Rheumatism. 2002 October; 46(10): 2665-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384925&dopt=Abstract

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Astroglial protein S-100 is an early and sensitive marker of hypoxic brain damage and outcome after cardiac arrest in humans. Author(s): Bottiger BW, Mobes S, Glatzer R, Bauer H, Gries A, Bartsch P, Motsch J, Martin E. Source: Circulation. 2001 June 5; 103(22): 2694-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11390339&dopt=Abstract

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Behavioural profiles of children and adolescents after pre- or perinatal unilateral brain damage. Author(s): Trauner DA, Nass R, Ballantyne A. Source: Brain; a Journal of Neurology. 2001 May; 124(Pt 5): 995-1002. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11335701&dopt=Abstract

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Biochemical markers for brain damage after cardiac surgery -- time profile and correlation with cognitive dysfunction. Author(s): Rasmussen LS, Christiansen M, Eliasen K, Sander-Jensen K, Moller JT. Source: Acta Anaesthesiologica Scandinavica. 2002 May; 46(5): 547-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027849&dopt=Abstract

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Blood pressure and tissue oxygenation in the newborn baby at risk of brain damage. Author(s): Weindling AM, Kissack CM. Source: Biology of the Neonate. 2001; 79(3-4): 241-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11275659&dopt=Abstract

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Brain damage after coronary artery bypass grafting. Author(s): Bendszus M, Reents W, Franke D, Mullges W, Babin-Ebell J, Koltzenburg M, Warmuth-Metz M, Solymosi L. Source: Archives of Neurology. 2002 July; 59(7): 1090-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117356&dopt=Abstract

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Brain damage after neonatal tetanus in a rural Kenyan hospital. Author(s): Barlow JL, Mung'Ala-Odera V, Gona J, Newton CR. Source: Tropical Medicine & International Health : Tm & Ih. 2001 April; 6(4): 305-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11348521&dopt=Abstract

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Brain damage and dexamethasone? Author(s): Wright NP, Wales JK. Source: Pediatrics. 2000 October; 106(4): 864. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11183177&dopt=Abstract

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Brain damage and retrograde amnesia: an electrographic control. Author(s): Hudspeth WJ. Source: Behav Biol. 1973 January; 8(1): 131-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4734963&dopt=Abstract

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Brain damage and tardive dyskinesia. Author(s): al-Adwani A. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1995 September; 167(3): 410-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7496660&dopt=Abstract

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Brain damage and the ordering of two temporally successive stimuli. Author(s): Swisher L, Hirsh IJ. Source: Neuropsychologia. 1972 July; 10(2): 137-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5055220&dopt=Abstract

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Brain damage due to alcohol consumption: an air-encephalographic, psychometric and electroencephalographic study. Author(s): Brewer C, Perrett L. Source: The British Journal of Addiction to Alcohol and Other Drugs. 1971 November; 66(3): 170-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5289282&dopt=Abstract

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Brain damage during post-operative care. Author(s): Regan WA. Source: Hosp Prog. 1972 July; 53(7): 6 Passim. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5036127&dopt=Abstract

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Brain damage from nondominant ECT. Author(s): Breggin PR. Source: The American Journal of Psychiatry. 1986 October; 143(10): 1320-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3766805&dopt=Abstract

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Brain damage in diabetes mellitus. Author(s): Bale RN. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1973 March; 122(568): 337-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4696456&dopt=Abstract

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Brain damage in the newborn. Author(s): Rodeck C, Smith JF. Source: The Journal of Pathology. 1972 July; 107(3): Pix. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5084944&dopt=Abstract

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Brain damage markers in children. Neurobiological and clinical aspects. Author(s): Leviton A, Dammann O. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(1): 9-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11883827&dopt=Abstract

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Brain damage when multiple sclerosis is diagnosed clinically. Author(s): Lassmann H. Source: Lancet. 2003 April 19; 361(9366): 1317-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711464&dopt=Abstract

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Brain damage, sex hormones and recovery: a new role for progesterone and estrogen? Author(s): Stein DG. Source: Trends in Neurosciences. 2001 July; 24(7): 386-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11410269&dopt=Abstract

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Brain damage: neglect disrupts the mental number line. Author(s): Zorzi M, Priftis K, Umilta C. Source: Nature. 2002 May 9; 417(6885): 138-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12000950&dopt=Abstract

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Brain potentials in human patients with extremely severe diffuse brain damage. Author(s): Kotchoubey B, Lang S, Baales R, Herb E, Maurer P, Mezger G, Schmalohr D, Bostanov V, Birbaumer N. Source: Neuroscience Letters. 2001 March 23; 301(1): 37-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11239711&dopt=Abstract

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Brain specific proteins in serum: do they reliably reflect brain damage? Author(s): Vos PE, Verbeek MM. Source: Shock (Augusta, Ga.). 2002 November; 18(5): 481-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412631&dopt=Abstract

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Cardiopulmonary bypass temperature and extension of intraoperative brain damage: controversies persist. Author(s): Gaudino M, Possati G. Source: The Journal of Thoracic and Cardiovascular Surgery. 2000 November; 120(5): 1013-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11044331&dopt=Abstract

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Carotid brainstem reflex myoclonus after hypoxic brain damage. Author(s): Hanakawa T, Hashimoto S, Iga K, Segawa Y, Shibasaki H. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2000 November; 69(5): 672-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11032627&dopt=Abstract

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Characterization of empathy deficits following prefrontal brain damage: the role of the right ventromedial prefrontal cortex. Author(s): Shamay-Tsoory SG, Tomer R, Berger BD, Aharon-Peretz J. Source: Journal of Cognitive Neuroscience. 2003 April 1; 15(3): 324-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729486&dopt=Abstract

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Children with irreversible brain damage associated with hypothyroidism and multiple intracranial calcifications. Author(s): Arii J, Tanabe Y, Makino M, Sato H, Kohno Y. Source: Journal of Child Neurology. 2002 April; 17(4): 309-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088091&dopt=Abstract

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Citalopram treatment of traumatic brain damage in a 6-year-old boy. Author(s): Andersen G, Stylsvig M, Sunde N. Source: Journal of Neurotrauma. 1999 April; 16(4): 341-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10225220&dopt=Abstract

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Classifying brain damage in preterm infants. Author(s): Paneth N. Source: The Journal of Pediatrics. 1999 May; 134(5): 527-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10228280&dopt=Abstract

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Clinical and MRI assessment of brain damage in MS. Author(s): Comi G, Rovaris M, Leocani L, Martinelli V, Filippi M. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2001 November; 22 Suppl 2: S123-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794475&dopt=Abstract

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Clinical, neurophysiologic, and neuropathological features of an infant with brain damage of total asphyxia type (Myers). Author(s): Natsume J, Watanabe K, Kuno K, Hayakawa F, Hashizume Y. Source: Pediatric Neurology. 1995 July; 13(1): 61-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7575852&dopt=Abstract

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Cobalt-57 as a SPET tracer in the visualization of ischaemic brain damage in patients with middle cerebral artery stroke. Author(s): Stevens H, Knollema S, Piers DA, Van de Wiele C, Jansen HM, De Jager AE, De Reuck J, Dierckx RA, Korf J. Source: Nuclear Medicine Communications. 1998 June; 19(6): 573-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10234662&dopt=Abstract

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Cognitive decline in AD and mild cognitive impairment is associated with global brain damage. Author(s): Van Der Flier WM, Van Den Heuvel DM, Weverling-Rijnsburger AW, Spilt A, Bollen EL, Westendorp RG, Middelkoop HA, Van Buchem MA. Source: Neurology. 2002 September 24; 59(6): 874-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297570&dopt=Abstract

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Comparison of task-central and task-peripheral forms of the Canter-BIP in diagnosing brain damage in adults. Author(s): Adams J. Source: Percept Mot Skills. 1971 December; 33(3): 1259-67. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5160043&dopt=Abstract

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Complex karyotype and absence of mutation in the c-kit receptor in aggressive mastocytosis presenting with pelvic osteolysis, eosinophilia and brain damage. Author(s): Jost E, Michaux L, Vanden Abeele M, Boland B, Latinne D, Godfraind C, Scheiff JM, Vaerman JL, Lecouvet F, Ferrant A. Source: Annals of Hematology. 2001 May; 80(5): 302-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11446735&dopt=Abstract

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Conceptualization and identification of depression in adults with brain damage by clients and rehabilitation clinical staff. Author(s): Kalpakjian CZ, Lam CS, Leahy BJ. Source: Brain Injury : [bi]. 2002 June; 16(6): 501-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12119085&dopt=Abstract

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Congenital varicella syndrome: case with isolated brain damage. Author(s): Dimova PS, Karparov AA. Source: Journal of Child Neurology. 2001 August; 16(8): 595-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11510932&dopt=Abstract

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Consecutive light microscopy, scanning-transmission electron microscopy and transmission electron microscopy of traumatic human brain oedema and ischaemic brain damage. Author(s): Castejon OJ, Castejon HV, Diaz M, Castellano A. Source: Histology and Histopathology. 2001 October; 16(4): 1117-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11642732&dopt=Abstract

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Cooling for acute ischemic brain damage (cool aid): an open pilot study of induced hypothermia in acute ischemic stroke. Author(s): Krieger DW, De Georgia MA, Abou-Chebl A, Andrefsky JC, Sila CA, Katzan IL, Mayberg MR, Furlan AJ. Source: Stroke; a Journal of Cerebral Circulation. 2001 August; 32(8): 1847-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11486115&dopt=Abstract

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Correlation of computed tomography findings and serum brain damage markers following severe head injury. Author(s): Raabe A, Grolms C, Keller M, Dohnert J, Sorge O, Seifert V. Source: Acta Neurochirurgica. 1998; 140(8): 787-91; Discussion 791-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9810445&dopt=Abstract

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Cortical extracellular sodium transients after human head injury: an indicator of secondary brain damage? Author(s): Alessandri B, Doppenberg E, Zauner A, Woodward J, Young HF, Bullock R. Source: Acta Neurochir Suppl (Wien). 1998; 71: 237-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9779194&dopt=Abstract

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Cortical motor reorganization following early brain damage and hemispherectomy demonstrated by transcranial magnetic stimulation. Author(s): Kastrup O, Leonhardt G, Kurthen M, Hufnagel A. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2000 August; 111(8): 1346-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10904214&dopt=Abstract

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CT and MR patterns of hypoxic ischemic brain damage following perinatal asphyxia. Author(s): Gururaj A, Sztriha L, Dawodu A, Nath KR, Varady E, Nork M, Haas D. Source: Journal of Tropical Pediatrics. 2002 February; 48(1): 5-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11866337&dopt=Abstract

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Defective pantomime of object use in left brain damage: apraxia or asymbolia? Author(s): Goldenberg G, Hartmann K, Schlott I. Source: Neuropsychologia. 2003; 41(12): 1565-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12887981&dopt=Abstract

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Delta activity as an early indicator for soman-induced brain damage: a review. Author(s): Carpentier P, Foquin A, Dorandeu F, Lallement G. Source: Neurotoxicology. 2001 June; 22(3): 299-315. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11456332&dopt=Abstract

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Determination of the timing of fetal brain damage from hypoxemia-ischemia. Author(s): Naeye RL, Lin HM. Source: American Journal of Obstetrics and Gynecology. 2001 January; 184(2): 217-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11174505&dopt=Abstract

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Developmental neuropathology and impact of perinatal brain damage. II: white matter lesions of the neocortex. Author(s): Marin-Padilla M. Source: Journal of Neuropathology and Experimental Neurology. 1997 March; 56(3): 219-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9056536&dopt=Abstract

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Developmental neuropathology and impact of perinatal brain damage. III: gray matter lesions of the neocortex. Author(s): Marin-Padilla M. Source: Journal of Neuropathology and Experimental Neurology. 1999 May; 58(5): 40729. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10331430&dopt=Abstract

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Dexamethasone and the prevention of neonatal hypoxic-ischemic brain damage. Author(s): Tuor UI. Source: Annals of the New York Academy of Sciences. 1995 September 15; 765: 179-95; Discussion 196-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7486605&dopt=Abstract

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Diffuse brain damage caused by acute twin-twin transfusion during late pregnancy. Author(s): Wada H, Nunogami K, Wada T, Niida Y, Yachie A, Koizumi S. Source: Acta Paediatr Jpn. 1998 August; 40(4): 370-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9745784&dopt=Abstract

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Diffusion-weighted imaging patterns of brain damage associated with cerebral venous thrombosis. Author(s): Ducreux D, Oppenheim C, Vandamme X, Dormont D, Samson Y, Rancurel G, Cosnard G, Marsault C. Source: Ajnr. American Journal of Neuroradiology. 2001 February; 22(2): 261-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11156766&dopt=Abstract

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Direction-selective motion blindness after unilateral posterior brain damage. Author(s): Blanke O, Landis T, Mermoud C, Spinelli L, Safran AB. Source: The European Journal of Neuroscience. 2003 August; 18(3): 709-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911768&dopt=Abstract

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Discrepancies between standardized measures of cognitive level and Halstead-Reitan impairment indices as inferences of brain damage following head injuries. Author(s): Persinger MA. Source: Percept Mot Skills. 1999 October; 89(2): 629-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10597599&dopt=Abstract

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Dissociation between autonomic responding and verbal report in right and left hemisphere brain damage during anticipatory anxiety. Author(s): Slomine B, Bowers D, Heilman KM. Source: Neuropsychiatry, Neuropsychology, and Behavioral Neurology. 1999 July; 12(3): 143-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10456796&dopt=Abstract

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Dissociation between the effects of interleukin-1 on excitotoxic brain damage and body temperature in the rat. Author(s): Grundy RI, Rothwell NJ, Allan SM. Source: Brain Research. 1999 May 29; 830(1): 32-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10350557&dopt=Abstract

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Do climbs to extreme altitude cause brain damage? Author(s): West JB. Source: Lancet. 1986 August 16; 2(8503): 387-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2874380&dopt=Abstract

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Does brain damage (hepatic encephalopathy) improve without any complication and sequellae after liver transplantation? Author(s): Ichida T. Source: Intern Med. 2000 November; 39(11): 871-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11065233&dopt=Abstract

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Does glutamate mediate brain damage in acute encephalitis? Author(s): Launes J, Siren J, Viinikka L, Hokkanen L, Lindsberg PJ. Source: Neuroreport. 1998 March 9; 9(4): 577-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9559919&dopt=Abstract

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Does malnutrition in early life lead to permanent brain damage? Author(s): McLaren DS. Source: J Med Liban. 1972; 25(3): 195-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4628751&dopt=Abstract

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Does pertussis vaccine cause brain damage? Author(s): Meade TW. Source: Lancet. 1986 August 2; 2(8501): 286. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2874309&dopt=Abstract

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Does traumatic subarachnoid hemorrhage caused by diffuse brain injury cause delayed ischemic brain damage? Comparison with subarachnoid hemorrhage caused by ruptured intracranial aneurysms. Author(s): Fukuda T, Hasue M, Ito H. Source: Neurosurgery. 1998 November; 43(5): 1040-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9802847&dopt=Abstract

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Dutch to examine testing boxers for brain damage. Author(s): Sheldon T. Source: Bmj (Clinical Research Ed.). 1998 August 8; 317(7155): 370. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9729092&dopt=Abstract

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Dysfunction in visual object recognition of patients with unilateral brain damage under the element presentation condition. Author(s): Shibasaki M, Toshima T. Source: J Clin Exp Neuropsychol. 1999 June; 21(3): 316-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10474171&dopt=Abstract

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Early brain damage and the development of motor behavior in children: clues for therapeutic intervention? Author(s): Hadders-Algra M. Source: Neural Plast. 2001; 8(1-2): 31-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11530887&dopt=Abstract

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Early cellular brain damage and systemic inflammatory response after cardiopulmonary resuscitation or isolated severe head trauma: a comparative pilot study on common pathomechanisms. Author(s): Mussack T, Biberthaler P, Gippner-Steppert C, Kanz KG, Wiedemann E, Mutschler W, Jochum M. Source: Resuscitation. 2001 May; 49(2): 193-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11382526&dopt=Abstract

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Early markers of brain damage in premature low-birth-weight neonates who suffered from perinatal asphyxia and/or infection. Author(s): Fotopoulos S, Pavlou K, Skouteli H, Papassotiriou I, Lipsou N, Xanthou M. Source: Biology of the Neonate. 2001; 79(3-4): 213-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11275654&dopt=Abstract

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Early neurobehavioral outcome after stroke is related to release of neurobiochemical markers of brain damage. Author(s): Wunderlich MT, Ebert AD, Kratz T, Goertler M, Jost S, Herrmann M. Source: Stroke; a Journal of Cerebral Circulation. 1999 June; 30(6): 1190-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10356098&dopt=Abstract

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Early prediction of irreversible brain damage after ischemic stroke at CT. Author(s): von Kummer R, Bourquain H, Bastianello S, Bozzao L, Manelfe C, Meier D, Hacke W. Source: Radiology. 2001 April; 219(1): 95-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11274542&dopt=Abstract

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Early release pattern of S100 protein as a marker of brain damage after warm cardiopulmonary bypass. Author(s): Shaaban Ali M, Harmer M, Vaughan RS, Dunne J, Latto IP. Source: Anaesthesia. 2000 August; 55(8): 802-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10947697&dopt=Abstract

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Early translaryngeal tracheostomy in patients with severe brain damage. Author(s): Stocchetti N, Parma A, Songa V, Colombo A, Lamperti M, Tognini L. Source: Intensive Care Medicine. 2000 August; 26(8): 1101-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11030167&dopt=Abstract

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Effect of brain damage and source location on left-right asymmetry of visual evoked potentials in a realistic model of the head. Author(s): Radai MM, Rosenfeld M, Abboud S. Source: Medical Engineering & Physics. 2003 June; 25(5): 349-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711232&dopt=Abstract

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Effect of extreme hypercapnia on hypoxic-ischemic brain damage in the immature rat. Author(s): Vannucci RC, Towfighi J, Brucklacher RM, Vannucci SJ. Source: Pediatric Research. 2001 June; 49(6): 799-803. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11385141&dopt=Abstract

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Effect of unilateral brain damage on perception of temporal order. Author(s): Carmon A, Nachshon I. Source: Cortex. 1971 December; 7(4): 411-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5156690&dopt=Abstract

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Effects of stimulus emotionality and sentence generation on memory for words in adults with unilateral brain damage. Author(s): Berrin-Wasserman S, Winnick WA, Borod JC. Source: Neuropsychology. 2003 July; 17(3): 429-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959509&dopt=Abstract

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Effects of theophylline on ventilatory poststimulus potentiation in patients with brain damage. Author(s): Mitrouska I, Kondili E, Prinianakis G, Siafakas N, Georgopoulos D. Source: American Journal of Respiratory and Critical Care Medicine. 2003 April 15; 167(8): 1124-30. Epub 2003 January 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531775&dopt=Abstract

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Effects of unilateral brain damage on grip selection, coordination, and kinematics of ipsilesional prehension. Author(s): Hermsdorfer J, Laimgruber K, Kerkhoff G, Mai N, Goldenberg G. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 1999 September; 128(1-2): 41-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10473738&dopt=Abstract

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Emotional processing deficits in individuals with unilateral brain damage. Author(s): Borod JC, Bloom RL, Brickman AM, Nakhutina L, Curko EA. Source: Applied Neuropsychology. 2002; 9(1): 23-36. Review. Erratum In: Appl Neuropsychol. 2002; 9(3): 192. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173747&dopt=Abstract

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Emotional versus nonemotional lexical perception in patients with right and left brain damage. Author(s): Cicero BA, Borod JC, Santschi C, Erhan HM, Obler LK, Agosti RM, Welkowitz J, Grunwald IS. Source: Neuropsychiatry, Neuropsychology, and Behavioral Neurology. 1999 October; 12(4): 255-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10527110&dopt=Abstract

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Error correction strategies for motor behavior after unilateral brain damage: shortterm motor learning processes. Author(s): Dancause N, Ptito A, Levin MF. Source: Neuropsychologia. 2002; 40(8): 1313-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11931934&dopt=Abstract

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Erythropoietin in the central nervous system, and its use to prevent hypoxic-ischemic brain damage. Author(s): Juul S. Source: Acta Paediatrica (Oslo, Norway : 1992). Supplement. 2002; 91(438): 36-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477263&dopt=Abstract

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Exacerbation of ischemic brain damage by localized striatal injection of interleukin1beta in the rat. Author(s): Stroemer RP, Rothwell NJ. Source: Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. 1998 August; 18(8): 833-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9701344&dopt=Abstract

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Excitatory amino acid-induced seizure activity and seizure-related brain damage--a possible therapeutic potential of glutamate antagonists. Author(s): Czuczwar SJ, Turski WA, Kleinrok Z. Source: Polish Journal of Pharmacology. 1998 January-February; 50(1): 85-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9662745&dopt=Abstract

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Expression in the placenta of neuronal markers for perinatal brain damage. Author(s): Wijnberger LD, Nikkels PG, van Dongen AJ, Noorlander CW, Mulder EJ, Schrama LH, Visser GH. Source: Pediatric Research. 2002 April; 51(4): 492-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11919335&dopt=Abstract

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Face recognition in children with early right or left brain damage. Author(s): Mancini J, de Schonen S, Deruelle C, Massoulier A. Source: Developmental Medicine and Child Neurology. 1994 February; 36(2): 156-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8132126&dopt=Abstract

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Failure of prospective memory after acquired brain damage: preliminary investigation and suggestions for future directions. Author(s): Cockburn J. Source: J Clin Exp Neuropsychol. 1996 April; 18(2): 304-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8780964&dopt=Abstract

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Familial hemiplegic migraine with irreversible brain damage. Author(s): Hayashi R, Tachikawa H, Watanabe R, Honda M, Katsumata Y. Source: Intern Med. 1998 February; 37(2): 166-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9550598&dopt=Abstract

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Fast-wave periodic complexes in a mentally retarded child who later developed subacute sclerosing panencephalitis: a modification of a classic EEG by preexisting brain damage? Author(s): Narayan SK, Kuruvilla A, Shanmugam J, Radhakrishnan VV. Source: Developmental Medicine and Child Neurology. 1997 November; 39(11): 766-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9393892&dopt=Abstract

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Fat-laden macrophages in cerebrospinal fluid as an indication of brain damage in children. Author(s): Chester DC, Emery JL, Penny SR. Source: Archives of Disease in Childhood. 1971 December; 46(250): 884. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5129207&dopt=Abstract

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Fat-laden macrophages in cerebrospinal fluid as an indication of brain damage in children. Author(s): Chester DC, Emery JL, Penny SR. Source: Journal of Clinical Pathology. 1971 November; 24(8): 753-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4943297&dopt=Abstract

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Fear recognition deficits after focal brain damage: a cautionary note. Author(s): Rapcsak SZ, Galper SR, Comer JF, Reminger SL, Nielsen L, Kaszniak AW, Verfaellie M, Laguna JF, Labiner DM, Cohen RA. Source: Neurology. 2000 February 8; 54(3): 575-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10680785&dopt=Abstract

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Feedback-based training of grip force control in patients with brain damage. Author(s): Kriz G, Hermsdorfer J, Marquardt C, Mai N. Source: Archives of Physical Medicine and Rehabilitation. 1995 July; 76(7): 653-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7605185&dopt=Abstract

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Fetal alcohol-induced brain damage and the problem of determining temporal vulnerability: a review. Author(s): West JR. Source: Alcohol Drug Res. 1987; 7(5-6): 423-41. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3304313&dopt=Abstract

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Fetal heart rate patterns in postasphyxiated fetal lambs with brain damage. Author(s): Ikeda T, Murata Y, Quilligan EJ, Parer JT, Theunissen IM, Cifuentes P, Doi S, Park SD. Source: American Journal of Obstetrics and Gynecology. 1998 November; 179(5): 132937. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9822525&dopt=Abstract

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Finger movements and fingers postures in pre-term infants are not a good indicator of brain damage. Author(s): Konishi Y, Prechtl HF. Source: Early Human Development. 1994 February; 36(2): 89-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8200324&dopt=Abstract

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First Alfred Meyer Memorial Lecture. Epileptic brain damage: a consequence and a cause of seizures. Author(s): Meldrum BS. Source: Neuropathology and Applied Neurobiology. 1997 June; 23(3): 185-201; Discussion 201-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9223128&dopt=Abstract

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For ischemic brain damage, is preclinical evidence of neuroprotection by presynaptic blockade of glutamate release enough? Author(s): Nava-Ocampo AA, Reyes-Perez H, Bello-Ramirez AM, Mansilla-Olivares A, Ponce-Monter H. Source: Medical Hypotheses. 2000 January; 54(1): 77-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10790730&dopt=Abstract

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Four case reports illustrating the contribution of intensive cognitive rehabilitation in patients neuropsychologically handicapped as a result of brain damage. Author(s): Annoni JM, Jenkins DG, Williams J. Source: Disability and Rehabilitation. 1995 November-December; 17(8): 449-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8573708&dopt=Abstract

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Free radicals and brain damage in the newborn. Author(s): Buonocore G, Perrone S, Bracci R. Source: Biology of the Neonate. 2001; 79(3-4): 180-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11275648&dopt=Abstract

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Free radicals and brain damage. Author(s): Siesjo BK, Agardh CD, Bengtsson F. Source: Cerebrovasc Brain Metab Rev. 1989 Fall; 1(3): 165-211. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2701375&dopt=Abstract

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Frontal lobe syndrome reassessed: comparison of patients with lateral or medial frontal brain damage. Author(s): Paradiso S, Chemerinski E, Yazici KM, Tartaro A, Robinson RG. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1999 November; 67(5): 664-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10519877&dopt=Abstract

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Function testing for chemical brain damage: a review. Author(s): Kilburn KH. Source: Archives of Environmental Health. 2001 March-April; 56(2): 132-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11339676&dopt=Abstract

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Functional implications of the minimal brain damage syndrome. Author(s): Wolff PH, Hurwitz I. Source: Semin Psychiatry. 1973 February; 5(1): 105-15. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4803376&dopt=Abstract

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Functional outcome assessment of adults with right hemisphere brain damage. Author(s): Tompkins CA, Lehman MT, Wyatt AD, Schulz R. Source: Seminars in Speech and Language. 1998; 19(3): 303-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9720134&dopt=Abstract

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Gastro-oesophageal reflux and oesophageal dysfunction in children and adolescents with brain damage. Author(s): Gustafsson PM, Tibbling L. Source: Acta Paediatrica (Oslo, Norway : 1992). 1994 October; 83(10): 1081-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7841709&dopt=Abstract

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Generalized versus selective cognitive impairments resulting from brain damage sustained in childhood. Author(s): Vargha-Khadem F. Source: Epilepsia. 2001; 42 Suppl 1: 37-40; Discussion 50-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11422355&dopt=Abstract

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Generating visual mental images: deficit after brain damage. Author(s): Stangalino C, Semenza C, Mondini S. Source: Neuropsychologia. 1995 November; 33(11): 1473-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8584181&dopt=Abstract

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Gesture use following right hemisphere brain damage. Author(s): Brady M, Mackenzie C. Source: International Journal of Language & Communication Disorders / Royal College of Speech & Language Therapists. 2001; 36 Suppl: 35-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11340810&dopt=Abstract

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Glucose, lactic acid, and perinatal hypoxic-ischemic brain damage. Author(s): Vannucci RC, Yager JY. Source: Pediatric Neurology. 1992 January-February; 8(1): 3-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1558572&dopt=Abstract

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Glutamate, calcium, and free radicals as mediators of ischemic brain damage. Author(s): Siesjo BK, Zhao Q, Pahlmark K, Siesjo P, Katsura K, Folbergrova J. Source: The Annals of Thoracic Surgery. 1995 May; 59(5): 1316-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7733760&dopt=Abstract

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Glycine and neuroprotective effect of hypothermia in hypoxic-ischemic brain damage. Author(s): Kvrivishvili G. Source: Neuroreport. 2002 November 15; 13(16): 1995-2000. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438913&dopt=Abstract

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GM1 ganglioside treatment facilitates behavioral recovery from bilateral brain damage. Author(s): Sabel BA, Slavin MD, Stein DG. Source: Science. 1984 July 20; 225(4659): 340-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6740316&dopt=Abstract

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Graft-induced recovery of cognitive function after diffuse and focal brain damage: implications for neural transplantation in man. Author(s): Hodges H. Source: Zh Vyssh Nerv Deiat Im I P Pavlova. 1995 January-February; 45(1): 29-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7754697&dopt=Abstract

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Grafts correct brain damage. Author(s): Kolata G. Source: Science. 1982 July 23; 217(4557): 342-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7089568&dopt=Abstract

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Granulocyte function in patients with brain damage and anoxia. Author(s): Dodsworth H, Harris R. Source: Acta Haematologica. 1971; 45(6): 350-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5000684&dopt=Abstract

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Gray-white matter discrimination--a possible marker for brain damage in heat stroke? Author(s): Szold O, Reider-Groswasser II, Ben Abraham R, Aviram G, Segev Y, Biderman P, Sorkine P. Source: European Journal of Radiology. 2002 July; 43(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065113&dopt=Abstract

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Growing skull fractures: progressive evolution of brain damage and effectiveness of surgical treatment. Author(s): Scarfo GB, Mariottini A, Tomaccini D, Palma L. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1989 June; 5(3): 163-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2758430&dopt=Abstract

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Hallucinogenic drugs and brain damage. Author(s): Acord LD. Source: Military Medicine. 1972 January; 137(1): 18-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4624238&dopt=Abstract

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Halstead's Category Test and lateralized brain damage. Author(s): Parsons OA, Jones B, Vega A. Source: Percept Mot Skills. 1971 December; 33(3): 1245-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5160042&dopt=Abstract

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Hemispatial neglect in young children with early unilateral brain damage. Author(s): Trauner DA. Source: Developmental Medicine and Child Neurology. 2003 March; 45(3): 160-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613771&dopt=Abstract

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Hemispheric asymmetry in a perceptual priming task: evidence from patients with unilateral brain damage. Author(s): Tsukiura T, Fujii T, Yamadori A, Hosokawa T. Source: Percept Mot Skills. 1999 April; 88(2): 457-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10483639&dopt=Abstract

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Hemispheric brain damage in unilateral status epilepticus. Author(s): Soffer D, Melamed E, Assaf Y, Cotev S. Source: Annals of Neurology. 1986 December; 20(6): 737-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3813502&dopt=Abstract

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Hemispheric semantics: effects on pictorial organization of patients with unilateral brain damage. Author(s): Zaidel DW, Edelstyn N. Source: The International Journal of Neuroscience. 1995 June; 82(3-4): 215-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7558650&dopt=Abstract

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Hemispheric specialization in the co-ordination of arm and trunk movements during pointing in patients with unilateral brain damage. Author(s): Esparza DY, Archambault PS, Winstein CJ, Levin MF. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 2003 February; 148(4): 488-97. Epub 2002 December 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582832&dopt=Abstract

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High alcohol consumption, liver toxic drugs and brain damage--a population study. Author(s): Mutzell S, Tibblin G. Source: Upsala Journal of Medical Sciences. 1989; 94(3): 305-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2609474&dopt=Abstract

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Horizontal space misrepresentation in unilateral brain damage. I. Visual and proprioceptive-motor influences in left unilateral neglect. Author(s): Doricchi F, Galati G, DeLuca L, Nico D, D'Olimpio F. Source: Neuropsychologia. 2002; 40(8): 1107-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11931915&dopt=Abstract

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Horizontal space misrepresentation in unilateral brain damage. II. Eye-head centered modulation of visual misrepresentation in hemianopia without neglect. Author(s): Doricchi F, Onida A, Guariglia P. Source: Neuropsychologia. 2002; 40(8): 1118-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11931916&dopt=Abstract

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How to diagnose human brain damage and inflammation. Author(s): Kleine TO. Source: Brain Research Bulletin. 2003 August 15; 61(3): 227-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909291&dopt=Abstract

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Hypertonic/hyperoncotic treatment for brain damage. Author(s): Rocha-e-Silva M. Source: Critical Care Medicine. 2003 October; 31(10): 2559-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530771&dopt=Abstract

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Hyponatremia associated with permanent brain damage. Author(s): Arieff AI. Source: Adv Intern Med. 1987; 32: 325-44. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3548254&dopt=Abstract

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Hyponatremia, convulsions, respiratory arrest, and permanent brain damage after elective surgery in healthy women. Author(s): Arieff AI. Source: The New England Journal of Medicine. 1986 June 12; 314(24): 1529-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3713746&dopt=Abstract

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Hypoxia is the cause of brain damage in hyponatremia. Author(s): Knochel JP. Source: Jama : the Journal of the American Medical Association. 1999 June 23-30; 281(24): 2342-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10386561&dopt=Abstract

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Hypoxia-ischaemia and the developing brain: hypotheses regarding the pathophysiology of fetal-neonatal brain damage. Author(s): Longo LD, Packianathan S. Source: British Journal of Obstetrics and Gynaecology. 1997 June; 104(6): 652-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9197867&dopt=Abstract

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Hypoxic brain damage after intramuscular self-injection of diclofenac for acute back pain. Author(s): Schabitz WR, Berger C, Knauth M, Meinck HM, Steiner T. Source: European Journal of Anaesthesiology. 2001 November; 18(11): 763-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11580784&dopt=Abstract

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Hypoxic/ischaemic brain damage, especially pallidal lesions, in heroin addicts. Author(s): Andersen SN, Skullerud K. Source: Forensic Science International. 1999 May 31; 102(1): 51-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10423852&dopt=Abstract

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Hypoxic-ischaemic brain damage in immature rats: effects of adrenoceptor modulation. Author(s): Yuan SZ, Runold M, Hagberg H, Bona E, Lagercrantz H. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 2001; 5(1): 29-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11277361&dopt=Abstract

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Hypoxic-ischemic brain damage in perinatal age group. Author(s): Kumar K. Source: Indian J Pediatr. 1999 July-August; 66(4): 475-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10798099&dopt=Abstract

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Illiteracy and brain damage--1. Aphasia testing in culturally contrasted populations (control subjects). Author(s): Lecours AR, Mehler J, Parente MA, Caldeira A, Cary L, Castro MJ, Dehaut F, Delgado R, Gurd J, de Fraga Karmann D, et al. Source: Neuropsychologia. 1987; 25(1B): 231-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2437493&dopt=Abstract

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Immediate S-100B and neuron-specific enolase plasma measurements for rapid evaluation of primary brain damage in alcohol-intoxicated, minor head-injured patients. Author(s): Mussack T, Biberthaler P, Kanz KG, Heckl U, Gruber R, Linsenmaier U, Mutschler W, Jochum M. Source: Shock (Augusta, Ga.). 2002 November; 18(5): 395-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412616&dopt=Abstract

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Impaired direction and extent specification of aimed arm movements in humans with stroke-related brain damage. Author(s): Velicki MR, Winstein CJ, Pohl PS. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 2000 February; 130(3): 362-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10706435&dopt=Abstract

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Impairments of vestibular system in infants at risk of early brain damage. Author(s): Vatovec J, Velikovic M, Smid L, Brenk K, Zargi M. Source: Scand Audiol Suppl. 2001; (52): 191-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11318465&dopt=Abstract

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Impedance pneumography for the detection of abnormal breathing patterns associated with brain damage. Author(s): North JB, Jennett S. Source: Lancet. 1972 July 29; 2(7770): 212-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4114212&dopt=Abstract

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Improvement of hypertonus after treatment for sleep disturbances in three patients with severe brain damage. Author(s): Tanaka H, Araki A, Ito J, Tasaki T, Miyamoto A, Cho K. Source: Brain & Development. 1997 June; 19(4): 240-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9187472&dopt=Abstract

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In the pursuit of proof of brain damage after whiplash injury. Author(s): Alexander MP. Source: Neurology. 1998 August; 51(2): 336-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9709998&dopt=Abstract

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Increased serum levels of the S-100 protein are associated with hypoxic brain damage after cardiac arrest. Author(s): Rosen H, Rosengren L, Herlitz J, Blomstrand C. Source: Stroke; a Journal of Cerebral Circulation. 1998 February; 29(2): 473-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9472892&dopt=Abstract

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Infantile hydrocephalus: clinical, histological, and ultrastructural study of brain damage. Author(s): Weller RO, Shulman K. Source: Journal of Neurosurgery. 1972 March; 36(3): 255-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5059964&dopt=Abstract

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Inflammatory mediators and neonatal brain damage. Author(s): Saliba E, Henrot A. Source: Biology of the Neonate. 2001; 79(3-4): 224-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11275656&dopt=Abstract

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Influences of venous involvement on postoperative brain damage following the anterior interhemispheric approach. Author(s): Kubota M, Saeki N, Yamaura A, Ono J, Ozawa Y. Source: Acta Neurochirurgica. 2001; 143(4): 321-5; Discussion 325-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11437284&dopt=Abstract

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Insulin, blood glucose levels, and ischemic brain damage. Author(s): Auer RN. Source: Neurology. 1998 September; 51(3 Suppl 3): S39-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9744832&dopt=Abstract

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Intelligence and brain damage in alcoholics. A study in patients of middle and upper social class. Author(s): Smith JW, Burt DW, Chapman RF. Source: Q J Stud Alcohol. 1973 June; 34(2): 414-22. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4713834&dopt=Abstract

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Interval between sustaining brain damage and development of personality change. Author(s): Vann D. Source: The Medical Journal of Australia. 1972 December 30; 2(27): 1507-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4655133&dopt=Abstract

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Intracranial pressure dynamics in patients with acute brain damage: a critical analysis with the aid of a mathematical model. Author(s): Ursino M, Iezzi M, Stocchetti N. Source: Ieee Transactions on Bio-Medical Engineering. 1995 June; 42(6): 529-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7790009&dopt=Abstract

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Intraocular contrast enhancement in Adams pattern III hypoxic brain damage: MRI. Author(s): Chen CJ. Source: Neuroradiology. 2000 January; 42(1): 54-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10663474&dopt=Abstract

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Intrathecal release of nitric oxide and its relation to final brain damage in patients with stroke. Author(s): Tarkowski E, Ringqvist A, Rosengren L, Jensen C, Ekholm S, Wennmalm A. Source: Cerebrovascular Diseases (Basel, Switzerland). 2000 May-June; 10(3): 200-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10773646&dopt=Abstract

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Investigations of micro-organic brain damage (MOBD) in heterozygotes of metachromatic leukodystrophy. Author(s): Tylki-Szymanska A, Lugowska A, Chmielik J, Kotowicz J, JakubowskaWinecka A, Zobel M, Berger J, Molzer B. Source: American Journal of Medical Genetics. 2002 July 15; 110(4): 315-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116203&dopt=Abstract

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Iodine deficiency as a cause of brain damage. Author(s): Delange F. Source: Postgraduate Medical Journal. 2001 April; 77(906): 217-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11264481&dopt=Abstract

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Ipsilesional deficits during fast diadochokinetic hand movements following unilateral brain damage. Author(s): Hermsdorfer J, Goldenberg G. Source: Neuropsychologia. 2002; 40(12): 2100-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208006&dopt=Abstract

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Judge “not satisfied” that whooping cough vaccine causes permanent brain damage. Author(s): Dyer C. Source: British Medical Journal (Clinical Research Ed.). 1988 April 23; 296(6630): 1189-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3132253&dopt=Abstract

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Judgment of spatial orientation in patients with focal brain damage. Author(s): De Renzi E, Faglioni P, Scotti G. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1971 October; 34(5): 48995. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4941476&dopt=Abstract

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Judo as a possible cause of anoxic brain damage. A case report. Author(s): Owens RG, Ghadiali EJ. Source: The Journal of Sports Medicine and Physical Fitness. 1991 December; 31(4): 6278. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1806745&dopt=Abstract

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Jugular bulb creatine kinase as an indication of slight transient brain damage. Author(s): Langton L, Moxon CP, Riddoch D, Westhead RA, Woolf AL. Source: Lancet. 1967 August 5; 2(7510): 278-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4165915&dopt=Abstract

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Knowledge and strategies for processing lexical metaphor after right or left hemisphere brain damage. Author(s): Tompkins CA. Source: Journal of Speech and Hearing Research. 1990 June; 33(2): 307-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2359271&dopt=Abstract

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Knowledge of the year, brain damage and memory for designs. Author(s): Orme JE. Source: Dis Nerv Syst. 1966 March; 27(3): 202-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5908307&dopt=Abstract

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Lack of anticipatory gaze-orienting responses in patients with right brain damage. Author(s): Ivanenko YP, Viaud-Delmon I, Mayer E, Valenza N, Annoni JM, Rohr A, Guyot JP, Berthoz A, Landis T. Source: Neurology. 2000 April 25; 54(8): 1656-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10762509&dopt=Abstract

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L-arginine levels in blood as a marker of nitric oxide-mediated brain damage in acute stroke: a clinical and experimental study. Author(s): Armengou A, Hurtado O, Leira R, Obon M, Pascual C, Moro MA, Lizasoain I, Castillo J, Davalos A. Source: Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. 2003 August; 23(8): 97884. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902842&dopt=Abstract

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Lasting cytotoxic edema as an indicator of irreversible brain damage: a case of neonatal stroke. Author(s): Rumpel H, Ferrini B, Martin E. Source: Ajnr. American Journal of Neuroradiology. 1998 October; 19(9): 1636-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9802484&dopt=Abstract

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Lasting recovery of motor function, following brain damage, with a single dose of amphetamine combined with physical therapy; changes in gene expression? Author(s): Bach-y-Rita P, Bjelke B. Source: Scandinavian Journal of Rehabilitation Medicine. 1991; 23(4): 219-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1785033&dopt=Abstract

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Late onset of extensive brain damage and hypertension in a patient with high-voltage electrical burns. Author(s): Eldad A, Neuman A, Weinberg A, Benmeir P, Rotem M, Chauoat M, Gomori JM, Wexler MR. Source: The Journal of Burn Care & Rehabilitation. 1992 March-April; 13(2 Pt 1): 214-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1587920&dopt=Abstract

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LDH isoenzymes in CSF in the diagnosis of neonatal brain damage. Author(s): Fernandez F, Quero J, Verdu A, Ferreiros MC, Daimiel E, Roche MC. Source: Acta Neurologica Scandinavica. 1986 July; 74(1): 30-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3766114&dopt=Abstract

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Left frontal transcranial magnetic stimulation reduces contralesional extinction in patients with unilateral right brain damage. Author(s): Oliveri M, Rossini PM, Traversa R, Cicinelli P, Filippi MM, Pasqualetti P, Tomaiuolo F, Caltagirone C. Source: Brain; a Journal of Neurology. 1999 September; 122 ( Pt 9): 1731-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468512&dopt=Abstract

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Left temporal lobe brain damage pattern on the WAIS, addendum. Author(s): Russell EW, Russell SL. Source: Journal of Clinical Psychology. 1993 March; 49(2): 241-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8486807&dopt=Abstract

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Left temporal lobe brain damage pattern on the Wechsler Adult Intelligence Scale. Author(s): Dobbins C, Russell EW. Source: Journal of Clinical Psychology. 1990 November; 46(6): 863-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2286684&dopt=Abstract

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Legal case briefs for nurse. TN: special shift request “unreasonable”: workers' compensation benefits denied; SD: aides fail to report condition to nurses: respiratory arrest & brain damage result. Author(s): Tammelleo AD. Source: Regan Rep Nurs Law. 1996 April; 36(11): 3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8711115&dopt=Abstract

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Legal case briefs for nurses. AK: failure to diagnose & treat E.R. pt.; arrest & brain damage--proximate cause. OH: failure in applicable standard of care: “loss of chance of survival” issue. Author(s): Tammelleo AD. Source: Regan Rep Nurs Law. 1994 January; 34(8): 3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8127972&dopt=Abstract

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Legal case briefs for nurses. CO: nurse fails to pass qualification tests: age discrimination against hospital alleged; TX: hernia pt. dies--ischemic brain damage: expert testimony re substandard care. Author(s): Tammelleo AD. Source: Regan Rep Nurs Law. 1994 November; 35(6): 3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7838968&dopt=Abstract

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Legal case briefs for nurses. PA: medicated pre-op patient falls: incident report excluded from evidence. CA: patient complains of “strange feeling”: failure to communicate--brain damage results. Author(s): Tammelleo AD. Source: Regan Rep Nurs Law. 1994 February; 34(9): 3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8171192&dopt=Abstract

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Leukocytes, macrophages and secondary brain damage following cerebral ischemia. Author(s): Tomita M, Fukuuchi Y. Source: Acta Neurochir Suppl (Wien). 1996; 66: 32-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8780794&dopt=Abstract

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Lexical tones in Thai after unilateral brain damage. Author(s): Gandour J, Ponglorpisit S, Khunadorn F, Dechongkit S, Boongird P, Boonklam R, Potisuk S. Source: Brain and Language. 1992 August; 43(2): 275-307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1393523&dopt=Abstract

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Locus of functional impairment in the production of speech rhythm after brain damage: a preliminary study. Author(s): Grela B, Gandour J. Source: Brain and Language. 1998 October 1; 64(3): 361-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9743548&dopt=Abstract

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Long-term evaluation of radiation-induced brain damage by serial magnetic resonance imaging. Author(s): Kato T, Sawamura Y, Tada M, Abe H, Shirato H. Source: Neurol Med Chir (Tokyo). 1996 December; 36(12): 870-5; Discussion 876. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9002715&dopt=Abstract

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Long-term sequelae of brain damage from closed head injury in children and adolescents. Author(s): Ruijs MB, Keyser A, Gabreels FJ. Source: Clinical Neurology and Neurosurgery. 1990; 92(4): 323-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1963822&dopt=Abstract

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Loss of CO2 reactivity of cerebral blood flow is associated with severe brain damage in mechanically ventilated very low birth weight infants. Author(s): Muller AM, Morales C, Briner J, Baenziger O, Duc G, Bucher HU. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 1997; 1(5-6): 157-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10728212&dopt=Abstract

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Management of moderate to severe alcohol-related brain damage (Korsakoff's syndrome). Author(s): Lennane KJ. Source: The Medical Journal of Australia. 1986 August 4-18; 145(3-4): 136, 141-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3736477&dopt=Abstract

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May hypocarbia cause ischaemic brain damage in the preterm infant? Author(s): Greisen G, Munck H, Lou H. Source: Lancet. 1986 August 23; 2(8504): 460. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2874442&dopt=Abstract

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Mechanisms of discourse comprehension impairment after right hemisphere brain damage: suppression in inferential ambiguity resolution. Author(s): Tompkins CA, Lehman-Blake MT, Baumgaertner A, Fassbinder W. Source: Journal of Speech, Language, and Hearing Research : Jslhr. 2001 April; 44(2): 400-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11324661&dopt=Abstract

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Mechanisms of ischemic brain damage. Author(s): Bhardwaj A, Alkayed NJ, Kirsch JR, Hurn PD. Source: Current Cardiology Reports. 2003 March; 5(2): 160-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583862&dopt=Abstract

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Mechanisms of secondary brain damage in global and focal ischemia: a speculative synthesis. Author(s): Siesjo BK, Katsura K, Zhao Q, Folbergrova J, Pahlmark K, Siesjo P, Smith ML. Source: Journal of Neurotrauma. 1995 October; 12(5): 943-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8594224&dopt=Abstract

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Minimal brain damage. Author(s): Anderson CM. Source: Ment Hyg. 1972 Spring; 56(2): 62-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5040910&dopt=Abstract

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Misuse of fetal monitor: brain damage results. Case in point: McGee v. Corometrics Medical Systems, Inc. (487 So. 2d 886-AL). Author(s): Tammelleo AD. Source: Regan Rep Nurs Law. 1986 July; 27(2): 4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3637905&dopt=Abstract

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Mitochondrial and MB isoenzymes of creatine kinase in cerebrospinal fluid from patients with hypoxic-ischemic brain damage. Author(s): Chandler WL, Clayson KJ, Longstreth WT Jr, Fine JS. Source: American Journal of Clinical Pathology. 1986 October; 86(4): 533-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3766466&dopt=Abstract

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Motor impersistence mistaken for uncooperativeness in a patient with right-brain damage. Author(s): Rosse RB, Ciolino CP. Source: Psychosomatics. 1986 July; 27(7): 532-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3737843&dopt=Abstract

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Movement in the ipsilesional hand is segmented following unilateral brain damage. Author(s): Sugarman H, Avni A, Nathan R, Weisel-Eichler A, Tiran J. Source: Brain and Cognition. 2002 March-April; 48(2-3): 579-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030511&dopt=Abstract

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Needs of parents of the child hospitalised with acquired brain damage. Author(s): Ramritu PL, Croft G. Source: International Journal of Nursing Studies. 1999 June; 36(3): 209-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10404290&dopt=Abstract

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Neonatal EEG: a powerful tool in the assessment of brain damage in preterm infants. Author(s): Watanabe K, Hayakawa F, Okumura A. Source: Brain & Development. 1999 September; 21(6): 361-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10487468&dopt=Abstract

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Neuronal death and survival in two models of hypoxic-ischemic brain damage. Author(s): Walton M, Connor B, Lawlor P, Young D, Sirimanne E, Gluckman P, Cole G, Dragunow M. Source: Brain Research. Brain Research Reviews. 1999 April; 29(2-3): 137-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10209230&dopt=Abstract

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Neuropathology of inflicted head injury in children. I. Patterns of brain damage. Author(s): Cochrane Database Syst Rev. 2002;(4):CD002088 Source: Brain; a Journal of Neurology. 2001 July; 124(Pt 7): 1290-8. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12519567

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Neuropsychological consequences of two patterns of brain damage shown by MRI in survivors of severe head injury. Author(s): Wilson JT, Hadley DM, Wiedmann KD, Teasdale GM. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1995 September; 59(3): 328-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7673970&dopt=Abstract

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Neurorehabilitation in the third millenium: new roles for our environment, behaviors, and mind in brain damage and recovery? Author(s): Ogden JA. Source: Brain and Cognition. 2000 February; 42(1): 110-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10739613&dopt=Abstract

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Neurosteroids, brain damage, and mental illness. Author(s): Herbert J. Source: Experimental Gerontology. 1998 November-December; 33(7-8): 713-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9951618&dopt=Abstract

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Nitric oxide-related brain damage in acute ischemic stroke. Author(s): Castillo J, Rama R, Davalos A. Source: Stroke; a Journal of Cerebral Circulation. 2000 April; 31(4): 852-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10753987&dopt=Abstract

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Non protein bound iron as early predictive marker of neonatal brain damage. Author(s): Buonocore G, Perrone S, Longini M, Paffetti P, Vezzosi P, Gatti MG, Bracci R. Source: Brain; a Journal of Neurology. 2003 May; 126(Pt 5): 1224-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690060&dopt=Abstract

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Nucleated red blood cell count at birth as an index of perinatal brain damage. Author(s): Buonocore G, Perrone S, Gioia D, Gatti MG, Massafra C, Agosta R, Bracci R. Source: American Journal of Obstetrics and Gynecology. 1999 December; 181(6): 1500-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10601935&dopt=Abstract

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Objective instrumental memory and performance tests for evaluation of patients with brain damage: a search for a behavioral diagnostic tool. Author(s): Harness BZ, Bental E, Carmon A. Source: Isr J Med Sci. 1976 March; 12(3): 215-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=931718&dopt=Abstract

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Observations on the growth in vitro of myeloid progenitor cells and fibroblasts from hemizygotes and heterozygotes for “complete” and “partial” hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency, and their relevance to the pathogenesis of brain damage in the Lesch-Nyhan syndrome. Author(s): McKeran RO, Howell A, Andrews TM, Watts RW, Arlett CF. Source: Journal of the Neurological Sciences. 1974 June; 22(2): 183-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4829193&dopt=Abstract

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On reconciling the “multidimensional” and “unitary” concepts of brain damage. Author(s): Adams J. Source: Percept Mot Skills. 1969 October; 29(2): 579-98. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4902938&dopt=Abstract

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On the theory and practice of shaking infants. Its potential residual effects of permanent brain damage and mental retardation. Author(s): Caffey J. Source: Am J Dis Child. 1972 August; 124(2): 161-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4559532&dopt=Abstract

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Organic brain damage and occupational solvent exposure. Author(s): Cherry NM, Labreche FP, McDonald JC. Source: Br J Ind Med. 1992 November; 49(11): 776-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1463678&dopt=Abstract

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Ornithinaemia. Another disorder of aminoacid metabolism associated with brain damage. Author(s): Bickel H, Feist D, Muller H, Quadbeck G, Kekomaki M. Source: Ger Med Mon. 1969 March; 14(3): 101-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5807485&dopt=Abstract

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Otoacoustic emissions and auditory assessment in infants at risk for early brain damage. Author(s): Vatovec J, Velickovic Perat M, Smid L, Gros A. Source: International Journal of Pediatric Otorhinolaryngology. 2001 April 27; 58(2): 13945. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11278022&dopt=Abstract

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Outcome after severe brain damage. Author(s): Prior PF, Scott DF. Source: Lancet. 1973 April 7; 1(7806): 770. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4120744&dopt=Abstract

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Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage. Author(s): Takagi Y, Mitsui A, Nishiyama A, Nozaki K, Sono H, Gon Y, Hashimoto N, Yodoi J. Source: Proceedings of the National Academy of Sciences of the United States of America. 1999 March 30; 96(7): 4131-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10097175&dopt=Abstract

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Oxygen toxicity in man. A A/Barber RE, Lee J, Hamilton WK: Oxygen toxicity in man. A prospective study in patients with irreversible brain damage. Author(s): Barber RE, Hamilton WK. Source: The New England Journal of Medicine. 1970 December 31; 283(27): 1478-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4921729&dopt=Abstract

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Pallidoreticular-rubral brain damage on magnetic resonance imaging after carbon monoxide poisoning. Author(s): Gandini C, Prockop LD, Butera R, Locatelli C, Manzo L. Source: Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging. 2002 April; 12(2): 102-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11977902&dopt=Abstract

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Pathophysiology of perinatal brain damage. Author(s): Evrard P. Source: Developmental Neuroscience. 2001; 23(3): 171-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11598315&dopt=Abstract

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Perception of emotions from faces and voices following unilateral brain damage. Author(s): Kucharska-Pietura K, Phillips ML, Gernand W, David AS. Source: Neuropsychologia. 2003; 41(8): 1082-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667543&dopt=Abstract

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Perception of facial affect in chronic schizophrenia and right brain damage. Author(s): Kucharska-Pietura K, Klimkowski M. Source: Acta Neurobiol Exp (Wars). 2002; 62(1): 33-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12004571&dopt=Abstract

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Perinatal brain damage: underlying mechanisms and neuroprotective strategies. Author(s): Berger R, Garnier Y, Jensen A. Source: Journal of the Society for Gynecologic Investigation. 2002 November-December; 9(6): 319-28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445595&dopt=Abstract

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Personal name recognition and associative priming in patients with unilateral brain damage. Author(s): Schweinberger SR. Source: Brain and Cognition. 1995 October; 29(1): 23-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8845121&dopt=Abstract

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Poly(ADP-ribose) polymerase as a key player in excitotoxicity and post-ischemic brain damage. Author(s): Meli E, Pangallo M, Baronti R, Chiarugi A, Cozzi A, Pellegrini-Giampietro DE, Moroni F. Source: Toxicology Letters. 2003 April 4; 139(2-3): 153-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628750&dopt=Abstract

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Post-traumatic epilepsy and recovery of function from experimental brain damage: a review. Author(s): Droogan J. Source: Seizure : the Journal of the British Epilepsy Association. 1995 September; 4(3): 163-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7582650&dopt=Abstract

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Prenatal brain damage and placental infarction--an autopsy study. Author(s): Burke CJ, Tannenberg AE. Source: Developmental Medicine and Child Neurology. 1995 June; 37(6): 555-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7789664&dopt=Abstract

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Prevalence, and intellectual outcome of unilateral focal cortical brain damage as a function of age, sex and aetiology. Author(s): Braun CM, Montour-Proulx I, Daigneault S, Rouleau I, Kuehn S, Piskopos M, Desmarais G, Lussier F, Rainville C. Source: Behavioural Neurology. 2001-2002; 13(3-4): 105-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446950&dopt=Abstract

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Qualitative cytology of cerebrospinal fluid as an indicator of neonatal brain damage and psychomotor outcome. Author(s): Dalens B, Bezou MJ, Raynaud EJ, Coulet M, Gaulme J. Source: Acta Paediatr Scand. 1981 March; 70(2): 161-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7234399&dopt=Abstract

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Quality of life with brain damage. Author(s): LaPointe LL. Source: Brain and Language. 2000 January; 71(1): 135-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10716828&dopt=Abstract

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Quantification of brain damage in cerebrotendinous xanthomatosis with magnetization transfer MR imaging. Author(s): Inglese M, DeStefano N, Pagani E, Dotti MT, Comi G, Federico A, Filippi M. Source: Ajnr. American Journal of Neuroradiology. 2003 March; 24(3): 495-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637303&dopt=Abstract

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Radiation-related brain damage and growth retardation among the prenatally exposed atomic bomb survivors. Author(s): Otake M, Schull WJ. Source: International Journal of Radiation Biology. 1998 August; 74(2): 159-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9712546&dopt=Abstract

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Radiological colpocephaly: a congenital malformation or the result of intrauterine and perinatal brain damage. Author(s): Landman J, Weitz R, Dulitzki F, Shuper A, Sirota L, Aloni D, Bar-Ziv J, Gadoth N. Source: Brain & Development. 1989; 11(5): 313-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2817296&dopt=Abstract

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Rarefaction of liquids in a spherical shell due to local radial loads with application to brain damage. Author(s): Suh CC, Yang WJ, McElhaney JH. Source: Journal of Biomechanics. 1972 March; 5(2): 181-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5020949&dopt=Abstract

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Reducing brain damage in boxers. Author(s): Pearn J. Source: The Medical Journal of Australia. 1998 April 20; 168(8): 418. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9594956&dopt=Abstract

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Regional cerebral correlates of global motion perception: evidence from unilateral cerebral brain damage. Author(s): Vaina LM, Cowey A, Eskew RT Jr, LeMay M, Kemper T. Source: Brain; a Journal of Neurology. 2001 February; 124(Pt 2): 310-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11157558&dopt=Abstract

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Rehabilitation of cognitive and motor functions in younger and older patients with vascular brain damage, rheumatologic illness and in post-surgery patients. Author(s): Valach L, Steck GC, Roschli C, Selz B. Source: International Journal of Rehabilitation Research. Internationale Zeitschrift Fur Rehabilitationsforschung. Revue Internationale De Recherches De Readaptation. 2002 June; 25(2): 133-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021599&dopt=Abstract

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Relating selective brain damage to impairments with voicing contrasts. Author(s): Ravizza SM. Source: Brain and Language. 2001 April; 77(1): 95-118. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11247658&dopt=Abstract

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Reversibility of alcohol-related brain damage: clinical and experimental observations. Author(s): Carlen PL, Wilkinson DA. Source: Acta Med Scand Suppl. 1987; 717: 19-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3478966&dopt=Abstract

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Role of the fetus in perinatal infection and neonatal brain damage. Author(s): Dammann O, Leviton A. Source: Current Opinion in Pediatrics. 2000 April; 12(2): 99-104. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10763757&dopt=Abstract

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Role of the ryanodine receptor in ischemic brain damage--localized reduction of ryanodine receptor binding during ischemia in hippocampus CA1. Author(s): Nozaki H, Tanaka K, Gomi S, Mihara B, Nogawa S, Nagata E, Kondo T, Fukuuchi Y. Source: Cellular and Molecular Neurobiology. 1999 February; 19(1): 119-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10079971&dopt=Abstract

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S100B in brain damage and neurodegeneration. Author(s): Rothermundt M, Peters M, Prehn JH, Arolt V. Source: Microscopy Research and Technique. 2003 April 15; 60(6): 614-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645009&dopt=Abstract

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Sensory and spatial components of somaesthetic deficits following right brain damage. Author(s): Smania N, Aglioti S. Source: Neurology. 1995 September; 45(9): 1725-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7675234&dopt=Abstract

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Serum creatine-kinase-BB and brain damage in high-risk newborn infants. Preliminary study with a new method for CK-BB estimation. Author(s): Amato M, Gambon R, Von Muralt G. Source: American Journal of Perinatology. 1986 July; 3(3): 161-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3718634&dopt=Abstract

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Serum S 100 B: a marker of brain damage in traumatic brain injury with and without multiple trauma. Author(s): Pelinka LE, Toegel E, Mauritz W, Redl H. Source: Shock (Augusta, Ga.). 2003 March; 19(3): 195-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630517&dopt=Abstract

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Speech and language therapy for dysarthria due to non-progressive brain damage. Author(s): Sellars C, Hughes T, Langhorne P. Source: Cochrane Database Syst Rev. 2002; (4): Cd002088. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519567&dopt=Abstract

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Speech and language therapy for dysarthria due to nonprogressive brain damage: a systematic Cochrane review. Author(s): Sellars C, Hughes T, Langhorne P. Source: Clinical Rehabilitation. 2002 February; 16(1): 61-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11837527&dopt=Abstract

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Standard forms--helpful clinical and investigative tools for determining cause and timing of inflicted brain damage in children. Author(s): Shaw A. Source: Child Abuse & Neglect. 2003 May; 27(5): 453-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718955&dopt=Abstract

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Symptomatic vasospasm after subarachnoid haemorrhage: assessment of brain damage by diffusion and perfusion-weighted MRI and single-photon emission computed tomography. Author(s): Leclerc X, Fichten A, Gauvrit JY, Riegel B, Steinling M, Lejeune JP, Pruvo JP. Source: Neuroradiology. 2002 July; 44(7): 610-6. Epub 2002 May 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12136364&dopt=Abstract

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Syndrome of minimal brain damage in young adults. Author(s): Shelley EM, Riester A. Source: Dis Nerv Syst. 1972 May; 33(5): 335-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4665834&dopt=Abstract

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Systematic review of prediction of poor outcome in anoxic-ischaemic coma with biochemical markers of brain damage. Author(s): Zandbergen EG, de Haan RJ, Hijdra A. Source: Intensive Care Medicine. 2001 October; 27(10): 1661-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685309&dopt=Abstract

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The assessment of brain damage from a psychometric point of view. Author(s): Schepers JM. Source: Forensic Sci. 1972 September; 1(3): 269-311. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4566609&dopt=Abstract

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The impact of synaptic depression following brain damage: a connectionist account of “access/refractory” and “degraded-store” semantic impairments. Author(s): Gotts SJ, Plaut DC. Source: Cognitive, Affective & Behavioral Neuroscience. 2002 September; 2(3): 187-213. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775185&dopt=Abstract

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The importance of breech delivery in the pathogenesis of brain damage. End results of a long-term follow-up. Author(s): Alexopoulos KA. Source: Clinical Pediatrics. 1973 April; 12(4): 248-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4121759&dopt=Abstract

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The law tries to decide whether whooping cough vaccine causes brain damage: Professor Gordon Stewart gives evidence. Author(s): Stewart GT. Source: British Medical Journal (Clinical Research Ed.). 1986 July 19; 293(6540): 203-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3089449&dopt=Abstract

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The perception of emotional chimeric faces in patients with depression, mania and unilateral brain damage. Author(s): Kucharska-Pietura K, David AS. Source: Psychological Medicine. 2003 May; 33(4): 739-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785476&dopt=Abstract

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The possible role of vitamin K deficiency in the pathogenesis of Alzheimer's disease and in augmenting brain damage associated with cardiovascular disease. Author(s): Allison AC. Source: Medical Hypotheses. 2001 August; 57(2): 151-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11461163&dopt=Abstract

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The structural basis of moderate disability after traumatic brain damage. Author(s): Adams JH, Graham DI, Jennett B. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2001 October; 71(4): 521-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11561038&dopt=Abstract

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The variety of visual perceptual impairments in pre-school children with perinatal brain damage. Author(s): Stiers P, van den Hout BM, Haers M, Vanderkelen R, de Vries LS, van Nieuwenhuizen O, Vandenbussche E. Source: Brain & Development. 2001 August; 23(5): 333-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11504606&dopt=Abstract

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Treatment of alcoholism with organic brain damage. Author(s): Walsh AC. Source: Jama : the Journal of the American Medical Association. 1972 June 5; 220(10): 1359. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4112319&dopt=Abstract

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Two patterns of perinatal brain damage and their conditions of occurrence. Author(s): Myers RE. Source: American Journal of Obstetrics and Gynecology. 1972 January 15; 112(2): 246-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4621486&dopt=Abstract

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Ultrasound-clinical correlations in the assessment of the newborn at risk for brain damage. Author(s): Ometto A, Fazzi E. Source: Italian Journal of Neurological Sciences. 1986 April; Suppl 5: 79-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3531085&dopt=Abstract

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Umbilical cord serum creatine kinase BB in the diagnosis of brain damage in the newborn: problems in interpretation. Author(s): Kumpel B, Wood SM, Anthony PP, Brimblecombe FS. Source: Archives of Disease in Childhood. 1983 May; 58(5): 382-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6859922&dopt=Abstract

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Understanding head injury and intellectual recovery from brain damage: is IQ an adequate measure? Author(s): Cahn G, Gould RE. Source: Bull Am Acad Psychiatry Law. 1996; 24(1): 135-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8891329&dopt=Abstract

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Unilateral brain damage after prolonged hemiconvulsions in the elderly associated with theophylline administration. Author(s): Mori H, Mizutani T, Yoshimura M, Yamanouchi H, Shimada H. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1992 June; 55(6): 466-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1619413&dopt=Abstract

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Unilateral brain damage, prosodic comprehension deficits, and the acoustic cues to prosody. Author(s): Pell MD, Baum SR. Source: Brain and Language. 1997 April; 57(2): 195-214. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9126413&dopt=Abstract

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Use of 31P magnetic resonance spectroscopy to characterize evolving brain damage after perinatal asphyxia. Author(s): Laptook AR, Corbett RJ, Uauy R, Mize C, Mendelsohn D, Nunnally RL. Source: Neurology. 1989 May; 39(5): 709-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2710361&dopt=Abstract

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Use of rat microglial cells for the study of a possible mechanism of brain damage in AIDS. Author(s): Levi G, Patrizia M, Agresti C, Petrucci T, Bernardo A. Source: Clin Neuropathol. 1993 September-October; 12(5): 290-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8222401&dopt=Abstract

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Use of risperidone in psychotic disorder following ischemic brain damage. Author(s): Zimnitzky BM, DeMaso DR, Steingard RJ. Source: Journal of Child and Adolescent Psychopharmacology. 1996 Spring; 6(1): 75-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9231301&dopt=Abstract

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Using malpractice claims data to successfully attack the problem of infant brain damage. Author(s): Ludlam JE. Source: Leg Med. 1991; : 227-44. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1821894&dopt=Abstract

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Utility of the seven subtest WAIS-R short form in a female sample with brain damage. Author(s): Ryan JJ, Weilage ME, Paolo AM, Miller DA, Morris J. Source: The International Journal of Neuroscience. 1998 April; 93(3-4): 197-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9639237&dopt=Abstract

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Varieties of colour naming defects associated with posterior brain damage: a neurolinguistic reappraisal. Author(s): De Vreese LP. Source: Funct Neurol. 1987 January-March; 2(1): 111-22. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3315873&dopt=Abstract

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Vasoparalysis associated with brain damage in asphyxiated term infants. Author(s): Pryds O, Greisen G, Lou H, Friis-Hansen B. Source: The Journal of Pediatrics. 1990 July; 117(1 Pt 1): 119-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2115079&dopt=Abstract

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Ventilatory post-stimulus potentiation in patients with brain damage. Author(s): Georgopoulos D, Mitrouska I, Koletsos K, Markopoulou K, Riggos D, Patakas D, Anthonisen NR. Source: American Journal of Respiratory and Critical Care Medicine. 1995 November; 152(5 Pt 1): 1627-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7582306&dopt=Abstract

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Verbal and figural Gestalt Completion Tests with lateralized occipital area brain damage. Author(s): Russell EW, Hendrickson ME, VanEaton E. Source: Journal of Clinical Psychology. 1988 March; 44(2): 217-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3360939&dopt=Abstract

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Virtual environments in brain damage rehabilitation: a rationale from basic neuroscience. Author(s): Rose FD, Attree EA, Brooks BM, Johnson DA. Source: Studies in Health Technology and Informatics. 1998; 58: 233-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10350924&dopt=Abstract

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Visual evoked potentials and alcohol-induced brain damage. Author(s): Levy LJ, Losowsky MS. Source: Alcohol and Alcoholism (Oxford, Oxfordshire). 1987; 22(4): 355-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3322311&dopt=Abstract

•

Visual motion perception after brain damage: I. Deficits in global motion perception. Author(s): Schenk T, Zihl J. Source: Neuropsychologia. 1997 September; 35(9): 1289-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9364498&dopt=Abstract

•

Visual motion perception after brain damage: II. Deficits in form-from-motion perception. Author(s): Schenk T, Zihl J. Source: Neuropsychologia. 1997 September; 35(9): 1299-310. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9364499&dopt=Abstract

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Visual short-term memory of stimulus velocity in patients with unilateral posterior brain damage. Author(s): Greenlee MW, Lang HJ, Mergner T, Seeger W. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 1995 March; 15(3 Pt 2): 2287-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7891167&dopt=Abstract

•

Visuospatial dysfunction following unilateral brain damage: dissociations in hierarchical and hemispatial analysis. Author(s): Delis DC, Kiefner MG, Fridlund AJ. Source: J Clin Exp Neuropsychol. 1988 August; 10(4): 421-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3403705&dopt=Abstract

•

What does brain damage tell us about the mechanisms of sleep? Author(s): Evans BM. Source: Journal of the Royal Society of Medicine. 2002 December; 95(12): 591-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12461144&dopt=Abstract

•

Which blood gas caused the brain damage? Author(s): Suwa K. Source: Acta Anaesthesiologica Scandinavica. Supplementum. 1995; 107: 215-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8599281&dopt=Abstract

•

Widespread brain damage in alcoholics. Author(s): Smith RB. Source: Med Ann Dist Columbia. 1972 November; 41(11): 684-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4628756&dopt=Abstract

•

Will brain damage after status epilepticus be history in 2010? Author(s): Treiman DM. Source: Prog Brain Res. 2002; 135: 471-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12143365&dopt=Abstract

•

Wisconsin Card Sorting Test performance in patients with focal frontal and posterior brain damage: effects of lesion location and test structure on separable cognitive processes. Author(s): Stuss DT, Levine B, Alexander MP, Hong J, Palumbo C, Hamer L, Murphy KJ, Izukawa D. Source: Neuropsychologia. 2000; 38(4): 388-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10683390&dopt=Abstract

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•

WIST predictions of brain damage: a follow-up to Albott and Gilbert. Author(s): Peake TH, Albott WL. Source: Journal of Clinical Psychology. 1981 January; 37(1): 180-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7204596&dopt=Abstract

•

Withdrawing artificial feeding from children with brain damage. Author(s): Cranford RE. Source: Bmj (Clinical Research Ed.). 1995 August 19; 311(7003): 464-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7647631&dopt=Abstract

•

Withdrawing artificial feeding from children with brain damage. Author(s): Shannon PE. Source: Bmj (Clinical Research Ed.). 1995 December 2; 311(7018): 1502. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8520353&dopt=Abstract

•

Withdrawing artificial feeding from children with brain damage. Tortuous arguments evade the issue. Author(s): Andrews K. Source: Bmj (Clinical Research Ed.). 1995 November 25; 311(7017): 1437. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8520303&dopt=Abstract

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CHAPTER 2. NUTRITION AND BRAIN DAMAGE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and brain damage.

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

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

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

Caramiphen and scopolamine prevent soman-induced brain damage and cognitive dysfunction. Author(s): Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona. [email protected] Source: Raveh, L Weissman, B A Cohen, G Alkalay, D Rabinovitz, I Sonego, H Brandeis, R Neurotoxicology. 2002 May; 23(1): 7-17 0161-813X

•

Changes of neuronal calcium channel following brain damage induced by injection of pertussis bacilli in rats. Author(s): Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China. Source: Chen, L Yang, Y Liu, L Cao, M Chin-J-Traumatol. 2002 August; 5(4): 224-7 10081275

•

Feeding rats diets enriched in lowbush blueberries for six weeks decreases ischemiainduced brain damage. Author(s): Department of Biology, University of Prince Edward Island, 550 University Ave, Charlottetown, PEI, Canada C1A 4P3. [email protected] Source: Sweeney, M I Kalt, W MacKinnon, S L Ashby, J Gottschall Pass, K T NutrNeurosci. 2002 December; 5(6): 427-31 1028-415X

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Methylprednisolone and vitamin E therapy in perinatal hypoxic-ischemic brain damage in rats. Author(s): Department of Neurosurgery, Gulhane School of Medicine, Ankara, Turkey. Source: Daneyemez, M Kurt, E Cosar, A Yuce, E Ide, T Neuroscience. 1999; 92(2): 693-7 0306-4522

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New insights into brain damage in stroke-prone rats: a nuclear magnetic imaging study. Author(s): Department of Pharmacological Sciences, University of Milan, Italy Source: Guerrini, Uliano Sironi, Luigi Tremoli, Elena Cimino, Mauro Pollo, Bianca Calvio, Anna Maria Paoletti, Rodolfo Asdente, Maria Stroke. 2002 Mar; 33(3): 825-30 1524-4628

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Selective blockade of endothelin-B receptors exacerbates ischemic brain damage in the rat. Author(s): Universite de Caen, CNRS-UMR 6551, Caen, France. [email protected] Source: Chuquet, J Benchenane, K Toutain, J MacKenzie, E T Roussel, S Touzani, O Stroke. 2002 December; 33(12): 3019-25 1524-4628

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The possible role of vitamin K deficiency in the pathogenesis of Alzheimer's disease and in augmenting brain damage associated with cardiovascular disease. Author(s): SurroMed Corporation, Mountain View, California 94043, USA. Source: Allison, A C Med-Hypotheses. 2001 August; 57(2): 151-5 0306-9877

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

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

•

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

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

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

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

•

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

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

•

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

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

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

•

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

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

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

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

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

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

•

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

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CHAPTER DAMAGE

3.

ALTERNATIVE

MEDICINE

AND

BRAIN

Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to brain damage. At the conclusion of this chapter, we will provide additional sources.

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

“Brainstem death,” “brain death” and death: a critical re-evaluation of the purported equivalence. Author(s): Shewmon DA. Source: Issues in Law & Medicine. 1998 Fall; 14(2): 125-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9807242&dopt=Abstract

•

“Mangifera indica L. extract (QF808) reduces ischaemia-induced neuronal loss and oxidative damage in the gerbil brain”. Author(s): Martinez Sanchez G, Candelario-Jalil E, Giuliani A, Leon OS, Sam S, Delgado R, Nunez Selles AJ. Source: Free Radical Research. 2001 November; 35(5): 465-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11767405&dopt=Abstract

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“Theory of mind” impairments and their relationship to executive functioning following frontal lobe excisions. Author(s): Rowe AD, Bullock PR, Polkey CE, Morris RG. Source: Brain; a Journal of Neurology. 2001 March; 124(Pt 3): 600-16. Erratum In: Brain 2001 May; 124(Pt 5): 1062. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11222459&dopt=Abstract

•

(-)-Epigallocatechin gallate protects against NO stress-induced neuronal damage after ischemia by acting as an anti-oxidant. Author(s): Nagai K, Jiang MH, Hada J, Nagata T, Yajima Y, Yamamoto S, Nishizaki T. Source: Brain Research. 2002 November 29; 956(2): 319-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445701&dopt=Abstract

•

Carotid brainstem reflex myoclonus after hypoxic brain damage. Author(s): Hanakawa T, Hashimoto S, Iga K, Segawa Y, Shibasaki H. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2000 November; 69(5): 672-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11032627&dopt=Abstract

•

GM1 monosialoganglioside pretreatment protects against soman-induced seizurerelated brain damage. Author(s): Ballough GP, Cann FJ, Smith CD, Forster JS, Kling CE, Filbert MG. Source: Mol Chem Neuropathol. 1998 May; 34(1): 1-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9778643&dopt=Abstract

•

Impaired direction and extent specification of aimed arm movements in humans with stroke-related brain damage. Author(s): Velicki MR, Winstein CJ, Pohl PS. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 2000 February; 130(3): 362-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10706435&dopt=Abstract

•

Lack of anticipatory gaze-orienting responses in patients with right brain damage. Author(s): Ivanenko YP, Viaud-Delmon I, Mayer E, Valenza N, Annoni JM, Rohr A, Guyot JP, Berthoz A, Landis T. Source: Neurology. 2000 April 25; 54(8): 1656-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10762509&dopt=Abstract

•

Neuroprotective effect of developmental docosahexaenoic acid supplement against excitotoxic brain damage in infant rats. Author(s): Hogyes E, Nyakas C, Kiliaan A, Farkas T, Penke B, Luiten PG.

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Source: Neuroscience. 2003; 119(4): 999-1012. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831859&dopt=Abstract •

Neuroprotective role of curcumin from curcuma longa on ethanol-induced brain damage. Author(s): Rajakrishnan V, Viswanathan P, Rajasekharan KN, Menon VP. Source: Phytotherapy Research : Ptr. 1999 November; 13(7): 571-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10548748&dopt=Abstract

•

Partial neuroprotection of in vivo excitotoxic brain damage by chronic administration of the red wine antioxidant agent, trans-resveratrol in rats. Author(s): Virgili M, Contestabile A. Source: Neuroscience Letters. 2000 March 10; 281(2-3): 123-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10704758&dopt=Abstract

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Rapid hypothermic aortic flush can achieve survival without brain damage after 30 minutes cardiac arrest in dogs. Author(s): Behringer W, Prueckner S, Kentner R, Tisherman SA, Radovsky A, Clark R, Stezoski SW, Henchir J, Klein E, Safar P. Source: Anesthesiology. 2000 December; 93(6): 1491-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11149445&dopt=Abstract

•

Virtual environments in brain damage rehabilitation: a rationale from basic neuroscience. Author(s): Rose FD, Attree EA, Brooks BM, Johnson DA. Source: Studies in Health Technology and Informatics. 1998; 58: 233-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10350924&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 brain damage; 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 Hypoglycemia Source: Integrative Medicine Communications; www.drkoop.com Infantile Colic Source: Integrative Medicine Communications; www.drkoop.com Low Blood Sugar Source: Integrative Medicine Communications; www.drkoop.com Meningitis Source: Integrative Medicine Communications; www.drkoop.com Roseola Source: Integrative Medicine Communications; www.drkoop.com Stress Source: Integrative Medicine Communications; www.drkoop.com Tias Source: Integrative Medicine Communications; www.drkoop.com Transient Ischemic Attacks Source: Integrative Medicine Communications; www.drkoop.com

•

Alternative Therapy Applied Kinesiology Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,711,00.html

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•

Herbs and Supplements Angelica Sinensis Source: Integrative Medicine Communications; www.drkoop.com Chinese Angelica Source: Integrative Medicine Communications; www.drkoop.com Cysteine Source: Healthnotes, Inc.; www.healthnotes.com Danggui Alternative names: Angelica sinensis, Chinese Angelica, Dang Gui, Danngui, Dong Qua, Tang Kuei, Tan Kue Bai zhi(Note: Dong quai should not be confused with Angelica root or Angelica seed.) Source: Integrative Medicine Communications; www.drkoop.com Dong Quai Alternative names: Angelica sinensis, Chinese Angelica, Dang Gui, Danngui, Dong Qua, Tang Kuei, Tan Kue Bai zhi(Note: Dong quai should not be confused with Angelica root or Angelica seed.) Source: Integrative Medicine Communications; www.drkoop.com Kava Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,798,00.html Pennyroyal Alternative names: Hedeoma pulegoides, Mentha pulegium Source: Healthnotes, Inc.; www.healthnotes.com Tang Kuei Source: Integrative Medicine Communications; www.drkoop.com Wormwood Alternative names: Artemisia absinthium Source: Healthnotes, Inc.; www.healthnotes.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 BRAIN DAMAGE Overview In this chapter, we will give you a bibliography on recent dissertations relating to brain damage. 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 “brain damage” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on brain damage, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Brain Damage 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 brain damage. 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 Comparison of the Performance of Children with Primary Reading Retardation and Children with Reading Retardation Secondary to Brain Damage on Subtests of the Gates-mckillop Reading Diagnostic Tests. by Sansbury, Russell Joseph, Phd from The University of Michigan, 1977, 165 pages http://wwwlib.umi.com/dissertations/fullcit/7718111

•

Alcohol-induced Brain Damage Morphology and Physiology in the Hippocampus Invitro by Durand, D; , Phd from University of Toronto (canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK58274

•

An Investigation of Knowledge among Counselor Educators, Educators in Clinical Psychology, and Psychiatrists Regarding Selected Aspects of Brain Damage. by Dubnick, Barbara, Edd from Ball State University, 1975, 126 pages http://wwwlib.umi.com/dissertations/fullcit/7616462

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•

An Investigation of Minimal Brain Damage and Delinquency with Implications for Counseling by Johnson, Robert Lee, Phd from University of Oregon, 1972, 121 pages http://wwwlib.umi.com/dissertations/fullcit/7228154

•

Cognitive and Perceptual-motor Indicators of Lateralized Vs. Diffuse Brain Damage in Adults by Gregory, Erin Kathleen Taylor; Ms from University of North Texas, 2002, 33 pages http://wwwlib.umi.com/dissertations/fullcit/1412076

•

Differential Cognitive Test Patterns in Children with Lateralized Brain Damage (kabc, Wisc-r, Neuropsychology) by Derienzo, Paula Jean, Phd from Syracuse University, 1984, 133 pages http://wwwlib.umi.com/dissertations/fullcit/8508214

•

Hemispheric Interaction in Number Processing of Patients with Lateralized Brain Damage by Bogdanova, Yelena; Phd from Boston University, 2003, 100 pages http://wwwlib.umi.com/dissertations/fullcit/3083822

•

Lateralizing Brain Damage with the Luria-nebraska Neuropsychological Battery Diagnostic Effectiveness As Compared to the Halstead-reitan Neuropsychological Test Battery by Stambrook, Michael; Phd from The University of Manitoba (canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK62534

•

Mental Rotation in the Right Brain-damaged Individual (brain Damage) by Weinberg, Joseph, Phd from New York University, 1992, 90 pages http://wwwlib.umi.com/dissertations/fullcit/9222973

•

Neuropsychological Assessment and the Differentiation of Chronic Schizophrenia from Brain Damage by Young, Donald Allen; Edd from University of Toronto (canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NL23522

•

The Diagnosis of Brain Damage in Children: Criterion Considerations. by Walnum, Arthur Raymond, Phd from Brigham Young University, 1976, 183 pages http://wwwlib.umi.com/dissertations/fullcit/7704859

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. PATENTS ON BRAIN DAMAGE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “brain damage” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on brain damage, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Brain Damage By performing a patent search focusing on brain damage, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on brain damage: •

2,4,6-trimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid esters as neuroprotective drugs Inventor(s): Bazan; Nicholas G. (Baton Rouge, LA), Builla-G.; Julio (Madrid, ES), Marcheselli; Victor L. (Covington, LA), Sunkel; Carlos (Madrid, ES) Assignee(s): Board of Supervisors of Louisiana State University and Agricultural and (Baton Rouge, LA) Patent Number: 6,566,359 Date filed: May 20, 2002 Abstract: A new series of derivatives of 2,4,6-trimethyl-1,4-dihydropyridine-3,5dicarboxylic acid and their synthesis have been discovered. Surprisingly, by modifying the substituent of the 3-carboxylic acid group, new compounds were produced with high activity as PAF receptor antagonists. These compounds were shown to protect neurons from brain damage that normally occurs in response to stroke and other cerebrovascular diseases. These compounds are also protective against edema generation resulting from traumatic breakdown of the blood-brain barrier. Moreover, these compounds were found to be non-toxic and cytoprotective of cells undergoing oxidative stress that would normally trigger apoptotic cell death; and to have activity as (a) antagonists of an intracellular platelet activating factor ("PAF")-binding site, (b) inhibitors of PAF- and cytokine-mediated c-aminoterminal jun kinase (JNK) and extracellular regulated kinase (ERK), and (c) transcriptional inhibitors of COX-2 expression. Excerpt(s): This invention pertains to a series of new derivatives of 2,4,6-trimethyl-1,4dihydropyridine-3,5-dicarboxylic acid, their synthesis, and the use of these compounds as platelet-activating factor antagonists, inhibitors of certain protein kinases, transcriptional inhibitors of COX-2 expression, and as agents effective in protecting brain tissue from injuries related to trauma or disease. Various derivatives of 1,4 dihydropyridines have been described with properties that include one or more of the following: platelet activating factor antagonist activity, coronary vessel dilators, antihypertensives, antiischemic, antithrombotic activity, cerebral vessel dilators, peripheral vessel dilators, renal vessel dilators. See U.S. Pat. Nos. 5,177,211; 5,070,205; 5,068,337; 4,937,242; 4,801,598; 4,788,205; 4,755,512; 3,996,234; and 3,974,274. See also, WO 90/12015 and EPO 0325 187. It has been known for sometime that brain ischemia promotes the accumulation of arachidonic acid. See N. G. Bazan, "Effects of ischemia and electroconvulsive shock on free fatty acid pool in the brain," Biochim. Biophys. Acta, vol. 218, pp. 1-10 (1970); N. G. Bazan, "Changes in free fatty acids of brain by drug induced convulsions, electroshock and anesthesia," J. Neurochem., vol. 18, pp. 1379-1385 (1971). In addition, newborn mammals and adult poikilotherms, unlike adult rodents and nonhuman primates, do not display an arachidonic acid accumulation induced by ischemia. See Bazan 1971; N. G. Bazan et al., "Regional distribution and rate of production of free fatty acids in rat brain," J. Neurochem., vol. 18, pp.1387-1393 (1971); and M. I. Aveldano et al., "Differential lipid deacylation during brain ischemia in a homeotherm and a poikilotherm. Content and composition of free fatty acids and triacylglycerols," Brain Res., vol.100, pp. 99-110 (1975). A connection has been suggested between brain damage and both the accumulation of arachidonic acid and the activation of phospholipase A.sub.2, because resistance to brain damage was shown in animals that do not accumulate arachidonic acid (e.g., newborn mammals and mature

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poikilotherms) but not in animals that accumulate arachidonic acid (e.g., adult mammals). This pattern of resistance to brain damage was shown in animal models subjected to ischemia, stroke, cerebral edema, and epilepsy. See N. G. Bazan et al., "Membrane lipids in the pathogenesis of brain edema: Phospholipids and arachidonic acid, the earliest membrane components changed at the onset of ischemia," In: Advances in Neurology, Vol 28: Brain Edema. (J. Cervos-Navarro and R. Ferszt, eds), Raven Press, New York, pp 197-205 (1980); N. G. Bazan et al., "Endogenous pools of arachidonic acid enriched membrane lipids in cryogenic brain edema," In: Recent Progress in the Study of Brain Edema, (K. G. Go and A. Baethmann, eds), Plenum Press, New York, pp 203-212 (1984); and N. G. Bazan et al., "Free arachidonic acid and membrane lipids in the central nervous system during bicuculline induced status epilepticus," In: Advances in Neurology Vol 34: Status Epilepticus, (A. V. Delgado-Escueta, C. G. Wasterlain, D. M. Treiman, R. J. Porter, eds), Raven Press, New York, pp 305-310 (1983). Web site: http://www.delphion.com/details?pn=US06566359__ •

Agent for treating ischemic brain damage Inventor(s): Kadokawa; Toshiaki (Hirakata, JP), Kurokawa; Mikio (Kobe, JP), Masuda; Yoshinobu (Katano, JP), Ochi; Yoshiaki (Sanda, JP), Zushi; Kayoko (Hirakata, JP) Assignee(s): Dainippon Pharmaceutical Co., Ltd. (Osaka, JP) Patent Number: 5,128,354 Date filed: June 25, 1990 Abstract: The present invention provides an agent for treating ischemic brain damage comprising 3-sulfamoylmethyl-1,2-benzisoxazole or its alkali metal salt as an active ingredient. This agent can be used for the prevention and/or treatment of cerebral ischemia-induced intracranial diseases or various symptoms associated therewith in mammals including human beings. Excerpt(s): The present invention relates to an agent for treating ischemic brain damage containing a 1,2-benzisoxazole derivative as an active ingredient. Unlike other organs, the brain exists under a particular environment: it is immersed in the cerebrospinal fluid within rigid bodies such as the skull and cerebral pachymeninx. It is one of the most active organs in energy metabolism and shows the highest rate of oxygen consumption out of all organs. Most of energy required for the brain neurons are derived from oxygen and glucose. These energy sources are scarcely stored in the brain and continuously supplied by the blood. Therefore, in the cerebral blood vessel itself, the mechanism for controlling cerebral blood flow develops well to stably supply energy sources for brain tissues and to maintain an external environment of the brain neurons constant. When the homeostatic mechanism in the brain is damaged by physical pressure such as hematoma, cerebral tumor or cerebral injury, the brain is placed in the situation of ischemia, and their neurons are exposed to hypoxic situation and cannot function properly. When the brain neurons fall into oxygen-deficiency state (hereinafter referred to as "cerebral hypoxia"), the permeability of membranes of the brain neurons changes; so the invasion of the extracellular fluid causes edema. When cerebral edema grows to a certain extent, the intracranial pressure rises to cause cerebral circulatory disturbance. The augmentation of cerebral hypoxia and the deficiency of glucose and accumulation of its metabolites, which are due to the cerebral circulatory disturbance, enlarge cerebral edema. As a result, the growth of cerebral edema and the rise of intracranial pressure are further accelerated; the compression of brain stem and the disturbance in pass of the cerebrospinal fluid occur and lead to the formation of a

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vicious circle of the augmentation of cerebral hypoxia, the growth of cerebral edema and the rise of intracranial pressure. Consequently, the lesion is enlarged so that even healthy brain tissues become hypoxic. In the end, the brain falls into the situation of circulatory insufficiency; so the damage is severe. This is the reason why cerebral hypoxia is called the common denominator of most diseases due to cerebral circulatory disturbances [Eur. Neurol.,17 (Supple.1), 113-120 (1978)]. With an increase of the proportion of the elderly in population, senile dementia is becoming a major problem of society. The great majority of senile dementia are composed of cerebrovascular dementia, Alzheimer-type dementia and the mixture thereof. Cerebrovascular dementia appears as secondary disease after cerebrovascular disease. As one of the causes of the disease is regarded the occurrence of neuronal damage in the brain resulting from ischemic condition at an attack. Accordingly, it is expected that agents having protective effects on neuronal damage in the brain after a transient ischemia, that is, neuroprotective activity, are useful for the prevention and treatment of senile dementia. Web site: http://www.delphion.com/details?pn=US05128354__ •

Alkylated bicycloalkaneamines for treatment of neurotoxic injury Inventor(s): Olney; John W. (Ladue, MO) Assignee(s): Washington University (St. Louis, MO) Patent Number: 4,837,218 Date filed: October 23, 1987 Abstract: Compounds, compositions and methods of treatment are described to control brain damage associated with anoxia or ischemia which typically follows such conditions as stroke, cardiac arrest or perinatal asphyxia. The treatment includes administration of an alkylated bicycloalkaneamine compound as an antagonist to inhibit excitotoxic actions at major neuronal exzcitatory amino acid receptor sites. Excerpt(s): This invention is in the field of clinical neurology and relates specifically to compounds, compositions and methods for neuroprotective purposes such as controlling brain damage which occurs during periods of anoxia or ischemia associated with conditions such as stroke, cardiac arrest or perinatal asphyxia. Unlike other tissue which can survive extended periods of hypoxia, brain tissue is particularly sensitive to deprivation of oxygen or energy. Permanent damage to neurons can occur during brief periods of hypoxia, anoxia or ischemia. Neurotoxic injury is known to be caused or accelerated by certain excitatory amino acids (EAA) found naturally in the central nervous system (CNS). Glutamate (Glu) is an endogenous amino acid which was early characterized as a fast excitatory transmitter in the mammalian brain. Glutamate is also known as a powerful neurotoxin capable of killing CNS neurons under certain pathological conditions which accompany stroke and cardiac arrest. Normally, high glutamate concentrations are maintained inside cells of the CNS by energy-dependent transport systems, but high concentrations are not allowed in the extracellular compartment where glutamate can exert excitotoxic action at excitatory synaptic receptors. Under low energy conditions such as hypoglycemia, hypoxia or ischemia, cells release glutamate and, because of the energy deficiency, the transport systems are unable to move glutamate back into the cell. Initial glutamate release stimulates further release of glutamate which results in an extracellular glutamate accumulation and a cascade of neurotoxic injury. It has been shown that the sensitivity of central neurons to hypoxia and ischemia can be reduced by the specific antagonism of postsynaptic glutamate receptors [see S. M. Rothman and J. W. Olney, "Glutamate and the

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Pathophysiology of Hypoxia-Ischemic Brain Damage," Annals of Neurology, Vol. 19, No. 2 (1986)]. Glutamate receptors, also known as excitatory amino acid (EAA) receptors, are of three types, each being named after the EAA glutamate analogues which selectively excite them, namely: Kainate (KA), N-methyl-D-aspartate (NMDA or NMA) and quisqualate (QUIS). Glutamate is believed to be a mixed (broad spectrum) agonist capable of binding to and exciting all three EAA receptor types. Web site: http://www.delphion.com/details?pn=US04837218__ •

Apparatus for preventing brain damage during cardiac arrest, CPR or severe shock Inventor(s): Brader; Eric W. (42 Canter Dr., Sewickley, PA 15143) Assignee(s): none reported Patent Number: 4,920,963 Date filed: April 4, 1988 Abstract: A method and apparatus for cooling the extracranial area including the face and, optionally, also including the mandible, during emergency care of cardiac arrest or severe shock; the method is preferably implemented by means of a head cooling apparatus which includes a watertight shroud for the head and which needs no refrigeration. The head cooling apparatus contains the unreacted constituents of an endothermic reaction, such as pellets of ammonium nitrate (NH.sub.4 NO.sub.3) stored adjacent a selectively avaiable reservoir of water, and thus needs no external coolants or refrigeration. Preferably, the head-cooling apparatus comprises a portable, selfcontained system which is suitable for storage, transport and/or use anywhere. Excerpt(s): The present invention is a method of and apparatus for inhibiting tissue metabolism in the area of the brain and, more particularly, is a method and apparatus for inducing localized hypothermia during the emergency treatment of cardiac arrest or severe shock. Systemic hypothermia can dramatically postpone neurologic deterioration in hypoxic or anoxic tissues. For example, accidental submersion in cold waters, and the commensurate systemic hypothermia thus produced, has consistently contributed to the neurologic survival of accident victims who otherwise would have sustained irreparable brain damage. Observation of this phenomenon led medical practitioners to induce, intentionally, systemic hypothermia in the course of various hypoxia and anoxiaproducing surgical procedures, in order to decrease both the systemic metabolism and the associated overall oxygen requirement of the patient. Whereas systemic hypothermia may be induced without difficulty in the hospital environment, emergency inducement of systemic hypothermia in a non-hospital setting can be difficult or impossible. As a result, induced systemic hypothermia forms no part of, for example, pre-hospital emergency cardiac care such as cardiopulmonary resuscitation (CPR), notwithstanding the beneficial metabolic inhibition which such hypothermia would provide. Similar emergency procedures in which hypothermia has not been induced to date include the pre-hospital emergency care administered to patients in severe shock. Web site: http://www.delphion.com/details?pn=US04920963__

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Automatic safety car seat using tension springs Inventor(s): Jesadanont; Mongkol (386/2 Soi Chalermsuk, (Pahonyothin 28) Assignee(s): none reported Patent Number: 5,746,467 Date filed: August 16, 1996 Abstract: The automatic safety seat in a vehicle are designed to minimize the seriousness of car-crash injuries during a frontal collision. When the vehicle collides against other vehicle at a relative velocity of 40 Km/h or up, the backrest is pushed to recline backward by action of springs and various mechanisms designed. A tension spring is one of the most important part used to bring the backrest to a reclining position. Collision results in pulling the upper part of occupants fastened by designed safety-belts to the backrest to recline backwards to the rearmost. Thus, pelvis, chest and head of the occupant are moved away to the farmost and can avoid striking with deforming frontal parts of the intruding car by frontal collision. Chest injuries and brain damage can be avoided. Excerpt(s): No type of car accident results in a greater hazard to drivers than a frontal collision. Presently, several safety features have been developed to reduce injuries to the occupants during a frontal collision. Several safety devices like the seat-belts with modifications (U.S. Pat. Nos. 5,411,319 and EP 0 529 265 A1 ), and the air bags (U.S. Pat. Nos. 5,409,262; 5,251,931 and 5,011,181) have been used. Those air bags are mostly installed in the interior of the steering wheel assembly which is most prone to serious damage upon a frontal collision. Those actuated electronically can be easily damaged during a collision. These all result in too many reports on failure of the air bag. Besides, at high speeds as or over 40 Km/h upon collision, the impact is so great that the air bag itself can cause serious damage to the occupant's body. Improvements have been made to vehicle seats to minimize the damage to the occupant. What currently proposed is to bring the occupant's body especially upper part and head away the farmost to avoid striking with deforming frontal part of the car. Lifting mechanisms has been described (U.S. Pat. No. 5,340,185) for raising a front edge section of a seat cushion. The design is too complex and questionable for functioning during a critical moment. Accordingly, there is a need for a simple, inexpensive, yet highly effective means to minimize injuries to an occupant in a vehicle upon a frontal collision. This invention proposes a system to fulfill such need. The automatic seats in a vehicle designed to minimize the seriousness of car-crash injuries during a frontal collision are described. A seat cushion is connected at its posterior end to a backrest whose two flanking steel bars each having a circular hole fits pivotally onto a cylindrical shaft protruding upright on the surface of each of the two thick steel plates mounted under the left and the right edges of the seat cushion. The backrest is held slightly reclining tightly in place via a spring of predetermined stiffness. Spring of tension type can be used. When the vehicle collides against the other vehicle or any other stationary object at a relative velocity of 40 Km/h or up, the backrest is pushed to recline backward by the action of the springs together with various mechanisms especially designed. The collision results in pulling the upper part of the body of the driver or the occupants fastened by the presently designed safety-belts to recline backwards to the rearmost. Thus, the pelvis, the chest and the head of an occupant sitting on this automatic safety car seat are moved away to the farmost and thus, can avoid striking with the deforming frontal parts of the car intruding by the frontal collision. The chest injuries and the brain damage can then be effectively avoided.

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Web site: http://www.delphion.com/details?pn=US05746467__ •

Automatic safety car seats and sheet-type safety-belt Inventor(s): Jesadanont; Mongkol (Faculty of Pharm. Sciences, Chulalongkorn U., Phyathai Rd., BKK 10330, TH) Assignee(s): none reported Patent Number: 5,810,417 Date filed: September 28, 1995 Abstract: The automatic seats in a vehicle are designed to minimize the seriousness of car-crash injuries during a frontal collision. When the vehicle collides against the other vehicle or any other stationary objects at a relative velocity of 40 Km/h or up, the backrest is pushed to recline backward by the action of the springs together with various mechanisms especially designed. Spring of either torsion type or tension type is used. The collision results in pulling the upper part of the body of the driver or the occupants fastened by the designed safety-belts to recline backwards. Thus, the pelvis, the chest and the head of an occupant sitting on this automatic safety car seat are moved away to the farmost and thus, can avoid striking with the deforming frontal parts of the car intruding by the frontal collision. The chest injuries and the brain damage can then be effectively avoided. The automatic safety seats in the vehicle are designed slightly different for either the front seat passengers or the rearseat passengers where modification is necessary for the rearseat. The seat-belts are specially designed to help dissipating the impact energy of the collision to minimize harm to the upper part of occupant's body fastened. Excerpt(s): In an event of a frontal collision, the front part of the car shows high degree of deformation which forces the steering column together with the instrument panel inwards. The steering wheel is often pushed downwards. Accordingly, several safety features have been developed over the past years in attempt to reduce serious injuries to the vehicle occupants. Numerous safety devices such as the seat-belts with various modifications (U.S. Pat. Nos. 5,411,319; 5,330,228; 5,288,104; 4,946,197; 4,909,539 and EP 0 529 265 A1), and the air bags (U.S. Pat. Nos. 5,409,262; 5,288,104; 5,251,931 and 5,011,181) have been used. Those air bags although have been provided variously of so many different designs, they are mostly installed in the interior of the steering wheel assembly which is a point most prone to serious damage upon a car accident of frontal collision type. Many of them are actuated electronically whose function can be easily damaged during a collision. These all reasons when put together result in surprisingly too many reports on functioning failure of the air bag system. In addition, although the air bag is supposed to absorb the impact energy created during the collision and reduces the severity of injuries to the human body, this is found not to be always true. Due to the fact that at high speeds as high as or over 40 Km/h upon collision, the impact is so great that the air bag itself can cause damage to the occupant's body and visceral organs especially in the thoracic portion. Only short time after the air bag restraint systems have been introduced in the market, it has been very well realized that air bags are quite poor device to minimize the damages to the occupant's body. Improvement and alternatives have been therefore variously proposed with the center of interest pointed at the design of the vehicle seats in attempt to minimize the damage on the occupant's body. The new concept currently and presently proposed is to bring the occupant's body especially the upper part and the head away backwards the farmost possible to avoid striking with the incoming deforming frontal part of the car such that damages to the

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brain and the thoracic portion of the occupant can be minimized. Various designs of the vehicle seats have been proposed. Many lifting mechanisms have been described (U.S. Pat. No. 5,340,185 and German patent document DE-OS 33 37 232) for raising a front or leading edge section of a seat cushion. The assembly is connected to the lifting mechanism via different means, so that during a significant frontal impact to the vehicle, the front edge section of the seat is raised. A French patent document FR-PS 1 012 718 describes how to tip a vehicle seat backwards, about a transverse axis of the motor vehicle. In the event of a frontal impact, a connecting rod is moved into the passenger compartment and detaches the seat from its front support, hence tipping the seat such that it rotates backwards about a transverse axis passing through the rear seat support. Since the connecting rod itself is prone to bending and jamming during its rearward movement, the actuation is thus unreliable. Furthermore, the connecting rod itself can be a serious safety hazard to the occupant while penetrating into the passenger compartment to detach the seat from its front support. Another German patent document DE-PS 36 31 881 discloses a vehicle seat whose front edge section is stiffened during a significant frontal impact to the vehicle. The stiffening action is achieved by a rather complex mechanism involving a stretching gear, a pyrotechnical drive, several actuating cables and more, which is rather too elaborate and costly. In fact, the more complex a system is, the more likely it will fail to function at the moment the action is needed as if there is just a small damage to only one single component of the whole system. Yet another French Patent FR-A 2 261 158 describes a prior art safety mechanism for a vehicle seat using a lifting mechanism to raise the front edge section of a vehicle seat to improve the supporting action of the seat cushion by enlarging the effective wedge angle. A support is provided with one end hinged to the stationary pivot joint attached to a seat support connection disposed on a lower middle portion of the seat cushion. The support is held by a spring to be in a lowered operating position. During a frontal collision, the seat moves forward by an inertia force associated with the seat and the passenger sitting thereon which overcomes the spring force. The support is then pivoted generally upward and thereby the seat's front edge. These all patents describing the lifting front edge of a vehicle seat suffer from the fact that upon lifting the front edge of a seat, the knees and the legs of the occupant are also lifted up to the level prone to being seriously injured by the intruding front panel. In addition, the knees and the legs and the airbag, if any, would be compressed onto the occupant's upper portion and thus may cause unnecessary additional serious injuries. In Japanese Patent Second Provisional Publication 61-35017 and Japanese Utility Model First Provisional Publication 3-26652, various seats have been disclosed using the reinforcing members installed in seat cushions and/or seatbacks to reinforce them. Such reinforced seats quite often have failed to exhibit the desired performance, in addition to making it uncomfortable for an occupant to sit on. Yet, another U.S. Pat. No. 5,407,244 discloses a safety seat and a safety arrangement of seats which can protect a seat occupant during a side-on vehicle collision. An electric-powered reclining device is used for pivoting the seatback connected to a rear end of the seat cushion to a desired angular position relative to the cushion. A microprocessor is used to control the power reclining device by limiting the angular position of the seatback of the second seat together with the seated occupant or to pivot the seatback of the second seat angularly corresponds to that of the first seat when no occupant on the second seat. Their system, however, is too complicated and operates electronically intended to provide safety during a side-on collision. The complexity of the system makes it questionable whether it would function properly to serve the invention purpose if a sudden action is needed where the great impact occurs might disturb all the electronic functions. While the U.S. Pat. No. 5,338,090 relates to a leg structure of a vehicle seat for absorbing a striking or impact energy exerted on a seat, the U.S. Pat. No. 5,409,262 discloses a safety system allowing a

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vehicle to collapse upon impact to absorb such impact energy with a seat tilting mechanism connected to the rear frame to tilt the passenger seat rearwardly. In the latter patent, a hood deflector is actuated to deflect the hood upwards acting as an additional barrier against any objects entering the passenger compartment. These patents described are all focused at bringing away the body of the occupant rearwards. The former one may be able to tilt the seat rearwards for only a too limit distance and the latter one is too costly in design. Accordingly, a need for a simple, inexpensive, yet highly effective means to minimize the severity of the injuries to an occupant in a vehicle upon a frontal collision has to be fulfilled since no type of accident reportedly represents a greater hazard to drivers and all the occupants than a frontal collision where the car body and the occupants encounter extreme loads. The present invention proposes herein a system to fulfill such need which can overcome all the above mentioned problems of the prior arts. By the action of the two springs flanking both sides of a vehicle seat and connecting to its backrest, during a significant frontal impact to a vehicle, the backrest together with its occupant fastened onto with the presently designed seat-belts, can be suddenly pushed rearwards to recline to the farmost position, thus striking of the head and the upper part of the occupant's body can be avoided successfully and effectively by a rather inexpensive mechanism. There is no need for any electronic or electrical devices. The mechanism involves only the simple mechanical and dynamic means by a well and skillful designed spring set connecting between the rear end of the seat cushion and the lower portion of its backrest. Web site: http://www.delphion.com/details?pn=US05810417__ •

Barbiturates as safening agents in conjunction with NMDA antagonists Inventor(s): Olney; John W. (1 Lorenzo La., Ladue, MO 63124) Assignee(s): none reported Patent Number: 5,474,990 Date filed: July 22, 1991 Abstract: Certain barbiturates have been shown to completely prevent the neurotoxic injury to cerebrocortical neurons that can be caused by NMDA antagonists. The use of barbiturates as "safening agents" allows NMDA antagonists (including powerful NMDA antagonists such as MK-801) to be used safely as neuroprotectants to prevent brain damage due to hypoxia/ischemia caused by strokes, cardiac arrest, perinatal asphyxia, and various other conditions. Excerpt(s): This invention is in the fields of pharmacology and neurology. It relates to two different classes of receptors on the surfaces of neurons, known as NMDA receptors, which are triggered by N-methyl-D-aspartate (NMDA), and GABA receptors, which are triggered by gamma-aminobutyric acid (GABA). This invention involves the use of NMDA antagonists (i.e., agents which block activity at NMDA receptors) as therapeutic agents which can prevent excitotoxic brain damage and nerve cell death during stroke, cardiac arrest, perinatal asphyxia, drowning, and various other events. Unfortunately, the currently available NMDA antagonists, when used for such purposes, exert toxic side effects that can kill or permanently damage neurons in certain regions of the brain. This invention relates to the discovery that certain types of barbiturates which function as GABAmimetic agents (i.e., they trigger activity at GABA receptors) function as "safening agents" to reduce the damaging side effects of NMDA antagonists. By reducing the damage caused by NMDA antagonists, the barbiturates

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disclosed herein allow the safe use of NMDA antagonists to treat stroke, cardiac arrest, and other conditions. Web site: http://www.delphion.com/details?pn=US05474990__ •

Brain damage monitor Inventor(s): Williams; Christopher Edward (C/- Auckland UniServices Ltd, UniServices House, 58 Symonds St., Auckland, NZ) Assignee(s): none reported Patent Number: 5,807,270 Date filed: December 18, 1996 Abstract: An impedance monitor (100) is adapted for use in long-term monitoring of intracellular (neuronal) swelling in the brains (102) of mammals over periods of hours or days. The monitor has an electrically isolated current source (103), supplying a one microampere AC square waveform at 200 Hz. This current is passed through an outer pair of electrodes (104, 105) of a four-electrode arrangement having skin electrodes, extradural electrodes, or in some cases surface electrodes embedded in surgical retractors. Sensing electrode pairs (107, 108) may also detect EEG activity. Impedance changes are displayed graphically (109). Multiple electrode arrays may be used for localization of affected portions of the brain. Even trans-cranially measured impedances reflect intracellular oedema and are clinically useful indicators of treatment efficacy and outcome in cases of ischaemia, asphyxia, trauma, and the like. Excerpt(s): This invention relates to the monitoring and management of oedema in certain tissues, in particular intracellular oedema within the brains of mammals, and the assessment of swelling following injury by me of electrical impedance measurements. It is adapted for long-term monitoring using suitable externally applied electrodes and also short-term monitoring of tissue trauma during surgery where surgical tools having embedded electrodes are used. The invention discloses mpedance monitoring equipment, and a method for use of the equipment. The monitoring of patients with acute head injuries, whether caused by externally induced trauma such as birth or accident, or by circulatory problems, has hitherto relied upon clinical signs but these may not appear until a time at which the damage may have become at least partially irreversible. Electroencephalography (EEG) tests preferably also including a frequency analysis device to reduce the data and indicate electrical activity is more suitable, though impractical outside a controlled environment. (Reliable EEG measurements require electrical screening from outside interference, a motionless subject, and relatively complex equipment). Web site: http://www.delphion.com/details?pn=US05807270__

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Brain damage testing Inventor(s): Craine; James F. (116 Kaapuni Dr., Kailua, HI 96734) Assignee(s): none reported Patent Number: 4,086,710 Date filed: October 25, 1973

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Abstract: A person's memory of sequences is tested by shifting a relationship between switches and colored lights which they control. Switches in a row light colored lamps in a fixed sequence. A two part circular switch with opposed contacts equal in number to the switches or colors may be turned to shift the sequence of colors which the switches control. One part of the circular switch may be inverted so that the sequence of colors controlled by the switches may be reversed and may be shifted in reversed order. Inserts positioned between the two parts of the circular switch change the sequential relationships of colored lights and switches. Excerpt(s): The speed at which one masters new problems and the amount of mistakes that one makes in achieving correct results are recognized in the prior art as useful measurements. Such tests are appreciably aided by the use of lights and switches to control the lights. Prior art devices include the Intelligence Testing Apparatus disclosed by James F. Craine in U.S. Pat. No. 2,870,549 issued Jan. 27, 1959. Dr. Craine's apparatus as described in that patent tests an individual's capability to adapt to changing situations. An individual is required to reproduce a geometric pattern from a card by lighting lamps in that pattern. When one switch arrangement is mastered, the arrangement is radically turned upside down or sideward in either direction, or a mirror image is created. The apparatus has the possibility of randomly arranging the switches so that their geometric arrangement has no relation to the geometric arrangement of lamps to be lighted. Another prior art device employs lights of varied colors on a board. Switches are set to light three lamps in a pattern. A subject lights a fourth light to complete the pattern. There is no unique switch-lamp relationship to present a problem to the subject. Web site: http://www.delphion.com/details?pn=US04086710__ •

Carbamoyl-2-pyrrolidinone compounds Inventor(s): Hasegawa; Etsuo (Honjo, JP), Honna; Takaji (Tokyo, JP), Kajitani; Makoto (Saitama, JP), Kasahara; Nobuo (Tokushima, JP), Kawaguchi; Akihiro (Honjo, JP), Toide; Katsuo (Tokushima, JP), Yamamoto; Junji (Tokushima, JP), Yasumoto; Mitsugi (Honjo, JP) Assignee(s): Taiho Pharmaceutical Company, Limited (Tokyo, JP) Patent Number: 5,447,944 Date filed: March 22, 1994 Abstract: The present invention provides carbamoyl-2 -pyrrolidinone compounds useful as medicaments for improving cerebral functions and activating cerebral metabolism or protecting against anoxic brain damage. Excerpt(s): The present invention relates to novel carbamoyl-2-pyrrolidinone compounds, and cerebral function improving compositions and cerebral metabolism activating or anoxic brain damage protecting compositions comprising the compound. Carbamoyl-2-pyrrolidinone compounds are disclosed as herbicides in French Patent No. 2018820, as horticultural fungicides in JP-A-52-25026, or as agents for improving the quality of citrus fruits in JP-A-54-66265, 55-81857 and 55-153763, whereas nothing has been described about their use in compositions for improving cerebral functions and in compositions for activating cerebral metabolism or protecting anoxic brain damage as disclosed in the present invention. Furthermore, even if some of the compounds defined in the claims appended hereto should be included in the group of compounds represented by the broad general formulae in the above prior-art literature, they have

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been deleted during the examination procedures, or are not identified in any way in the detailed description of the specifications. Thus, they have not been disclosed in any way specifically and are novel compounds. The other compounds of the present invention are novel compounds which have not been described in any literature. Web site: http://www.delphion.com/details?pn=US05447944__ •

Compounds for treatment of cholinergic neurotoxins Inventor(s): Olney; John W. (Ladue, MO) Assignee(s): Washington University (St. Louis, MO) Patent Number: 5,011,853 Date filed: January 26, 1990 Abstract: This invention discloses the use of muscarinic anti-cholinergic agents for reducing or preventing the toxic or lethal effects (such as seizures and brain damage) caused by cholinergic neurotoxins. The parent application disclosed that certain muscarinic anti-cholinergics classified as aryl-cycloalkyl-alkanolamines are effective in reducing or preventing the neurotoxicity of soman, a powerful nerve gas. This invention extends that discovery and identifies other muscarinic anti-cholinergic agents, including scopolamine, benactyzine, and benztropine, as highly effective and useful agents to protect against two major classes of cholinergic neurotoxins (acetylcholine receptor agonists, and cholinesterase inhibitors). Analogs of those compounds may also be effective in protecting against cholinergic neurotoxicity, as can be determined through routine screening tests using rats. It has been discovered that protection against seizures induced by lithium and pilocarpine (drugs that are widely available and used frequently in research) provides a good indicator of effectiveness against soman, a nerve gas which is heavily restricted and extremely dangerous. Excerpt(s): This invention is in the fields of pharmacology and neurology. It relates specifically to compounds and methods for reducing the neurotoxic effects of cholinergic agents. The background of the invention is discussed in the parent application Ser. No. 398,721, which was invented by the same inventor and is assigned to the same assignee. The contents of that patent application are incorporated herein by reference. The parent application describes the toxic and lethal effects of cholinergic neurotoxins such as pilocarpine, an experimental drug which is of interest to researchers studying the causes and mechanisms of epilepsy (Clifford et al 1987; complete citations are provided below), and soman, a nerve gas that poses a threat in chemical warfare (McLeod et al 1984). Either of those substances can cause continuous seizure activity which persists for hours and causes disseminated brain damage, which typically is fatal unless adequately treated. The parent application discloses that a class of compounds referred to as aryl-cycloalkyl-alkanolamines are effective in protecting lab animals against convulsions or death when they are exposed to soman, even when the arylcycloalkyl-alkanolamines are administered only after the onset of seizure activity. Those compounds have a biological activity which can be classified as muscarinic anticholinergic activity, since they antagonize (i.e, inhibit the activation or effects of) the muscarine class of acetylcholine receptors on the surfaces of neurons in the central nervous system. Aryl-cycloaklyl-alkanolamine drugs include procyclidine, biperiden, triperiden, and trihexyphenidyl. Web site: http://www.delphion.com/details?pn=US05011853__

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Drug system Inventor(s): Kloog; Yoel (Herzelia, IL), Sokolovsky; Mordechai (Tel Aviv, IL) Assignee(s): Ramot - University Authority for Applied Research and Industrial (Tel Aviv, IL) Patent Number: 4,994,446 Date filed: January 3, 1989 Abstract: The invention relates to a drug system for the treatment and alleviation of the symptoms of epilepsy; as anticonvulsant agent, and for the prevention or alleviation of brain damage due to strokes. The drug system comprises as active ingredient a compound such as MK-801, phencyclidine or as thienyl-cyclohexyl-piperidine (TCP), which is administered in such a manner that it encounters and binds to the N-methyl-Daspartate (NMDA) receptor channels. This is in the presence of glutamate or glycine, or similarly acting amino-acid, which is either present in the patient, or which can be administered separately. The effective drug can be effectively locked in the receptor channels by means of a glutamate antagonist, such as AP-5. Excerpt(s): The present invention relates to a novel drug system for use in the treatment of, and for the alleviation of the symptoms of a variety of diseases and states of ill-health in mammals, and especially in humans. Amongst others the drug system is of use an antiepileptic, as anticonvulsant, for the preparation or alleviation of brain damage caused by strokes etc. The drug system is based on a combination of drugs of the MK801 and PCP type, in combination with, or in sequential administration of certain excitatory amino acids, such as glutamate, glycine and aspartate, as well as related analogs, which substantially increase the rate of binding of the effective drug to the specific receptor. MK-801 is bound to the N-methyl-D-aspartate receptor, and it would seem that MK-801 acts as steric blocker of the NMDA channel. When a prolonged action of the drug is required, there is further administered an antagonist to such amino-acid, such as a glutamate antagonist, resulting in the freezing of the drug in the channel. The activity of PCP (phencyclidine) is discussed in NIDA Notes 2 (1987) 9. This article sets out the binding of PCP to two different receptors of the nerve membranes. MK-801, (+)5-methyl-10,11-dihydro-5H-dibenzo-[a,d]-cyclohepten-5,10-imine maleate is known as potent anticonvulsant, and it is also known that MK-801 is a potent N-methyl-Daspartate (NMDA) antagonist: Proc. Nat. Acad. Sci. U.S.A. 83 (1986) 7104. The kinetic characterization of the phencyclidine-NMDA receptor interaction, setting out evidence of a steric blockage of the channel was described in Biochem. 27 (1988) 843. It is known that there exist a number of excitatory amino acid antagonists, some of which block the neurotoxic activity of N-methyl-aspartate (NMDA). Amongst the most effective of these are phencyclidine (PCP) and MK-801, see Europ. J. Pharmac. 141 (1987) 357. Web site: http://www.delphion.com/details?pn=US04994446__

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Method for determination of weights, suitable for elimination, of a neural network using a computer Inventor(s): Neuneier; Ralph (Munchen, DE), Tresp; Volker (Munchen, DE), Zimmermann; Hans-Georg (Starnberg/Percha, DE) Assignee(s): Siemens Aktiengesellschaft (Munich, DE) Patent Number: 6,311,172 Date filed: September 23, 1998

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Abstract: The training phase of a neural network NN is stopped before an error function, which is to be minimized in the training phase, reaches a minimum (301). A first variable (EG) is defined using, for example, the optimal brain damage method or the optimal brain surgeon method, on the assumption that the error function is at the minimum. Furthermore, a second variable (ZG) is determined which provides an indication of the manner in which the value of the error function varies when a weight (w.sub.i) is removed from the neural network (NN). The first variable (EG) and the second variable (ZG) are used to classify the weight (w.sub.i) as being suitable or unsuitable for removal from the neural network (NN). Excerpt(s): The removal from a neural network of weights that have only a small information content in terms of training data to be approximated considerably improves the generalization characteristic of the neural network whose dimensionality has been reduced. Furthermore, a smaller number of training data items is required to train the reduced neural network. The rate of learning and the rate of classification in the test phase are also increased. The removal of weights from a neural network is called pruning. Various pruning methods are known. For example, in a first prior art A. Zell, Simulation Neuronaler Netze (Simulation of neural networks), (1994), Addison-Wesley, 1st Edition, ISBN 3-89319-554-8, pp. 319-328 discloses a so-called optimal brain damage (OBD) method. In this method, the second derivatives of the error function are used on the basis of the individual weights in the neural network, in order to select those weights which should be removed. This method has the disadvantage that it operates only subject to the precondition that the training phase has converged, that is to say that the error function, which is minimized during the training phase, has reached a local minimum or a global minimum of the error function. In this case, the disadvantage of this known method is primarily that, using this method, one may in general investigate only considerably overtrained neural networks for weights to be removed. Web site: http://www.delphion.com/details?pn=US06311172__ •

Method for determining bilirubin concentration from skin reflectance Inventor(s): DeWitt; David P. (West Lafayette, IN), Hannemann; Robert E. (West Lafayette, IN), Wiechel; John F. (Houston, TX) Assignee(s): Purdue Research Foundation (West Lafayette, IN) Patent Number: 4,029,085 Date filed: March 26, 1976 Abstract: A method is disclosed for determining the bilirubin concentration in the blood serum of a person from measurement of the spectral reflectance of the skin. The disclosed method detects the severity of jaundice, a common neonatal condition, and enables determination of the type of treatment regimen needed to prevent the bilirubin level from becoming sufficiently high to cause kernicterus which can result in brain damage. The method includes measuring the reflectance of the skin within a predetermined frequency spectrum, and more particularly at a number of specific wavelengths in the visible portion of the spectrum. Excerpt(s): This invention relates to a method for detecting jaundice and establishing the level of severity by direct determination of the bilirubin concentration in the blood serum from measurement of the spectral reflectance of the skin at selected wavelengths. Jaundice, as is well known, is a condition one of the characterizations of which is yellowness of the skin of a person and is due to deposition of bile pigment resulting

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from excess bilirubin, known as hyperbilirubinemia, in the blood. Bilirubin, in its indirect form, is potentially harmful, for example, to the central nervous system of a newborn infant. The severity of the damage caused is related to the level of bilirubin in the serum of the blood. In its most severe form, this damage is called kernicterus. After jaundice has been detected, treatment regimens, such as exchange transfusions and phototherapy, are commonly used, when considered necessary, to prevent levels of bilirubin known to cause kernicterus. It is currently felt that lower levels of bilirubin may also be one of the causes for minimal brain dysfunction, a condition thought to be responsible for a large majority of learning disorders in children. If such a relationship is true, early detection and treatment of lower level hyperbilirubinemia becomes even more critical. Web site: http://www.delphion.com/details?pn=US04029085__ •

Method for diagnosing and distinguishing stroke and diagnostic devices for use therein Inventor(s): Jackowski; George (Kettleby, CA) Assignee(s): Syn X Pharma (Mississauga, CA) Patent Number: 6,235,489 Date filed: February 22, 2000 Abstract: A method for determining whether a subject has had a stroke and, if so, the type of stroke which includes analyzing the subject's body fluid for at least four selected markers of stroke, namely, myelin basic protein, S100 protein, neuronal specific enolase and a brain endothelial membrane protein such as thrombomodulin or a similar molecule. The data obtained from the analyses provide information as to the type of stroke, the onset of occurrence and the extent of brain damage and allow a physician to determine quickly the type of treatment required by the subject. Excerpt(s): This application hereby claims foreign priority benefits under 35 USC 119(a)(d) of Canadian Patent Application 2,263,063, filed Feb. 26, 1999. This application is directed to a method for diagnosing whether a subject has had a stroke and, if so, differentiating between the different types of stroke. More specifically, the method includes analyzing the subject's body fluid for at least four selected markers of stroke. There are also described diagnostic devices and kits for use in the method. The impact of stroke on the health of human beings is very great when considered in terms of mortality and even more devastating when disability is considered. For example, stroke is the third leading cause of death in adults in the United States, after ischemic heart disease and all forms of cancer. For people who survive, stroke is the leading cause of disability. The direct medical costs due to stroke and the cost of lost employment amount to billions of dollars annually. Approximately 85% of all strokes are ischemic (thrombotic and embolic) with the remainder being hemorrhagic. Web site: http://www.delphion.com/details?pn=US06235489__

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Method of reducing brain damage resulting from seizures Inventor(s): Ballough; Gerald Paul Harding (Drexel Hill, PA), Filbert; Margaret Gillespie (Ellicott City, MD) Assignee(s): The United States of America as represented by the Secretary of the Army (Washington, DC) Patent Number: 6,211,230 Date filed: January 19, 2000 Abstract: A method of reducing brain damage resulting from seizures caused by an organophosphorus nerve agent includes administering to a patient a therapeutically effective amount of HU-211. The organophosphorus nerve agent may be GB (sarin), GD (soman), GA (tabun) or GF. The therapeutically effective amount of HU-211 is in the range of about 48 mg to about 200 mg per day. Excerpt(s): The present invention relates in general to reducing brain damage resulting from seizures and in particular to reducing brain damage resulting from seizures caused by nerve agents. One aspect of chemical warfare involves exposing the enemy to nerve agents. The best defense to nerve agent exposure is, of course, to prevent the soldier from being exposed to the nerve agent. However, exposure to nerve agents may occur and must be treated. Certain nerve agents cause seizures. Examples of organophosphorus nerve agents that cause seizures are GB (sarin), GD (soman), GA (tabun) and GF. It cannot be certain that every victim on the chemical battlefield will receive the fielded therapy regimen (atropine, 2-PAM, diazepam) within the prescribed window of opportunity. These victims may experience prolonged seizure episodes lasting one or more hours. Availability of a drug that will stop development of the lesions after prolonged seizure epilectus would be a valuable adjunct to the current therapeutic regimens. Throughout the specification, certain publications are identified parenthetically by author and date. A complete identification of these publications is given at the end of the specification. The publication entitled "Neuroprotective Effects of HU-211 on Brain Damage Resulting from Soman-induced Seizures" by Filbert, M. G.; Forster, J. S.; Smith, C. D.; Ballough, G. P.; Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, Oct. 1998, is hereby expressly incorporated by reference. Exposure to high concentrations of the nerve agent soman (pinacolylymethylphosphonofluoridate), an organophosphorus (OP) inhibitor of cholinesterases, leads to the development of seizures (Taylor, 1985) and brain damage (Shih and McDonough, 1997; Ballough el al. 1998). Seizure-related brain damage (SRBD) resulting from exposure to soman is considered to be excitotoxic (Olney et al., 1983). Soman-induced seizures are initiated by the high levels of acetylcholine that accumulate as a result of the irreversible inhibition of acetylcholinesterase (AChE). As the duration of seizures increases, excitatory amino acids released by elevated levels of acetylcholine assume control over the seizures and are maintained by this neurotransmitter system (Shih and McDonough, 1997; Olney et al., 1983; Sparenborg et al., 1992). This conclusion is supported by studies demonstrating that soman-induced seizures and the resulting brain damage can be ameliorated by administration of antagonists of N-methyl-Daspartate (NMDA) such as MK-801 (Braitman and Sparenborg, 1989; Clifford et al., 1989, 1990). Because MK-801 produces neurotoxic effects (Fix et al., 1993), it is not likely to be useful clinically. Therefore, a need exists for a clinically useful neuroprotectant to reduce brain damage caused by organophosphorus nerve agent-induced seizures. Web site: http://www.delphion.com/details?pn=US06211230__

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Method of treating ischemic, hypoxic and anoxic brain damage Inventor(s): Jacobson; Kenneth A. (Silver Spring, MD), Von Lubitz; Dag K. J. E. (Brighton, MI) Assignee(s): The United States of America as represented by the Departmant of Health and (Washington, DC) Patent Number: 6,316,423 Date filed: March 4, 1999 Abstract: The present invention provides a method of treating ischemic, hypoxic or anoxic brain damage in an animal comprising administering to an animal afflicted with ischemic, hypoxic, or anoxic brain damage, or an animal in imminent danger of suffering ischemic, hypoxic, or anoxic brain damage, a therapeutically effective amount of ADAC, or an analogue thereof. Excerpt(s): The present invention relates to a method of using certain adenosine amine congeners in the prevention and treatment of brain damage caused by ischemia, hypoxia, and anoxia. Despite intense research aimed at the development of effective therapeutic interventions, the means of preventing post-ischemic brain damage are still elusive. Among the numerous therapies currently under testing, approaches based on the stimulation of adenosine A.sub.1 receptors offer a substantial promise in reducing ischemia-related structural and functional damage (for recent reviews, see Rudolphi et al., Cerebrovasc. Brain Metab. Rev., 4, 346 (1992); Miller et al., J. Neurotrauma Suppl., 2, S563 (1992); von Lubitz et al., N.Y. Acad. Sci., 765, 163 (1995)). Multiple studies have shown that acute stimulation of adenosine A.sub.1 receptors results in decreased calcium influx, enhanced membrane hyperpolarization, suppressed release of neurotransmitters (including neurotoxic glutamate), and depression of NMDA receptor excitability (reviewed by Schubert et al., Neuroprotective mechanisms of endogenous adenosine action and pharmacological implications, in: Pharmacology of Cerebral Ischemia, ed. J. Krieglstein, H. Oberpichler (Wissenschaftliche Verlagsgesselsschaft mbH, Stuttgart), 417 (1990); Rudolphi et al., supra; von Lubitz et al., J. Mol. Neurosci., 2, 53 (1992); von Lubitz et al., Adenosine: a Drototherapeutic concept in neurodegeneration, in Neuroprotective agents: Clinical and Experimental Aspects, B. Trembly and W. Slikker, Jr., (eds.) Ann. N.Y. Acad. Sci., 765, 163 (1995a)). As a result of these effects, neuronal excitability and firing rate are reduced causing, in turn, a substantial reduction of brain metabolic demands (Schubert et al., supra). Web site: http://www.delphion.com/details?pn=US06316423__

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Methods and resuscitation

pharmaceutical

compositions

for

enhanced

cardiopulmonary

Inventor(s): Gold; Barbara S. (Minneapolis, MN), Lurie; Keith G. (Minneapolis, MN) Assignee(s): Regents of the University of Minnesota (Minneapolis, MN) Patent Number: 5,588,422 Date filed: November 17, 1992 Abstract: Methods and pharmaceutical compositions for resuscitating patients suffering from cardiac arrest are disclosed. The methods comprise the performance of cardiopulmonary resuscitation techniques which result in active inducement of venous blood transport into the heart and arterial blood transport from the heart. During the

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performance of such techniques, the patient is administered with an amount of an arterial constrictor sufficient to increase arterial blood pressure and with an amount of a venodilator sufficient to enhance arterial blood flow to the brain and heart. Pharmaceutical compositions comprise both the arterial constrictor and venodilator present in a single formulation. The methods are found to both enhance patient survival and reduce heart and brain damage. Excerpt(s): The present invention relates generally to methods and pharmaceutical compositions for the enhanced performance of cardiopulmonary resuscitation techniques. More particularly, the present invention relates to the administration of certain pharmaceutical compositions to a patient undergoing cardiopulmonary resuscitation techniques which result in the active transport of venous blood back to the patient's thorax and heart. Sudden cardiac arrest is a major cause of death worldwide and can arise from a variety of circumstances, including heart disease, electrical shock and other trauma, suffocation, and the like. To enhance patient survival and reduce the likelihood of damage to the brain and heart resulting from oxygen deprivation, it is essential that a patient's respiration and blood circulation be restored as soon as possible. Over the years a number of artificial resuscitation techniques have been developed with such objectives in mind. Of particular interest to the present invention, cardiopulmonary resuscitation (CPR) techniques have been developed which rely on external chest compression. In particular, manual CPR techniques rely on the manual application of a downward force on the patient's chest in order to force blood from the heart and expel air from the lungs. Ventilation by either mouth-to-mouth or mechanical techniques is performed concurrently with the chest compression in order to force air back into the patient's lungs. Such manual CPR techniques, however, partially rely on the natural elasticity of the chest in order to actively draw venous blood back into the heart, which turns out to be highly inefficient. Long term survival in cardiac arrest patients who have undergone standard CPR is usually below 10%. Web site: http://www.delphion.com/details?pn=US05588422__ •

Rat or mouse exhibiting behaviors associated with human schizophrenia Inventor(s): Jaskiw; George E. (Lyndhurst, OH), Lipska; Barbara K. (Annandale, VA), Weinberger; Daniel R. (Washington, DC) Assignee(s): The United States of America as represented by the Secretary of the (Washington, DC) Patent Number: 5,549,884 Date filed: October 28, 1992 Abstract: This invention provides a unique and surprisingly accurate animal model for human schizophrenia. The animals are brain damaged while prepubescent. The brain damage consists of a ventral hippocampus lesion induced by exposure of the hippocampus region to a neurotoxin. When the animal reaches puberty, abnormal behavior and a number of biological phenomena associated with schizophrenic symptoms emerge. These animals are useful for assaying pharmaceutical compounds for anti-schizophrenic activity. Excerpt(s): The present invention provides methods of assaying the anti-schizophrenic potential of pharmaceutical compositions. The methods comprise the following steps: (a) inducing or creating a lesion in the ventral hippocampus of a prepubescent mammal, i.e., a mammal which has not yet reached puberty, using a neurotoxin so that the lesion

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is able to induce abnormal behavior in postpubescent mammals; (b) nurturing or raising the mammal until postpuberty, i.e., until the mammal reaches sexual maturity; (c) administering to the mammal a pharmaceutical composition thought to have antischizophrenic properties; and (d) determining the mammal's response to the pharmaceutical composition. The anti-schizophrenic potential of the pharmaceutical composition is assessed by objectively measuring the mammal's behavior following administration of the pharmaceutical composition. The mammal's behavior is measured or monitored using standard tests well-known by those skilled in the art. The behaviors which are measured typically include the following: locomotor activity in a cage, in unfamiliar or novel environments, after injection or administration of drugs (e.g., amphetamines), after mild electric shock, after exposure to sensory stimuli (e.g., noise), in water (swim test), after immobilization, in social interactions, and in various learning and reward paradigms. The present invention also provides methods of assaying the anti-excessive limbic dopamine activity potential of pharmaceutical compositions. The methods comprise the following steps: (a) inducing a lesion in the ventral hippocampus of a prepubescent mammal using a neurotoxin so that the lesion is able to induce excessive limbic dopamine activity in postpubescent mammals; (b) nurturing or raising the mammal until postpuberty; (c) administering a pharmaceutical composition thought to have anti-excessive limbic dopamine activity; and (d) determining the mammal's response to the pharmaceutical composition. The anti-excessive limbic dopamine activity potential of the pharmaceutical composition is assessed by objectively measuring the mammal's behavior following administration of the pharmaceutical composition. The mammal's behavior is measured or monitored using standard tests well-known by those skilled in the art. Web site: http://www.delphion.com/details?pn=US05549884__ •

Rehabilitative garment for persons afflicted with brain damage Inventor(s): Harlem; Davida P. (3564 Chimney Swift Dr., Huntington Valley, PA 19006), Harlem; Steven H. (3564 Chimney Swift Dr., Huntington Valley, PA 19006) Assignee(s): none reported Patent Number: 5,799,328 Date filed: May 5, 1997 Abstract: A garment designed to help in the physiological and psychological rehabilitation of a hemiplegic patient. Disposed on the shirt sleeves and the pants legs of the garment are graspable elements, such as hoops or handles. Within each of the shirt sleeves and pants legs are reinforced areas that are joined to the graspable elements. The reinforced areas branch out across the material of the shirt sleeve or the pants leg. As a result, when a pulling force is applied to the graspable element, the force is transferred throughout the sleeve or leg by the reinforced areas. This enables a sleeve to be pulled onto an arm or a pants leg to be pulled onto a leg by applying a pulling force to just one position, thereby providing the ability for a person to use a partially disabled arm when dressing. In a preferred embodiment, small weights are positioned within the garment at various points along the sleeves and pants legs. The weights provide an increased tactile sensation to the arms and legs as the arms and legs are moved. The enhanced tactile sensation promotes improved proprioception, thereby helping a hemiplegic patient recognize and control the position of their limbs when moving his/her limbs. Color coding is provided on the garment to facilitate exteroception.

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Excerpt(s): The present invention relates to garments specifically designed for the disabled. More particularly, the present invention relates to garments for the upper and lower torso that promote the physical, cognitive and emotional rehabilitation of people with central nervous system impairments such as those caused by a cerebral vascular accident. Each year thousands of people incur brain damage due to trauma, stroke, transient ischemic attack, tumor growth and like afflictions. Often such brain damage results in hemiplegia or hemiparesis where the patient becomes either paralyzed or partially paralyzed on their right or left sides. Such damage to the central nervous system can have many symptoms other than partial or total physical paralysis. In many instances, a patient can experiences hemianopsia wherein the patient loses half a field of vision in both eyes. This commonly causes the patient to ignore or neglect items in the non-visible field. Since either the left or right field of vision is neglected, left/right directional confusion commonly occurs. Central nervous system damage, resulting in hemiparesis or hemiplegia also may be characterized by abnormal left/right proprioception, wherein tactile stimuli from the effected half of the body are not perceived by the brain in the normal manner. As a result, the patient may have difficulty in controlling muscle response in non-paralyzed portions of the effected body half. This leads to difficulties in maintaining balance and makes it difficult for a patient to perceive the position of his/her limbs. As can be understood, a patient having difficulties perceiving and moving half of his/her body faces tremendous difficulties in dressing himself/herself. Dressing oneself is one of those fundamental activities that is greatly disheartening and frustrating to a person newly afflicted with central nervous system damage. However, dressing oneself is also one of those fundamental activities that must be mastered before the patient can again become self-sufficient. As such, the ability of a patient to dress himself/herself is a milestone that raises the emotional well being of the patient by showing him/her that he/she is well on his/her way to recovery and selfsufficiency. Web site: http://www.delphion.com/details?pn=US05799328__ •

Substituted 4,6-di-tertiary-butyl 5-hydroxy-pyrimidines Inventor(s): Belliotti; Thomas R. (Phoenixville, PA), Connor; David T. (Ann Arbor, MI), Kostlan; Catherine R. (Saline, MI) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 5,356,898 Date filed: July 1, 1993 Abstract: The present invention is novel compounds which are 4,6-di-tertiary-butyl-5hydroxy-1,3-pyrimidine substituted 1,2,4- and 1,3,4-thiadiazoles and oxadiazoles, and 1,2,4-triazoles, and pharmaceutically acceptable additions and base salts thereof, pharmaceutical compositions and methods of use therefor. The invention compounds are now found to have activity as inhibitors of 5-lipoxygenase and/or cyclooxygenase providing treatment of conditions advantageously affected by such inhibition including inflammation, arthritis, pain, fever, and particularly rheumatoid arthritis, osteoarthritis, other inflammatory conditions, psoriasis, allergic diseases, asthma, inflammatory bowel disease, GI ulcers, cardiovascular conditions, including ischemic heart disease and atherosclerosis, and ischemia-induced cell damage, particularly brain damage caused by stroke. They can also be used topically for treating acne, sunburn, psoriasis, and eczema. Also included are leukotriene mediated pulmonary, gastrointestinal, inflammatory, dermatological, and cardiovascular conditions. The disclosed compounds

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also have potential utility as antioxidants. The preferred use is in treating inflammatory conditions. Thus, the present invention is also a pharmaceutical composition or method of manufacturing a pharmaceutical composition for the use of treating the noted conditions. Excerpt(s): The present invention is novel compounds which are 4,6-di-tertiary-butyl-5hydroxy-1, 3-pyrimidine substituted 1,2,4- and 1,3,4-thiadazoles and oxadiazoles, and 1,2,4-triazoles, and pharmaceutically acceptable acid addition or base salts thereof, pharmaceutical compositions and methods of use therefor. The invention compounds are now found to have activity as inhibitors of 5-lipoxygenase and/or cyclooxygenase providing treatment of conditions advantageously affected by such inhibition including inflammation, arthritis, pain, fever, and particularly rheumatoid arthritis, osteoarthritis, other inflammatory conditions, psoriasis, allergic diseases, asthma, inflammatory bowel disease, GI ulcers, cardiovascular conditions, including ischemic heart disease and atherosclerosis, and ischemia-induced cell damage, particularly brain damage caused by stroke. They can also be used topically for treating acne, sunburn, psoriasis, and eczema. Also included are leukotriene mediated pulmonary, gastrointestinal, inflammatory, dermatological, and cardiovascular conditions. The disclosed compounds also have potential utility as antioxidants. The preferred use is in treating inflammatory conditions. Thus, the present invention is also a pharmaceutical composition or method of manufacturing a pharmaceutical composition for the use of treating the noted conditions. 3,5-Ditertiarybutyl-4-hydroxyphenyl substituted 1,2,4- and 1,3,4-thiadiazoles and oxadiazoles, and 1,2,4-triazoles are known to provide activity as inhibitors of 5lipoxygenase and/or cyclooxygenase. See U.S. application Ser. No. 07/277,171, filed Nov. 29, 1988, now abandoned, and U.S. application Ser. No. 07/426/814, filed Oct. 30, 1989, now pending. Pyrimidine is not noted in this reference. Structure activity relationships of certain ditertiaryphenols and homologs thereof are discussed by Lazer, E. S., et al in "Effect of Structure on Potency and Selectivity in 2,6-Disubstituted 4-(2Arylethenyl)phenol Lipoxygenase Inhibitors of J. Med. Chem. 1990, 33, 1892-1998. Again, pyrimidines are not noted in this reference and so compounds therein differ from the present invention. Numerous references disclose 2-amino-5-hydroxy pyrimidines. Compounds having other N containing groups in place of the amino are also disclosed, however, in each such compound all attachments are through the N. Such disclosed pyrimidines may also be substituted at the 4- and/or 6-positions with various groups including alkyls. No reference shows a tertiarybutyl in both the 4- and the 6-positions in combination with a 5-hydroxy together with any group other than the N or S containing substituent in the 2-position as now found in the present invention. For example, UK patent application number 2045736 and the Bioch. J. 1951, 48, p. 400 shows the simple 2amino-5-hydroxy-4,6-dimethylpyrimidine. Other substituted 2-aminopyrimidines are shown in European patent application numbers 89312736.5 and 86305466.4 (equivalent to U.S. Pat. No. 4,711,888), European publication numbers 319170, 233416, 164204, and U.S. Pat. Nos. 4,859,679 and 4,940,712. Web site: http://www.delphion.com/details?pn=US05356898__ •

Support harness Inventor(s): Jordan; Ruth Frances (3095 Monticello Blvd., Cleveland Hts., OH 44118) Assignee(s): none reported Patent Number: 4,050,737 Date filed: August 30, 1976

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Abstract: A support harness for a child who, due to brain damage or disease, lacks trunk or head control sufficient to achieve or maintain a normal sitting position, said support harness being characterized in that it comprises two layers of a fabric which combines firmness and softness and which is of shape to define a back portion with upper and lower strap means for fastening the harness to the backrest of a chair; laterally extending side flaps (with foam rubber or like padding therein) adapted to be wrapped over the sides of the child's body between the armpits and the hips and across the chest and abdomen and secured together in overlapping relation by releasable fastening means; a longitudinal flap from the lower end of the back portion which is of progressively narrowing width to pass through the child's crotch and upwardly over the overlapped lateral flaps; and shoulder straps for releasably interconnecting the upper ends of said longitudinal flap and back portion.The support harness herein is further characterized in that it may be provided with a flat, rigid back portion for use with chairs having rounded backrests or for use in conjunction with adult-size chairs with a foam rubber pillow or pillows inserted between the backrest of the chair and the rigid back portion of the harness so that the child's legs will hang comfortably from the front edge of the chair. Excerpt(s): One known form of support device intended for supporting a physically handicapped child in normal sitting position comprises a padded vest-like garment which embraces the child's trunk and which has mounted in the upper middle portion of the back and in the corresponding portion of the backrest of a chair mating male and female coupling parts to releasably hold that portion of the device against the backrest. However, aside from the expense and inconvenience of providing and mounting such mating coupling parts in the garment and in the backrest of the chair for access for coupling and uncoupling movement, such construction does not properly support the handicapped child in normal erect sitting position because the hips can slide sidewise and forwardly with respect to the upper middle portion of the back of the garment. Furthermore, such support device can only be used with certain chairs wherein the backrest coupling part may be mounted for access for coupling and uncoupling to and from the mating garment coupling part. As evident, such known form of safety or support harness is not suitable for supporting a child with cerebral palsy or other neurological disease in normal sitting position. A support harness for firmly but comfortably supporting a child with cerebral palsy or other neurologic disease in a normal sitting position in any chair or seat while the child's arms, legs, and head are completely free of any restraint. For a child subject to seizures, the support harness is provided with quick release fastening means for removing the child from the harness and the chair to which the harness is tied and strapped. On the other hand, for a hyperactive child the support harness has the quick release fastening means positioned so as not to be accessible for inadvertent release by the child. Web site: http://www.delphion.com/details?pn=US04050737__ •

Therapeutic compositions Inventor(s): Veech; Richard L. (Rockville, MD) Assignee(s): BTG International Limited (London, GB) Patent Number: 6,207,856 Date filed: July 31, 2000 Abstract: Compositions comprising ketone bodies and/or their metabolic precursors are provided that are suitable for administration to humans and animals and which have

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the properties of, inter alia, (i) increasing cardiac efficiency, particularly efficiency in use of glucose, (ii) for providing energy source, particularly in diabetes and insulin resistant states and (iii) treating disorders caused by damage to brain cells, particularly by retarding or preventing brain damage in memory associated brain areas such as found in Alzheimer's and similar conditions.These compositions may be taken as nutritional aids, for example for athletes, or for the treatment of medical conditions, particularly those associated with poor cardiac efficiency, insulin resistance and neuronal damage. The invention further provides methods of treatment and novel esters and polymers for inclusion in the compositions of the invention. Excerpt(s): The present invention relates to compositions suitable for administration to humans and animals which have the properties of, inter alia, (i) increasing cardiac efficiency, particularly efficiency in use of glucose, (ii) for providing energy source, particularly in diabetes and insulin resistant states and (iii) treating disorders caused by damage to brain cells, particularly by retarding or preventing brain damage in memory associated brain areas such as found in Alzheimer's and similar conditions. These compositions may be taken as nutritional aids, for example for athletes, or for the treatment of medical conditions, particularly those associated with poor cardiac efficiency, insulin resistance and memory loss. The invention further provides methods of treatment and novel esters and polymers for inclusion in the compositions of the invention. Abnormal elevation of blood sugar occurs not only in insulin deficient and non insulin dependent diabetes but also in a variety of other diseases. The hyperglycaemia of diabetes results from an inability to metabolize and the over production of glucose. Both types of diabetes are treated with diet; Type I diabetes almost always requires additional insulin, whereas non-insulin dependent diabetes, such as senile onset diabetes, may be treated with diet and weight loss, although insulin is increasingly used to control hyperglycaemia. Increased sympathetic stimulation or elevated glucagon levels, in addition to increasing glycogenolysis in liver, also stimulate free fatty acid release from adipocytes. After acute myocardial infarction or during heart failure, increased sympathetic nervous activity or administration of sympathornimetics accelerate glycogenolysis, decrease release of insulin from P cells of the pancreas and cause relative insulin resistance. While the importance of diet, or substrate availability, is taken as a given in the treatment of diabetes, the critical effects of substrate choice in insulin resistant states has not been widely appreciated or applied in clinical practice. Instead contemporary interest has focused upon the complex signalling cascade which follows the binding of insulin to its receptor. This increasingly complex cascade of messages involving protein tyrosine kinases and phosphatases, inositol and other phospholipids, while holding promise for the ultimate understanding of non-insulin dependent diabetes, has yet to provide significant new therapies for either diabetes or insulin resistance. Web site: http://www.delphion.com/details?pn=US06207856__ •

Treatment with combined NMDA and non-NMDA antagonists to reduce excitotoxic CNS damage Inventor(s): Olney; John W. (St. Louis, MO) Assignee(s): Washington University (St. Louis, MO) Patent Number: 5,834,465 Date filed: May 1, 1992

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Abstract: This invention involves a pharmaceutical mixture for preventing or reducing excitotoxic brain damage caused by hypoxia/ischemia (such as stroke) and various other factors. This mixture comprises an NMDA antagonist and a non-NMDA antagonist, both of which penetrate blood-brain barriers (BBB's) and which, in combination, provide greater protection against excitotoxic damage than can be provided by any quantity of either agent by itself. Suitable NMDA antagonists can be either competitive antagonists which bind directy to the NMDA binding site in the NMDA receptor complex, or non-competitive agents that interact with other binding sites such as the PCP, glycine, or polyamine binding sites. Suitable non-NMDA antagonists include a quinoxalinedione compound referred to as NBQX, and a 2,3benzodiazepine compound referred to as GYKI 52466. If an NMDA antagonist is used which is stronger than dextromethorphan, the mixture of an NMDA and a non-NMDA antagonist preferably should be administered in combination with a third agent that functions as a "safening agent" to prevent or reduce the neurotoxic side effects caused by strong NMDA antagonists. Two classes of safening agents have been identified: (1) anticholinergic agents such as scopolamine and, (2) barbiturates which act as direct agonists of gamma-amino-butyric acid (GABA) receptors, such as secobarbital, pentobarbital, and thiamylal. Excerpt(s): This invention pertains to neurology and neuropharmacology. It describes methods and compounds which are safer and more effective than others currently available for protecting the brain against acute damage in conditions such as stroke, epilepsy, and physical trauma. Since glutamic and aspartic acid are amino acids, this neurotransmitter system is called the excitatory amino acid (EAA) system. In order to transmit a nerve signal or impulse from one neuron to another, a neuron releases glutamate or aspartate into the fluid which fills the synaptic gap between the transmitting neuron and the receiving neuron. A molecule of glutamate or aspartate reacts with a receptor on the surface of the receiving cell, thereby causing the opening of an ion channel which allows calcium and sodium ions to enter the cell. The flow of ions into the cell provokes several reactions; typically, the excited neuron transmits the nerve impulse to other neurons, by releasing glutamate at some or all its own synapses. A molecule of glutamate or aspartate does not bond to an EAA receptor; instead, it immediately disengages from the receptor and returns to the fluid in the synaptic gap between the transmitting neuron and the receiving neuron. Web site: http://www.delphion.com/details?pn=US05834465__ •

Use of aminoglycosides to protect against excitotoxic neuron damage Inventor(s): Marangos; Paul J. (Encinitas, CA) Assignee(s): Cypros Pharmaceutical Corporation (Carlsbad, CA) Patent Number: 5,677,288 Date filed: April 15, 1994 Abstract: A method is disclosed for reducing excitotoxic damage to neurons, which can occur as a result of stroke, cardiac arrest, or other events or conditions. This method involves administering an aminoglycoside that suppresses the flow of calcium ions into neurons through N-type calcium channels. To be effective for such use, an aminoglycoside must suppress N-channel activity at a potency greater than streptomycin. Aminoglycosides which meet this criterion (which includes neomycin and Gentamicin) can suppress the depolarizing activation of neurons, which in turn controls the release of glutamate, a neurotransmitter that becomes an endogenous toxin under

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excitotoxic conditions. Numerous aminoglycosides were tested in in vitro screening tests using brain cell membrane fragments to evaluate N-channel blocking potency. Aminoglycosides with the highest N-channel blocking potency were then tested using (1) in vitro tests on hippocampal brain tissue, to evaluate recovery of neuronal activity after a period of oxygen deprivation; (2) in vivo tests to evaluate the control of induced seizures in intact adult mammals; and (3) in vivo tests to evaluate the reduction of brain damage due to surgically-induced ischemia in intact adult mammals. The results showed that (1) aminoglycosides which are more potent than streptomycin in blocking N-channel ion flow are effective in reducing excitotoxic brain damage, without causing undesired side effects, and (2) the effectiveness of all BBB-permeable aminoglycosides tested to date in preventing excitotoxic brain damage is directly correlated with their potency in suppressing N-channel activity. Evaluation of chemical structures also indicates a correlation between the number of primary amino groups on an aminoglycoside, and its potency as an N-channel blocker and neuroprotective agent. Excerpt(s): This invention relates to pharmacology and neurology, and involves drugs that can prevent or reduce nerve cell death or damage due to conditions such as stroke, drowning, cardiac arrest, or various injuries or diseases. Neurons and entire regions of the brain can be severely damaged or killed during conditions or events such as strokes, drowning, carbon monoxide poisoning, cardiac arrest, or internal hemorrhaging due to rupture of an aneurysm. Various types of head injuries or other physical traumas, surgical damage, and certain types of poisons can also lead to permanent brain damage involving "excitotoxicity" (discussed below), which involves the excessive release or abnormal accumulation of excitatory neurotransmitters such as glutamic and aspartic acid. Seizures or convulsions due to epilepsy, head trauma, or other causes also involve the excessive release of excitatory neurotransmitters; although relatively mild seizures are not presumed to cause neuronal death or permanent damage, some types of severe seizures which cannot be halted by normal drugs, such as temporal lobe epilepsy (status epilepticus), are believed to cause permanent brain damage and neuronal death due to excitotoxicity. In addition, several types of progressive neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS) are also believed to involve excessive neurotransmitter release or accumulation as a component of the disease process. These problems are severely aggravated by the inability of nerve cells to regenerate or repair themselves after injury; a child who suffers only a few minutes of perinatal asphyxia during birth may spend an entire lifetime horribly crippled by the injuries such damage can inflict, and many people who have suffered from strokes live the remainder of their lives partially paralyzed or unable to speak or remember major events in their lives. Brain damage is an extremely pressing medical problem which inflicts devastating suffering and tragedy on individuals and their families, and enormous expense on insurance companies and government agencies. These costs are so high, largely because pharmaceutical management of neuron damage is woefully inadequate. Although stroke is the third leading cause of death in the United States, there is, at present, not a single drug treatment which has been approved by the Food and Drug Administration for preventing or reducing brain damage due to stroke. Web site: http://www.delphion.com/details?pn=US05677288__

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Use of ibogaine in reducing excitotoxic brain damage Inventor(s): Olney; John W. (1 Lorenzo La., St. Louis, MO 63124) Assignee(s): none reported Patent Number: 5,629,307 Date filed: March 6, 1995 Abstract: This invention discloses that ibogaine, a plant derivative, can be used as a safe NMDA antagonist at relatively high dosages (including dosages high enough to cause hallucinations), to reduce or prevent excitotoxic brain damage due to stroke, cardiac arrest, trauma or other forms of neuronal injury or degeneration, without causing the neurotoxic side effects caused by other NMDA antagonist drugs. The relative safety of ibogaine is due to antagonist activity at neuronal sigma receptors, which had not been known prior to discovery by the Applicant. This invention also discloses that ibogaine also can be administered in combination with (1) drugs that suppress activity at muscarinic acetylcholine receptors, or (2) drugs which suppress activity at the kainic acid subclass of glutamate receptors, to reduce or avoid the hallucinatory effects of ibogaine and provide a higher level of neuroprotective activity. Excerpt(s): Ibogaine is a drug found in the roots of Tabernanthe iboga, a shrub from Gabon, in equatorial west central Africa. Ibogaine has been known since the 1800's as an agent which at low doses has psychostimulant properties, and at high doses can induce a hallucinatory (oneirophrenic) state. For this reason it has been used in the Gabonese society for initiation ceremonial rites. Ibogaine has also been used as an adjunctive agent in psychotherapy and psychoanalysis, and more recently has been described as an agent that may be able to suppress symptoms of dependence or withdrawal from addictive drugs. Discovery of this property of ibogaine led to the issuance of a number of U.S. patents to Howard S. Lotsof, including U.S. Pat. No. 4,499,096 (issued in 1985, concerning heroin addiction), U.S. Pat. No. 4,587,243 (issued in 1986, concerning cocaine and amphetamine abuse), U.S. Pat. No. 4,857,523 (issued in 1989, concerning alcohol abuse), U.S. Pat. No. 5,026,697 (issued in 1991, concerning tobacco and nicotine), and U.S. Pat. No. 5,152,994 (issued in 1992, concerning people suffering from multiple drug dependencies). Lotsof's assertions regarding the usefulness of ibogaine in reducing various types of drug dependencies are consistent with evidence generated in several studies on laboratory animals. For example, in rats, ibogaine reduces morphine selfadministration and ameliorates symptoms associated with morphine withdrawal and decreases preference for cocaine consumption; see, e.g., Glick et al 1991, Glick et al 1992, Sershen et al 1992, Cappendijk and Dzoljic 1993, and Sershen et al 1994 (full citations to articles are provided below). Web site: http://www.delphion.com/details?pn=US05629307__

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Use of kainic acid antagonists to prevent toxic side effects of NMDA antagonists Inventor(s): Olney; John W. (1 Lorenzo La., St. Louis, MO 63124) Assignee(s): none reported Patent Number: 5,767,130 Date filed: March 20, 1995 Abstract: This invention discloses that kainic acid receptor antagonists (KA antagonists) can act as "safener" agents to reduce or prevent adverse side effects caused by NMDA

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antagonists. NMDA antagonists can reduce excitotoxic brain damage due to stroke, cardiac arrest, asphyxia, etc., but they also cause toxic damage to certain types of neurons, as well as psychotomimetic effects such as hallucinations. Co-administration of a KA antagonist can (1) reduce or prevent such undesired side effects, and (2) increase the extent of neuronal protection provided to the CNS, beyond the levels of protection that can be provided by NMDA antagonists alone, or non-NMDA antagonists alone. Therefore, co-administration of a KA antagonist allows NMDA antagonists to be used more safely and effectively. Excerpt(s): The present invention is in the fields of neurology and pharmacology, and pertains to methods and preparations for treating or preventing toxic side effects of drugs that block neuronal receptors referred to as NMDA receptors. Background information on the glutamate transmitter system and on NMDA glutamate receptors is provided in a number of reference works, including Choi 1988 and Olney 1989 (full citations are provided below). The most relevant features of this information are summarized in the following paragraphs. Glutamate (the ionized form of glutamic acid, an amino acid; abbreviated as Glu) is recognized as the predominant excitatory neurotransmitter (messenger molecule) in the central nervous system (CNS) of all mammals. For a review, see the chapter by Olney, entitled "Glutamate," in The Encyclopedia of Neuroscience (1987 or 1995 editions). Glu is involved in transmitting messages from one nerve cell (neuron) to another in many different circuits within the CNS that serve many important functions. Glu mediates these functions by being released from a transmitting neuron, into a synapse (a signal-transmitting junction between two neurons). Immediately after entering the synaptic fluid that fills the synapse, the Glu contacts and briefly binds to a response at a synapse, the Glu contacts and briefly binds to a response at a receptor molecule on the surface of a receiving neuron. Binding of Glu to the synaptic receptor initiates signal transfer by causing the opening of an ion channel which allows ionic current flow across the membrane of the neuron, thereby altering its chemical state. This is considered an excitatory process, because it stimulates an increased level of electrochemical activity in the receiving neuron. Web site: http://www.delphion.com/details?pn=US05767130__ •

Use of MEK1 inhibitors as protective agents against damage due to ischemia Inventor(s): Alessandrini; Alessandro (Cambridge, MA), Bonventre; Joseph (Wayland, MA), Moskowitz; Michael A. (Belmont, MA), Namura; Shobu (Osaka, JP) Assignee(s): The General Hospital Corporation (Boston, MA) Patent Number: 6,150,401 Date filed: January 6, 1999 Abstract: The invention relates to the use of MEK1 inhibitors to reduce tissue damage resulting from ischemia and/or reperfusion, particularly brain damage associated with ischemia resulting from stroke. Pharmaceutical compositions, kits and perfusion fluids including MEK1 inhibitors are also provided. Excerpt(s): The invention relates to treatments for tissue damage associated with ischemia, particularly brain damage associated with ischemia resulting from stroke. Ischemic diseases are significant causes of mortality in industrialized nations. It is well established that tissue damage results from ischemia (stoppage of blood flow to the tissue) followed by reperfusion of the tissue. The ischemic injury with the consecutive

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reperfusion is responsible for the disturbance of microcirculation with ensuing tissue damage and organ dysfunction. One well-known example of ischemia and its effects is stroke, which is a condition resulting from a reduction or blockage of blood flow to the brain (cerebral ischemia). About 500,000 Americans suffer strokes each year, 80% of which are caused by a blood clot blocking one of the cerebral blood vessels. Symptoms of stroke include weakness, numbness or paralysis of the face, arm or leg; sudden loss or dimness of vision; loss of speech or difficulty using or understanding language; sudden, severe unexplained headache; or unexplained dizziness, unsteadiness or sudden falls (particularly if associated with one of the above symptoms). Web site: http://www.delphion.com/details?pn=US06150401__

Patent Applications on Brain Damage As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to brain damage: •

Cell therapy for chronic stroke Inventor(s): Kondziolka, Douglas; (Pittsburgh, PA), McGrogan, Michael P.; (San Carlos, CA), Sanberg, Paul R.; (Springhill, FL), Snable, Gary L.; (Atherton, CA) Correspondence: QUARLES & BRADY LLP; RENAISSANCE ONE; TWO NORTH CENTRAL AVENUE; PHOENIX; AZ; 85004-2391; US Patent Application Number: 20030211085 Date filed: September 30, 2002 Abstract: A method of treating stroke in a patient who has undergone a stroke comprising administering at least 2 million suitable neuronal cells to at least one brain area involved in the stroke. The method comprises the step of using a twist drill or a burr to form a hole in the skull through which the cells could be administered. Exemplary cells are hNT neuronal cells, HCN-1 cells, fetal pig cells, neural crest cells, neural stem cells, or a combination thereof. Also disclosed herein is a pharmaceutical composition of 95% pure hNT neuronal cells, which composition further includes a vial containing PBS and human neuronal cells. This vial is provided in a container with liquid nitrogen, whereby the composition is frozen and maintained at -170.degree. C. before use. Also disclosed are methods of improving speech, cognitive, sensory, and motor function in a person who has experienced brain damage which interferes with function by administering a sterile composition of a sufficient number of neuronal cells or neural stem cells to the damaged area. Also disclosed is a method of replacing central nervous cells lost to neurodegenerative disease, trauma, ischemia or poisoning. Excerpt(s): This invention is in the medical treatment of neurological deficits resulting from stroke; more specifically, the invention applies cell therapy to restore lost cognitive, motor, sensory and speech function resulting from stroke. In the United States, according to the National Institutes of Health, stroke is the third leading cause of death and the most common cause of adult disability. With an incidence of approximately 750,000 patients, approximately 30% (250,000) die, 30% (250,000) become

9 This

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

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severely and permanently disabled, and 30% (250,000) recover with little or no functional deficits. Currently four million Americans are living with the effects of stroke, and two thirds of those have moderate to severe impairments. In addition, improving diagnostic methods, such as diffusion-weighted imaging (showing dead brain tissue) and perfusion-weighted imaging (showing oxygen-starved but live brain tissue), are helping diagnose more new and old strokes. Stroke is defined as a sudden, nonconvulsive, focal neurologic deficit that is related either to cerebral ischemia or hemorrhage. The neurologic deficit created reflects the location and size of the cerebral infarction. Lacunar infarction is one type of ischemic stroke that is usually of small volume, and which may be typified by various clinical syndromes (e.g., hemiparesis with ataxia in the same limb, pure motor hemiplegia). When located in a region of noncritical brain tissue, lacunar stroke is often not associated with symptoms. However, when located in a critical structure such as the internal capsule, thalamus, basal ganglia or brain stem, significant neurologic disability can occur. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Inner cushions for helmets Inventor(s): Clavell, Rafael Calonge; (Barcelona, ES) Correspondence: STEINBERG & RASKIN, P.C.; 1140 AVENUE OF THE AMERICAS, 15th FLOOR; NEW YORK; NY; 10036-5803; US Patent Application Number: 20030131400 Date filed: December 31, 2001 Abstract: For the present we register a hybrid Inner Cushion for Helmets based on a Composite Foam sandwiched between two foils. The cushions or paddings used in the last century by helmets manufacturers (mainly made with expanded polystyrene, EPS or expanded polypropylene, EPP) absorb impacts by elastic deformation of the material, producing a significant bounce back after being compressed. The composite foams of the present invention avoid the `bounce back on head` effect by converting a large fraction of the incoming kinetic energy in plastic deformation of the material. Thus, the `bounce effect` or `counter-coup lesions`, which largely enhance the first impact brain damage, can be greatly reduced. Two covering foils, either made by a metal (i.e. aluminum) or a combination of a metal and a polymer (i.e. mylar), protect the cushion material against environment and other eventual damaging agents. Furthermore, in order to verify the integrity of the cushion after an impact, some testing procedures have been envisaged, such as the electrical capacitance produced by the two covering foils, which will largely depend on their separating average distance and on the dielectric constant of the inner part of the cushion. Excerpt(s): The present invention proposes an Inner Cushion (IC) for helmets having a shock absorbing padding consisting of either an inorganic (i.e. containing silica aerogel) or organic (i.e. containing carbon aerogel, an RF aerogel, a viscoelastic polymer foam, etc.) composite foam, mixed with other Organic or Mineral Foam and an external metal or metal-polymer foil protector in both sides. The majority of helmet manufacturers utilize EPS (Expanded Polystyrene) or EPP (Expanded Polypropylene) materials for absorbing impacts. Those materials provide a good kinematic behavior in the head deceleration, but from the dynamic point of view, the stored energy in the elastic material will be returned to the deforming agent, i.e. the head, producing further damages to the brain. Two common causes of brain damage are head wounds and severe blows to the head. Head wounds describe wounds which actually extend into the

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brain itself, such as might be the case if a person was shot in the head or if they suffered a crush in part of the skull in an accident. If the skull becomes broken then the brain is vulnerable to direct damage, this is an open head injury. Alternatively, the brain may become damaged even if the skull remains intact if the head receives a very severe blow-a closed head injury. In such cases the damage can be both from the direct strike against the inside of the skull (coup) or from the resulting forces of rotation which cause the brain to strike against the skull at the opposite side of the head (countercoup). These two types of injuries constitute the two most common causes of brain damage in young adults (often resulting from car or motorbike accidents). A further complication of closed head injury is the fact that local neurons tend to develop edema where neurons close to the site of injury swell, retain fluid and become less excitable. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for preventing and treating alzheimer's disease and brain damage associated with cardiov ascular disease and head injury Inventor(s): Allison, Anthony Clifford; (Belmont, CA) Correspondence: Barbara J. Luther Chartered; 18124 Wedge Parkway, #516; Reno; NV; 89511; US Patent Application Number: 20020016372 Date filed: June 11, 2001 Abstract: A method for preventing and treating AD is supplementation with vitamin K so that the concentration of the vitamin in the circulation is sufficient for its functions outside the liver. Vitamin K supplementation will also be useful to reduce brain damage associated with cardiovascular disease and injury. Vitamin K can be administered orally, subcutaneously, intramuscularly or intravenously. The vitamin K can be phylloquinone, menaquinones of varying chain lengths, or menadione. Preferred forms of the vitamin are all-trans menadione and menaquinone-4. These are formulated so as to ensure efficient absorption from the gastrointestinal tract and rapid bioavailability in the brain following administration. Excerpt(s): This application claims the benefit of the priority of U.S. Provisional Application No. 60/222,143, filed Jul. 31, 2000. The present invention relates to a method of medical treatment. More specifically the method provides for preventing the development of Alzheimer's disease (AD) in predisposed persons and for treatment of patients with dementias suggestive of AD. The treatment will also limit brain damage associated with cardiovascular disease and head injury. Alzheimer's disease (AD) is a type of dementia accompanied by characteristic pathological changes. The brains of patients with AD show extracellular deposits of.beta.-amyloid protein, often associated with altered neurons or dendrites. Most cases also show within neurons neurofibrillary tangles composed of paired helical filaments containing a highly phosphorylated form of the tau protein of microtubules. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of reducing injury to mammalian cells Inventor(s): Tymianski, Michael; (Toronto, CA) Correspondence: BELL, BOYD & LLOYD LLC; P.O. Box 1135; Chicago; IL; 60690-1135; US Patent Application Number: 20030050243 Date filed: July 30, 2002 Abstract: A method of inhibiting the binding between N-methyl-D-aspartate receptors and neuronal proteins in a neuron the method comprising administering to the neuron an effective inhibiting amount of a peptide replacement agent for the NMDA receptor or neuronal protein interaction domain that effect said inhibition of the NMDA receptor neuronal protein. The method is of value in reducing the damaging effect of injury to mammalian cells. Postsynaptic density-95 protein (PSD-95) couples neuronal N-methylD-aspartate receptors (NMDARs) to pathways mediating excitotoxicity and ischemic brain damage. This coupling was disrupted by transducing neurons with peptides that bind to modular domains on either side of the PSD-95/NMDAR interaction complex. This treatment attenuated downstream NMDAR signaling without blocking NMDAR activity, protected cultured cortical neurons from excitotoxic insults and dramatically reduced cerebral infarction volume in rats subjected to transient focal cerebral ischemia. The treatment was effective when applied either before, or one hour after, the onset of excitotoxicity in vitro and cerebral ischemia in vivo. This approach prevents negative consequences associated with blocking NMDAR activity and constitutes practical therapy for stroke. Excerpt(s): This application is a continuation-in-part application of Ser. No. 09/584,555, filed May 31, 2000. This invention relates to methods of reducing the damaging effect of an injury to mammalian cells by treatment with compounds which reduce the binding between N-methyl-D-aspartate receptors and neuronal proteins; pharmaceutical compositions comprising said compounds and methods for the preparation of said pharmaceutical compositions. Ischemic or traumatic injuries to the brain or spinal cord often produce irreversible damage to central nervous system (CNS) neurons and to their processes. These injuries are major problems to society as they occur frequently, the damage is often severe, and at present there are still no effective pharmacological treatments for acute CNS injuries. Clinically, ischemic cerebral stroke or spinal cord injuries manifest themselves as acute deteriorations in neurological capacity ranging from small focal defects, to catastrophic global dysfunction, to death. It is currently felt that the final magnitude of the deficit is dictated by the nature and extent of the primary physical insult, and by a time-dependent sequence of evolving secondary phenomena which cause further neuronal death. Thus, there exists a theoretical time-window, of uncertain duration, in which a timely intervention might interrupt the events causing delayed neurotoxicity. However, little is known about the cellular mechanisms triggering and maintaining the processes of ischemic or traumatic neuronal death, making it difficult to devise practical preventative strategies. Consequently, there are currently no clinically useful pharmacological treatments for cerebral stroke or spinal cord injury. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods and apparatus for effectuating a lasting change in a neural-function of a patient Inventor(s): Balzer, Jeffrey; (Allison Park, PA), Firlik, Andrew D.; (Ridgefield, CT), Gliner, Bradford E.; (Sammamish, WA), Levy, Alan J.; (Bellevue, WA), Morgan, Carlton B.; (Bainbridge Island, WA) Correspondence: PERKINS COIE LLP; PATENT-SEA; P.O. BOX 1247; SEATTLE; WA; 98111-1247; US Patent Application Number: 20020087201 Date filed: March 8, 2001 Abstract: The following disclosure describes several methods and apparatus for intracranial electrical stimulation to treat or otherwise effectuate a change in neuralfunctions of a patient. Several embodiments of methods in accordance with the invention are directed toward enhancing or otherwise inducing a lasting change in neural activity to effectuate a particular neural-function. Such lasting change in neural activity is defined as "neuroplasticity." The methods in accordance with the invention can be used to treat brain damage (e.g., stroke, trauma, etc.), brain disease (e.g., Alzheimer's, Pick's, Parkinson's, etc.), and/or brain disorders (e.g., epilepsy, depression, etc.). The methods in accordance with the invention can also be used to enhance neuralfunction of normal, healthy brains (e.g., learning, memory, etc.), or to control sensory functions (e.g., pain). Certain embodiments of methods in accordance with the invention electrically stimulate the brain at a stimulation site where neuroplasticity is occurring. The stimulation site may be different than the region in the brain where neural activity is typically present to perform the particular neural function according to the functional organization of the brain. In one embodiment in which neuroplasticity related to the neural-function occurs in the brain, the method can include identifying the location where such neuroplasticity is present. In an alternative embodiment in which neuroplasticity is not occurring in the brain, an alternative aspect is to induce neuroplasticity at a stimulation site where it is expected to occur. Several embodiments of these methods that are expected to produce a lasting effect on the intended neural activity at the stimulation site use electrical pulses that increase the resting membrane potential of neurons at the stimulation site to a subthreshold level. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/217,981, filed Jul. 31, 2000, which is incorporated herein in its entirety. Several embodiments of methods and apparatus in accordance with the invention are related to electrically stimulating a region in the cortex or other area of the brain to bring about a lasting change in a physiological function and/or a mental process of a patient. Many problems or abnormalities with body functions can be caused by damage, disease and/or disorders of the brain. A stroke, for example, is one very common condition that damages the brain. Strokes are generally caused by emboli (e.g., obstruction of a vessel), hemorrhages (e.g., rupture of a vessel), or thrombi (e.g., clotting) in the vascular system of a specific region of the cortex, which in turn generally causes a loss or impairment of a neural function (e.g., neural functions related to face muscles, limbs, speech, etc.). Stroke patients are typically treated using physical therapy to rehabilitate the loss of function of a limb or another affected body part. For most patients, little can be done to improve the function of the affected limb beyond the recovery that occurs naturally without intervention. One existing physical therapy technique for treating stroke patients constrains or restrains the use of a working body part of the patient to force the patient to use the affected body part. For example, the loss of use of a limb is treated by restraining the other limb. Although this type of physical therapy has shown some

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experimental efficacy, it is expensive, time-consuming and little-used. Stroke patients can also be treated using physical therapy plus adjunctive therapies. For example, some types of drugs, such as amphetamines, that increase the activation of neurons in general, appear to enhance neural networks; these drugs, however, have limited efficacy because they are very non-selective in their mechanisms of action and cannot be delivered in high concentrations directly at the site where they are needed. Therefore, there is a need to develop effective treatments for rehabilitating stroke patients and patients that have other types of brain damage. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and compositions for modulating brain damage Inventor(s): Follett, Pamela L.; (Boxboro, MA), Jensen, Frances E.; (Chestnut Hill, MA), Rosenberg, Paul; (Newton, MA), Volpe, Joseph; (Brookline, MA) Correspondence: LAHIVE & COCKFIELD; 28 STATE STREET; BOSTON; MA; 02109; US Patent Application Number: 20030092730 Date filed: August 5, 2002 Abstract: Methods and compositions for modulating brain damage mediated by nonNMDA ionotropic glutamate receptor antagonists are provided. Methods for inhibiting neuronal cell damage and death in the brain following an injury (e.g., ischemic/hypoxic injury) and methods for inhibiting cell damage and death in conditions such as periventricular leukomalacia, cerebral palsy, mental retardation, and neonatal stroke, are also provided. These methods generally involve treating a subject with a nonNMDA ionotropic glutamate receptor antagonist. Pharmaceutical and packaged formulations that include non-NMDA ionotropic glutamate receptor antagonists are also provided. Excerpt(s): The present application is a Continuation-In-Part application of and claims priority from U.S. Continuation patent application Ser. No. 10/121,892, filed on Apr. 12, 2002, and from U.S. patent application Ser. No. 09/922,564, filed on Aug. 3, 2001. All of the above applications are expressly incorporated by reference. Preterm infants, particularly those of low birth weight and gestational age, often present neurodevelopmental deficits which include global cognitive delay, cerebral palsy, blindness, and deafness. Deficits such as cognitive delay and cerebral palsy may be attributed, at least in part, to hypoxic/ischemic damage in white and/or grey matter of the brain. A common example of white matter injury observed in infants as a complication of premature birth is referred to as periventricular leukomalacia (PVL). PVL is the principal neuropathological correlate of cerebral palsy. The lesion is defined by focal necrosis of the deep periventricular white matter involving all cellular components, combined with a more diffuse white matter injury that appears selective for developing oligodendrocytes (OLs) (Gilles and Averill (1977) Ann. Neurol. 2:49-56; Dambska et al. (1989) J. Child Neurol. 4:291-298; and Rorke (1998) In Pathology of Perinatal Brain Injury New York: Raven). Reduced cerebral myelin is the most prominent subsequent cerebral abnormality observed in premature infants with evidence of PVL in the neonatal period (Paneth et al. (1990) J. Pediatr. 116:975-984; Rorke (1992) Brain Pathol. 2:211-221; Iida et al. (1995) Pediatr. Neurol. 13:296-304; Olsen et al. (1997) Ann. Neurol. 41:754-761; Skranes et al. (1997) Neuropediatrics 28:149-154; and Inder et al. (1999) Ann Neurol. 46:755-760).

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

Neural regeneration peptides and methods for their use in treatment of brain damage Inventor(s): Hughes, Paul; (Auckland, NZ), Sieg, Frank; (Auckland, NZ) Correspondence: FLIESLER DUBB MEYER & LOVEJOY, LLP; FOUR EMBARCADERO CENTER; SUITE 400; SAN FRANCISCO; CA; 94111; US Patent Application Number: 20030211990 Date filed: August 22, 2002 Abstract: The invention discloses a family of neuronal migration-inducing, proliferationpromoting and neurite outgrowth promoting factors, termed NRP compounds, and provides compositions and methods for the use of NRP compounds in the treatment of brain injury and neurodegenerative disease. NRP-1 compounds induce neurons and neuroblasts to proliferate and migrate into areas of damage caused by acute brain injury or chronic neurodegenerative disease, such as stroke, trauma, nervous system infections, demyelinating diseases, dementias, and metabolic disorders. NRP compounds may be administered directly to a subject or to a subject's cells by a variety of means including orally, intraperitoneally, intravascularly, and directly into the nervous system of a patient. Excerpt(s): This application claims the priority under 35 USC 119(e) to U.S. Provisional Application Serial No. 60/314,952, filed Aug. 24, 2001, which is incorporated into this application fully by reference. This application is also related to U.S. Utility Patent Application titled "Assay Methods for Neuroregeneration Peptides," Frank Sieg and Paul Hughes, inventors, Attorney Docket No: NRNZ 1023 US2, incorporated herein fully by reference. This invention is directed to compositions and methods for the use of peptides that promote neuronal migration, proliferation, survival and/or neurite outgrowth. More specifically, this invention is directed to the use of such peptides in the treatment of brain injury and neurodegenerative disease. Moderate to severe traumatic brain injury (TBI), and focal or global ischemia can result in significant neuronal cell loss and loss of brain function within a short time period after the insult. There are no treatments currently available to prevent cell death that occurs in the brain as a consequence of head injury or damage caused by disease. To date, there is also no treatment available to restore neuronal function. Treatments available at present for chronic neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Multiple Sclerosis only target symptoms. No drugs are currently available to intervene in the disease process or prevent cell death. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Pharmaceutical combinations Inventor(s): Brearley, Christopher John; (Sandwich, GB), Butler, Paul; (Sandwich, GB), Chahwala, Suresh Babubhai; (Sandwich, GB), Chopp, Michael; (Sandwich, GB), Krams, Michael; (Sandwich, GB), Looby, Michael; (Sandwich, GB), MacIntyre, Fiona; (Sandwich, GB), McElroy, Andrew Brian; (Sandwich, GB), McHarg, Aileen Dorothy; (Sandwich, GB) Correspondence: Paul H. Ginsburg; Pfizer Inc.; 20th Floor; 235 East 42nd Street; New York; NY; 10017-5755; US Patent Application Number: 20020098179 Date filed: October 1, 2001 Abstract: This invention relates, inter alia, to methods of treating pathophysiological conditions involving neutrophils, comprising administering to a patient in need of such treatment a combination therapy comprising at least one Neutrophil Inhibitory Factor (NIF) and at least one other agent that protects neurons from toxic insult, inhibits the inflammatory reaction after brain damage or promotes cerebral reperfusion (i.e. neuroprotective or thrombolytic/fibrinolytic agents), or a pharmaceutically acceptable salt thereof. Excerpt(s): The present invention relates, inter alia, to methods of treating pathophysiological conditions involving neutrophils, comprising administering to a patient in need of such treatment a combination therapy comprising at least one Neutrophil Inhibitory Factor (NIF) and at least one other agent that protects neurons from toxic insult, inhibits the inflammatory reaction after brain damage or promotes cerebral reperfusion (i.e. neuroprotective or thrombolytic/fibrinolytic agents), or a pharmaceutically acceptable salt thereof. Leukocytes are a class of cells comprised of lymphocytes, monocytes and granulocytes. The lymphocytes include within their class, T-cells (as helper T-cells and cytotoxic or suppressor T-cells), B-cells (as circulating Bcells and plasma cells), natural killer (NK) cells and antigen-presenting cells. Monocytes include within their class, circulating blood monocytes, Kupffer cells, intraglomerular mesangial cells, alveolar macrophages, serosal macrophages, microglia, spleen sinus macrophages and lymph node sinus macrophages. Granulocytes include within their class, neutrophils, eosinophils, basophils, and mast cells (as mucosa-associated mast cells and connective tissue mast cells). Thus, neutrophils and eosinophils are a subset of leukocytes. Neutrophils are an essential component of the host defence system against microbial invasion. In response to soluble inflammatory mediators released by cells at the site of injury, neutrophils migrate into tissue from the bloodstream by crossing the blood vessel wall. At the site of injury, activated neutrophils kill foreign cells by phagocytosis and/or by the release of cytotoxic compounds, such as oxidants, proteases and cytokines. Despite their importance in fighting infection, neutrophils themselves can promote tissue damage. During an abnormal inflammatory response, neutrophils can cause significant tissue damage by releasing toxic substances at the vascular wall or in uninjured tissue. Alternatively, neutrophils that adhere to the capillary wall or clump together in venules may produce tissue damage by ischaemia ("no reflow" phenomenon). Such abnormal inflammatory responses have been implicated in the pathogenesis of a variety of clinical disorders including adult respiratory distress syndrome (ARDS); ischaemia-reperfusion injury following myocardial infarction, shock, stroke, and organ transplantation; acute and chronic allograft rejection; vasculitis; sepsis; rheumatoid arthritis; and inflammatory skin diseases (Harlan et al., 1990 Immunol. Rev. 114, 5). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Procedures to prevent Alzheimer's or enhance recovery from brain damage by use of procedures that enhance REM sleep Inventor(s): Dewan, Edmond M.; (Lexington, MA) Correspondence: William G. Auton; ESC/JAZ; 40 Wright Street; Hanscom AFB; MA; 01731-2903; US Patent Application Number: 20030150465 Date filed: July 13, 2001 Abstract: A brain damaged patient who is improving will have a higher percentage of REM sleep than one who is not. The improvement we studied is that occurring over a period of weeks and months, so it cannot be attributed to the return of function of temporarily damaged, but not destroyed, brain tissue. Improvement was therefore to be considered as new learning or programming. Patients suffering from aphasia as the result of a discrete cerebrovascular accident or of trauma are able to enhance their improvement by increasing amounts of REM sleep inducing activities (such as having a regular sleep schedule with a systematic schedule of phase changes in circadian rhythms) and diminishing REM sleep reducers such as caffeine, noise or a use of tranquilizers. Excerpt(s): The present invention relates generally to recovery from brain disorders and more specifically to a procedure to enhance REM sleep. Alzheimer's Disease is a progressive neurodegenerative disorder affecting 7% of the population over 65 years of age and characterized clinically by progressive loss of intellectual function. This impairment of function is caused by the presence of neuritic plaques in the neocortex and the loss of presynaptic markers of cholinergic neurons. Neuritic plaques are composed of degenerative axons and nerve terminals, often surrounding an amyloid core and usually containing reactive glial elements. Another characteristic pathologic feature of Alzheimer's Disease is the neurofibrillary tangle, which is an intraneuronal mass which corresponds to an accumulation of abnormally phosphorylated tau protein polymerized into fibrillar structures termed paired helical filaments. In addition, the neurofibrillary tangle also contains highly phosphorylated neurofilament proteins. Even the earliest papers on Alzheimer's Disease were clear that both "senile" plaques and neurofibrillary tangles had to be present in abundance to allow a post-mortem diagnosis of the disease. Many treatments for recovery from brain disorders center around the presumption of chemical agents. An example of this approach is described in U.S. Pat. No. 6,228,878, May 8, 2001, Methods for treating or preventing Alzheimer's disease using substituted 2-aryl-3-morpholinopropa- nones, DeBernardis, John, the disclosure of which is incorporated herein by reference. An alternative to prescriptive chemical agents is using procedures to enhance REM sleep, as described below. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Processing EEG signals to predict brain damage Inventor(s): Williams, Christopher Edward; (Auckland, NZ) Correspondence: HELLER EHRMAN WHITE & MCAULIFFE LLP; 275 MIDDLEFIELD ROAD; MENLO PARK; CA; 94025-3506; US Patent Application Number: 20030023183 Date filed: May 6, 2002

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Abstract: Rapid and accurate in-vivo assessment of cerebral white matter injury particularly for pre-term infants, for timely treatment and/or prediction of outcomes has been very limited. This invention exploits the discovery that reduced highfrequency EEG intensity, particularly as shown by the upper spectral edge frequency, is a good indicator of cerebral white matter neural injury and is well correlated with MRI results. With more experience of clinical cases, a set of simple rules such as "if the spectral edge value is below 8 Hz there is a high likelihood of injury" may be validated, yet the EEG technology involved is largely invisible to the user. In the invention, EEG signals are processed by software to obtain, store, and graphically display bilaterally collected EEG spectral edge and intensity values over from hours to weeks. Rejection of corrupted signals by filtering and gating means is responsive to incoming signal characteristics, to additional inputs such as motion sensors or impedance tests, and to patient data (gestational age in particular). The invention includes the software and methods of use. Excerpt(s): This application is a continuation-in-part of application Ser. No. 09/509,186, filed Apr. 7, 2000. application Ser. No. 09/509,196 is a 371 of PCT International Application No. PCT/NZ98/00142, filed Sep. 23, 1998, which in turn claims the priority of New Zealand Application No. 328820, filed Sep. 23, 1997. Each of these applications is incorporated into this application by reference. This invention relates to a apparatus for display of a processed, condensed derivative of electroencephalographic (EEG) signals. Cerebral/neural injuries in pre-term infants are telatively difficult to assess and to track during their course, using skills and equipment available at the time of this application; yet intervention may be highly desirable. Magnetic resonance imaging (MRI) is the only reliable non-invasive assessment available to a neo-natal intensive care unit. MRI is limited to (a) revealing lesions in older infants, typically over 34 weeks, and (b) to showing structural correlates of changes that are already too late for intervention, it being 3-4 days before MRI scans show injury. Ultrasound imaging is significantly less reliable than MRI in this area. It has been estimated that up to 70% of cases of apparent hypoxic-ischemic injury are missed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

System method for reducing brain injury particularly in newborn infants Inventor(s): Coldham, Dlana Katrina; (Auckland, NZ), Gunn, Alistair; (Auckland, NZ), Gunn, Alistair Jan; (Auckland, NZ), Gunn, Bernard Maurice; (Auckland, NZ), Gunn, Christopher Bernard; (Auckland, NZ), Gunn, Derek Ivan; (Auckland, NZ), Gunn, Tania R.; (Auckland, NZ) Correspondence: NIXON & VANDERHYE P.C.; 1100 North Glebe Road, 8th Floor; Arlington; VA; 22201-4714; US Patent Application Number: 20020091431 Date filed: October 25, 2001 Abstract: A method for preventing or reducing the development of delayed brain damage in a patient, comprises applying headwear (1) to the patient's head and circulating a fluid coolant through conduits (3) or passages in the headwear to cool the brain and thermostatically controlling the coolant temperature within a predetermined range to maintain the brain at a temperature sufficiently below normal for an extended period sufficient to prevent the death of neurons, glial or other cells that would otherwise die as a consequence of direct injury to the brain or other injury to the patient likely to cause injury to the brain.

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Excerpt(s): The invention comprises apparatus and a method for preventing or reducing delayed brain damage in a patient, and headwear for fitting to a patient's head for use with the apparatus and method of the invention. During brain injury, the brain is deprived of freshly oxygenated blood. Following this, neurons in the brain die soon after or at a later stage occurring hours to days after the insult and are not capable of regeneration. Glial cells, which are non-neuronal cells essential for normal brain functioning, also die. Permanent loss of function is a likely outcome of a severe injury to the brain. Perinatal hypoxic-ischemic injury continues to be a major cause of death or later neurodevelopmental sequelae. This type of head injury in the neonate occurs during asphyxial, traumatic, toxic, infectious, metabolic, ischemic or hypoxic insults to the brain. Specifically, perinatal asphyxia caused by cord occlusion or associated with intrauterine growth retardation; perinatal asphyxia associated with failure of adequate resuscitation or respiration; near miss drowning, near miss cot death, carbon monoxide poisoning, ammonia or other gaseous intoxication, coma, hypoglycaemia and status epileptics; stroke; cerebral trauma. Experimental and clinical studies have shown that hypoxic ischemic encephalopathy (HIE) is an evolving process. Following the primary phase of energy failure during asphyxia cerebral metabolism may initially recover in a latent phase, but then deteriorate in a secondary phase of brain injury 6 to 15 hours later. In the human infant the severity of delayed energy failure after asphyxia is correlated with adverse neurodevelopmental outcome at one and four years of age. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Therapeutic compositions (II) Inventor(s): Veech, Richard Lewis; (Rockville, MD) Correspondence: Nixon & Vanderhye; Eighth Floor; 1100 North Glebe Road; Arlington; VA; 22201-4714; US Patent Application Number: 20010014696 Date filed: March 6, 2001 Abstract: Compositions comprising ketone bodies and/or their metabolic precursors are provided that are suitable for administration to humans and animals and which have the properties of, inter alia, (i) increasing cardiac efficiency, particularly efficiency in use of glucose, (ii) for providing energy source, particularly in diabetes and insulin resistant states and (iii) treating disorders caused by damage to brain cells, particularly by retarding or preventing brain damage in memory associated brain areas such as found in Alzheimer's and similar conditions.These compositions may be taken as nutritional aids, for example for athletes, or for the treatment of medical conditions, particularly those associated with poor cardiac efficiency, insulin resistance and neuronal damage. The invention further provides methods of treatment and novel esters and polymers for inclusion in the compositions of the invention. Excerpt(s): The present invention relates to compositions suitable for administration to humans and animals which have the properties of increasing levels of (R)-3hydroxybutyrate ((R)-3-hydroxybutyric acid or D-.beta.-hydroxybutyrate) when so administered; particularly when administered orally, topically, subcutaneously or parenterally, but most advantageously orally. Administration of (R)-3-hydroxybutyric acid has a number of beneficial actions on the human and animal body. These include inter alia, increasing cardiac efficiency, e.g. in heart failure, provision of an alternative energy source to glucose, e.g. in diabetes and insulin resistant states, and treating disorders caused by damage to neuronal cells, e.g. CNS cells, particularly by retarding

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or preventing brain damage such as found in Alzheimer's and Parkinsonism and similar diseases and conditions. Sodium hydroxybutyrate has been shown to increase cerebral circulation and regional vasomotor reflexes by up to 40% (Biull. Eksp. Biol. Med Vol 88 11, pp 555-557). EP 0780123 A1 further teaches use of acetoacetate,.beta.hydroxybutyrate, monohydric, dihydric or trihydric alcohol esters of these or linear oligomers of 2 to 10 repeats of.beta.-hydroxybutyrate for suppressing cerebral edema, protecting cerebral function, rectifying cerebral energy metabolism and reducing the extent of cerebral infarction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Treatment of brain damage Inventor(s): Hodges, Helen; (London, GB) Correspondence: Saliwanchik Lloyd & Saliwanchik; Suite A-1; 2421 NW 41st Street; Gainesville; FL; 32606-6669; US Patent Application Number: 20020037277 Date filed: March 29, 2000 Abstract: The present invention relates to the treatment of brain damage by cellular transplantation. According to one aspect of the invention, a method for treating a motor, sensory and/or cognitive deficit comprises administering a composition comprising pluripotent cells into the damaged brain in a region contra-lateral to that containing the site of damage. The cells are preferably conditionally immortal. Excerpt(s): This invention relates to the treatment of disorders associated with damage to the brain. In particular, this invention relates to treatment of disorders by cellular transplantation into a damaged brain. Stroke is the largest cause of adult disability worldwide. The incidence of stroke is about 1.3% of the US population, and 39.4% of victims show significant residual impairments, ranging from hemiplegia to restricted limb use and speech defects. Approximately 60% of strokes are caused by occlusion of the middle cerebral artery (MCAo), resulting in damage in the striatum and cortex with consequent deficits to sensory and motor systems. There is therefore a substantial clinical need for treatments that reduce or alleviate the deficits. Typical therapies for stroke are aimed at interrupting the cascade of events that lead to intraneuronal calcium accumulation and cell death, and to provide stimulation through rehabilitation, e.g. physiotherapy, to promote intracerebral reorganisation. However, pharmacological treatments must be administered quickly to protect against cell death that typically occurs within three hours of occlusion. In addition, the therapy based on rehabilitation appears to be limited to a period of 3-6 months after stroke, after which residual disabilities do not undergo appreciable reduction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with brain damage, 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:

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Under “Issued Patents,” click “Quick Search.” Then, type “brain damage” (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 brain damage. You can also use this procedure to view pending patent applications concerning brain damage. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON BRAIN DAMAGE Overview This chapter provides bibliographic book references relating to brain damage. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on brain damage 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 “brain damage” (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 brain damage: •

Dying of Enoch Wallace: Life, Death and the Changing Brain Source: New York, NY: McGraw-Hill. 2001. 260 p. Contact: Available from McGraw Hill. 2 Penn Plaza, New York, NY 10121. (212) 9045951; FAX: 212) 904-4091. Internet: http://books.mcgraw- hill.com. PRICE: $24.95. ISBN: 0071362088. Also available in electronic format (Adobe Acrobat or Microsoft reader, eISBN0071374485). Summary: This book chronicles advances in the understanding and treatment of brain diseases such as Alzheimer's disease (AD) over the past century. It highlights such events as the realization that many nerve growth and survival factors operate within the brain and the peripheral nervous system, and the discovery that neurons can be produced in the adult brain. These and related discoveries have led to a reevaluation of brain function and treatment and the possibility of reversing brain damage such as that caused by AD. The documentation of these developments is intertwined with the story

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of Enoch Wallace, a fictionalized man with AD, to present the experience of AD from a more personal perspective. The author uses this character's day-to-day struggles to illustrate the neuroscientific breakthroughs in more practical, human terms. •

When the Brain Dies First Source: Danbury, CT: Grolier Publishing. 2000. 144 p. Contact: Available from Grolier Publishing. 90 Sherman Turnpike, Danbury, CT 06816. (800) 621-1115. Internet: http://www.publishing.grolier.com. PRICE: $25.00. ISBN: 0531115437. Summary: This book examines the different causes of brain damage and the death of brain cells. It includes information about Alzheimer's disease and other disorders that cause dementia. Eleven chapters address the following topics: the structure and function of the healthy brain; closed head injuries; when the skull is opened through accidents or injuries, or for the purpose of brain surgery; brain death by infection; Alzheimer's disease; Parkinson's, Huntington's, and other degenerative diseases; brain death by stroke and vascular dementia; brain death by toxic chemicals, drug, and diet; life and death choices when the brain dies first; caring for people with injured brains and dementia; and preventing or delaying the onset of brain diseases. The book includes a glossary, a list of resources for additional information, and an index.

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Broken Connections: Alzheimer's Disease: Part I: Origin and Course: The World of the Patient Source: Amsterdam, Netherlands: Swets and Zeitlinger B. V. Lisse. 1994. 171 p. Contact: Available from Taylor and Francis. 1900 Frost Road, Suite 101, Bristol, PA 19007-1598. (215) 785-5800. PRICE: $20.00. ISBN: 9026513348. Summary: This book is part 1 of a two-part guide for the daily care and nursing of patients with Alzheimer's disease (AD) (see AZBK04767 for part 2). It examines the origin and course of AD, describing the comparatively predictable course of the functional decline and the order in which the cognitive and motor functions usually are lost. It connects the behavioral manifestations of AD with the underlying neurologic pathology. Topics include: dementia, intellectual life, and the gradual deterioration in which the acquired functions are lost; AD, its discoverer, and detailed AD data in diagrams of the brain and nervous system; the care and nursing of AD patients; how changes in human behavior become manifest; how brain damage causes regression and influences behavior; the development and functioning of the sensory, motor, and pyramidal systems; how human behavior can be influenced by AD-induced disturbances in brain function; stages in caregiving that closely correspond to the evolutionary phases of the disease; and ways of dealing with losses due to the disease. The author distinguishes four illness phases: phase 1 has an indiscernible beginning; in phase 2 the patient's perception of his or her environment becomes fragmented; in phase 3 the patient has no notion of time and space; and in phase 4 the patient loses his or her self-awareness. 303 references.

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Narrative Discourse in Neurologically Impaired and Normal Aging Adults Source: San Diego, CA: Singular Publishing Group, Inc. 1993. 337 p. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 238-6777. Fax (800) 774-8398 or (619)

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238-6789. E-mail: [email protected]. Website: www.singpub.com. PRICE: $65.00 plus shipping and handling. ISBN: 1565930835. Summary: This book, intended for researchers and students in neuropsychology, speech-language pathology, cognitive psychology, and linguistics, is a collection of papers on narrative ability in non-standard populations. Chapters are organized around four sections: theoretical considerations, aspects of narrative ability in healthy elderly adults, the effects of focal damage to the right and left cerebral hemispheres, and the effects of diffuse brain damage such as that associated with the dementia in Alzheimer's disease. The book is intended to complement studies done with standard subject populations, in order to add dimension to the body of literature on narrative discourse and how it involves different aspects of human language and cognition. Each chapter includes references; a subject index concludes the text.

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 “brain damage” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “brain damage” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “brain damage” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

A comparison of the Halstead-Reitan neuropsychological test battery and other procedures in the assessment of brain damage in South Africa by M. J. Adan; ISBN: 0796903549; http://www.amazon.com/exec/obidos/ASIN/0796903549/icongroupinterna

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Acquired Apraxia of Speech in Aphasic Adults: Theoretical and Clinical Issues (Brain Damage, Behavior and Cognition: Developments in Clinical Neuro) by Paula SquareStorer (Editor) (1992); ISBN: 086377184X; http://www.amazon.com/exec/obidos/ASIN/086377184X/icongroupinterna

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Acquired Neurological Speech/Language Disorders in Childhood (Brain Damage, Behaviour and Cognition) by Bruce E. Murdoch (Editor) (1990); ISBN: 085066490X; http://www.amazon.com/exec/obidos/ASIN/085066490X/icongroupinterna

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Addiction & Brain Damage by Richter D; ISBN: 0709902549; http://www.amazon.com/exec/obidos/ASIN/0709902549/icongroupinterna

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Addiction and Brain Damage by Derek Richter; ISBN: 0839141394; http://www.amazon.com/exec/obidos/ASIN/0839141394/icongroupinterna

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Alcohol, drugs, and brain damage : proceedings of a symposium [on] effects of chronic use of alcohol and other psychoactive drugs on cerebral function; ISBN: 0888680090; http://www.amazon.com/exec/obidos/ASIN/0888680090/icongroupinterna

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Asphyxia and Fetal Brain Damage by Dev Maulik (Editor); ISBN: 0471184276; http://www.amazon.com/exec/obidos/ASIN/0471184276/icongroupinterna

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Assessment and Management of Emotional and Psychosocial Reactions to Brain Damage and Aphasia by Peter Wahrborg; ISBN: 0951472836; http://www.amazon.com/exec/obidos/ASIN/0951472836/icongroupinterna

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Assessment and Management of Emotional Reactions to Brain Damage and Aphasia (Far Communication Disorders Series) by Peter Wahrborg, Peter Whahrborg; ISBN: 1879105187; http://www.amazon.com/exec/obidos/ASIN/1879105187/icongroupinterna

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Assessment of Brain Damage: A Neuropsychological Key Approach by Elbert W., Russell, et al; ISBN: 0471745502; http://www.amazon.com/exec/obidos/ASIN/0471745502/icongroupinterna

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Brain Damage by Herbert Burkholz; ISBN: 0689120095; http://www.amazon.com/exec/obidos/ASIN/0689120095/icongroupinterna

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Brain Damage by Burkholz Herbert; ISBN: 0747232938; http://www.amazon.com/exec/obidos/ASIN/0747232938/icongroupinterna

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Brain damage : medico-legal aspects; ISBN: 187511436X; http://www.amazon.com/exec/obidos/ASIN/187511436X/icongroupinterna

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Brain Damage and Mental Retardation: A Psychological Evaluation by J Khanna; ISBN: 0398026319; http://www.amazon.com/exec/obidos/ASIN/0398026319/icongroupinterna

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Brain Damage and Recovery: Research and Clinical Perspectives by Stanley Finger; ISBN: 0122567803; http://www.amazon.com/exec/obidos/ASIN/0122567803/icongroupinterna

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Brain damage and the mind by Moyra Williams; ISBN: 0140801405; http://www.amazon.com/exec/obidos/ASIN/0140801405/icongroupinterna

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Brain Damage Claims: Coping With Neuropsychological Evidence by David Faust, et al (1991); ISBN: 1879689006; http://www.amazon.com/exec/obidos/ASIN/1879689006/icongroupinterna

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Brain damage in boxers: a study of the prevalence of traumatic encephalopathy among ex-professional boxers by Anthony Herber Roberts; ISBN: 0272760218; http://www.amazon.com/exec/obidos/ASIN/0272760218/icongroupinterna

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Brain Damage in School Age Children by Council for Exceptional Children; ISBN: 0865860068; http://www.amazon.com/exec/obidos/ASIN/0865860068/icongroupinterna

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Brain Damage in the Newborn & Its Neurologic Sequels: Pathplogic and Clinical Correlation by Abraham Towbin (1998); ISBN: 0966055101; http://www.amazon.com/exec/obidos/ASIN/0966055101/icongroupinterna

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Brain Damage in the Preterm Infant by Nigel Paneth (Author), et al (1994); ISBN: 189868300X; http://www.amazon.com/exec/obidos/ASIN/189868300X/icongroupinterna

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Brain Damage Plastic World: Surreal Poems [DOWNLOAD: ADOBE READER] by William Moss (2002); ISBN: B0000CBX68; http://www.amazon.com/exec/obidos/ASIN/B0000CBX68/icongroupinterna

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Brain Damage, Behaviour, and the Mind by Moyra Williams; ISBN: 0471997048; http://www.amazon.com/exec/obidos/ASIN/0471997048/icongroupinterna

Books

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Brain Damage, Brain Repair by James W. Fawcett (Editor), et al (2003); ISBN: 0198523378; http://www.amazon.com/exec/obidos/ASIN/0198523378/icongroupinterna

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Category Specificity in Brain and Mind (Brain Damage, Behaviour and Cognition) by Emer M. E. Forde (Editor), Glyn W. Humphreys (Editor); ISBN: 1841692905; http://www.amazon.com/exec/obidos/ASIN/1841692905/icongroupinterna

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Cellular & Molecular Mechanisms of Ischemic Brain Damage by Bo K. Siesjo (Editor), Tadeusz Wieloch (Editor); ISBN: 0781702771; http://www.amazon.com/exec/obidos/ASIN/0781702771/icongroupinterna

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Cerebral Reorganization of Function After Brain Damage by Harvey S. Levin (Editor), Jordan Grafman (Editor); ISBN: 0195120264; http://www.amazon.com/exec/obidos/ASIN/0195120264/icongroupinterna

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Characteristics of Aphasia: Brain Damage, Behavioral and Cognition: Developments in Clinical Neuropsychology by Chris Code (Editor); ISBN: 0850664462; http://www.amazon.com/exec/obidos/ASIN/0850664462/icongroupinterna

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Classic Cases in Neuropsychology (Brain Damage, Behaviour & Cognition Series) by Chris Code (Editor), et al (1996); ISBN: 0863773958; http://www.amazon.com/exec/obidos/ASIN/0863773958/icongroupinterna

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Clinical and Neuropsychological Aspects of Closed Head Injury (Brain Damage, Behaviour and Cognition) by John T. E. Richardson, John T.E. Richardson; ISBN: 086377752X; http://www.amazon.com/exec/obidos/ASIN/086377752X/icongroupinterna

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Clinical Neuropsychology of Alcoholism (Brain Damage, Behaviour and Cognition Series) by Robert G. Knight, et al (1994); ISBN: 0863773273; http://www.amazon.com/exec/obidos/ASIN/0863773273/icongroupinterna

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Cognitive Rehabilitation in Perspective (Brain Damage, Behavior and Cognition Developments in Clinical neuropsycholoGy) by R.L. Wood, Ian Fussey (Editor); ISBN: 0850664454; http://www.amazon.com/exec/obidos/ASIN/0850664454/icongroupinterna

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Cognitive Retraining Using Microcomputers (Brain Damage, Behaviour & Cognition) by Veronica A. Bradley, et al (1993); ISBN: 0863772021; http://www.amazon.com/exec/obidos/ASIN/0863772021/icongroupinterna

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Communication Disorders Following Traumatic Brain Injury (Brain Damage, Behaviour and Cognition) by Skye McDonald (Editor), et al; ISBN: 0863777252; http://www.amazon.com/exec/obidos/ASIN/0863777252/icongroupinterna

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Conversation and Brain Damage by Charles Goodwin (Editor) (2003); ISBN: 0195129539; http://www.amazon.com/exec/obidos/ASIN/0195129539/icongroupinterna

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Current Progress in the Understanding of Secondary Brain Damage from Trauma and Ischemia (Acta Neurochirurgica. Supplement, 73) by A. Baethmann (Editor), et al (1999); ISBN: 3211833137; http://www.amazon.com/exec/obidos/ASIN/3211833137/icongroupinterna

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David: A Mother's Story of Her Son's Recovery from a Coma and Brain Damage by Dorothy, Landvater; ISBN: 0131969560; http://www.amazon.com/exec/obidos/ASIN/0131969560/icongroupinterna

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Developmental Cognitive Neuropsychology (Brain Damage, Behaviour and Cognition) by Christine Temple; ISBN: 0863774016; http://www.amazon.com/exec/obidos/ASIN/0863774016/icongroupinterna

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Developmental Disorders of the Frontostriatal System: Neuropsychological, Neuropsychiatric and Evolutionary Perspectives (Brain Damage, Behaviour and Cognition) by John L. Bradshaw (2002); ISBN: 1841692271; http://www.amazon.com/exec/obidos/ASIN/1841692271/icongroupinterna

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Developmental Neuropsychology: A Clinical Approach (Brain Damage, Behaviour and Cognition) by Vicki Anderson, et al (2003); ISBN: 0863777058; http://www.amazon.com/exec/obidos/ASIN/0863777058/icongroupinterna

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Discourse Ability and Brain Damage: Theoretical and Emperical Perspectives (Springer Studies in Neuropsychology) by Yves Joanette, Hiram H. Brownell (Editor) (1990); ISBN: 0387970444; http://www.amazon.com/exec/obidos/ASIN/0387970444/icongroupinterna

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Early Brain Damage: Neurobiology and Behavior (Behavioral Biology) by C. Robert Almli (Editor); ISBN: 0120529025; http://www.amazon.com/exec/obidos/ASIN/0120529025/icongroupinterna

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Early Brain Damage: Research Orientations and Clinical Observations (Behavioral Biology) by Robert Almli (Editor); ISBN: 0120529017; http://www.amazon.com/exec/obidos/ASIN/0120529017/icongroupinterna

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Evaluation and Education of Children With Brain Damage, by Morton. Bortner; ISBN: 039800191X; http://www.amazon.com/exec/obidos/ASIN/039800191X/icongroupinterna

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Functional Recovery from Brain Damage by M. W. Van Hof; ISBN: 0444803947; http://www.amazon.com/exec/obidos/ASIN/0444803947/icongroupinterna

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George Carlin: Sometimes a Little Brain Damage Can Help by George Carlin; ISBN: 0894712713; http://www.amazon.com/exec/obidos/ASIN/0894712713/icongroupinterna

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How to Survive High School With Minimal Brain Damage; ISBN: 0881661074; http://www.amazon.com/exec/obidos/ASIN/0881661074/icongroupinterna

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How to Survive High School With Minimal Brain Damage by Doug Lansky, Aaron Dorfman (Contributor); ISBN: 0671658905; http://www.amazon.com/exec/obidos/ASIN/0671658905/icongroupinterna

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Lipid Mediators in Ischemic Brain Damage and Experimental Epilepsy (New Trends in Lipid Mediators Research, Vol 4) by Nicolas G. Bazan (Editor) (1990); ISBN: 3805550685; http://www.amazon.com/exec/obidos/ASIN/3805550685/icongroupinterna

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Mechanisms of secondary brain damage : current state; ISBN: 3211824219; http://www.amazon.com/exec/obidos/ASIN/3211824219/icongroupinterna

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Mechanisms of Secondary Brain Damage in Cerebral Ischemia and Trauma (Acta Neurochirurgica. Supplementum, 66) by A. Baethmann (Editor), et al; ISBN: 3211828176; http://www.amazon.com/exec/obidos/ASIN/3211828176/icongroupinterna

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Mechanisms of Secondary Brain Damage: Current State (Acta Neurochirurgica, Supplementum 57) by A. Baethmann, et al; ISBN: 0387824219; http://www.amazon.com/exec/obidos/ASIN/0387824219/icongroupinterna

Books

163

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Molecular Mechanisms of Ischemic Brain Damage (Progress in Brain Research, Vol 63) by K. Kogure, et al; ISBN: 0444806547; http://www.amazon.com/exec/obidos/ASIN/0444806547/icongroupinterna

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Neurobehavior of Language and Cognition - Studies of Normal Aging and Brain Damage by Lisa Tabor Connor (Editor), Loraine K. Obler (Editor); ISBN: 0792378776; http://www.amazon.com/exec/obidos/ASIN/0792378776/icongroupinterna

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Neurobehavioural Disability and Social Handicap Following Traumatic Brain Injury (Brain Damage, Behaviour and Cognition) by Rodger Ll. Wood (Editor), et al; ISBN: 0863778895; http://www.amazon.com/exec/obidos/ASIN/0863778895/icongroupinterna

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Neurobiology of Ischemic Brain Damage (Progress in Brain Research, Vol 96) by Kyuya Kogure (Editor), et al; ISBN: 0444896031; http://www.amazon.com/exec/obidos/ASIN/0444896031/icongroupinterna

•

Neuropsychiatry, Neuropsychology, and Clinical Neuroscience: Emotion, Evolution, Cognition, Language, Memory, Brain Damage, and Abnormal by Rhawn Joseph, Joseph Rhawn; ISBN: 0683044850; http://www.amazon.com/exec/obidos/ASIN/0683044850/icongroupinterna

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Neuropsychological Studies of Nonfocal Brain Damage (1988); ISBN: 3540966056; http://www.amazon.com/exec/obidos/ASIN/3540966056/icongroupinterna

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Neuropsychological Studies of Nonfocal Brain Damage: Dementia and Trauma (Springer Series in Neuropsychology) by Harry A. Whitaker (Editor) (1988); ISBN: 0387966056; http://www.amazon.com/exec/obidos/ASIN/0387966056/icongroupinterna

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Neuropsychology and the Dementias (Brain Damage, Behaviour and Cognition: Developments in Clinical neuropsychOlogy) by Siobhan Hart, et al (1997); ISBN: 0863771971; http://www.amazon.com/exec/obidos/ASIN/0863771971/icongroupinterna

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Neuropsychology of the Amnestic Syndrome (Brain Damage, Behaviour & Cognition) by Alan J. Parkin, et al; ISBN: 0863772013; http://www.amazon.com/exec/obidos/ASIN/0863772013/icongroupinterna

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Newborn at High Risk of Brain Damage: Euraibi International Workshop, Siena, April 2001 (Biology of the Neonate) (2001); ISBN: 3805572123; http://www.amazon.com/exec/obidos/ASIN/3805572123/icongroupinterna

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PERINATAL BRAIN DAMAGE by Pape; ISBN: 0801637872; http://www.amazon.com/exec/obidos/ASIN/0801637872/icongroupinterna

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Perinatal Events and Brain Damage in Surviving Children by F. Kubli, et al; ISBN: 0387181113; http://www.amazon.com/exec/obidos/ASIN/0387181113/icongroupinterna

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Perinatal Events and Brain Damage in Surviving Children; ISBN: 3540181113; http://www.amazon.com/exec/obidos/ASIN/3540181113/icongroupinterna

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Preoperative Events: Their Effects on Behavior Following Brain Damage (Comparative Cognition an Neuroscience Series) by Jay Schulkin (Editor) (1989); ISBN: 0805805354; http://www.amazon.com/exec/obidos/ASIN/0805805354/icongroupinterna

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Preventable Brain Damage: Brain Vulnerability and Brain Health by Donald I. Templer, et al (1992); ISBN: 0826174000; http://www.amazon.com/exec/obidos/ASIN/0826174000/icongroupinterna

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Recovery from Brain Damage: Reflections and Directions (Advances in Experimental Medicine and Biology, 325) by F.D. Rose, et al (1992); ISBN: 0306443449; http://www.amazon.com/exec/obidos/ASIN/0306443449/icongroupinterna

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Recovery from Brain Damage: Research and Theory by Stanley Finger (Editor) (1978); ISBN: 0306311070; http://www.amazon.com/exec/obidos/ASIN/0306311070/icongroupinterna

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Shock, Sepsis, and Organ Failure: Brain Damage Secondary to HemorrhagicTraumatic Shock, Sepsis, and Traumatic Brain Injury by G. Schlag (Editor), et al; ISBN: 3540624198; http://www.amazon.com/exec/obidos/ASIN/3540624198/icongroupinterna

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Shock, Sepsis, and Organ Failure: I Brain Damage Secondary to HemorrhagicTraumatic Shock: II Brain Damage Secondary to Sepsis: III Brain Damage Secondary to Traumatic Brain Injury by Austria)/ Schlag, Gunther/ Traber, D. Wiggers Bernard Conference 1996 Krumbach (1997); ISBN: 0387624198; http://www.amazon.com/exec/obidos/ASIN/0387624198/icongroupinterna

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Society pays the high costs of minimal brain damage in America by Camilla May Anderson; ISBN: 0802703739; http://www.amazon.com/exec/obidos/ASIN/0802703739/icongroupinterna

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Spatial Neglect: A Clinical Handbook for Diagnosis and Treatment (Brain Damage, Behaviour and Cognition) by Ian H. Robertson, Peter W. Halligan (2001); ISBN: 0863778100; http://www.amazon.com/exec/obidos/ASIN/0863778100/icongroupinterna

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Status epilepticus, mechanisms of brain damage and treatment; ISBN: 0890046239; http://www.amazon.com/exec/obidos/ASIN/0890046239/icongroupinterna

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The Learning of Motor Control Following Brain Damage: Experimental and Clinical Studies by Theodorus Wilhelmus Mulder (1985); ISBN: 902650649X; http://www.amazon.com/exec/obidos/ASIN/902650649X/icongroupinterna

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The Neuropsychology of Schizophrenia (Brain Damage, Behaviour and Cognition Series) by Anthony S. David, John C. Cutting (Editor); ISBN: 0863773036; http://www.amazon.com/exec/obidos/ASIN/0863773036/icongroupinterna

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The Shattered Mind: The Person After Brain Damage by Howard Gardner; ISBN: 0394719468; http://www.amazon.com/exec/obidos/ASIN/0394719468/icongroupinterna

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Then Came Brain Damage-19.95 by Alex Hawkins; ISBN: 5553446899; http://www.amazon.com/exec/obidos/ASIN/5553446899/icongroupinterna

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Transcortical Aphasias (Brain Damage, Behaviour and Cognition) by Marcelo L. Berthier; ISBN: 0863778402; http://www.amazon.com/exec/obidos/ASIN/0863778402/icongroupinterna

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Understanding and Living With Brain Damage by Patrick E. Logue; ISBN: 0398034192; http://www.amazon.com/exec/obidos/ASIN/0398034192/icongroupinterna

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Understanding Brain Damage (1991); ISBN: 0443022240; http://www.amazon.com/exec/obidos/ASIN/0443022240/icongroupinterna

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Understanding Brain Damage: A Primer of Neuropsychological Evaluation by Kevin W. Walsh; ISBN: 0443043205; http://www.amazon.com/exec/obidos/ASIN/0443043205/icongroupinterna

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Unilateral Neglect: Clinical and Experimental Studies (Brain Damage, Behaviour & Cognition) by Ian H. Robertson, John C. Marshall (Editor) (1993); ISBN: 0863772080; http://www.amazon.com/exec/obidos/ASIN/0863772080/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 “brain damage” (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:10 •

Brain damage and behavior; a clinical-experimental study, by Jerome L. Schulman [et al.]. Author: Schulman, Jerome L.; Year: 1966; Springfield, Ill. Thomas [c1965]

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Brain damage and mental retardation. Author: Khanna, J. L.; Year: 1969; Springfield, Ill., Thomas [c1968]

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Brain damage and the mind. Author: Williams, Moyra.; Year: 1959; [Baltimore] Penguin Books [1970]

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Brain damage by inborn errors of metabolism; symposium organized by the Interdisciplinary Society of Biological Psychiatry, Amsterdam, 6 October 1967. Author: Interdisciplinary Society of Biological Psychiatry.; Year: 1965; Haarlem, Bohn, 1968

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Brain damage in boxers; a study of the prevalence of traumatic encephalopathy among ex-professional boxers. Author: Roberts, A. H. (Anthony Herber); Year: 1968; London, Pitman [1969]; ISBN: 272760218

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Brain damage in the fetus and newborn from hypoxia and asphyxia.; Year: 1964; Columbus, Ohio, Ross Laboratories [c1967]

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Evaluation and education of children with brain damage. Author: Bortner, Morton.; Year: 1965; Springfield, Ill., Thomas [c1968]

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Management of brain damaged children; a parents' and teachers' guide, by Frances G. Berko, Martin J. Berko [and] Stephanie C. Thompson. Author: Berko, Frances G.; Year: 1968; Springfield, Ill., Thomas [c1970]

10

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.

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Chapters on Brain Damage In order to find chapters that specifically relate to brain damage, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and brain damage 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 “brain damage” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on brain damage: •

Brain Damage in Aphasia Source: in Benson, D.F.; Ardila, A. Aphasia: A Clinical Perspective. New York, NY: Oxford University Press, Inc. 1996. p. 61-87. Contact: Available from Oxford University Press, Inc. 200 Madison Avenue, New York, NY 10016. (800) 334-4249 or (212) 679-7300. PRICE: $49.95 plus shipping and handling. ISBN: 0195089340. Summary: This chapter on brain damage in aphasia is from a book that presents an integrated analysis of the language disturbances associated with brain pathology. The authors note that the underlying disease process must be recognized and treated along with the language problem; both the type of language therapy offered and the patient's prognosis depend on the basic pathology. The authors discuss some of the more common brain disorders associated with aphasia, including vascular disorders (thrombosis, embolism, hemorrhage), trauma, intracranial neoplasms, infections (including intracranial abscess), and miscellaneous causes of aphasia, including multiple sclerosis, epilepsy, Alzheimer's disease, Jakob-Creutzfeldt disease, and progressive aphasia. The authors continue by discussing localization techniques (to locate the neuroanatomical site of brain damage in cases of aphasia), neuropathology, neurosurgery, posttrauma skull defects, the neurologic examination, and brain-imaging studies. The authors conclude that the localization of aphasia-producing lesions has advanced tremendously in the past several decades, particularly with the advent of noninvasive techniques that can produce accurate anatomical localizations. 10 figures. 2 tables. (AA-M).

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CHAPTER 7. MULTIMEDIA ON BRAIN DAMAGE Overview In this chapter, we show you how to keep current on multimedia sources of information on brain damage. 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 brain damage is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “brain damage” 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 “brain damage” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on brain damage: •

Street Smarts Contact: Milestone Productions, 1565 16th Ave, San Francisco, CA, 94122, (415) 641-8436. Summary: This video uses clay animation to provide basic information about the dangers of substance abuse and HIV/AIDS. The first module of the video emphasizes the fact that although people using drugs on the street may look like they're having fun, they are actually at great risk for transmitting HIV. The video strongly discourages the use of alcohol, crack, and ice. The first module also explains that HIV is transmitted by sharing needles, by having sex with someone infected by HIV, and by the birth of a child to an HIV-positive mother. The second module warns the viewer that people who use drugs can become violent, may get involved in prostitution, could suffer from brain damage, and might not protect themselves from HIV/AIDS. It also stresses the importance of getting help with drug addiction and staying in school. The third module emphasizes that youth should recognize the potential for trouble. Youth are strongly encouraged to make their own decisions about drugs and sex and to protect themselves

168 Brain Damage

from HIV/AIDS and other STDs. The video also discusses sexual abstinence and the use of condoms. A review section is also provided. •

AIDS: A Matter of Life Contact: Philadelphia Department of Public Health, AIDS Activities Coordinating Office, 1101 Market 9th Fl, Philadelphia, PA, 19107, (215) 685-5600, http://www.phila.gov/departments/health/AIDS/AIDS.html. Summary: Through interviews with Persons with AIDS (PWA's) from diverse backgrounds, this videorecording presents a macroview of Human immunodeficiency virus (HIV) transmission. It examines the physical, emotional, and psychological implications of the disease for patients and family. The videorecording addresses modes of contagion involving needle sharing, bisexual and multiple sex partners, and blood transfusions. It also stresses methods of prevention including safer sexual conduct and use of condoms. It mentions symptoms and illnesses that arise from the Acquired immunodeficiency syndrome (AIDS), such as nausea and fatigue, often followed by brain damage, pneumonia, and thrush. The role of the church as a support system is also examined.

Bibliography: Multimedia on Brain Damage 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 brain damage (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 brain damage: •

Dystocia and arrests in labor and prevention of brain damage [videorecording] Source: the University of Texas Medical School at Houston; produced by UT-TV, Houston; Year: 1991; Format: Videorecording; [Houston, Tex.: UT/TV], c1991

•

Hypoxic brain damage [videorecording]: clinical diagnosis, intervention and outcome Source: presented by the Department of Pediatrics, Emory University School of Medicine; Year: 1983; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1983

•

The Brain damaged child [motion picture] Source: Eastern Pennsylvania Psychiatric Institute; Year: 1968; Format: Motion picture; University Park, Pa.: Pennsylvania State Univ. Psychological Cinema Register, [1968]

•

Verbal impairment associated with brain damage [motion picture] Source: Institute of Physical Medicine and Rehabilitation, New York University Medical Center; produced by Public Health Service Audiovisual Facility; Year: 1966; Format: Motion picture; Atlanta: National Medical Audiovisual Center; [Washington: for sale by National Audiovisual Center, 1966]

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CHAPTER 8. PERIODICALS AND NEWS ON BRAIN DAMAGE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover brain damage.

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

Separated Guatemalan twin has brain damage Source: Reuters Health eLine Date: July 09, 2003

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Study: Pot doesn't cause permanent brain damage Source: Reuters Health eLine Date: June 27, 2003

170 Brain Damage

•

Antioxidants counter alcohol brain damage in rats Source: Reuters Health eLine Date: June 03, 2003

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US transplant girl has severe brain damage Source: Reuters Health eLine Date: February 21, 2003

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Brain damage in boxers seen long before symptoms Source: Reuters Health eLine Date: November 14, 2002

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Flashing light could spot brain damage before birth Source: Reuters Health eLine Date: September 06, 2002

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'Silent' brain damage common after bypass surgery Source: Reuters Health eLine Date: July 18, 2002

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Gas may block brain damage during surgery Source: Reuters Health eLine Date: May 30, 2002

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Post-stroke anger may be due to brain damage Source: Reuters Health eLine Date: April 09, 2002

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Doctors test method to cut brain damage in babies Source: Reuters Health eLine Date: January 31, 2002

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Women seem more vulnerable to Ecstasy brain damage Source: Reuters Health eLine Date: November 30, 2001

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Alcoholics may reverse brain damage by quitting Source: Reuters Health eLine Date: November 14, 2001

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Loud 'rave' music could boost meth brain damage Source: Reuters Health eLine Date: November 02, 2001

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Green tea chemical may prevent brain damage Source: Reuters Health eLine Date: October 12, 2001

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Study charts path of brain damage in schizophrenia Source: Reuters Health eLine Date: September 24, 2001

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Technique temporarily simulates brain damage Source: Reuters Health eLine Date: August 28, 2001

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Fever during labor linked to infant brain damage Source: Reuters Health eLine Date: July 19, 2001

Periodicals and News

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Brain damage case reveals mind's filing system Source: Reuters Health eLine Date: May 21, 2001

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Ecstasy may cause permanent brain damage in fetus Source: Reuters Health eLine Date: May 03, 2001

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “brain damage” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “brain damage” (or synonyms). If you know the name of a company that is relevant to brain damage, 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/.

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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 “brain damage” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “brain damage” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on brain damage: •

Hallucinations, Paranoia: Practical Suggestions for Understanding Problem Behaviors Source: Caring and Sharing. [Newsletter] 9(4): 7-8. Winter 1990. Contact: Available from Alzheimer's Association, South Central Kansas Chapter. P.O. Box 2763, Wichita, KS 67201. (316) 261-9099. PRICE: Call for price information. Summary: This second of 2 articles on the topic 'Understanding Difficult Behaviors,' discusses the definition and possible causes of paranoia, delusions, and hallucinations, which are sometimes seen in Alzheimer's disease patients. Paranoia is defined as unrealistic, blaming beliefs. Paranoia results from damage to the part of the brain that makes judgments and separates facts from fiction. Delusions are beliefs that are contrary to fact and remain fixed or persistent despite all evidence to the contrary. Hallucinations are sensory experiences that cannot be verified by anyone other than the person experiencing them. Possible physiological or medical causes for these disorders include sensory deficits, medications, brain damage due to Alzheimer's disease progression, or trauma. Environmental causes include unfamiliar environment or caregivers, or disruption in routines. Coping strategies include having vision and hearing tested, seeking medical evaluation, medications, seeking psychiatric evaluation, and employing approaches with the patient that instill trust, understanding, and empathy. Caregivers must not take accusations personally and must recognize that the person cannot control these behaviors.

Academic Periodicals covering Brain Damage Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to brain damage. In addition to these sources, you can search for articles covering brain damage 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.”

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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 9. 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 brain damage. 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 nonprofit 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 brain damage. 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.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to brain damage: Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed •

Systemic - U.S. Brands: Acel-Imune; Certiva; Infanrix; Tripedia http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202201.html

Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed and Haemophilus B Conjugate Vaccine •

Systemic - U.S. Brands: Tetramune http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202911.html

Measles Virus Vaccine Live •

Systemic - U.S. Brands: Attenuvax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202338.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. 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

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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 Institute11: •

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/

11

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

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

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

•

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

•

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

•

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

•

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

•

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

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 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:13 •

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

12

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

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “brain damage” using the “Detailed Search” option. Go directly to the following hyperlink: 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 the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “brain damage” (or synonyms) into the “For these words:” box. The following is a sample result: •

Estimating the Utilization and Costs of Formal and Informal Care Provided to BrainImpaired Adults: Briefing Paper Source: San Francisco, CA: Institute for Health and Aging, University of California-San Francisco. 1986. 62 p. Contact: Available from Institute for Health and Aging, University of California-San Francisco. San Francisco, CA 94143. (415) 362-3620. PRICE: $9.00. Summary: This briefing paper for policy makers presents the findings and recommendations of a study of the literature of costs of formal and informal care for adults suffering from brain damage and degenerative brain disorders. The study sought to: identify a methodology for assessing the costs of illness for brain impairment, identify data relevant to costs and service utilization of brain impairment, and develop a research agenda for studying the cost of illness and financing mechanisms for services for brain-impaired adults and their families. The results of the study are discussed in detail. The study identified the two highest recommendations as: (1) better data and data collection procedures need developing to obtain accurate information on brainimpaired adults and their families; and (2) a comprehensive study (preferentially, longitudinal) is needed of the cost of illness of brain-impaired adults. Ten additional recommendations are elaborated.

•

Recovery from traumatic brain injury in children Source: Arlington, VA: National Center for Education in Maternal and Child Health. 1997. 8 pp. Contact: Available from Librarian, National Center for Education in Maternal and Child Health, 2000 15th Street, North, Suite 701, Arlington, VA 22201-2617. Telephone: (703) 524-7802 / fax: (703) 524-9335 / e-mail: [email protected] / Web site: http://www.ncemch.org. Photocopy available at no charge; also available from the Web site at no charge. Summary: This report summarizes a Maternal and Child Health funded project presented at a seminar July 16, 1997. This project examines the impact of pediatric moderate-to-severe traumatic brain damage on families and whether the child's

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recovery is influenced by the family environment. The report ends with reaction to the project and discussion and a publication list. [Funded by the Maternal and Child Health Bureau]. •

Practice Parameter: Management of Hyperbilirubinemia in the Healthy Term Newborn: Technical Report Source: Elk Grove Village, IL: American Academy of Pediatrics. 1994. 66 p. Contact: Available from American Academy of Pediatrics. Publications Department, 141 Northwest Point Boulevard, P.O. Box 927, Elk Grove Village, IL 60009-0927. (800) 4339016 or (708) 228-5005. Fax (708) 228-1281. PRICE: $9.95 (members) or $14.95 (nonmembers) plus $4.75 shipping and handling (as of 1996). Item Number AC0019. ISBN: 0910761698. Summary: This technical report supports the practice parameter for evaluating and treating neonatal hyperbilirubinemia. The first part of the report presents evidence pertaining to the incidence of brain damage caused by hyperbilirubinemia in healthy term neonates. Specific topics in the practice parameter are discussed in the next section, including the estimated impact of the practice parameter, phototherapy, difficulties with measuring bilirubin levels, and the impact of breast-feeding. The remainder of the report consists of detailed summaries of recent literature (1989 to 1993) on healthy jaundiced infants. 2 tables. 135 references.

The NLM Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “brain damage” (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

14 15

Items Found 38208 489 912 81 7 39697

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

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).

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HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “brain damage” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists19 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.20 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.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for 16

Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.

17

The HSTAT URL is http://hstat.nlm.nih.gov/.

18

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. 19 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 20

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. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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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/.

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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 brain damage can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to brain damage. 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 brain damage. 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 “brain damage”:

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Other guides Aneurysms http://www.nlm.nih.gov/medlineplus/aneurysms.html Brain Cancer http://www.nlm.nih.gov/medlineplus/braincancer.html Brain Diseases http://www.nlm.nih.gov/medlineplus/braindiseases.html Head and Brain Injuries http://www.nlm.nih.gov/medlineplus/headandbraininjuries.html Stroke http://www.nlm.nih.gov/medlineplus/stroke.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on brain damage. 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: •

Special Populations: Traumatic Brain Injury Source: Rockville, MD: American Speech-Language-Hearing Association (ASHA). 1999. [1 p.]. 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. PRICE: Single copy free. Summary: Communication disorders are among the behavioral disturbances that can result from traumatic brain injury (TBI). Thus, speech language pathologists and audiologists are important members of the team of health care professionals involved in the rehabilitation of these patients. This fact sheet reviews some of the statistics about people with TBI and reviews the language and communication disorders that may result from this trauma. The fact sheet notes that approximately 50,000 of the estimated two million people who have TBI each year in the U.S. have severe, persisting communication problems as a result. Left hemisphere brain damage can result in aphasia; right hemisphere damage can cause communication disorders such as problems in appropriate use of language. Hematomas and pressure-producing skull

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fractures can result in facial paralysis, deafness, muscle disorders, and loss of sensory function. 8 references. •

About Cerebral Palsy Source: South Deerfield, MA: Channing L. Bete Company, Inc. 1997. 16 p. Contact: Available from Channing L. Bete Company, Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733; Fax (800) 499-6464; http://www.channing.bete.com. PRICE: $1.25 each for 1-24 copies; bulk rates available. Item Number 39503A-5-96. Summary: This booklet describes cerebral palsy, a group of brain disorders that affects movement. Cerebral palsy (CP) results from brain damage that occurs before, during, or shortly after birth. CP affects muscle tone and coordination and can be mild or severe. This booklet describes the challenges faced by a person with CP, including physical, mental, and social challenges. The booklet reviews the causes and effects of CP; other conditions that often appear with CP; diagnostic considerations; classification of the types of CP (spastic, athetoid, ataxic, and mixed); therapy for CP (physical, occupational, speech and language); other methods for managing CP (orthotic devices, medications, surgery); use of specialized equipment for communication, learning, mobility, and daily living; special programs for people with CP, including early intervention programs, special education, and school-age programs; and legislation that regulates these special programs. The booklet concludes with a brief section of the answers to questions commonly asked by parents of a child recently diagnosed with CP. The toll-free telephone numbers of three resource organizations are also provided. The booklet is illustrated with simple line drawings of families and children in a variety of everyday settings; simple anatomical drawings are included in the sections about the physiology of CP.

•

American Speech-Language-Hearing Association Answers Questions About Adult Aphasia Source: Rockville, MD: American Speech-Language-Hearing Association (ASHA). 199x. (2 p.). 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. PRICE: Single copy free; bulk orders available. Item Number 0210114. Summary: This brochure provides basic information about adult aphasia. Aphasia is defined as a condition in which an individual has difficulty expressing thoughts and understanding what is said or written by others. The brochure, written in question and answer format, covers some of the language problems associated with aphasia, why it takes a person with aphasia so long to respond, swearing in individuals with aphasia, related communication problems caused by stroke or head injury, some of the physical problems connected with brain damage, spontaneous recovery, and support available for the person with aphasia. The brochure stresses both the importance of seeking therapy from a speech-language pathologist and the vital role that family and friends can play in rehabilitation. The brochure includes the toll-free telephone number of the American Speech-Language-Hearing Association (800-638-8255).

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•

Syphilis : What You Need to Know Contact: Education Programs Associates, Health Education Resource Center, 1 W Campbell Ave Ste 45, Campbell, CA, 95008, (408) 374-3720, http://www.cfhc.org. Summary: This brochure, for the general public, discusses the sexually transmitted disease (STD), syphilis. The first symptom of syphilis is a sore that does not hurt. Other symptoms include rash, fever, sore throat, joint pain, and loss of hair. Syphilis is treated with antibiotic shots or pills. Individuals with syphilis need to protect themselves by ensuring that partners are treated, taking all of the prescribed medication even if symptoms disappear, avoiding sex during treatment, reporting any drug side effects or new symptoms immediately to a health care provider, and undergoing follow-up treatment after the antibiotic regimen has been completed. If left untreated, syphilis can cause blindness, heart disease, brain damage, insanity, or death. Pregnant women with syphilis can infect their infants, which can lead to stillbirth or birth defects. When persons with syphilis have chancre sores, they are at a greater risk of catching the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). To help to prevent STDs, individuals should practice safer sex with condoms and foam during each sexual encounter. The brochure provides contact information for services from which individuals can learn more about syphilis.

•

Adult Aphasia Source: Bethesda, MD: National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH). June 2001. [4 p.]. Contact: Available from NIDCD Information Clearinghouse. 1 Communication Avenue, Bethesda, MD 20892-3456. Voice (800) 241-1044. TTY (800) 241-1055. Fax (301) 907-8830. E-mail: [email protected]. Website: www.nidcd.nih.gov. PRICE: Single copy free. Summary: This fact sheet covers aphasia, a communication disorder that can affect a person's ability to use and understand spoken or written words. It results from damage to the side of the brain dominant for language (the left side in most people). Aphasia usually occurs suddenly and often results from a stroke or head injury, but it can also develop slowly because of a brain tumor, an infection, or dementia. The fact sheet covers the types of aphasia, aphasia treatment options, and aphasia research at the National Institute on Deafness and Other Communication Disorders (NIDCD), including new approaches to the evaluation of patients with aphasia, new approaches to characterization, new therapeutic approaches (notably, drug therapy), and research being undertaken to understand recovery processes in the brain (with the use of magnetic resonance imaging, or MRI). In general, treatment strives to improve a person's ability to communicate. Treatment is most effective when it begins early in the recovery process and is maintained consistently over time. Major factors that influence the level of improvement include the cause of the brain damage, the area of the brain that was damaged, the extent of the injury, and the person's general health. The fact sheet notes the contact address and telephone number for the NIDCD Information Clearinghouse and lists other information resource organizations.

•

Tuberculosis in Pregnancy and Lactation Contact: Center for Pulmonary and Infectious Disease Control, University of Texas Health Center at Tyler, 11937 US Hwy 271, Tyler, TX, 75708-3154, (903) 877-7790, http://research.uthct.edu/cpidc/.

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Summary: This fact sheet presents information for pregnant women and mothers about tuberculosis (TB). Active TB must be treated immediately with prescribed to prevent its spread to children or infants. Children and infants are at a high risk for TB infection, which can cause brain damage or death. During pregnancy, a slightly different regimen of drugs is used that is not likely to affect the baby. Breastfeeding is not affected by the medications for TB, specifically, Isoniazid (INH), and it is best to continue breastfeeding when on anti-TB medicines. A positive skin test for TB infection means that the immune system recognizes a previous infection with TB. Testing during pregnancy is recommended in some cases. Treatment with INH may be postponed until a few months after delivery due to the possible effect of medication on the mother's liver. Women infected with the human immunodeficiency virus (HIV) are at special risk for TB, and infants born to mothers with HIV may be predisposed to TB. However, it is extremely rare for TB to be transferred to an infant in the womb. •

Multi-Infarct Dementia Fact Sheet Source: Bethesda, MD: National Institute on Aging. May 2002. 1 p. Contact: Alzheimer's Disease Education and Referral (ADEAR) Center. P.O. Box 8250, Silver Spring, MD 20907-8250. (800) 438-4380; (301)495-3334; FAX: (301) 495-3334. Email: [email protected]. Website: www.alzheimers.org/pubs/mid.htm. PRICE: Free. NIH Publication number 02-3433. Order number Z-43. Summary: This fact sheet provides basic information about multi-infarct dementia, including its causes, symptoms, evaluation and diagnosis, and treatment. It also suggests ways family members and friends can help someone with multi-infarct dementia cope with mental and physical problems. Multi-infarct dementia is the most common form of vascular dementia and accounts for 10 to 20 percent of all cases of progressive dementia. It is caused by a series of strokes that disrupt blood flow and damage or destroy brain tissue. The most important risk factor for multi-infarct dementia is high blood pressure. While no treatment can reverse the brain damage caused by a stroke, medicines are available to control risk factors and help prevent more strokes. The fact sheet includes a list of organizations that offer more information.

•

What Is Syphilis? Contact: California Department of Health Services, Office of AIDS, California AIDS Clearinghouse, 1443 N Martel Ave, Los Angeles, CA, 90046-4207, (323) 845-4180, http://www.hivinfo.org/cac/cachouse.shtml. Summary: This fact sheet provides general information about syphilis, a sexually transmitted disease (STD). In the incubation stage of syphilis infection, there are no symptoms, and it may take as long as ninety days from exposure for a blood test to detect it. In the primary stage, a painless sore forms on the penis, vagina, anus, or mouth and goes away without treatment; glands in the groin area may swell; blood tests will detect syphilitic bacteria; and infected individuals are highly contagious. In the secondary stage of syphilis, individuals may get more sores and rashes, particularly around the hands and feet and can spread this STD easily. In the latent stage of syphilis, persons do not show any signs of the STD, will test positive for it, and may experience serious health problems as a result of not having been treated. If left untreated, syphilis can cause brain damage, heart disease, and other long-term health problems. Practicing safer sex with condoms and seeing a doctor regularly can help to prevent syphilis. Individuals with syphilis can be treated with an antibiotic injection. Patients will need a repeat blood test one week after treatment and then every month until cured. They

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should tell their health care providers if they are pregnant, should inform their sex partners so they can get tested, and should avoid having sex until cured. The fact sheet provides contact information for services from which individuals can learn more about STDs and the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). •

Be Wise, Immunize!: Vaccinate on Time Source: Cleveland, OH: Learning Curve of Weingart Design. 199x. [2 p.]. Contact: Available from Learning Curve of Weingart Design. 4614 Prospect Avenue, Number 421, Cleveland, OH 44103-4314. (800) 795-9295. Fax (216) 881-7177. Website: www.learningcurve1.com. PRICE: $10.00 for a pack of 100; single copies are not available. Summary: This oversized bookmark lists the latest recommendations for pediatric immunizations from the Centers for Disease Control (CDC). The bookmark reminds parents that getting the shots (vaccinations) and getting all of them, is one of the most important things they can do for their babies. The front of the bookmark lists the age and recommended immunizations. The reverse side lists each of the immunizations and briefly notes what each one covers. Included are vaccines against hepatitis B, which causes liver damage; Hib (haemophilus influenzae b), which causes brain infection and brain damage; DTP or DTaP, which protects against diphtheria (serious breathing problems that can lead to paralysis and heart failure), pertussis (whooping cough), and tetanus (causes painful muscle spasms leading to lockjaw); polio (OPV), a disease that can paralyze arms and legs; MMR, measles, mumps, and rubella (rubella is German measles, a more serious form of measles that can lead to birth defects in babies); and varicella, or chicken pox. The schedule printed on the front of the bookmark is recommended by the American Academy of Pediatrics and the American Academy of Family Physicians.

•

Psychiatric Complications of Dementia Source: Tuscaloosa, AL: Dementia Education and Training Program. 1996. 14 p. Contact: University Supply Store. Attn: Jef Smith, PO Box 870291, Ferguson Center, Tuscaloosa, AL 35487. (800) 825-6802. PRICE: $3.00. Summary: This pamphlet for families and other lay caregivers is designed to explain the psychiatric complications of Alzheimer's disease and other dementias. It explains how damage to the brain caused by dementia also can cause depression, auditory and visual hallucinations, delusions, anger and other personality changes, and sundowning (restlessness in the late afternoon or evening). The text is accompanied by color photographs of the normal brain and the brain damaged by Alzheimer's disease. Ten facts about the psychiatric complications of dementia are listed. 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:

Patient Resources

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Questions and Answers About Malignant Hyperthermia (MH) Summary: Answers questions about malignant hyperthermia (MH), a condition that could be fatal or result in brain damage, failed kidneys and impaired function of other major organs in healthy individual Source: Malignant Hyperthermia Association of the United States http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4529 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 brain damage. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

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

•

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

•

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

•

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

•

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

•

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

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

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the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “brain damage” (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 “brain damage”. 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 “brain damage” (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 “brain damage” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.22

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

22

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

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)23: •

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

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

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

•

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

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

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

•

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

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

•

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/

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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/

23

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

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

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

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

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

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

•

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

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

•

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

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

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

•

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/

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

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

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

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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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).

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

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BRAIN DAMAGE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Absenteeism: Chronic absence from work or other duty. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [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] ACE: Angiotensin-coverting enzyme. A drug used to decrease pressure inside blood vessels. [NIH]

Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [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] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] 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

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microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] 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] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and

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stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] 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] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [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]

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Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnesia: Lack or loss of memory; inability to remember past experiences. [EU] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [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] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [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] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent

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variable. [NIH] Anaphylactic: Pertaining to anaphylaxis. [EU] 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] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [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] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angiopathy: Disease of the blood vessels (arteries, veins, and capillaries) that occurs when someone has diabetes for a long time. There are two types of angiopathy: macroangiopathy and microangiopathy. In macroangiopathy, fat and blood clots build up in the large blood vessels, stick to the vessel walls, and block the flow of blood. In microangiopathy, the walls of the smaller blood vessels become so thick and weak that they bleed, leak protein, and slow the flow of blood through the body. Then the cells, for example, the ones in the center of the eye, do not get enough blood and may be damaged. [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] Anomalies: Birth defects; abnormalities. [NIH] Anoxia: Clinical manifestation of respiratory distress consisting of a relatively complete absence of oxygen. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH]

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Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antiepileptic: An agent that combats epilepsy. [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] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU]

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Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antitussive: An agent that relieves or prevents cough. [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] 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] 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] Apraxia: Loss of ability to perform purposeful movements, in the absence of paralysis or sensory disturbance, caused by lesions in the cortex. [NIH] Aqueous: Having to do with water. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arcus Senilis: A corneal disease in which there is a deposition of phospholipid and cholesterol in the corneal stroma and anterior sclera. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU]

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Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Articular: Of or pertaining to a joint. [EU] Articulation: The relationship of two bodies by means of a moveable joint. [NIH] Artifacts: Any visible result of a procedure which is caused by the procedure itself and not by the entity being analyzed. Common examples include histological structures introduced by tissue processing, radiographic images of structures that are not naturally present in living tissue, and products of chemical reactions that occur during analysis. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] 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] Atherectomy: Endovascular procedure in which atheromatous plaque is excised by a cutting or rotating catheter. It differs from balloon and laser angioplasty procedures which enlarge vessels by dilation but frequently do not remove much plaque. If the plaque is removed by surgical excision under general anesthesia rather than by an endovascular procedure through a catheter, it is called endarterectomy. [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,

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or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Audition: The sense of hearing. [NIH] 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] 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] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [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

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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] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Belladonna: A species of very poisonous Solanaceous plants yielding atropine (hyoscyamine), scopolamine, and other belladonna alkaloids, used to block the muscarinic autonomic nervous system. [NIH] Benactyzine: A centrally acting muscarinic antagonist. Benactyzine has been used in the treatment of depression and is used in research to investigate the role of cholinergic systems on behavior. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benztropine: A centrally active muscarinic antagonist that has been used in the symptomatic treatment of Parkinson's disease. Benztropine also inhibits the uptake of dopamine. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bicuculline: Isoquinoline alkaloid from Dicentra cucullaria and other plants that is a competitive antagonist at GABA-A receptors and thus causes convulsions. [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] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical Phenomena: Biochemical functions, activities, and processes at organic and molecular levels in humans, animals, microorganisms, and plants. [NIH]

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Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and displays. [NIH] Biogenic Amines: A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology. [NIH] Biological Phenomena: Biological functions and activities at the organic and molecular levels in humans, animals, microorganisms, and plants. For biochemical and metabolic processes, biochemical phenomena is available. [NIH] Biological Psychiatry: An interdisciplinary science concerned with studies of the biological bases of behavior - biochemical, genetic, physiological, and neurological - and applying these to the understanding and treatment of mental illness. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [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] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Biotypes: Causes septicemic and pneumonic pasteurellosis in cattle and sheep, usually in conjunction with a virus infection such as parainfluenza 3. Also recorded as a cause of acute mastitis in cattle. [NIH] Biperiden: A muscarinic antagonist that has effects in both the central and peripheral nervous systems. It has been used in the treatment of arteriosclerotic, idiopathic, and postencephalitic parkinsonism. It has also been used to alleviate extrapyramidal symptoms induced by phenothiazine derivatives and reserpine. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in

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a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood 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 transfusion: The administration of blood or blood products into a blood vessel. [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 Viscosity: The internal resistance of the blood to shear forces. The in vitro measure of whole blood viscosity is of limited clinical utility because it bears little relationship to the actual viscosity within the circulation, but an increase in the viscosity of circulating blood can contribute to morbidity in patients suffering from disorders such as sickle cell anemia and polycythemia. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [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] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Fluids: Liquid components of living organisms. [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] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [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] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or

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within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary 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 Diseases: Pathologic conditions affecting the brain, which is composed of the intracranial components of the central nervous system. This includes (but is not limited to) the cerebral cortex; intracranial white matter; basal ganglia; thalamus; hypothalamus; brain stem; and cerebellum. [NIH] Brain Hypoxia: Lack of oxygen leading to unconsciousness. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Injuries: Acute and chronic injuries to the brain, including the cerebral hemispheres, cerebellum, and brain stem. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with diffuse axonal injury or coma, posttraumatic. Localized injuries may be associated with neurobehavioral manifestations; hemiparesis, or other focal neurologic deficits. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [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] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Butylated Hydroxytoluene: Antioxidant used in foods, cosmetics, petroleum products, etc.

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It may inhibit some neoplasms and facilitate others. [NIH] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [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] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] 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] Carbon Monoxide Poisoning: Toxic asphyxiation due to the displacement of oxygen from oxyhemoglobin by carbon monoxide. [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] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH]

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Cardiopulmonary Resuscitation: The artificial substitution of heart and lung action as indicated for heart arrest resulting from electric shock, drowning, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation and closed-chest cardiac massage. [NIH] Cardiopulmonary Resuscitation: The artificial substitution of heart and lung action as indicated for heart arrest resulting from electric shock, drowning, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation and closed-chest cardiac massage. [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] Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. [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] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] 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] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [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 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

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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 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] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] 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 Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Hemorrhage: Bleeding into a cerebral hemisphere of the brain, including lobar, subcortical white matter, and basal ganglia hemorrhages. Commonly associated conditions include hypertension; intracranial arteriosclerosis; intracranial aneurysm; craniocerebral trauma; intracranial arteriovenous malformations; cerebral amyloid angiopathy; and cerebral infarction. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH]

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Cerebrotendinous Xanthomatosis: A primary fatty degeneration of the cornea occurring physiologically as an arcus senilis. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrovascular Disorders: A broad category of disorders characterized by impairment of blood flow in the arteries and veins which supply the brain. These include cerebral infarction; brain ischemia; hypoxia, brain; intracranial embolism and thrombosis; intracranial arteriovenous malformations; and vasculitis, central nervous system. In common usage, the term cerebrovascular disorders is not limited to conditions that affect the cerebrum, but refers to vascular disorders of the entire brain including the diencephalon; brain stem; and cerebellum. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] 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] Chancre: The primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection. [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] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] 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] 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] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinergic Agents: Any drug used for its actions on cholinergic systems. Included here are agonists and antagonists, drugs that affect the life cycle of acetylcholine, and drugs that affect the survival of cholinergic neurons. The term cholinergic agents is sometimes still used in the narrower sense of muscarinic agonists, although most modern texts discourage that usage. [NIH] 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

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eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [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] 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] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] C-kit receptor: A protein on the surface of some cells that binds to stem cell factor (a substance that causes certain types of cells to grow). Altered forms of this receptor may be associated with some types of cancer. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [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] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple

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mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] 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] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] 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] Colloidal: Of the nature of a colloid. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Communication Disorders: Disorders of verbal and nonverbal communication caused by receptive or expressive language disorders, cognitive dysfunction (e.g., mental retardation), psychiatric conditions, and hearing disorders. [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]

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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] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] 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] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] 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] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH]

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Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibres. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [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 Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] 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 myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Callosum: Broad plate of dense myelinated fibers that reciprocally interconnect regions of the cortex in all lobes with corresponding regions of the opposite hemisphere. The corpus callosum is located deep in the longitudinal fissure. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [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] Cortices: The outer layer of an organ; used especially of the cerebrum and cerebellum. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to

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stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cost of Illness: The personal cost of acute or chronic disease. The cost to the patient may be an economic, social, or psychological cost or personal loss to self, family, or immediate community. The cost of illness may be reflected in absenteeism, productivity, response to treatment, peace of mind, quality of life, etc. It differs from health care costs, meaning the societal cost of providing services related to the delivery of health care, rather than personal impact on individuals. [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] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Criterion: A standard by which something may be judged. [EU] 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] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curcuma longa: A relative of the ginger plant, whose roots ease stomach pains. [NIH] Curcumin: A dye obtained from tumeric, the powdered root of Curcuma longa Linn. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. [NIH] Cyanosis: A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

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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] 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] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [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] Defibrillation: The act to arrest the fibrillation of (heart muscle) by applying electric shock across the chest, thus depolarizing the heart cells and allowing normal rhythm to return. [EU] 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

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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] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] 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] Demyelinating Diseases: Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [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] 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] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermatitis: Any inflammation of the skin. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Dextromethorphan: The d-isomer of the codeine analog of levorphanol. Dextromethorphan

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shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is a NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is used widely as an antitussive agent, and is also used to study the involvement of glutamate receptors in neurotoxicity. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffuse Axonal Injury: A relatively common sequela of blunt head injury, characterized by a global disruption of axons throughout the brain. Associated clinical features may include neurobehavioral manifestations; persistent vegetative state; dementia; and other disorders. [NIH]

Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dihydropyridines: Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimness: A result of alcohol's toxic effect on the optic nerve. [NIH] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [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] Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU]

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Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [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] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] 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] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] 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

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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] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [NIH] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [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] Elasticity: Resistance and recovery from distortion of shape. [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] Electric shock: A dangerous patho-physiological effect resulting from an electric current passing through the body of a human or animal. [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] Electroencephalography: Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] 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] Electroshock: Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Ellagic Acid: A fused four ring compound occurring free or combined in galls. Isolated from the kino of Eucalyptus maculata Hook and E. Hemipholia F. Muell. Activates Factor XII of the blood clotting system which also causes kinin release; used in research and as a dye.

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[NIH]

Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [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] Emergency Treatment: First aid or other immediate intervention for accidents or medical conditions requiring immediate care and treatment before definitive medical and surgical management can be procured. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [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, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes

Dictionary 233

it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] 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] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH] Erythrocyte Transfusion: The transfer of erythrocytes from a donor to a recipient or reinfusion to the donor. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythroid Progenitor Cells: Committed, erythroid stem cells derived from myeloid stem cells. The progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E). BFU-E differentiate into CFU-E on stimulation by erythropoietin, and then further differentiate into erythroblasts when stimulated by other factors. [NIH] Erythropoiesis: The production of erythrocytes. [EU]

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Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [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] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors. [NIH] Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expert Testimony: Presentation of pertinent data by one with special skill or knowledge representing mastery of a particular subject. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular

Dictionary 235

proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [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] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Facial: Of or pertaining to the face. [EU] Facial Paralysis: Severe or complete loss of facial muscle motor function. This condition may result from central or peripheral lesions. Damage to CNS motor pathways from the cerebral cortex to the facial nuclei in the pons leads to facial weakness that generally spares the forehead muscles. Facial nerve diseases generally results in generalized hemifacial weakness. Neuromuscular junction diseases and muscular diseases may also cause facial paralysis or paresis. [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] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Fetal Alcohol Syndrome: A disorder occurring in children born to alcoholic women who continue to drink heavily during pregnancy. Common abnormalities are growth deficiency (prenatal and postnatal), altered morphogenesis, mental deficiency, and characteristic facies - small eyes and flattened nasal bridge. Fine motor dysfunction and tremulousness are observed in the newborn. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of

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other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibrinolytic Agents: Fibrinolysin or agents that convert plasminogen to fibrinolysin (plasmin). [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [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] Flatus: Gas passed through the rectum. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Flurothyl: A convulsant primarily used in experimental animals. It was formerly used to induce convulsions as a alternative to electroshock therapy. [NIH] Flush: Transient, episodic redness of the face and neck caused by certain diseases, ingestion of certain drugs or other substances, heat, emotional factors, or physical exertion. [EU] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Free Association: Spontaneous verbalization of whatever comes to mind. [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]

Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] 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] Gallate: Antioxidant present in tea. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually

Dictionary 237

between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Ganglioside: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]

Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] 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] 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] 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] Geriatric: Pertaining to the treatment of the aged. [EU] Geriatric Psychiatry: A subspecialty of psychiatry concerned with the mental health of the aged. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH] Ginger: Deciduous plant rich in volatile oil (oils, volatile). It is used as a flavoring agent and

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has many other uses both internally and topically. [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] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [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] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

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] Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Government Agencies: Administrative units of government responsible for policy making and management of governmental activities in the U.S. and abroad. [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] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of

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peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]

Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [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] Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haematoma: A localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel. [EU] Haemophilus: A genus of Pasteurellaceae that consists of several species occurring in animals and humans. Its organisms are described as gram-negative, facultatively anaerobic, coccobacillus or rod-shaped, and nonmotile. [NIH] Haemophilus influenzae: A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through VIII. [NIH]

Haemorrhage: The escape of blood from the vessels; bleeding. Small haemorrhages are classified according to size as petechiae (very small), purpura (up to 1 cm), and ecchymoses (larger). The massive accumulation of blood within a tissue is called a haematoma. [EU] Hallucinogen: A hallucination-producing drug, a category of drugs producing this effect. The user of a hallucinogenic drug is almost invariably aware that what he is seeing are hallucinations. [NIH] Handicap: A handicap occurs as a result of disability, but disability does not always constitute a handicap. A handicap may be said to exist when a disability causes a substantial and continuing reduction in a person's capacity to function socially and vocationally. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] 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] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH]

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Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Hearing Disorders: Conditions that impair the transmission or perception of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways. [NIH] Heart Arrest: Sudden and usually momentary cessation of the heart beat. This sudden cessation may, but not usually, lead to death, sudden, cardiac. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Heat Stroke: A condition characterized by cessation of sweating, hot dry skin, delirium, collapse, and coma and resulting from prolonged exposure to high environmental temperature. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemianopsia: Partial or complete loss of vision in one half of the visual field(s) of one or both eyes. Subtypes include altitudinal hemianopsia, characterized by a visual defect above or below the horizontal meridian of the visual field. Homonymous hemianopsia refers to a visual defect that affects both eyes equally, and occurs either to the left or right of the midline of the visual field. Binasal hemianopsia consists of loss of vision in the nasal hemifields of both eyes. Bitemporal hemianopsia is the bilateral loss of vision in the temporal fields. Quadrantanopsia refers to loss of vision in one quarter of the visual field in one or both eyes. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [NIH] Hemiplegia: Severe or complete loss of motor function on one side of the body. This condition is usually caused by BRAIN DISEASES that are localized to the cerebral hemisphere opposite to the side of weakness. Less frequently, BRAIN STEM lesions; cervical spinal cord diseases; peripheral nervous system diseases; and other conditions may manifest as hemiplegia. The term hemiparesis (see paresis) refers to mild to moderate weakness involving one side of the body. [NIH] Hemodilution: Reduction of blood viscosity usually by the addition of cell free solutions. Used clinically l) in states of impaired microcirculation, 2) for replacement of intraoperative blood loss without homologous blood transfusion, and 3) in cardiopulmonary bypass and hypothermia. [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

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glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin M: A group of abnormal hemoglobins in which amino acid substitutions take place in either the alpha or beta chains but near the heme iron. This results in facilitated oxidation of the hemoglobin to yield excess methemoglobin which leads to cyanosis. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhagic stroke: A disorder involving bleeding within ischemic brain tissue. Hemorrhagic stroke occurs when blood vessels that are damaged or dead from lack of blood supply (infarcted), located within an area of infarcted brain tissue, rupture and transform an "ischemic" stroke into a hemorrhagic stroke. Ischemia is inadequate tissue oxygenation caused by reduced blood flow; infarction is tissue death resulting from ischemia. Bleeding irritates the brain tissues, causing swelling (cerebral edema). Blood collects into a mass (hematoma). Both swelling and hematoma will compress and displace brain tissue. [NIH] Hemorrhaging: A copious discharge of blood from the blood vessels. [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] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Herbicides: Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses, and woody 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] Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]

Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [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]

Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH]

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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] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercapnia: A clinical manifestation of abnormal increase in the amount of carbon dioxide

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in arterial blood. [NIH] Hyperglycaemia: Abnormally increased content of sugar in the blood. [EU] 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] 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] Hypoglycemia: Abnormally low blood sugar [NIH] Hypotension: Abnormally low blood pressure. [NIH] 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] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Hypoxemia: Deficient oxygenation of the blood; hypoxia. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Ibogaine: One of several indole alkaloids extracted from Tabernanthe iboga, Baill. It has a complex pharmacological profile and interacts with multiple systems of neurotransmission. Ibogaine has psychoactive properties and appears to modulate tolerance to opiates. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Immortal: Stage when the mother cell and its descendants will multiply indefinitely. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and

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disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]

Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]

Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] 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 or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU]

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Inertia: Inactivity, inability to move spontaneously. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] 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]

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] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

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] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate 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] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [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] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or

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silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [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] Internal Capsule: White matter pathway, flanked by nuclear masses, consisting of both afferent and efferent fibers projecting between the cerebral cortex and the brainstem. It consists of three distinct parts: an anterior limb, posterior limb, and genu. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] 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] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Aneurysm: A saclike dilatation of the walls of a blood vessel, usually an artery. [NIH]

Intracranial Arteriosclerosis: Vascular diseases characterized by thickening, hardening, and remodeling of the walls of intracranial arteries. There are three subtypes: (1) atherosclerosis, marked by fatty depositions in the innermost layer of the arterial walls, (2) Monckeberg's sclerosis, which features calcium deposition in the media and (3) arteriolosclerosis, which refers to sclerosis of small caliber arteries. Clinically, this process may be associated with transient ischemic attack, brain infarction, intracranial embolism and thrombosis, or intracranial aneurysm. [NIH] Intracranial Embolism: The sudden obstruction of a blood vessel by an embolus. [NIH]

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Intracranial Embolism and Thrombosis: Embolism or thrombosis involving blood vessels which supply intracranial structures. Emboli may originate from extracranial or intracranial sources. Thrombosis may occur in arterial or venous structures. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intracranial Pressure: Pressure within the cranial cavity. It is influenced by brain mass, the circulatory system, CSF dynamics, and skull rigidity. [NIH] Intramuscular: IM. Within or into muscle. [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] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ipsilateral: Having to do with the same side of the body. [NIH] Irradiation: The use of high-energy radiation from x-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 from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

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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] Kainate: Glutamate receptor. [NIH] Kainic Acid: (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose. [NIH] Karyotype: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Language Development: The gradual expansion in complexity and meaning of symbols and sounds as perceived and interpreted by the individual through a maturational and learning process. Stages in development include babbling, cooing, word imitation with cognition, and use of short sentences. [NIH] Language Development Disorders: Conditions characterized by language abilities (comprehension and expression of speech and writing) that are below the expected level for a given age, generally in the absence of an intellectual impairment. These conditions may be associated with deafness; brain diseases; mental disorders; or environmental factors. [NIH] Language Disorders: Conditions characterized by deficiencies of comprehension or expression of written and spoken forms of language. These include acquired and developmental disorders. [NIH] Language Tests: Tests designed to assess language behavior and abilities. They include tests of vocabulary, comprehension, grammar and functional use of language, e.g., Development Sentence Scoring, Receptive-Expressive Emergent Language Scale, Parsons Language Sample, Utah Test of Language Development, Michigan Language Inventory and Verbal Language Development Scale, Illinois Test of Psycholinguistic Abilities, Northwestern Syntax Screening Test, Peabody Picture Vocabulary Test, Ammons Full-Range Picture

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Vocabulary Test, and Assessment of Children's Language Comprehension. [NIH] Language Therapy: Rehabilitation of persons with language disorders or training of children with language development disorders. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Learning Disorders: Conditions characterized by a significant discrepancy between an individual's perceived level of intellect and their ability to acquire new language and other cognitive skills. These disorders may result from organic or psychological conditions. Relatively common subtypes include dyslexia, dyscalculia, and dysgraphia. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [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] Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [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] Linkages: The tendency of two or more genes in the same chromosome to remain together

250 Brain Damage

from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [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] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Lobule: A small lobe or subdivision of a lobe. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lockjaw: Inability to open the mouth due to tonic contracture of the muscles of the jaw. [NIH]

Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] 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

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column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a spinal tap. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [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] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [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] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant Hyperthermia: Rapid and excessive rise of temperature accompanied by muscular rigidity following general anesthesia. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Malondialdehyde: The dialdehyde of malonic acid. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely

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expressed in behaviour. [EU] Mastocytosis: A group of diseases resulting from proliferation of mast cells. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [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] 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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Mental deficiency: A condition of arrested or incomplete development of mind from inherent causes or induced by disease or injury. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from

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cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. [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] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [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] 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] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [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] Middle Cerebral Artery: The largest and most complex of the cerebral arteries. Branches of the middle cerebral artery supply the insular region, motor and premotor areas, and large regions of the association cortex. [NIH] Middle Cerebral Artery Infarction: Terminal branch of the internal carotid artery which supplies the lateral portion of the cortex, the optic chiasm, the optic tract, and the optic radiations. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Miotic: 1. Pertaining to, characterized by, or producing miosis : contraction of the pupil. 2. An agent that causes the pupil to contract. 3. Meiotic: characterized by cell division. [EU] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [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

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of the species. [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] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] 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] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Perception: The real or apparent movement of objects through the visual field. [NIH] 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 Cortex: Area of the frontal lobe concerned with primary motor control. It lies anterior to the central sulcus. [NIH] Motor Skills: Performance of complex motor acts. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder

Dictionary 255

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] Multiple Trauma: Physical insults or injuries occurring simultaneously in several parts of the body. [NIH] Muscarine: A toxic alkaloid found in Amanita muscaria (fly fungus) and other fungi of the Inocybe species. It is the first parasympathomimetic substance ever studied and causes profound parasympathetic activation that may end in convulsions and death. The specific antidote is atropine. [NIH] Muscarinic Agonists: Drugs that bind to and activate muscarinic cholinergic receptors (receptors, muscarinic). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate. [NIH] Muscular Diseases: Acquired, familial, and congenital disorders of skeletal muscle and smooth muscle. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myeloid Progenitor Cells: One of the two stem cells derived from hematopoietic stem cells the other being the lymphoid progenitor cell. Derived from these myeloid progenitor cells are the erythroid progenitor cells and the myeloid cells (monocytes and granulocytes). [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]

Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] 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

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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] Nadir: The lowest point; point of greatest adversity or despair. [EU] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] 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] Needle Sharing: Usage of a single needle among two or more people for injecting drugs. Needle sharing is a high-risk behavior for contracting infectious disease. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neomycin: Antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C. It acts by inhibiting translation during protein synthesis. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [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 Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]

Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]

Neurobehavioral Manifestations: Signs and symptoms of higher cortical dysfunction

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caused by organic conditions. These include certain behavioral alterations and impairments of skills involved in the acquisition, processing, and utilization of knowledge or information. [NIH]

Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurologist: A doctor who specializes in the diagnosis and treatment of disorders of the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular 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] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts 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] 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]

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Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Niche: The ultimate unit of the habitat, i. e. the specific spot occupied by an individual organism; by extension, the more or less specialized relationships existing between an organism, individual or synusia(e), and its environment. [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 is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitroprusside: (OC-6-22)-Pentakis(cyano-C)nitrosoferrate(2-). A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins. [NIH] Nitrous Oxide: Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. It is also used as a food aerosol in the preparation of whipping cream. [NIH]

Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [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]

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Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] 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] Occipital Lobe: Posterior part of the cerebral hemisphere. [NIH] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] Oligodendroglial: A cell that lays down myelin. [NIH] Oncology: The study of cancer. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in

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eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orthotic Devices: Apparatus used to support, align, prevent, or correct deformities or to improve the function of movable parts of the body. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [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] Osteolysis: Dissolution of bone that particularly involves the removal or loss of calcium. [NIH]

Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oximetry: The determination of oxygen-hemoglobin saturation of blood either by withdrawing a sample and passing it through a classical photoelectric oximeter or by electrodes attached to some translucent part of the body like finger, earlobe, or skin fold. It includes non-invasive oxygen monitoring by pulse oximetry. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic

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nerve. [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] Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. [NIH] Papule: A small circumscribed, superficial, solid elevation of the skin. [EU] 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 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] Parasympathomimetic: 1. Producing effects resembling those of stimulation of the parasympathetic nerve supply to a part. 2. An agent that produces effects similar to those produced by stimulation of the parasympathetic nerves. Called also cholinergic. [EU] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] 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] 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]

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Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Peduncle: A narrow supporting part, a stem. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [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] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [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] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Periventricular Leukomalacia: Rare form of epilepsy. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU]

Dictionary 263

Petechiae: Pinpoint, unraised, round red spots under the skin caused by bleeding. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [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] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [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] Phencyclidine: A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to ketamine in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (receptors, N-methyl-Daspartate). As a drug of abuse, it is known as PCP and Angel Dust. [NIH] Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory GABA subtype receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [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 formation of an ester bond between the compound and a phosphorus moiety. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs

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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] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilocarpine: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. [NIH] Piloerection: Involuntary erection or bristling of hairs. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [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 Activating Factor: A phospholipid derivative formed by platelets, basophils, neutrophils, monocytes, and macrophages. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including hypotension, thrombocytopenia, neutropenia, and bronchoconstriction. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the

Dictionary 265

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] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Policy Making: The decision process by which individuals, groups or institutions establish policies pertaining to plans, programs or procedures. [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] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] 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] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [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] Potentiate: 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

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the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] 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] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [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] 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] Procyclidine: A muscarinic antagonist that crosses the blood-brain barrier and is used in the treatment of drug-induced extrapyramidal disorders and in parkinsonism. [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] 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] Proprioception: The mechanism involved in the self-regulation of posture and movement through stimuli originating in the receptors imbedded in the joints, tendons, muscles, and

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labyrinth. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostitution: The practice of indulging in promiscuous sexual relations for money. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]

Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

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] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Proximate cause: The abnormal event in a causal chain lying closest to an accidental event. [NIH]

Pruritic: Pertaining to or characterized by pruritus. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease

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characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoanalysis: The separation or resolution of the psyche into its constituent elements. The term has two separate meanings: 1. a procedure devised by Sigmund Freud, for investigating mental processes by means of free association, dream interpretation and interpretation of resistance and transference manifestations; and 2. a theory of psychology developed by Freud from his clinical experience with hysterical patients. (From Campbell, Psychiatric Dictionary, 1996). [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]

Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotomimetic: Psychosis miming. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by

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pus. [EU] Pyramidal Cells: Projection neurons in the cerebral cortex and the hippocampus. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region. [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] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quinoxaline: AMPA/Kainate antagonist. [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] 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] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] 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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] 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] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH]

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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] Recovery of Function: A partial or complete return to the normal or proper physiologic activity of an organ or part following disease or trauma. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral 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] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] 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] Rehabilitative: Instruction of incapacitated individuals or of those affected with some mental disorder, so that some or all of their lost ability may be regained. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

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] Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use. [NIH]

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Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] 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] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrograde Amnesia: Amnesia extending backward, to include material antedating the onset of amnesia proper. [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] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH]

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Rubella: An acute, usually benign, infectious disease caused by a togavirus and most often affecting children and nonimmune young adults, in which the virus enters the respiratory tract via droplet nuclei and spreads to the lymphatic system. It is characterized by a slight cold, sore throat, and fever, followed by enlargement of the postauricular, suboccipital, and cervical lymph nodes, and the appearances of a fine pink rash that begins on the head and spreads to become generalized. Called also German measles, roetln, röteln, and three-day measles, and rubeola in French and Spanish. [EU] Ryanodine: Insecticidal alkaloid isolated from Ryania speciosa; proposed as a myocardial depressant. [NIH] Saline: A solution of salt and water. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Sarin: An organophosphorous ester compound that produces potent and irreversible inhibition of cholinesterase. It is toxic to the nervous system and is a chemical warfare agent. [NIH]

Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secobarbital: A barbiturate that is used as a sedative. Secobarbital is reported to have no anti-anxiety activity. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol

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triphosphate system, and the cyclic GMP system. [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] Sedatives, Barbiturate: Those derivatives of barbituric or thiobarbituric acid that are used as hypnotics or sedatives. The structural class of all such derivatives, regardless of use, is barbiturates. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] 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] Semantics: The relationships between symbols and their meanings. [NIH] 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] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] 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] Serous: Having to do with serum, the clear liquid part of blood. [NIH] 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 Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sexual Abstinence: Refraining from sexual intercourse. [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]

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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] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Skull Fracture, Depressed: A skull fracture characterized by inward depression of a fragment or section of cranial bone, often compressing the underlying dura mater and brain. Depressed cranial fractures which feature open skin wounds that communicate with skull fragments are referred to as compound depressed skull fractures. [NIH] Skull Fractures: Fractures of the skull which may result from penetrating or nonpenetrating head injuries or rarely bone diseases (see also fractures, spontaneous). skull fractures may be classified by location (e.g., skull fracture, basilar), radiographic appearance (e.g., linear), or based upon cranial integrity (e.g., skull fracture, depressed). [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Behavior: Any behavior caused by or affecting another individual, usually of the same species. [NIH] Social Class: A stratum of people with similar position and prestige; includes social stratification. Social class is measured by criteria such as education, occupation, and income. [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,

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maintenance of fluid volume, and electrolyte balance. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Soman: An organophosphorus compound that inhibits cholinesterase. It causes seizures and has been used as a chemical warfare agent. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmodic: Of the nature of a spasm. [EU] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] 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-Language Pathology: The study of speech or language disorders and their diagnosis and correction. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Diseases: Pathologic conditions which feature spinal cord damage or dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord. [NIH] Spinal Cord Injuries: Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., wounds, gunshot; whiplash injuries; etc.). [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and

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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] Spirochete: Lyme disease. [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] 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]

Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cell Factor: Hematopoietic growth factor and the ligand of the c-kit receptor CD117 (proto-oncogene protein C-kit). It is expressed during embryogenesis and provides a key signal in multiple aspects of mast-cell differentiation and function. [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] Sterile: Unable to produce children. [NIH] Stillbirth: The birth of a dead fetus or baby. [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] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH] Streptomycin: O-2-Deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5- deoxy-3-Cformyl-alpha-L-lyxofuranosyl-(1-4)-N,N'-bis(aminoiminomethyl)-D-streptamine. Antibiotic substance produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis. [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] Striatum: A higher brain's domain thus called because of its stripes. [NIH]

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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] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] 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]

Substrate: A substance upon which an enzyme acts. [EU] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [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] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] 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] 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]

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Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] 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] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Teratogenesis: Production of monstrous growths or fetuses. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Tetani: Causal agent of tetanus. [NIH]

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Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] 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]

Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thiobarbituric Acid Reactive Substances: Low-molecular-weight end products, probably malondialdehyde, that are formed during the decomposition of lipid peroxidation products. These compounds react with thiobarbituric acid to form a fluorescent red adduct. [NIH] Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [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 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] Thoracic: Having to do with the chest. [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] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU]

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Thrombolytic Therapy: Use of infusions of fibrinolytic agents to destroy or dissolve thrombi in blood vessels or bypass grafts. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [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] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Plasminogen Activator: A proteolytic enzyme in the serine protease family found in many tissues which converts plasminogen to plasmin. It has fibrin-binding activity and is immunologically different from urinary plasminogen activator. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. EC 3.4.21.68. [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] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH]

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Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] 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] Tracheostomy: Surgical formation of an opening into the trachea through the neck, or the opening so created. [NIH] Traction: The act of pulling. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [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] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trauma, Nervous System: Traumatic injuries to the brain, cranial nerves, spinal cord, autonomic nervous system, or neuromuscular system, including iatrogenic injuries induced by surgical procedures. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Trihexyphenidyl: A centrally acting muscarinic antagonist used in the treatment of parkinsonism and drug-induced extrapyramidal movement disorders and as an antispasmodic. [NIH] Trophic: Of or pertaining to nutrition. [EU] 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] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It

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has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [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] Tunica Intima: The innermost coat of blood vessels, consisting of a thin lining of endothelial cells longitudinally oriented and continuous with the endothelium of capillaries on the one hand and the endocardium of the heart on the other. [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] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Univalent: Pertaining to an unpaired chromosome during the zygotene stage of prophase to first metaphase in meiosis. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Plasminogen Activator: A proteolytic enzyme that converts plasminogen to plasmin where the preferential cleavage is between arginine and valine. It was isolated originally from human urine, but is found in most tissues of most vertebrates. EC 3.4.21.73. [NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH]

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Varicella: Chicken pox. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasogenic: Acute peripheral circulatory failure due to loss of capillary tone associated with a reduced circulating blood volume. [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] 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] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] 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] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular fibrillation: Rapid, irregular quivering of the heart's ventricles, with no effective heartbeat. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and

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treatment of diseases in animals. [NIH] Vial: A small bottle. [EU] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visual Cortex: Area of the occipital lobe concerned with vision. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [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] 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]

Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Wounds, Gunshot: Disruption of structural continuity of the body as a result of the discharge of firearms. [NIH] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH]

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X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [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]

287

INDEX A Abdomen, 138, 205, 216, 233, 239, 246, 250, 262, 276, 279, 284 Abdominal, 205, 206, 261, 262 Aberrant, 11, 205 Abscess, 166, 205, 273 Absenteeism, 205, 226 Acatalasia, 205, 219 Acceptor, 205, 250, 260 ACE, 75, 205 Acetone, 205, 248 Acetylcholine, 128, 132, 142, 205, 221, 258 Acetylcholinesterase, 17, 132, 205 Acne, 136, 137, 205, 271 Acoustic, 100, 205 Acrylonitrile, 205, 271 Actin, 205, 257 Adaptability, 205, 219, 220 Adaptation, 9, 205, 264 Adduct, 206, 279 Adenine, 206, 268 Adenosine, 133, 206, 218, 243, 263, 279 Adipocytes, 139, 206, 224 Adjustment, 205, 206 Adolescence, 18, 206, 262 Adoptive Transfer, 33, 206 Adrenal Cortex, 206, 225, 266 Adrenal Glands, 206, 208 Adrenergic, 6, 206, 210, 230, 233, 277, 282 Adverse Effect, 206, 270, 274 Aerosol, 206, 258 Aetiology, 94, 206 Afferent, 206, 226, 246, 266 Affinity, 21, 206, 212, 229, 274 Age Groups, 37, 206 Aged, 80 and Over, 206 Agonist, 121, 206, 230, 248, 258, 264 Albumin, 12, 207, 264 Aldehydes, 207, 284 Alertness, 207, 218 Algorithms, 207, 215 Alkaline, 58, 207, 208, 218 Alkaloid, 207, 213, 214, 222, 254, 255, 258, 261, 270, 272, 279 Alleles, 207, 241 Allograft, 151, 207 Allylamine, 207 Alpha Particles, 207, 269

Alternative medicine, 171, 207 Aluminum, 145, 207 Ameliorated, 132, 207 Amine, 133, 207, 242 Amino Acid Sequence, 207, 210, 237 Amino Acid Substitution, 208, 241 Amino Acids, 36, 140, 207, 208, 212, 215, 234, 237, 262, 267, 273, 280, 281 Ammonia, 41, 154, 207, 208, 277 Amnesia, 62, 208, 271 Amniotic Fluid, 208, 237 Amphetamine, 86, 142, 208, 215, 228 Amygdala, 16, 46, 208, 213, 249, 279 Amyloid, 8, 27, 146, 152, 208, 220 Amyloidosis, 8, 208 Anaerobic, 208, 239 Anaesthesia, 72, 208, 244 Anal, 26, 61, 208, 250 Analgesic, 208, 223, 229, 249, 254, 258, 259 Analog, 208, 228 Analogous, 37, 208, 281 Analysis of Variance, 44, 208 Anaphylactic, 209, 264 Anaphylatoxins, 209, 223 Anaplasia, 209, 256 Anatomical, 9, 37, 47, 166, 191, 209, 212, 225, 229, 244, 272 Anemia, 28, 209, 216, 240 Anesthesia, 26, 27, 118, 209, 212, 232, 248, 251 Anesthetics, 209, 213, 233 Aneurysm, 141, 209, 283 Angiogenesis, 209, 252 Angiography, 23, 29, 209 Angiopathy, 209, 220 Animal model, 24, 26, 35, 41, 44, 46, 50, 53, 119, 134, 209 Anions, 207, 209, 247, 273, 277 Anomalies, 42, 46, 209, 278 Anoxia, 79, 120, 121, 133, 209 Antagonism, 120, 209, 218, 279 Anterior Cerebral Artery, 209, 220 Antibacterial, 210, 275 Antibiotic, 192, 193, 209, 210, 256, 262, 266, 275, 276 Antibodies, 14, 33, 210, 239, 244, 251, 254, 264

288 Brain Damage

Antibody, 49, 206, 210, 216, 223, 239, 242, 244, 245, 247, 252, 254, 269, 275, 285 Anticonvulsant, 129, 210 Antidepressant, 210, 236 Antidote, 210, 255 Antiepileptic, 53, 129, 210 Antigen, 12, 151, 206, 210, 223, 242, 243, 244, 245, 252 Antigen-Antibody Complex, 210, 223 Antigen-presenting cell, 151, 210 Anti-inflammatory, 210, 228, 229, 238 Antioxidant, 12, 27, 31, 41, 55, 57, 111, 210, 217, 236, 260 Antipsychotic, 210, 270, 271 Antipyretic, 211, 229 Antispasmodic, 211, 259, 272, 281 Antithrombotic, 118, 211 Antitussive, 211, 229, 259 Anus, 193, 208, 211 Anxiety, 70, 211, 266, 272 Aorta, 211, 218, 225, 283 Aphasia, 4, 20, 23, 55, 82, 152, 160, 161, 166, 190, 191, 192, 211 Apoptosis, 11, 22, 27, 31, 32, 34, 211, 219 Apraxia, 69, 159, 211 Aqueous, 211, 214, 227, 242 Arachidonate 12-Lipoxygenase, 211, 250 Arachidonate 15-Lipoxygenase, 211, 250 Arachidonate Lipoxygenases, 211, 250 Arachidonic Acid, 118, 211, 249, 267 Arcus Senilis, 211, 221 Arginine, 6, 86, 209, 211, 258, 282 Aromatic, 211, 215, 263, 277 Arterial, 49, 133, 207, 212, 217, 220, 243, 246, 247, 267, 278 Arteries, 23, 209, 211, 212, 216, 219, 220, 221, 225, 246, 247, 253, 255, 280 Arterioles, 16, 212, 216, 218, 253 Arteriovenous, 212, 220, 221, 253 Articular, 212, 249, 260 Articulation, 212, 230 Artifacts, 45, 212 Ascites, 212, 259 Aspartate, 21, 55, 58, 60, 121, 125, 129, 132, 140, 147, 212, 229, 248, 263 Aspartic, 140, 141, 212, 234 Aspartic Acid, 140, 141, 212 Asphyxia, 31, 67, 69, 72, 100, 120, 125, 126, 141, 143, 154, 159, 165, 212, 258 Assay, 6, 58, 150, 212 Astrocytes, 33, 35, 36, 59, 212, 254 Ataxia, 145, 212, 242, 279

Atherectomy, 212, 232 Atrium, 212, 218, 283 Atrophy, 10, 35, 212, 257 Atropine, 132, 213, 214, 255, 272 Attenuated, 15, 147, 213 Atypical, 213, 271 Audition, 37, 213 Auditory, 3, 4, 8, 19, 37, 92, 194, 213, 234, 240, 266 Autoimmune disease, 213, 255 Autonomic, 70, 205, 210, 213, 214, 226, 258, 262, 277, 281 Autonomic Nervous System, 213, 214, 262, 277, 281 Autopsy, 13, 47, 94, 213 Axonal, 58, 213 Axons, 152, 213, 228, 229, 246, 259, 269 B Back Pain, 82, 213 Bacteria, 193, 210, 213, 214, 232, 233, 238, 253, 269, 273, 275, 276, 281, 282 Bacterial Physiology, 206, 213 Bactericidal, 213, 234 Bacteriophage, 213, 281 Barbiturate, 213, 272 Basal Ganglia, 145, 210, 212, 213, 217, 220, 237, 249, 259 Basal Ganglia Diseases, 212, 213 Base, 30, 57, 136, 137, 206, 213, 228, 237, 248, 269, 278 Basophils, 151, 214, 239, 249, 264 Belladonna, 213, 214 Benactyzine, 128, 214 Benign, 214, 217, 237, 239, 256, 269, 272 Benztropine, 128, 214 Beta-pleated, 208, 214 Bewilderment, 214, 224 Bicuculline, 119, 214 Bilateral, 7, 79, 214, 240, 261 Bile, 130, 214, 247, 250 Bile Acids, 214 Bile Acids and Salts, 214 Bile Pigments, 214, 247 Bilirubin, 130, 185, 207, 214, 242 Binding Sites, 140, 214 Bioassay, 17, 214 Bioavailability, 146, 214 Biochemical, 11, 17, 25, 26, 28, 35, 49, 55, 58, 63, 97, 207, 214, 215, 260, 273, 279 Biochemical Phenomena, 214, 215 Biochemical reactions, 215, 279 Bioengineering, 5, 182, 215

Index 289

Biogenic Amines, 58, 215 Biological Phenomena, 134, 215 Biological Psychiatry, 48, 165, 215 Biological Transport, 215, 229 Biomarkers, 58, 215 Biosynthesis, 211, 215, 273 Biotechnology, 60, 165, 171, 183, 215 Biotransformation, 215 Biotypes, 215, 239 Biperiden, 128, 215 Bladder, 215, 221, 244, 254, 255, 267, 282 Blastocyst, 215, 224, 264 Blood Cell Count, 91, 215, 240 Blood Coagulation, 216, 218, 280 Blood Glucose, 57, 84, 216, 240, 246 Blood Platelets, 216, 273, 279 Blood pressure, 10, 57, 64, 134, 193, 216, 219, 243, 254, 258, 259, 274 Blood transfusion, 168, 216, 240 Blood Viscosity, 216, 240 Blood Volume, 216, 283 Blood-Brain Barrier, 8, 11, 24, 118, 140, 216, 249, 266 Blot, 41, 216, 244 Blotting, Western, 216, 244 Body Fluids, 215, 216, 218, 274, 282 Bone Marrow, 216, 234, 244, 251, 254 Bone scan, 216, 272 Boron, 216, 226 Bowel, 208, 216, 245, 246 Brachytherapy, 216, 246, 247, 269, 285 Bradykinin, 217, 258, 264 Brain Diseases, 157, 158, 190, 217, 248 Brain Hypoxia, 217, 279 Brain Infarction, 217, 246 Brain Injuries, 31, 190, 217 Brain Ischemia, 34, 118, 217, 221 Brain Neoplasms, 217, 242, 279 Brain Stem, 58, 119, 145, 217, 220, 221, 257 Branch, 52, 135, 201, 217, 231, 251, 253, 257, 261, 268, 275, 279 Breakdown, 11, 35, 38, 42, 58, 118, 217, 229, 237 Bronchi, 217, 233, 279, 281 Bronchial, 217, 242, 279 Bronchiseptica, 217, 262 Bronchoconstriction, 217, 264 Burns, 87, 217 Burns, Electric, 217 Butylated Hydroxytoluene, 41, 217 Butyric Acid, 140, 218 Bypass, 15, 66, 170, 218, 255, 280

C Caffeine, 152, 218, 268 Calcium, 25, 33, 78, 106, 133, 140, 155, 218, 223, 246, 252, 255, 260, 261, 267, 274 Calcium Channels, 140, 218, 261 Capillary, 15, 25, 151, 217, 218, 283 Carbohydrates, 218, 220 Carbon Dioxide, 218, 227, 237, 242, 264, 271, 283 Carbon Monoxide Poisoning, 93, 141, 154, 218 Carcinogenic, 218, 245 Carcinogens, 218, 260 Cardiac arrest, 12, 20, 30, 63, 83, 111, 120, 121, 125, 133, 134, 140, 141, 142, 143, 218 Cardiology, 34, 89, 218 Cardiopulmonary, 12, 14, 66, 72, 121, 133, 134, 218, 219, 240 Cardiopulmonary Bypass, 14, 72, 218, 240 Cardiopulmonary Resuscitation, 12, 72, 121, 133, 134, 219 Cardiovascular, 66, 98, 106, 136, 137, 146, 208, 218, 219, 249, 273 Cardiovascular disease, 98, 106, 146, 219 Carotid Arteries, 20, 219 Case report, 77, 85, 219, 222 Case series, 219, 222 Caspase, 11, 14, 219 Catalase, 58, 205, 219 Catecholamine, 219, 230 Cations, 219, 247 Caudal, 219, 229, 243, 259, 265 Caudate Nucleus, 209, 213, 219, 259 Causal, 12, 26, 219, 267, 278 Cause of Death, 14, 32, 131, 134, 141, 144, 154, 219 Cell Death, 11, 14, 30, 32, 50, 118, 125, 141, 150, 155, 211, 219, 256 Cell Differentiation, 219, 274, 276 Cell Division, 213, 220, 252, 253, 264, 266, 273 Cell membrane, 42, 44, 141, 215, 218, 220, 228, 237, 263 Cell proliferation, 220, 274 Cell Respiration, 220, 271 Cell Survival, 54, 220 Central Nervous System, 9, 31, 39, 42, 74, 119, 120, 128, 131, 136, 143, 147, 205, 208, 213, 217, 218, 220, 221, 222, 228, 234, 237, 238, 239, 242, 249, 253, 254, 255, 257, 259, 263, 265, 272, 273, 279

290 Brain Damage

Central Nervous System Infections, 220, 239, 242 Centrifugation, 220, 240 Cerebellar, 46, 59, 212, 220, 270 Cerebellum, 9, 12, 46, 58, 59, 217, 220, 221, 225, 265, 270 Cerebral Arteries, 220, 253 Cerebral hemispheres, 159, 213, 217, 220, 221, 278 Cerebral Hemorrhage, 8, 26, 35, 220 Cerebral Infarction, 26, 145, 147, 155, 217, 220, 221, 242 Cerebral Palsy, 36, 138, 149, 191, 220, 275 Cerebrospinal, 8, 75, 90, 94, 119, 220, 242, 251, 276 Cerebrospinal fluid, 8, 75, 90, 94, 119, 220, 242, 251, 276 Cerebrotendinous Xanthomatosis, 95, 221 Cerebrovascular, 6, 7, 8, 10, 15, 32, 85, 118, 120, 152, 213, 219, 221, 279 Cerebrovascular Disorders, 6, 221, 279 Cerebrum, 220, 221, 225, 278 Cervical, 221, 240, 272 Chancre, 192, 221 Character, 158, 221, 227 Chemical Warfare, 128, 132, 221, 272, 275 Chemokines, 33, 221 Chemotactic Factors, 221, 223 Cholesterol, 211, 214, 221, 225 Choline, 42, 44, 58, 205, 221 Cholinergic, 8, 17, 128, 140, 152, 210, 214, 221, 255, 258, 261 Cholinergic Agents, 128, 140, 221 Cholinesterase Inhibitors, 128, 221 Chromatin, 211, 222, 233, 258 Chromosome, 222, 248, 249, 273, 282 Chronic Disease, 222, 226 Circadian, 152, 222 Circadian Rhythm, 152, 222 Circulatory system, 222, 247 Citrus, 127, 222 C-kit receptor, 68, 222, 276 Clamp, 53, 222 Clinical Medicine, 222, 266 Clinical study, 23, 222 Clinical trial, 5, 31, 59, 183, 222, 267, 269 Cloning, 215, 222 Coagulation, 216, 222, 241, 264, 280 Coca, 222 Cocaine, 142, 222 Codeine, 223, 228, 259 Cofactor, 223, 267, 280

Cognition, 7, 17, 18, 19, 20, 45, 48, 58, 63, 90, 91, 94, 159, 161, 162, 163, 164, 165, 223, 248 Colitis, 223, 245 Collagen, 223, 235, 236, 237, 252, 265 Collapse, 125, 217, 223, 240 Colloidal, 207, 223, 273 Combination Therapy, 11, 151, 223 Combinatorial, 55, 223 Communication Disorders, 78, 160, 161, 182, 190, 192, 223 Complement, 159, 209, 223, 224, 248, 264 Complementary and alternative medicine, 109, 113, 224 Complementary medicine, 109, 224 Compress, 224, 241 Computational Biology, 183, 224 Computed tomography, 68, 97, 224, 272 Computerized axial tomography, 224, 272 Computerized tomography, 224 Conception, 224, 235 Concomitant, 47, 224 Condoms, 168, 192, 193, 224 Conduction, 16, 224 Confusion, 136, 224, 230, 243 Conjugated, 214, 224, 227 Connective Tissue, 151, 216, 223, 224, 236, 237, 251, 271, 278 Connective Tissue Cells, 224 Consciousness, 208, 224, 227, 228, 230, 233, 241, 271, 276 Constriction, 6, 224, 225, 247, 283 Constriction, Pathologic, 225, 283 Consumption, 13, 17, 65, 80, 142, 225, 260 Continuum, 42, 225 Contracture, 225, 250 Contraindications, ii, 225 Contralateral, 225, 252, 259, 270 Convulsions, 81, 118, 128, 141, 210, 213, 214, 225, 236, 243, 255 Convulsive, 145, 225, 231 Coordination, 73, 191, 220, 225, 254 Cornea, 221, 225 Coronary, 64, 118, 219, 225, 253, 255 Coronary Artery Bypass, 64, 225 Coronary heart disease, 219, 225 Coronary Thrombosis, 225, 253, 255 Corpus, 46, 58, 225, 262, 266, 279 Corpus Callosum, 46, 58, 225, 279 Corpus Luteum, 225, 266 Cortical, 6, 27, 37, 39, 43, 51, 58, 62, 68, 69, 94, 147, 225, 234, 256, 266, 269, 273, 279

Index 291

Cortices, 16, 47, 225, 240 Cortisol, 207, 225 Cortisone, 226, 228 Cost of Illness, 184, 226 Cranial, 23, 126, 220, 226, 239, 247, 256, 259, 262, 274, 281 Cranial Nerves, 226, 281 Craniocerebral Trauma, 213, 220, 226, 239, 242, 279 Creatine, 42, 44, 86, 90, 96, 99, 226 Creatine Kinase, 86, 90, 99, 226 Creatinine, 226 Criterion, 116, 140, 226 Cues, 8, 16, 100, 226 Cultured cells, 11, 226 Curative, 226, 279 Curcuma longa, 111, 226 Curcumin, 111, 226 Cyanosis, 226, 241 Cyclic, 218, 226, 239, 258, 263, 272, 279 Cysteine, 14, 113, 221, 226 Cystine, 226 Cytochrome, 14, 40, 58, 227 Cytokine, 12, 35, 36, 118, 227 Cytoplasm, 211, 214, 220, 227, 233, 239, 254, 257, 258, 278 Cytoskeleton, 227, 253 Cytotoxic, 86, 151, 227, 269, 274 Cytotoxicity, 55, 207, 227 D Data Collection, 184, 227 Databases, Bibliographic, 183, 227 Decarboxylation, 215, 227, 242 Decidua, 227, 264 Defense Mechanisms, 25, 57, 227 Defibrillation, 20, 227 Degenerative, 152, 158, 184, 227, 241, 260, 271 Deletion, 211, 227 Delirium, 210, 227, 240 Delivery of Health Care, 226, 228, 240 Delusions, 172, 194, 228, 261 Dementia, 4, 18, 120, 146, 158, 159, 163, 192, 193, 194, 210, 228, 229, 257 Demyelinating Diseases, 150, 228 Dendrites, 146, 228, 257, 269 Dendritic, 9, 17, 58, 228 Density, 15, 29, 147, 220, 228, 259, 275 Dentate Gyrus, 32, 228, 242 Depolarization, 228, 274 Depressive Disorder, 228, 250 Deprivation, 25, 49, 120, 134, 141, 228

Dermatitis, 228, 231 Deuterium, 228, 242 Dexamethasone, 25, 64, 70, 228 Dextroamphetamine, 208, 228, 253 Dextromethorphan, 140, 228 Diabetes Mellitus, 65, 229, 238, 241 Diagnostic procedure, 117, 171, 229 Diastolic, 229, 243 Diclofenac, 82, 229 Diclofenac Sodium, 229 Diencephalon, 221, 229, 243, 257, 266, 278, 279 Diffuse Axonal Injury, 217, 229 Diffusion, 25, 30, 39, 41, 43, 70, 97, 145, 215, 229, 245 Digestion, 214, 216, 229, 246, 250, 276 Dihydropyridines, 118, 229 Dilatation, 209, 229, 246, 266, 283 Dilatation, Pathologic, 229, 283 Dilation, 212, 217, 229, 242, 283 Dimness, 144, 229 Diphtheria, 176, 194, 229 Direct, iii, 12, 25, 31, 35, 36, 47, 51, 130, 131, 140, 146, 153, 175, 222, 229, 230, 261, 270, 278 Discrimination, 79, 88, 229 Disease Progression, 172, 229 Disease-Free Survival, 39, 229 Disinfectant, 229, 234 Disorientation, 224, 228, 230 Dissociation, 70, 206, 230 Distal, 213, 225, 230, 231, 267 Diuresis, 218, 230, 279 Dizziness, 144, 230 Dopa, 21, 230, 249 Dopamine, 21, 47, 135, 208, 210, 214, 223, 228, 230, 249, 254, 263, 271 Dorsal, 16, 44, 230, 256, 265, 275 Dorsum, 230, 237 Drive, ii, vi, 105, 124, 230 Drug Interactions, 176, 230 Drug Tolerance, 230, 280 Duodenum, 214, 230, 276 Dura mater, 230, 252, 260, 274 Dyes, 208, 214, 230, 258 Dysarthria, 97, 230 Dyskinesia, 64, 210, 231 Dyslexia, 231, 249 E Ectoderm, 231, 256 Eczema, 136, 137, 231

292 Brain Damage

Edema, 25, 29, 32, 35, 86, 118, 119, 146, 155, 231, 241, 247, 255, 259 Effector, 30, 205, 223, 231, 258, 263 Effector cell, 231, 258 Efficacy, 11, 13, 31, 126, 149, 231 Elasticity, 134, 231 Elective, 81, 231 Electric shock, 135, 219, 227, 231 Electrode, 126, 231 Electroencephalography, 62, 126, 231 Electrolyte, 228, 231, 265, 275 Electrons, 210, 214, 231, 247, 251, 260, 269 Electrophysiological, 13, 17, 24, 49, 52, 53, 61, 231 Electroshock, 118, 231, 236 Elementary Particles, 231, 251, 258, 267 Ellagic Acid, 58, 231 Emboli, 148, 232, 247 Embolism, 166, 232, 247 Embolus, 232, 245, 246 Embryo, 215, 219, 231, 232, 244 Embryology, 232, 257 Emergency Treatment, 121, 232 Empirical, 8, 40, 232 Encephalitis, 33, 71, 232 Encephalitis, Viral, 232 Encephalopathy, 49, 154, 160, 165, 232 Endarterectomy, 63, 212, 232 Endocrine Glands, 232 Endothelial cell, 25, 33, 35, 216, 232, 280, 282 Endothelium, 24, 232, 258, 282 Endothelium, Lymphatic, 232 Endothelium, Vascular, 232 Endothelium-derived, 232, 258 Endotoxic, 233, 250 Endotoxin, 233, 282 Entorhinal Cortex, 233, 242 Environmental Health, 77, 182, 184, 233 Enzymatic, 25, 28, 215, 218, 223, 233, 236, 242 Eosinophilia, 68, 233 Eosinophils, 151, 233, 239, 249 Epidemiological, 53, 233 Epigastric, 233, 261 Epilepticus, 51, 57, 119, 164, 233 Epinephrine, 206, 215, 230, 233, 258, 282 Epithelium, 232, 233 Erectile, 233, 262 Erythema, 233, 277 Erythrocyte Indices, 216, 233 Erythrocyte Transfusion, 31, 233

Erythrocytes, 209, 215, 216, 233 Erythroid Progenitor Cells, 233, 255 Erythropoiesis, 31, 233 Erythropoietin, 31, 50, 74, 233, 234 Esophagus, 234, 270, 276 Estrogen, 65, 234 Ethanol, 12, 17, 40, 59, 111, 234 Evoke, 234, 276 Evoked Potentials, 63, 73, 101, 234 Excitability, 133, 234 Excitatory, 32, 36, 43, 74, 120, 129, 132, 140, 141, 143, 234, 238, 248 Excitatory Amino Acid Agonists, 234, 248 Excitatory Amino Acid Antagonists, 129, 234 Excitatory Amino Acids, 32, 36, 43, 120, 129, 132, 234 Excitotoxicity, 40, 94, 141, 147, 234 Exhaustion, 209, 234 Exocrine, 234, 261 Exogenous, 215, 231, 234 Expert Testimony, 88, 234 Expiration, 234, 271 Extensor, 234, 268 External-beam radiation, 234, 247, 269, 285 Extracellular, 6, 11, 53, 68, 118, 119, 120, 146, 208, 212, 224, 234, 235, 236, 252, 253, 274 Extracellular Matrix, 224, 234, 235, 236, 252 Extracellular Matrix Proteins, 235, 252 Extracellular Space, 11, 234, 235, 253 Extraction, 30, 235 Extrapyramidal, 210, 215, 230, 235, 266, 281 Extravasation, 235, 240 F Facial, 6, 42, 46, 93, 191, 235 Facial Paralysis, 191, 235 Family Planning, 183, 235 Fat, 75, 206, 209, 211, 214, 216, 218, 225, 232, 235, 248, 250, 255, 271 Fatigue, 168, 235, 240 Fatty acids, 118, 207, 235, 238, 250, 267, 280 Femoral, 218, 235 Femoral Artery, 218, 235 Fetal Alcohol Syndrome, 12, 46, 59, 235 Fetus, 27, 51, 96, 165, 171, 234, 235, 264, 266, 276, 282 Fibrillation, 227, 235

Index 293

Fibrin, 216, 235, 236, 264, 279, 280 Fibrinogen, 235, 264, 279 Fibrinolytic, 151, 236, 280 Fibrinolytic Agents, 151, 236, 280 Fibroblasts, 92, 224, 236 Fibrosis, 41, 207, 225, 236, 272 Fissure, 225, 228, 236, 266 Flatus, 236, 237 Fluorescence, 15, 236 Fluoxetine, 29, 236 Flurothyl, 57, 236 Flush, 111, 236 Fold, 23, 59, 236, 260 Forearm, 216, 236 Fossa, 220, 236 Free Association, 236, 268 Frontal Lobe, 7, 8, 110, 209, 220, 236, 254, 266 Functional magnetic resonance imaging, 37, 45, 47, 236 Fungi, 236, 239, 253, 255, 285 Fungus, 236, 255 G Gallate, 110, 236 Gamma Rays, 236, 269 Ganglia, 205, 213, 237, 256, 262, 277 Ganglion, 237, 256, 259 Ganglioside, 79, 237 Gap Junctions, 237, 278 Gas, 50, 102, 128, 170, 208, 218, 229, 236, 237, 242, 258, 283 Gas exchange, 237, 283 Gastrointestinal, 136, 137, 146, 217, 221, 233, 234, 237, 249, 273, 277, 282 Gastrointestinal tract, 146, 221, 234, 237, 249, 273, 282 Gelatin, 237, 238 Gene, 13, 26, 28, 30, 40, 52, 54, 86, 165, 207, 215, 237, 264, 273 Gene Expression, 13, 28, 86, 237 Genetic Code, 237, 259 Genetics, 8, 45, 85, 237 Genotype, 237, 263 Geriatric, 4, 237 Geriatric Psychiatry, 4, 237 Gestation, 27, 237, 262, 264 Gestational, 149, 153, 237 Gestational Age, 149, 153, 237 Ginger, 226, 237 Gland, 206, 226, 238, 251, 261, 267, 273, 276, 280 Glottis, 238, 262

Glucocorticoid, 228, 238 Glucose, 25, 78, 119, 139, 154, 216, 229, 238, 240, 243, 245, 246 Glucose Intolerance, 229, 238 Glutamic Acid, 143, 238 Glutathione Peroxidase, 58, 238 Glycerol, 218, 238, 263 Glycerophospholipids, 238, 263 Glycine, 78, 129, 140, 214, 238, 273 Glycols, 238, 242 Glycoprotein, 234, 235, 238, 280, 282 Governing Board, 238, 266 Government Agencies, 141, 238, 266 Graft, 54, 79, 238, 242, 244, 255 Grafting, 64, 225, 238 Gram-negative, 217, 233, 238, 239 Granule, 32, 228, 239 Granulocytes, 151, 239, 255, 274, 284 Grasses, 239, 241 Groin, 193, 239 Guanylate Cyclase, 239, 258 H Habitat, 239, 258 Habitual, 221, 239 Haematoma, 239 Haemophilus, 194, 239 Haemophilus influenzae, 194, 239 Haemorrhage, 97, 239 Hallucinogen, 239, 263 Handicap, 31, 163, 239 Haptens, 206, 239 Headache, 144, 218, 239, 242, 243 Headache Disorders, 239 Health Care Costs, 226, 240 Hearing Disorders, 223, 240 Heart Arrest, 219, 240 Heart attack, 219, 240 Heart failure, 139, 154, 194, 240, 259 Heartbeat, 240, 283 Heat Stroke, 79, 240 Hematocrit, 14, 216, 233, 240 Hematoma, 119, 240, 241 Hematopoietic Stem Cells, 240, 255 Heme, 214, 227, 240, 241 Hemianopsia, 136, 240 Hemiparesis, 136, 145, 217, 240 Hemiplegia, 136, 145, 155, 240 Hemodilution, 50, 240 Hemoglobin, 23, 49, 209, 216, 226, 233, 240, 241, 260 Hemoglobin M, 23, 226, 241

294 Brain Damage

Hemorrhage, 6, 10, 26, 35, 48, 71, 145, 166, 226, 239, 241, 255, 268, 277 Hemorrhagic stroke, 9, 241 Hemorrhaging, 141, 241 Hemostasis, 9, 241, 273 Hepatic, 71, 207, 228, 241 Hepatic Encephalopathy, 71, 241 Hepatitis, 194, 241 Hepatocytes, 241 Hepatotoxicity, 41, 241 Herbicides, 127, 241 Hereditary, 8, 241, 257 Heredity, 237, 241 Hernia, 88, 241 Herpes, 33, 241 Herpes Zoster, 241 Heterogeneity, 206, 241 Heterozygotes, 85, 92, 241 Hippocampus, 13, 17, 22, 29, 30, 32, 50, 52, 53, 58, 59, 96, 115, 134, 228, 242, 249, 257, 269, 277 Histamine, 209, 210, 215, 242 Histology, 5, 15, 68, 242, 257 Homogeneous, 225, 242 Homologous, 207, 240, 241, 242, 273, 278 Hormonal, 213, 242 Hormone, 214, 222, 225, 226, 233, 234, 242, 246, 266, 271, 272, 274, 280 Host, 151, 213, 242, 244, 249, 284 Human Development, 18, 76, 182, 242 Hybrid, 145, 242 Hydrocephalus, 83, 242, 247 Hydrogen Peroxide, 219, 238, 242, 250, 277 Hydrolysis, 205, 212, 215, 242, 263, 267 Hydroxides, 242 Hydroxyl Radical, 43, 242 Hyperbilirubinemia, 131, 185, 242, 247 Hypercapnia, 73, 242 Hyperglycaemia, 139, 243 Hypersensitivity, 243, 249, 271 Hypertension, 87, 219, 220, 243, 247 Hypoglycaemia, 154, 228, 243 Hypoglycemia, 112, 120, 243 Hypotension, 210, 225, 243, 264 Hypothalamus, 213, 217, 229, 243, 249, 279 Hypothermia, 68, 78, 121, 240, 243 Hypothyroidism, 66, 243 Hypoxanthine, 92, 243, 284 Hypoxemia, 31, 69, 243 I Iatrogenic, 243, 281

Ibogaine, 142, 243 Id, 107, 111, 195, 200, 202, 243 Idiopathic, 215, 243 Imaging procedures, 243, 281 Immortal, 155, 243 Immune response, 33, 210, 213, 226, 239, 243, 244, 277, 284 Immune system, 12, 33, 193, 210, 231, 243, 244, 249, 251, 255, 263, 282, 284 Immunization, 206, 244 Immunoblotting, 15, 244 Immunodeficiency, 168, 192, 193, 194, 244 Immunodeficiency syndrome, 168, 244 Immunogenic, 244, 250 Immunoglobulin, 210, 244, 254 Immunohistochemistry, 41, 244 Immunologic, 206, 221, 237, 244, 269 Immunology, 206, 244 Immunotherapy, 206, 244 Impairment, 3, 19, 42, 46, 51, 58, 67, 70, 88, 89, 148, 152, 168, 184, 212, 214, 221, 228, 231, 244, 248, 252 Implant radiation, 244, 246, 247, 269, 285 Impotence, 233, 244, 261 In situ, 33, 34, 244 In vitro, 11, 13, 15, 25, 33, 36, 40, 53, 54, 92, 141, 147, 216, 244 In vivo, 11, 15, 25, 28, 33, 35, 40, 54, 111, 141, 147, 244, 253, 260, 280 Incision, 244, 247 Incontinence, 242, 244, 272 Incubation, 193, 244, 262 Incubation period, 244, 262 Indicative, 159, 244, 261, 283 Induction, 40, 58, 210, 231, 244, 248 Inertia, 124, 245 Infancy, 18, 21, 245 Infant, Newborn, 206, 245 Infarction, 25, 26, 30, 94, 145, 220, 241, 245, 270 Infiltration, 33, 245 Inflammation, 31, 33, 34, 40, 54, 81, 136, 137, 205, 207, 210, 223, 228, 232, 236, 241, 245, 249, 252, 255, 260, 271, 278, 283 Inflammatory bowel disease, 136, 137, 245 Infusion, 245, 255, 281 Ingestion, 236, 245, 265 Inhalation, 206, 245, 265 Initiation, 54, 142, 245, 276 Initiator, 14, 245 Inlay, 245, 271 Innervation, 44, 245

Index 295

Inorganic, 145, 242, 245 Inositol, 44, 58, 139, 245, 272 Inotropic, 230, 245 Inpatients, 4, 245 Insight, 21, 39, 245 Insulator, 245, 255 Insulin, 84, 139, 154, 246, 248 Insulin-dependent diabetes mellitus, 246 Intensive Care, 73, 97, 153, 246 Interleukin-1, 50, 70, 74, 246 Interleukin-2, 246 Intermediate Filaments, 246, 257 Internal Capsule, 145, 209, 246 Internal radiation, 246, 247, 269, 285 Interneurons, 17, 32, 246 Interstitial, 216, 235, 246, 247, 285 Intestine, 214, 216, 230, 242, 246, 270, 276, 284 Intoxication, 15, 58, 154, 228, 246, 284 Intracellular, 12, 25, 53, 118, 126, 218, 245, 246, 258, 265, 270, 272, 274 Intracranial Aneurysm, 71, 220, 246 Intracranial Arteriosclerosis, 220, 246 Intracranial Embolism, 221, 246, 247 Intracranial Embolism and Thrombosis, 221, 246, 247 Intracranial Hemorrhages, 242, 247, 279 Intracranial Hypertension, 239, 242, 247 Intracranial Pressure, 119, 247 Intramuscular, 82, 247 Intrinsic, 52, 206, 247 Invasive, 21, 39, 44, 49, 59, 153, 247, 251, 260 Involuntary, 213, 235, 247, 255, 264, 270, 274, 275 Ion Channels, 52, 212, 247, 258, 278 Ions, 140, 214, 218, 230, 231, 242, 247, 267 Ipsilateral, 9, 37, 47, 50, 247, 252, 270 Irradiation, 54, 247, 285 Ischemic stroke, 10, 25, 41, 43, 47, 49, 68, 72, 91, 145, 247 Isoenzyme, 226, 247 J Jaundice, 130, 242, 247 Jealousy, 248, 261 Joint, 124, 192, 212, 248, 260, 278 K Kainate, 53, 55, 121, 248, 269 Kainic Acid, 52, 57, 142, 248 Karyotype, 68, 248 Kb, 182, 248 Ketamine, 21, 248, 263

Ketone Bodies, 138, 154, 205, 248 Kinetic, 129, 145, 248 L Labile, 223, 248 Labyrinth, 248, 267, 283 Laceration, 248, 279 Language Development, 37, 248, 249 Language Development Disorders, 248, 249 Language Disorders, 159, 223, 248, 249, 275 Language Tests, 44, 248 Language Therapy, 97, 166, 249 Latent, 154, 193, 249 Learning Disorders, 131, 249 Lesion, 9, 18, 19, 36, 37, 41, 45, 102, 120, 134, 149, 225, 249, 250, 278 Lethal, 20, 128, 213, 249 Lethargy, 242, 243, 249 Leukocytes, 35, 88, 151, 214, 215, 216, 221, 233, 239, 249, 254, 258, 282 Leukotrienes, 211, 249 Levo, 230, 249 Levodopa, 230, 249 Levorphanol, 228, 249 Library Services, 200, 249 Ligaments, 225, 249 Ligands, 33, 249 Ligation, 34, 249 Limbic, 47, 135, 208, 249, 266 Limbic System, 208, 249, 266 Linkages, 240, 249 Lipid, 35, 40, 50, 58, 118, 162, 221, 238, 246, 250, 255, 260, 279 Lipid A, 40, 250 Lipid Peroxidation, 35, 58, 250, 260, 279 Lipopolysaccharide, 34, 239, 250 Lipoxygenase, 136, 137, 211, 249, 250 Lithium, 128, 210, 250 Liver, 41, 71, 80, 139, 146, 193, 194, 205, 207, 208, 211, 214, 234, 241, 250, 272 Liver scan, 250, 272 Liver Transplantation, 71, 250 Lobe, 53, 77, 209, 220, 250 Lobule, 59, 250 Localization, 24, 126, 166, 244, 250 Localized, 21, 45, 55, 74, 96, 121, 208, 217, 229, 239, 240, 245, 250, 259, 264, 279 Lockjaw, 194, 250 Locomotion, 250, 264 Locomotor, 135, 250 Longitudinal study, 10, 250

296 Brain Damage

Loop, 241, 250 Lumbar, 31, 213, 250, 276 Lumbar puncture, 31, 250, 276 Lupus, 251, 278 Lymph, 151, 221, 222, 232, 251, 272 Lymph node, 151, 221, 251, 272 Lymphatic, 232, 245, 251, 259, 272, 276 Lymphatic system, 251, 272, 276 Lymphocyte, 210, 251, 252 Lymphoid, 210, 251, 255 M Macrophage, 246, 251 Magnetic Resonance Imaging, 10, 29, 41, 42, 51, 88, 93, 192, 251, 272 Magnetic Resonance Spectroscopy, 39, 42, 44, 100, 251 Malformation, 95, 251 Malignant, 195, 217, 251, 256, 269 Malignant Hyperthermia, 195, 251 Malnutrition, 71, 207, 212, 251 Malondialdehyde, 251, 279 Mammary, 225, 251 Mandible, 121, 251, 271 Mania, 98, 251 Manic, 210, 250, 251 Manifest, 147, 158, 213, 240, 251 Mastocytosis, 68, 252 Matrix metalloproteinase, 35, 252 Medial, 22, 77, 252, 259 Mediate, 11, 40, 71, 230, 252 Mediator, 230, 246, 252, 273 MEDLINE, 183, 252 Medullary, 229, 252 Meiosis, 252, 278, 282 Melanin, 252, 263, 282 Meninges, 220, 226, 230, 252, 275 Meningitis, 28, 32, 36, 60, 112, 252 Menstrual Cycle, 252, 266 Mental deficiency, 235, 252 Mental Health, iv, 4, 182, 186, 237, 252, 268 Mental Processes, 230, 252, 268 Mental Retardation, 15, 36, 51, 62, 92, 149, 160, 165, 223, 252 Mesencephalic, 252, 270 Metabolic disorder, 150, 252 Metabolite, 5, 39, 44, 215, 252 Metastasis, 252, 253, 256 Metastatic, 54, 217, 253 Methamphetamine, 44, 253 MI, 133, 136, 152, 203, 253 Microbe, 253, 280

Microbiology, 206, 213, 253 Microcirculation, 144, 240, 253 Microdialysis, 6, 11, 253 Microorganism, 223, 253, 261, 284 Microscopy, 9, 15, 29, 68, 96, 253 Microtubule-Associated Proteins, 253, 257 Microtubules, 146, 246, 253, 257 Middle Cerebral Artery, 13, 24, 25, 41, 47, 48, 51, 55, 67, 155, 253 Middle Cerebral Artery Infarction, 47, 253 Migration, 9, 54, 150, 253 Miotic, 253, 264 Mitochondrial Swelling, 253, 256 Mitosis, 211, 253 Mobility, 191, 254 Modeling, 39, 254 Modification, 75, 123, 254, 269 Molecule, 131, 140, 143, 210, 214, 223, 230, 231, 232, 242, 254, 260, 269, 274, 283 Monitor, 59, 90, 126, 226, 254, 259 Monoamine, 208, 228, 254, 282 Monoclonal, 49, 244, 247, 254, 269, 285 Monoclonal antibodies, 244, 254 Monocytes, 9, 151, 246, 249, 254, 255, 264 Mononuclear, 254, 282 Morphine, 142, 223, 254, 256, 259 Morphogenesis, 32, 235, 254 Morphological, 11, 13, 17, 24, 34, 46, 59, 232, 236, 254 Morphology, 17, 25, 50, 59, 115, 254 Motility, 254, 273 Motion Perception, 95, 101, 254 Motion Sickness, 254, 256, 272 Motor Activity, 225, 254 Motor Cortex, 8, 9, 59, 254, 270 Motor Skills, 10, 47, 254 Mucosa, 151, 251, 254 Multiple sclerosis, 65, 166, 254 Multiple Trauma, 97, 255 Muscarine, 128, 255 Muscarinic Agonists, 221, 255 Muscular Diseases, 235, 255 Mydriatic, 229, 255, 272 Myelin, 49, 131, 149, 228, 255, 259 Myeloid Cells, 255 Myeloid Progenitor Cells, 92, 255 Myocardial infarction, 139, 151, 225, 253, 255 Myocardial Reperfusion, 255, 270 Myocardial Reperfusion Injury, 255, 270 Myocarditis, 229, 255 Myocardium, 253, 255

Index 297

Myoclonus, 66, 110, 255 N Nadir, 15, 256 Narcotic, 249, 254, 256, 258 Nausea, 168, 210, 256 Necrosis, 32, 34, 149, 211, 217, 220, 245, 253, 255, 256, 270 Needle Sharing, 168, 256 Neocortex, 55, 69, 152, 256, 257 Neomycin, 140, 256 Neonatal, 5, 32, 36, 43, 47, 50, 59, 61, 64, 70, 82, 84, 86, 87, 90, 91, 94, 96, 130, 149, 185, 256 Neonatal period, 149, 256 Neoplasms, 166, 206, 217, 218, 256, 269 Nerve Growth Factor, 31, 256 Networks, 34, 130, 149, 256 Neural Crest, 144, 256 Neural Pathways, 47, 256 Neuroanatomy, 46, 249, 256 Neurobehavioral Manifestations, 217, 229, 256 Neurodegenerative Diseases, 141, 150, 213, 257 Neurofibrillary Tangles, 146, 152, 257 Neurofilaments, 257 Neurologic, 5, 20, 26, 30, 32, 36, 121, 138, 145, 158, 160, 166, 217, 242, 257 Neurologist, 61, 257 Neuromuscular, 205, 235, 257, 281 Neuromuscular Junction, 205, 257 Neuronal, 5, 8, 9, 12, 14, 26, 27, 28, 30, 31, 33, 36, 40, 44, 48, 52, 53, 55, 57, 58, 75, 90, 106, 109, 110, 120, 126, 131, 133, 139, 141, 142, 143, 144, 147, 149, 150, 154, 218, 257 Neuropharmacology, 42, 52, 140, 257 Neuropsychological Tests, 46, 257 Neuropsychology, 46, 61, 70, 73, 74, 116, 159, 161, 162, 163, 164, 257 Neurosciences, 34, 48, 52, 65, 257 Neurosurgery, 6, 24, 34, 43, 50, 66, 71, 77, 79, 83, 85, 88, 91, 98, 99, 106, 110, 166, 257 Neurotoxic, 21, 27, 33, 40, 120, 125, 128, 129, 132, 133, 140, 142, 257 Neurotoxicity, 15, 25, 34, 128, 147, 229, 248, 257 Neurotoxin, 52, 120, 134, 257 Neurotransmitters, 133, 141, 234, 258 Neutrons, 207, 247, 258, 269 Neutropenia, 258, 264

Neutrophils, 35, 151, 211, 239, 249, 258, 264 Niche, 54, 258 Nicotine, 16, 142, 258 Nitric Oxide, 6, 15, 25, 27, 30, 35, 36, 50, 85, 86, 258 Nitrogen, 35, 144, 207, 235, 258, 281 Nitroprusside, 6, 258 Nitrous Oxide, 27, 258 Nonverbal Communication, 223, 258, 268 Norepinephrine, 206, 230, 258, 270 Normotensive, 10, 259 Nuclear, 26, 35, 67, 106, 213, 231, 237, 246, 249, 256, 259, 279 Nuclei, 6, 58, 207, 208, 209, 231, 235, 249, 251, 253, 258, 259, 265, 267, 272 Nucleic acid, 30, 40, 237, 243, 258, 259, 268 Nucleus Accumbens, 16, 259 O Occipital Lobe, 259, 284 Oedema, 68, 126, 259 Oligodendroglial, 54, 259 Oncology, 34, 259 On-line, 11, 55, 203, 259 Opacity, 228, 259 Opium, 254, 259, 261 Optic Chiasm, 243, 253, 259 Optic Nerve, 229, 259, 261, 271 Organ Transplantation, 151, 259 Organelles, 220, 227, 254, 259 Orthotic Devices, 191, 260 Osmotic, 207, 253, 260, 273 Osteoarthritis, 136, 137, 260 Osteolysis, 68, 260 Ovum, 225, 227, 237, 260, 266, 284 Oxidants, 27, 151, 260 Oxidation, 40, 205, 210, 211, 215, 226, 227, 238, 241, 250, 260 Oxidation-Reduction, 215, 260 Oxidative Stress, 22, 30, 31, 40, 51, 57, 118, 260 Oximetry, 28, 49, 260 Oxygen Consumption, 119, 260, 271 Oxygenation, 14, 49, 64, 241, 243, 260 Oxygenator, 218, 260 P Pachymeningitis, 252, 260 Palliative, 261, 279 Palsy, 138, 149, 191, 261 Pancreas, 139, 205, 215, 246, 261, 282 Papaverine, 6, 259, 261 Papule, 221, 261

298 Brain Damage

Paralysis, 136, 144, 194, 211, 235, 240, 252, 261, 275 Paranoia, 172, 261 Parasympathomimetic, 255, 261 Paresis, 235, 240, 261 Parkinsonism, 155, 210, 215, 249, 261, 266, 281 Paroxysmal, 239, 261, 262, 284 Particle, 261, 275, 281 Patch, 53, 261 Pathogen, 33, 36, 244, 261 Pathogenesis, 12, 15, 27, 52, 54, 92, 98, 106, 119, 151, 261 Pathologic, 32, 152, 211, 217, 225, 242, 243, 261, 268, 271, 275 Pathologic Processes, 211, 261 Pathophysiology, 6, 32, 36, 82, 93, 121, 261 Patient Education, 190, 198, 200, 203, 261 Pediatrics, 15, 28, 31, 51, 52, 64, 67, 69, 96, 98, 101, 168, 185, 194, 262 Peduncle, 262, 270 Pelvic, 68, 262, 267 Penicillin, 209, 262 Penis, 193, 224, 262 Peptide, 8, 14, 26, 147, 262, 267, 280 Perception, 7, 73, 74, 93, 98, 101, 158, 240, 262, 272 Perfusion, 6, 11, 15, 29, 41, 43, 58, 97, 143, 145, 243, 262 Pericardium, 262, 278 Perinatal, 16, 18, 25, 48, 49, 51, 61, 63, 69, 72, 75, 78, 82, 91, 93, 95, 96, 99, 100, 106, 120, 125, 141, 149, 154, 163, 262 Peripheral Nervous System, 157, 215, 228, 231, 240, 257, 261, 262, 277 Peripheral Nervous System Diseases, 240, 262 Peritoneal, 212, 259, 262 Peritoneal Cavity, 212, 259, 262 Periventricular Leukomalacia, 149, 262 Pertussis, 71, 106, 176, 194, 262, 284 Petechiae, 239, 263 Petroleum, 217, 263 PH, 77, 97, 263 Phagocyte, 260, 263 Phagocytosis, 12, 151, 263 Pharmacokinetic, 263 Pharmacologic, 15, 26, 35, 51, 209, 263, 281 Phencyclidine, 21, 129, 263 Phenobarbital, 53, 263 Phenotype, 33, 42, 46, 263 Phenylalanine, 263, 282

Phosphodiesterase, 6, 263 Phospholipases, 263, 274 Phospholipids, 58, 119, 139, 235, 245, 263 Phosphorus, 58, 218, 263 Phosphorylated, 146, 152, 263 Phosphorylation, 26, 263 Phototherapy, 131, 185, 263 Physical Examination, 237, 263 Physical Therapy, 86, 148, 264 Physiologic, 57, 207, 215, 230, 252, 256, 264, 269, 270, 271 Physiology, 8, 19, 60, 115, 191, 218, 231, 257, 264, 283 Pigment, 130, 214, 264 Pilocarpine, 128, 264 Piloerection, 243, 264 Pilot study, 42, 63, 68, 72, 264 Placenta, 75, 264, 266 Plants, 207, 212, 213, 214, 215, 218, 221, 222, 238, 241, 254, 258, 264, 281 Plasma, 31, 40, 82, 151, 207, 210, 216, 220, 232, 235, 237, 238, 240, 241, 264, 267, 273 Plasma cells, 151, 210, 264 Plasma protein, 207, 232, 264, 267, 273 Plasmin, 236, 264, 280, 282 Plasminogen, 236, 264, 280, 282 Plasticity, 9, 22, 36, 47, 48, 49, 53, 59, 264 Platelet Activating Factor, 118, 264 Platelet Activation, 264, 274 Platelet Aggregation, 209, 258, 265, 280 Platelets, 211, 258, 264, 265, 280 Pleomorphic, 259, 265 Pleural, 259, 265 Pleural cavity, 259, 265 Poisoning, 144, 228, 246, 256, 265 Policy Making, 238, 265 Polymerase, 35, 94, 265 Polymers, 139, 154, 265, 267, 277 Polymorphic, 228, 265 Polysaccharide, 210, 265 Pons, 51, 217, 235, 265 Posterior, 70, 100, 102, 122, 208, 212, 213, 220, 230, 246, 259, 261, 265 Postnatal, 25, 36, 235, 265, 276 Postoperative, 27, 84, 265 Postsynaptic, 120, 147, 265, 274, 278 Post-traumatic, 14, 94, 217, 239, 265 Potassium, 52, 265 Potentiate, 25, 35, 265 Potentiation, 22, 73, 101, 221, 265, 274 Practice Guidelines, 186, 266 Preclinical, 76, 266

Index 299

Precursor, 21, 29, 54, 211, 221, 230, 231, 233, 249, 258, 263, 264, 266, 267, 281, 282 Prefrontal Cortex, 44, 66, 266 Pregnancy Tests, 237, 266 Premedication, 266, 272 Prenatal, 15, 42, 46, 59, 94, 232, 235, 266 Presynaptic, 76, 152, 266, 278 Prevalence, 23, 56, 94, 160, 165, 266 Probe, 253, 266 Procyclidine, 128, 266 Progeny, 32, 266 Progesterone, 65, 266 Progression, 11, 21, 35, 54, 209, 266 Progressive, 17, 34, 53, 79, 97, 141, 152, 166, 193, 219, 228, 230, 239, 256, 257, 260, 264, 266 Projection, 227, 246, 258, 259, 266, 269, 270 Prone, 52, 106, 122, 123, 266 Prophase, 266, 278, 282 Proprioception, 135, 136, 266 Prospective study, 93, 250, 267 Prostaglandins, 211, 267 Prostate, 215, 267, 282 Prostitution, 167, 267 Protease, 223, 267, 280 Protective Agents, 143, 267 Protein C, 207, 213, 267 Protein Kinases, 118, 267 Protein S, 30, 131, 165, 215, 237, 256, 267, 276 Proteolytic, 223, 235, 264, 267, 280, 282 Prothrombin, 267, 279 Protocol, 46, 56, 267 Protons, 207, 242, 251, 267, 269 Proximal, 230, 266, 267, 273 Proximate cause, 87, 267 Pruritic, 231, 267 Psoriasis, 136, 137, 267, 271 Psychiatric, 168, 172, 194, 223, 268 Psychiatry, 7, 21, 38, 44, 45, 64, 65, 66, 77, 85, 91, 98, 99, 110, 165, 237, 268, 283 Psychic, 268, 273 Psychoanalysis, 142, 268 Psychology, 7, 9, 11, 18, 29, 36, 37, 39, 45, 55, 56, 59, 87, 101, 103, 115, 159, 230, 257, 268 Psychomotor, 94, 228, 268 Psychophysiology, 257, 268 Psychotherapy, 142, 268 Psychotomimetic, 143, 208, 228, 268 Puberty, 134, 268 Public Health, 13, 18, 57, 168, 186, 268

Public Policy, 183, 268 Publishing, 60, 158, 268 Pulmonary, 136, 137, 192, 216, 225, 249, 268, 283 Pulmonary Artery, 216, 268, 283 Pulse, 49, 254, 260, 268 Purines, 268, 273, 284 Purpura, 239, 268 Purulent, 205, 268 Pyramidal Cells, 228, 269 Q Quality of Life, 18, 20, 57, 226, 269 Quaternary, 269, 272 Quinoxaline, 60, 269 R Race, 230, 248, 253, 269 Radiation, 39, 54, 88, 95, 231, 234, 236, 246, 247, 269, 272, 277, 285 Radiation therapy, 39, 234, 246, 247, 269, 285 Radioactive, 216, 242, 244, 246, 247, 250, 254, 259, 269, 272, 285 Radiography, 209, 237, 269 Radioisotope, 269, 281 Radiolabeled, 216, 247, 269, 285 Radiological, 13, 95, 269 Radiology, 5, 29, 38, 72, 79, 269 Radiotherapy, 216, 247, 269, 285 Randomized, 231, 269 Reactive Oxygen Species, 12, 43, 55, 58, 269 Receptor, 9, 13, 21, 33, 35, 55, 96, 118, 120, 121, 128, 129, 133, 139, 140, 142, 143, 147, 149, 205, 210, 222, 229, 230, 234, 248, 263, 269, 273, 274 Receptors, Serotonin, 270, 273 Recombinant, 31, 270, 283 Recovery of Function, 20, 29, 52, 94, 270 Rectum, 211, 236, 237, 244, 245, 267, 270 Recurrence, 222, 270 Red Nucleus, 6, 212, 270 Reductase, 270, 279 Refer, 1, 223, 230, 236, 241, 246, 250, 258, 270, 283 Reflex, 66, 110, 270 Reflux, 78, 270 Refraction, 270, 275 Refractory, 98, 270 Regeneration, 150, 154, 270 Regimen, 22, 130, 132, 192, 193, 231, 270 Rehabilitative, 52, 59, 135, 270 Relapse, 58, 270

300 Brain Damage

Relaxant, 261, 270 Reliability, 13, 270 Reperfusion, 20, 27, 30, 33, 43, 55, 143, 151, 255, 270 Reperfusion Injury, 151, 270 Reserpine, 215, 270 Resorption, 242, 271 Respiration, 134, 154, 218, 254, 271 Respiratory distress syndrome, 151, 271 Restoration, 30, 43, 255, 264, 270, 271, 284 Resuscitation, 12, 72, 134, 154, 219, 271 Retina, 259, 271 Retinoids, 271, 284 Retinopathy, 50, 271 Retrograde, 64, 271 Retrograde Amnesia, 64, 271 Rheumatism, 63, 271 Rheumatoid, 136, 137, 151, 260, 271 Rheumatoid arthritis, 136, 137, 151, 271 Ribose, 35, 94, 206, 271 Rigidity, 247, 251, 261, 264, 271 Risk factor, 3, 8, 193, 267, 271 Risperidone, 100, 271 Rod, 124, 222, 239, 271 Rubber, 138, 205, 271 Rubella, 194, 272 Ryanodine, 96, 272 S Saline, 13, 15, 136, 272 Saphenous, 225, 272 Saphenous Vein, 225, 272 Sarin, 132, 272 Scans, 41, 48, 51, 153, 272 Schizoid, 272, 284 Schizophrenia, 93, 116, 134, 164, 170, 261, 271, 272, 284 Schizotypal Personality Disorder, 272, 284 Sclerosis, 141, 150, 246, 255, 272 Scopolamine, 106, 128, 140, 214, 272 Screening, 3, 126, 128, 141, 222, 248, 272 Secobarbital, 140, 272 Second Messenger Systems, 258, 272 Secretion, 12, 222, 242, 243, 246, 272, 273 Secretory, 273, 278 Sedative, 213, 223, 272, 273 Sedatives, Barbiturate, 273 Segmentation, 23, 273 Segregation, 45, 273 Seizures, 41, 48, 52, 53, 57, 62, 76, 128, 132, 138, 141, 228, 233, 261, 273, 275, 276 Semantics, 40, 80, 273 Senile, 120, 139, 152, 273

Sepsis, 151, 164, 273 Septal, 17, 209, 249, 273 Serine, 273, 280 Serotonin, 29, 47, 210, 215, 236, 270, 271, 273, 281 Serous, 232, 273 Serum, 13, 55, 63, 66, 68, 83, 96, 97, 99, 130, 206, 207, 209, 223, 226, 273, 282 Serum Albumin, 13, 273 Sex Characteristics, 206, 268, 273 Sexual Abstinence, 168, 273 Shock, 22, 66, 82, 97, 118, 121, 134, 145, 151, 164, 231, 255, 273, 281 Side effect, 27, 50, 54, 125, 140, 141, 142, 143, 175, 192, 206, 210, 274, 280 Signal Transduction, 30, 245, 274 Signs and Symptoms, 270, 274 Skeletal, 222, 226, 255, 274, 275 Skeleton, 205, 248, 274 Skull, 79, 119, 144, 146, 158, 166, 190, 226, 247, 274, 278 Skull Fracture, Depressed, 274 Skull Fractures, 79, 191, 274 Smooth muscle, 9, 207, 209, 218, 224, 242, 254, 255, 261, 274, 275, 277 Sneezing, 262, 274 Social Behavior, 46, 274 Social Class, 84, 274 Social Environment, 269, 274 Sodium, 6, 20, 68, 140, 155, 229, 274, 277 Solvent, 92, 205, 234, 238, 260, 275 Soma, 269, 275 Soman, 69, 106, 110, 128, 132, 275 Somatic, 16, 33, 206, 226, 249, 252, 253, 261, 262, 266, 275 Sound wave, 224, 275 Spasm, 211, 225, 252, 275 Spasmodic, 262, 275 Spastic, 191, 275 Spasticity, 275 Spatial disorientation, 230, 275 Specialist, 196, 229, 275 Species, 35, 214, 233, 239, 242, 248, 252, 253, 254, 255, 259, 269, 274, 275, 277, 281, 284 Specificity, 17, 29, 56, 161, 206, 211, 218, 275 Spectrum, 39, 121, 130, 226, 275 Speech-Language Pathology, 159, 275 Spinal Cord Diseases, 240, 275 Spinal Cord Injuries, 147, 275 Spinal Nerves, 262, 275

Index 301

Spinal tap, 251, 276 Spirochete, 276, 278 Spleen, 151, 208, 251, 276 Sporadic, 257, 276 Staging, 272, 276 Status Epilepticus, 51, 53, 57, 80, 102, 119, 141, 276 Steel, 122, 222, 276 Stem Cell Factor, 222, 276 Stem Cells, 144, 233, 234, 255, 276 Sterile, 144, 276 Stillbirth, 192, 276 Stimulant, 208, 218, 228, 242, 253, 276 Stimulus, 37, 73, 101, 102, 230, 231, 234, 245, 247, 270, 276, 279 Stomach, 205, 226, 234, 237, 242, 256, 262, 270, 276 Strand, 34, 58, 265, 276 Streptococci, 36, 276 Streptomycin, 140, 276 Stress, 33, 35, 40, 51, 58, 110, 112, 213, 219, 226, 231, 256, 260, 271, 276 Striatum, 16, 44, 155, 259, 276 Styrene, 271, 277 Subacute, 75, 245, 277 Subarachnoid, 6, 71, 97, 239, 247, 277 Subclinical, 245, 273, 277 Subcutaneous, 206, 231, 259, 277 Subiculum, 242, 277 Subspecies, 275, 277 Substance P, 252, 273, 276, 277 Substrate, 15, 47, 139, 277, 282 Sunburn, 136, 137, 277 Superoxide, 28, 35, 55, 58, 277 Superoxide Dismutase, 28, 55, 58, 277 Supplementation, 146, 277 Suppression, 17, 19, 89, 277 Sweat, 243, 277 Sympathetic Nervous System, 213, 257, 277 Sympathomimetic, 208, 228, 230, 233, 253, 258, 277, 282 Symptomatic, 53, 97, 214, 277 Symptomatic treatment, 214, 277 Synapses, 9, 59, 140, 221, 258, 278 Synapsis, 278 Synaptic, 17, 22, 37, 52, 53, 59, 98, 120, 140, 143, 258, 274, 278 Synaptic Transmission, 258, 278 Synaptic Vesicles, 278 Syphilis, 192, 193, 221, 278

Systemic, 34, 57, 63, 72, 121, 176, 208, 211, 216, 217, 228, 229, 233, 245, 247, 257, 259, 264, 269, 278, 285 Systemic lupus erythematosus, 63, 278 Systolic, 243, 278 T Tardive, 64, 210, 278 Telencephalon, 213, 278 Temporal, 8, 14, 26, 39, 49, 53, 54, 56, 73, 76, 87, 141, 208, 239, 240, 242, 278 Temporal Lobe, 53, 87, 141, 208, 278 Teratogenesis, 42, 278 Teratogenic, 12, 42, 278 Tetani, 278, 279 Tetanic, 279 Tetanus, 64, 176, 194, 278, 279 Thalamic, 212, 279 Thalamic Diseases, 212, 279 Thalamus, 145, 217, 229, 249, 266, 279 Theophylline, 73, 99, 268, 279 Therapeutics, 31, 176, 279 Thigh, 235, 239, 279 Thiobarbituric Acid Reactive Substances, 58, 279 Thioredoxin, 93, 279 Third Ventricle, 243, 279 Thoracic, 66, 78, 123, 213, 279 Thorax, 134, 205, 250, 279 Threshold, 56, 57, 234, 243, 279 Thrombin, 11, 235, 265, 267, 279, 280 Thrombocytopenia, 264, 279 Thrombolytic, 35, 151, 264, 279, 280 Thrombolytic Therapy, 35, 280 Thrombomodulin, 131, 267, 280 Thrombosis, 166, 247, 267, 277, 280 Thromboxanes, 211, 280 Thrombus, 225, 245, 247, 255, 265, 279, 280, 283 Thyroid, 243, 280, 282 Thyrotropin, 243, 280 Thyroxine, 207, 263, 280 Tissue Plasminogen Activator, 11, 25, 280 Tolerance, 13, 54, 205, 238, 243, 280 Tomography, 36, 251, 280 Tonic, 250, 280 Tooth Preparation, 205, 280 Topical, 234, 242, 280 Torsion, 123, 245, 280 Toxicity, 12, 17, 93, 230, 280 Toxicokinetics, 280 Toxicology, 94, 184, 281 Toxins, 40, 210, 218, 232, 245, 254, 281

302 Brain Damage

Tracer, 67, 281 Trachea, 217, 280, 281 Tracheostomy, 73, 281 Traction, 222, 281 Transduction, 26, 30, 274, 281 Transfection, 215, 281 Transfusion, 70, 281 Translation, 256, 281 Translocation, 14, 281 Transmitter, 120, 143, 205, 212, 230, 234, 247, 252, 258, 278, 281, 282 Transplantation, 54, 79, 155, 244, 281 Trauma, Nervous System, 150, 281 Trees, 271, 281 Trihexyphenidyl, 128, 281 Trophic, 17, 281 Tryptophan, 223, 273, 281 Tubercle, 259, 281 Tuberculosis, 192, 193, 225, 251, 281 Tubulin, 253, 281 Tumor marker, 215, 282 Tumor Necrosis Factor, 14, 282 Tunica Intima, 232, 282 Tyramine, 215, 282 Tyrosine, 21, 40, 139, 230, 282 U Ubiquitin, 257, 282 Ultrasonography, 237, 282 Unconscious, 209, 227, 243, 282 Univalent, 242, 260, 282 Urethra, 262, 267, 282 Urinary, 221, 242, 244, 255, 272, 280, 282, 284 Urinary Plasminogen Activator, 280, 282 Urine, 215, 226, 230, 244, 248, 282 Uterus, 221, 225, 227, 266, 282 V Vaccine, 71, 85, 98, 176, 267, 282 Vagina, 193, 282 Varicella, 68, 194, 283 Vasculitis, 151, 221, 283 Vasoactive, 16, 283 Vasoconstriction, 6, 233, 283 Vasodilation, 15, 261, 283 Vasodilator, 36, 217, 230, 242, 255, 258, 261, 283 Vasogenic, 32, 283 Vasomotor, 155, 283

Vector, 281, 283 Vein, 209, 212, 259, 272, 283 Venereal, 278, 283 Venous, 49, 70, 84, 133, 134, 212, 216, 217, 220, 247, 259, 267, 283 Venous blood, 133, 134, 216, 217, 220, 283 Venous Thrombosis, 70, 283 Ventilation, 134, 219, 283 Ventral, 16, 44, 134, 243, 259, 265, 276, 283 Ventricle, 208, 219, 242, 259, 268, 278, 279, 283 Ventricular, 20, 242, 255, 283 Ventricular fibrillation, 20, 283 Venules, 151, 216, 218, 232, 253, 283 Vertebrae, 275, 283 Vestibular, 83, 283 Vestibule, 283 Veterinary Medicine, 183, 283 Vial, 144, 284 Villi, 242, 284 Viral, 33, 232, 281, 284 Virulence, 213, 280, 284 Virus, 33, 168, 176, 192, 193, 194, 213, 215, 220, 272, 281, 284 Viscera, 275, 284 Visceral, 123, 213, 226, 249, 284 Visual Cortex, 44, 284 Visual field, 240, 254, 259, 284 Vitamin A, 146, 245, 284 Vitro, 13, 16, 25, 115, 141, 284 Vivo, 11, 15, 25, 33, 35, 41, 141, 153, 284 W White blood cell, 20, 210, 249, 251, 258, 264, 284 Whooping Cough, 85, 98, 194, 262, 284 Withdrawal, 53, 142, 228, 284 Womb, 193, 282, 284 Wound Healing, 252, 284 Wounds, Gunshot, 275, 284 X Xanthine, 27, 284 Xanthine Oxidase, 27, 284 Xenograft, 209, 284 X-ray, 224, 236, 247, 259, 269, 272, 285 X-ray therapy, 247, 285 Y Yeasts, 236, 263, 285

Index 303

304 Brain Damage