RAIN A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Brain: 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: 0-597-84260-4 1. Brain-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.
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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. 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 ........................................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Brain ........................................................................................... 12 E-Journals: PubMed Central ....................................................................................................... 72 The National Library of Medicine: PubMed ................................................................................ 84 Academic Periodicals covering Brain......................................................................................... 123 Dissertations on Brain ............................................................................................................... 123 CHAPTER 2. NUTRITION AND BRAIN ............................................................................................ 129 Overview.................................................................................................................................... 129 Finding Nutrition Studies on Brain .......................................................................................... 129 Federal Resources on Nutrition ................................................................................................. 137 Additional Web Resources ......................................................................................................... 138 CHAPTER 3. ALTERNATIVE MEDICINE AND BRAIN ...................................................................... 143 Overview.................................................................................................................................... 143 The Combined Health Information Database............................................................................. 143 National Center for Complementary and Alternative Medicine................................................ 144 Additional Web Resources ......................................................................................................... 156 General References ..................................................................................................................... 180 CHAPTER 4. CLINICAL TRIALS AND BRAIN .................................................................................. 181 Overview.................................................................................................................................... 181 Recent Trials on Brain ............................................................................................................... 181 Keeping Current on Clinical Trials ........................................................................................... 199 CHAPTER 5. PATENTS ON BRAIN .................................................................................................. 201 Overview.................................................................................................................................... 201 Patents on Brain ........................................................................................................................ 201 Patent Applications on Brain..................................................................................................... 218 Keeping Current ........................................................................................................................ 238 CHAPTER 6. BOOKS ON BRAIN ...................................................................................................... 239 Overview.................................................................................................................................... 239 Book Summaries: Federal Agencies............................................................................................ 239 Book Summaries: Online Booksellers......................................................................................... 249 The National Library of Medicine Book Index ........................................................................... 249 Chapters on Brain ...................................................................................................................... 251 Directories.................................................................................................................................. 263 CHAPTER 7. MULTIMEDIA ON BRAIN ........................................................................................... 265 Overview.................................................................................................................................... 265 Video Recordings ....................................................................................................................... 265 Audio Recordings....................................................................................................................... 267 Bibliography: Multimedia on Brain ........................................................................................... 268 CHAPTER 8. RESEARCHING MEDICATIONS ................................................................................... 269 Overview.................................................................................................................................... 269 U.S. Pharmacopeia..................................................................................................................... 269 Commercial Databases ............................................................................................................... 277 Researching Orphan Drugs ....................................................................................................... 278 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 283 Overview.................................................................................................................................... 283 NIH Guidelines.......................................................................................................................... 283 NIH Databases........................................................................................................................... 285 Other Commercial Databases..................................................................................................... 293
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The Genome Project and Brain .................................................................................................. 293 APPENDIX B. PATIENT RESOURCES ............................................................................................... 299 Overview.................................................................................................................................... 299 Patient Guideline Sources.......................................................................................................... 299 News Services and Press Releases.............................................................................................. 325 Newsletters on Brain.................................................................................................................. 327 Newsletter Articles .................................................................................................................... 328 Associations and Brain .............................................................................................................. 331 Finding Associations.................................................................................................................. 338 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 341 Overview.................................................................................................................................... 341 Preparation................................................................................................................................. 341 Finding a Local Medical Library................................................................................................ 341 Medical Libraries in the U.S. and Canada ................................................................................. 341 ONLINE GLOSSARIES................................................................................................................ 347 Online Dictionary Directories ................................................................................................... 349 BRAIN DICTIONARY.................................................................................................................. 351 INDEX .............................................................................................................................................. 461
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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 is indexed in search engines, such as www.google.com or others, a nonsystematic 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, 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, 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. 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, 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. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON BRAIN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on brain.
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, 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” (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: •
Aging Brain: Limitations in Our Knowledge and Future Approaches Source: Archives of Neurology. 54: 1201-1205. October 1997. Summary: In this journal article, the author discusses current information about the normal and abnormal aging of the brain and directions for future research. He reviews advances in treatments for cerebrovascular diseases, the role of genetics testing for the apolipoprotein E4 allele in determining Alzheimer's disease (AD), and the possibility of true senile dementia among the oldest population. Finally, he addresses the mechanisms underlying neuronal degeneration in AD and related disorders. 17 references.
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Medial temporal and whole-brain atrophy in dementia with Lewy bodies: A volumetric MRI study Source: Neurology. 51: 357-362. August 1998. Summary: This article describes a Japanese study that examined whether medial temporal MRI volumetry was useful in clinically differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). Researchers compared the volumes of the hippocampal formation, the amygdaloid complex, and the whole brain in 27 patients with probable DLB, 27 patients with probable AD, and 27 normal elderly subjects (controls) using an MRI-based volumetric technique. Data showed that hippocampal volume in the DLB group was significantly larger than that in the AD group, but significantly smaller than in the control group. No significant differences appeared in the amygdala and whole-brain volume between the DLB group and the AD group, but the atrophies of the amygdala and whole brain were more severe in the DLB group than in the control group. The authors conclude that these findings indicate the usefulness of MRI hippocampal volumetry for clinically discriminating between patients with DLB and patients with AD. 3 figures, 1 table, 45 references.
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Brain Donation in Normal Aging: Procedures, Motivations, and Donor Characteristics From the Biologically Resilient Adults in Neurological Studies (BRAiNS) Project Source: Gerontologist. 41(6): 716-722. 2001. Summary: This article describes the characteristics of donors in the Biologically Resilient Adults in Neurological Studies (BRAiNS) projects. For more than a decade, the University of Kentucky Alzheimer's Disease Research Center has been recruiting healthy older adults into a program involving annual assessments of mental status, biannual medical and neurological exams, and prearranged postmortem brain examination. Nearly 600 individuals over age 60 years have been enrolled as donors. Of these, 255 (50.7 percent) did so because they had family (39.9 percent) or friends (10.7 percent) with Alzheimer's disease (AD). These individuals are likely motivated by the desire to help others by finding a cause, cure, or treatment for AD. The next most common reasons were the personal referral by another participant (31.8 percent) and the perception that brain donation would not interfere with the donor's choice of cremation (15.5 percent) or close casket funeral (1.8 percent). The findings suggest that rates of brain autopsy may be increased by giving families information about the medical and scientific value of the procedure. 1 figure, 2 tables, 43 references.
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Silent Brain Infarcts and the Risk of Dementia and Cognitive Decline Source: New England Journal of Medicine. 348(13): 1215-1222. March 27, 2003. Summary: This article examines the association between silent brain infarcts and the risk of dementia and cognitive decline in older people. The sample consisted of 1,015 participants in the prospective, population-based Rotterdam Scan Study, who were age 60 to 90 years and free of dementia and stroke at baseline. Participants underwent neuropsychological testing and cerebral magnetic resonance imaging at baseline in 1995 to 1996 and again in 1999 to 2000, and were monitored for dementia throughout the study period. During 3,697 person-years of follow-up (mean follow-up of 3.6 years per person), 30 of the 1,015 participants (3 percent) developed dementia. The presence of silent brain infarcts at baseline more than doubled the risk of dementia and was associated with worse performance on neuropsychological tests and a steeper decline in cognitive function. Silent thalamic infarcts were associated with a decline in memory performance, and nonthalamic infarcts with a decline in psychomotor speed. When
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those with silent infarcts at baseline were subdivided into those with and without additional infarcts at follow-up, the decline in cognitive function was limited to those with additional silent infarcts. 2 figures, 3 tables, 32 references. (AA-M). •
Specificity of Brain Activation Patterns in People at Genetic Risk for Alzheimer Disease Source: American Journal of Geriatric Psychiatry. 10(1): 44-51. January/February 2002. Summary: This article examines the specificity of brain activation patterns in people at genetic risk for Alzheimer's disease (AD). Previous studies with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have revealed differences in neural metabolism and activity between carriers and noncarriers of the apolipoprotein E4 (apoE4) allele. People without dementia carrying the apoE4 allele show greater magnitude and extent of brain activation than noncarriers in regions required for memory, suggesting they perform additional cognitive work to accomplish the same task. To determine whether the fMRI differences are specific to a memory task or generalizable to any difficult cognitive task, researchers performed fMRI and compared images for 25 individuals with and without the apoE4 allele. In the most difficult conditions all participants showed increased MR signal in the prefrontal cortex, indicating increased cognitive effort. However, the two groups showed no differences in activation patterns even at the most difficult task level, suggesting that additional cognitive effort in people at genetic risk for AD is specific to episodic encoding and is not merely a reflection of task difficulty. 3 figures, 2 tables, 25 references. (AA-M).
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Do We Need (and Use) Computed Tomography of the Brain in Every Dementia Evaluation? Source: Journal of Mental Health and Aging. 4(4): 435- 441. Winter 1998. Summary: This article explores the clinical utility of three clinical prediction rules for using computed tomography of the brain in evaluating dementia. An analysis was conducted on evaluations of 152 persons with possible dementia. The evaluations included a computed tomography of the brain, neuropsychological tests and assessment of patient function. Analysis revealed limited value of computed tomography in predicting the presence of potentially treatable lesions and reducing the number of brain imaging procedures recommended. Additionally, none of four potentially treatable brain lesions identified by computed tomography was considered the primary cause of the patient's dementia. A prediction rule for using brain imaging to evaluate dementia patients should include a pragmatic outcome measure, such as change in treatment plan, and should be easily applied by physicians. 2 tables, 18 references. (AA-M).
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Localization of Neurofibrillary Tangles and Beta-Amyloid Plaques in the Brains of Living Patients With Alzheimer's Disease Source: American Journal of Geriatric Psychiatry. 10(1): 24-35. January-February 2002. Summary: This article reports the use of 2-(1-{6-[(2-[18F]fluoroethyl)- (methyl)amino]2naphthyl}ethylidene)malononitrile ([18F]FDDNP) as a molecular imaging probe using positron emission tomography (PET) for the localization of neurofibrillary tangles (NFTs) and beta-amyloid plaques (APs) in the brain of living patients with Alzheimer's disease (AD). Previous work demonstrated the in vitro binding characteristics of [18F]FDDNP to synthetic beta-amyloid (1-40) fibrils and to NFTs and APs in human AD brain specimens. In the present study, greater accumulation and slower clearance were observed AP and NFT dense brain areas and correlated with lower memory
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performance scores. The relative residence time of the probe in brain regions affected by AD was significantly greater in patients with AD (n=9) than in controls (n=7). The authors conclude that this noninvasive technique for monitoring AP and NFT development should facilitate diagnostic assessment of patients with AD and assist in monitoring responses to experimental treatments. 6 figures, 1 table, 45 references. (AAM). •
Rethinking Estrogen and the Brain (editorial) Source: Journal of the American Geriatrics Society. 46(7): 918-920. July 1998. Summary: This editorial discusses the article by Yaffe, K., et al. (Journal of the American Geriatrics Society 46(7): 816-821. July 1998) that demonstrates that women with high endogenous estrone levels performed significantly worse on two of three cognitive function tests than women with lower levels of estrone. Estradiol levels were unrelated to change in test performance. The author concludes that this study of endogenous estrogen and change in cognitive function fails to support the hypothesis that estrogen preserves brain function. The author discusses how well the estrogen-memory data meet the standard epidemiologic criteria for causality, confounding factors, compliance bias, and misclassification bias, and concludes that enthusiasm for the neuroprotective effects of estrogen appear to have outrun the actual data. All observational studies have limitations, and clinical trials are small and few. The unexpected results highlight the need for some restraint until results are available from other clinical trials. 27 references.
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Estrogen Makes the Brain a Sex Organ Source: Journal of Clinical Psychiatry. 58(10): 421-422. October 1997. Summary: This journal article briefly reviews recent advances in knowledge about understanding of the effects of estrogen on the brain. Estrogen is one of the agents currently under investigation for the prevention or treatment of Alzheimer's disease. It has well documented actions on several neurotransmitter systems, including serotonergic, adrenergic, and cholinergic pathways and receptors. However, findings from molecular neuroscience suggest that estrogen may not act like a traditional neurotransmitter. Its receptors are present in the cell nucleus of certain neurons, where they can directly influence the expression of genes in the central nervous system. In addition, estrogen can exert dramatic cyclical influences on synapses in certain neurons during the menstrual cycle, with early-cycle estrogen erecting synapses and late-cycle estrogen withdrawal dismantling them. 1 figure, 5 references.
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Herpes Simplex Virus Type 1 in Brain and Risk of Alzheimer's Disease Source: Lancet. 349: 241-244. January 25, 1997. Summary: This journal article describes a possible association between herpes simplex virus type 1 (HSV1) and apolipoprotein E4 (apoE4) in Alzheimer's disease (AD). Researchers studied 84 brain samples from 46 AD patients and 75 brain samples from 44 people without dementia. DNA was extracted from the brain samples, and polymerase chain reaction (PCR) amplification was used to detect the HSV1 thymidine kinase gene and the host apoE gene. Multiple regression analysis suggests that the apoE4 allele frequency was significantly higher in AD patients positive for HSV1 in the brain (58.8 percent) than in the HSV1-negative AD group (10 percent), the HSV1-positive nondementia group (3.6 percent), or the HSV1-negative nondementia group (6.3 percent). The odds ratio for apoE4 compared with the HSV1-negative nondementia group was 16.8 in the HSV1-positive AD group, 1.67 in the HSV1-negative AD group,
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and 0.56 in the HSV1-positive nondementia group. In a separate comparison of apoE gene statuses in 40 people with and 33 without recurrent cold sores, the apoE4 allele frequencies were 36 percent and 9 percent, respectively. The authors conclude that the combination of HSV1 in the brain and the presence of an apoE4 allele appears to be a strong risk factor for AD. 1 figure, 5 tables, 26 references. (AA-M). •
Using Serial Registered Brain Magnetic Resonance Imaging To Measure Disease Progression in Alzheimer Disease: Power Calculations and Estimates of Sample Source: Archives of Neurology. 57: 339-344. March 2000. Summary: This journal article describes a study to evaluate the rate of brain atrophy by using Magnetic Resonance Imaging (MRI) as a marker of disease progression for use in clinical trials for in Alzheimer's disease (AD). Eighteen AD patients were matched with controls who underwent brain scans every 12 months. The researchers also used the data to estimate the sample sizes that would be necessary for clinical drug trials. The rate of brain atrophy for AD patients was 2.37 percent per year, and for the control group was.41 percent. Results suggest that serial MRI volume images are a powerful method of quantification of brain atrophy that can be used to monitor progression of AD in clinical trials. 4 tables, 37 references. (AA-M).
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Brain Regions Associated With Episodic Retrieval in Normal Aging and Alzheimer's Disease Source: Neurology. 52: 1861-1870. June 1999. Summary: This journal article describes a Swedish study that examined patterns of brain activation during verbal episodic retrieval in eight people with probable early-onset Alzheimer's disease (AD) and mild or very mild dementia from a university hospital compared to eight healthy older people. They were given 6 word lists comprising 12 common words of varied lengths. Using positron emission tomography, researchers assessed blood flow during two retrieval conditions involving completion of word stems (baseline and cued recall). People with AD had a marked performance deficit in cued recall, although the groups were indistinguishable on the baseline task. Both groups showed bilateral activity in orbital and dorsolateral prefrontal cortex, left precuneus, and right cerebellum, and decreased activity in distinct left temporal regions during cued recall. AD-related increases in activity during cued recall were observed in the left orbital prefrontal cortex and left cerebellum. The researchers conclude that a large distributed network involved in episodic memory retrieval functions relatively normally in early AD. Retrieval activations seen in the control group may reflect ADrelated failures in semantic processing and successful recollection of target information. 2 figures, 3 tables, 51 references. (AA-M).
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Antibodies to a-Synuclein Detect Lewy Bodies in Many Down's Syndrome Brains With Alzheimer's Disease Source: Annals of Neurology. 45(3): 353-357. March 1999. Summary: This journal article describes an immunohistochemical examination of brains from 20 individuals with Down syndrome (DS). The sample included 16 cases that met pathological criteria for Alzheimer's disease (AD), ages 53-70 years at death, and 4 very young cases (mean age of 1.3 years at death) with no evidence of AD. Samples from various regions of the brain were examined using antibodies to alpha-synuclein, betasynuclein, and gamma-synuclein. Alpha-synuclein-positive Lewy bodies and dystrophic neurites and neuropil threads were frequent in 50 percent of amygdala samples from the
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DS brains with AD. These lesions were less common in other brain regions and were not found in the very young DS cases or in two older DS cases without a history of behavioral decline. None of the brain samples contained beta-synuclein or gammasynuclein abnormalities. The authors conclude that alpha-synuclein-positive Lewy bodies and neuritic processes frequently occur with AD in DS patients. 1 figure, 1 table, 24 references. •
Ovarian Steroids and the Brain: Implications for Cognition and Aging Source: Neurology. 48(Supplement 7): S8-S15. May 1997. Summary: This journal article describes neural actions of gonadal hormones on nonreproductive brain structures and processes, with particular emphasis on the effects of estrogen and progestin on the hippocampal formation and basal forebrain of the rat. These brain structures play a prominent role in learning and memory, and are sites of neural degeneration in Alzheimer's disease and other dementing illnesses. The article also discusses ovarian steroid influences on the midbrain and brainstem monoaminergic systems, in light of their widespread involvement with brain functions that subserve movement and affective states. 90 references.
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Effect of Estrogen on Brain Activation Patterns in Postmenopausal Women During Working Memory Tasks Source: JAMA. The Journal of the American Medical Association. 281(13): 1197-1202. April 7, 1999. Summary: This journal article describes the effects of estrogen on brain activation patterns in post-menopausal women during verbal and nonverbal working memory tasks. Forty-six postmenopausal women, aged 33 to 61 years, were enrolled in a randomized, double-blind, placebo-controlled trial. Women were randomly assigned to 21 days of treatment with conjugated equine estrogens (1.25 mg/d) or placebo, followed by a washout period of 14 days before crossover to the other treatment. Brain activation patterns were measured with functional magnetic resonance imaging during tasks involving verbal and nonverbal working memory. Treatment with estrogen increased activation in the inferior parietal lobule during storage of verbal material, whereas it decreased activation during storage of nonverbal material. Estrogen also produced a sharpening of the hemisphere encoding/retrieval asymmetry effect; it increased activation in the right superior frontal gyrus during retrieval tasks, with greater left hemisphere activation during encoding. Estrogen did not affect actual performance on the verbal and nonverbal memory tasks. The results suggest that it may be possible to affect functional brain organization in older women. 4 figures, 34 references. (AA-M).
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Inheritance of the ApoEe4 Allele Increases the Rate of Brain Atrophy in Dementia Patients Source: Dementia and Geriatric Cognitive Disorders. 10: 262-268. 1999. Summary: This journal article discusses the influence of the apolipoprotein E4 (apoE4) allele on the rate of brain atrophy in patients with dementia and those at risk for dementia. Eighty-one people consecutively referred to a memory clinic underwent a comprehensive examination which included cerebral magnetic resonance imaging (MRI). The participants were divided into the following diagnostic groups: Alzheimer's disease (AD, n=23); objective cognitive impairment (n=27); subjective cognitive impairment (n=17); and other dementia (OD, n=14). All participants underwent apoE genotyping and were reexamined after an average period of 16 months. ApoE4 carriers
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had a significantly larger increase in ventricular volume than the apoE4 noncarriers. In all diagnostic groups, the apoE4 carriers had a greater rate of ventricular volume increase than the noncarriers. However, the difference was significant only for the OD group. No significant changes were seen for whole brain volume or volume of the temporal and medial temporal lobes. The presence of an apoE4 allele did not affect the rate of cognitive decline. 6 tables, 33 references. •
Patterns of Brain Activation in People At Risk for Alzheimer's Disease Source: NEJM. New England Journal of Medicine. 343(7): 450-456. August 17, 2000. Summary: This journal article examined the relationship between brain responses to tasks requiring memory and the genetic risk of Alzheimer's disease (AD). The study involved 30 people who were neurologically normal, 16 of whom were carriers of the apolipoprotein e4 (APOE e4) allele and 14 of whom were homozygous for the APOE e3 allele. The researchers determined patterns of brain activation during functional MRI scanning while participants memorized and recalled pairs of words and while they rested between the tasks. The researchers reassessed the memory of 14 participants 2 years later. Analysis indicated that both the magnitude and extent of brain activation in regions affected by AD were greater among the carriers of the APOE e4 allele than among the carriers of the APOE 3 allele. The authors concluded that patterns of brain activation during tasks that require memory differ according to the genetic risk of AD and may predict a subsequent memory decline. 3 figures, 2 tables, 34 references.
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Brain Choline Acetyltransferase and Mental Function in Alzheimer Disease Source: Archives of Neurology. 56: 1121-1123. September 1999. Summary: This journal article examines the association between brain levels of choline acetyltransferase (ChAT) and neuropsychological function in patients with Alzheimer's disease (AD). The participants were eight AD patients undergoing dural and cortical brain biopsy in the right frontal region, in some cases a as prelude to surgical implantation of intraventricular pumps or placement of a ventriculoperitoneal shunt. ChAT levels were determined in fresh brain tissues from the biopsy samples. All patients underwent neuropsychological testing no more than 2 weeks before surgical biopsy. The results showed significant positive correlations between ChAT levels and scores on two neuropsychological tests, the Mini-Mental State Examination and the Logical Memory subtest of the Wechsler Memory Scale. The results indicate that degeneration of the cholinergic system in vivo correlates with decreasing cognitive function in patients with AD. 1 figure, 2 tables, 26 references
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Brain Aging and Midlife Tofu Consumption Source: Journal of the American College of Nutrition. 19(2): 242-255. 2000. Summary: This journal article explores the associations between midlife tofu consumption and changes in brain function and structure in later life. Investigators used data for surviving participants of a longitudinal study established in 1965. Information on the consumption of selected foods was available from standardized interviews, and was used to classify tofu consumption into four intake levels. Cognitive function was tested when participants were aged 71 to 93 years. Brain atrophy was assessed using neuroimage and autopsy. Cognitive function data also were analyzed for wives of a sample of study participants who had been living with the participants at the time of their dietary interviews. Poor cognitive test performance, enlargement of ventricles, and low brain weight were each significantly and independently associated with higher
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midlife tofu consumption. A similar association of midlife tofu intake with poor late life cognitive function also was observed among the wives of study participants. 3 figures, 8 tables, 56 references. (AA-M). •
Altered Brain Activation in Cognitively Intact Individuals at High Risk for Alzheimer's Disease Source: Neurology. 53: 1391-1396. 1999. Summary: This journal article explores whether brain function is altered in cognitively normal individuals at high risk for Alzheimer's disease (AD) several years before the typical age of onset for this disease. Researchers studied healthy, right-handed women, aged 40 to 65 years, at high (n=14) or low (n=12) risk for developing AD based on family history and apolipoprotein E allele status. The groups did not differ significantly in age, education, and cognitive status. Functional magnetic resonance imaging was used to examine cortical activation during visual naming and letter fluency tasks. The regional patterns of brain activation were similar in the two groups. However, the high risk group showed areas of significantly reduced activation in the mid and posterior inferotemporal regions bilaterally during both tasks, despite identical naming and letter fluency performance. The findings indicate that individuals at high risk for AD may exhibit reduced brain activation in key areas engaged during naming and fluency tasks, and this decreased activation may be present years before the clinical symptoms of AD typically appear. 2 figures, 2 tables, 32 references.
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Alzheimer's Disease: Seeking New Ways to Preserve Brain Function Source: Geriatrics. 54(2): 42-47. February 1999. Summary: This journal article presents an interview with Dr. Kenneth Davis and explores options for primary care treatment of patients with Alzheimer's disease (AD). Dr. Davis is the chairman of the department of psychiatry and director of the Alzheimer's Disease Research Center at Mt. Sinai School of Medicine in New York City. Dr. Davis describes the current understanding of the pathophysiology of AD and discusses some potential causes and risk factors. He outlines diagnostic criteria and responds to questions about treatment goals and strategies using cholinesterase inhibitors. Other topics covered include genetic testing, research, and the future of primary care for patients with AD and their families. A suggested reading list and Internet resources are provided. 7 references.
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Some Developments in Brain Ageing and Dementia Source: British Journal of Biomedical Science. 54: 201-215. 1997. Summary: This journal article reviews some of the biological, neurophysiological, and cognitive changes associated with aging of the human brain, both those which occur throughout life and those which develop in the senescent (postmaturity) period. It also explores the changes associated with age-related diseases such as Alzheimer's disease (AD), idiopathic Parkinson's disease (IPD), and dementia with Lewy bodies (DLB). This discussion focuses on the neuropathology and neurochemistry of these neurodegenerative diseases, the major risk factors (age, gender, genetic factors, and education), the relationship between aging and AD, and future prospects for the treatment of AD, IPD, and DLB. Long-term treatment goals and strategies include the following: enhancing cholinergic transmissions in AD, direct prevention of beta amyloid formation or abnormal tau phosphorylation by inhibiting relevant metabolic enzymes, monoamine oxidase-B inhibition, manipulation of neuronal growth factors, and
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hormone replacement therapy. Additional long-term treatment strategies include the use of nonsteroidal antiinflammatory drugs (to counter adverse consequences of disease-related inflammatory responses) and prospects for direct neuronal implantation. The authors note that given the clinical, genetic, pathological and pharmacological heterogeneity of AD, it is unlikely that any one treatment approach will be effective in all cases. 2 figures, 3 tables, 95 references. (AA-M). •
Functional Brain Imaging With Single-Photon Emission Computed Tomography in the Diagnosis of Alzheimer's Disease Source: International Psychogeriatrics. 9(Supplement 1): 223-227. 1997. Summary: This journal article reviews the clinical applications of single-photon emission computed tomography (SPECT) in the diagnosis of Alzheimer's disease (AD). It summarizes findings from studies of regional cerebral brain flow in AD using SPECT with technetium-99m-labeled brain-retained tracers. It also discusses the potential value of SPECT as a diagnostic adjunct in patients with mild cognitive or behavioral symptoms, as a diagnostic adjunct in dementia patients with a diagnosis of probable AD, and for determining the relative contributions of degenerative and vascular pathology in cases of mixed dementia. Finally, it explores methodological issues for the optimal use of SPECT in AD cases. 15 references.
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Neurologist's Perspective on the Aging Brain Source: Archives of Neurology. 54: 1211-1214. October 1997. Summary: This journal article, written by a neurologist, provides a historical and philosophical perspective on Alzheimer's disease (AD). The author describes the diversity of clinical presentations that are seen among patients with the same disease process. He cites examples from his neurological practice to illustrate the varied ways that AD can manifest itself in patients' lives and how patients react and adapt to cognitive and perceptual changes. He traces the evolution of neurologists' perspectives on dementia from a focus on regression and deficits to a recognition of the compensations and adaptations that can occur in an effort to preserve the self. Thus, music sessions, story telling, religious services, plays, art groups, therapeutic gardens, and kitchens, for example, can help anchor patients, temporarily awaken their memories, and momentarily bring back the personal self, even in fairly advanced stages of AD. The author describes current interest in the healthy aging brain and the potential for continuing development throughout adulthood and old age. He notes that aging does not necessarily entail neurological illness and observes that a sizeable proportion of people can live more than 100 years without significant intellectual decline. 17 references.
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HSV-1 in Brain and Risk of Alzheimer's Disease Source: Lancet. 351: 1330-1331. May 2, 1998. Summary: This letter to the editor briefly summarizes a study of herpes simplex virus 1 (HSV-1) and the apolipoprotein E4 (apoE4) allele as risk factors for developing Alzheimer's disease (AD). Researchers examined brains from 73 older people (aged 5393 years) with neuropathologically confirmed AD and 33 people (aged 43-95 years) without AD. The brain samples were classified as HSV-1 positive or HSV-1 negative, and apoE gene status was determined. There was no significant difference in the apoE4 allele frequency between HSV-1 positive and HSV-1 negative patients with AD, and the HSV-1 positive ratio did not differ significantly between cases with and without AD.
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Susceptibility to HSV-1 was not increased among apoE4 allele carriers, regardless of AD status. The authors conclude that HSV-1 does not appear to increase the risk for AD, either alone or when combined with the presence of an apoE4 allele. 1 table, 5 references.
Federally Funded Research on Brain The U.S. Government supports a variety of research studies relating to brain. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to brain. 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. The following is typical of the type of information found when searching the CRISP database for brain: •
Project Title: AGE-DEPENDENT MOLECULAR RESPONSES TO BRAIN INJURY. Principal Investigator & Institution: Natale, Joanne E.; Children's Research Institute Washington, D.C., Dc 20010 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Acquired brain damage arises both from the primary insult and delayed, secondary cell death in sub-cortical structures such as the thalamus. Our research and that of others have demonstrated that delayed apoptotic cell death in the immature thalamus occurs much more rapidly than in the adult thalamus. Understanding the increased vulnerability of the immature brain is therefore essential for the development of targeted therapies. Thus, this research-training program seeks to define the molecular basis for age-dependent responses to secondary brain injury, leading to effective therapies for the brain-injured child. A validated and reliable in vivo murine model of occipital cortical ablation leading to thalamocortical neuronal death will be used to determine these age-dependent responses. Given the importance of such research and the availability of this murine model, a 5-year, multidisciplinary research and training program that focuses on thalamocortical neuronal death following target deprivation neurotropin withdrawal injury is proposed. Based on compelling preliminary data obtained from analyses of 12,000 element microarrays that identified both induction of pro-apoptotic genes and repression of genes encoding antioxidants such as metallothionein I and II, the research will address three hypotheses. 1) Neuronal maturity will influence the sequence of coordinately regulated gene expression leading to target deprivation-induced neuronal apoptosis. Using both stereologic and gene expression techniques, in vivo progression of delayed, secondary neuronal injury in
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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mouse pups and adults will be compared. 2) Neurotrophin administration rescues thalamocortical projection neurons from apoptotic cell death. Using similar techniques, the response to brain derived neurotropic factor versus placebo administration will be compared. 3) Modifying compensatory response to oxidative stress in the immature brain to resemble those found in the mature brain will slow the rate of targetdeprivation-induced cell death. The effects on cell death, oxidant injury, and gene expression will be compared in transgenic mice with augmented metallothionein I expression. This research grant extends the investigator's capabilities through mentorship and training in specific techniques (e.g. laser capture microdissection). In addition, it will provide sophisticated skills in the analysis and interpretation of data required to address complex pathophysiological processes from the genetic to the cellular level. Mentors in molecular genetics and neuroscience as well as the resources of the Mental Retardation and Developmental Disabilities Research Center will support well-defined training objectives. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AGING OF BRAIN--EFFECTS OF PERINATAL NUTRITION Principal Investigator & Institution: Blusztajn, Jan K.; Professor; Pathology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-MAR-1991; Project End 31-MAR-2004 Summary: The overall goal of the proposed studies is to determine the mechanisms by which the availability of choline and folic acid during the prenatal period modifies brain structure and function in development, adulthood and old age. Our major premise is that the development of the brain during critical periods in embryogenesis is sensitive to changes in maternal diet, and specifically, is influenced by changes in the intake of choline and folic acid. We found that rats treated with choline during specific perinatal periods inhibited improved memory function which lasted throughout their lifespan, i.e. supplementation with choline in development prevented age-related deterioration in learning and memory. Moreover, variations in maternal choline intake during the second half of pregnancy caused biochemical, structural, and electrophysiological changes in the brains of the offspring. We also found that memory performance in rats was improved by prenatal supplementation with folic acid. The proposed studies will be conducted using a unified experimental design common to all projects. Dr. Blusztajn will determine the molecular mechanisms involved in the brain reorganization that is governed by choline and folate availability by studying signal transduction pathways and developmental patterns of gene expression in brain. Dr. Swartzwelder will measure synaptic function and plasticity (long-term potentiation in hippocampus of rats exposed to varying levels of choline or folate in utero. Dr. Meck will examine age-related changes in conditioned stimulus processing (attention) as a function of the prenatal availability of choline and folate. Dr. Williams will determine if supplementation with folate in early development leads to life long changes in spatial memory, brain anatomy, and neurochemistry, as has been documented for choline supplementation, and will investigate whether choline supplementation with folate in early development leads to lifelong changes in spatial memory, brain anatomy, and neurochemistry, as has been documented for choline supplementation, and will investigate whether choline supplementation either prenatal or across the lifespan ameliorates behavioral, anatomical, and biochemical deficits seen in mice lacking the gene for apolipoprotein Ea molecular involved in the transport of phosphatidylcholine within brain. Dr. Zeisel will study metabolic interrelationships between folate and choline in order to determine if they share a common mechanism of action on brain organization. He will determine
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the effects of choline and folate on patterns of fetal brain cell division and apoptosis, and will investigate the mechanism by which choline deficiency causes apoptosis. Dr. Kowall will provide neuroanatomy core services for the five projects. The ultimate goal of our studies is to related our results to age-related changes in memory in humans, and to develop perinatal nutritional strategies which will benefit people. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AN ORGANOTYPIC MODEL OF TRAUMATIC BRAIN INJURY Principal Investigator & Institution: Bottlang, Michael; Emanuel Hospital and Health Center Portland, or 97208 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2005 Summary: The past decade has witnessed intense scientific activity to investigate molecular mechanisms of traumatic brain injury, driven by overwhelming evidence that neuropotection by pharmacological inhibition of apoptosis has the potential to dramatically reduce the effects of brain trauma. Key requisite for the systematic investigation of neuroprotective agents is an accurately characterized, clinically relevant in vitro brain injury model. Despite this obvious need, the ability to deliver such defined, realistic trauma to specimens in vitrolags far behind the sophistication of molecular and biochemical assays used to measure the response. In a collaborative effort between neurobiologists and bioengineers, we therefore developed an in vitrobrain injury model which subjects organotypic brain cultures to angular acceleration-induced shear injury. In this model, organotypic brain cultures realistically model the in vivoapparent heterogeneous cell population in a three-dimensional cellular matrix, while angular acceleration-induced shear strain delivers a scalable, defined, and clinically relevant mechanical insult. We hypothesize that our acceleration model of organotypic brain cultures can realistically reproduce traumatic brain injury, where the delivered shear strain magnitude can be quantified on a cellular level. Exercising our model, we will be able to determine cell type specific injury vulnerability, and to determine if caspase-8 and caspase-9 affect cell death following brain trauma. We propose to complete a formal experimental characterization of our novel brain injury system, including assessment of the delivered angular acceleration magnitude and determination of the constitutive properties of the organotypic specimen (Aim 1). The resulting experimental source data will be directly applicable to formulate a realistic analytical model that allows computational simulation of the shear injury throughout the brain specimen for any point in time during the primary mechanical insult (Aim 2). Based on and concomitant to this rigorous system characterization, we will exercise the brain injury model to establish a dose/response history (Aim 3), and we will delineate the effects of hypoxic brain injury (Aim 4), secondary to the mechanical insult. Finally, we will employ our arganotypic trauma model to determine the neuroprotective potential of caspase-8 and caspase-9 (Aim 5). Upon successful completion, the results of this integrative research approach will yield a well-characterized, scalable, reproducible and clinically relevant brain injury model. Considering the vast interest in therapeutic interventions now under development aimed at inhibiting the cascade of secondary effects of primarily mechanical brain injuries, our organotypic trauma model will directly address the rapidly increasing demand for a well characterized, experimental system to deliver a clinically relevant traumatic insult - and may prove crucial for the discovery of caspase-based neuroprotective mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANALYSIS OF MARROW STROMAL CELL INTERACTION WITH TISSUE Principal Investigator & Institution: Zhang, Zheng G.; Senior Staff; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAY-2008 Summary: Stroke and traumatic brain injury are major causes of morbidity and disability and functional recovery is slow and uncertain. Our preliminary data demonstrate that intravenously transplanted bone marrow stromal cells (MSCs) migrate to the stroked and injured brain tissue and improve functional recovery, This application is concerned with elucidating the cellular and molecular mechanisms responsible for the beneficial effect of MSC therapy on stroke and traumatic brain injury. The major hypothesis to be tested is that the MSCs delivered to the brain after stroke and traumatic brain injury enhance angiogenesis, promote axonal and dendritic sprouting and synapse formation, reduce cell death in the boundary regions of injured brain, and promote neurogenesis in the subventricular zone and dentate gyrus and thereby reduce neurological deficits, in addition, we propose to test the hypothesis that therapeutic benefit derives from MSC-induced increase in brain of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and brain-derived neurotrophic factor (BDNF). This hypothesis will be tested by blocking receptors and using gone knock-out mice. Specifically, by blocking VEGF receptor 2, we will examine the effect of VEGF on MSC-enhanced angiogenesis. Using bFGF-/- and BDNF-/-mice, we will examine the effects of bFGF and BDNF on MSC-induced axonal and dendritic sprouting and synapse formation and neurogenesis. Angiogenesis, neurogenesis and axonal and dendritic sprouting and synapse formation will be measured using Laser Scanning Confocal Microscopy, and a novel software program for three dimensional image analysis. We believe that these are unique and fresh approaches that may provide fundamental insights into the cellular and molecular mechanisms underlying the therapeutic benefit provided by MSC cellular therapy of stroke and traumatic brain injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AUTOMATED ANALYSIS OF HEALTHY AND DISEASED BRAIN TISSUE Principal Investigator & Institution: Fischl, Bruce; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Neurodegenerative and psychiatric disorders, as well as healthy aging, are all frequently associated with structural changes in the brain. These changes can cause alterations in the imaging properties of brain tissue, as well as changes in morphometric properties of the brain, such as volume, folding and surface area. This can be problematic, as analysis techniques that quantify morphometric changes without accounting for variability in the imaging properties of the tissue are liable to generate erroneous results in situations in which the tissue parameters have changed. In this grant application support is sought to construct a set of accurate and automated tools for the analysis of structural neuroimaging data. These tools will quantify alterations in brain morphometry, as well as changes in the tissue parameters that give rise to image contrast in magnetic resonance images. It is hypothesized that explicitly basing the analysis tools upon knowledge of the underlying physical principles that govern the imaging process will allow the characterization of subtle
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structural changes that have previously gone undetected. Aim 1 of this application is to develop a set of scans and optimization techniques that will allow for the accurate estimation of the underlying tissue parameters (i.e., T1, T2, proton density). Additional effort will be focused on removing various sources of inaccuracies in the data acquisition. This includes using optimization techniques to derive MR protocols with optimal contrast-to-noise, as well as the correction of various sources of distortion that arise in MR images such as gradient nonlinearities and real-time online correction of within-scan subject motion. This latter technique is of particular importance, as it will allow the tools to be applied to patient populations for which within-scan motion is frequently problematic. Aim 2 is to use a database of manually labeled datasets as the basis for the construction of an automated whole-brain segmentation procedure designed to assign a neuroanatomical label to every voxel in the brain (e.g. thalamus, caudate, putamen, etc). The segmentation procedure will disambiguate structures with similar tissue properties based on their location within the brain, as well as their spatial relationships to neighboring structures, encoded using an anisotropic markov random field. It is important to note that basing the segmentation upon the intrinsic tissue parameters renders the procedure largely insensitive to the details of a particular pulse sequence. Aim 3 is to employ the multi-spectral tissue parameters as the basis for surface-based morphometric analysis. The final aim is to validate the accuracy of the procedures, as well as their robustness to changes in scanner protocol. Upon completion of tool development they will be applied to the study of a variety of disorders, focusing on schizophrenia. Alzheimer's and Huntington's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BLOOD FLOW AND METABOLIC CONTROLS IN THE FETAL BRAIN Principal Investigator & Institution: Power, Gordon G.; Center for Perinatal Biology; Loma Linda University Loma Linda, Ca 92350 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Scanned from the applicant's description): Cerebral blood flow is of fundamental importance for normal development of the brain during fetal life. Oxygen stores of the body are minimal yet cerebral metabolic rate is high, and thus prompt adjustments of flow are necessary to match oxygen supply with oxygen need. Inadequate blood flow and oxygen delivery in the perinatal period cause tragic lifelong consequences including cerebral palsy and mental retardation. Until the present time, there has not been any method to measure cerebral blood flow in utero on a continuous basis. In the last two years, we have successfully adapted laser Doppler flowmetry to measure cerebral blood flow in the chronically prepared, near-term fetal sheep. Using the method, we have shown that nitric oxide mediates about 60 percent of the increase in flow that occurs in response to hypoxic stress. We have also obtained early evidence that the brain enters a state of regulated hypometabolism upon hypoxic stress, presumably by curtailing nonessential metabolic activities, and thereby rations oxygen use. In this reapplication, we propose six specific aims. First, we will compare the results of laser Doppler flowmetry with those obtained with fluorescent microspheres. We believe this comparison is an essential step for a complete validation of the new methodology. At the same time, we will validate a new method we have developed to measure heat production and oxygen use by the fetal brain. Second, we will continue to investigate the role of nitric oxide in mediating the increases of cerebral blood flow and reductions in metabolic rate in response to acute hypoxia. Third, we will test whether adenosine mediates the flow increases and hypometabolism that compensate during
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fetal hypoxia, i.e. whether it plays a role similar to that which we have already shown for nitric oxide. Fourth, we will test the importance of carbon dioxide in regulation of the fetal circulation and inquire about its interactions with nitric oxide and adenosine. Fifth, we will carry out experiments to distinguish between regulated hypometabolism of the fetal brain and the inevitable reduction of 02 use that accompanies oxygen starvation. Sixth, we will test whether the mechanisms controlling blood flow and metabolic rate in the brain are blunted after gestation at high elevations with exposure of the fetus to hypoxemia for several months. These studies will provide continuous measurements of cerebral perfusion and local heat production from a small region of the fetal brain for the first time. Our broad goal is to establish the control factors for oxygen delivery and use by the fetal brain and thereby to optimize brain development and minimize hypoxic injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BLOOD-BRAIN BARRIER IN CEREBRAL ISCHEMIA Principal Investigator & Institution: O'donnell, Martha E.; Human Physiology; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The long term goal of this project is to identify blood-brain barrier (BBB) ion transporters that mediate ischemia induced brain edema, a major cause of brain damage in stroke. During the early hours of cerebral ischemia, brain edema formation occurs in the presence of an intact BBB. In this process, BBB endothelial cells transport Na and Cl from blood into brain interstitium, with osmotically obliged water following. The specific ion transporters responsible are unknown, however BBB luminal Na and Cl transporters appear to play a key role. Much evidence indicates that hypoxia, which rapidly develops during ischemia, aglycemia occurring as glucose is depleted, and also centrally-released vasopressin are mediators of ischemia-induced brain edema formation. A novel aspect of this proposed project is the preliminary finding that a Na-K-Cl cotransporter appears to be localized in the luminal membrane of brain microvessel endothelial cells and that vasopressin, hypoxia and aglycemia stimulate activity of the cotransporter. This has led to the central hypothesis that a Na-K-Cl cotransporter, located at the luminal membrane of the BBB, is stimulated during ischemia to increase transport of Na and Cl with osmotically obliged water from blood to brain, causing edema formation. The present project has three specific aims. The first aim is to test the hypothesis that Na-K-Cl cotransport is present in luminal membranes of cerebral microvascular endothelial cells (CMEC). These studies will evaluate bovine brain microvessel luminal and abluminal membrane preparations for cotransport activity by radioisotopic flux analyses. Also, the in situ distribution of the cotransporter will be examined by immunoelectron microscopy of brain sections. The second aim is to test the hypothesis that Na-K-CI cotransport of BBB endothelial cells is stimulated by agents that mediate ischemia-induced cerebral edema. Here, the effects of hypoxia, aglycemia and vasopressin on cotransport activity will be examined in cultured human and bovine CMEC and freshly isolated bovine cerebral microvessels. The third aim is to test the hypothesis that inhibition of Na-K-Cl cotransport activity attenuates ischemia-induced brain edema. To do this, the effect of inhibiting the cotransporter on ischemia-induced changes in rat brain Na and water will be examined by nuclear magnetic resonance methods, which allow in vivo changes in brain Na and water to be followed in real time. The proposed studies should reveal whether therapeutic approaches aimed at blocking BBB Na-K-Cl cotransporter activity may be of value for attenuating ischemia-induced brain edema.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BLOOD-BRAIN BARRIER TRANSPORT 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 2002; Project Start 25-JUL-1996; Project End 31-MAY-2003 Summary: (adapted from applicant's abstract) Because of its juxtaposition to blood, the cerebral endothelium (which forms the blood-brain barrier, BBB) has been thought to be relatively resistant to the effects of cerebral ischemia. However, examination of taurine, glutamine and myo-inositol influx into brain (all Na+-dependent processes) indicate a marked early (<1 hour) reduction in transport during focal cerebral ischemia suggesting that endothelial cell injury could play a role in primary, rather than secondary, ischemic brain damage. This may be particularly the case if efflux from as well as influx into brain are affected since those efflux systems are involved in controlling the concentration of potentially toxic factors in the brain extracelluar space. This proposal, therefore, has two major goals: to determine whether energy-dependent efflux from brain to blood is inhibited during cerebral ischemia (Specific Aims 1 and 2) and to examine whether changes in influx and efflux transport mechanisms at the blood-brain barrier contribute to ischemic brain damage (Specific Aim 3). The cerebral volume of distribution reached by [3H] vinblastine (a P-glycoprotein substrate) and p-[3H] aminohippuric acid (PAH, an organic acid transporter substrate) will be determined following middle cerebral artery occlusion in rat and mouse (Specific Aim 1). Whether an increased volume of distribution with ischemia reflects a change in influx or an alteration in efflux at the blood-brain barrier will then be determined, the latter by examining the effect of cerebral ischemia in the absence of BBB P-glycoprotein (the mdr la knock out mouse) or during probenecid-induced inhibition of organic acid transport. Specific Aim 2 will examine the mechanism by which ischemia inhibits efflux, by examining PAH, L-glutamate and methyl aminosobutyric acid efflux (an A-system amino acid transporter substrate) uptake into choroid plexus using ventriculo-cisternal perfusion. Specific Aim 3 will determine the effect of altering specific transporters at the BBB on ischemic brain injury and will examine whether drugs known to ameliorate the effect of reperfusion on blood-brain barrier disruption actually have their effects by altering transport during ischemia. Determining whether early BBB dysfunction should be an alternate therapeutic target early during cerebral ischemia, the finding that there is an inhibition of energy-dependent efflux at the BBB during ischemia has major implications for drug delivery to the injured brain. P-glycoprotein and the organic acid transporter both play a major role in limiting the access of some drugs to the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BRAIN ACTIVATION PROFILES OF MATH DIFFICULTIES IN CHILD Principal Investigator & Institution: Papanicolaou, Andrew C.; Professor and Director; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-JUL-2008 Summary: Recent advances in functional brain imaging have identified brain activation profiles that help outline the neural circuitry necessary for many cognitive functions. Using Magnetic Source Imaging (MSI), we have identified aberrant activation profiles
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that are characteristic of children with dyslexia and shown that successful educational intervention not only results in improved reading performance, but also in normalization of the aberrant brain activation patterns. In the present project we will use MSI in an attempt to identify aberrant activation patterns underlying different types of math disabilities (Aim 1), and to determine whether successful intervention that results in improved performance in arithmetic tasks, results changes in the corresponding brain activity patterns (Aim 2). For Aim 1, 80 third graders (20 per group) with only math disabilities (MD), MD and reading disabilities (RD), only RD, and controls studied in Project 1 (Cognition) will complete MSI studies based on single digit addition and subtraction tasks, and tasks involving number comparison and number concepts. These tasks are expected to differentially activate anterior and posterior components of the complex neural network that mediates number processing. We expect to find differences in the activation patterns associated with MD (mostly biparietal) and MD-RD (mostly left fronto- temporal). In Years 2-3, third graders (20 per group per year) with MD and MD-RD will be randomly assigned to interventions involving a word identification control condition and math instruction conditions involving fact retrieval, procedural knowledge, and both fact retrieval and procedural knowledge. These children will receive MSI scans before and after intervention using addition, number comparison, and number concept tasks. These studies will be repeated with new cohorts of similarly defined third graders in Years 4 and 5, with an arithmetic word problem intervention added to fact retrieval. In both studies, we expect to see significant changes in the brain activation patterns associated with different types of math disabilities in response to successful intervention. This study is conducted in parallel to the MRI studies in Project 3 (MRI) and both should contribute significantly to an understanding of brain function in children with math disabilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAIN EDEMA IN HUMAN INTRACEREBRAL HEMORRHAGE Principal Investigator & Institution: Zazutia, Allyson; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-MAY-2008 Summary: Spontaneous intracerebral hemorrhage (ICH) is associated with greater mortality and more severe neurological deficits than any other stroke subtype. Initial mortality remains high at 26-50%, and survivors often have significant residual disability. To date, no medical or surgical therapy has been shown to improve outcome. Understanding the manner in which ICH induces brain injury is critical to developing effective treatments. Delayed neurological deterioration after ICH has been reported to occur in one-quarter to two-thirds of patients. While clinical worsening in association with hematoma enlargement is well-documented, few data are available delineating other causes of neurological deterioration following ICH in human subjects. This research plan will investigate the mechanism, extent and clinical importance of edema as a mechanism of secondary brain injury following ICH in human subjects using modern neuroimaging techniques. Two Specific Aims will be carried out. Specific Aim 1: To ascertain the time course, extent and clinical significance of brain edema formation in 20 patients with acute ICH.3D MPRAGE MRI and the brain boundary shift integral (BBSI) will be used to measure changes in brain volume in 20 patients with acute supratentorial ICH. Studies will be performed within 24 hours of ICH onset, on day 3-4, and on day 7 or discharge. Clinical course will be monitored on a daily basis during the first week. Twenty patients with ischemic stroke and twenty normal volunteers will serve as positive and negative controls, respectively. Specific Aim 2: To measure peri-
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clot blood brain barrier permeability in 20 patients with spontaneous supratentorial ICH. Initial measurements will be made with positron emission tomography (PET) and 11 C-methyl alpha aminoisobutyric acid (MeAIB) at 24-48 hours after onset and again on either day 3-4 (first 10 patients) or day 6-7 (second 10 patients). If Specific Aims 1 and 2 demonstrate that brain edema after acute ICH is associated with clinical deterioration, then trials of agents aimed at reducing brain edema, would be appropriate. We then would be able to use the BBSI and MelAB permeability to evaluate the physiological efficacy of different treatments and to choose appropriate agents and doses to design clinical intervention trials. If edema does not occur, it would suggest that design of such trials would be unlikely to improve patient outcome and other approaches to treatment should be sought. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAIN ENERGY METABOLISM AND HYPOGLYCEMIA Principal Investigator & Institution: Boyle, Patrick J.; Associate Professor of Medicine; Internal Medicine; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 06-APR-1999; Project End 31-MAR-2004 Summary: The brain is an obligate glucose consumer and is unable to synthesize or store more than a few minutes of glucose for use during hypoglycemia. Normal subjects who experience recurrent hypoglycemia have increased rates of brain glucose uptake during subsequent hypoglycemia and therefore have no need to signal for counterregulatory hormone responses to increase systemic glucose production. This alteration leads to symptomatic unawareness of subnormal glucose concentrations. In patients with type 1 diabetes this adaptation contributes to an increased risk of serious hypoglycemia (seizures, comas, and episodes requiring the assistance of others in order to recover). The precise mechanism by which this adaptation occurs and the time course over which it can be induced have not been elucidated. In concert with low systemic glucose concentrations, cortisol concentrations rise during hypoglycemia and may be involved in inducing an increased brain glucose uptake. Over-insulinization associated with hypoglycemia may also play a role in the development of increased brain glucose uptake and the development of hypoglycemia unawareness. Each of the aforementioned issues will be addressed in normal man in experiments planned for the initial years of this proposal. Past experiments at the University of New Mexico have demonstrated that rates of brain oxygen utilization fail to decrease during hypoglycemia despite significant reductions in whole brain glucose uptake. Two possible mechanisms seem tenable: 1) that the amount of glucose metabolized anaerobically decreases and/or 2) alternate fuels like lactate, ketones or glutamate are oxidized instead of glucose. Experiments utilizing uniformly labeled 13C-glucose kinetics and determining the rate of appearance of uniformly labeled 13C-lactate in cortical venous effluent will assess whether or not rates of anaerobic glycolysis decrease during hypoglycemia. Also, since the brain may have the capacity to consume lactate or ketones during hypoglycemia, kinetic modeling utilizing stable isotopes of these potential fuels will be completed to assess their use as alternate fuels. These studies will help define basic brain metabolism pertinent to over 1 million patients with type 1 diabetes. Better metabolic control, the key to the prevention of long-term complications of diabetes, will thus become more achievable. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BRAIN H2D MRS: IMPLEMATION AND INITIAL APPLICATIONS Principal Investigator & Institution: Wang, Zhiyue J.; Assistant Professor; Radiology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant) The long-term objective is to apply 2D 1H magnetic resonance spectroscopy (MRS) techniques in studies of pediatric neurological disorders. 1H MRS is valuable for evaluating neurological brain diseases. However, there are limitations in current clinical 1H MRS examinations. Most peaks are crowded in a narrow aliphatic spectral window, and numerous low concentration metabolites are overshadowed by a few metabolites present in higher levels, and much valuable information is lost. Most metabolites have coupled spins, and 2D MRS separates the peaks in a second frequency dimension, greatly increasing the information content of the data. Application of 2D MRS in clinical examinations will enhance the abilities for diagnoses and patient management, and improve the understanding of disease processes. The specific aims are: (1) to implement 2D spin-echo double-quantum MRS pulse sequences for in vivo measurement of brain metabolites in 1.5T clinical scanners: (1a) to implement a localized pulse sequence optimized for GABA measurement; (1b) to implement localized pulse sequences for general detection of metabolites; (1c) to implement whole-brain measurement pulse sequences for general detection of metabolites. (2) to assign and evaluate peaks detected in the normal brain: (2a) to acquire spectra from metabolite solutions; (2b) to acquire brain spectra and baselines due to macromolecules in a group of adult normal volunteers; (2c) to assign the in vivo peaks and measure metabolite levels, and to determine optimal pulse sequences for studies of Aim 3; (2d) to acquire age-matched control spectra from normal children. (3) to explore the utility of the 2D MRS techniques in patients between the ages of 7 and 11 years: (3a) to study the effects of the ketogenic diet (KD) on brain GABA levels in seizure patients; (3b) to measure the brain?s level of branched chain amino-acids (BCAA) and keto-acids (BCKA) in maple syrup urine disease (MSUD); (3c) to test the hypothesis that low levels of brain galactitol are present even under a lactose restrictive diet; (3d) to study unassigned, unusual spectral peaks found in routine clinical MRS examinations. A localized 1D double-quantum filtered MRS pulse sequence will be modified into several 2D double quantum MRS pulses for localized and whole brain measurement. Different pulse parameters will be used for different types of spin systems. A frequency selective coherent transfer pulse will be used for optimal detection of GABA, and a broadband coherent transfer pulse will be used for all other 2D pulse sequences. The measurement procedures will be applied to normal subjects first. MRS measured GABA level before and after initiation of KD therapy will be compared in seizure patients and correlated with response. The MRS measurement of BCAAs and BCKAs will be conducted during metabolic crisis and in normal conditions in MSUD and correlated with clinical condition and serum BCAA and urine BCKA. In galactosemia, 2D MRS will be used to look for low levels of galactitol, and the MRS results will be correlated with the urine galactitol levels. 2D MRS will also be used to characterize unusual peaks found in clinical practice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BRAIN IMAGING-ACUPUNCTURE AND OSTEOARTHRITIS Principal Investigator & Institution: Farrar, John T.; Senior Scholar; Biostatistics and Epidemiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAY-2005
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Summary: (provided by applicant): The use of acupuncture has been developing an increasing acceptance as a form of medical therapy to treat pain and other disease processes, supported by a growing number of clinical trials. Recent experimental studies in both animal and humans have begun to demonstrate some measurable physiologic effects that are associated with acupuncture, suggesting the possibility of a neurophysiologic explanation. In addition, brain research continues to uncover a complex set of endogenous neurologic control systems, such that it has become clear that the brain plays a major role in the modulation of pain perception and control. If acupuncture can be demonstrated to have a consistent effect on specific areas of the brain, it will become possible to explore the potential efficacy of acupuncture based on measurable neurophysiologic responses. The development of functional brain imaging has provided several methods of studying the activity of the human brain under controlled conditions. Functional imaging techniques that measure changes in cerebral blood flow (CBF) are thought to reflect focal increased activity in brain function. Single photon emission computed tomography (SPECT), and several methods of functional magnetic resonance imaging (f-MRI) begun to define the brain regions where changes in the CBF are associated with the experience of pain, with preliminary data on acupuncture as well. But consistent pathways and structures with pain and acupuncture have not been defined. In order to carefully explore the significance of changes that occur in CBF with acupuncture therapy, the brain scans should be correlated with clinical response in a clinical trial setting of a common, well defined, and easily diagnosed painful condition which has been shown to respond to acupuncture. A recently published controlled but unblinded clinical trial of osteoarthritis (OA) of the knee has shown some efficacy vs stand care, and is likely to be a good model. However, basic information is required about the specific model before trying to design a study larger definitive trial. The information required include: 1) If there are any consistent areas of the brain that show CBF changes when acupuncture is used in knee OA compared to identical acupuncture in normal subjects (without pain); 2) If there are consistent changes in the acupuncture treated knee OA group compared to a blinded control group treated with placebo acupuncture; and 3) since SPECT and f-MRI have substantially different risks and benefits for such a study, do both SPECT and f-MRI provide similar information. Defining the areas of interest and the techniques to use, will allow a comprehensive study of the effect on CBF of acupuncture therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAIN MORBIDITY IN TREATMENT-NAIVE ALCOHOLICS Principal Investigator & Institution: Fein, George; Scientist; Neurobehavioral Research, Inc. Corte Madera, Ca 94925 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Most studies of the impact of alcohol dependence on the brain have examined individuals in treatment. They may embody a bias, called "Berkson?s fallacy", if the association between variables (e.g., alcoholism and brain atrophy or brain function) differ between the population of alcoholics in treatment and alcoholics in the general population. We hypothesize that treatment-naive alcoholics have less psychiatric comorbidity compared to treatment samples, and that this reduced psychiatric morbidity is associated with a lessened severity of impairments in brain structure and function. The major goals of the proposed research are to determine: 1) whether treatment-naive alcoholics differ in brain structure and function from alcoholics recruited from treatment centers, 2) whether treatment-naive alcoholics differ from alcoholics recruited from treatment centers in the presence and severity of
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comorbid mood and externalizing disorder symptoms and traits, 3) what factors are associated with impairments in brain structure and function in treatment-naive alcoholics and in alcoholics drawn from treatment centers (including presence and severity of comorbid mood, anxiety, and externalizing disorder symptoms and traits, presence of the APOE-4 allele, premorbid headsize as a measure of functional reserve (as indexed by intracranial vault volume on MRI), and the frequency (and severity) of withdrawal symptoms), 4) whether males and females differ in these comparisons, and 5) to follow the treatment-naive alcoholics for future longitudinal assessment of factors that predict the course of their alcoholism (especially the seeking of treatment, and changes in brain structure and function). We will study 380 subjects over five years: 220 treatment-naive alcohol-dependent subjects, 80 alcohol-dependent subjects in outpatient treatment, and 80 lifetime light/non-drinker controls. The treatment sample will be drawn from outpatient treatment centers. The treatment-naive sample will be recruited from the Marin County First Offender Drinking Driver (FODD) program. The light/non-drinker controls will be recruited from the community. Brain structure will be examined using MRI, and will include segmentation of the brain into its? component tissue classes, delineation of specific structures (e.g., the hippocampus, cerebellum, and corpus callosum), and transformation of the images into a standard coordinate system (to facilitate analysis of regional cortical volume differences). Functional assessment will include neuropsychological and behavioral testing and electrophysiological recordings, focusing on inhibitory/disinhibitory processes, executive functions, visuospatial abilities, gait and balance, and processing and memory of emotional stimuli. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAIN TARGETING OF THYROTROPIN RELEASING HORMONE ANALOGS Principal Investigator & Institution: Prokai, Laszlo; Center for Drug Discovery; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 05-AUG-1999; Project End 31-JUL-2004 Summary: Thyrotropin-releasing hormone (TRH) analogues offer potential treatment of various maladies of the central nervous system (associated mainly with cholinergic hypofunction due to motorneuron diseases, Alzheimer's disease, electroconvulsive shock therapy, etc.). The main objective of the project is to develop and evaluate chemical delivery systems for targeting centrally active analogues into the central nervous system (CNS) by a chemical-enzymatic approach. Due to covalently attached lipophilic functional groups (a 1,4-dihydrotrigonellyl and a lipophilic moiety) a "packaged" peptide crosses the BBB by passive transport and, once in the CNS, converts to an ionic trigonellyl derivative that is retained at the target site. Then, the biologically active peptide is obtained by sequential metabolism. New brain-targeting systems will be designed and synthesized based on systematically modifying a lead compound ([Leu2]TRH) to improve sequestration of the analog in the brain and/or enhance postdelivery stability of the biologically active peptide. These modifications will allow for a decrease of the systemically administered dose and also for an increase in the residence time of the experimental or therapeutic agent in the CNS. Our hypothesis is that the efficacy of CNS-sequestration can be improved by using alpha-hydroxyglycine to achieve carboxy-terminal amidation via peptidylamidoglycolate lyase (PGL, EC 4.3.2.5) action because of the higher rate of enzymatic bioactivation after esterase cleavage of the protecting ester function. Analogues in which the carboxy-terminal prolinamide is replaced by L-pipecolic acid or the amino-terminal pyroglutaminyl residue is subtituted by an unnatural moiety will also be incorporated into appropriate targeting systems.
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The design and development will be supported by theoretical calculations. The newly designed analogs will be tested for binding to brain TRH receptors to compare their intrinsic activity with that of the lead compound. In vitro stability and metabolism experiments will address optimization and practical development. Stability studies in brain tissue will address rates, sites and extent of peptide activation and/or cleavage to probe crucial steps in the CNS-sequestration. In vivo distribution and metabolism studies will assess the efficacy of the strategy to transport and sequester the TRH analogs in the brain. We will examine pharmacokinetics of brain-delivery, "lock-in" of the predicted precursors, and the release of the biologically active peptide after parenteral administration of the synthesized targeting systems. Comparative pharmacodynamic evaluation of the effect of brain-delivered analogues will be addressed via in vivo cerebral microdialysis studies in which changes in acetylcholine levels due to treatment will be assayed. Ultimately, pharmacological experiments will be carried out in animals to survey the potential of the approach to treat maladies associated with the loss of cholinergic functions. The antagonism of pentobarbitalinduced sleeping will be used as general paradigm to assess the acute effects of braintargeted compounds. Behavioral observations, dose-dependence and duration of action will also be addressed by appropriate method or study designs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAIN VENTRICLE DEVELOPMENT AND MENTAL HEALTH Principal Investigator & Institution: Sive, Hazel L.; Associate Professor; Whitehead Institute for Biomedical Res Biomedical Research Cambridge, Ma 02142 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): Brain ventricles are a highly conserved system of cavities that contain cerebrospinal fluid and are believed to protect the brain from injury, remove waste, and carry chemical signals. Blockage of free fluid circulation leads to hydrocephalus, one of the most common birth defects. Additionally, abnormalities in brain ventricle structure and size have been extensively documented in individuals affected with schizophrenia and autism. This exploratory proposal seeks to understand the genetic basis for brain ventricle formation, using the zebrafish as a model, and definition of a set of brain ventricle mutants as the foundation for the study. The longer term goal is to understand the role that genes corresponding to these mutants play in formation of the brain ventricular system, and to address whether their misfunction contributes to the etiology of autism, schizophrenia and related disorders. The zebrafish has proven an excellent genetic and molecular model for issues in developmental biology including brain formation and function, and has served as a model for many human diseases. It is hypothesized that ventricle morphology and function may alter brain function, and conversely, that ventricle formation and maintenance is dependent on normal brain function. In preliminary studies, the timecourse of brain ventricle formation in the zebrafish has been described and 3 mutants with defects in brain ventricle development have been examined. It is proposed, firstly, to continue characterization of these mutants by analyzing (i) molecular and cell biological changes relative to wild type fish embryos, (ii) cell autonomy of their function and (iii) epistatic interactions between them (hierarchy of function). Secondly, 28 mutants reported to have brain ventricle phenotypes, but otherwise unstudied, that were derived from chemical mutagenesis screens will be further analyzed. Additional mutants will be defined in collaboration with Dr. Nancy Hopkins, MIT, by screening through 275 retroviral insertional mutants for which candidate genes have been identified. Brain ventricle mutants will be categorized as a prelude to cloning corresponding genes. This
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study will define a large collection of genes required for normal brain ventricle formation, and which may display abnormal activity in patients with mental health disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMOKINES IN A NOVEL MURINE MODEL OF DTH IN THE BRAIN Principal Investigator & Institution: Ransohoff, Richard M.; Professor; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-MAY-2005 Summary: (provided by applicant) This research will be done primarily in Poland as an extension of NIH grant # 1 R01 NS 32151 "Chemokines in CNS inflammation." Leukocyte infiltration into the central nervous system (CNS) is a key event in many neuroimmunologic diseases. The recruitment of lymphocytes and macrophages into the brain is likely the result of chemokine (chemoattractant cytokine) expression in the CNS. In the parent grant we analyze how specific pairs of chemokines and their receptors govern recruitment of inflammatory cells to the CNS during animal model of multiple sclerosis (MS) - experimental autoimmune encephalomyelitis (EAE). In this proposal, we would like to extend those studies and analyze the role of chemokines and chemokine receptors in a newly described focal model of MS-like CNS lesions induced by intracerebral injection of bacillus Calmette-Guerin (BCG). This model is an example of brain delayed type hypersensitivity (DTH) reaction and is characterized by the presence of a single mononuclear inflammatory focus in brain striatum. Unlike EAE brain, the DTH model is induced by non-CNS antigen (BCG) and allows observation of bystander damage to the brain triggered by inflammatory reaction. Similar types of CNS damage is postulated for MS pathogenesis. This research will concentrate on the following three Specific Aims: 1) Development and characterization of the murine model of brain DTH reaction. Initially, murine model of brain DTH reaction will be described. Originally this model was described in rats a few years ago. Mouse DTH model will enable us to use several murine reagents not available for rats and use genetically modified animals in the future. 2) Analysis of chemokines and chemokine receptor expression in brain DTH model. Once the histopathology of a new model is described, we will address the potential role of chemokines in its development. Expression of chemokines and chemokine receptors in the brain during development of DTH lesion will be analyzed. This project will be concluded with Aim 3) Prevention and treatment of brain DTH model with chemokine inhibitors. Some chemokines and their receptors are most likely upregulated in the brain during BCG-induced model of neuroinflammation. This observation may lead to modulation of this pathology with anti-chemokine strategy. Upregulated chemokines will also be targeted in Aim 3. Research proposed here will complement ongoing studies by the parent grant without overlap. Results of those studies may suggest new therapeutic strategies for neuroinflammatory disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHOLINE TRANSPORTER MEDIATED BRAIN DRUG DELIVERY Principal Investigator & Institution: Allen, David D.; Associate Professor; Pharmaceutical Sciences; Texas Tech University Health Scis Center Health Sciences Center Lubbock, Tx 79430 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2004
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Summary: (Adapted from applicant's abstract): Treatment of brain disease can be limited because of the difficulty of getting water-soluble drugs into the brain. The blood-brain barrier (BBB) restricts brain drug uptake due to its anatomical structure. Site-directed brain delivery is an ideal approach to overcome these limitations. At the BBB, there are proteins that transport water soluble nutrients such as glucose and amino acids into brain to enable normal function. Choline is an essential nutrient and is taken up into brain by a transport system as well. This transporter offers an opportunity as a vector-mediated system to deliver drugs to the brain. Our hypothesis is that the bloodbrain barrier choline transporter will facilitate brain uptake of drugs that normally would not have access the brain. To be able to use this strategy to improve brain drug uptake, a full understanding of the active site substrate specificity of this transport protein is necessary. To investigate our hypothesis, we will use a combination of physiological and computer modeling based methods. The in situ brain perfusion method will be used in adult rats to evaluate BBB transport processes. We have shown that N-n-octyl nicotinium iodide (NONI) binds and is transported by this transporter. Further, NONI significantly blocks nicotine's effects in brain dopamine systems in vitro. We will further evaluate its brain uptake profile and the substrate specificity of the BBB transporter. Inhibitor constants (Ki) will be determined and compared to the Km of choline and Vmax values will be assessed to evaluate potential brain uptake. Molecular modeling maps and comparative molecular field analysis force fields will extend in vivo studies and reduce future need for animal studies. In vivo microdialysis will be used to evaluate changes in dopamine concentrations as a result of peripheral NONI administration. This application is a focused plan that will lead to development of new choline and nicotine analog drugs that will bind the BBB choline transporter and afford advances in therapy for brain disorders such as Parkinson's disease, Alzheimer's disease and stroke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COGNITION AND METHYLPHENIDATE--FMRI STUDY OF ADHD ADULTS Principal Investigator & Institution: Rao, Stephen M.; Professor; Neurology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2004 Summary: (Adapted from applicant's abstract): Attention Deficit Disorder (ADHD) is a common neurodevelopmental disorder that defines a group of individuals with developmentally inappropriate levels of inattention and hyperactivity-impulsivity. Long-term follow-up studies indicate that ADHD persists into adulthood in 30-66 percent of cases. Neuropsychological studies have identified a wide range of cognitive deficits in ADHD, including impairments on measures of response inhibition, sustained attention/working memory, timing perception/reproduction, and conceptual reasoning, prompting the suggesting that ADHD is associated with abnormal functioning of the prefrontal cortex and its subcortical connections. As a result of significant technological advances in human brain imaging, it is now possible to identify functional brain abnormalities that may underlie the cognitive deficits in ADHD. The long-range goal of this project, therefore, is to apply whole-brain fMRI to better understand the brain- mediated neurocognitive deficits in ADHD adults and to elucidate the mechanisms of action of psychostimulants commonly used to treat this disorder. The first hypothesis to be tested is that, relative to healthy individuals, unmedicated ADHD subjects will evidence minimal or no task- induced regional brain activation in frontostriatal circuitry. The second hypothesis is that methylphenidate
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(M)P will produce increases in task- induced functional activity in frontostriatal circuity in both ADHD and normal subjects. Third, the investigator hypothesizes that MP will "normalize" task-induced functional specificity in ADHD individuals relative to normal subjects. Three specific aims will be addressed: 1) to determine the regional changes in functional brain activation in unmedicated ADHD adults in response to performing cognitive tasks involving response inhibition, working memory, timing perception/reproduction, and conceptual reasoning, 2) to determine the effects of MP on task-activated brain activation patterns in normal subjects using a double-blind, placebo-controlled, cross-over design, and 3) to determine the effects of MP on taskactivated brain activation patterns in ADHD subjects using a double-blind, placebocontrolled, cross- over design. The proposed fMRI experiments, therefore, should not only enhance our understanding of the brain abnormalities associated with ADHD, but should also provide a general blueprint for evaluating the neurocognitive effects of drugs in normal and abnormal populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONFERENCE ON FUNCTIONAL MAPPING OF THE HUMAN BRAIN Principal Investigator & Institution: Fox, Peter T.; Director, Research Imaging Center; Research Imaging Center; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-MAY-2005 Summary: Five years of funding is requested from the Human Brain Project for the annual meeting of the Organization for Human Brain Mapping (OHBM). The mission of the OHBM is to promote the field of structural and functional brain mapping. In particular, OHBM emphasizes non-invasive, image-based investigation of the functional organization of the human brain. The principal activity of the OBHM is to organize an annual, international meeting. Past meetings have been highly successful. These were held in: Paris, France, 1995; Boston, MA 1996; Copenhagen, Denmark, 1997; Montreal, Canada, 1998; Dusseldorf, Germany, 1999. Upcoming meetings are planned for: San Antonio, TX, 2000; Brighton, England 2001; and, Sendai, Japan, 2002. The general plan is to have the meeting alternate between the US and a non-US site. For meetings inside the US, funding from the HBP will be used for student stipends. Abstracts submitted with a student as first author will be rank ordered, using the abstract-review scores. The top 100 students will be offered $500 stipends, to partially defray the costs of attending the meeting. For meetings outside the US, funding from the HBP will be used to pay cost for US speakers to present as invited speakers, both as Keynote speakers in the Scientific Program and as presentors in the Educational Program. This meeting has relevance for the Human Brain Project of the NIMH in the following ways. First, virtually every presentation relates to the function and structure of the human brain, in both health and disease. Second, one sixth of the scientific program (two of twelve themes) is devoted to the latest methods for image acquisition, analysis and metanalysis, i.e., neuroinformatics. Third, the entire educational program is devoted exclusively to the methods used to study the brain, with a strong emphasis on image analysis and other aspects of neuroinformatics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--NEUROPATHOLOGY/BRAIN BANK Principal Investigator & Institution: Perl, Daniel P.; Professor; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029
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Timing: Fiscal Year 2002; Project Start 01-MAR-1997; Project End 31-MAR-2007 Summary: (provided by applicant): Over the years, neuropathologic characterization of autopsy-derived brain tissues has occupied a central position in research on amyotrophic lateral sclerosis-parkinsonism dementia complex of Guam. Within this Program, the Neuropathology-Brain Bank core (core C) will continue to receive brain specimens (both fixed and frozen) from the Clinical core (core B) on Guam. These brain specimens will be derived from three sources, a) cases showing clinical evidence of agerelated neurodegeneration who have been identified and followed by the Clinical core, b) deceased members of a large cohort of elderly Chamorros (age 65 or above) who have been identified and longitudinally assessed for neurologic and cognitive function (see subproject by Galasko) and c) specimens that were obtained in conjunction with prior research studies on Guam in order to construct a brain tissue repository that is more fully representative of all forms of neurodegenerative disease on Guam as well as include additional examples of specimens derived from patient who died in the earlier phases of the disease outbreak. The core will 1) provide supervision and advice to the Clinical core (core B) to enable the Program to obtain optimally fixed and preserved autopsy-derived brain specimens with a minimum amount of postmortem delay 2) carry out MRI examinations on all fixed brain specimens, 3) perform dissection, preservation and storage of received brain specimens and distribute appropriate tissue samples to investigators within the Program, 4) perform complete neuropathologic evaluation and diagnosis of each brain specimen, 5) determine the extent and distribution of relevant neuropathologic lesions in these specimens, 6) incorporate these data above in the neuropathology database, 7) obtain Guam-derived brain specimens obtained in conjunction with prior NINCDS registry studies that were evaluated neuropathologically and are being stored in the Brain Research Institute, Niigata, Japan, and 8) retain in a preserved state brain samples obtained in conjunction with the above and serve as a national/international brain bank repository to make available appropriate brain tissue specimens to qualified researchers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYCLOOXYGENASE AND ANTI-INFLAMMATORY DRUGS IN AD Principal Investigator & Institution: Pasinetti, Giulio M.; Professor; Psychiatry; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: Non steroidal anti-inflammatory drugs are among the most promising classes of drugs for the prevention and possibly treatment of Alzheimer's disease (AD). A rapidly increasing number of large-scale therapeutic trials of such drugs are being initiated. The most likely target of NSAIDs in the brain is cyclooxygenase (COX)-2. We found that COX-2, but not COX-1 expression, is elevated in the neurons of AD brain, where it correlates with amyloid plaque density and neuronal atrophy. In this revised application, using a combination of in situ hybridization and immunocytochemical techniques, we will further study the regional distribution and cell-type expression of COX-2 and other inflammatory markers in the AD brain. To determine the relationship between COX-2 expression in the AD brain and clinical measures of disease activity, COX-2 expression will be correlated with antemortem assessment of dementia. Because therapeutic trials of potential disease-modifying regimens select patients at one or more stages of clinical disease, these studies will determine the relationship between AD clinical stage and COX-2 expression. In parallel studies the effect of COX inhibitors on COX-2 mediated responses in the brain will be explored using a transgenic mouse model of human (h)COX-2 overexpression in neurons. In preliminary studies using
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primary neuron cultures derived from these transgenic mice, we found that hCOX-2 overexpression potentiates beta amyloid (Abeta) neurotoxicity in vitro through potentiation of oxidative stress mechanisms. We will use this model system to compare the neuroprotective activity of various COX inhibitors on Abeta toxicity in vitro, and to study the mechanism of such neuroprotection. Based in part on the outcome of these studies, we will then test the brain activity of NSAID regimens administered systemically. We have established in our preliminary studies that transgenic mice with neuronal overexpression of hCOX-2 show increased lipid peroxidation in brain as measured by levels of malondialdehyde (MDA) along with elevated prostaglandin (PG)F2alpha. Preliminary studies also indicate increased expression of components of the complement cascade in the brain of hCOX-2 transgenics. Based on our evidence that COX-2 in neurons is indeed the appropriate target for NSAID regimens in AD, this transgenic model provides a unique method of measuring relevant brain activity of COX inhibitors. The outcome of the proposed studies will be immediately relevant to the design of human trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOMEGALOVIRUS IN THE BRAIN Principal Investigator & Institution: Van Den Pol, Anthony N.; Professor; Neurosurgery; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (provided by applicant): Cytomegalovirus is the leading viral cause of congenital disease, often producing serious neurological deficits. CMV attacks the developing central nervous system (CNS) resulting in serious brain disorders that include microencephaly, epilepsy, deafness, microgyria, mental retardation, sensory loss, motor problems, and psychiatric disturbances. In addition, CMV is a clinically important opportunistic virus that can lead to serious neurological disease in AIDS patients. Despite the clinical importance of CMV infections of the brain, relatively little experimental work has been done in this area, and many basic questions remained unanswered. The present application addresses basic mechanisms of viral spread into the brain, and once in the brain, spread by intracellular transport or extracellular diffusion to other brain cells. The hypothesis that CMV can be spread through axonal transport will be studied with in vitro and in vivo models. Although CMV appears to have no absolute host cell preference in the brain, the hypothesis that CMV shows relative cellular preferences will be tested in living brain slices at different developmental ages. A recombinant mouse CMV expressing green fluorescent protein will be used to identify infected cells. Neurons in vitro are all killed by CMV, whereas mature neurons in vivo are protected against CMV. Using a mouse model of immunosuppression, parallel to AIDS, we will test the hypothesis that cell-mediated immunity protects neurons in vivo from CMV proliferation. Neuronal activity plays an important role in establishing the correct circuitry during brain development. The hypothesis that early infection by CMV can generate disturbances in the electrophysiological activity of developing neurons will be tested with whole cell patch clamp recording using current and voltage clamp electrophysiology, and with calcium digital imaging, using primary mouse neuron cultures and brain slices. Virus mediated changes in intracellular ion levels, ion currents, transmitter responses, and membrane properties will be compared in CMV infected and control cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEPRESSION AND BRAIN STRUCTURE IN TYPE 1 DIABETES Principal Investigator & Institution: Jacobson, Alan M.; Senior Vice President; Joslin Diabetes Center Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): There is growing evidence that type 1 diabetes leads to an increased prevalence of depressive disorders and preliminary data suggesting that the metabolic disturbances associated with diabetes, both severe hypoglycemia and persistent hyperglycemia, lead to changes in brain structure and cognition. These findings, together with research on structural changes in the brain among depressed patients without diabetes, suggest that diabetes could cause structural changes in the brain that lead to depression. No studies have evaluated mechanisms underlying the etiology of depression among patients with type 1 diabetes. Using a cross sectional research design, we propose to study six groups of subjects: All subjects (N = 180) will be ages 30-40, right-handed and matched according to age, gender and SES. Diabetic patients will have between a 15-25 year history of types of diabetes. There will be three groups of diabetic subjects without psychiatric history: 1. Well controlled (0-1 episodes of severe hypoglycemia; mean HbA1c over history of diabetes equal to or 3 episodes of severe hypoglycemia; mean HbA1c over time equal to or 9.0%; 0-1 hypoglycemic episodes). A fourth group of diabetic subjects with a history of unipolar major depression and who equally represent the glycemic control characteristics of the other three diabetic groups will also be studied. In addition, two non-diabetic control groups (history of depression; no psychiatric history) will also be studied. We will assess these patients as to brain structure, using Magnetic Resonance Imaging (MRI); depression, using the Structured Clinical Interview for DMS IV (SCID); and cognition using the Wechsler Adult Intelligence Scale III (WAIS III) and other neuropsychological tests of memory, psychomotor speed and mental efficiency. We will also evaluate medical factors (e.g., glycemic control-HbA1c; and history of severe hypoglycemia). We will examine whether: 1) structural abnormalities are more common in diabetic subjects compared to the matched community controls; 2) there is a relationship between diabetes specific medical variables, such as long-term glycemic control, and brain structure abnormalities; 3) structural abnormalities are more common in diabetic patients with a history of unipolar major depression than diabetic patients without a history of depression; and 4) the frequency of structural abnormalities in the brain among diabetic patients with a lifetime history of unipolar depression differs from the depression control group. The proposed research will, for the first time, provide evidence regarding the linkage between structural changes in the brain and depressive disorder in diabetes, and evidence about the relationship of type I diabetes and its attendant metabolic disturbances to structural changes in the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVELOPMENTAL GENETICS OF MAMMALIAN BRAIN SEXUAL DIMORPH Principal Investigator & Institution: Vilain, Eric J.; Charles R. Drew University of Med & Sci 1621 E 120Th St Los Angeles, Ca 90059 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2008 Summary: The goal of the proposed studies is to understand which molecules are responsible for the differences between male and female brains. It is well known that testosterone, secreted by the testes before or after birth, acts on the male brain to masculinize specific neural networks, which results in specific masculine behavior. The
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classical view is that gonadal androgens are the only factors involved in the masculinization of the brain. We propose to explore an alternative possibility. Sex differences in behavior may be caused in part by genetic factors influencing the development of the brain. We will search for the genes responsible for brain sexual dimorphims by determining which genes are differentially expressed between male and female brains, and where in the brain these genes are expressed (Specific Aims 1 and 2). We will characterize the profile of expression of these genes in order to test their relevance to the development of brain sexual dimorphisms (Specific Aim 3). The ultimate goal of this project is to create mouse models in which female mice express male genes only in their brain, in order to elucidate the role of these genes in sexual behavior. This proposal intends to improve the general understanding of the sexual differentiation of the brain. It will also impact significantly our knowledge of a number of neurological and psychiatric disorders where sex differences are observed, such as Alzheimer's disease, schizophrenia, and depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIFFUSE BRAIN ABNORMALITY IN SICKLE CELL DISEASE Principal Investigator & Institution: Steen, R Grant.; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2002; 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
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Project Title: DIFFUSE REHABILITATION
OPTICAL
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IMAGING
FOR
STROKE
Principal Investigator & Institution: Strangman, Gary E.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The candidate's primary interest is to understand the reorganization and recruitment associated with sensorimotor learning in healthy and stroke populations. The proposed research will test two primary hypotheses: 1) that a relatively new brain imaging technique, diffuse optical tomography (DOT), is able to detect and map learning-related modulations in brain function, and 2) that learningrelated modulations in primary and secondary motor cortices are larger - both spatially and in amplitude - and less lateralized in hemiparetic stroke patients than the changes in these regions in control subjects. To test these hypotheses, the research project will first characterize and validate the DOT technique by employing simultaneous DOT and functional magnetic resonance imaging (fMRI) as both healthy and patient volunteers perform motor tasks. The fMRI activation maps will serve as a spatial "gold standard" to which the simultaneously acquired optical imaging maps will be co-registered and compared. Comparisons will be performed within and between populations, with data analysis enhanced by models of the physiological noise in the DOT recordings as well as tuning of DOT image reconstruction algorithms. We expect this approach to provide a validated technique for detecting hemodynamic changes in the brain with the advantages of portability, unobtrusiveness, low cost, and spectroscopic information. The final component of the research plan will be a pilot application of DOT brain imaging during a gait re-acquisition task. This DOT application will be performed in a rehabilitation setting, infeasible for other brain imaging methods. In conjunction with the proposed research plan, the candidate seeks training in one primary and one secondary area. The primary area of training will be in stroke: The etiology and consequences thereof, associated rehabilitation, as well as general patient-focused research methods. The secondary area will cover cutting-edge DOT image reconstruction and data analysis techniques. Completion of this training will allow the candidate to pursue an independent research program in basic and clinical neuroscience addressing questions related to functional brain reorganization in healthy and patient populations. Importantly, use of the DOT technology in such a research program is expected to enable the investigation of tasks and populations that are otherwise beyond the reach of existing brain imaging technologies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIRECT BRAIN INTERFACE BASED ON EVENT DETECTION IN ECOG Principal Investigator & Institution: Levine, Simon P.; Professor of Biomedical Engineering; Phys Med and Rehabilitation; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 26-APR-2001; Project End 31-MAR-2006 Summary: (Verbatim from the Applicant's Abstract) A number of people with physical disabilities have difficulty performing any physical movement and would benetit trom a direct brain interface, an interface that accepts commands directly from the brain. The University of Michigan Direct Brain Interface (UMDBI) research partnership is a collaboration which includes the Departments of Biomedical Engineering, Electrical Engineering and Computer Science, Physical Medicine and Rehabilitation, Neurology,
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Surgery and Radiology from the University of Michigan; the Departments of Neurology from the Henry Ford Hospital, and the Institute of Biomedical Engineering from the Technical University Graz. These partners propose to address the functional evaluation of a direct brain interface and the optimization of detection methods used in the direct brain interface. The (time-domain based) template matching detection method developed by the UM-DBI has demonstrated sufficient accuracy in off-line experiments to warrant real-time, on-line implementation and testing with subjects at the University of Michigan and Henry Ford Hospitals who have implanted electrodes for purposes related to epilepsy surgery. (While these subjects are not members of the target user population, the presence of implanted cortical electrodes in these subjects provides a unique opportunity for direct brain interface development). The proposed functional evaluation includes: 1) Development of an on-line, real-time testing system for direct brain interface methods; 2) Examination of the ability of subjects to learn to voluntarily improve event-related potential (ERP) quality and detection performance given appropriate feedback; 3) Determination of the accuracy and speed with which a direct brain interface can be used to perform functional tasks; and 4) Identification of the relationship between the location of electrocorticogram (ECoG) recorded brain events and the activated portion of the brain as observed through functional magnetic resonance imaging. Improvements in the accuracy by which brain events can be detected will be approached through development and optimization of time-domain based detection methods (performed primarily at UM) and evaluation of the performance of frequency-domain based detection methods on ECoG (performed primarily at Graz). In addition, off-line analysis will be used to I) Investigate the ability of current detection methods to differentiate between brain activity related to different actions and 2) Determine the increased accuracy of event detection achievable using ECoG versus EEG. The proposed research is intended to conclusively demonstrate that a direct brain interface based on the detection of human ERPs recorded intracranially can be used for control of functional tasks. While a simple direct brain interface would be a valuable tool for people with severe disabilities, it is intended that an initial interface would also form the foundation for future generations of direct brain interfaces of ever increasing complexity which would rely on advanced signal processing methods (such as those explored here). Beyond the scope of the proposed work, the results of these studies will form the foundation for clinical testing of the direct brain interface with individuals from the target user populations using subdural electrodes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DYNAMIC IMAGING OF SYNAPTIC INHIBITION Principal Investigator & Institution: Augustine, George J.; Professor; Neurobiology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 10-APR-2002; Project End 31-MAR-2004 Summary: While many methods are available for functional imaging of excitatory processes in the brain, until now there has been no practical way to image synaptic inhibition in the brain. The goal of this project is to adopt clomeleon, a geneticallyencoded indicator protein, for imaging Cl-dependent synaptic inhibition in the brain. This indicator was produced by fusing the chloride-sensitive yellow fluorescent protein with the chloride-insensitive cyan fluorescent protein; the ratio of fluorescence resonance energy transfer (FRET) dependent emission of these two fluorophores varies in proportion to the intracellular concentration of chloride ions ([Cl-]i). The proposed experiments will use a genetic strategy to target expression of clomeleon to subsets of neurons in the mouse brain. This should allow many novel experimental analyses of the
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physiological functions of Cl-. During the Phase I experiments proposed here, fluorescence imaging methods will be use to look for neuron-specific variations in resting [Cl-]i and changes in [Cl-]i associated with activation of inhibitory synaptic pathways in neurons of hippocampal, cerebellar, and cortical tissue slices. In Phase II, these experimental procedures will be extended to in vivo conditions to image the temporal and spatial patterns of synaptic inhibition in neural networks of the intact brain. This new technology should provide the first experimental views of the dynamics of synaptic inhibition in the brain and offers the promise of elucidating many important features of brain activity during normal function and as a consequence of drug abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EARLY BRAIN DEVELOPMENT IN HIGH RISK CHILDREN Principal Investigator & Institution: Gilmore, John H.; Professor; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Despite the widespread belief that schizophrenia is a disorder of abnormal early brain development and numerous theories to that effect, there is little direct evidence to support this idea. This is in part due to the fact that until recently, the clinical study of human fetal and neonatal brain development was limited by a lack of appropriate tools with which to carry out such studies. Ultrasound and magnetic resonance imaging (MRI) are ideal techniques for the study of brain development in the human fetus, neonate, and child. Using ultrasound, it is possible to image the developing lateral cerebral ventricles in utero. Using high resolution MRI, it is possible to examine brain structure and its development from the neonatal period through childhood and into the period of risk for the onset of schizophrenia. The primary hypothesis of this research program is that abnormalities of brain structure and development, reflected in ventricle size and shape, along with abnormalities in total brain volume and white matter integrity in fetal and neonatal brain, are markers of abnormal development of thalamo-limbic-cortical circuits, associated abnormal GABA interneuron development, and ultimate susceptibility to schizophrenia. This will be the first study to use ultrasound to prospectively study prenatal and neonatal brain development in the offspring of women with schizophrenia. It will also prospectively study the development of fetuses with mild enlargement of the lateral ventricles, a structural abnormality that is hypothesized to represent an endophenotype of risk for schizophrenia. Subjects will have 2D ultrasounds in the second and third trimesters, and a 3D ultrasound and an MRI at 2 weeks after birth. Early childhood development will be followed prospectively at ages 1 and 2 years with the Mullen Scales of Early Learning and an assessment of working memory and attention, neurocognitive processes in which GABA interneurons play an important role. The identification of the timing of ventricle enlargement will provide a focus for studies of neurodevelopmental mechanisms that underlie schizophrenia. Understanding the causes of early abnormalities of ventricle structure will provide important information about genetic and environmental risk factors in schizophrenia. Finally, the study of lateral ventricle development will allow the early identification of children at high risk for schizophrenia and other neurodevelopmental disorders, ultimately making early intervention possible to prevent or mitigate this risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENHANCED DRUG DELIVERY TO METASTATIC BRAIN TUMORS Principal Investigator & Institution: Black, Keith L.; Director; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Brain capillary endothelium and its contiguous cells, pericytes and astrocytes, are the structural and functional components of the blood-brain barrier (BBB). Microvessels supplying brain tumors retain characteristics of the BBB, forming a blood-tumor barrier (BTB). While adequate delivery of drugs occurs to systemic tumors, the BTB limits delivery of antineoplastic agents to metastatic brain tumors. Drugs such as Herceptin, which is effective in treating metastatic tumors outside the brain have a high failure rate within the brain due to inadequate delivery across the BTB. The incidence of metastatic brain tumors is ten-fold higher than primary brain tumors. We have demonstrated that calcium-sensitive potassium (KCa) channel agonists selectively increase drug delivery across the BTB, and have postulated the biochemical mechanisms of this selective BTB permeability increase. We also have preliminary data suggesting that ATP-sensitive potassium (KATP) channel agonists selectively increase BTB permeability independent of KCa channels. These novel observations allow for a pharmacological mechanism for selectively increasing drug delivery across the BTB. This proposal will (a) further understand the mechanisms of KCa, and KATP channel activation in increasing BTB permeability and (b) optimize delivery of effective concentrations of drugs to metastatic breast and lung tumors in rats and humans via potassium channel-based mechanisms. We build on our data showing the ability of KCa channel agonists to selectively increase drug delivery across the BTB in rat glioma models and preliminary evidence suggesting that the BTB permeability increase may relate to over expression of KCa channels on glioma cells and tumor capillary endothelium. In this grant we will investigate 5 specific aims. Aim 1: To determine whether KCa and KATP channels are over expressed in metastatic brain tumor microvessels and tumor cells and whether increased expression correlates with increased permeability induced by KCa and KATP agonists. To test whether tumor cells can induce over expression of KCa or KATP channels on brain endothelial cells. Aim 2: To test by quantitative electron microscopy whether the mechanism of KATP channel agonist-induced BTB permeability increase is due to increased endothelial vesicular transport or opening of tight junctions. To test whether increased vesicle formation is correlated with changes in endothelial and tumor cell membrane potential. Aim 3: To investigate whether KCa and KATP channel agonists increase delivery of therapeutic monoclonal antibodies and chemotherapeutic drugs across the BTB into metastatic human breast and lung cancer in nude rats/mice. Aim 4: In nude rats/mice harboring metastatic breast and lung tumors we will investigate whether increased drug delivery across the BTB using KCa or KATP agonists results in inhibition of tumor growth, and whether survival is increased. Aim 5: The ability of a KATP channel agonist, minoxidil, to increase delivery of an anti-tumor drug to patients with brain tumors will be determined by LC-MS-MS in resected tumor tissues. This grant is responsive to the recent Brain Tumor PRG recommendation in 2001 to support studies to improve delivery of drugs across the BBB, particularly for metastatic brain tumors. Overall, these studies will further delineate the role of KCa and KATP channel activation as a mechanism for selective delivery of anti-cancer agents across the BTB and could potentially result in improved control of disease in patients with metastatic brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPIDEMIOLOGY OF BRAIN ABNORMALITIES IN FEBRILE SEIZURES Principal Investigator & Institution: Hesdorffer, Dale C.; Assistant Professor; Gertrude H Sergievsky Center; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-MAY-2004 Summary: This project proposes to investigate associations between brain abnormalities detectable with current MRI technology among children under 5 years of age with a first febrile seizure and (1) febrile seizure type, (2) family history of febrile seizures, (3) developmental delays in cognition and behavior, and (4) febrile seizure recurrence. The authors will study these factors in 252 cases with first febrile seizure and 252 febrile children without seizure, frequency matched to cases on age, gender, and month of ascertainment. At baseline, we will compare: (1) the prevalence of brain abnormalities detected on MRI performed within 72 hours of the first febrile seizure by febrile seizure type; (2) the prevalence of febrile seizure in siblings of comparison children compared to cases with and without brain abnormality; and (3) the cognitive and behavioral function of cases with and without brain abnormality and of comparison children. Children will be followed over time for febrile seizure recurrence, and cognitive and behavioral function. This study aims to determine whether: (1) brain abnormalities are more common among children with complex versus simple febrile seizures; (2) brain abnormalities are inversely associated with a family history of febrile seizures in first degree relatives; (3) brain abnormalities are associated with developmental delay; and (4) once the influence of family history of febrile seizures is removed, brain abnormalities are not associated with an increased risk of recurrent febrile seizures. Answers to these questions may improve the clinical management of subgroups of children at risk for long-term disability so that future at-risk children can benefit from early interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ESTROGEN, NADPH OXIDASE, AND NEUROTRAUMA Principal Investigator & Institution: Bruce-Keller, Annadora J.; Assistant Professor; Sanders-Brown Ky Res Ctr/Aging; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Traumatic brain injury (TBI) afflicts almost 500,000 Americans a year, but unfortunately, existing treatments have only minimal ability to prevent secondary brain damage accompanying traumatic brain injury. Epidemiological data that suggests that women fare better then men following TBI, but the basis for this difference is not understood. It is likely that action of female sex hormones, particularly estrogen, may have significant effects on the progression of brain injury, and recent data from our laboratory suggests that estrogen has potent antiinflammatory properties that could account for its ability to attenuate traumatic brain injury. In particular, data indicates that estrogen is able to decrease oxidative burst activity and subsequent redox-based inflammatory signaling in glial cells, thereby attenuating neurotoxic brain inflammation. Therefore, it is proposed that estrogen acts to preserve brain function following TBI by decreasing both blood-brain barrier (BBB) breech and neuronal injury, and that these distinct endpoints are mediated by a single mechanism: modulation of the glial oxidative burst. Specific Aim 1 will test the hypothesis that estrogen is able to significantly attenuate oxidative burst activity in astrocytes, microglial cells, and endothelial cells both in vitro and in vivo, and will
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determine the role of estrogen receptors in this process through use of estrogen receptor knockout mice. Specific Aim 2 will test the hypothesis that by directly interfering with oxidative burst activity, estrogen blocks the release of matrix metalloproteinases and thus preserves blood-brain barrier integrity in mice following traumatic brain injury. Specific Aim 3 will build upon these studies by testing the hypothesis that by decreasing oxidative burst activity and redox signaling, estrogen blocks the formation of neurotoxic inflammatory mediators (excitotoxins and cytokines), culminating in decreased injury and increased recovery following traumatic brain injury. Completion of these studies will result in a thorough understanding of the mechanisms of estrogen-mediated neuroprotection in TBI and could highlight a novel target for therapeutic intervention following brain trauma in both women and men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXCERCISE INDUCED RISE IN SEVERITY OF ALTITUDE ILLNESS Principal Investigator & Institution: Roach, Robert C.; New Mexico Resonance 2301 Yale Blvd Se, Ste C1 Albuquerque, Nm 87106 Timing: Fiscal Year 2002; Project Start 10-SEP-2001; Project End 31-JUL-2005 Summary: (Applicant's abstract): Many hundreds of studies of acute mountain sickness (AMS) over the past two centuries have examined the role of ventilation, pulmonary gas exchange and fluid balance, yet the pathophysiology of AMS remains largely unsolved. AMS incurs significant medical risks and costs since as many as 5 percent of cases can develop life-threatening high altitude cerebral edema (HACE). AMS itself is a substantial public health problem with a prevalence of 15-65 percent in visitors to high altitude. This proposal focuses on the role of brain swelling, which can include elevated brain water and blood volume, in the pathophysiology of AMS. This proposal uses exercise as a tool to develop more severe symptoms of AMS sooner than would be the case in resting subjects. Our approach departs from the traditional paradigm, followed by many of us in this field, of searching for clues to the pathophysiology of AMS in the observed peripheral responses (pulmonary, renal, vascular). Our rationale for focusing on brain swelling is that a) the symptoms of AMS are largely neurological; b) HACE, considered the end-stage of severe AMS, has recently been identified as a vasogenic edema, opening the door for a role for blood-brain barrier (BBB) permeability in AMS; c) new, noninvasive techniques make measurement of brain water and blood volume possible; and d) available experimental evidence and theoretical arguments support a significant role for brain swelling in the pathophysiology of AMS. We recently showed that exercise caused a more than 3 fold rise in AMS symptom severity, a drop in arterial oxygen saturation (SaO2) during exercise, and slight fluid retention. We also recently showed that subjects ill with AMS had a small drop in plasma volume and a large rise in extracellular water compared to those that remained free of AMS. In further studies, magnetic resonance imaging revealed that most brains swell when humans ascend to high altitude. Our overall hypothesis is that brain swelling causes the symptoms of AMS. Our approach is to apply several new and innovative technologies to solving the pathophysiology of AMS. These include noninvasive techniques to measure and manipulate cerebral blood volume, intracranial pressure, BBB opening, cerebrospinal volumes and selected cellular, molecular and genetic responses to hypoxia in people developing AMS. Our three specific aims are 1) to determine the role of elevated brain water in brain swelling and AMS; 2) to determine the role of BBB permeability in AMS; and 3) to determine the role of select cellular, molecular and genetic factors in AMS. The results from the proposed studies will increase our understanding of the role of the
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brain, brain water and brain swelling in other conditions, both those associated with oxygen depravation, and those where the primary insult is to the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE EXPRESSION IN ALZHEIMER'S DISEASE Principal Investigator & Institution: Lukiw, Walter J.; Neurology; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Provided by applicant): Alzheimer's disease (AD) represents an insidious, progressive, neurodestructive process of the human brain clinically characterized by the deterioration of memory and higher cognitive function. Familial AD and the more prevalent sporadic AD share final common neuropathological features that include a presenilin-1 (PS1) mediated catabolism of b-amyloid precursor protein (BAPP) generating neurotoxic amyloid-beta (AB) peptides that are deposited as insoluble senile plaque (SP). AB peptides and SPs increase reactive oxygen species (ROS) production which, in turn, fuel the expression of brain genes that promote proinflammatory (PI) episodes and brain cell death. The appearance in both familial and sporadic AD brain of reactive astrocytes, activated microglia and PI cytokines such as interleukin-1 beta (IL-1 beta) associated with AB and SP suggests that AD brain may be in a chronic state of inflammation. Abundant data that NSAIDs may be effective in ameliorating AD progression further supports a PI component to AD etiopathology. The goal of this project is to clarify the contributions of two key PI gene signaling pathways in AD brain which culminate in excessive stimulation of the neuroinflammatory response: (a) the inducible oxidoreductase cyclooxygenase-2 (COX-2) gene, which encodes the prostaglandin synthase responsible for prostanoid and other PI mediator production and (b) the presenilin-1 (PS1) gene, which drives aberrant processing of BAPP to accelerate AB production, Inducible COX-2 and PS1 gene over expression can both be regarded as upstream PI signaling events centrally involved in AD pathophysiology. The generation of ROS by AB also activates the binding to promoter DNA of NF-kB, a potent PI transcription factor (TF). Thus, NF-kB-DNA binding, driving COX-2 and PS1 gene transcription represent pivotal activating forces for PI signaling. The COX-2 and PS1 genes (a) exhibit down-regulation during human brain development, (b) are both sharply up-regulated in AD hippocampus, (c) are co-induced by AB42+ IL-I beta] in cultured human brain cells and (d) share at least 9 DNA regulatory motifs in their immediate promoters, including multiple AP1-, HIF1-, NF-Kb and STAT1-DNA binding sites, suggesting correlated gene activation. Using human control and AD brain analysis, human neural cells in primary culture and COX-2- and PS1-promoter, luciferase-reporter transfection models, we propose to test the hypothesis that signaling factors including PI TFs are key in the control of COX-2-and PS1-transcription-mediated over-stimulation of PI pathways that fuel neuronal cell degeneration in AD brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HARVARD PEDIATRIC BRAIN TUMOR CENTER Principal Investigator & Institution: Kieran, Mark W.; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: The Harvard Pediatric Brain Tumor Center will join the Pediatric Brain Tumor Clinical Trials Consortium, endorse its Constitution, participate in committee activities, give absolute priority to Consortium protocols, and collaborate with other
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Consortium members. Our multi-disciplinary group is committed to: 1) Ensuring that, each year, more than 15 patients with newly diagnosed or recurrent brain tumors are available for Consortium studies; 2) Acting as a resource for the Consortium in those areas where our expertise will assist the Consortium in ensuring its success; our commitment to being a resource will include members from all areas, including our departments of Neurosurgery, Radiation Oncology, Oncology, Neurology, Pathology, Radiology, Gene Therapy and Angiogenesis. 3) Proposing novel studies that meet the Consortium's goals. In that regard, we have already developed three proposals: i) Phase I study of endostatin, an angiogenic inhibitor, in pediatric patients with poor prognosis malignancies; ii) Phase I study of GM3, a novel ganglioside in pediatric patients with malignant brain tumors; iii) a Phase I study of oxaliplatin as a radiation sensitizer in pediatric brain stem gliomas. 4) Developing and expanding a pediatric brain tumor tissue bank. We will cooperate with Consortium partners to develop a new central tissue bank or a virtual tissue bank. On request, we will also make material from the Harvard Brain Tumor Tissue Bank, which currently has over 1500 adult and 200 pediatric samples, available to Consortium members. 5) Continuing to develop our current expertise in several areas, including: anti-angiogenic molecules (Dr. Judah Folkman); biodegradable wafers containing endostatin (Dr. Peter Black); novel gene therapy vectors (Dr. Richard Mulligan); proton beam and stereotactic radiation therapy (Dr. Nancy Tarbell); small molecule signal transduction inhibitors (Dr. Chuck Stiles); Multivoxal high resolution magnetic resonance spectroscopy (Dr. Aria Tzika); and molecular characterization of brain tumors (Dr. David Louis). In summary, we will bring the full thrust of a Comprehensive Cancer Center and the full services of a pediatric center to enhance the Consortium and our mutual missions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIV-1 GP120-INDUCED ENDOTHELIAL CELL DYSFUNCTION Principal Investigator & Institution: Kanmogne, Georgette; Pathology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The human immunodeficiency virus (HIV) invades the brain in the early stages of infection For patients in the advanced stage of infection, dysfunction of the central nervous system (CNS) is a common cause of morbidity and often leads to progressive dementia, cerebral atrophy and death. Evidence suggest that HIV and /or HIV-associated proteins are critical to the pathogenesis of the HIVassociated dementia (HAD)complex.To elucidate the pathogenesis of HAD, it is important to understand by what mechanisms HIV invades the brain. Breakdown of the blood-brain barrier is commonly seen in patients with HAD, despite the lack of productive HIV-infection of the brain endothelium. The HIV-1 envelope protein gp120 is present in the brain of patients with HIV encephalitis, and is neurotoxic Recent evidence from our laboratory, and by others, suggests a direct effect of gp120 on the brain endothelium. It is our hypothesis that gp120 directly causes blood-brain barrier dysfunction and plays a major role in viral invasion of the brain To test this hypothesis, we plan the following aims. Aim 1: To test the hypothesis that HIV-1 gp120 proteins are toxic to human brain microvascular endothelial cells and directly induce a disruption and/or damage of the blood-brain barrier we will measure endothelial cell permeability and apoptosis. Aim 2 To test the hypothesis that exposure of gp120 proteins to human brain microvascular endothelial cells result in the loss of tight junction proteins we will assess the expression of occludin, claudia-5 and zonula occludens-1 using western blotting and immunofluorescence. Aim 3: To determine if chemokine receptors are
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involved in gp120-induced blood-brain barrier disruption and/or damage Aim 4: To determine the signal transduction pathways involved in gp120-induced blood-brain barrier dysfunction. Data from these experiments will help determine the role that gp120 plays in the breach of blood-brain barrier integrity and HIV invasion of the brain, and will suggest therapeutic approaches to preventing gp120-mediated dysfunction of the brain endothelium during HIV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN PERINATAL BRAIN INJURY AND OUTCOME: MRI ASSESSEMNT Principal Investigator & Institution: Grant, P E.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): The proposed study combines the candidate's background in pediatric neuroradiology and physics as well as local expertise in MR imaging of acute brain injury, MR analysis of brain structure and neonatal brain physiology. The goal is to build the candidate's expertise in stateoftheart neuroimaging techniques and her knowledge of neonatal physiology in order to better study the links between MR observables and neonatal brain injury. The candidate is in the perfect environment to extend the MR imaging tools used in the adult population to the neonatal population. The proposed 5year research training Program consists of 1) neonatal neurophysiology, 2) theories and practice of diffusion, perfusion, spectroscopy and structural MR image analysis, and 3) clinical research design, experimental statistics and ethics. The research goal is to develop MR techniques that predict the severity of brain injury in the acute period and to quantitatively assess the structural outcome at 2 years of age. We hypothesize that regions of decreased apparent diffusion (ADC) identified in the acute time period can be associated with different physiological environments, as determined by perfusion weighted imaging and proton spectroscopy. We also hypothesize that these observed physiological variables in the first days of life predict the severity of both the primary and secondary brain injury at 2 years of age. The project is expected to only help the candidate establish an independent research career and to contribute to an understanding of perinatal brain injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IN UTERO GENE THERAPY Principal Investigator & Institution: Wolfe, John H.; Professor; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-MAY-1993; Project End 31-MAY-2006 Summary: (provided by applicant): The lysosomal storage diseases are inherited metabolic deficiencies that produce fatal degenerative syndromes affecting multiple organ systems. Studies of bone marrow and neural stem cell transplantation, germline and somatic gene transfer, and injections of purified enzyme have shown that supplying the normal enzyme early in life may significantly reduce pathology compared to treatments initiated at older ages. However, the central nervous system (CNS) has been especially difficult to treat due to the blood-brain barrier. Metabolic diseases that affect the CNS typically have global lesions and gene delivery within the brain has been relatively limited, particularly in large mammals. The goal of these studies is to develop methods to transfer a functional gene into the diseased fetal brain at therapeutic levels in a widely disseminated manner. Early treatment is expected to reduce the severity of
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pathology later in life or prevent it all together. Animal models with Beta-glucuronidase (GUSB) deficiency, causing mucopolysaccharidosis (MPS) VII (Sly disease), will be studied. We have developed two approaches for delivering the normal gene to the brain side of the blood-brain barrier. 1) Transplanting neural progenitor cells, which migrate extensively in the brain if transplanted during development. We have shown that NSCs differentiate into neurons and glial cells that are indistinguishable from the host brain cells. We will evaluate the fate of the engineered cells, the expression of the transferred GUSB, the long-term effects on pathology, and the safety of the treatments. 2) We have recently found that injection of AAV2 vectors into the cerebral lateral ventricles during development results in wide circulation via the cerebrospinal fluid (CSF) and transduction of many structures. Expression of the transferred cDNA is maintained for extended periods of time. The MPS VII model system is a paradigm for delivering gene products to the brain for other lysosomal storage diseases, in many of which the brain is the most severely compromised organ and will be the primary target for therapy, as well as for other metabolic disorders where global lesions in the brain must be treated. The MPS VII model system is exceptionally well suited for characterizing the engraftment potential of neural progenitor cells and the fate of direct vector transduction, in both the mouse and large animals under actual disease conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTEGRATED BRAIN FUNCTIONAL IMAGING SYSTEM-IBFIS Principal Investigator & Institution: Baumann, Stephen B.; Psychology Software Tools, Inc. 2050 Ardmore Blvd, Ste 200 Pittsburgh, Pa 15221 Timing: Fiscal Year 2001; Project Start 22-SEP-1998; Project End 31-MAR-2004 Summary: The project will provide an extendable, open hardware/software solution for functional Magnetic Resonance Imaging (fMRi) of cortical activity. It will integrate commercial products and university developed tools to provide a reliable, documented, supported, and low-cost way of adding fMRI to an existing MRI site. The research involves developing: 1) robust fMRI paradigms for visual, motor, language driving, visual mapping, working memory, and language mapping; 2) hardware and software to support event- related fMRI paradigms with millisecond timing resolution; 3) hardware and software to monitor and compensate for cardiac and respiration effects; 4) a protocol specification system that generates recommended pulse sequence parameters for fMRI studies; 3) an open-architecture JAVA-based wrapper to connect fMRI analysis tools; 6) a computerized laboratory notebook system to organize and maintain analysis images, specifications and researcher commentaries; and 7) a region of interest (ROI) database management system to allow particle-based queries and summaries of fMRI results. This research will produce a commercial integrated system for fMRI by the end of the project. The widespread accessibility of these new techniques will lead to a substantial acceleration in the growth of our understanding of cortical function by facilitating research involved in understanding brain function and mental disorders. PROPOSED COMMERCIAL APPLICATIONS: This will provide an integrated system for brain imaging for research and clinical brain activation mapping. Anticipated benefits include cognitive assessment, brain mapping and treatment of brain disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTERACTIVE MULTIPLE GENE EXPRESSION MAP FOR THE BRAIN Principal Investigator & Institution: Sugaya, Kiminobu; Associate Professor; Psychiatry; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612
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Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: (provided by applicant): Current molecular biological techniques allow us to visualize semi-quantitative levels of gene expression in situ. For example, autoradiographical image data from in situ hybridization histochemistry (ISHH) provides a wealth of information, which if made readily available could be beneficial for neuroscience researchers. However, in most cases due to the scope of their particular research interests this ISHH data has been widely overlooked by many researchers. Thus, much of the gene expression data tends to get discarded or at best becomes unavailable for future review by other researchers. For example, one researcher may have vested interests in the gene expression of brain type nitric oxide synthase (bNOS) in cholinergic nuclei, and other researchers may have interests in the serotonergic nuclei. Until this proposal, there has been no considerable effort to facilitate the sharing of such bNOS gene expression data amongst researchers. In essence, for their particular research interests, these investigators will need to repeat the same bNOS ISHH for their publications, time and time again. In order to eliminate such progress-retarding redundancy, we propose a data sharing system (interactive Multiple Gene Expression Map, IMGEM) that will be available as an interactive brain map of gene expression. This interactive tool will provide benefits essential for continuing to make great strides in discovery and mapping of gene expression by neuroscientists. We will employ the technological advantages of electronic databasing by creating a series of brain atlases as follows: 1) IMGEM will contain 2D images of all brain sections with multiple levels of resolution, 2) by the 2D and 3D image analysis, IMGEM will facilitate the comparison of multiple gene expressions and morphological structures (Niss1-stain), 3) by three dimensional reconstruction of the image data, IMGEM will allow for free rotation of the 3D image and virtual-sectioning of the brain will be possible in any desired plane, 4) IMGEM will include a server-side, graphical interface discussion board (or discussion forum) capability, which will be capable of receiving responses or input from IMGEM users in real-time; and as an additional benefit, IMGEM will be readily edited and updated to reflect the real-time input of online users, 5) IMGEM will be seamlessly integrated with other currently available online databases and hyperlinks to other data resources on the Internet will be highlighted and easily accessible via IMGEM's userfriendly design and navigation. The long-term goal of this current proposal is to gain further insights from the information available (data in the present and future) for brain gene expression mapping; and in so doing, to seek to better apply this collective knowledge for our continued understanding of normal and diseased human brain function. Our laboratory has been providing prominent ISHH data in serial brain sections with special expertise in the combination of ISHH and immunohistochemistry techniques in the same brain section. The applicant has exhibited skilled experience in creation of a commercial software package for multi dimensional data analysis, construction of relational database system on network, computer aided manipulation of imaging data and in programming of HTML, DHTML, VRML, JAVA, CGI and Perl scripts, languages necessary to accomplish the scope of the IMGEM project. Thus, we believe that our laboratory is uniquely, qualified to pursue this current proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTRACRANIAL STRAIN IN MILD TRAUMATIC HEAD INJURY Principal Investigator & Institution: Bayly, Philip V.; Mechanical Engineering; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005
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Summary: (provided by applicant): The goal of this project is to develop the technology needed to measure deformation and strain fields in the brain of the mouse or rat during mild traumatic closed-head injury. The project addresses the need for information on neuronal strain in closed-head trauma and its relationship to subsequent injury and impairment. The technology will be applied to the immature rat; it also is applicable to the mouse and mature rat. Our long-term objectives are to: (1) determine the strain fields within the brain that result from impacts or skull accelerations; (2) characterize the response of the intact brain to high strains. Measurement of brain deformation will increase our understanding of brain injury and will advance trauma therapy and prevention. Injury and degeneration can be studied with respect to the fundamental parameter: strain. Results for the immature rat are relevant to brain injury in young children. Specific aims are: AIM 1: Develop instrumentation and MR tagging procedures to obtain images of deformation in the immature rat brain during mild head injury: An MR-compatible system to deliver calibrated impacts will be developed. MR images of deformed tag lines in the brain of a prone, anesthetized, immature rat will be acquired during delivery of light, sub-concussive impacts to the head. Impact energy and velocity will be prescribed within a range based on prior published studies and on pilot studies using euthanized animals. Motion will be repeated to acquire resolved images of the deformed tag lines. The imaging procedure will be directly analogous to that used in cardiac MRI cine studies in the rat and mouse heart. In vivo studies will provide fundamental data on brain deformation in this trauma model. AIM 2: Develop software to estimate strain fields, quantify strain, and compare to overall levels of neuronal degeneration. Software developed for analysis of cardiac strain will be adapted to compute strain fields in the brain and to characterize strain as a function of location and impact characteristics (amplitude, duration). Histopathological studies will be performed post-trauma in rats that receive multiple light impacts during imaging, and in rats receiving a single larger impact, to determine total neuronal degeneration. Hypotheses: Strain will increase predictably with impact energy. In both groups, total neuronal degeneration is expected to increase with peak strain and the area of high strain in a manner characterized by sigmoid "dose-response" curves. This is an interdisciplinary project involving impact mechanics, MR tagging, histopathology, and brain injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MR METABOLIC BRAIN IMAGING OF THE INFANT BRAIN Principal Investigator & Institution: Vigneron, Daniel B.; Associate Professor; Radiology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 20-APR-2001; Project End 31-MAR-2004 Summary: (provided by applicant): Current radiologic techniques are severely limited in their ability to assess neurologic status in newborns and infants. New methods to noninvasively assess infant brain physiology are required both to better understand normal brain development and to detect and characterize neurologic anomalies. We have recently developed 3D MR spectroscopic imaging techniques to detect metabolite levels throughout the majority of the baby brain. 3D MRSI is a significant advance over the single voxel MRS used in prior studies of the infant brain. With the new technique, hundreds of spectra can be obtained throughout the brain in a single acquisition at spatial resolution of 1cc, which is 5-fold better than typically used in single voxel MRS. The preliminary results have demonstrated the ability of 3D MRSI to detect metabolic variations due to anatomic location, development and brain injury. In these studies we have also applied MR diffusion tensor imaging to provide complementary biologic
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information by detecting physiologic changes associated with the degree and preferred direction of water diffusion. In this exploratory research project, we will apply these new metabolic and functional imaging techniques to the study of infants between ages 1 month and two years. The main focus will be patients with developmental delay resulting from destructive lesions, inborn errors of metabolism, and developmental brain malformations. Anatomic variation of metabolic and diffusion parameters will be measured and correlated with the type and severity of the neurologic abnormality (motor, visual, cognitive). We will also add these techniques to MR exams of agematched infants being examined for macrocephaly, microcephaly, suspected mild trauma, or febrile seizures. Only those with normal development and normal neurologic exams will be included. We expect a large percentage (>80%) of this group to develop normally; thus, they will provide normative data, obviating recruitment of volunteer infants. As most of these patients are truly normal, we will avoid the difficulty and ethical concerns of studying and thus sedating normal volunteer infants in this exploratory study. Moreover, the inclusion of patients with normal neurologic development will provide important, currently lacking data on the metabolic and water diffusion changes that occur temporally and anatomically in this 1-24 month age group. Through this project we will develop and evaluate new MR imaging methods to noninvasively monitor infant brain physiology. These exciting new techniques have the potential to greatly enhance future studies (both research and clinical) of pediatric brain disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MTDNA MUTATIONS IN BRAIN AGING: A SINGLE-CELL APPROACH Principal Investigator & Institution: Khrapko, Konstantin; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): The long-term goal of the proposed research is to study the mechanisms responsible for age-related degenerative processes of the human brain. The understanding of these mechanisms may help to find ways to slow the corresponding processes thus moving the onset of deterioration outside the normal human lifespan. We propose to explore if accumulation of somatic mutations in mtDNA of critical cell types in the brain is one of the causative factors in the age-related deterioration of the brain. Two hypotheses are proposed. First, mutations in mtDNA could work as the primary cause of the dysfunction of certain brain areas by disrupting cellular metabolism, facilitating cell death, increasing the generation of reactive oxygen radicals, and possibly other mechanisms. Second, the presence of mutated mtDNA may render aged cells sensitive to various biochemical insults associated with specific lateonset neurodegenerative diseases. These hypotheses are supported by our preliminary finding that a majority of individual pigmented neurons in the substantia nigra in the old but not in the young brain accumulates very high levels of clonally expanded mtDNA deletions. The observed levels of deletions in pigmented neurons are above the physiological threshold and thus are highly likely to interfere with cellular function as well as with the ability of the cell to respond to the various stresses. Key to testing of these hypotheses is the analysis of the distribution of mtDNA mutations and physiological states of the cells in various areas of the brain at the single cell level, which represents the core of the proposed research. The specific aims of the application are: (1) To develop and optimize the arsenal of methods necessary for precise quantification and characterization of mtDNA mutations in single cells of the brain.
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These methods will include laser capture microdissection for single cell isolation, amplification of full length mitochondrial genomes from single cells, single cell competitive PCR, and single cell limiting dilution PCR. (2) To identify brain areas and cell types in which mtDNA mutations are most likely to play a causative role in the aging process. This will be done by measuring mutation load in individual cells of substantia nigra, cortex and putamen. These areas are known to be rich in mtDNA deletions and are associated with brain functions that decline with age, and are affected in the major late onset neurodegenerative diseases. (3) To test the hypothesis that clonal expansions of mtDNA mutations in individual cells contribute to mitochondrial defects, neural dysfunction and degeneration in normal aging and late-onset neurodegenerative diseases. This will be done by comparing the mutational load of cells that stained positive for various markers of mitochondrial dysfunction, oxidative stress and cell degeneration to non-staining control cells. We will also study the distribution the mutations as a function of age and the severity of the disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTIDISCIPLINARY ASSESSMENT OF SEVERE BRAIN INJURY Principal Investigator & Institution: Schiff, Nicholas D.; Assistant Professor; Neurology and Neuroscience; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 19-SEP-2001; Project End 31-JUL-2004 Summary: A recent NIH Consensus Statement (JAMA 1999 282:974) noted that 70-90,000 Americans each year incur long-term substantial loss of function from traumatic brain injury (TBI). The panel further noted that "the more problematic consequences involve the individual's cognition, emotional function, and behavior." The present studies are aimed at developing pilot data to guide a controlled trial for the use of deep brain stimulation technologies in selected TBI patients: those with recovery limited to regained consciousness, minimal self-awareness, and minimal interpersonal communication. Study patients will either be in a minimally conscious state (MCS) or have emerged from a MCS but remain incapable of independent activities of daily living as measured by the Disability Rating Scale. Emergence from MCS is suggested by reliable and consistent demonstration of functional interaction. Many of these patients demonstrate preserved, but fluctuating, capacities for basic communication, memory, attention, intention, and awareness of self and environment. These observations provide clinical evidence that their limited functional capacities do not represent entirely irreversible damage. The immediate goals of the proposed studies are to define appropriate clinical and imaging criteria and outcome measures to evaluate patients for selection into deep brain stimulation studies, and to evaluate physiological measures that can aid the design of stimulation parameters. We present preliminary neuroimaging data both from patients in chronic vegetative states, and from patients with other neurological conditions with implanted deep brain stimulators that demonstrate selective functional brain activations during neurostimulation. We detail potential strategies for selection of patients and for choosing targets within the thalamic intralaminar nuclei of these patients for electrical stimulation. The strategy of selection of patients for neuromodulation of impaired cognitive function will be evaluated via neuroimaging tools and neuropsychologic evaluation. The proposal combines the unique clinical expertise and experience of neurological, functional stereotactic neurosurgical, and neurorehabilitation investigators. To achieve these goals we will develop a strong multi- disciplinary team with recognized expertise in both investigational and therapeutic studies of brain injured patient populations. The long-
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range goal of the studies proposed here is to provide a foundation for rational therapies for chronic cognitive disabilities following complex brain injuries. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NANOPARTICLE BRAIN DELIVERY OF IRON CHELATORS FOR AD Principal Investigator & Institution: Liu, Gang; Radiology; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The goals of this initial research are to develop and test novel iron-chelatorman particle systems for removing excess metals (iron, aluminium, and others) from the brains of Alzheimer's disease (AD) patients and to lay the groundwork for further development of these systems in iron chelation: therapy. Although strong evidence (McLachlan et al., Lancet 337:1304.8, 1991) has shown that iron chelation can benefit AD patients by depleting excess metals from body, problems with toxicity, route of administration and restricted ability of the iron chelators to cross the BBB, have impeded the further development of this approach, We hypothesize that these impediments may be overcome by conjugating iron chelators to nanoparticles, which may serve as a vehicle to carry the chelators into the brain and bring ironchelator complexes out using low density lipoprotein (LDL) transport mechanisms. Moreover, the brain targeting ability of the systems may increase the efficacy of excess metal depletion and hence lower potential toxicity and difficulty of administration, This pilot study will focus on synthesizing iron chelators and conjugating them with nanoparticles by covalently bonding. Also, the potential of the chelator nanoparticle systems to target the brain and cross the brain-blood barrier (BBB) will be determined by protein absorption pattern using 2-D gel technology. More important, an in vivo study using Alzheimer transgenic mice treated with these systems will be performed and thereby provide the insight in whether the systems can cross the BBB, bring iron out of the brain and protect against oxidative damage in the brain. These can be detected by using histochemical, ICP-MS, and immunochemical analyses. These mice are suited well to serve as a model in this study because of increased iron and oxidative damage levels in their brain. The same increases have already been found in the brain of the patients with Alzheimer's disease. We believe that the use of nanoparticles as a brain targeting vehicle may provide the possibility of iron chelation therapy for AD and this study may lay the groundwork for further development of iron chelator nanoparticle systems in iron chelation therapy. Moreover, this investigation may also provide some insights into iron chelation treatment for some other neurodegenerative diseases, such as Parkinson's disease and Friedreich's ataxia as well as:other: iron overload mediated diseases. Overall, this: exploratory: study may open the door for the use of iron chelator nanoparticle systems to target diseased organs for iron chelation therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEURAL BASIS OF ENDOGENEOUS POTENTIALS IN HUMANS Principal Investigator & Institution: Halgren, Eric; President; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-SEP-1982; Project End 31-JUL-2006 Summary: (provided by applicant) Human brain function can be probed by measuring the minute currents produced by active neurons using electroencephalography (EEG) and magnetoencephalography (MEG). Neuronal activity also results in localized changes in blood flow, which can be measured using functional magnetic resonance
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imaging (fMRI). fMRI provides direct localization of brain activation during cognition, but with poor temporal resolution. Conversely, EEG/MEG provide millisecond accuracy, but the location in the brain where they arise is hard to determine. The first aim of this grant is to combine the spatial resolution of fMRI with the temporal resolution of BEG/MEG to produce spatiotemporal maps of brain activation. The accuracy of these maps will be validated using EEG recordings from directly within the brain (conducted in order to localize the seizure focus in patients with pharmacoresistant epilepsy). Maps will be made for a variety of processing stages used in perception, memory, language, and action, including those associated with the eventrelated potential (ERP) components N2, P3a, P3b, P 170, N400, RP, ERN, ELAN, P600 and CNV. These maps will help reveal where and when brain areas are active during thought. The second aim of the grant is to better understand what kind of neuronal activity these maps represent. Linear microelectrode arrays will be used in the same subjects and tasks to estimate population synaptic currents (neuronal inputs) and neuronal firing (outputs) in different cortical layers. The ?activation? found in the whole-brain studies will thus be characterized as excitation vs inhibition, input vs output, and top-down vs bottom-up interactions. The proposed studies should provide insights into how the different brain imaging modalities view functional brain activity, and how they may be integrated in order to trace the passage of activation through the thinking human brain. This technique should also be useful for localizing pathological activity. In addition, the proposed studies may help in the construction of functional neural models for cognition. Such models are necessary to understand how cognition is disrupted in neuropsychiatric disorders. Finally, more complete knowledge regarding the generators of cognitive potentials should greatly increase their value as functional tests for specific brain systems in patients with neurological or psychiatric disease. 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 peri-natal unilateral brain lesions in the middle cerebral artery distribution from stroke or hemorrhage, and matched controls, will receive neuropsychological,
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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 •
Project Title: NEUROIMAGING LANGUAGE IN THE NORMALLY DEVELOPING BRAIN Principal Investigator & Institution: Dapretto, Mirella; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: The proposed study will use both functional and structural magnetic resonance imaging (fMRI and MRI) to begin to delineate the neural systems associated with the emergency of high-level linguistic functions in normally developing children, aged 7 to 14. More specifically, this pilot project has two main goals. First, we will use fMRI to qualify and quantify developmental changes in the pattern or cortical activity (in terms of localization, magnitude, spatial extent, and inter-regional connectivity) associated with language processing at the level of closed formal linguistic systems (i.e., phonology, semantics, syntax), as well as with language processing in its broader communicative context (i.e., prosody, discourse, pragmatics). Second, we will relate the developmental changes in the neural networks subserving language processing observed with fMRI, to age-related changes in brain morphometry (in terms of regional volume, gray and white matter concentrations, shape, and asymmetry) as assessed by structural MRI. The findings of the proposed cross-sectional study will form the cornerstone of a longitudinal research program aimed at fully elucidating the neural developments associated with the emergence of mature linguistic competence in normally developing children. Furthermore, these developmental findings will provide normative data for evaluating the patterns of brain dysfunction associated with the linguistic and communicative impairments observed in a variety of developmental disorders (e.g., dyslexia, autism, early-onset schizophrenia). By delineating the relationship among language processing, brain function, and brain structure, this study will begin to bridge the informational gap on the neural basis of language in the normally developing brain. Moreover, the proposed project will highlight how an integrated nature of brain-behavior interactions. At a theoretical level, a deeper understanding of the neural basis of language processing, particularly of how it changes and develops as a function of learning, will enlighten our thinking about the origin and modularity of language. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEUROTROPHIC FACTOR GENE THERAPY FOR BRAIN INJURY Principal Investigator & Institution: Kozlowski, Dorothy A.; Biological Sciences; De Paul University 1 E Jackson Blvd Chicago, Il 60604
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Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2005 Summary: (provided by applicant): The main objective of this application is to begin to develop a new therapeutic approach for traumatic brain injury - neurotrophic factor gene therapy with adenoviral vectors. While great strides have been made in the management of traumatic brain injury, no treatments exist which prevent and minimize neuronal loss following brain injury, the main cause of long-term disabilities in headinjured patients. Animal studies have revealed many potential therapeutic agents for brain injury, however, these compounds are administered in a global manner, producing possible side effects detrimental to the maintenance of the trauma patient. Gene therapy is a way in which to chronically present these therapeutic agents to a specific area of the brain, using genetically engineered viruses, without major global side effects. In order to develop gene therapy for traumatic brain injury, two factors must be addressed: 1) the production of novel genes in injured brain tissue, induced by an adenoviral vector, must be demonstrated, measured, and optimized in the rat and 2) the neuroprotective ability of a therapeutic gene in an animal model of brain injury must be demonstrated. These are the focus of the specific aims of this proposal. They are: 1) to determine the optimal viral vector concentration that will provide the greatest number of infected brain cells with minimal amounts of neural toxicity when injected into the normal and injured cortex, 2) to examine the neuroprotective effects of virally mediated glial cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) expression in the cortex following a cortical contusion, and 3) to explore whether a virally mediated neurotrophic factor (either GDNF or BDNF) injected after a cortical contusion can rescue and protect neurons and behavioral function. In addition, this proposal will measure transgene expression in compromised cortical tissue. Together, these studies will develop a framework for further investigations of gene therapy for traumatic brain injury. Future questions will address the therapeutic windows of opportunity, long-term behavioral and cognitive function, and the optimization of new therapeutic genes and viral vectors for traumatic brain injury. In addition, these studies will provide a comprehensive research-training program for undergraduates in the fields of neurobiology, molecular biology, and animal behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE & IMMUNOPATHOGENESIS OF CRYPTOCOCCAL MENINGITIS Principal Investigator & Institution: Sopori, Mohan L.; Senior Scientist and Director; Lovelace Biomedical & Environmental Res Environmental Research Inst Albuquerque, Nm 87185 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Opportunistic infections of the central nervous system are common complication in acquired immunodeficiency syndrome (AIDS) patients. Cryptococcus neoformans (Cne) is an encapsulated yeast that causes often fatal cryptococcal meningoencephalitis (CM) in 7-30% of AIDS patients. While highly active anti-retroviral therapy has successfully decreased the incidence of many opportunistic infections, it is less effective in decreasing the incidence of opportunistic fungal infections in advanced AIDS patients. The host's response to Cne is a complex interplay between the innate and adaptive immunities. In animal models, the inability to increase the brain levels of proinflammatory cytokines or promote leukocyte migration into the brain is typically associated with lethal CM. Thus, "proinflammatory" responses are required to contain Cne infection in the central nervous system. Epidemiological studies
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show that cigarette smoking is a significant risk factor in cryptococcosis and other opportunistic fungal infections, and >85% of AIDS patients with cryptococcosis are cigarette smokers. However, the mechanism by which smoking affects the pathogenesis of Cne is totally unknown. We have demonstrated that cigarette smoke suppresses the immune system, and nicotine (NT) is a major immunosuppressive component of cigarette smoke that causes T cell anergy and inhibits the inflammatory responses. Our preliminary studies suggest that chronic NT treatment inhibits chemokinesis/chemotaxis and the migration of leukocytes to the site of inflammation, decreases brain IL-1beta expression in response to an inflammatory stimuli such as turpentine and Cne, and promotes growth and early dissemination of Cne into the brain. Therefore, we hypothesize that cigarette smoke/NT modulates both the innate and adaptive immune responses to Cne, thus facilitating its dissemination to the brain and the development CM. To test this hypothesis and to identify mechanism(s) by which NT facilitates brain infection by Cne, the following studies are proposed: 1. To investigate the effects of NT on Cne-induced innate immunity, including the expression of proinflammatory cytokines/chemokines in the brain and the response of leukocytes to cytokines/chemokines that are affected by Cne, to establish the kinetics of Cne and leukocyte migration into the brain and the development of CM, and to examine the effects of NT on the Cne-induced fever response. 2. To ascertain the effects on the adaptive immune responses including generation of anti-Cne antibodies, proliferative and delayed-type hypersensitivity responses to cryptococcal antigens, and generation of cytotoxic T cells to immunodominant epitopes of Cne proteins, as well as to evaluate the protective function of T cells that migrate into the brain after Cne infection. 3. To investigate the mechanisms by which NT suppresses the migration of leukocytes toward the site of infection. These studies, we believe, will delineate the mechanism(s) by which smoking/NT encourages dissemination of Cne and, perhaps, other fungal infections into the brain of AIDS patients, and identify potential therapeutic targets for treatment of CM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE AND BRAIN DEVELOPMENT Principal Investigator & Institution: Chen, Wei-Jung A.; Human Anatomy and Medical Neurobiology; Texas A&M University Health Science Ctr College Station, Tx 778433578 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: The overall purpose of this proposal is to evaluate developmental nicotineinduced neurotoxicity. Despite the Surgeon General's warning concerning the harmful effects of smoking on the developing fetus, there is still a disturbing number of pregnant women who smoke during pregnancy. This proposal will utilize a rat model system to examine how and to what extent nicotine affects the developing brain. The proposal will test several hypotheses that are categorized into three Specific Aims. Specific Aim number 1 will test two hypotheses: 1) that nicotine exposure during all three trimesters equivalent will result in region-specific reductions in neuronal numbers in two important brain regions (hippocampus and cerebellum) in neonates and young adults; and 2) that the long-term brain deficits resulting from developmental nicotine exposure will be manifested through and correlated with specific behavioral impairments, spatial learning and parallel bars tasks, respectively. The exposure regimen used in Specific Aim number 1 is especially clinically relevant, since most pregnant women who smoke do so throughout pregnancy. Specific Aim number 2 will test two hypotheses: 1) that nicotine exposure during the third trimester equivalent (the brain growth spurt period) will lead to more severe neuronal loss than exposure restricted to first or first and
Studies 51
second trimesters equivalent, and 2) that the cessation of nicotine exposure gestation will be beneficial to the developing brain. Specific Aim number 2 is important in addressing the questions regarding temporal vulnerability and the potential interaction between brain-regional specificity and temporal factors in mediating differential effects on nicotine-induced neuronal loss. Specific Aim number 3 will begin to address the question of mechanisms underlying nicotine-induced neuronal loss by testing the hypothesis that the application of specific neurotrophic factors (brain-derived neurotrophic factor [BDNF] and glial-derived neurotrophic factor [GDNF]) will attenuate nicotine-induced neuronal loss in an organotypic explant culture system. Specific Aim number 3 is the fist step to identify the involvement of specific neurotrophic factors as one of the underlying mechanisms for developmental nicotineinduced neuronal loss. The proposal will incorporate innovative in vivo and in vitro approaches to evaluate nicotine's toxicity during brain development, and many of the experimental techniques (artificial-rearing for third trimester equivalent exposure, 3-D stereological cell counting, organotypic explant culture system) proposed to be implemented in this proposal are novel to developmental nicotine research. The proposed studies will contribute to and broaden our knowledge of the harmful consequences from maternal smoking during pregnancy, provide a better understanding of the potential risk that may influence the severity of nicotine-induced brain deficits during different stages of development, and lead to a focus on mechanistic issues regarding developmental nicotine-induced neurotoxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL TREATMENT APPROACHES FOR PEDIATRIC BRAIN TUMORS Principal Investigator & Institution: Pollack, Ian F.; Walter Dandy Professor of Neurosurgery; Neurological Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Brain tumors are the leading cause of cancer-related deaths among children. Despite considerable efforts to refine the treatment of these tumors, the overall prognosis of affected patients has improved minimally during the last decade. To improve outcome, coordinated efforts are required to evaluate new treatment approaches in parallel with correlative studies of tumor biology to identify novel therapeutic strategies. Our proposal for inclusion in the Pediatric Brain Tumor Clinical Trials Consortium (PBTCTC) reflects our institutional commitment to contribute to such studies. To accomplish the goal of developing more effective therapies for children with brain tumors, we propose to: 1) share institutional expertise with clinicians and researchers at other consortium centers; 2) design and conduct innovative pilot, phase I, and phase II clinical trials for children with brain tumors, and provide adequate patient populations for their timely completion; and 3) share brain tumor specimens and other data that will be useful in the conduct of clinical, pharmacological, and correlative laboratory and imaging studies. This proposal describes the extensive neuro-oncology activities at the Children s Hospital of Pittsburgh (CHP) and the University of Pittsburgh Medical Center (UPMC). Our group has been at the forefront of applying stereotactic radiosurgical approaches to the treatment of brain tumors and in translating novel preclinical therapeutic strategies to the clinical arena. The broad-based biological and molecular therapeutics efforts for brain tumors reflect the depth of institutional resources within the University of Pittsburgh Cancer Institute (UPCI). Promising approaches that are currently being translated to clinical studies that could be adopted
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Brain
by the Consortium include cytokine-based glioma vaccines and novel signal transduction inhibitors. Innovative imaging modalities for evaluating disease response are provided by institutional PET and MR Research Centers. Our group is also leading multi-institutional molecular marker studies on childhood high-grade gliomas, which could potentially be incorporated in PBTCTC studies. CHP, UPMC, and UPCI will provide essential support for consortium-related clinical trials through such facilities as the General Clinical Research Center, the Tumor Tissue Bank, the Pediatric Brain Tumor Registry, the Center for Image-Guided Neurosurgery, and the Imaging Core facilities. In addition to the above, our institution is a regional and national referral center for childhood brain tumors, with approximately 80 new or recurrent brain tumor patients per year, and 20 to 25 children who are entered on institutional pilot or cooperative phase I or phase II studies. With these clinical and scientific resources, our institution is well poised to collaborate with other members of the PBTCTC to rapidly evaluate new treatments by enrolling patients in studies of the Consortium and to develop promising new therapeutic strategies through translational laboratory studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHOPHYSIOLOGY OF NEUROIMMUNE COMMUNICATION Principal Investigator & Institution: Quan, Ning; Oral Biology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 15-AUG-2001; Project End 31-JUL-2004 Summary: Two neuroimmune communication pathways, the ascending vagus nerve and cells of the blood-brain barrier, have recently been identified to relay signals of peripheral infection to the brain by inducing the expression of IL-1 and TNF-alpha in the central nervous system (CNS). Chronic expression of IL-1 and TNF-alpha in the CNS, however, has been shown to contribute to the pathogenesis of many CNS diseases including chronic fatigue syndrome, AIDS dementia, and various neurodegenerative diseases. Whether chronic peripheral infection can cause CNS diseases by driving chronic production of IL-1 and TNF-alpha in the brain has not been studied. In a recently created infectious disease model, striking patterns of neuropathological changes were found in the brain without infiltration of either the pathogen or peripheral inflammatory cells into the brain parenchyma. The neuropathological changes were closely associated with the chronic expression of IL-1 and TNF-alpha in the brain. These pathological changes was enhanced by blocking the inhibitory mechanisms for IL-1 and TNF-alpha expression and reduced by intracerebral administration of specific antagonists of IL-1 and TNF-alpha. Therefore, it is hypothesized that induction of IL-1 and TNF-alpha in the brain by chronic peripheral infection is a mechanism for the pathogenesis of CNS diseases. Using this infectious disease model, the following specific aims are proposed to test this hypothesis: 1) Determine and characterize the neurotoxic effects mediated by chronic CNS production of IL-1 and/or TNF-alpha; and 2) Determine the role of glucocorticoids and prostaglandins in regulating the chronic expression of IL-1 and TNF-alpha in the brain. Specific Aim 1 is designed to characterize the neurotoxic effects attributable to the chronic expression of IL-1 and/or TNF-alpha in the brain induced by neuroimmune activation. In Aim 2, whether glucocorticoids and prostaglandins importantly controls the levels of chronic expression IL-1 and TNF-alpha and the manifestation of related neurotoxic effects in the brain will be determined. Glucocorticoids and prostaglandins are the two major feedback inhibitory regulators for IL-1 and TNF-alpha expression. Finally, the use of anti-inflammatory drugs in modulating the neurotoxic effects of chronic CNS production of IL-1 and TNF- alpha will also be evaluated in Specific Aim 2. This study will attempt to elucidate the
Studies 53
mechanisms of neurotoxicity caused by chronic activation of the pathways for neuroimmune communication. The results will also provide critical information regarding the use of anti-inflammatory drugs for the treatment of CNS diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PEDIATRIC BRAIN TUMOR CLINICAL TRIAL CONSORTIUM Principal Investigator & Institution: Prados, Michael D.; Professor; Neurological Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: The University of California San Francisco (UCSF) has a long history of commitment to the treatment of children with brain tumors. Clinical and laboratory investigators in the Brain Tumor Research Center (BTRC) have over 25 years of experience in funded research of the biology and treatment of these diseases. Brain tumors are now the leading cause of cancer-related death in children. Currently available treatment for tumors such as brainstem glioma and malignant astrocytoma will not effectively control tumor growth for many of these children. In other types of brain tumors, treatment may control disease but will cause significant toxicity such as developmental and growth delay. For children who progress following initial therapy, few effective alternatives exist. Substantial gains for these children will only come about by an understanding of the biology of these diverse tumors, and the use of innovative treatment strategies based upon these data. Novel treatment approaches will require the expertise of physicians and researchers at institutions with the unique talents and resources available to employ these technologies. Clinical collaborations will be needed to efficiently conduct phase-I and II studies because of the small numbers of patients seen at various medical centers. UCSF has the physician talent, patient population, treatment and diagnostic resources, and Institutional commitment to collaborate with and achieve the goals of a Pediatric Brain Tumor Clinical Trials Consortium (PBTCTC). We plan to utilize state of the art neuroimaging to diagnosis and monitor children with brain tumors. Advanced neurosurgical navigational techniques will be used for maximal tumor resection. Specialized methods of radiation therapy and unique drug therapy will be available, including but not limited to interstitial brachytherapy, radiosurgery, and experimental chemotherapy and gene therapy. Scientists in the BTRC will continue to use human tumor tissue to study the biology of childhood brain tumors, with the goal to translate this biologic information into newer, non-toxic, disease-specific treatments. UCSF will collaborate with the PBTCTC to achieve its Consortium goals, and contribute to its scientific agenda, taking a leadership role in study concept proposals and biologic studies. The aim of these treatment approaches is to increase disease-free and overall survival in children with brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: PEDIATRIC BRAIN TUMOR CLINICAL TRIALS CONSORTIUM Principal Investigator & Institution: Geyer, J R.; Children's Hospital and Reg Medical Ctr Box 5371, 4800 Sand Point Way Ne, Ms 6D-1 Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Therapeutic advances in pediatric neurooncology over the last two decades have been limited. New clinical research opportunities exist including novel approaches in the areas of cytotoxic drugs, radiation therapy and immunotherapy which require evaluation. No single institution accrues sufficient numbers of children with brain
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tumors to conduct trials of such new approaches in a timely fashion, and only a limited number of institutions have the sophisticated equipment and skills required to implement and evaluate such therapies. Therefore, to expeditiously evaluate innovative therapies, a Pediatric Brain Tumor Clinical Trials Consortium (PBTCTC) is required. The University of Washington Pediatric Neuro-Oncology Program brings the requisite personnel, resources and research expertise, discussed in this application, to contribute substantially to the goals of the PBTCTC. The Pediatric Neuro-Oncology Program was established in 1980 and was thus one of the initial programs recognizing the need for multidisciplinary care of children with brain tumors. The program includes a broad range of clinical and laboratory investigators. The goal of this application is to describe the efforts of this broad multidisciplinary group on issues relevant to improving the outcome of children with brain tumors in concert with PBTCC. In particular, our extensive experience with leadership in national cooperative clinical trials in pediatric brain tumor therapy, together with leading programs in radiation therapy, neuroimaging, neurosurgery, and neuropathology provides the critical mass and expertise required to effectively contribute to clinical evaluation of innovative brain tumor treatments. Our laboratory-based investigations of the molecular aspects of pediatric and adult brain tumors as well as a unique institutional program aimed at developing targeted therapy for malignancies also have the potential to contribute to the development of novel approaches to brain tumor therapy, in concert with the PBTCTC. Specifically we propose to: 1) effectively contribute to the clinical trials program of the PBTCTC; 2) provide laboratory-based analysis of molecular aspects of brain tumors required for the development of novel prognostic and therapeutic approaches; 3) develop novel methods of imaging brain tumors, including methods for rapid assessment of response to therapy; 4) develop novel targeted therapies for brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PEDIATRIC BRAIN TUMOR CONSORTIUM--CHOP MEMBERSHIP Principal Investigator & Institution: Phillips, Peter C.; Professor of Neurology, Oncology and Pe; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: The overall objective of this proposal is to improve therapeutic outcomes for children with primary brain tumors. This will be accomplished by Phase I and II clinical evaluations of promising new therapeutic drugs, delivery technologies, biological therapies, and radiation treatment strategies conducted by a newly-established Pediatric Brain Tumor Clinical Trials Consortium (PBTC). This consortium will combine the experience and resources of eight outstanding medical institutions in an organizational structure designed to facilitate a rapid and successful study of new therapies for childhood brain tumors. A second objective is to utilize the consortium mechanism to share brain tumor specimens as well as other clinical and laboratory data and to conduct research pertaining to neuroimaging, pharmacology, and the biology of childhood brain tumors. To achieve these objectives, the PBTC must rely on the special strengths and resources of each participating institution. Accordingly, we propose the following Specific Aims to advance PBTC goals: Aim 1. to participate as a Member Institution in PBTC clinical trials, laboratory, and neuroimaging studies; Aim 2. to develop new experimental therapies for CNS tumors in children and propose these strategies for phase I/II clinical trials by the PTBC; Aim 3. to propose and facilitate the development and study of intrathecal therapies for the prophylaxis or treatment of childhood CNS tumors; and Aim 4. to propose and develop neuroimaging studies of
Studies 55
regional tumor pharmacokinetics and brain tumor biology for participation by PBTC members. The Children's Hospital of Philadelphia (CHOP) has: (1) an outstanding multi- disciplinary clinical team of internationally-recognized leaders in pediatric neurooncology, radiation oncology, neurosurgery, neuro-radiology, pharmacology, and new drug development; (2) a large number of patients with childhood primary brain tumors available for study; (3) state-of-the-art facilities for diagnostic and research neuroimaging (MRI, MRSpectroscopy, PET, SPECT), neurosurgery (computer imageguided surgery), and radiation therapy (stereotaxic radiosurgery, Gamma Knife, brachytherapy); (4) an NIH-funded brain tumor bank which stores brain tumor biopsies from CHOP, NYU, and Beth Israel (NYC) (5) internationally-recognized expertise in neuro-pathology; (6) extensive institutional resources for biostatistics and clinical trial data management and a reputation for excellence in clinical care and research; (7) experience in the organization and coordination of multi-institutional clinical trials; and (8) a large number of high quality, clinically relevant, peer reviewed and NIH funded brain tumor research studies. These programmatic and institutional strengths support the feasibility of our specific aims, are responsive to the criteria for consortium participation specified by the RFA, and substantially enhance the likelihood that the PBTC will achieve its long-term goals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PEDIATRIC BRAIN TUMOR RESEARCH CENTER Principal Investigator & Institution: Blaney, Susan; Assistant Professor; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: The Texas Children s Cancer Center(TCCC) Brain Tumor Program (BTP) is a multidisciplinary, highly integrated program of clinical and laboratory research dedicated to improving survival rates of children with central nervous system(CNS) tumors. The Program is one of the largest of its kind in the United States, each year evaluating more than 50 children. The BTP is composed of clinical and laboratory investigators whose research encompasses the entire spectrum of pediatric neurooncology. They are exceptionally qualified to design, conduct, and monitor clinical trials for children with brain tumors. In national cooperative group clinical research and in numerous studies sponsored by the National Cancer Institute and private industry, the BTP has led new approaches to the treatment of infants with brain tumors, introduced new agents against brain tumors through Phase I and Phase II clinical trials, and pioneered the use of highly conformal radiation therapy (RT) to decrease toxicity to normal structures surrounding brain tumors. The BTP works closely with the Gene Therapy Program, Molecular Neuro-Oncology Program, and Clinical Pharmacology Group, all within TCCC, to translate advances in laboratory and pre-clinical science to treatment of children with brain tumors. Examples of ongoing clinical trials include those seeking to determine the impact of intrathecal chemotherapy and highly conformal radiation therapy on the survival of infants with brain tumors, the activity of various new agents against leptomeningeal disease, the activity of various agents against malignant glioma, the use of bone marrow transplant for recurrent medulloblastoma, and the efficacy of gene therapy for children with refractory brain tumors. The BTP utilizes the most modern diagnostic neuroimaging modalities and innovative technologies such as functional MR, MR spectroscopy, and 18F imaging. Its neurosurgeons utilize state- of-the-art operating microscopes and guidance systems. RT is delivered through the most technically advanced conformal system. The BTP neuropathologists have complete diagnostic capabilities to classify tumors according to
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WHO criteria. The BTP maintains a storage bank of tumor specimens for institutional and cooperative group correlative studies. The BTP has an innovative molecular neurooncology program that uses high-throughput technologies to study differential gene expression in pediatric brain tumors. BTP investigators are committed to utilizing their resources for the Pediatric Brain Tumor Clinical Trial Consortium (PBTCTC) studies. The TCCC BTP serves a culturally and ethnically diverse population. It receives considerable research support from Texas Children s Hospital, the largest children s hospital in the United States and from Baylor College of Medicine, one of the top ten medical schools in the country. The unique expertise of the TCCC BTP make it ideally suited to be a Participating Member of the PBTCTC. It offers leadership in the development of new agents, in new uses of sophisticated radiotherapy, and in the application of new approaches to brain tumor therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PERSISTENT TRAUMATIC BRAIN INJURY
NEUROPSCHIATRIC
DISORDERS
IN
MILD
Principal Investigator & Institution: Strickland, Tony L.; Professor; Charles R. Drew University of Med & Sci 1621 E 120Th St Los Angeles, Ca 90059 Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 31-JUL-2005 Summary: The primary goal of this project is to determine if the presence of substantial abuse is associated with differential patterns of sustained neuropsychiatric disorders in mild traumatic brain injury (MTBI) patients. Traumatic brain injury (TBI) represents a major pubic health concern in the United States and worldwide. Neurocognitive and neuropsychiatric sequelae secondary to MTBI usually resolve within 90 days, however, for a significant minority of patients symptoms persist and can be severe. Incidence estimates of TBI based on U.S. studies are about 200 per 100,000 per year, thus yielding approximately 470,000 cases of brain injury annually. The most common causes of TBI include motor vehicle accidents, falls, assaults, firearm injuries, and sports. The majority of TBI is classified as mild. Toxicology studies of TBI patients reveal that they were often under the influence at the time of their acquired brain traumas. However, importantly, the relative contribution of acquired brain trauma versus substance-induced persistent neuropsychiatric pathology is incompletely understood. Understanding differential patterns of neuropsychiatric outcomes in minority patients is particularly important, because of the increased prevalence of intentional and unintentional injuries in the groups. Due to a dramatic surge in alcohol and other drugs in the past decade, there is a pressing need to study the associated neuropsychiatric aspects, particularly when substance abuse is combined with acquired brain trauma. It is now well-established that substance abuse, especially the abuse of alcohol and stimulants, can lead to hypertensive encephalopathy and ischemic brain hemorrhage, and that depression and other neuropsychiatric symptomatology are common (Bigler, 2001; Pulse Watch, 2000; Strickland, et al., 1998). Despite that alcohol and stimulants can induce significant cerebral pathology, little is known about differences in the magnitude of neuropsychiatric impairment, duration of symptoms, or the specific brain region(s) adversely impacted when substance abuse co-occurs with MTBI. Existing information is even less complete regarding differences in neurobehavioral outcomes secondary to ethnic, cultural, and socioeconomic influences. To strengthen our understanding of differences in neuropsychiatric and quality of life (QOL) outcomes in MTBI patients, this proposed project utilizes a five-year, between- and within-subject, repeated-measures design to investigate these parameters in a sample of 200 subjects. Fifty MTBI subjects positive for substance abuse will be evaluated within thirty days of injury (Time 1), and
Studies 57
three months later (Time 2). Fifty non-MBTI and non-substance abusing subjects will be evaluated (Time 1), and three months later (Time 2). The proposed study has the following specific aims: 1. To determine if severity and duration of neuropsychiatric impairment in MTBI is associated with the presence of substance abuse. 2. To compare severity of neuropsychiatric and neuropsychological functioning between MTBI and substance abuse subjects over time (three months after initial assessment). 3. To identify and describe factors that are associated with improvement in neuropsychiatric symptoms via evaluation of primary or secondary analyses (such as interventions, demographics, or socioeconomics). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHOTOPERIODIC CONTROL OF OBESITY Principal Investigator & Institution: Bartness, Timothy J.; Professor; Biology; Georgia State University University Plaza Atlanta, Ga 30303 Timing: Fiscal Year 2002; Project Start 01-SEP-1984; Project End 31-JUL-2004 Summary: (applicant's abstract): Obesity is a disease of literally and figuratively enormous proportions. A model of naturally occurring obesity, photoperiod-induced seasonal obesity in Siberian hamsters, was chosen for study. Siberian hamsters are naturally obese when housed in long "summer-like" days. This obesity gradually develops and is expressed fully when the animals are adults. When Siberian hamsters are exposed to short days, as in fall/winter, they lose body fat. With subsequent increasing day lengths, as occurs in spring/summer, they regain their body fat; thus, the obesity is reversible, unlike most of the animal models of human obesity. It seems that a better understanding of the fundamental processes involved in the development and reversal of obesity might result from studying this natural cycle of body fat because, in these animals, it is seasonally advantageous for them to be obese at one time of year and lean at another time of the year. Two aspects of the control of fatness are the focus of this grant proposal: 1) the connections of the brain to body fat by the sympathetic nervous system, and 2) the regulation of total body fat as revealed by the compensatory increases in fat that are triggered after surgically-produced decreases in fatness (lipectomy). Attempts will be made to identify a brain controller of the number of fat cells in the body, including the chemical means by which the brain communicates with fat depots to increase or decrease fat cell number. Further attempts will be made to identify how the brain "knows" when body fat is decreased after we remove some of it experimentally (lipectomy). Tests will be done directly to one brain area, the paraventricular nucleus, to determine whether it is involved in the control of the shortday-induced decreases in fatness, as seems to be suggested by the neural circuitry connecting this brain area to body fat. Finally, a new strategy/tactic will be used to identify the chemicals in the brain that are part of the neural circuit connecting the brain to fat and that may be involved in the reversal from obese to the lean state. This multidisciplinary approach should provide new information about the importance of the control of body fat by the brain. In addition, these findings should provide insight into the fundamental processes involved in the development, maintenance, and especially the reversal of obesity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHYSIOLOGIC RESPONSE TO OSMOTIC THERAPY IN BRAIN EDEMA Principal Investigator & Institution: Diringer, Michael N.; Professor; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130
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Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-MAY-2008 Summary: Acute brain injury is complicated by mass effect, a major cause of secondary injury by critically reducing cerebral perfusion pressure or producing tissue shifts which can lead to herniation. While the etiology and mechanisms responsible for this mass effect may differ considerably depending on the clinical condition, treatment options are limited. Traditionally osmotic agents have been the mainstay of medical treatment employing mannitol and recently hypertonic saline solutions. Despite numerous investigations and mannitors ubiquitous use, considerable controversy persists regarding its 1) mechanism of action (whether it reduces cerebral blood volume [CBV] or brain water), 2) differential effect in normal and abnormal brain, 3) effect on cerebral blood flow (CBF) and oxygen metabolism (CMRO2), 4) loss of efficacy over time, and 5) uptake into injured brain, which could lead to "rebound edema." In part because of some of these concerns, hypertonic saline (HS) has been introduced as an alternative agent; however, its physiologic effect and clinical efficacy compared to mannitol is unknown. Optimal use of these osmotic agents to treat brain swelling requires a detailed knowledge of their physiological effects in human subjects under the clinical conditions in which they are used. To this end, we will carry out the following Specific Aims: 1) measure the effect of a single bolus of mannitol or HS (23.4%) on regional CBF, CMRO2, CBV in patients with traumatic brain injury (TBI) and large hemispheric infarctions (LHI). We will measure CBF, CBV and CMRO2 using PET before and after a bolus of equi-osmolar (5.49 mOsm/kg ) doses of mannitol (1.0 gm/kg ) or HS (0.686 ml/kg), in 10 patients each with LHI and midline shift and 10 patients each with severe TBI; 2) measure the effect of a single bolus of mannitol or HS (23.4%) on regional brain volume in patients with LHI. In 20 patients we will measure regional change in brain volume using MRI before and after the same doses of mannitol and HS used in Aim 1. TBI patients will not be studied due to the MRI incompatibility of ICP monitors; 3) measure the extent that mannitol crosses the blood-brain-barrier in patients with TBI and LHI receiving osmotic therapy. In 15 patients with each entity we will measure blood: brain permeability of mannitol using PET and carbon-11 labeled-mannitol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF INTERLEUKIN-6 IN THE AGING BRAIN Principal Investigator & Institution: Johnson, Rodney W.; Professor; Animal Sciences; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: (applicant's abstract): The expression and action of inflammatory cytokine molecules in the brain requires tight regulation since they alter cognitive and motivational systems and if over-expressed can be neurotoxic. Preliminary data presented in this application indicate that microglia cultured from brain of aged mice spontaneously secrete copious amounts of the inflammatory cytokine, interleukin-6 (IL6). Consequently, a positive correlation between age and IL-6 concentration in brain has been found, even in healthy mice. We believe that chronic over-expression of the IL-6 gene in the brain of the elderly may establish a state that is permissive to the onset of neurodegenerative disease and be causally related to anorexia and impaired memory and learning. Unfortunately, little to nothing is known about how aging affects IL-6 gene expression in the brain, which is the focus of this proposal. Here, several approaches are proposed to (1) define the expression of IL-6 in the brain of aged mice, (2) determine the effects of age on the transcription factors that regulate IL-6 gene expression in brain and in glial cells; (3) explore the ability to regulate IL-6 gene
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expression in the brain of aged mice with supplemental dehydroepiandrosterone (DHEA), and (4) describe the effects of DHEA on the transcription factors regulating the IL-6 gene. Specifically, we will employ immunohistochemistry and in situ hybridization to map IL-6 expression in aged mouse brain, and two-color flow cytometry to evaluate the proportion of astrocytes and microglia cultured from brain of neonate, adult, and aged mice expressing IL-6. We will determine if the increase in IL-6 production in aged brain is due to an increase in active Nuclear Factor-KB or a decrease in Recombinant Signal Sequence Binding-Protein JK, which has been recently shown to inhibit spontaneous IL-6 production by occupying the IL-6-KB site in the IL-6 promoter/enhancer region. Moreover, the critical possibility that the age-related change(s) in transcription factors regulating IL-6 gene expression in the brain is due to the decline in DHEA, which occurs with age, will be tested. These novel studies will provide needed information to better understand, treat, or prevent the neuropathophysiological manifestations of old age. There are strong preliminary data supporting each of the objectives and all of the techniques needed to successfully complete these studies in mice have been developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNDROME
RESPONSE
TO
IRON
TREATMENT
FOR
RESTLESS
LEG
Principal Investigator & Institution: Earley, Christopher J.; Associate Professor; Neurology and Neurosurgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: Restless Legs Syndrome (RLS) is a common, dopamine- responsive, sensorymotor disorder whose symptoms predominant at night and often lead to significant sleep loss and changes in one's quality of life. Altered CNS iron metabolism may play a pivotal role in RLS. Decreasing serum ferritin has been shown to correlate with increasing RLS symptoms. RLS patients have been found to have decreased CSF ferritin and increased CSF transferrin, which suggests a decrease in brain iron stores. Finally, open-labeled, non-controlled iron therapy has been effective in treating some patients with RLS. We have developed preliminary data strongly supporting our basic model that RLS results from altered dopaminergic mechanisms, which are precipitated by a relative or absolute reduction of iron in the brain. We have also developed data that indicate there may be a decrease in the normal transfer of iron from serum to brain tissue possibly related to abnormal transport across the blood brain barrier. This indicates that the use of IV iron might at least partly correct the brain iron deficits in RLS. We will, therefore, test the hypothesis that: (1) IV iron therapy will improve the CNS iron status. (2) IV iron therapy will improve symptoms in RLS patients. (3) Improvements in CNS iron status with IV iron treatment will parallel improvements measures of RLS. And, (4) the response to IV iron therapy differs based upon age at onset of RLS symptoms. A 1000 mg of iron or placebo will be given as a single intravenous dose to RLS patients in a randomized, double-blind trial. It is anticipated that a single IV treatment will provide relief of RLS symptoms for an extended period of time (2-12 months). Post-infusion changes in CNS iron status will be evaluated using CSF measurements of ferritin and other iron- related proteins and MRI measurements of brain iron stores. Post-infusion changes in RLS will be assessed using standard subjective (Diary; rating scale) and objective (PSG, SIT, Leg Activity Meters) measures of clinical status. CSF and serum iron values, MRI measures of brain iron and full clinical evaluations with sleep and immobilization tests will be obtained prior to treatment, two
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weeks after treatment and again at 12 months later or when symptoms return. Clinical ratings, Leg Activity Meter recordings and serum ferritin will be obtained monthly after treatment. CSF ferritin changes will be compared to those predicted from our prior studies. Symptoms will be correlated with CSF ferritin and MRI iron values. Our studies demonstrated possible differences in response to iron for early-and late-onset RLS. So treatment response based on the age of symptom onset will be evaluated separately. An expected finding that IV iron reduces the brain iron insufficiency and dramatically reduces the RLS symptoms strongly supports our model of RLS caused by brain iron insufficiency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SELECTIVE ATTENTION AND CONTROL MECHANISMS IN THE BRAIN Principal Investigator & Institution: Hopfinger, Joseph B.; Psychology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Accurate perception and action depend on the ability of brain attention systems to focus on the most relevant subset of stimuli in the environment. Attention can be directed in a voluntary (top-down) manner, or it may be captured reflexively either by salient sensory stimuli (sensory-driven reflexive attention) or by implicit memories (memory-driven reflexive attention). The experiments proposed here will test current theories and neural models of attentional control by investigating the brain mechanisms supporting each of these types of attention (voluntary, sensorydriven, and memory-driven). Since the momentary focus of attention is normally determined by the interplay between voluntary and reflexive systems, a further objective of these studies is to elucidate the interactions between these attention systems in the brain.In these experiments, event-related brain potentials (ERPs) will be recorded to provide a measure of the timing of neural activity relating to the control of attention and its subsequent effects on visual processing. Functional magnetic resonance imaging (fMRI) will be used to identify the brain regions involved in these attention mechanisms. In these studies: (1) We will investigate the neural mechanisms and temporal dynamics involved in voluntarily shifting the focus of attention. (2) We will directly contrast voluntary attention and sensory-driven reflexive attention, testing both the potential overlap in neural control systems as well as the differential effects of this control on subsequent visual processing. (3) We will investigate the combined versus competitive effects of voluntary and sensory-driven reflexive attention on visual cortical processing. (4) We will investigate the neural mechanisms of "attentional control settings" (ACS) -- task-dependent non-spatial strategic processes that have been shown to modulate the behavioral effects of reflexive attentional orienting. (5) We will test the hypothesis that these ACS share a common pool of mental resources with voluntary attention and working memory, and that under high levels of cognitive load, ACS will not modulate the effects of reflexive attention. (6) We will test whether reflexive orienting driven by implicitly learned predictive relationships modulates subsequent processing as early as does sensory-driven reflexive attention. (7) Finally, we will investigate the neural mechanisms by which memory, specifically item familiarity, reflexively captures attention. We will test the extent to which this type of attention relies upon brain mechanisms thought to underlie voluntary or sensory-driven reflexive attention. Voluntary and reflexive attention mechanisms support a variety of essential human behaviors that, when compromised by damage or disease, have significant impact on human health and the quality of life. Elucidating the brain mechanisms that
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support the control of attention holds promise for enhancing the understanding, diagnosis and treatment of attentional deficits that are key components of a variety of mental disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPATIAL-SYMBOLIC BRAIN INFORMATION MANAGEMENT SYSTEM Principal Investigator & Institution: Bowden, Douglas M.; Professor; National Primate Research Ctr; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2001; Project Start 16-SEP-1996; Project End 31-MAY-2004 Summary: In the past two decades, new imaging technology has given neurologists noninvasive tools that reveal the structure of the brain with a clarity that is little short of miraculous. At the same time, neuroscientists, usually in animal studies, have developed ways to reveal hundreds of chemical and functional features of the brain that are relevant to human brain function. The problem of integrating new knowledge to the benefit of human patients is exploding in both magnitude and complexity. This project addresses that problem by creating software to test the feasibility and effectiveness of a Brain Information Management System for knowledge obtained from human and nonhuman primate research. The system will allow the most precise possible indexation of written and pictorial information into a knowledge base that is accessible through the standard terminology of the National Library of Medicine's Unified Medical Language System. Clinicians and neuroscientists any place in the country will be able to access the system via the World Wide Web to determine what is known about the involvement of any brain structure with any of the characteristics described in the neuroscientific knowledge base. In addition, links directly into websites at other institutions will allow immediate access to relevant information about the clinical significance of specific brain structures. The computerized Brain Information Management System is intended to accelerate the application of basic neuroscientific knowledge in the clinical disciplines of neurosurgery, neurology and neuropsychiatry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SUPPRESSION OF BRAIN TUMOR GROWTH BY INTEGRIN ANTAGONIST Principal Investigator & Institution: Laug, Walter E.; Children's Hospital Los Angeles 4650 Sunset Blvd Los Angeles, Ca 90027 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: Inhibition of angiogenesis has evolved as a promising new tool for the adjuvant treatment of various cancers. Since brain tumors are the most angiogenic neoplasms known, anti-angiogenesis might prove to be especially effective for this deadly disease. A novel antagonist of alphavbeta3 and alphavbeta5 integrins, EMD 121 974, was used in our study. This cyclic RGDfV pentapeptide inhibits neo-vascularization through irreversibly binding to the alphav-integrins of sprouting capillary vessels. Human brain tumors stereotactically xenografted into the forebrain of athymic mice responded with growth arrest and subsequent regression when treated daily with this peptide. In contrast, all animals receiving the cyclic RADfV control peptide died within 6-8 weeks from progressive tumors. We propose to expand on these findings by determining the overall survival, the length and optimal dose of peptide administration for tumor eradication, and to investigate for side effects from this peptide. Tumor growth and neo-vascularization in animals receiving the active or inactive peptide will
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be monitored with a novel MRI scanning technique, specifically designed for mice, and these data will be compared with histological findings. Since only orthotopically transplanted tumors (brain), but not heterotopically injected brain tumor cells (subcutis) showed growth inhibition, we propose to investigate whether the unique biochemical environment of the brain, or its capillary endothelial cells are responsible for this response. Growth and survival of capillary endothelial cells derived from the brain and subcutis, and cultured on brain specific matrix proteins will be compared in the presence and absence of RGDfV. Furthermore, the possibility of induction of direct brain tumor cell apoptosis by RGDfV will be tested by growing brain tumor cells on various matrix proteins in the presence or absence of the active peptide. In vivo studies to substantiate a direct tumoricidal effect of RGDfV on brain tumors will be with the administration of monoclonal Ab only reacting with human alphav-integrins and the use of tumors not expressing alphav-integrins. These studies will demonstrate whether the growth suppressive effect of RGDfV in brain tumors is solely due its antiangiogenetic action or whether this peptide also has a tumoricidal effect due its prevention of interaction of brain tumor cells with brain specific matrix proteins. Overall, our data may lead to a novel, adjuvant treatment of malignant brain tumors. 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 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2002; 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 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
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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: THE IMMUNE RESPONSE IN MAST CELL DEFICIENT MICE Principal Investigator & Institution: Silver, Rae; Professor; Psychology; Barnard College 3009 Broadway New York, Ny 10027 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): The number of brain mast cells increases under specific social, stressful, and disease states. Also important, is the discovery that brain mast cells can cross the BBB. Although mast cells are best known for their role in mediating allergic reactions, it has become increasingly evident that they also play a protective role in defense against bacterial infection. Mast cells are heterogeneous, and their mediator content is dependent on their microenvironment, suggesting that brain mast cells should be studied as a unique population - as distinct from those in the periphery. The present application proposes to develop a mouse model which will be used in understanding the phenomenology and functional consequences of mast cells in the brain. Pilot data indicate that mast cell deficient animals lack a complete Acute Phase Response (APR) to bacterial infection. To examine the involvement of mast cells in mounting an immune response, we explore 2 social/behavioral/endocrine conditions in which the brain mast cell population is augmented: a cohabitation paradigm and a stress paradigm. Next, we test the hypothesis that prior exposure (which increases brain mast cell numbers) results in altered response to challenge of the immune system in mast cell rich brain loci. Specifically, we ask whether the mast cell number, activation state is augmented when their numbers in the brain are elevated. To test the hypothesis that brain mast cells have immunological consequences, we determine if increased mast cell numbers results in altered T cell surveillance in mast cell rich brain regions. We propose to test these hypotheses in mast cell deficient mice, in their wild type littermates and in mast cell reconstituted animals. This application will determine whether mast cells play a role in mounting an immune response in the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE NEUROANATOMY OF COGNITION IN TRAUMATIC BRAIN INJURY Principal Investigator & Institution: Levine, Brian T.; Rotman Research Institute 3560 Bathurst St Toronto, Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant) Traumatic brain injury (TBI) is the most common cause of disability in young adults. While much of this disablement is attributable to mental difficulties, the brain mechanisms underlying these difficulties are poorly understood. There is tremendous variability in TBI effects even among patients with similar injury characteristics. This wide range of behavioral outcomes implies variability in neural reorganization supporting these mental operations. We will explore the neural correlates of mental functioning following TBI with functional magnetic resonance
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imaging (fMRI), a technique for studying dynamic brain function (i.e., functional neuroanatomy). Our focus is on executive functioning and memory, the primary cognitive deficits affecting real-life adjustment following TBI. The activation tasks will include two measures of response inhibition and three measures of memory. The functional neuroanatomy of response inhibition will also be examined pre- and postrehabilitation using a training program that targets executive deficits. Each experiment capitalizes on an established paradigm from our previous behavioral research with brain-injured patients or our functional neuroimaging research with healthy adults. In addition to standard image analysis techniques emphasizing local brain activations, we will employ multivariate techniques that stress functional interactions across the brain. These techniques are necessary to characterize the task- and performance-related chances in brain connectivity fundamental to the neuropathology of TBI. These studies should impact the direct care of patients with TBI through the development of diagnostic imaging techniques that can be used to characterize brain-behavior relationships and assess functional neuroanatomical changes due to natural recovery and rehabilitation. Moreover, we expect these findings to increase the understanding of neural changes (i.e., neural compensation or re-organization) in response to brain injury in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE UNFOLDED PROTEIN RESPONSE AFTER BRAIN ISCHEMIA Principal Investigator & Institution: Degracia, Donald J.; Emergency Medicine; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Brain ischemia and reperfusion injury prevents greater than 90% of the 70,000 patients per year resuscitated from cardiac arrest from resuming their normal lives. Our long-term goal is sufficient understanding of the injury mechanisms to formulate clinically effective therapy. Inhibition of protein synthesis during brain reperfusion correlates with regional selective vulnerability and neuronal death, and is due to modification of two translation initiation factors: the phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 (eIF2alpha), and the proteolytic fragmentation of eukaryotic initiation factor 4G (eIF4G). eIF2 phosphorylation and eIF4G fragmentation affect not only the overall protein synthesis rate, but also which peptides are synthesized from the available mRNAs. Moreover, the kinase that phosphorylates eIF2alpha immediately after brain ischemia and reperfusion, PERK, is known to be activated only by the endoplasmic reticulum stress signaling system termed the unfolded protein response (UPR). The UPR can signal either an adaptive pro-survival response, or it can trigger cell death. Thus suppression of protein translation is likely to be part of a more comprehensive cellular response that determines the ultimate fate of reperfused neurons. We hypothesize: (1) the UPR is activated during early brain reperfusion, (2) vulnerable, but not resistant, neurons fail to resolve the UPR, and (3) there is synthesis of only a limited number of proteins during early reperfusion, as a consequence of eIF2alpha phosphorylation and eIF4G fragmentation, that may determine the outcome of neuronal recovery or death. Our Specific Aims are the following. Aim I will compare in ischemia and reperfusion vulnerable and resistant brain regions the activation of the UPR by characterizing activation of its three effectors ATF6, IRE1alpha, and PERK. Aim 2 will examine in ischemia and reperfusion vulnerable and resistant brain regions whether the UPR is resolved (by determining if synthesis of the pro-survival proteins GRP78, XBP-1, GADD34 and SERCA2b occurs), or if the UPR fails to resolve (by determining if
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synthesis of the pro-cell death proteins ATF4 and CHOP occurs). Aim 3 will identify those proteins being synthesized by residual translation during the early hours of reperfusion and compare them between ischemia and reperfusion vulnerable and resistant brain regions. This approach provides an integrated examination during brain ischemia and reperfusion of: (1) the occurrence and the consequences of UPR activation, (2) the consequences of translation initiation factor alterations on residual protein synthesis, and (3) the relationship of these two events to the selective vulnerability of the brain to ischemia and reperfusion injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THERAPEUTIC SEQUESTRATION.
INTERVENTIONS
FOR
HIV-1
CNS
Principal Investigator & Institution: Eddington, Natalie D.; Professor and Chair; Pharmaceutical Sciences; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): HIV-1 enters the Central Nervous System (CNS) after the primary infection and contributes to the neurological deficits observed in patients. Moderate to high viral titers are found in the CNS due to the fact that the majority of anti-retroviral agents are unable to achieve sufficient levels in the brain. The Blood Brain Barrier (BBB) possesses tight junctions and various Multi-Drug Resistance (MDR) transporters such as P-glycoprotein (Pgp) and Multi-drug Resistance Associated Protein (MRP-2), which serve to significantly minimize brain anti-retroviral drug delivery to the brain. Thus, the hypothesis of this therapeutic intervention proposal is that anti-retroviral drug delivery to the brain can be enhanced in order to manageHIV-1 related neuroinvasion by reversibly opening tight junctions and by modulation of MDR (P-glycoprotein,MRP) mediated efflux at the BBB. In order to test this hypothesis, the following three specific aims (SA) will be pursued SA1 To examine the ability of Zonula Occludens Toxin (Zot) to enhance the BBB transport, brain uptake and activity of two "model" antiretroviral agents (AZT, zidovudine) using cell culture techniques and the SCID mice. Preliminary studies have shown that Zot is capable of reversibly opening tight junctions in the BBB, as well as significantly (p < 0 05) increasing brain levels of hydrophilic and hydrophobic agents (e g, paclitaxel, doxorubicin).Uninfected SCID mice and SCID mice inoculated with HIV-1 infected monocytes in the brain caudate and putamen will be used. Antiretroviral brain levels and viral titers will be determined. SA 2 To examine the effect of MDR modulation on the BBB transport, brain uptake and activity of AZT and saquinavir (substrates of MRP-1 and Pgp) two "model" antiretroviral agents using cell culture techniques and the SCID mouse model. To examine the effect of MDR modulation on the in vitro BBB transport and brain distribution of on AZT and saquinavir (substrates of MRp-2 and Pgp)using cell culture techniques and the SCID mice SA3.To examine the concomitant effect of Zot and the MDR inhibitors on the BBB transport, brain uptake and activity of AZT and saquinavir using SCID mice. Obtaining therapeutic CNS levels of anti-retroviral agents is essential to minimizing HIV-1 in the CNS. As such, this proposal offers a viable approach to address this complication of HIV/AIDS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TOBACCO SMOKE CHEMICALS AND STROKE ALTER BRAIN K+ EFFLUX Principal Investigator & Institution: Abbruscato, Thomas J.; Pharmaceutical Sciences; Texas Tech University Health Scis Center Health Sciences Center Lubbock, Tx 79430
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Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 31-MAR-2009 Summary: (provided by applicant): In terms of cost to society and disability to patients, stroke ranks with Alzheimer's disease as the two most important neurological disorders. Nicotine, a major constituent of tobacco smoke has been shown to have important effects on neuronal injury and brain edema formation in stroke and hampers brain recovery after stroke. It is known that the blood-brain barrier (BBB), which is formed by the cerebral endothelium, plays a critical role in the regulation of water and electrolyte balance within the central nervous system (CNS). Exciting preliminary data in our laboratory suggests that nicotine down regulates the BBB expression and function of a key ion transporter, Na, K,2Cl-cotransporter, which normally mediates brain-to-blood removal of potassium ions during in vitro stroke conditions. With respect to brain ischemia, maintenance of low brain extracellular potassium concentration is necessary for proper neuronal conduction and recovery after stroke. In vitro and in vivo investigations into smoke constituent alteration of BBB properties is critically important and is the focus of this research application. The objective of this application is to systematically test the effects of nicotine and smoke constituents on BBB potassium transport during stroke conditions and determine the physiological role of nAChRs on BBB ion transport. The central hypothesis of our work is that nicotine decreases brain-toblood potassium transport through nicotinic acetylcholine receptor (nAChR) activation at the blood-brain barrier that impairs ion transport necessary for stroke adaption. We plan to utilize sophisticated, well characterized in vivo models designed to mimic nicotine and tobacco smoke constituent exposure coupled to validated models of stroke. This focused research plan will identify possible therapeutic targets at the blood-brain barrier to prevent brain edema and altered CNS potassium homeostasis during nicotine or smoke constituent exposure coupled to stroke conditions. We hope that new stroke treatments will utilize a combination of agents that modulate multiple processes (both BBB breakdown and ischemic neuronal death) providing the most efficacious treatment of stroke for both smoking and non-smoking patients. This research plan will also identify key biochemical and molecular mechanisms involved in nicotine and other tobacco smoke constituent alteration in BBB function during stroke so that individualized stroke therapies could be designed to improve health outcomes for smokers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRAINING WITHDRAWAL
IN
FUNCTIONAL
IMAGING
AND
ALCOHOL
Principal Investigator & Institution: Myrick, Donald L.; Psychiatry and Behavioral Scis; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: APPLICANT'S ABSTRACT: This application for a Mentored-Patient Oriented Research Career Development Award is designed to provide the candidate with skills and expertise in the use of functional neuroimaging in the area of alcoholism. The proposed research project integrates the candidate's skills in the clinical treatment of alcoholism with a training plan designed to develop skills in neuroimaging. Functional neuroimaging is a powerful tool to investigate brain activity. One area of alcoholism that has been relatively understudied by this new technology is the syndrome of alcohol withdrawal (AW). Alcoholism is characterized by neuronal adaptation to chronic alcohol use. Upon cessation of heavy alcohol use, alcohol dependent patients display an AW syndrome that likely reflects this neuroadaption. While acute AW symptoms are only manifest for 2-5 days, it is likely that readaption of the neuronal change takes much
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longer. There is a paucity of research that has systematically studied regional brain activity in humans during AW. Previous functional imaging studies have indicated that there is a global reduction in brain activity in AW. However, there is increased activity in the temporal lobes. The proposed project is focused on this area of investigation. Specifically, brain "activity" will be examined using a form of functional neuroimaging, known as SPECT imaging. In addition, both resting and drug (procaine)-stimulated activity states will be examined. The limbic system, a component of the temporal lobes, has been implicated as a significant brain component mediating AW. Accordingly, the limbic system, in general, and the amygdala in particular, will be the neuroanatomical targets of interest to this study. The proposed studies will extend and enhance prior work by attending to possible confounding issues ignored in other studies. In addition, the proposed studies will utilize state-of-the-art methodology and a novel methodological approach (pharmacological probe) to investigate brain activity in AW. Establishing the neuronal regions involved in the AW period may aid in understanding the neurobiology of AW. If specific abnormalities are documented, they may prove to be fruitful targets for pharmacological interventions in potentially preventing relapse to alcohol use. Finally, the utilization of the challenge paradigm proposed in these studies to unmask brain alterations and/or to exacerbate brain activity alterations that exist in the resting state could be a valuable model to help in the evaluation of new pharmacological intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSGENIC MICE--MODEL FOR STUDYING HIV INFECTION OF THE Principal Investigator & Institution: Goldstein, Harris; Associate Professor; Pediatrics; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Approximately 20% of HIV-1-infected infected individuals develop neurological disease associated with the presence of HIV-1-infected cells in the brain. The effectiveness of high activity antiretroviral therapy (HAART) in markedly reducing plasma viral loads has raised the possibility that HIV infection may be successfully "purged" from the systemic immune system. However, HIV-1-infected cells in the brain may function as an important reservoir from which HIV can be reintroduced back into the lymphoid tissues after cessation of anti-retroviral therapy. Therefore, we propose to determine if the brain can function as an in vivo sanctuary for HIV-1-infected cells such as microglia that can migrate from the brain and infect peripheral lymphoid tissues. In addition, we will examine the in vivo effectiveness of a novel therapeutic approach consisting of HAART combined with targeted toxin therapy to reduce the numbers of HIV-1-infected cells in the brain. We also propose to study the mechanisms of the in vivo trafficking of HIV-1-infected cells into the brain. Although much is known about the clinical manifestations of HIVD, there are many gaps in our understanding of the pathophysiology of the disease including the mechanism by which HIV crosses the blood brain barrier. There is much data to support the possibility that HIV-1 infection is introduced into the brain by the infiltration of HIV- 1-infected cells. We will examine the mechanism of entry of HIV-1- infected cells by investigating the in vivo effect of different factors such as cellular activation, chemokine production and cytokine secretion on the migration of HIV-1-infected cells into the brain. Information generated from these studies should provide insights into the mechanism of cellular trafficking into the brain that may permit the development and in vivo testing of new therapeutic strategies aimed at preventing entry of HIV-1-infected cells into the brains. Blocking the
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migration of HIV-1-infected cells into the brain may be an important new therapeutic strategy to use for acutely infected individuals and for infants born to HIV-1-infected mothers. These in vivo studies will be performed using novel transgenic mouse models that we have recently developed that display productive HIV-1 infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSGENIC MALFORMATION
MURINE
MODEL
OF
BRAIN
VASCULAR
Principal Investigator & Institution: Yang, Guo-Yuan; Anesthesia and Perioperative Care; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): The long-term objectives of this proposal are to explore the roles of angiogenesis in the brain, especially the role of brain arteriovenous malformations (BAVMs). We have intensively studied BAVM tissue removed during surgery. We will continue this study and develop an in vivo animal model of non-tumor angiogenesis relevant to cerebrovascular diseases including BAVMs. In vivo gene transfer into the brain with adenoviral vectors provides a useful tool inducing focal, non-tumor angiogenesis in the adult rodent brain. The PI has used this technique to induce stable overexpression of a variety of genes in the mouse brain. We hypothesize that adenoviral-mediated vascular endothelial growth factor (VEGF) gene transduction into the mouse brain induces VEGF overexpression. VEGF signaling, combined with VEGF-induced upregulation of the angiopoietin/Tie-2 signaling pathway, stimulates focal vascular network formation. Furthermore, transforming growth factor beta-1 (TGF-b1) activates TGF-b1, ALK-5, and Smad 2/3 signal pathways, promoting regional angiogenesis formation in the brain tissue. The specific aims of this proposal are to determine: 1) whether VEGF protein production will be increased following adenoviralVEGF (AdVEGF) gene transfer in the adult mouse brain, and whether overexpression of VEGF will induce focal clusters of microvasculature formation; 2) whether TbR-ll, ALK5, and Smad 2/3 will be upregulated in the TGF-bl transgenic mouse brain following AdVEGF gene transduction. Furthermore, to quantify whether endothelial cell proliferation and support cell differentiation will be increased, and finally, to identify how mature these neo-microvasculature are in the mouse brain with both TGFb1 and VEGF overexpression. The experimental components include: 1) highly reproducible adenoviral vector gene transfer in mice; 2) specific VEGF and TGF-b1 pathway detection; and 3) using unique TGF-b transgenic mice. Combining these genetic techniques may lead to the development of a novel, reproducible, and useful animal model. This non-tumor angiogenesis rodent preparation will serve as a model of disordered human cerebral angiogenesis, leading relatively quickly to the ability to test new therapeutic approaches for cerebrovascular disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT OF STROKE WITH MARROW STROMAL CELLS Principal Investigator & Institution: Li, Yi; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAY-2008 Summary: Stroke is the number three cause of death and a leading cause of serious, long-term disability. Treatment of stroke is restricted to thrombolysis within a threehour window after ictus. There are also no treatments for stroke specifically designed to
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promote functional recovery. Preliminary data demonstrate that intravenously (iv) injected bone marrow stromal cells (MSCs) one day or one week after onset of symptoms reduces functional deficits associated with cerebral ischemia. This therapeutic benefit lasts for months. Intravenously injected MSCs enter ischemic brain and therein promote increased growth factor expression, e.g., BDNF, bFGF, VEGF. tn tight of these findings, two primary specific aims are proposed. First, MSC therapy is developed preclinically. Aim 1: To select effective doses and to test the safety and toxicity of iv administration of MSCs in young adult and old rodents subjected to stroke. The major hypotheses being tested in this aim are: MSCs injected iv selectively enter lesioned ischemic brain and improve neurological functional recovery; treatment of stroke within a range of MSC doses is safe and effective; therapeutic benefits are dependent on cellular dose, therapeutic window, and animal age. In Aim 2, the molecular and cellular mechanisms responsible for the therapeutic effect of MSC treatment of stroke are investigated. Aim 2: To provide insight into the mechanisms relating MSC treatment to functional recovery, to measure: levels of growth and trophic factor expression (BDNF, bFGF, VEGF) in the ischemic brain, the spatial and temporal profiles and the phenotypic fate of MSCs in ischemic brain, and the response of endogenous proliferating cells in brain to MSC administration. The corresponding major hypotheses tested are: that growth and trophic factor expressions are enhanced in compromised brain by MSC administration; MSCs administered iv are mostly distributed in the boundary zone of the ischemic lesion; with time, the neural phenotype of MSCs increase; the growth and trophic factors produced in the ischemic brain with resident MSCs alter the compromised brain, e.g. MSCs enhance proliferation of endogenous cells in the ischemic brain. A series of experiments are therefore designed to measure: MSC phenotypic changes, cell fusion and the long-term status of resident MSCs, and the proliferation of cells within select regions of the ischemic brain. The goals of this application are to develop MSC therapy as an effective and safe treatment of stroke. The long-term benefits of MSCs reside in an ability to harvest and amplify a patient's MSCs and to re-inject them iv to treat stroke and possibly other forms of central nervous system disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT OF TRAUMATIC BRAIN INJURY WITH MARROW STROMAL CELLS Principal Investigator & Institution: Mahmood, Asim; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAY-2008 Summary: This project is designed to investigate the effects of intravenous transplantation of bone marrow stromal cells on brain after traumatic brain injury. Traumatic brain injury (TBI) is an important cause of human morbidity and as many as 50,000 Americans are killed and an equal number are disabled by head trauma each year. Currently, treatment of TBI primarily consists of evacuating mass lesions and providing an optimal milieu for the brain to recover. Preliminary data indicate that bone marrow stromal cells (MSCs) induce functional benefit in animals subjected to TBI. In this application, functional response of young male rats and mice subjected to TBI after intravenous (i.v.) administration of MSCs will be measured, and effective doses of MSCs will be determined. A battery of functional outcome measurements will be performed to test for enhanced recovery resulting from MSC treatment (Specific Aim 1). We propose, that therapeutic benefit from MSC treatment of TBI derives from the production of growth factors in brain by the interaction of MSCs with injured brain. To support this
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hypothesis, growth factors produced in brain in response to different doses of MSCs will be measured for different degrees of injury in rats, and a temporal profile of growth factor production will be measured and related to functional response (Specific Aim 2). The MSC enhancement of these growth factors may affect endogenous cell proliferation and their phenotype in the subventdcular zone (SVZ) and the hippocampal formation in animals subjected to TBI. Of basic interest, is the fate of the MSCs in brain after TBI, whether they are modified and express over the long-term markers of other cell types. To address these questions, the temporal profile for cell phenotype of exogenous MSCs in injured brain and endogenous cell proliferation and phenotype in the SVZ and hippocampal formation will be measured in rats subjected to TBI and treated with MSCs. Cell phenotype and cell proliferation measurements will also be performed in mice receiving MSCs from transgenic GFP mice. If intravenous transplantation of marrow stromal cells succeeds in improving functional outcome, a new avenue will be opened for further development of therapeutic interventions to improve outcome after traumatic brain injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: UCP5-- BALANCING METABOLISM AND OXIDATION IN AGING BRAIN Principal Investigator & Institution: Dugan, Laura L.; Associate Professor; Neurology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: (Adapted from the abstract provided by the applicant): Age is the single greatest risk factor for most neurodegenerative disorders, even those that are genetically based. This delayed onset is believed to reflect an interaction between the risk factors for a neurodegenerative disease, and the aging process itself. Oxidative damage to mitochondrial DNA accumulates in brain of older individuals in many species, including man. This observation has led to the speculation that oxidative injury to mitochondria causes loss of mitochondrial metabolic reserve during aging, and that this contributes to the age-dependent onset of neurodegenerative processes. One class of proteins uniquely situated to contribute to, or modify, these age-dependent changes in mitochondrial function are the mitochondrial uncoupling proteins (UCPs). Mitochondrial uncoupling proteins are specifically designed to impair the efficiency of energy production by mitochondria to produce heat. Outside the nervous system, UCPs regulate body weight, temperature, and the response to starvation. Recently, however, we and others have shown that these proteins also regulate mitochondrial free radical production. Three UCPs (UCP2, 4, and 5) are expressed in brain, where their function(s) is essentially unknown. Our laboratory has been studying UCP5, and has determined that it is a neuronal protein with high expression in the forebrain of both mouse and man. We also found that over-expression of UCP5 in neurons decreased mitochondrial free radical production, a potentially beneficial effect, but decreased the efficiency of mitochondrial function and enhanced the vulnerability of neurons to injury and subsequent degeneration. We hypothesize that UCP5 in brain may be a two-edged sword which trades lower mitochondrial free radical production for greater mitochondrial metabolic inefficiency. We propose to determine whether expression and/or activity of UCP5 is altered in brain during aging. We will also determine whether this results in 1) constitutively higher levels of free radical production by mitochondria in older brain, and 2) increased vulnerability of brain to metabolic stress when UCP5 expression is induced. We will first identify factors, such as hormones or caloric restriction, which regulate expression and activity of UCP5. We will then use
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biochemical and fluorescence imaging techniques to evaluate mitochondrial function and free radical formation. Initial experiments will be performed in cultured neurons with modified levels of UCP5 or after treatment with agents to modify UCP5 levels or activity. We will then look at how altering UCP5 expression/activity impacts mitochondrial function and free radical production in brain of old mice. For many of these experiments, we will use Thy1-YFP mice, which exhibit neuronal expression of a fluorescent protein, to allow imaging of neuronal mitochondria in brain slices. Finally, we will generate mice deficient in UCP5 to study the normal function of UCP5 in brain and to elucidate how absence of UCP5 affects mitochondrial function and radical production in brain during aging, with the eventual goal of determining whether UCP5 contributes to the age-dependence of neurodegenerative disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: XE SPECT AND FMR IMAGING OF REORGANIZATION POST STROKE Principal Investigator & Institution: Deutsch, Georg; Associate Professor; Radiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 29-SEP-1999; Project End 31-MAY-2004 Summary: (Verbatim from the Applicant's Abstract) This project evaluates the extent to which recovery from stroke depends on restitution of function in temporarily impaired cerebral tissue versus reorganization in unaffected brain. A new, dynamic 133 Xenon clearance single Photon Emission Computed Tomography (SPECT) technique, that provides quantification of absolute rCBF through the entire brain, will be used to separate permanent from temporary brain dysfunction following stroke as well as help identify the extent to which unaffected brain can compensate for permanently damaged function through the rCBF patterns elicited by motor and cognitive tasks. High filed (4.1 Tesla) functional magnetic resonance imaging (fMRI) during additional sensory motor and cognitive tasks will be used to compliment and further refine the regional activation data identified in individual patietns by Xenon SPECT. Xenon SPECT during rest and CO2 stress will initially serve to identify diaschisis in peri-infarct regions by determining the volume of brain tissue with reduced blood flow which is in excess of the measured anatomic infarction size. Xe SPECT and fMRI scans during cognitive task activation will ten be used to examine the functional status of peri-infact regions and address the possibility of reorganization in spared brain. A series of tasks that normally induce hemisphere and region specific rCBF activation will provide evidence for crosshemispheric of ipsilateral compensation during recovery and will also be used to help assess the status and viability of low flow tissue. 128 unilateral stoke patietns and 40 controls will be followed with all neuroimaging procedures at 1 month, 6 month, and 1 year intervals. Neurological, behavioral and cognitive status evaluations will be conducted at the same intervals, providing correlatable functional status data. The extent to which recovery of function may involve "relearning" by brain regions not affected by the stroke will be assessed by evaluating, in well recovered patients, rCBF patterns during cognitive tasks that were initially compromised. Evaluation will consist of comparison with normal controls performing identical tasks. The overall study will provide rationale, based on physiological measurements, for patient management and rehabilitation strategy, including the use of facilitatory versus compensatory rehabilitation techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ZN DEFICIENCY IMPAIRS BBB INTEGRITY FR OXIDATIVE STRESS Principal Investigator & Institution: Bray, Tammy M.; Dean; Human Nutrition; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 15-MAY-1999; Project End 31-MAY-2002 Summary: (Verbatim from the Applicant's Abstract) The importance of Zn in brain function and neurobiology is widely acknowledged, and many human neurological diseases have been linked to Zn deficiency. However, the mechanism by which dietary Zn deficiency may lead to pathology in the brain, an organ highly susceptible to oxidative damage, is not yet clear. Investigations into the effect of oxidative stress on brain function are often complicated by the high propensity of brain tissue to develop artifactual indices of oxidative stress in vivo. We will pioneer the application of noninvasive in vivo MRI and 31P-NMR techniques to study the role of Zn nutrition in maintaining the integrity of the blood brain barrier(BBB) and brain energy metabolism under oxidative stress. Further, we will identify possible cellular and molecular mechanisms for Zn deficiency pathology under oxidative stress. Hence the focus of this proposal is to examine the role of Zn nutrition in coping with oxidative stress to prevent brain disorders. The long term goal of this research is to understand the basic mechanism underlying the relationship between dietary Zn and optimal central nervous system(CNS) function. We speculate that sub-optimal Zn nutrition weakens BBB integrity and that oxidative stress superimposed upon Zn deficiency disrupts the protective function of the BBB, an event that may be pivotal in the pathogenesis of many brain disorders. Consequently, perturbations of cerebral homeostasis following loss of BBB integrity may lead to impaired energy metabolism and increased oxidative stress within the brain, a sequence of metabolic and biochemical changes by which Zn deficiency may contribute to the development of brain disorders. Thus, the hypothesis of this project is that Zn protects the BBB against oxidative stress through its antioxidant and membrane stabilization properties and therefore helps to maintain the homeostasis of brain metabolism and prevent brain disorders. To test this hypothesis, we will quantify changes in BBB permeability and brain energy metabolism, assess the balance between free radical defense and free radical generation, and measure the extent of oxidative damage in the brain of Zn deficient rats during exposure to hyperoxia. In addition, the possible underlying mechanisms will be explored. This research will contribute significantly to our understanding of the mechanistic roles of Zn in the etiology of brain disorders and lead to the development of better strategies for disease prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age.
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unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “brain” (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 in the PubMed Central database: •
3H-labeled MK-801 binding to the excitatory amino acid receptor complex from rat brain is enhanced by glycine. by Reynolds IJ, Murphy SN, Miller RJ.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299377
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A brain sexual dimorphism controlled by adult circulating androgens. by Cooke BM, Tabibnia G, Breedlove SM.; 1999 Jun 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22121
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Adenovirus-Mediated Gene Delivery into Neuronal Precursors of the Adult Mouse Brain. by Yoon SO, Lois C, Alvirez M, Alvarez-Buylla A, Falck-Pedersen E, Chao MV.; 1996 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38168
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Alteration of the Leptin Network in Late Morbid Obesity Induced in Mice by Brain Infection with Canine Distemper Virus. by Bernard A, Cohen R, Khuth ST, Vedrine B, Verlaeten O, Akaoka H, Giraudon P, Belin MF.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104257
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Anatomical relationship between the basal ganglia and the basal nucleus of Meynert in human and monkey forebrain. by Haber S.; 1987 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304439
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ATM is a cytoplasmic protein in mouse brain required to prevent lysosomal accumulation. by Barlow C, Ribaut-Barassin C, Zwingman TA, Pope AJ, Brown KD, Owens JW, Larson D, Harrington EA, Haeberle AM, Mariani J, Eckhaus M, Herrup K, Bailly Y, Wynshaw-Boris A.; 2000 Jan 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15423
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Behavioral alterations associated with apoptosis and down-regulation of presenilin 1 in the brains of p53-deficient mice. by Amson R, Lassalle JM, Halley H, Prieur S, Lethrosne F, Roperch JP, Israeli D, Gendron MC, Duyckaerts C, Checler F, Dausset J, Cohen D, Oren M, Telerman A.; 2000 May 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25831
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Blood-brain barrier protein recognized by monoclonal antibody. by Sternberger NH, Sternberger LA.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299500
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Blood-brain barrier transport of cationized immunoglobulin G: enhanced delivery compared to native protein. by Triguero D, Buciak JB, Yang J, Pardridge WM.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287353
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The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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Bovine brain cytosol contains three immunologically distinct forms of inositolphospholipid-specific phospholipase C. by Ryu SH, Suh PG, Cho KS, Lee KY, Rhee SG.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299140
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Brain cDNA clone for human cholinesterase. by McTiernan C, Adkins S, Chatonnet A, Vaughan TA, Bartels CF, Kott M, Rosenberry TL, La Du BN, Lockridge O.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299147
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Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. by Griffin WS, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, White CL 3rd, Araoz C.; 1989 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298116
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Brain is the Major Site of Estrogen Synthesis in a Male Songbird. by Schlinger BA, Arnold AP.; 1991 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51624
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Brain L-glutamate decarboxylase: purification and subunit structure. by Denner LA, Wei SC, Lin HS, Lin CT, Wu JY.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304276
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Brain phospholipase C isozymes: differential mRNA localizations by in situ hybridization. by Ross CA, MacCumber MW, Glatt CE, Snyder SH.; 1989 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287032
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Brain protein kinase C phosphorylating poly(arginine,serine) or lamin B is stimulated by anions and by an activator purified from bovine serum albumin preparations. by Abdel-Ghany M, el-Gendy K, Zhang S, Raden D, Racker E.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286784
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Brain size does not predict general cognitive ability within families. by Schoenemann PT, Budinger TF, Sarich VM, Wang WS.; 2000 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18335
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Brain-type prostaglandin D synthetase occurs in the rat cochlea. by Tachibana M, Fex J, Urade Y, Hayaishi O.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299363
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cAMP and forskolin decrease gamma-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes. by Heuschneider G, Schwartz RD.; 1989 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287035
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Castration reversibly alters levels of cholecystokinin immunoreactivity within cells of three interconnected sexually dimorphic forebrain nuclei in the rat. by Simerly RB, Swanson LW.; 1987 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304590
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Cellular localization of 1B236/myelin-associated glycoprotein mRNA during rat brain development. by Higgins GA, Schmale H, Bloom FE, Wilson MC, Milner RJ.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286850
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Central Nervous System Neurons Migrate on Astroglial Fibers from Heterotypic Brain Regions in vitro. by Gasser UE, Hatten ME.; 1990 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54152
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Centrally truncated and stabilized porcine neuropeptide Y analogs: design, synthesis, and mouse brain receptor binding. by Krstenansky JL, Owen TJ, Buck SH, Hagaman KA, McLean LR.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287272
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Changes in brain gene expression shared by scrapie and Alzheimer disease. by Duguid JR, Bohmont CW, Liu NG, Tourtellotte WW.; 1989 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298037
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Characterization of a purified nicotinic receptor from rat brain by using idiotypic and anti-idiotypic antibodies. by Abood LG, Langone JJ, Bjercke R, Lu X, Banerjee S.; 1987 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299124
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Cloning of a brain protein identified by autoantibodies from a patient with paraneoplastic cerebellar degeneration. by Dropcho EJ, Chen YT, Posner JB, Old LJ.; 1987 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=305128
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Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy. by Cooper EC, Aldape KD, Abosch A, Barbaro NM, Berger MS, Peacock WS, Jan YN, Jan LY.; 2000 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18332
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Complete amino acid sequence of rat brain hexokinase, deduced from the cloned cDNA, and proposed structure of a mammalian hexokinase. by Schwab DA, Wilson JE.; 1989 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286957
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Correlation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity with bloodbrain barrier monoamine oxidase activity. by Kalaria RN, Mitchell MJ, Harik SI.; 1987 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304903
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Critical Role for Glial Cells in the Propagation and Spread of Lymphocytic Choriomeningitis Virus in the Developing Rat Brain. by Bonthius DJ, Mahoney J, Buchmeier MJ, Karacay B, Taggard D.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136288
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DARPP-32 mediates serotonergic neurotransmission in the forebrain. by Svenningsson P, Tzavara ET, Liu F, Fienberg AA, Nomikos GG, Greengard P.; 2002 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122494
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Deduced primary structure of the beta subunit of brain type II Ca2+/calmodulindependent protein kinase determined by molecular cloning. by Bennett MK, Kennedy MB.; 1987 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304527
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Development of Antibodies Against the Rat Brain Somatostatin Receptor. by Theveniau M, Rens-Domiano S, Law SF, Rougon G, Reisine T.; 1992 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49072
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Developmentally regulated expression of the nerve growth factor receptor gene in the periphery and brain. by Buck CR, Martinez HJ, Black IB, Chao MV.; 1987 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304802
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Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain. by Nayak P, Chatterjee AK.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152642
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Different classes of glutamate receptors mediate distinct behaviors in a single brainstem nucleus. by Dye J, Heiligenberg W, Keller CH, Kawasaki M.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298418
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Differential expression of alpha and beta thyroid hormone receptor genes in rat brain and pituitary. by Bradley DJ, Young WS 3rd, Weinberger C.; 1989 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298035
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Differential expression of three gap junction proteins in developing and mature brain tissues. by Dermietzel R, Traub O, Hwang TK, Beyer E, Bennett MV, Spray DC, Willecke K.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298664
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Differential Expression of Three Glutamate Receptor Genes in Developing Rat Brain: An in situ Hybridization Study. by Pellegrini-Giampietro DE, Bennett MV, Zukin RS.; 1991 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51617
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Differential localization of calmodulin-dependent enzymes in rat brain: evidence for selective expression of cyclic nucleotide phosphodiesterase in specific neurons. by Kincaid RL, Balaban CD, Billingsley ML.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304374
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Direct visualization and cellular localization of D1 and D2 dopamine receptors in rat forebrain by use of fluorescent ligands. by Ariano MA, Monsma FJ Jr, Barton AC, Kang HC, Haugland RP, Sibley DR.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298324
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Distinct angiotensin II receptor in primary cultures of glial cells from rat brain. by Raizada MK, Phillips MI, Crews FT, Sumners C.; 1987 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=305149
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Distinct cellular and regional localization of immunoreactive protein kinase C in rat brain. by Mochly-Rosen D, Basbaum AI, Koshland DE Jr.; 1987 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=305150
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Distribution of D2 dopamine receptor mRNA in rat brain. by Meador-Woodruff JH, Mansour A, Bunzow JR, Van Tol HH, Watson SJ Jr, Civelli O.; 1989 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298119
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Distribution of neurotensin/neuromedin N mRNA in rat forebrain: unexpected abundance in hippocampus and subiculum. by Alexander MJ, Miller MA, Dorsa DM, Bullock BP, Melloni RH Jr, Dobner PR, Leeman SE.; 1989 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297586
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Distribution of Parthenogenetic Cells in the Mouse Brain and Their Influence on Brain Development and Behavior. by Allen ND, Logan K, Lally G, Drage DJ, Norris ML, Keverne EB.; 1995 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40696
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Dynamic imaging of coherent sources: Studying neural interactions in the human brain. by Gross J, Kujala J, Hamalainen M, Timmermann L, Schnitzler A, Salmelin R.; 2001 Jan 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14650
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Electrophysiological and autoradiographical evidence of V1 vasopressin receptors in the lateral septum of the rat brain. by Raggenbass M, Tribollet E, Dreifuss JJ.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299384
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Elevated levels of an exocrine pancreatic secretory protein in Alzheimer disease brain. by Ozturk M, de la Monte SM, Gross J, Wands JR.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286481
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Estrogen receptor-[alpha] mediates the brain antiinflammatory activity of estradiol. by Vegeto E, Belcredito S, Etteri S, Ghisletti S, Brusadelli A, Meda C, Krust A, Dupont S, Ciana P, Chambon P, Maggi A.; 2003 Aug 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=170966
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Evidence that brain prostaglandin E2 is involved in physiological sleep-wake regulation in rats. by Matsumura H, Honda K, Choi WS, Inoue S, Sakai T, Hayaishi O.; 1989 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297685
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Evolutionary expression of the neuronal form of the src protein in the brain. by Yang XM, Martinez R, Le Beau J, Wiestler O, Walter G.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287351
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Expanded Distribution of mRNA for Nerve Growth Factor, Brain-Derived Neurotrophic Factor, and Neurotrophin 3 in the Rat Brain After Colchicine Treatment. by Ceccatelli S, Ernfors P, Villar MJ, Persson H, Hokfelt T.; 1991 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52926
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Face Encoding and Recognition in the Human Brain. by Haxby JV, Ungerleider LG, Horwitz B, Maisog JM, Rapoport SI, Grady CL.; 1996 Jan 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40160
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Ferritin: isolation of aluminum-ferritin complex from brain. by Fleming J, Joshi JG.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299428
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Four additional members of the ras gene superfamily isolated by an oligonucleotide strategy: molecular cloning of YPT-related cDNAs from a rat brain library. by Touchot N, Chardin P, Tavitian A.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299511
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Growth of cholesterol-reducing Eubacterium on cholesterol-brain agar. by Brinkley AW, Gottesman AR, Mott GE.; 1980 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=291731
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Guanine nucleotide-binding protein regulation of melatonin receptors in lizard brain. by Rivkees SA, Carlson LL, Reppert SM.; 1989 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287245
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Human immunodeficiency virus type 1 tropism for brain microglial cells is determined by a region of the env glycoprotein that also controls macrophage tropism. by Sharpless NE, O'Brien WA, Verdin E, Kufta CV, Chen IS, Dubois-Dalcq M.; 1992 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=289063
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Human salivary gustin is a potent activator of calmodulin-dependent brain phosphodiesterase. by Law JS, Nelson N, Watanabe K, Henkin RI.; 1987 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304499
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Identification of cellular and extracellular sites of amyloid precursor protein extracytoplasmic domain in normal and Alzheimer disease brains. by Tate-Ostroff B, Majocha RE, Marotta CA.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286551
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Immortality of cell cultures derived from brains of mice and hamsters infected with Creutzfeldt-Jakob disease agent. by Manuelidis EE, Fritch WW, Kim JH, Manuelidis L.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304318
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Immunocytochemical localization of beta II subspecies of protein kinase C in rat brain. by Saito N, Kose A, Ito A, Hosoda K, Mori M, Hirata M, Ogita K, Kikkawa U, Ono Y, Igarashi K, et al.; 1989 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287142
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Immunocytochemical localization of the beta I subspecies of protein kinase C in rat brain. by Hosoda K, Saito N, Kose A, Ito A, Tsujino T, Ogita K, Kikkawa U, Ono Y, Igarashi K, Nishizuka Y, et al.; 1989 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286697
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Immunohistochemical localization of a neuronal nicotinic acetylcholine receptor in mammalian brain. by Deutch AY, Holliday J, Roth RH, Chun LL, Hawrot E.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299613
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Immunohistochemical Localization of the D1 Dopamine Receptor in Rat Brain Reveals its Axonal Transport, Pre- and Postsynaptic Localization, and Prevalence in the Basal Ganglia, Limbic, System and Thalamic Reticular Nucleus. by Huang Q, Zhou D, Chase K, Gusella JF, Aronin N, DiFiglia M.; 1992 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50683
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Induction of interleukin-1 and tumor necrosis factor alpha in brain cultures by human immunodeficiency virus type 1. by Merrill JE, Koyanagi Y, Zack J, Thomas L, Martin F, Chen IS.; 1992 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=289014
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Influenza viruses induce autoantibodies to a brain-specific 37-kDa protein in rabbit. by Laing P, Knight JG, Hill JM, Harris AG, Oxford JS, Webster RG, Markwell MA, Paul SM, Pert CB.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286833
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Interaction of [3H]MK-801 with multiple states of the N-methyl-D-aspartate receptor complex of rat brain. by Javitt DC, Zukin SR.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286550
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Intra-blood-brain barrier synthesis of human immunodeficiency virus antigen and antibody in humans and chimpanzees. by Goudsmit J, Epstein LG, Paul DA, van der Helm HJ, Dawson GJ, Asher DM, Yanagihara R, Wolff AV, Gibbs CJ Jr, Gajdusek DC.; 1987 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304979
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Isolates of human immunodeficiency virus type 1 from the brain may constitute a special group of the AIDS virus. by Cheng-Mayer C, Weiss C, Seto D, Levy JA.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298325
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Isolation, partial amino acid sequence, and immunohistochemical localization of a brain-specific calcium-binding protein. by Winsky L, Nakata H, Martin BM, Jacobowitz DM.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298662
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Large-scale purification of Japanese encephalitis virus from infected mouse brain for preparation of vaccine. by Aizawa C, Hasegawa S, Chih-Yuan C, Yoshioka I.; 1980 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=291283
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Link between D1 and D2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain. by Seeman P, Niznik HB, Guan HC, Booth G, Ulpian C.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298666
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Localization of D1 Dopamine Receptor mRNA in Brain Supports a Role in Cognitive, Affective, and Neuroendocrine Aspects of Dopaminergic Neurotransmission. by Fremeau RT Jr, Duncan GE, Fornaretto M, Dearry A, Gingrich JA.; 1991 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51535
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Localization of the mRNA for the dopamine D2 receptor in the rat brain by in situ hybridization histochemistry. by Mengod G, Martinez-Mir MI, Vilaro MT, Palacios JM.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298322
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Major role for neuronal death during brain development: refinement of topographical connections. by Catsicas S, Thanos S, Clarke PG.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299499
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Mapping of neurokinin-like immunoreactivity in the human brainstem. by Covenas R, Martin F, Belda M, Smith V, Salinas P, Rivada E, Diaz-Cabiale Z, Narvaez JA, Marcos P, Tramu G, Gonzalez-Baron S.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149367
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Membrane docosahexaenoate is supplied to the developing brain and retina by the liver. by Scott BL, Bazan NG.; 1989 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287028
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Memory systems in the brain and localization of a memory. by Thompson RF, Kim JJ.; 1996 Nov 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33628
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Molecular cloning of a brain-specific calcium/calmodulin-dependent protein kinase. by Lin CR, Kapiloff MS, Durgerian S, Tatemoto K, Russo AF, Hanson P, Schulman H, Rosenfeld MG.; 1987 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298983
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mRNA for low density lipoprotein receptor in brain and spinal cord of immature and mature rabbits. by Hofmann SL, Russell DW, Goldstein JL, Brown MS.; 1987 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299061
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Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at bloodbrain barrier sites. by Cordon-Cardo C, O'Brien JP, Casals D, Rittman-Grauer L, Biedler JL, Melamed MR, Bertino JR.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286540
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Multiple forms of basic fibroblast growth factor: amino-terminal cleavages by tumor cell- and brain cell-derived acid proteinases. by Klagsbrun M, Smith S, Sullivan R, Shing Y, Davidson S, Smith JA, Sasse J.; 1987 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304536
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Neural Cell Adhesion Molecule (N-CAM) Inhibits Astrocyte Proliferation After Injury to Different Regions of the Adult Rat Brain. by Krushel LA, Sporns O, Cunningham BA, Crossin KL, Edelman GM.; 1995 May 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41936
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Neuroanatomical patterns of the mu, delta, and kappa opioid receptors of rat brain as determined by quantitative in vitro autoradiography. by Tempel A, Zukin RS.; 1987 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=305074
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Neuroprotection with noninvasive neurotrophin delivery to the brain. by Wu D, Pardridge WM.; 1999 Jan 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15126
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NEW EMBO MEMBER'S REVIEW Matrix metalloproteinases in the adult brain physiology: a link between c-Fos, AP-1 and remodeling of neuronal connections? by Kaczmarek L, Lapinska-Dzwonek J, Szymczak S.; 2002 Dec 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139096
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N-Methyl-d-aspartate antagonists and apoptotic cell death triggered by head trauma in developing rat brain. by Pohl D, Bittigau P, Ishimaru MJ, Stadthaus D, Hubner C, Olney JW, Turski L, Ikonomidou C.; 1999 Mar 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26815
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Peripheral nerve damage facilitates functional innervation of brain grafts in adult sensory cortex. by Ebner FF, Erzurumlu RS, Lee SM.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286548
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Phospholipase C associated with particulate fractions of bovine brain. by Lee KY, Ryu SH, Suh PG, Choi WC, Rhee SG.; 1987 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298898
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Phospholipase C I and II brain isozymes: immunohistochemical localization in neuronal systems in rat brain. by Gerfen CR, Choi WC, Suh PG, Rhee SG.; 1988 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280173
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Photostimulation Using Caged Glutamate Reveals Functional Circuitry in Living Brain Slices. by Callaway EM, Katz LC.; 1993 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47202
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pp60c-src expression in the developing rat brain. by Cartwright CA, Simantov R, Cowan WM, Hunter T, Eckhart W.; 1988 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280206
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Protein kinase C zeta subspecies from rat brain: its structure, expression, and properties. by Ono Y, Fujii T, Ogita K, Kikkawa U, Igarashi K, Nishizuka Y.; 1989 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287072
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Protooncogene expression identifies a transient columnar organization of the forebrain within the late embryonic ventricular zone. by Johnston JG, van der Kooy D.; 1989 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286622
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Purification and characterization of a nicotinic acetylcholine receptor from rat brain. by Whiting P, Lindstrom J.; 1987 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304257
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Purification of a putative brain somatostatin receptor. by He HT, Johnson K, Thermos K, Reisine T.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286720
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Quantitative autoradiography of brain binding sites for the vesicular acetylcholine transport blocker 2-(4-phenylpiperidino)cyclohexanol (AH5183). by Marien MR, Parsons SM, Altar CA.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304319
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Quinolinic acid phosphoribosyltransferase: preferential glial localization in the rat brain visualized by immunocytochemistry. by Kohler C, Okuno E, Flood PR, Schwarcz R.; 1987 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304897
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Refractoriness to melatonin occurs independently at multiple brain sites in Siberian hamsters. by Freeman DA, Zucker I.; 2001 May 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33488
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Retinal transplants can drive a pupillary reflex in host rat brains. by Klassen H, Lund RD.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299204
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Reversal of age-related learning deficits and brain oxidative stress in mice with superoxide dismutase/catalase mimetics. by Liu R, Liu IY, Bi X, Thompson RF, Doctrow SR, Malfroy B, Baudry M.; 2003 Jul 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166262
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Screening an expression library with a ligand probe: isolation and sequence of a cDNA corresponding to a brain calmodulin-binding protein. by Sikela JM, Hahn WE.; 1987 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304797
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Severity of neurological signs and degree of inflammatory lesions in the brains of rats with Borna disease correlate with the induction of nitric oxide synthase. by Zheng YM, Schafer MK, Weihe E, Sheng H, Corisdeo S, Fu ZF, Koprowski H, Dietzschold B.; 1993 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=237996
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Site of anticonvulsant action on sodium channels: autoradiographic and electrophysiological studies in rat brain. by Worley PF, Baraban JM.; 1987 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304800
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Spatiotemporal relationship of embryonic cholinesterases with cell proliferation in chicken brain and eye. by Layer PG, Sporns O.; 1987 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304188
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Specific binding of atrial natriuretic factor in brain microvessels. by Chabrier PE, Roubert P, Braquet P.; 1987 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304588
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Structure of the mouse gene encoding CD4 and an unusual transcript in brain. by Gorman SD, Tourvieille B, Parnes JR.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299356
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Task-related and item-related brain processes of memory retrieval. by Duzel E, Cabeza R, Picton TW, Yonelinas AP, Scheich H, Heinze HJ, Tulving E.; 1999 Feb 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15598
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Temporal binding via cortical coincidence detection of specific and nonspecific thalamocortical inputs: A voltage-dependent dye-imaging study in mouse brain slices. by Llinas RR, Leznik E, Urbano FJ.; 2002 Jan 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117580
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Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. by Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koistinaho J.; 1998 Dec 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28119
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The beta-amyloid protein precursor of Alzheimer disease has soluble derivatives found in human brain and cerebrospinal fluid. by Palmert MR, Podlisny MB, Witker DS, Oltersdorf T, Younkin LH, Selkoe DJ, Younkin SG.; 1989 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297834
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The increasingly plastic, hormone-responsive adult brain. by Breedlove SM, Jordan CL.; 2001 Mar 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33338
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The molecular cloning of a type II regulatory subunit of the cAMP-dependent protein kinase from rat skeletal muscle and mouse brain. by Scott JD, Glaccum MB, Zoller MJ, Uhler MD, Helfman DM, McKnight GS, Krebs EG.; 1987 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298820
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The neuropeptide cerebellin is a marker for two similar neuronal circuits in rat brain. by Mugnaini E, Morgan JI.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299612
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Tubulofilaments in negatively stained scrapie-infected brains: relationship to scrapieassociated fibrils. by Narang HK, Asher DM, Gajdusek DC.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299374
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Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains. by Perry G, Friedman R, Shaw G, Chau V.; 1987 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304795
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Widespread Activation of Calcium-Activated Neutral Proteinase (Calpain) in the Brain in Alzheimer Disease: A Potential Molecular Basis for Neuronal Degeneration. by Saito K, Elce JS, Hamos JE, Nixon RA.; 1993 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46148
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, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “brain” (or synonyms) into the 6
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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search box, and click “Go.” The following is the type of output you can expect from PubMed for brain (hyperlinks lead to article summaries): •
A case of brain abscess by Eikenella corrodens in a HIV-positive patient. Author(s): Poggesi L, Scheggi V, Ammannati F, Bono P. Source: Ann Ital Med Int. 2003 July-September; 18(3): 162-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14621427&dopt=Abstract
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A comprehensive analysis of 22q11 gene expression in the developing and adult brain. Author(s): Maynard TM, Haskell GT, Peters AZ, Sikich L, Lieberman JA, LaMantia AS. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 November 25; 100(24): 14433-8. Epub 2003 Nov 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14614146&dopt=Abstract
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A novel image fusion visualizes the angioarchitecture of the perforating arteries in the brain. Author(s): Shimizu S, Suzuki H, Maki H, Maeda M, Miya F, Benali K, Trousset Y, Taki W. Source: Ajnr. American Journal of Neuroradiology. 2003 November-December; 24(10): 2011-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14625225&dopt=Abstract
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A novel LIM and SH3 protein (lasp-2) highly expressing in chicken brain. Author(s): Terasaki AG, Suzuki H, Nishioka T, Matsuzawa E, Katsuki M, Nakagawa H, Miyamoto S, Ohashi K. Source: Biochemical and Biophysical Research Communications. 2004 January 2; 313(1): 48-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14672696&dopt=Abstract
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Aching atrophy. More than unpleasant, chronic pain shrinks the brain. Author(s): Melton L. Source: Scientific American. 2004 January; 290(1): 22-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14682034&dopt=Abstract
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Adenylate cyclase activity in postmortem brain of suicide subjects: reduced response to beta-adrenergic stimulation. Author(s): Valdizan EM, Gutierrez O, Pazos A. Source: Biological Psychiatry. 2003 December 15; 54(12): 1457-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14675811&dopt=Abstract
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Altering the properties of the blood-brain barrier: disruption and permeabilization. Author(s): Fortin D. Source: Prog Drug Res. 2003; 61: 125-54. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14674611&dopt=Abstract
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Aminopeptidase A, generating one of the main effector peptides of the brain reninangiotensin system, angiotensin III, plays a key role in central control of blood pressure. Author(s): Rozenfeld R, Reaux A, Iturrioz X, Fassot C, Fournie-Zaluski MC, David C, Maigret B, Roques BP, Corvol P, Llorens-Cortes C. Source: Proc West Pharmacol Soc. 2003; 46: 39-44. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14699881&dopt=Abstract
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An experimental environment for the production, exchange and discussion of fused radiology images, for the management of patients with residual brain tumour disease. Author(s): Sakellaropoulos GC, Kagadis GC, Karystianos C, Karnabatidis D, Constantoyannis C, Nikiforidis GC. Source: Medical Informatics and the Internet in Medicine. 2003 June; 28(2): 135-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14692590&dopt=Abstract
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An ultrastructural study of the brain in fatal Plasmodium falciparum malaria. Author(s): Pongponratn E, Turner GD, Day NP, Phu NH, Simpson JA, Stepniewska K, Mai NT, Viriyavejakul P, Looareesuwan S, Hien TT, Ferguson DJ, White NJ. Source: The American Journal of Tropical Medicine and Hygiene. 2003 October; 69(4): 345-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14640492&dopt=Abstract
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Anatomical and functional brain variables associated with clozapine response in treatment-resistant schizophrenia. Author(s): Molina V, Reig S, Sarramea F, Sanz J, Francisco Artaloytia J, Luque R, Aragues M, Pascau J, Benito C, Palomo T, Desco M. Source: Psychiatry Research. 2003 November 30; 124(3): 153-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14623067&dopt=Abstract
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Are developmental disorders like cases of adult brain damage? Implications from connectionist modelling. Author(s): Thomas M, Karmiloff-Smith A. Source: The Behavioral and Brain Sciences. 2002 December; 25(6): 727-50; Discussion 750-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14598624&dopt=Abstract
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Armoured brain. Author(s): Bennett S, Plint A, Vassilyadi M. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 November 25; 169(11): 1145; Author Reply 1145. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14638638&dopt=Abstract
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Assembly of alpha4beta2 nicotinic acetylcholine receptors assessed with functional fluorescently labeled subunits: effects of localization, trafficking, and nicotineinduced upregulation in clonal mammalian cells and in cultured midbrain neurons. Author(s): Nashmi R, Dickinson ME, McKinney S, Jareb M, Labarca C, Fraser SE, Lester HA. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 December 17; 23(37): 11554-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14684858&dopt=Abstract
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Assessment of treatment response by autoradiography with (14)C-aminocyclopentane carboxylic acid, (67)Ga-DTPA, and (18)F-FDG in a herpes simplex virus thymidine kinase/ganciclovir brain tumor model. Author(s): Miyagawa T, Oku T, Sasajima T, Dasai R, Beattie B, Finn R, Tjuvajev JG, Blasberg R. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 November; 44(11): 1845-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602869&dopt=Abstract
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Atrial and brain natriuretic peptides as markers of response to resynchronisation therapy. Author(s): Molhoek SG, Bax JJ, van Erven L, Bootsma M, Steendijk P, Lentjes E, Boersma E, van der Laarse A, van der Wall EE, Schalij MJ. Source: Heart (British Cardiac Society). 2004 January; 90(1): 97-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14676258&dopt=Abstract
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Attention-grabbing motion in the human brain. Author(s): Culham J. Source: Neuron. 2003 October 30; 40(3): 451-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14642268&dopt=Abstract
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Auras and other hallucinations: windows on the visual brain. Author(s): Wilkinson F. Source: Prog Brain Res. 2004; 144: 305-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14650857&dopt=Abstract
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Automatic activation of the semantic network in schizophrenia: evidence from eventrelated brain potentials. Author(s): Condray R, Siegle GJ, Cohen JD, van Kammen DP, Steinhauer SR. Source: Biological Psychiatry. 2003 December 1; 54(11): 1134-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14643080&dopt=Abstract
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Autoregulation of cerebral blood flow in fetuses with congenital heart disease: the brain sparing effect. Author(s): Donofrio MT, Bremer YA, Schieken RM, Gennings C, Morton LD, Eidem BW, Cetta F, Falkensammer CB, Huhta JC, Kleinman CS. Source: Pediatric Cardiology. 2003 September-October; 24(5): 436-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14627309&dopt=Abstract
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Awakenings from persistent vegetative state: report of three cases with parkinsonism and brain stem lesions on MRI. Author(s): Matsuda W, Matsumura A, Komatsu Y, Yanaka K, Nose T. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 November; 74(11): 1571-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14617720&dopt=Abstract
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BAY 38-7271: a novel highly selective and highly potent cannabinoid receptor agonist for the treatment of traumatic brain injury. Author(s): Mauler F, Horvath E, De Vry J, Jager R, Schwarz T, Sandmann S, Weinz C, Heinig R, Bottcher M. Source: Cns Drug Rev. 2003 Winter; 9(4): 343-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14647528&dopt=Abstract
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Beyond the ivory tower. A distant mirror for the brain. Author(s): Zimmer C. Source: Science. 2004 January 2; 303(5654): 43-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14704413&dopt=Abstract
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Binocular rivalry in split-brain observers. Author(s): O'Shea RP, Corballis PM. Source: Journal of Vision (Charlottesville, Va.). 2003; 3(10): 610-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14640884&dopt=Abstract
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Blood pressure and outcome after severe pediatric traumatic brain injury. Author(s): Vavilala MS, Bowen A, Lam AM, Uffman JC, Powell J, Winn HR, Rivara FP. Source: The Journal of Trauma. 2003 December; 55(6): 1039-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14676648&dopt=Abstract
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Blood pressure and the brain. Author(s): Welch TR, Roizen NJ, Daniels S. Source: The Journal of Pediatrics. 2003 December; 143(6): 699-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14657808&dopt=Abstract
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Blood-brain barrier permeability to ammonia in liver failure: a critical reappraisal. Author(s): Ott P, Larsen FS. Source: Neurochemistry International. 2004 March; 44(4): 185-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602081&dopt=Abstract
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Blood-brain barrier, hot water and seizures. Author(s): Janigro D, Hallene K. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2003 November; 24(4): 231. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14658037&dopt=Abstract
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BR96-DOX immunoconjugate targeting of chemotherapy in brain tumor models. Author(s): Muldoon LL, Neuwelt EA. Source: Journal of Neuro-Oncology. 2003 October; 65(1): 49-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14649885&dopt=Abstract
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Brain abscess--an unusual complication of ventriculo-peritoneal shunt. Author(s): Pandey P, Suri A, Singh AK, Mahapatra AK. Source: Indian J Pediatr. 2003 October; 70(10): 833-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14649482&dopt=Abstract
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Brain activation and the phonological loop: the impact of rehearsal. Author(s): Logie RH, Venneri A, Della Sala S, Redpath TW, Marshall I. Source: Brain and Cognition. 2003 November; 53(2): 293-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14607167&dopt=Abstract
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Brain activation pattern during a verbal fluency test in healthy male and female volunteers: a functional magnetic resonance imaging study. Author(s): Weiss EM, Siedentopf C, Hofer A, Deisenhammer EA, Hoptman MJ, Kremser C, Golaszewski S, Felber S, Fleischhacker WW, Delazer M. Source: Neuroscience Letters. 2003 December 11; 352(3): 191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14625017&dopt=Abstract
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Brain activity during intra- and cross-modal priming: new empirical data and review of the literature. Author(s): Carlesimo GA, Turriziani P, Paulesu E, Gorini A, Caltagirone C, Fazio F, Perani D. Source: Neuropsychologia. 2004; 42(1): 14-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14615073&dopt=Abstract
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Brain amino acid abnormalities in liver disease--a postmortem study. Author(s): Musshoff F, Schmidt P, Madea B, Schoenemeier S, Buerrig KF, Jacob B, Bonte W, Daldrup T. Source: J Forensic Sci. 2003 November; 48(6): 1379-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14640289&dopt=Abstract
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Brain angiotensinergic activity: the state of our current knowledge. Author(s): Speth RC, Brown TE, Barnes RD, Wright JW. Source: Proc West Pharmacol Soc. 2003; 46: 11-5. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14699876&dopt=Abstract
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Brain as the Sea of Marrow. Author(s): Song S, Sanchez-Ramos J. Source: Experimental Neurology. 2003 November; 184(1): 54-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14637080&dopt=Abstract
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Brain bioenergetics and cognitive ability. Author(s): Rae C, Scott RB, Lee M, Simpson JM, Hines N, Paul C, Anderson M, Karmiloff-Smith A, Styles P, Radda GK. Source: Developmental Neuroscience. 2003 September-October; 25(5): 324-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14614259&dopt=Abstract
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Brain but not lung functions impaired after a chlorine incident. Author(s): Kilburn KH. Source: Ind Health. 2003 October; 41(4): 299-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14620664&dopt=Abstract
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Brain function. Author(s): Greenfield SA. Source: Archives of Disease in Childhood. 2003 November; 88(11): 954-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14612351&dopt=Abstract
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Brain haemorrhage in five infants with coagulopathy. Author(s): Vorstman EB, Anslow P, Keeling DM, Haythornthwaite G, Bilolikar H, McShane MT. Source: Archives of Disease in Childhood. 2003 December; 88(12): 1119-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14670783&dopt=Abstract
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Brain hemorrhage as a complication of type I cryoglobulinemia vasculopathy. Author(s): Mazzola L, Antoine JC, Camdessanche JP, Barral FG, Reynaud J, Michel D. Source: Journal of Neurology. 2003 November; 250(11): 1376-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14648158&dopt=Abstract
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Brain imaging and prophylactic therapy in children with migraine: recommendations versus reality. Author(s): Schor NF. Source: The Journal of Pediatrics. 2003 December; 143(6): 776-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14657827&dopt=Abstract
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Brain imaging and proton magnetic resonance spectroscopy in patients with phenylketonuria. Author(s): Moller HE, Weglage J, Bick U, Wiedermann D, Feldmann R, Ullrich K. Source: Pediatrics. 2003 December; 112(6 Pt 2): 1580-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14654669&dopt=Abstract
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Brain lesion volume and neuropsychological function predict efficacy of treatment for depression in multiple sclerosis. Author(s): Mohr DC, Epstein L, Luks TL, Goodkin D, Cox D, Goldberg A, Chin C, Nelson S. Source: Journal of Consulting and Clinical Psychology. 2003 December; 71(6): 1017-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14622077&dopt=Abstract
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Brain modules of hallucination: an analysis of multiple patients with brain lesions. Author(s): Braun CM, Dumont M, Duval J, Hamel-Hebert I, Godbout L. Source: Journal of Psychiatry & Neuroscience : Jpn. 2003 November; 28(6): 432-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14631455&dopt=Abstract
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Brain N-acetylaspartate as a molecular water pump and its role in the etiology of Canavan disease: a mechanistic explanation. Author(s): Baslow MH. Source: Journal of Molecular Neuroscience : Mn. 2003; 21(3): 185-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14645985&dopt=Abstract
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Brain natriuretic peptide predicts right heart failure in patients with acute pulmonary embolism. Author(s): Kruger S, Graf J, Merx MW, Koch KC, Kunz D, Hanrath P, Janssens U. Source: American Heart Journal. 2004 January; 147(1): 60-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14691420&dopt=Abstract
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Brain or brawn: how FGF signaling gives us both. Author(s): Akai J, Storey K. Source: Cell. 2003 November 26; 115(5): 510-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14651843&dopt=Abstract
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Brain phenylalanine concentrations in phenylketonuria: research and treatment of adults. Author(s): Moats RA, Moseley KD, Koch R, Nelson M Jr. Source: Pediatrics. 2003 December; 112(6 Pt 2): 1575-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14654668&dopt=Abstract
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Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor alpha in mice. Author(s): Inoue H, Jiang XF, Katayama T, Osada S, Umesono K, Namura S. Source: Neuroscience Letters. 2003 December 11; 352(3): 203-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14625020&dopt=Abstract
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Brain renin-angiotensin system. Lessons from functional genomics. Author(s): Baltatu O, Bader M. Source: Neuroendocrinology. 2003 November; 78(5): 253-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14657606&dopt=Abstract
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Brain reorganization after stroke. Author(s): Green JB. Source: Topics in Stroke Rehabilitation. 2003 Fall; 10(3): 1-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14681816&dopt=Abstract
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Brain retraction injury. Author(s): Zhong J, Dujovny M, Perlin AR, Perez-Arjona E, Park HK, Diaz FG. Source: Neurological Research. 2003 December; 25(8): 831-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14669526&dopt=Abstract
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Brain temperature and cerebral blood flow imaging in patients with severe subarachnoid hemorrhage: report of two cases. Author(s): Otawara Y, Ogasawara K, Yukawa H, Tomitsuka N, Kubo Y, Ogawa A, Suzuki M. Source: Surgical Neurology. 2003 December; 60(6): 549-52; Discussion 552. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14670677&dopt=Abstract
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Brain weight: what does it mean? Author(s): Lindboe CF. Source: Clin Neuropathol. 2003 November-December; 22(6): 263-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14672503&dopt=Abstract
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Brain, conscious experience and the observing self. Author(s): Baars BJ, Ramsoy TZ, Laureys S. Source: Trends in Neurosciences. 2003 December; 26(12): 671-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14624851&dopt=Abstract
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Brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms in Parkinson's disease and age of onset. Author(s): Hong CJ, Liu HC, Liu TY, Lin CH, Cheng CY, Tsai SJ. Source: Neuroscience Letters. 2003 December 15; 353(1): 75-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14642442&dopt=Abstract
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Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: a role in depression. Author(s): Eisch AJ, Bolanos CA, de Wit J, Simonak RD, Pudiak CM, Barrot M, Verhaagen J, Nestler EJ. Source: Biological Psychiatry. 2003 November 15; 54(10): 994-1005. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14625141&dopt=Abstract
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Brainstem cranial-nerve lesions in an infant with hypoxic cerebral injury. Author(s): Sugama S, Ariga M, Hoashi E, Eto Y. Source: Pediatric Neurology. 2003 September; 29(3): 256-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14629914&dopt=Abstract
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Brainstem death: implications in India. Author(s): Sethi NK, Sethi PK. Source: J Assoc Physicians India. 2003 September; 51: 910-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14710981&dopt=Abstract
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Brainstem encephalitis with Kikuchi-Fujimoto disease. Author(s): Shafqat S, Memon SB, Hyder S, Hasan SH, Smego RA Jr. Source: J Coll Physicians Surg Pak. 2003 November; 13(11): 663-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14700498&dopt=Abstract
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Can shaking alone cause fatal brain injury? A biomechanical assessment of the Duhaime shaken baby syndrome model. Author(s): Cory CZ, Jones BM. Source: Med Sci Law. 2003 October; 43(4): 317-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14655963&dopt=Abstract
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Can the brain be protected through exercise? Lessons from an animal model of parkinsonism. Author(s): Smith AD, Zigmond MJ. Source: Experimental Neurology. 2003 November; 184(1): 31-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14637076&dopt=Abstract
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Cancerous stem cells can arise from pediatric brain tumors. Author(s): Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M, Kornblum HI. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 December 9; 100(25): 15178-83. Epub 2003 November 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14645703&dopt=Abstract
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Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer's disease brains. Author(s): Benito C, Nunez E, Tolon RM, Carrier EJ, Rabano A, Hillard CJ, Romero J. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 December 3; 23(35): 11136-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14657172&dopt=Abstract
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Cdk5 in the adult non-demented brain. Author(s): Fischer A, Sananbenesi F, Spiess J, Radulovic J. Source: Current Drug Targets. Cns and Neurological Disorders. 2003 December; 2(6): 375-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14683465&dopt=Abstract
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Cerebral blood flow in chronic symptomatic mild traumatic brain injury. Author(s): Bonne O, Gilboa A, Louzoun Y, Kempf-Sherf O, Katz M, Fishman Y, BenNahum Z, Krausz Y, Bocher M, Lester H, Chisin R, Lerer B. Source: Psychiatry Research. 2003 November 30; 124(3): 141-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14623066&dopt=Abstract
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Chemokines and their receptors in the brain: pathophysiological roles in ischemic brain injury. Author(s): Minami M, Satoh M. Source: Life Sciences. 2003 December 5; 74(2-3): 321-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14607260&dopt=Abstract
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Childhood brain tumors and depressive disorders. Author(s): Connemann BJ, Kassubek J. Source: The New England Journal of Medicine. 2003 November 6; 349(19): 1868-9; Author Reply 1868-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602887&dopt=Abstract
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Chipping away at brain function: mining for insights with microarrays. Author(s): Henry GL, Zito K, Dubnau J. Source: Current Opinion in Neurobiology. 2003 October; 13(5): 570-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14630220&dopt=Abstract
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Clinical gene therapy for brain tumors. Liposomal delivery of anticancer molecule to glioma. Author(s): Yoshida J, Mizuno M. Source: Journal of Neuro-Oncology. 2003 December; 65(3): 261-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14682376&dopt=Abstract
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Clinical significance of acute-phase brain natriuretic peptide in acute myocardial infarction treated with direct coronary angioplasty. Author(s): Katayama T, Nakashima H, Yonekura T, Honda Y, Suzuki S, Yano K. Source: J Cardiol. 2003 November; 42(5): 195-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14658407&dopt=Abstract
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Clinical trials of adenoviruses in brain tumors: a review of Ad-p53 and oncolytic adenoviruses. Author(s): Vecil GG, Lang FF. Source: Journal of Neuro-Oncology. 2003 December; 65(3): 237-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14682374&dopt=Abstract
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Cloning of a novel orphan G protein-coupled receptor (GPCR-2037): in situ hybridization reveals high mRNA expression in rat brain restricted to neurons of the habenular complex. Author(s): Berthold M, Collin M, Sejlitz T, Meister B, Lind P. Source: Brain Research. Molecular Brain Research. 2003 December 12; 120(1): 22-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14667573&dopt=Abstract
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Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain. Author(s): Bisogno T, Howell F, Williams G, Minassi A, Cascio MG, Ligresti A, Matias I, Schiano-Moriello A, Paul P, Williams EJ, Gangadharan U, Hobbs C, Di Marzo V, Doherty P. Source: The Journal of Cell Biology. 2003 November 10; 163(3): 463-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14610053&dopt=Abstract
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Combination fusion protein therapy of refractory brain tumors: demonstration of efficacy in cell culture. Author(s): Liu TF, Cohen KA, Willingham MC, Tatter SB, Puri RK, Frankel AE. Source: Journal of Neuro-Oncology. 2003 October; 65(1): 77-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14649887&dopt=Abstract
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Comparison between successful and failed sit-to-stand trials of a patient after traumatic brain injury. Author(s): Zablotny CM, Nawoczenski DA, Yu B. Source: Archives of Physical Medicine and Rehabilitation. 2003 November; 84(11): 17215. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14639576&dopt=Abstract
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Comparison of PCR-amplified JC virus control region sequences from multiple brain regions in PML. Author(s): Yasuda Y, Yabe H, Inoue H, Shimizu T, Yabe M, Yogo Y, Kato S. Source: Neurology. 2003 December 9; 61(11): 1617-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14663055&dopt=Abstract
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Complementary techniques for unbiased stereology of brain ultrastructure. Author(s): Marrone DF, LeBoutillier JC, Petit TL. Source: Journal of Electron Microscopy. 2003; 52(4): 425-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14599105&dopt=Abstract
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Complete response of brain metastases originating in breast cancer to capecitabine therapy. Author(s): Siegelmann-Danieli N, Stein M, Bar-Ziv J. Source: Isr Med Assoc J. 2003 November; 5(11): 833-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14650117&dopt=Abstract
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Computed tomography and magnetic resonance imaging findings of brain damage by hanging. Author(s): Nakajo M, Onohara S, Shinmura K, Nakajo M, Amitani H, Munamoto T, Baba Y. Source: Journal of Computer Assisted Tomography. 2003 November-December; 27(6): 896-900. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14600457&dopt=Abstract
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Confocal imaging of xenobiotic transport across the blood-brain barrier. Author(s): Miller DS. Source: J Exp Zoolog Part a Comp Exp Biol. 2003 November 1; 300(1): 84-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14598390&dopt=Abstract
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Contemporary issues in mild traumatic brain injury. Author(s): Rees PM. Source: Archives of Physical Medicine and Rehabilitation. 2003 December; 84(12): 188594. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14669199&dopt=Abstract
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Correlation of regional metabolic rates of glucose with glasgow coma scale after traumatic brain injury. Author(s): Hattori N, Huang SC, Wu HM, Yeh E, Glenn TC, Vespa PM, McArthur D, Phelps ME, Hovda DA, Bergsneider M. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 November; 44(11): 1709-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602850&dopt=Abstract
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Coupled reductions in brain oxidative phosphorylation and synaptic function can be quantified and staged in the course of Alzheimer disease. Author(s): Rapoport SI. Source: Neurotox Res. 2003; 5(6): 385-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14715441&dopt=Abstract
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Creatine kinase BB in brain in schizophrenia. Author(s): Burbaeva GSh, Savushkina OK, Boksha IS. Source: World J Biol Psychiatry. 2003 October; 4(4): 177-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14608589&dopt=Abstract
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CT-guided stereotactic biopsies of brain stem lesions: personal experience and literature review. Author(s): Boviatsis EJ, Kouyialis AT, Stranjalis G, Korfias S, Sakas DE. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2003 October; 24(3): 97-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14600819&dopt=Abstract
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Current and future strategies in radiotherapy of childhood low-grade glioma of the brain. Part II: Treatment-related late toxicity. Author(s): Kortmann RD, Timmermann B, Taylor RE, Scarzello G, Plasswilm L, Paulsen F, Jeremic B, Gnekow AK, Dieckmann K, Kay S, Bamberg M. Source: Strahlentherapie Und Onkologie : Organ Der Deutschen Rontgengesellschaft. [et Al]. 2003 September; 179(9): 585-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14628124&dopt=Abstract
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De novo germinoma in the brain in association with Klinefelter's syndrome: case report and review of the literature. Author(s): Kaido T, Sasaoka Y, Hashimoto H, Taira K. Source: Surgical Neurology. 2003 December; 60(6): 553-8; Discussion 559. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14670679&dopt=Abstract
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Decompressive craniectomy in severe brain injury. Author(s): Messing-Junger AM, Marzog J, Wobker G, Sabel M, Bock WJ. Source: Zentralblatt Fur Neurochirurgie. 2003; 64(4): 171-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14634882&dopt=Abstract
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Decrease of serotonin receptor 2C in schizophrenia brains identified by highresolution mRNA expression analysis. Author(s): Castensson A, Emilsson L, Sundberg R, Jazin E. Source: Biological Psychiatry. 2003 December 1; 54(11): 1212-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14643089&dopt=Abstract
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Deep brain stimulation for cervical dystonia. Author(s): Krauss JK. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 November; 74(11): 1598. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14617734&dopt=Abstract
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Deep brain stimulation for Parkinson's disease. Author(s): Benabid AL. Source: Current Opinion in Neurobiology. 2003 December; 13(6): 696-706. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14662371&dopt=Abstract
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Delayed-onset deficits in verbal encoding strategies among patients with mild traumatic brain injury. Author(s): Bruce JM, Echemendia RJ. Source: Neuropsychology. 2003 October; 17(4): 622-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14599275&dopt=Abstract
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Delineation of brain structures from positron emission tomography images with deformable models. Author(s): Mykkanen J, Tohka J, Ruotsalainen U. Source: Stud Health Technol Inform. 2003; 95: 33-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14663959&dopt=Abstract
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Depression assessment after traumatic brain injury: an empirically based classification method. Author(s): Seel RT, Kreutzer JS. Source: Archives of Physical Medicine and Rehabilitation. 2003 November; 84(11): 16218. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14639561&dopt=Abstract
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Detection of structural differences between the brains of schizophrenic patients and controls. Author(s): Kovalev VA, Petrou M, Suckling J. Source: Psychiatry Research. 2003 November 30; 124(3): 177-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14623069&dopt=Abstract
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Development of human brain functions. Author(s): Johnson MH. Source: Biological Psychiatry. 2003 December 15; 54(12): 1312-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14675794&dopt=Abstract
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Developmental differences in behavioral and event-related brain responses associated with response preparation and inhibition in a go/nogo task. Author(s): Jonkman LM, Lansbergen M, Stauder JE. Source: Psychophysiology. 2003 September; 40(5): 752-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14696728&dopt=Abstract
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Diffuse brain oedema in idiopathic intracranial hypertension: a quantitative magnetic resonance imaging study. Author(s): Bastin ME, Sinha S, Farrall AJ, Wardlaw JM, Whittle IR. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 December; 74(12): 1693-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14638893&dopt=Abstract
100 Brain
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Diffusion imaging may predict reversible brain lesions in eclampsia and severe preeclampsia: initial experience. Author(s): Loureiro R, Leite CC, Kahhale S, Freire S, Sousa B, Cardoso EF, Alves EA, Borba P, Cerri GG, Zugaib M. Source: American Journal of Obstetrics and Gynecology. 2003 November; 189(5): 1350-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14634567&dopt=Abstract
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Distinct cytokine profile in SIDS brain: a common denominator in a multifactorial syndrome? Author(s): Kadhim H, Kahn A, Sebire G. Source: Neurology. 2003 November 11; 61(9): 1256-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14610131&dopt=Abstract
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Distribution and pharmacology of alanine-serine-cysteine transporter 1 (asc-1) in rodent brain. Author(s): Helboe L, Egebjerg J, Moller M, Thomsen C. Source: The European Journal of Neuroscience. 2003 October; 18(8): 2227-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14622183&dopt=Abstract
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Dual diagnoses: the person with a spinal cord injury and a concomitant brain injury. Author(s): Arzaga D, Shaw V, Vasile AT. Source: Sci Nurs. 2003 Summer; 20(2): 86-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14626031&dopt=Abstract
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Ear of stimulation determines schizophrenia-normal brain activity differences in an auditory paired-stimuli paradigm. Author(s): Clementz BA, Dzau JR, Blumenfeld LD, Matthews S, Kissler J. Source: The European Journal of Neuroscience. 2003 November; 18(10): 2853-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14656334&dopt=Abstract
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Editorial comment: diagnosis of focal brain lesions--old lessons retaught. Author(s): Price RW. Source: Aids Read. 2003 November; 13(11): 553. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14649626&dopt=Abstract
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Effect of co-morbid traumatic brain injury on functional outcome of persons with spinal cord injuries. Author(s): Macciocchi SN, Bowman B, Coker J, Apple D, Leslie D. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2004 January; 83(1): 22-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14709971&dopt=Abstract
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Effect of early targeted indomethacin on the ductus arteriosus and blood flow to the upper body and brain in the preterm infant. Author(s): Osborn DA, Evans N, Kluckow M. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2003 November; 88(6): F477-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602694&dopt=Abstract
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Effective treatment of the central nervous system in lysosomal storage diseases: save that brain! Author(s): Peters C. Source: The Journal of Laboratory and Clinical Medicine. 2003 December; 142(6): 361-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14713887&dopt=Abstract
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Elevated brain serotonin transporter availability in patients with obsessivecompulsive disorder. Author(s): Pogarell O, Hamann C, Popperl G, Juckel G, Chouker M, Zaudig M, Riedel M, Moller HJ, Hegerl U, Tatsch K. Source: Biological Psychiatry. 2003 December 15; 54(12): 1406-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14675805&dopt=Abstract
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Elevation of plasma brain natriuretic peptide is a hallmark of diastolic heart failure independent of ventricular hypertrophy. Author(s): Yamaguchi H, Yoshida J, Yamamoto K, Sakata Y, Mano T, Akehi N, Hori M, Lim YJ, Mishima M, Masuyama T. Source: Journal of the American College of Cardiology. 2004 January 7; 43(1): 55-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14715184&dopt=Abstract
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Endomorphins, endogenous opioid peptides, provide antioxidant defense in the brain against free radical-induced damage. Author(s): Lin X, Yang DJ, Cai WQ, Zhao QY, Gao YF, Chen Q, Wang R. Source: Biochimica Et Biophysica Acta. 2003 November 20; 1639(3): 195-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14636951&dopt=Abstract
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Epilepsy associated with pediatric brain tumors: the neuro-oncologic perspective. Author(s): Shuper A, Yaniv I, Michowitz S, Kornreich L, Schwartz M, Goldberg-Stern H, Cohen IJ. Source: Pediatric Neurology. 2003 September; 29(3): 232-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14629907&dopt=Abstract
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Estrogen research. Brain researchers try to salvage estrogen treatments. Author(s): Wickelgren I. Source: Science. 2003 November 14; 302(5648): 1138-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14615509&dopt=Abstract
102 Brain
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Evidence of correlated functional magnetic resonance imaging signals between distant human brains. Author(s): Standish LJ, Johnson LC, Kozak L, Richards T. Source: Alternative Therapies in Health and Medicine. 2003 January-February; 9(1): 128, 122-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14640097&dopt=Abstract
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Expectation enhances the regional brain metabolic and the reinforcing effects of stimulants in cocaine abusers. Author(s): Volkow ND, Wang GJ, Ma Y, Fowler JS, Zhu W, Maynard L, Telang F, Vaska P, Ding YS, Wong C, Swanson JM. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 December 10; 23(36): 11461-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14673011&dopt=Abstract
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Experience-dependent activation patterns in human brain during visual-motor associative learning. Author(s): Eliassen JC, Souza T, Sanes JN. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 November 19; 23(33): 10540-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14627638&dopt=Abstract
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Expression of brain natriuretic peptide by human bone marrow stromal cells. Author(s): Song S, Kamath S, Mosquera D, Zigova T, Sanberg P, Vesely DL, SanchezRamos J. Source: Experimental Neurology. 2004 January; 185(1): 191-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14697330&dopt=Abstract
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Expression of PRiMA in the mouse brain: membrane anchoring and accumulation of 'tailed' acetylcholinesterase. Author(s): Perrier NA, Kherif S, Perrier AL, Dumas S, Mallet J, Massoulie J. Source: The European Journal of Neuroscience. 2003 October; 18(7): 1837-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14622217&dopt=Abstract
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Expression of tenascin-C in various human brain tumors and its relevance for survival in patients with astrocytoma. Author(s): Leins A, Riva P, Lindstedt R, Davidoff MS, Mehraein P, Weis S. Source: Cancer. 2003 December 1; 98(11): 2430-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14635078&dopt=Abstract
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Fetal brain activity in response to a visual stimulus. Author(s): Fulford J, Vadeyar SH, Dodampahala SH, Moore RJ, Young P, Baker PN, James DK, Gowland PA. Source: Human Brain Mapping. 2003 December; 20(4): 239-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14673807&dopt=Abstract
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FGF17b and FGF18 have different midbrain regulatory properties from FGF8b or activated FGF receptors. Author(s): Liu A, Li JY, Bromleigh C, Lao Z, Niswander LA, Joyner AL. Source: Development (Cambridge, England). 2003 December; 130(25): 6175-85. Epub 2003 November 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602678&dopt=Abstract
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Food chain of evidence points to brain toxin. Author(s): Hampton T. Source: Jama : the Journal of the American Medical Association. 2003 December 3; 290(21): 2788-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14657048&dopt=Abstract
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Frameless stereotactic brain biopsy procedures using the Stealth Station: indications, accuracy and results. Author(s): Gralla J, Nimsky C, Buchfelder M, Fahlbusch R, Ganslandt O. Source: Zentralblatt Fur Neurochirurgie. 2003; 64(4): 166-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14634881&dopt=Abstract
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GABA(A) receptor subunit and gephyrin protein changes differ in the globus pallidus in Huntington's diseased brain. Author(s): Thompson-Vest NM, Waldvogel HJ, Rees MI, Faull RL. Source: Brain Research. 2003 December 24; 994(2): 265-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14642653&dopt=Abstract
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Ghrelin: a novel player in the gut-brain regulation of growth hormone and energy balance. Author(s): St-Pierre DH, Wang L, Tache Y. Source: News in Physiological Sciences : an International Journal of Physiology Produced Jointly by the International Union of Physiological Sciences and the American Physiological Society. 2003 December; 18: 242-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14614157&dopt=Abstract
104 Brain
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Glatiramer acetate-specific T cells in the brain express T helper 2/3 cytokines and brain-derived neurotrophic factor in situ. Author(s): Aharoni R, Kayhan B, Eilam R, Sela M, Arnon R. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 November 25; 100(24): 14157-62. Epub 2003 Nov 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14614135&dopt=Abstract
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High levels of orexin A in the brain of the mouse model for phenylketonuria: possible role of orexin A in hyperactivity seen in children with PKU. Author(s): Surendran S, Campbell GA, Tyring SK, Matalon K, McDonald JD, Matalon R. Source: Neurochemical Research. 2003 December; 28(12): 1891-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14649732&dopt=Abstract
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High-field magnetic resonance techniques for brain research. Author(s): Kim DS, Garwood M. Source: Current Opinion in Neurobiology. 2003 October; 13(5): 612-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14630227&dopt=Abstract
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How does connectivity between cortical areas depend on brain size? Implications for efficient computation. Author(s): Karbowski J. Source: Journal of Computational Neuroscience. 2003 November-December; 15(3): 34756. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14618069&dopt=Abstract
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Human immunodeficiency virus type 1 tat-mediated cytotoxicity of human brain microvascular endothelial cells. Author(s): Khan NA, Di Cello F, Nath A, Kim KS. Source: Journal of Neurovirology. 2003 December; 9(6): 584-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602571&dopt=Abstract
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Human serum amyloid P component attenuates the bacterial lipopolysaccharideinduced increase in blood-brain barrier permeability in mice. Author(s): Veszelka S, Urbanyi Z, Pazmany T, Nemeth L, Obal I, Dung NT, Abraham CS, Szabo G, Deli MA. Source: Neuroscience Letters. 2003 November 27; 352(1): 57-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14615049&dopt=Abstract
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Hyperglycemia and outcomes from pediatric traumatic brain injury. Author(s): Cochran A, Scaife ER, Hansen KW, Downey EC. Source: The Journal of Trauma. 2003 December; 55(6): 1035-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14676647&dopt=Abstract
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Hyperhomocysteinemia as an independent risk factor for silent brain infarction. Author(s): Kim NK, Choi BO, Jung WS, Choi YJ, Choi KG. Source: Neurology. 2003 December 9; 61(11): 1595-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14663048&dopt=Abstract
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Hypointensity on diffusion-weighted MRI of the brain related to T2 shortening and susceptibility effects. Author(s): Hiwatashi A, Kinoshita T, Moritani T, Wang HZ, Shrier DA, Numaguchi Y, Ekholm SE, Westesson PL. Source: Ajr. American Journal of Roentgenology. 2003 December; 181(6): 1705-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14627600&dopt=Abstract
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Identifying corollary discharges for movement in the primate brain. Author(s): Wurtz RH, Sommer MA. Source: Prog Brain Res. 2004; 144: 47-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14650839&dopt=Abstract
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Imaging of murine brain tumors using a 1.5 Tesla clinical MRI system. Author(s): van Furth WR, Laughlin S, Taylor MD, Salhia B, Mainprize T, Henkelman M, Cusimano MD, Ackerley C, Rutka JT. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2003 November; 30(4): 326-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14672264&dopt=Abstract
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Immunohistochemical expression of E-cadherin in metastatic brain tumors. Author(s): Shabani HK, Kitange G, Tsunoda K, Anda T, Tokunaga Y, Shibata S, Kaminogo M, Hayashi T, Ayabe H, Iseki M. Source: Brain Tumor Pathol. 2003; 20(1): 7-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14604226&dopt=Abstract
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Impairment of the blood-brain barrier can result in tacrolimus-induced reversible leucoencephalopathy following heart transplantation. Author(s): Kaczmarek I, Groetzner J, Meiser B, Mueller M, Landwehr P, Ueberfuhr P, Bruning R, Reichart B. Source: Clinical Transplantation. 2003 October; 17(5): 469-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14703933&dopt=Abstract
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Incidence of inflicted traumatic brain injury in infants. Author(s): Miller M. Source: Jama : the Journal of the American Medical Association. 2003 November 19; 290(19): 2542-3; Author Reply 2543. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14625325&dopt=Abstract
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Increased prevalence of sublinical brain perfusion abnormalities in patients with autoimmune thyroiditis: evidence of Hashimoto's encephalitis? Author(s): Zettinig G, Asenbaum S, Fueger BJ, Hofmann A, Diemling M, Mittlboeck M, Dudczak R. Source: Clinical Endocrinology. 2003 November; 59(5): 637-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14616889&dopt=Abstract
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Increases in plasma levels of atrial and brain natriuretic peptides after running a marathon: are their effects partly counterbalanced by adrenocortical steroids? Author(s): Niessner A, Ziegler S, Slany J, Billensteiner E, Woloszczuk W, Geyer G. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2003 December; 149(6): 555-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14640997&dopt=Abstract
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Induced gamma-band activity and human brain function. Author(s): Kaiser J, Lutzenberger W. Source: The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry. 2003 December; 9(6): 475-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14678580&dopt=Abstract
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Induction of intercellular adhesion molecule-1 on human brain endothelial cells by HIV-1 gp120: role of CD4 and chemokine coreceptors. Author(s): Stins MF, Pearce D, Di Cello F, Erdreich-Epstein A, Pardo CA, Sik Kim K. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2003 December; 83(12): 1787-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14691297&dopt=Abstract
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Inhibition of brain energy metabolism by the alpha-keto acids accumulating in maple syrup urine disease. Author(s): Sgaravatti AM, Rosa RB, Schuck PF, Ribeiro CA, Wannmacher CM, Wyse AT, Dutra-Filho CS, Wajner M. Source: Biochimica Et Biophysica Acta. 2003 November 20; 1639(3): 232-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14636955&dopt=Abstract
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Inhibitory control of acquired motor programs in the human brain. Author(s): Gerloff C, Hummel F. Source: Suppl Clin Neurophysiol. 2003; 56: 170-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14677391&dopt=Abstract
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Instruction-specific brain activations during episodic encoding. a generalized level of processing effect. Author(s): Petersson KM, Sandblom J, Elfgren C, Ingvar M. Source: Neuroimage. 2003 November; 20(3): 1795-810. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14642489&dopt=Abstract
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Interactive specification of regions of interest on brain surfaces. Author(s): Shiffman S, Ng YR, Brosnan TJ, Eliez S, Links JM, Kelkar UV, Reiss AL. Source: Neuroimage. 2003 November; 20(3): 1811-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14642490&dopt=Abstract
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Is blindsight in normals akin to blindsight following brain damage? Author(s): Marzi CA, Minelli A, Savazzi S. Source: Prog Brain Res. 2004; 144: 295-303. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14650856&dopt=Abstract
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Is the brain cortex a fractal? Author(s): Kiselev VG, Hahn KR, Auer DP. Source: Neuroimage. 2003 November; 20(3): 1765-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14642486&dopt=Abstract
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Isolated brain injury as a cause of hypotension in the blunt trauma patient. Author(s): Mahoney EJ, Biffl WL, Harrington DT, Cioffi WG. Source: The Journal of Trauma. 2003 December; 55(6): 1065-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14676652&dopt=Abstract
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Isolated superior rectus palsy due to contralateral midbrain infarction. Author(s): Kwon JH, Kwon SU, Ahn HS, Sung KB, Kim JS. Source: Archives of Neurology. 2003 November; 60(11): 1633-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14623739&dopt=Abstract
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Line bisection in the split brain. Author(s): Hausmann M, Corballis MC, Farbi M. Source: Neuropsychology. 2003 October; 17(4): 602-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14599273&dopt=Abstract
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Local gene knockdown in the brain using viral-mediated RNA interference. Author(s): Hommel JD, Sears RM, Georgescu D, Simmons DL, DiLeone RJ. Source: Nature Medicine. 2003 December; 9(12): 1539-44. Epub 2003 November 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14634645&dopt=Abstract
108 Brain
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Localization of a brain sulfotransferase, SULT4A1, in the human and rat brain: an immunohistochemical study. Author(s): Liyou NE, Buller KM, Tresillian MJ, Elvin CM, Scott HL, Dodd PR, Tannenberg AE, McManus ME. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 2003 December; 51(12): 1655-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14623933&dopt=Abstract
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Long-term follow-up of thalamic deep brain stimulation for essential and parkinsonian tremor. Author(s): Kumar R, Lozano AM, Sime E, Lang AE. Source: Neurology. 2003 December 9; 61(11): 1601-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14663050&dopt=Abstract
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LRP: a bright beacon at the blood-brain barrier. Author(s): Herz J. Source: The Journal of Clinical Investigation. 2003 November; 112(10): 1483-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14617749&dopt=Abstract
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Mapping individual brains to guide restorative therapy after stroke: rationale and pilot studies. Author(s): Cramer SC, Benson RR, Burra VC, Himes D, Crafton KR, Janowsky JS, Brown JA, Lutsep HL. Source: Neurological Research. 2003 December; 25(8): 811-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14669523&dopt=Abstract
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Measurement of urinary S100B protein concentrations for the early identification of brain damage in asphyxiated full-term infants. Author(s): Gazzolo D, Marinoni E, Di Iorio R, Bruschettini M, Kornacka M, Lituania M, Majewska U, Serra G, Michetti F. Source: Archives of Pediatrics & Adolescent Medicine. 2003 December; 157(12): 1163-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14662567&dopt=Abstract
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Metastatic carcinoma: an unusual cause of focal brain lesions in HIV infection. Author(s): Gaba AG, Sparano JA. Source: Aids Read. 2003 November; 13(11): 547-8, 551-3, 558-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14649625&dopt=Abstract
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Minimizing oxidative injury to the developing brain: the therapeutic quest continues. Author(s): Maulik D. Source: J Matern Fetal Neonatal Med. 2003 August;14(2):73-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14629085&dopt=Abstract
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Modulation of tremor amplitude during deep brain stimulation at different frequencies. Author(s): Beuter A, Titcombe MS. Source: Brain and Cognition. 2003 November; 53(2): 190-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14607145&dopt=Abstract
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Molecular cloning, characterization and brain mapping of the melanocortin 5 receptor in the goldfish. Author(s): Cerda-Reverter JM, Ling MK, Schioth HB, Peter RE. Source: Journal of Neurochemistry. 2003 December; 87(6): 1354-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14713292&dopt=Abstract
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Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors. Part 1: Growth factor and Ras signaling pathways. Author(s): Newton HB. Source: Expert Rev Anticancer Ther. 2003 October; 3(5): 595-614. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14599084&dopt=Abstract
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Mood changes with deep brain stimulation of STN and GPi: results of a pilot study. Author(s): Okun MS, Green J, Saben R, Gross R, Foote KD, Vitek JL. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 November; 74(11): 1584-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14617726&dopt=Abstract
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Multiple mechanisms control brain aromatase activity at the genomic and nongenomic level. Author(s): Balthazart J, Baillien M, Charlier TD, Cornil CA, Ball GF. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 September; 86(3-5): 367-79. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14623533&dopt=Abstract
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Mycoplasma pneumoniae infection as a treatable cause of brainstem encephalitis. Author(s): Lanczik O, Lecei O, Schwarz S, Hennerici M. Source: Archives of Neurology. 2003 December; 60(12): 1813; Author Reply 1813-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14676065&dopt=Abstract
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Neurochemistry of consciousness: cholinergic pathologies in the human brain. Author(s): Perry EK, Perry RH. Source: Prog Brain Res. 2004; 145: 287-99. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14650923&dopt=Abstract
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Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial. Author(s): Meyers CA, Smith JA, Bezjak A, Mehta MP, Liebmann J, Illidge T, Kunkler I, Caudrelier JM, Eisenberg PD, Meerwaldt J, Siemers R, Carrie C, Gaspar LE, Curran W, Phan SC, Miller RA, Renschler MF. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2004 January 1; 22(1): 157-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14701778&dopt=Abstract
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Neurologic intensive care resource use after brain tumor surgery: an analysis of indications and alternative strategies. Author(s): Ziai WC, Varelas PN, Zeger SL, Mirski MA, Ulatowski JA. Source: Critical Care Medicine. 2003 December; 31(12): 2782-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14668615&dopt=Abstract
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Neuronal expression of cell cycle-related proteins after brain ischaemia in man. Author(s): Love S. Source: Neuroscience Letters. 2003 December 15; 353(1): 29-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14642430&dopt=Abstract
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Neuronal nicotinic acetylcholine receptors: not just in brain. Author(s): Spindel ER. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2003 December; 285(6): L1201-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14604850&dopt=Abstract
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Neuronal representation of occluded objects in the human brain. Author(s): Olson IR, Gatenby JC, Leung HC, Skudlarski P, Gore JC. Source: Neuropsychologia. 2004; 42(1): 95-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14615079&dopt=Abstract
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Neuroscience. Brain model puts most sophisticated regions front and center. Author(s): Helmuth L. Source: Science. 2003 November 14; 302(5648): 1133. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14615503&dopt=Abstract
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Neuroscience: genomics on the brain. Author(s): Abbott A. Source: Nature. 2003 December 18; 426(6968): 757. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14685199&dopt=Abstract
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Nitric oxide synthase expression and enzymatic activity in human brain tumors. Author(s): Broholm H, Rubin I, Kruse A, Braendstrup O, Schmidt K, Skriver EB, Lauritzen M. Source: Clin Neuropathol. 2003 November-December; 22(6): 273-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14672505&dopt=Abstract
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Now you feel it, now you don't: frontal brain electrical asymmetry and individual differences in emotion regulation. Author(s): Jackson DC, Mueller CJ, Dolski I, Dalton KM, Nitschke JB, Urry HL, Rosenkranz MA, Ryff CD, Singer BH, Davidson RJ. Source: Psychological Science : a Journal of the American Psychological Society / Aps. 2003 November; 14(6): 612-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14629694&dopt=Abstract
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N-terminal pro-brain natriuretic peptide as a diagnostic marker of early pulmonary artery hypertension in patients with systemic sclerosis and effects of calcium-channel blockers. Author(s): Allanore Y, Borderie D, Meune C, Cabanes L, Weber S, Ekindjian OG, Kahan A. Source: Arthritis and Rheumatism. 2003 December; 48(12): 3503-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14674001&dopt=Abstract
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N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial necrosis, and the effect of an invasive strategy in unstable coronary artery disease. Author(s): Jernberg T, Lindahl B, Siegbahn A, Andren B, Frostfeldt G, Lagerqvist B, Stridsberg M, Venge P, Wallentin L. Source: Journal of the American College of Cardiology. 2003 December 3; 42(11): 190916. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14662251&dopt=Abstract
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Organ weight effects of drowning and asphyxiation on the lungs, liver, brain, heart, kidneys, and spleen. Author(s): Hadley JA, Fowler DR. Source: Forensic Science International. 2003 November 26; 137(2-3): 239-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14738080&dopt=Abstract
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p38 mitogen-activated protein kinase modulates expression of tumor necrosis factorrelated apoptosis-inducing ligand induced by interferon-gamma in fetal brain astrocytes. Author(s): Lee J, Shin JS, Park JY, Kwon D, Choi SJ, Kim SJ, Choi IH. Source: Journal of Neuroscience Research. 2003 December 15; 74(6): 884-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14648593&dopt=Abstract
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Patients undergoing surgical resection of primary brain tumors should receive pharmacologic venous thromboprophylaxis. Author(s): Begelman SM, Green D. Source: The Medical Clinics of North America. 2003 November; 87(6): 1179-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14680299&dopt=Abstract
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Peptide transport across the blood-brain barrier. Author(s): Kastin AJ, Pan W. Source: Prog Drug Res. 2003; 61: 79-100. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14674609&dopt=Abstract
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Perioperative hemodynamic heterogeneity of brain dead organ donors. Author(s): Duke PK, Ramsay MA, Gunning TC, Paulsen AW, Roberts LC. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1992; 5 Suppl 1: S719-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14621918&dopt=Abstract
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Plasma amino-terminal pro-brain natriuretic peptide and accuracy of heart-failure diagnosis in primary care: a randomized, controlled trial. Author(s): Wright SP, Doughty RN, Pearl A, Gamble GD, Whalley GA, Walsh HJ, Gordon G, Bagg W, Oxenham H, Yandle T, Richards M, Sharpe N. Source: Journal of the American College of Cardiology. 2003 November 19; 42(10): 1793800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14642690&dopt=Abstract
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Predicting neonatal brain injury: are we there yet? Author(s): Dennery PA. Source: Archives of Pediatrics & Adolescent Medicine. 2003 December; 157(12): 1151-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14662562&dopt=Abstract
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Predictive value of Glasgow Coma Scale after brain trauma: change in trend over the past ten years. Author(s): Balestreri M, Czosnyka M, Chatfield DA, Steiner LA, Schmidt EA, Smielewski P, Matta B, Pickard JD. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2004 January; 75(1): 161-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14707332&dopt=Abstract
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Prehospital hyperventilation after brain injury: a prospective analysis of prehospital and early hospital hyperventilation of the brain-injured patient. Author(s): Lal D, Weiland S, Newton M, Flaten A, Schurr M. Source: Prehospital Disaster Med. 2003 January-March; 18(1): 20-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14694896&dopt=Abstract
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Primary and secondary brain tumors at MR imaging: bicentric intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine. Author(s): Knopp MV, Runge VM, Essig M, Hartman M, Jansen O, Kirchin MA, Moeller A, Seeberg AH, Lodemann KP. Source: Radiology. 2004 January; 230(1): 55-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14695387&dopt=Abstract
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Prognostic value of interleukin-1 beta levels after acute brain injury. Author(s): Tasci A, Okay O, Gezici AR, Ergun R, Ergungor F. Source: Neurological Research. 2003 December; 25(8): 871-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14669533&dopt=Abstract
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Progress in clinical neurosciences: therapeutic hypothermia in severe traumatic brain injury. Author(s): Zygun DA, Doig CJ, Auer RN, Laupland KB, Sutherland GR. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2003 November; 30(4): 307-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14672261&dopt=Abstract
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Progress report of a Phase I study of the intracerebral microinfusion of a recombinant chimeric protein composed of transforming growth factor (TGF)-alpha and a mutated form of the Pseudomonas exotoxin termed PE-38 (TP-38) for the treatment of malignant brain tumors. Author(s): Sampson JH, Akabani G, Archer GE, Bigner DD, Berger MS, Friedman AH, Friedman HS, Herndon JE 2nd, Kunwar S, Marcus S, McLendon RE, Paolino A, Penne K, Provenzale J, Quinn J, Reardon DA, Rich J, Stenzel T, Tourt-Uhlig S, Wikstrand C, Wong T, Williams R, Yuan F, Zalutsky MR, Pastan I. Source: Journal of Neuro-Oncology. 2003 October; 65(1): 27-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14649883&dopt=Abstract
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Progressive brain volume loss during adolescence in childhood-onset schizophrenia. Author(s): Sporn AL, Greenstein DK, Gogtay N, Jeffries NO, Lenane M, Gochman P, Clasen LS, Blumenthal J, Giedd JN, Rapoport JL. Source: The American Journal of Psychiatry. 2003 December; 160(12): 2181-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14638588&dopt=Abstract
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Proton magnetic resonance spectroscopic imaging of the brain in childhood autism. Author(s): Levitt JG, O'Neill J, Blanton RE, Smalley S, Fadale D, McCracken JT, Guthrie D, Toga AW, Alger JR. Source: Biological Psychiatry. 2003 December 15; 54(12): 1355-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14675799&dopt=Abstract
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Proton MR spectroscopy of mitochondrial diseases: analysis of brain metabolic abnormalities and their possible diagnostic relevance. Author(s): Bianchi MC, Tosetti M, Battini R, Manca ML, Mancuso M, Cioni G, Canapicchi R, Siciliano G. Source: Ajnr. American Journal of Neuroradiology. 2003 November-December; 24(10): 1958-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14625217&dopt=Abstract
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Psychological distress and family burden following spinal cord injury: concurrent traumatic brain injury cannot be overlooked. Author(s): Buchanan KM, Elias LJ. Source: Axone. 2001 March; 22(3): 16-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14625968&dopt=Abstract
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Psychosocial status after pediatric traumatic brain injury: a subtype analysis using the Child Behavior Checklist. Author(s): Hayman-Abello SE, Rourke BP, Fuerst DR. Source: Journal of the International Neuropsychological Society : Jins. 2003 September; 9(6): 887-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14632248&dopt=Abstract
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Quality of life and post-concussion symptoms in adults after mild traumatic brain injury: a population-based study in western Sweden. Author(s): Emanuelson I, Andersson Holmkvist E, Bjorklund R, Stalhammar D. Source: Acta Neurologica Scandinavica. 2003 November; 108(5): 332-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14616303&dopt=Abstract
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Quality-of-life benefits and evidence of antitumour activity for patients with brain metastases treated with gefitinib. Author(s): Katz A, Zalewski P. Source: British Journal of Cancer. 2003 December; 89 Suppl 2: S15-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14661048&dopt=Abstract
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Radiosurgery in the treatment of malignant brain tumors. Author(s): Simonova G, Roman L. Source: Expert Rev Anticancer Ther. 2003 December; 3(6): 879-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14686709&dopt=Abstract
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Re: Endotracheal intubation in the field does not improve outcome in trauma patients who present without an acutely lethal traumatic brain injury. Bochicchio GV, Ilahi O, Joshi M, Bochicchio K, Scalea TM. J.Trauma. 2003;54:307-11. Author(s): Floccare DJ. Source: The Journal of Trauma. 2003 December; 55(6): 1184; Author Reply 1184-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14676673&dopt=Abstract
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Recurrent primary fibrosarcoma of the brain treated with the GliaSite brachytherapy system: case report. Author(s): Fraser RW, Limentani SA, Dollar JD, Asher A. Source: Surgical Neurology. 2003 December; 60(6): 579-83; Discussion 583-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14670686&dopt=Abstract
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Regional brain atrophy rate predicts future cognitive decline: 6-year longitudinal MR imaging study of normal aging. Author(s): Rusinek H, De Santi S, Frid D, Tsui WH, Tarshish CY, Convit A, de Leon MJ. Source: Radiology. 2003 December; 229(3): 691-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14657306&dopt=Abstract
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Reliability of peak cardiorespiratory responses in patients with moderate to severe traumatic brain injury. Author(s): Bhambhani Y, Rowland G, Farag M. Source: Archives of Physical Medicine and Rehabilitation. 2003 November; 84(11): 162936. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14639562&dopt=Abstract
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Report of a male patient with brain metastases from breast cancer. Author(s): Nieder C, Jost PJ, Grosu AL, Peschel C, Molls M. Source: Breast (Edinburgh, Scotland). 2003 October; 12(5): 345-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14659151&dopt=Abstract
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Review article: altered states of consciousness, theories of recovery, and assessment following a severe traumatic brain injury. Author(s): Duff D. Source: Axone. 2001 September; 23(1): 18-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14621499&dopt=Abstract
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Role of basal ganglia-brainstem systems in the control of postural muscle tone and locomotion. Author(s): Takakusaki K, Oohinata-Sugimoto J, Saitoh K, Habaguchi T. Source: Prog Brain Res. 2004; 143: 231-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14653168&dopt=Abstract
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Roles of diverse glutamate receptors in brain functions elucidated by subunit-specific and region-specific gene targeting. Author(s): Mori H, Mishina M. Source: Life Sciences. 2003 December 5; 74(2-3): 329-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14607261&dopt=Abstract
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Schizophrenia and Parkinson's disease lead to equal motor-related changes in cortical and subcortical brain activation: an fMRI fingertapping study. Author(s): Muller JL, Deuticke C, Putzhammer A, Roder CH, Hajak G, Winkler J. Source: Psychiatry and Clinical Neurosciences. 2003 December; 57(6): 562-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14629703&dopt=Abstract
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Scientists find connections in the brain between physical and emotional pain. Author(s): Vastag B. Source: Jama : the Journal of the American Medical Association. 2003 November 12; 290(18): 2389-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14612461&dopt=Abstract
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Sensorimotor recovery in children after traumatic brain injury: analyses of gait, gross motor, and fine motor skills. Author(s): Kuhtz-Buschbeck JP, Hoppe B, Golge M, Dreesmann M, Damm-Stunitz U, Ritz A. Source: Developmental Medicine and Child Neurology. 2003 December; 45(12): 821-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14667074&dopt=Abstract
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Serotonergic brainstem abnormalities in Northern Plains Indians with the sudden infant death syndrome. Author(s): Kinney HC, Randall LL, Sleeper LA, Willinger M, Belliveau RA, Zec N, Rava LA, Dominici L, Iyasu S, Randall B, Habbe D, Wilson H, Mandell F, McClain M, Welty TK. Source: Journal of Neuropathology and Experimental Neurology. 2003 November; 62(11): 1178-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14656075&dopt=Abstract
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Serum and brain concentrations of methylphenidate: implications for use and abuse. Author(s): Swanson JM, Volkow ND. Source: Neuroscience and Biobehavioral Reviews. 2003 November; 27(7): 615-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14624806&dopt=Abstract
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Side of brain infarction and long-term risk of sudden death in patients with symptomatic carotid disease. Author(s): Algra A, Gates PC, Fox AJ, Hachinski V, Barnett HJ; North American Symptomatic Carotid Endarterectomy Trial Group. Source: Stroke; a Journal of Cerebral Circulation. 2003 December; 34(12): 2871-5. Epub 2003 November 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14631091&dopt=Abstract
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Significance of plasma N-terminal pro-brain natriuretic peptide in patients with systemic sclerosis-related pulmonary arterial hypertension. Author(s): Mukerjee D, Yap LB, Holmes AM, Nair D, Ayrton P, Black CM, Coghlan JG. Source: Respiratory Medicine. 2003 November; 97(11): 1230-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14635979&dopt=Abstract
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Simulation of brain death from fulminant de-efferentation. Author(s): Friedman Y, Lee L, Wherrett JR, Ashby P, Carpenter S. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2003 November; 30(4): 397-404. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14672276&dopt=Abstract
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Social rejection may be pain to the brain. Author(s): Burton A. Source: Lancet. Neurology. 2003 December; 2(12): 717. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14649240&dopt=Abstract
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Somatotropic-axis deficiency affects brain substrates of selective attention in childhood-onset growth hormone deficient patients. Author(s): Lijffijt M, Van Dam PS, Kenemans JL, Koppeschaar HP, de Vries WR, Drent ML, Wittenberg A, Kemner C. Source: Neuroscience Letters. 2003 December 19; 353(2): 123-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14664916&dopt=Abstract
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Stereotactic co-registration of magnetic resonance imaging and histopathology in post-mortem multiple sclerosis brain. Author(s): Schmierer K, Scaravilli F, Barker GJ, Gordon R, MacManus DG, Miller DH. Source: Neuropathology and Applied Neurobiology. 2003 December; 29(6): 596-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14636166&dopt=Abstract
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Stereotactic radiosurgery for brain metastases from gastrointestinal tract cancer. Author(s): Hasegawa T, Kondziolka D, Flickinger JC, Lunsford LD. Source: Surgical Neurology. 2003 December; 60(6): 506-14; Discussion 514-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14670663&dopt=Abstract
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Still unresolved issues with brain-type natriuretic peptide measurement in the critically ill patient. Author(s): Giannitsis E, Katus HA. Source: Critical Care Medicine. 2003 November; 31(11): 2703-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14605548&dopt=Abstract
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Stimulus complexity enhances auditory discrimination in patients with extremely severe brain injuries. Author(s): Kotchoubey B, Lang S, Herb E, Maurer P, Schmalohr D, Bostanov V, Birbaumer N. Source: Neuroscience Letters. 2003 December 4; 352(2): 129-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14625040&dopt=Abstract
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Stretching the truth. Why hippocampal neurons are so vulnerable following traumatic brain injury. Author(s): McCarthy MM. Source: Experimental Neurology. 2003 November; 184(1): 40-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14637077&dopt=Abstract
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Structural and functional aspects of the blood-brain barrier. Author(s): Begley DJ, Brightman MW. Source: Prog Drug Res. 2003; 61: 39-78. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14674608&dopt=Abstract
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Successful brainstem cavernous malformation resection after repeated hemorrhages during pregnancy. Author(s): Flemming KD, Goodman BP, Meyer FB. Source: Surgical Neurology. 2003 December; 60(6): 545-7; Discussion 547-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14670675&dopt=Abstract
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Survival benefit of stereotactic radiosurgery for metastatic brain tumors in patients with controlled primary lesions and no other distant metastases. Author(s): Niibe Y, Karasawa K, Nakamura O, Shinoura N, Okamoto K, Yamada R, Fukino K, Tanaka Y. Source: Anticancer Res. 2003 September-October; 23(5B): 4157-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14666618&dopt=Abstract
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Synuclein aggregation: possible role in traumatic brain injury. Author(s): Bramlett HM, Dietrich WD. Source: Experimental Neurology. 2003 November; 184(1): 27-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14637075&dopt=Abstract
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Taste-olfactory convergence, and the representation of the pleasantness of flavour, in the human brain. Author(s): de Araujo IE, Rolls ET, Kringelbach ML, McGlone F, Phillips N. Source: The European Journal of Neuroscience. 2003 October; 18(7): 2059-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14622239&dopt=Abstract
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Temporal discrimination in the split brain. Author(s): Funnell MG, Corballis PM, Gazzaniga MS. Source: Brain and Cognition. 2003 November; 53(2): 218-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14607151&dopt=Abstract
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The brain and the I: neurodevelopment and personal identity. Author(s): Mahowald MB. Source: J Soc Philos. 1996 Winter; 27(3): 49-60. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14621716&dopt=Abstract
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The brainstem and vulnerability to sudden infant death syndrome. Author(s): Thach BT. Source: Neurology. 2003 November 11; 61(9): 1170-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14610114&dopt=Abstract
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The emotional brain: neural correlates of cat sexual behavior and human male ejaculation. Author(s): Holstege G, Georgiadis JR. Source: Prog Brain Res. 2004; 143: 39-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14653149&dopt=Abstract
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The impact of brain death on survival after heart transplantation: time is of the essence. Author(s): Cantin B, Kwok BW, Chan MC, Valantine HA, Oyer PE, Robbins RC, Hunt SA. Source: Transplantation. 2003 November 15; 76(9): 1275-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14627902&dopt=Abstract
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The longitudinal relation between brain lesion load and atrophy in multiple sclerosis: a 14 year follow up study. Author(s): Chard DT, Brex PA, Ciccarelli O, Griffin CM, Parker GJ, Dalton C, Altmann DR, Thompson AJ, Miller DH. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 November; 74(11): 1551-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14617714&dopt=Abstract
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The musician's brain: functional imaging of amateurs and professionals during performance and imagery. Author(s): Lotze M, Scheler G, Tan HR, Braun C, Birbaumer N. Source: Neuroimage. 2003 November; 20(3): 1817-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14642491&dopt=Abstract
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The relation between brain MRI lesions and depressive symptoms in multiple sclerosis. Author(s): Benesova Y, Niedermayerova I, Mechl M, Havlikova P. Source: Bratisl Lek Listy. 2003; 104(4-5): 174-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14604264&dopt=Abstract
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The relationship of brain and cervical cord volume to disability in clinical subtypes of multiple sclerosis: a three-dimensional MRI study. Author(s): Lin X, Blumhardt LD, Constantinescu CS. Source: Acta Neurologica Scandinavica. 2003 December; 108(6): 401-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14616292&dopt=Abstract
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The self: clues from the brain. Author(s): LeDoux J. Source: Annals of the New York Academy of Sciences. 2003 October; 1001: 295-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14625368&dopt=Abstract
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The significance of the mutated divalent metal transporter (DMT1) on iron transport into the Belgrade rat brain. Author(s): Moos T, Morgan EH. Source: Journal of Neurochemistry. 2004 January; 88(1): 233-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14675167&dopt=Abstract
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Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein. Author(s): Yepes M, Sandkvist M, Moore EG, Bugge TH, Strickland DK, Lawrence DA. Source: The Journal of Clinical Investigation. 2003 November; 112(10): 1533-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14617754&dopt=Abstract
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Transcranial magnetic brain stimulation and the cerebellum. Author(s): Wessel K. Source: Suppl Clin Neurophysiol. 2003; 56: 441-5. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14677420&dopt=Abstract
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Transcranial magnetic stimulation in brainstem lesions and lesions of the cranial nerves. Author(s): Urban PP. Source: Suppl Clin Neurophysiol. 2003; 56: 341-57. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14677411&dopt=Abstract
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Traumatic brain injury and automotive design: making motor vehicles safer. Author(s): Nirula R, Kaufman R, Tencer A. Source: The Journal of Trauma. 2003 November; 55(5): 844-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14608154&dopt=Abstract
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Traumatic brain injury. Author(s): Dutton RP, McCunn M. Source: Current Opinion in Critical Care. 2003 December; 9(6): 503-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14639070&dopt=Abstract
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Treatment of brain metastases from melanoma. Author(s): McWilliams RR, Brown PD, Buckner JC, Link MJ, Markovic SN. Source: Mayo Clinic Proceedings. 2003 December; 78(12): 1529-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14661682&dopt=Abstract
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Unintentional traumatic brain injury in children: the lived experience. Author(s): Chisholm J, Bruce B. Source: Axone. 2001 September; 23(1): 12-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14621498&dopt=Abstract
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Update on the therapeutic approaches to brain tumors. Author(s): Lallana EC, Abrey LE. Source: Expert Rev Anticancer Ther. 2003 October; 3(5): 655-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14599089&dopt=Abstract
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Use of brain natriuretic peptide levels for risk assessment in non-ST-elevation acute coronary syndromes. Author(s): White HD, French JK. Source: Journal of the American College of Cardiology. 2003 December 3; 42(11): 191720. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14662252&dopt=Abstract
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Utility of brain natriuretic peptide to predict right ventricular dysfunction and clinical outcome in patients with acute pulmonary embolism. Author(s): Thabut G, Logeart D. Source: Circulation. 2003 September 30; 108(13): E94; Author Reply E94-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14631970&dopt=Abstract
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Validation of a model for evaluating outcome after traumatic brain injury. Author(s): Bush BA, Novack TA, Malec JF, Stringer AY, Millis SR, Madan A. Source: Archives of Physical Medicine and Rehabilitation. 2003 December; 84(12): 18037. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14669187&dopt=Abstract
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Vesicular glutamate transporters in the brain. Author(s): Hisano S. Source: Anatomical Science International / Japanese Association of Anatomists. 2003 December; 78(4): 191-204. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14686474&dopt=Abstract
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Violence-related traumatic brain injury: a population-based study. Author(s): Gerhart KA, Mellick DC, Weintraub AH. Source: The Journal of Trauma. 2003 December; 55(6): 1045-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14676649&dopt=Abstract
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Walter Moxon and his thoughts about language and the brain. Author(s): Buckingham HW. Source: Journal of the History of the Neurosciences. 2003 September; 12(3): 292-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14628545&dopt=Abstract
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Water transport becomes uncoupled from K+ siphoning in brain contusion, bacterial meningitis, and brain tumours: immunohistochemical case review. Author(s): Saadoun S, Papadopoulos MC, Krishna S. Source: Journal of Clinical Pathology. 2003 December; 56(12): 972-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14645363&dopt=Abstract
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White matter fiber tracking in patients with space-occupying lesions of the brain: a new technique for neurosurgical planning? Author(s): Clark CA, Barrick TR, Murphy MM, Bell BA. Source: Neuroimage. 2003 November; 20(3): 1601-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14642471&dopt=Abstract
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Who makes good use of memory aids? Results of a survey of people with acquired brain injury. Author(s): Evans JJ, Wilson BA, Needham P, Brentnall S. Source: Journal of the International Neuropsychological Society : Jins. 2003 September; 9(6): 925-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14632251&dopt=Abstract
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Wild-type measles virus in brain tissue of children with subacute sclerosing panencephalitis, Argentina. Author(s): Barrero PR, Grippo J, Viegas M, Mistchenko AS. Source: Emerging Infectious Diseases. 2003 October; 9(10): 1333-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14609476&dopt=Abstract
Academic Periodicals covering Brain Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to brain. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, 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.”
Dissertations on Brain 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. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “brain” (or a synonym) in their titles. The following covers recent dissertations found when using this search procedure: •
The Homeroom Concept: A Special Education Approach to Rehabilitation in Traumatic Brain Injury (Brain Injury) by Goyer, Victor Joseph, EDD from Clark University, 1990, 237 pages http://wwwlib.umi.com/dissertations/fullcit/9026081
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The Identification and Utilization of Standardized Instruments with Traumatic Brain Injury Clients at the Alliance of Texas Head Injury Rehabilitation Facilities (Head Injury) by Spiegel, Doris M., EDD from Texas A&M University, 1990, 111 pages http://wwwlib.umi.com/dissertations/fullcit/9106899
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The Impact of Patient-centered Information on Patients' Treatment Adherence, Satisfaction, and Outcomes in Traumatic Brain Injury Rehabilitation by Pegg, Phillip Oliver, Jr.; PhD from Virginia Commonwealth University, 2003, 330 pages http://wwwlib.umi.com/dissertations/fullcit/3094840
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The Influence of Drugs of Abuse on Rat Brain Histamine Studies with Ethanol by Prell, George D; PhD from University of Ottawa (Canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK65721
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The 'Kitab Al-Hawi' of Razi (ca. 900 Ad), Book One of the 'Hawi' on Brain, Nerve, and Mental Disorders: Studies in the Transmission of Medical Texts from Greek into Arabic into Latin (Iran, Abu Bakr Muhammad B. Zakariyya Ar-Razi) by Bryson, Jennifer S.; PhD from Yale University, 2000, 380 pages http://wwwlib.umi.com/dissertations/fullcit/9991125
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The Moral Identity of Traumatic Brain Injury Survivors (Medical Ethics, Disability) by Thobaben, James R., PhD from Emory University, 1994, 528 pages http://wwwlib.umi.com/dissertations/fullcit/9425890
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The Prevalence of Traumatic Brain Injury in Battered Women Residing in Northern New Jersey Shelters by Marcantonis, Eleni; PsyD from The Wright Institute, 2003, 80 pages http://wwwlib.umi.com/dissertations/fullcit/3098093
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The Recovery of the Function of Reading after Traumatic Brain Injury (rehabilitation, Cognition) by Seymour, Jeanette, PhD from Temple University, 1985, 407 pages http://wwwlib.umi.com/dissertations/fullcit/8521140
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The Relationship between the Wechsler Intelligence Scale for Children-third Edition and the Test of Memory and Learning in a Pediatric Traumatic Brain Injury Population by Schmidt, Mark Edward; PhD from Texas Woman's University, 2003, 74 pages http://wwwlib.umi.com/dissertations/fullcit/3084186
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The Relationship of Functional Academic Achievement to the Clinical Categories of Brain Injury and Emotional Disturbance. by Ardi, Dana Beth, PhD from Boston College, 1978, 158 pages http://wwwlib.umi.com/dissertations/fullcit/7813771
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The Th2 Bias in CNS Immune Privilege: Induction of Humoral, Cellular, and Cytokine Immune Responses to Soluble Protein Antigen Administered into the Cerebrospinal Fluid of Mice with Normal Blood Brain Barrier Permeability by Park, Joel Thomas, II; PhD from Brown University, 2003, 347 pages http://wwwlib.umi.com/dissertations/fullcit/3087323
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The Transition of Students with Traumatic Brain Injuries from Hospital to School: a Nationwide Survey (Rehabilitation) by Beard, Gene Huntley, EDD from University of South Carolina, 1992, 106 pages http://wwwlib.umi.com/dissertations/fullcit/9239012
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'This Is Your Brain on Drugs': the Public Policy of Anti-drug Programming. An Exploratory Analysis of Media and Other Sources of Drug Information for Adolescents by Patterson, Valerie Elaine Lyles, PhD from Florida International University, 1995, 266 pages http://wwwlib.umi.com/dissertations/fullcit/9601813
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Transient Decrease in Brain Protein Synthesis after in Vivo Administration of a Psychotropic Drug: Mechanism and Developmental Effects by Holbrook, Larry A; PhD from University of Toronto (Canada), 1977 http://wwwlib.umi.com/dissertations/fullcit/NK36692
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Traumatic Brain Injury and Substance Abuse: A Comparative Analysis of Family Functioning by Depompei, Roberta Ann, PhD from The University of Akron, 1991, 214 pages http://wwwlib.umi.com/dissertations/fullcit/9207613
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Traumatic Brain Injury of a Child: Effects on the Marital Relationship and Parenting by Lyth-Frantz, Lori, PhD from State University of New York at Buffalo, 1998, 183 pages http://wwwlib.umi.com/dissertations/fullcit/9822169
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Traumatic Brain Injury Survivors and the Relationship of Neuropsychological and Demographic Variables to Functional Outcome by Minarik, Mary Jane; PhD from Alliant International University, Los Angeles, 2003, 111 pages http://wwwlib.umi.com/dissertations/fullcit/3087071
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Using Suggestive-Accelerative Learning and Teaching with Survivors of Traumatic Brain Injury to Stimulate Higher Mental Functions by Farnsworth, Kristy, PhD from The Fielding Institute, 1996, 109 pages http://wwwlib.umi.com/dissertations/fullcit/9722582
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Using Suggestive-Accelerative Learning and Teaching with Survivors of Traumatic Brain Injury to Stimulate Higher Mental Functions by Farnsworth, Kristy, PhD from The Fielding Institute, 1996, 109 pages http://wwwlib.umi.com/dissertations/fullcit/9722582
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A Holistic Instructional Approach for University Students (Brain Functioning) by Rini, James Richard, EDD from University of Florida, 1990, 138 pages http://wwwlib.umi.com/dissertations/fullcit/9106469
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A Nationwide Study of Goal Attainment among Health Resources and Services Administration-Funded Traumatic Brain Injury State Demonstration Grantees by Schutz, William Vaclav, Jr.; PhD from University of Pittsburgh, 2001, 252 pages http://wwwlib.umi.com/dissertations/fullcit/3026086
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A Neuropsychological Day Treatment Program for Mild Traumatic Brain Injury Evaluation and Rehabilitation by McCawley, Patrick Victor; PsyD from Carlos Albizu University, 2003, 103 pages http://wwwlib.umi.com/dissertations/fullcit/3082908
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Acquired Brain Injury (ABI) in High School Students: Prevalence, Experiences, and Significance for Public Policy (brain Injury) by Topalian, Sandra J., PhD from Brandeis U., the F. Heller Grad. Sch. for Adv. Stud. in Soc. Wel., 1994, 214 pages http://wwwlib.umi.com/dissertations/fullcit/9432323
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Angular Acceleration Attenuation for Brain Injury Prevention in Ice Hockey by Therrien, Rene Gilles, PhD from The Pennsylvania State University, 1979, 155 pages http://wwwlib.umi.com/dissertations/fullcit/8006064
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Brain Dominance and Self-actualization (brain Processing, Mental Health, Cerebral Dominance, Hemisphericity, Personal Orientation Inventory (POI), Herrmann Brain Dominance Instrument (HBDI)) by Bernhoft, Franklin Otto, PhD from Brigham Young University, 1985, 239 pages http://wwwlib.umi.com/dissertations/fullcit/8603360
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Caregiver Coping Resources and the Care of a Relative with Traumatic Brain Injury (Home Care) by Caperton, Rebecca Clendenin, PhD from Memphis State University, 1993, 122 pages http://wwwlib.umi.com/dissertations/fullcit/9402977
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Cognitive Processing Theory: A Basis for Instruction for Adolescents with Traumatic Brain Injury (reading Comprehension) by Wright, Carol Lynn, PhD from University of Florida, 1995, 226 pages http://wwwlib.umi.com/dissertations/fullcit/9618789
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Coping Behavior of Patients and Their Families to a Life-Threatening Illness (Brain Tumor). by Hung, Aileen Wu, DSW from Columbia University, 1976, 575 pages http://wwwlib.umi.com/dissertations/fullcit/7809908
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CRE-Binding Transcription Factors Mediate Distinct Effects of Antidepressant Drugs in the Brain by Conti, Alana Caroline; PhD from University of Pennsylvania, 2003, 133 pages http://wwwlib.umi.com/dissertations/fullcit/3087387
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Development and Evaluation of a Videotape to Teach Self-Feeding Skills for BrainInjured Patients to Nursing Students by MacKenzie, Carol Anne, PhD from Temple University, 1990, 265 pages http://wwwlib.umi.com/dissertations/fullcit/9100309
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Education and Related Services for Students with Traumatic Brain Injury and Their Families: An Analysis of the Views of Three Groups of Leaders in the Field by Ruoff, Janis Kaye, PhD from Gallaudet University, 1995, 155 pages http://wwwlib.umi.com/dissertations/fullcit/9536101
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Effect of Holistic and Non-Holistic Teaching Strategies on Cerebral Hemispheric Laterality (Cerebral Dominance, Neuroeducation, EEG Studies, Right Brain) by Wilson, Thomas Ross, III, PhD from Washington State University, 1986, 132 pages http://wwwlib.umi.com/dissertations/fullcit/8702570
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Effects of Cerebellar Injury and Insulin-Like Growth Factor 1 Administration on Functional Recovery in a Rat Model of Traumatic Brain Injury by Reynolds, Laura Patricia Ruth; MSC from Dalhousie University (Canada), 2003, 131 pages http://wwwlib.umi.com/dissertations/fullcit/MQ79593
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Experimental Traumatic Brain Injury and Cell Death: In Vivo and in Vitro Aspects by Mattiasson, Gustav Johannes; PhD from Lunds Universitet (Sweden), 2003, 136 pages http://wwwlib.umi.com/dissertations/fullcit/f60321
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Exploring Relationships between Mild Traumatic Brain Injury and Special Education by Irons, Mary Jane; PhD from University of Virginia, 2001, 105 pages http://wwwlib.umi.com/dissertations/fullcit/3003874
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Frontal Lobe Functioning in Children with Focal Frontal Brain Injury, Non-Focal Brain Injury and Matched Controls (Lurian Tasks, Wisconsin Card Sorting Test) by Couch, Kathy Watkins, PhD from University of Georgia, 1985, 105 pages http://wwwlib.umi.com/dissertations/fullcit/8606032
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'I Have Softening of the Brain and I Will Soon Be Dead': Understanding Acute Psychotic Decompensation from the Patient's Perspective by Dunn, Shannon Denise; PhD from Loyola University of Chicago, 2002, 216 pages http://wwwlib.umi.com/dissertations/fullcit/3039280
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Lateralized Sex Differences in Human Cognitive Functioning (Stroke, Blood Flow, Brain, Neuropsychological) by Larue, Linda Jane, PhD from Rutgers the State University of New Jersey - New Brunswick, 1986, 107 pages http://wwwlib.umi.com/dissertations/fullcit/8612125
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Localized Chemotherapy Delivery to the Brain: Improving Drug Distribution with Polymer Conjugation by Fleming, Alison Blake; PhD from Cornell University, 2003, 200 pages http://wwwlib.umi.com/dissertations/fullcit/3075861
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Long-Term Consequences of Severe Traumatic Brain Injury on Adults: A Qualitative Study of Families' Perceptions of Impact and Public Policy by Wood, Wendy Michelle, PhD from Virginia Commonwealth University, 1993, 342 pages http://wwwlib.umi.com/dissertations/fullcit/9319851
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Making It Visible: Defining Nursing Practice with Traumatic Brain Injured Adults in a Rehabilitation Setting by Currie, Kelly Susan Michelle; MN from Dalhousie University (Canada), 2003, 174 pages http://wwwlib.umi.com/dissertations/fullcit/MQ79508
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Mediation and Modulation of Blood Glucose Responses to Stress by Adrenal Hormones and Brain Norepinephrine Implications for Behavioral Responses to Stress by Bialik, Robert J; PhD from Carleton University (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL39349
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Meta-Analyses of the Effectiveness of Traumatic Brain Injury Interventions by Stratton, Tamara Anne; PhD from The University of Utah, 2003, 121 pages http://wwwlib.umi.com/dissertations/fullcit/3075100
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Metabolic, Neurochemical, and Histological Responses to Activation Following Traumatic Brain Injury in the Rat by Ip, Emily Yu-yen; PhD from University of California, Los Angeles, 2003, 177 pages http://wwwlib.umi.com/dissertations/fullcit/3081177
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Mind over Matter: Independent Living for Brain Injury Survivors by Forkosch, Joel Anton, PhD from University of Pennsylvania, 1994, 467 pages http://wwwlib.umi.com/dissertations/fullcit/9521028
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Mortality and Life Expectancy after Traumatic Brain Injury Rehabilitation by Harrison-Felix, Cynthia Lee; PhD from University of Colorado Health Sciences Center, 2003, 288 pages http://wwwlib.umi.com/dissertations/fullcit/3098183
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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
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Nitrogen and Oxygen Radicals in Ischemic and Hypoxic Injury of the Brain by Dobrucki, Wawrzyniec Lawrence; PhD from Ohio University, 2003, 158 pages http://wwwlib.umi.com/dissertations/fullcit/3089485
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Prolonged Calcium Flux Following Traumatic Brain Injury Occurs Via InjuryInduced Molecular Alterations in the NMDA Receptor by Osteen, Cheri Lynne; PhD from University of California, Los Angeles, 2003, 200 pages http://wwwlib.umi.com/dissertations/fullcit/3081155
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Psycholinguistic Abilities and Oral Word Recognition Associated with Relative Level of Personality Adjustment in Primary School-Age Children with 'Minimal Brain Dysfunction.' by Celebre, Gerald, EDD from Temple University, 1971, 160 pages http://wwwlib.umi.com/dissertations/fullcit/7119976
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Risk Factors to School-Aged Traumatic Brain Injury Survivor's Academic Success by Leuenberger, Sharon Lynn, PhD from State University of New York at Buffalo, 1998, 97 pages http://wwwlib.umi.com/dissertations/fullcit/9822165
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Social and Recreational Patterns of Adolescent Survivors of Traumatic Brain Injury and Their Families (Social Patterns) by Alcouloumre, Debra S., EDD from Columbia University Teachers College, 1995, 515 pages http://wwwlib.umi.com/dissertations/fullcit/9525478
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Substance Abuse and Brain Injury As Predictors of Health Care Utilization and Other Measures of Outcome in Adults Following an Automobile Accident by White, Jeffrey David; PhD from University of South Carolina, 2003, 93 pages http://wwwlib.umi.com/dissertations/fullcit/3098717
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Sustained Attention and Processing Speed in Children with Traumatic Brain Injury (TBI) and Children with Attention-Deficit Hyperactivity Disorder (ADHD) by Hagen, Jody Lynn; PhD from University of Montana, 2003, 62 pages http://wwwlib.umi.com/dissertations/fullcit/3090736
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The Comparative Effects of Three-Week and Six-Week Periods of Residential Camping on Physical Fitness and Adaptive Behavior in Children and Youth with Brain Dysfunction Syndromes by Lefebvre, Claudette B., PhD from New York University, 1972, 163 pages http://wwwlib.umi.com/dissertations/fullcit/7220643
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The Development and Implementation of the Positive Kids Model: a Whole-brain Teaching Approach for Children Ages 3 to 12 Focussing on Health Behaviors and the Spiritual Component of Commitment As a Holistic Approach to Substance-abuse Prevention (substanc by Mfune, Saustin Sampson Kazgeba, Dmin from Andrews University, 1992, 386 pages http://wwwlib.umi.com/dissertations/fullcit/9225980
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The Effects of a Selected Mental Challenge on the Fluid Intelligence, Perceived Health Status, and Affective Functions of Selected Texas A&M University Retirees (Brain Aging) by Hoover, Lonnie Daniel, PhD from Texas A&M University, 1991, 178 pages http://wwwlib.umi.com/dissertations/fullcit/9216938
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The Effects of Group Psychotherapy on Mental Status, Social Adaptation, and Depression in Elderly Persons in Long-Term Care with Age-Onset Organic Brain Syndrome by Christopher, Frima, PhD from New York University, 1986, 161 pages http://wwwlib.umi.com/dissertations/fullcit/8706305
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CHAPTER 2. NUTRITION AND BRAIN Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and brain.
Finding Nutrition Studies on Brain 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. Once you have entered 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” (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 is a typical result when searching for recently indexed consumer information on brain: •
Acute and chronic effects of protein and carbohydrate ingestion on brain tryptophan levels and serotonin synthesis. Source: Fernstrom, J.D. Nutrition-reviews (USA). (May 1986). volume 44(suppl.) page 25-36.
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Biochemical regulation of brain function. Source: Lovenberg, W.M. Nutrition-reviews (USA). (May 1986). volume 44(suppl.) page 6-11.
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Blood-brain barrier transport of nutrients. Source: Pardridge, W.M. Nutrition-reviews (USA). (May 1986). volume 44(suppl.) page 15-25.
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Brain boosters: can supplements sharpen you memory? Source: Welland, D. Environmental-nutrition (USA). (October 1998). volume 21(10) page 1, 4.
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Diet and brain function. Source: Krassner, M.B. Nutrition-reviews (USA). (May 1986). volume 44(suppl.) page 1215.
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Nutrition and brain function: trace elements. Source: Sandstead, H.H. Nutrition-reviews (USA). (May 1986). volume 44(suppl.) page 37-41.
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Silicon: a nutritional beneficence for bones, brains and blood vessels? Source: Seaborn, C.D. Nielsen, F.H. Nutrition-today (USA). (August 1993). volume 28(4) page 13-18.
Additional consumer oriented references include: •
Battling brain diseases: diet links to Alzheimer's and Parkinson's. Source: Antinoro, L. Environ-nutr. New York : Environmental Nutrition, Inc.,. April 2001. volume 24 (4) page 1, 4. 0893-4452
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Brain cholecystokinin receptors and satiety. Source: Nutr-Rev. New York, N.Y. : Springer-Verlag New York Inc. Sept 1990. volume 48 (9) page 359-360. 0029-6643
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Brain neurochemistry and macronutrient selection: a role for serotonin feedback? Source: Anonymous Nutr-Revolume 1992 January; 50(1): 21-2 0029-6643
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Bs are for brain power. Source: Tufts-Univ-diet-nutr-lett. New York, N.Y. : Tufts University Diet and Nutrition Letter, 1983-c1997. March 1996. volume 14 (1) page 6-7. 0747-4105
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Caffeine can increase brain serotonin levels. Source: Anonymous Nutr-Revolume 1988 October; 46(10): 366-7 0029-6643
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Calcium-binding proteins: differential regulation in intestine, kidney, and brain. Source: Nutr-Rev. New York, N.Y.: Springer-Verlag New York Inc. June 1991. volume 49 (6) page 191-194. 0029-6643
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Deficiency and excess of iron in brain function and dysfunction. Author(s): Faculty of Medicine with Technion, Eve Topf and US National Parkinson Foundation Centers of Excellence for Research in Neurodegenerative Diseases, Haifa, Israel. Source: Youdim, M B Nutr-Revolume 2001 August; 59(8 Pt 2): S83-5; discussion S85-7 0029-6643
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Docosahexaenoic acid sources for the developing brain during intrauterine life. Author(s): Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
[email protected] Source: Yavin, E Glozman, S Green, P Nutr-Health. 2001; 15(3-4): 219-24 0260-1060
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Does dietary tryptophan influence serotonin release from brain neurons? Source: Anonymous Nutr-Revolume 1987 March; 45(3): 87-9 0029-6643
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Does tight glucose control enhance brain sensitivity to low glucose? Source: Herold, K C Polonsky, K S Diabetes-Care. 1991 February; 14(2): 141-3 0149-5992
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Effect of parenteral linoleate on fatty acid composition of infant brain and liver. Source: Anonymous Nutr-Revolume 1987 August; 45(8): 232-4 0029-6643
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Exercise, physical activity, nutrition, and the brain. Author(s): German Sport University. Source: Hollmann, W Struder, H K Nutr-Revolume 1996 April; 54(4 Pt 2): S37-43 00296643
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Food for the infant's brain. Source: Warner, J. BNF-nutr-bull. London : The British Nutrition Foundation. March 1998. volume 23 (suppl.1) page 65-76. 0141-9684
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Infant vitamin B6 deficiency and preconvulsant activity in brain. Source: Anonymous Nutr-Revolume 1988 October; 46(10): 358-60 0029-6643
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Iron deficiency and brain proteins. Source: Anonymous Nutr-Revolume 1987 October; 45(10): 317-9 0029-6643
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Iron in the brain. Source: Beard, J.L. Connor, J.R. Jones, B.C. Nutrition-reviews (USA). (June 1993). volume 51(6) page 157-170. iron brain deficiency diseases globulins 0029-6643
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Lead-associated protein in kidney and brain. Source: Nutrition-reviews (USA). (October 1986). volume 44(10) page 347-348. lead toxicity proteins detoxification kidneys brain mineral metabolism 0029-6643
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Leptin and bone: does the brain control bone biology? Author(s): University of North Carolina, Greensboro 27412-5001, USA. Source: Fleet, J C Nutr-Revolume 2000 July; 58(7): 209-11 0029-6643
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Macronutrients and neurotransmitter formation during brain development. Author(s): Department of Physiology, Biophysics and Neuroscience, Center of Research and Advanced Studies, Mexico, D.F., Mexico. Source: Hernandez Rodriguez, J Manjarrez Gutierrez, G Nutr-Revolume 2001 August; 59(8 Pt 2): S49-57; discussion S58-9 0029-6643
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Maintaining memory: remember better by feeding your brain. Source: Antinoro, L. Environ-nutr. New York : Environmental Nutrition, Inc.,. March 2001. volume 24 (3) page 1, 4. 0893-4452
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n-3 Fatty acids in the brain and retina: evidence for their essentiality. Source: Neuringer, M. Connor, W.E. Nutrition-reviews (USA). (September 1986). volume 44(9) page 285-294. laboratory animals brain eyes nutritional requirements deficiency diseases experiments 0029-6643
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Nutrition. Can taking vitamins protect your brain? Source: Anonymous Harv-Health-Lett. 2000 August; 25(10): 2-3 1052-1577
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Ontogeny of brain and cognition: relevance to nutrition research. Author(s): Institute Universitaire de Geriatrie de Montreal, Department of Medicine, Universite de Montreal, Quebec, Canada. Source: Lecours, A R Mandujano, M Romero, G Nutr-Revolume 2001 August; 59(8 Pt 2): S7-11; discussion S11-2 0029-6643
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Proceedings of the 3rd Nestle Nutrition Conference. Nutrition and Brain Function from Infancy to Old Age. Mexico City, Mexico, March 30-31, 2000. Source: Anonymous Nutr-Revolume 2001 August; 59(8 Pt 2): S1-101 0029-6643
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Rodolfo Llinas. A grand unification theory of the brain. Source: Herbert, W US-News-World-Repage 2000 January 3-10; 128(1): 68-9 0041-5537
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The impact of the supply of glucose to the brain on mood and memory. Author(s): University of Wales Swansea, Swansea SA28PD, Wales, United Kingdom. Source: Benton, D Nutr-Revolume 2001 January; 59(1 Pt 2): S20-1 0029-6643
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The importance of energy and nutrient supply in human brain evolution. Author(s): Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Canada. Source: Cunnane, S C Harbige, L S Crawford, M A Nutr-Health. 1993; 9(3): 219-35 02601060
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The role of dietary fatty acids in biology: their place in the evolution of the human brain. Author(s): Institute of Brain Chemistry and Human Nutrition, Hackney Hospital, London, UK. Source: Crawford, M A Nutr-Revolume 1992 April; 50(4 ( Pt 2)): 3-11 0029-6643
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Vitamin A functions in the regulation of the dopaminergic system in the brain and pituitary gland. Author(s): Department of Nutritional Sciences, University of California, Berkeley 947203104, USA. Source: Wolf, G Nutr-Revolume 1998 December; 56(12): 354-5 0029-6643
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Ways that foods can affect the brain. Source: Wurtman, R.J. Nutrition-reviews (USA). (May 1986). volume 44(suppl.) page 26. diet neurotropic drugs appetite carbohydrates choline tyrosine 0029-6643
The following information is typical of that found when using the “Full IBIDS Database” to search for “brain” (or a synonym): •
(2S,3R) beta-methyl-2',6'-dimethyltyrosine-L-tetrahydroisoquinoline-3-carboxylic acid [(2S,3R)TMT-L-Tic-OH] is a potent, selective delta-opioid receptor antagonist in mouse brain. Author(s): Department of Pharmacology, University of Arizona, Tucson, Arizona 85724, USA. Source: Hosohata, K Varga, E V Alfaro Lopez, J Tang, X Vanderah, T W Porreca, F Hruby, V J Roeske, W R Yamamura, H I J-Pharmacol-Exp-Ther. 2003 February; 304(2): 683-8 0022-3565
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Alcohol consumption in traumatic brain injury: attenuation of TBI-induced hyperthermia and neurocognitive deficits. Author(s): Department of Neurobiology and Brain Research Institute, UCLA School of Medicine, Los Angeles, California 90095-1763, USA.
[email protected] Source: Taylor, A N Romeo, H E Beylin, A V Tio, D L Rahman, S U Hovda, D A JNeurotrauma. 2002 December; 19(12): 1597-608 0897-7151
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Aluminium related changes in brain histology: protection by calcium and nifedipine. Author(s): Lady Brabourne College, P 1/2, Surawardy Avenue, Calcutta 700017, India. Source: Basu, S Das Gupta, R Chaudhuri, A N Indian-J-Exp-Biol. 2000 September; 38(9): 948-50 0019-5189
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Binding site of salsolinol: its properties in different regions of the brain and the pituitary gland of the rat. Author(s): Neuroendocrine Research Laboratory, Department of Human Morphology and Developmental Biology, Semmelweis University, IX Tuzolto u. 58, Budapest H1094, Hungary. Source: Homicsko, K G Kertesz, I Radnai, B Toth, B E Toth, G Fulop, F Fekete, M I Nagy, G M Neurochem-Int. 2003 January; 42(1): 19-26 0197-0186
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Brain manganese concentrations in rats following manganese tetroxide inhalation are unaffected by dietary manganese intake. Author(s): CIIT Centers for Health Research, Research Triangle Park, NC 27709-2137, USA.
[email protected] Source: Dorman, D C Struve, M F Wong, B A Neurotoxicology. 2002 July; 23(2): 185-95 0161-813X
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Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain. Author(s): Department of Molecular Medicine, Hematology and Oncology, Osaka University Graduate School of Medicine, C9, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
[email protected] Source: Kuratsune, H Yamaguti, K Lindh, G Evengard, B Hagberg, G Matsumura, K Iwase, M Onoe, H Takahashi, M Machii, T Kanakura, Y Kitani, T Langstrom, B Watanabe, Y Neuroimage. 2002 November; 17(3): 1256-65 1053-8119
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Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: long-term follow-up. Author(s): Department of Neuroscience, University of Turin, Via Cherasco 15, I-10126 Turin, Italy. Source: Tavella, A Bergamasco, B Bosticco, E Lanotte, M Perozzo, P Rizzone, M Torre, E Lopiano, L Neurol-Sci. 2002 September; 23 Suppl 2: S111-2 1590-1874
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Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain. Author(s): Department of Physiology, Sikkim Manipal Institute of Medical Sciences, 5th Mile, Tadong, Gangtok 737102, Sikkim, India.
[email protected] Source: Nayak, P Chatterjee, A K BMC-Neurosci. 2003 February 25; 4(1): 4 1471-2202
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Effect of acupuncture on the auditory evoked brain stem potential in Parkinson's disease. Author(s): Second Clinical College, Nanjing University of Traditional Chinese Medicine, Nanjing 210029. Source: Wang, L He, C Liu, Y Zhu, L J-Tradit-Chin-Med. 2002 March; 22(1): 15-7 02546272
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Effect of undernutrition on GMP-PNP binding and adenylate cyclase activity from rat brain. Author(s): Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Source: Rotta, L N Nogueira, C W da Silva, L Soares, F A Perry, M L Souza, D O CellMol-Neurobiol. 2002 June; 22(3): 365-72 0272-4340
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Effects of 17beta-estradiol on blood-brain barrier disruption during focal ischemia in rats. Author(s): Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901-1977, USA.
[email protected] Source: Chi, O Z Liu, X Weiss, H R Horm-Metab-Res. 2002 September; 34(9): 530-4 00185043
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Effects of manganese (Mn) on the developing rat brain: oxidative-stress related endpoints. Author(s): Department of Physiology and Pharmacology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1083, USA. Source: Weber, S Dorman, D C Lash, L H Erikson, K Vrana, K E Aschner, M Neurotoxicology. 2002 July; 23(2): 169-75 0161-813X
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Effects of oral cadmium exposure through puberty on plasma prolactin and gonadotropin levels and amino acid contents in various brain areas in pubertal male rats. Author(s): Laboratorio de Toxicologia, Facultad de Ciencias, Universidad de Vigo, Orense, Spain.
[email protected] Source: Lafuente, A Esquifino, A I Neurotoxicology. 2002 July; 23(2): 207-13 0161-813X
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Expression patterns of antioxidant proteins in brains of patients with sporadic Creutzfeldt-Jacob disease. Author(s): F. Hoffmann-La Roche Ltd, Pharmaceuticals Division, Basel, Switzerland. Source: Krapfenbauer, K Yoo, B C Fountoulakis, M Mitrova, E Lubec, G Electrophoresis. 2002 August; 23(15): 2541-7 0173-0835
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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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Frontal brain asymmetry in restrained eaters. Author(s): Psychobiology Department, Complutense University, Madrid, Spain. Source: Silva, J R Pizzagalli, D A Larson, C L Jackson, D C Davidson, R J J-AbnormPsychol. 2002 November; 111(4): 676-81 0021-843X
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Gene expression of transferrin and transferrin receptor in brains of control vs. irondeficient rats. Author(s): Department of Nutrition, The Pennsylvania State University, S-126, Henderson Building, University Park, PA 16802, USA. Source: Han, J Day, J R Connor, J R Beard, J L Nutr-Neurosci. 2003 February; 6(1): 1-10 1028-415X
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Human nature is unique in the mismatch between the usual diet and the need for “food for the brain” (marine fat, DHA). Adding marine fat is beneficial in
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schizophrenia and manic-depressive psychosis. This underlines brain dysfunction in these neurological disorders is associated with deficient intake of marine fat(DHA). Source: Saugstad, L F Nutr-Health. 2002; 16(1): 41-4 0260-1060 •
Identification of new thyroid hormone-regulated genes in rat brain neuronal cultures. Author(s): Laboratory of Human Genetics, Laval University Medical Research Center, Quebec, Canada. Source: Martel, J Cayrou, C Puymirat, J Neuroreport. 2002 October 28; 13(15): 1849-51 0959-4965
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Inhibition of fibrin-induced neurogenic pulmonary edema by previous unilateral left-vagotomy correlates with increased levels of brain nitric oxide synthase in the nucleus tractus solitarii of rats. Author(s): Department of Anesthesiology, Nagoya University School of Medicine, Showa-ku, Nagoya 466-8550, Japan. Source: Feng, G G Nishiwaki, K Kondo, H Shimada, Y Ishikawa, N Auton-Neurosci. 2002 November 29; 102(1-2): 1-7 1566-0702
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Lead stimulates the glutathione system in selective regions of rat brain. Author(s): Laboratory of Pathobiochemistry of the Central Nervous System, Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland.
[email protected] Source: Struzynska, L Sulkowski, G Lenkiewicz, A Rafalowska, U Folia-Neuropathol. 2002; 40(4): 203-9
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Levodopa response motor complications--GABA receptors and preproenkephalin expression in human brain. Author(s): Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, Pavillon CHUL, CHUQ, 2705, Laurier Boulevard, G1V 4G2, Sainte-Foy, Que, Canada. Source: Calon, F Di Paolo, T Parkinsonism-Relat-Disord. 2002 September; 8(6): 449-54 1353-8020
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Lithium modulates expression of TRH receptors and TRH-related peptides in rat brain. Author(s): Research Service, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA. Source: Sattin, A Senanayake, S S Pekary, A E Neuroscience. 2002; 115(1): 263-73 03064522
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Manganese action in brain function. Author(s): Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, 422-8526, Shizuoka, Japan.
[email protected] Source: Takeda, A Brain-Res-Brain-Res-Revolume 2003 January; 41(1): 79-87 0165-0173
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Marine fat and brain function in manic-depressive psychosis and schizophrenia: circumstantial evidence for a 2nd aquatic period. Source: Saugstad, L F Nutr-Health. 2002; 16(1): 11-2 0260-1060
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MgATP and phosphoinositides activate Na(+)/Ca(2+) exchange in bovine brain vesicles. Comparison with other Na(+)/Ca(2+) exchangers. Author(s): Laboratorio de Biofisica, Instituto de Investigacion Medica Mercedes y Martin Ferreyra, Casilla de Correo 389, 5000 Cordoba, Argentina.
[email protected]
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Source: Berberian, G Asteggiano, C Pham, C Roberts, S Beauge, L Pflugers-Arch. 2002 Aug; 444(5): 677-84 0031-6768 •
Moderate zinc deficiency increases cell death after brain injury in the rat. Author(s): Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee 32306-4340, USA. Source: Yeiser, E C Vanlandingham, J W Levenson, C W Nutr-Neurosci. 2002 October; 5(5): 345-52 1028-415X
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Movement-related modulation of neural activity in human basal ganglia and its LDOPA dependency: recordings from deep brain stimulation electrodes in patients with Parkinson's disease. Author(s): Department of Neurological Sciences, IRCCS Ospedale Maggiore, Policlinico, University of Milan, Padiglione Ponti, Via F. Sforza 35, 20122 Milan, Italy. Source: Priori, A Foffani, G Pesenti, A Bianchi, A Chiesa, V Baselli, G Caputo, E Tamma, F Rampini, P Egidi, M Locatelli, M Barbieri, S Scarlato, G Neurol-Sci. 2002 September; 23 Suppl 2: S101-2 1590-1874
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Pathways leading to apoptotic neurodegeneration following trauma to the developing rat brain. Author(s): Department of Neonatology, Charite Children's Hospital, Humboldt University, 13353 Berlin, Germany. Source: Felderhoff Mueser, U Sifringer, M Pesditschek, S Kuckuck, H Moysich, A Bittigau, P Ikonomidou, C Neurobiol-Dis. 2002 November; 11(2): 231-45 0969-9961
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Protective effects of curcumin against ischaemia/reperfusion insult in rat forebrain. Author(s): Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. Source: Ghoneim, A I Abdel Naim, A B Khalifa, A E El Denshary, E S Pharmacol-Res. 2002 September; 46(3): 273-9 1043-6618
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Proton magnetic resonance spectroscopy of brain-stem lesions. Author(s): Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7510, USA. Source: Smith, J K Londono, A Castillo, M Kwock, L Neuroradiology. 2002 October; 44(10): 825-9 0028-3940
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Relationships among brain metabolites, cognitive function, and viral loads in antiretroviral-naive HIV patients. Author(s): Medical Department, Brookhaven National Laboratory, Upton, New York 11973-5000, USA.
[email protected] Source: Chang, L Ernst, T Witt, M D Ames, N Gaiefsky, M Miller, E Neuroimage. 2002 November; 17(3): 1638-48 1053-8119
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Signaling events mediating activation of brain ethanolamine plasmalogen hydrolysis by ceramide. Author(s): Departamento de Bioquimica y Biologia Molecular I, Facultad de Quimicas, Universidad Complutense de Madrid, Madrid, Spain. Source: Latorre, E Collado, M P Fernandez, I Aragones, M D Catalan, R E Eur-JBiochem. 2003 January; 270(1): 36-46 0014-2956
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Simultaneous repetitive movements following pallidotomy or subthalamic deep brain stimulation in patients with Parkinson's disease. Author(s): Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
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Source: Levy, R Lang, A E Hutchison, W D Lozano, A M Dostrovsky, J O Exp-Brain-Res. 2002 December; 147(3): 322-31 0014-4819 •
The decrease in antioxidant potential in human brain tumours. Author(s): Department of Neurosurgery, Medical Academy of Bialystok, Bialystok, Poland. Source: Dudek, H Farbiszewski, R Michno, T Witek, A Kozlowski, A Rydzewska, M Rocz-Akad-Med-Bialymst. 2002; 47: 113-22
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The effects of dietary sulfur amino acid deficiency on rat brain glutathione concentration and neural damage in global hemispheric hypoxia-ischemia. Author(s): College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Sask., S7N 5C9, Canada. Source: Bobyn, P J Franklin, J L Wall, C M Thornhill, J A Juurlink, B H Paterson, P G Nutr-Neurosci. 2002 December; 5(6): 407-16 1028-415X
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Time-dependent changes in rat brain cholinergic receptor expression after experimental brain injury. Author(s): Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536-0082, USA. Source: Verbois, S L Scheff, S W Pauly, J R J-Neurotrauma. 2002 December; 19(12): 156985 0897-7151
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Traumatic brain injury and subarachnoid hemorrhage: in vivo occult pathology demonstrated by magnetic resonance spectroscopy may not be “ischaemic”. A primary study and review of the literature. Author(s): Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK. Source: Macmillan, C S Wild, J M Wardlaw, J M Andrews, P J Marshall, I Easton, V J Acta-Neurochir-(Wien). 2002 September; 144(9): 853-62; discussion 862 0001-6268
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to brain; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Folic Acid Source: Integrative Medicine Communications; www.drkoop.com Folic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,887,00.html Niacin Source: Integrative Medicine Communications; www.drkoop.com Niacin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,892,00.html Pantothenic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,882,00.html
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Vitamin B1 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B3 (Niacin) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B9 (Folic Acid) Alternative names: Folate, Folic Acid Source: Integrative Medicine Communications; www.drkoop.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com •
Minerals Acetyl-l-carnitine Source: Healthnotes, Inc.; www.healthnotes.com Calcium Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,884,00.html Carnitine Source: Prima Communications, Inc.www.personalhealthzone.com Carnitine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10012,00.html Carnitine (L-carnitine) Source: Integrative Medicine Communications; www.drkoop.com Chromium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10018,00.html Copper Source: Integrative Medicine Communications; www.drkoop.com Fluoxetine Source: Healthnotes, Inc.; www.healthnotes.com Folate Source: Integrative Medicine Communications; www.drkoop.com
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Folate Source: Prima Communications, Inc.www.personalhealthzone.com Gabapentin Source: Healthnotes, Inc.; www.healthnotes.com Iron Source: Healthnotes, Inc.; www.healthnotes.com L-carnitine Source: Integrative Medicine Communications; www.drkoop.com Lecithin and Choline Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10040,00.html Lecithin/phosphatidylcholine/choline Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,890,00.html Manganese Source: Integrative Medicine Communications; www.drkoop.com Paroxetine Source: Healthnotes, Inc.; www.healthnotes.com Vinpocetine Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com •
Food and Diet Athletic Performance Source: Healthnotes, Inc.; www.healthnotes.com Chili Peppers Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,132,00.html Low-Purine Diet Source: Healthnotes, Inc.; www.healthnotes.com Low-Salt Diet Source: Healthnotes, Inc.; www.healthnotes.com
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Octopus Source: Healthnotes, Inc.; www.healthnotes.com Omega-3 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com Omega-3 Fatty Acids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,992,00.html Pain Source: Healthnotes, Inc.; www.healthnotes.com Variety Meats Source: Healthnotes, Inc.; www.healthnotes.com Water Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 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. At the conclusion of this chapter, we will provide additional sources.
The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “brain” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: •
Ginkgo: A Practical Guide Source: Garden City Park, NY: Avery Publishing Group. 1998. 172 p. Contact: Avery Publishing Group. 120 Old Broadway, Garden City Park, NY 11040. (800) 548-5757; INTERNATIONAL: (516) 741-2155; FAX: (516) 742-1892. PRICE: $9.95. ISBN: 0895298120. Summary: This book is designed to help consumers use 'Ginkgo biloba' safely and effectively to promote health, prevent illness, and treat disease. Chapter 1 reviews the history of Ginkgo in herbal medicine; and Chapter 2 examines the attitudes toward herbal medicines in Chinese, Indian, and Western cultures. Chapter 3 discusses the science of Ginkgo, including its key active components and its actions in the body. Chapters 4 through 7 focus on specific applications of Ginkgo and its effects in disorders of the brain, the heart and circulatory system, the senses, and sexuality. Chapter 8 discusses the use of Ginkgo in other conditions such as radiation exposure, sun damage,
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allergies, asthma, and hepatitis; and offers advice to consumers about the reasons for taking Ginkgo, methods of taking it, and how much to take. Chapter 9 summarizes the health benefits of using Ginkgo. The book includes a glossary and an index. •
Power of More Than One: The Role of Support Groups in Mind/Body Healing Source: Alternative and Complementary Therapies. 4(2): 84-88. April 1998. Summary: This journal article discusses the role of support groups in mind/body healing. According to the article, the mind/body science of psychoneuroimmunology has established that the brain and the rest of the body communicate directly, and supports the focus on the interaction of mind, body, and the immune system that is at the core of holistic health practices. Scientific research that emphasizes the effectiveness of support groups in people with cancer is discussed. This article discusses a therapist's impression of the importance of support groups in the lives of people with cancer. It provides a list of readings and organizations, including contact information. It also contains 2 tables and 8 references.
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Alternative Medicine Update Source: Alternative Health Practitioner. 3(3): 157-160. Fall/Winter 1997. Summary: This journal article reports the results of 12 studies funded by the Office of Alternative Medicine in 1993 and 1994. The studies were classified as either mind/body interventions or as pharmacological or biological treatments. The 10 mind/body intervention studies include the following therapies: biofeedback, dance movement therapy, guided imagery, hypnotic imagery, music therapy, prayer, and yoga. Conditions studied include pain, diabetes mellitus, cystic fibrosis, asthma, immunity, cancer, AIDS, brain injury, and drug abuse. The two pharmacological and biological studies were 'Enzyme Therapy and Experimental Memory Metastasis' and 'Pharmacological Treatment of Cancer by Antioxidants.'.
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 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” (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: •
Acute demyelination: diagnostic difficulties and the need for brain biopsy. Author(s): Maarouf M, Kuchta J, Miletic H, Ebel H, Hesselmann V, Hilker R, Sturm V. Source: Acta Neurochirurgica. 2003 November; 145(11): 961-9; Discussion 969. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14628201&dopt=Abstract
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Alcoholism risk and the P300 event-related brain potential: modality, task, and gender effects. Author(s): Reese C, Polich J.
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Source: Brain and Cognition. 2003 October; 53(1): 46-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14572502&dopt=Abstract •
Alterations in brain and immune function produced by mindfulness meditation: three caveats. Author(s): Smith JC. Source: Psychosomatic Medicine. 2004 January-February; 66(1): 148-52; Author Reply 148-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14747650&dopt=Abstract
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An aminopyridazine-based inhibitor of a pro-apoptotic protein kinase attenuates hypoxia-ischemia induced acute brain injury. Author(s): Velentza AV, Wainwright MS, Zasadzki M, Mirzoeva S, Schumacher AM, Haiech J, Focia PJ, Egli M, Watterson DM. Source: Bioorganic & Medicinal Chemistry Letters. 2003 October 20; 13(20): 3465-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14505650&dopt=Abstract
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An experimental environment for the production, exchange and discussion of fused radiology images, for the management of patients with residual brain tumour disease. Author(s): Sakellaropoulos GC, Kagadis GC, Karystianos C, Karnabatidis D, Constantoyannis C, Nikiforidis GC. Source: Medical Informatics and the Internet in Medicine. 2003 June; 28(2): 135-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14692590&dopt=Abstract
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Anatomical and functional brain variables associated with clozapine response in treatment-resistant schizophrenia. Author(s): Molina V, Reig S, Sarramea F, Sanz J, Francisco Artaloytia J, Luque R, Aragues M, Pascau J, Benito C, Palomo T, Desco M. Source: Psychiatry Research. 2003 November 30; 124(3): 153-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14623067&dopt=Abstract
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Antioxidants in Alzheimer's disease-vitamin C delivery to a demanding brain. Author(s): Quinn J, Suh J, Moore MM, Kaye J, Frei B. Source: Journal of Alzheimer's Disease : Jad. 2003 August; 5(4): 309-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14624026&dopt=Abstract
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Automatic processing of grammar in the human brain as revealed by the mismatch negativity. Author(s): Pulvermuller F, Shtyrov Y. Source: Neuroimage. 2003 September; 20(1): 159-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14527578&dopt=Abstract
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Basal forebrain cholinergic modulation of auditory activity in the zebra finch song system. Author(s): Shea SD, Margoliash D. Source: Neuron. 2003 December 18; 40(6): 1213-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14687554&dopt=Abstract
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Brain activity during intra- and cross-modal priming: new empirical data and review of the literature. Author(s): Carlesimo GA, Turriziani P, Paulesu E, Gorini A, Caltagirone C, Fazio F, Perani D. Source: Neuropsychologia. 2004; 42(1): 14-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14615073&dopt=Abstract
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Brain flow changes before and after deep brain stimulation of the subthalamic nucleus in Parkinson's disease. Author(s): Antonini A, Marotta G, Benti R, Landi A, De Notaris R, Mariani C, Gerundini P, Pezzoli G, Gaini SM. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2003 October; 24(3): 151-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14598061&dopt=Abstract
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Brain ganglioside and glycoprotein sialic acid in breastfed compared with formulafed infants. Author(s): Wang B, McVeagh P, Petocz P, Brand-Miller J. Source: The American Journal of Clinical Nutrition. 2003 November; 78(5): 1024-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14594791&dopt=Abstract
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Brain mechanics For neurosurgery: modeling issues. Author(s): Kyriacou SK, Mohamed A, Miller K, Neff S. Source: Biomechanics and Modeling in Mechanobiology. 2002 October; 1(2): 151-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14595547&dopt=Abstract
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Brain phenylalanine concentrations in phenylketonuria: research and treatment of adults. Author(s): Moats RA, Moseley KD, Koch R, Nelson M Jr. Source: Pediatrics. 2003 December; 112(6 Pt 2): 1575-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14654668&dopt=Abstract
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Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor alpha in mice. Author(s): Inoue H, Jiang XF, Katayama T, Osada S, Umesono K, Namura S.
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Source: Neuroscience Letters. 2003 December 11; 352(3): 203-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14625020&dopt=Abstract •
Brain reorganization after stroke. Author(s): Green JB. Source: Topics in Stroke Rehabilitation. 2003 Fall; 10(3): 1-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14681816&dopt=Abstract
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Brainstem auditory evoked-potentials in dairy cows recorded with Nape-Vertex derivation. Author(s): Dondi M, Bianchi E, Callegari D, Quintavalla F. Source: Veterinary Research Communications. 2003 September; 27 Suppl 1: 745-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14535512&dopt=Abstract
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Children processing music: electric brain responses reveal musical competence and gender differences. Author(s): Koelsch S, Grossmann T, Gunter TC, Hahne A, Schroger E, Friederici AD. Source: Journal of Cognitive Neuroscience. 2003 July 1; 15(5): 683-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12965042&dopt=Abstract
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Contact call-driven zenk mRNA expression in the brain of the budgerigar (Melopsittacus undulatus). Author(s): Brauth SE, Tang YZ, Liang W, Roberts TF. Source: Brain Research. Molecular Brain Research. 2003 September 10; 117(1): 97-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499486&dopt=Abstract
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Coupled reductions in brain oxidative phosphorylation and synaptic function can be quantified and staged in the course of Alzheimer disease. Author(s): Rapoport SI. Source: Neurotox Res. 2003; 5(6): 385-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14715441&dopt=Abstract
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Critical decision-speed and information transfer in the “Graz Brain-Computer Interface”. Author(s): Krausz G, Scherer R, Korisek G, Pfurtscheller G. Source: Applied Psychophysiology and Biofeedback. 2003 September; 28(3): 233-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uid s=12964454&dopt=Abstract
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Detection of Recurrent Brain Tumor. Comparison of MR Registered Camera-Based and Dedicated PET Images. Author(s): Coleman RE, Hawk TC, Hamblen SM, Cnmt, Laymon CM, Turkington TG.
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Source: Clinical Positron Imaging : Official Journal of the Institute for Clinical P.E.T. 1999 January; 2(1): 57-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14516554&dopt=Abstract •
Dietary fatty acids alter blood pressure, behavior and brain membrane composition of hypertensive rats. Author(s): de Wilde MC, Hogyes E, Kiliaan AJ, Farkas T, Luiten PG, Farkas E. Source: Brain Research. 2003 October 24; 988(1-2): 9-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14519522&dopt=Abstract
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Does stress damage the brain? Understanding trauma-related disorders from a mindbody perspective. Author(s): Middleton W. Source: The Australian and New Zealand Journal of Psychiatry. 2003 October; 37(5): 6334. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14511102&dopt=Abstract
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Ear of stimulation determines schizophrenia-normal brain activity differences in an auditory paired-stimuli paradigm. Author(s): Clementz BA, Dzau JR, Blumenfeld LD, Matthews S, Kissler J. Source: The European Journal of Neuroscience. 2003 November; 18(10): 2853-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14656334&dopt=Abstract
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EEG Biofeedback of low beta band components: frequency-specific effects on variables of attention and event-related brain potentials. Author(s): Egner T, Gruzelier JH. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2004 January; 115(1): 131-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14706480&dopt=Abstract
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Effect of neurofeedback on motor recovery of a patient with brain injury: a case study and its implications for stroke rehabilitation. Author(s): Wing K. Source: Topics in Stroke Rehabilitation. 2001 Autumn; 8(3): 45-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14523737&dopt=Abstract
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Effects of neonatal treatment with phytoestrogens, genistein and daidzein, on sex difference in female rat brain function: estrous cycle and lordosis. Author(s): Kouki T, Kishitake M, Okamoto M, Oosuka I, Takebe M, Yamanouchi K. Source: Hormones and Behavior. 2003 August; 44(2): 140-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13129486&dopt=Abstract
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Electro-acupuncture for treatment of dysequillibrium due to cerebellum or brain stem infarction. Author(s): Zhao H, Liu Z, Liu X. Source: J Tradit Chin Med. 2003 December; 23(4): 274. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14719296&dopt=Abstract
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Electro-acupuncture preconditioning abrogates the elevation of c-Fos and c-Jun expression in neonatal hypoxic-ischemic rat brains induced by glibenclamide, an ATP-sensitive potassium channel blocker. Author(s): Jiang KW, Zhao ZY, Shui QX, Xia ZZ. Source: Brain Research. 2004 February 13; 998(1): 13-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14725963&dopt=Abstract
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Electroacupuncture reduces the extent of lipid peroxidation by increasing superoxide dismutase and glutathione peroxidase activities in ischemic-reperfused rat brains. Author(s): Siu FK, Lo SC, Leung MC. Source: Neuroscience Letters. 2004 January 9; 354(2): 158-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14698462&dopt=Abstract
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Event-related brain potential changes after Choto-san administration in stroke patients with mild cognitive impairments. Author(s): Yamaguchi S, Matsubara M, Kobayashi S. Source: Psychopharmacology. 2004 January; 171(3): 241-9. Epub 2003 November 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14615873&dopt=Abstract
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Evidence of correlated functional magnetic resonance imaging signals between distant human brains. Author(s): Standish LJ, Johnson LC, Kozak L, Richards T. Source: Alternative Therapies in Health and Medicine. 2003 January-February; 9(1): 128, 122-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14640097&dopt=Abstract
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Feasibility of long-term intraventricular therapy with mafosfamide (n = 26) and etoposide (n = 11): experience in 26 children with disseminated malignant brain tumors. Author(s): Slavc I, Schuller E, Falger J, Gunes M, Pillwein K, Czech T, Dietrich W, Rossler K, Dieckmann K, Prayer D, Hainfellner J. Source: Journal of Neuro-Oncology. 2003 September; 64(3): 239-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14558599&dopt=Abstract
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Functional lesions and human action monitoring: combining repetitive transcranial magnetic stimulation and event-related brain potentials. Author(s): Rollnik JD, Schroder C, Rodri;guez-Fornells A, Kurzbuch AR, Dauper J, Moller J, Munte TF.
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Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2004 January; 115(1): 145-153. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14706482&dopt=Abstract •
Ginkgo biloba prevents mobile phone-induced oxidative stress in rat brain. Author(s): Ilhan A, Gurel A, Armutcu F, Kamisli S, Iraz M, Akyol O, Ozen S. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2004 February; 340(1-2): 153-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14734207&dopt=Abstract
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Haloperidol impairs auditory filial imprinting and modulates monoaminergic neurotransmission in an imprinting-relevant forebrain area of the domestic chick. Author(s): Gruss M, Bock J, Braun K. Source: Journal of Neurochemistry. 2003 November; 87(3): 686-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14535951&dopt=Abstract
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Hypericum perforatum extract demonstrates antioxidant properties against elevated rat brain oxidative status induced by amnestic dose of scopolamine. Author(s): El-Sherbiny DA, Khalifa AE, Attia AS, Eldenshary Eel-D. Source: Pharmacology, Biochemistry, and Behavior. 2003 December; 76(3-4): 525-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14643852&dopt=Abstract
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In vivo approaches to quantifying and imaging brain arachidonic and docosahexaenoic acid metabolism. Author(s): Rapoport SI. Source: The Journal of Pediatrics. 2003 October; 143(4 Suppl): S26-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14597911&dopt=Abstract
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Increased recovery of brain acetylcholinesterase activity in dichlorvos-intoxicated European eels Anguilla anguilla by bath treatment with N-acetylcysteine. Author(s): Pena-Llopis S, Ferrando MD, Pena JB. Source: Dis Aquat Organ. 2003 August 4; 55(3): 237-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677510&dopt=Abstract
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Inflammation is detrimental for neurogenesis in adult brain. Author(s): Ekdahl CT, Claasen JH, Bonde S, Kokaia Z, Lindvall O. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 November 11; 100(23): 13632-7. Epub 2003 October 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14581618&dopt=Abstract
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Influence of electroacupuncture on the mRNA of heat shock protein 70 and 90 in brain after cerebral ischemia/reperfusion of rats. Author(s): Sun N, Shi J, Chen L, Liu X, Guan X.
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Source: J Huazhong Univ Sci Technolog Med Sci. 2003; 23(2): 112-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12973923&dopt=Abstract •
Inhibitory effect of genistein on activation of STAT3 induced by brain ischemia/reperfusion in rat hippocampus. Author(s): Li HC, Zhang GY. Source: Acta Pharmacologica Sinica. 2003 November; 24(11): 1131-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14627498&dopt=Abstract
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Lack of maternal dietary exposure effects of bisphenol A and nonylphenol during the critical period for brain sexual differentiation on the reproductive/endocrine systems in later life. Author(s): Takagi H, Shibutani M, Masutomi N, Uneyama C, Takahashi N, Mitsumori K, Hirose M. Source: Archives of Toxicology. 2003 October 1 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14520509&dopt=Abstract
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Learning deficits in forebrain-restricted brain-derived neurotrophic factor mutant mice. Author(s): Gorski JA, Balogh SA, Wehner JM, Jones KR. Source: Neuroscience. 2003; 121(2): 341-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14521993&dopt=Abstract
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Memory function and brain glucose metabolism. Author(s): Hoyer S. Source: Pharmacopsychiatry. 2003 June; 36 Suppl 1: S62-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130391&dopt=Abstract
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Mismatch negativity in evoked brain potentials in adolescents in normal conditions and attention deficit in response to presentation of short-duration acoustic stimuli. Author(s): Aleksandrov AA, Karpina NV, Stankevich LN. Source: Neuroscience and Behavioral Physiology. 2003 September; 33(7): 671-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14552534&dopt=Abstract
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Modification by docosahexaenoic acid of age-induced alterations in gene expression and molecular composition of rat brain phospholipids. Author(s): Barcelo-Coblijn G, Hogyes E, Kitajka K, Puskas LG, Zvara A, Hackler L Jr, Nyakas C, Penke Z, Farkas T. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 September 30; 100(20): 11321-6. Epub 2003 Sep 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13679584&dopt=Abstract
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Modulation of cold pain in human brain by electric acupoint stimulation: evidence from fMRI. Author(s): Zhang WT, Jin Z, Huang J, Zhang L, Zeng YW, Luo F, Chen AC, Han JS. Source: Neuroreport. 2003 August 26; 14(12): 1591-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14502082&dopt=Abstract
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Neuroprotective effects of bilobalide, a component of Ginkgo biloba extract (EGb 761) in global brain ischemia and in excitotoxicity-induced neuronal death. Author(s): Chandrasekaran K, Mehrabian Z, Spinnewyn B, Chinopoulos C, Drieu K, Fiskum G. Source: Pharmacopsychiatry. 2003 June; 36 Suppl 1: S89-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130395&dopt=Abstract
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Non-invasive imaging methods for the characterization of the pathophysiology of brain ischemia. Author(s): Hossmann KA. Source: Acta Neurochir Suppl. 2003; 86: 21-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14753397&dopt=Abstract
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Omega-6/omega-3 ratio and brain-related functions. Author(s): Yehuda S. Source: World Review of Nutrition and Dietetics. 2003; 92: 37-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14579682&dopt=Abstract
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Omental transposition to the brain as a surgical method for treating Alzheimer's disease. Author(s): Goldsmith HS, Wu W, Zhong J, Edgar M. Source: Neurological Research. 2003 September; 25(6): 625-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14503017&dopt=Abstract
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Overcoming the blood-brain barrier to taxane delivery for neurodegenerative diseases and brain tumors. Author(s): Rice A, Michaelis ML, Georg G, Liu Y, Turunen B, Audus KL. Source: Journal of Molecular Neuroscience : Mn. 2003; 20(3): 339-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501017&dopt=Abstract
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PET imaging of brain function while puncturing the acupoint ST36. Author(s): Yin L, Jin X, Qiao W, Sun J, Shi X, Tian J, Yin D, Yao S, Shao M, Zeng H, Shan B, Tang Y, Zhu K. Source: Chinese Medical Journal. 2003 December; 116(12): 1836-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14687469&dopt=Abstract
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Possible mechanisms underlying the protective effects of SY-21, an extract of a traditional Chinese herb, on transient brain ischemia/reperfusion-induced neuronal death in rat hippocampus. Author(s): Chen M, Wang Y, Liu Y, Hou XY, Zhang QG, Meng FJ, Zhang GY. Source: Brain Research. 2003 November 7; 989(2): 180-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556939&dopt=Abstract
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Protection of brain cells against AMPA-induced damage by Asiasari Radix extracts. Author(s): Han Y, Kwon EH, Kim SJ. Source: Phytotherapy Research : Ptr. 2003 September; 17(8): 882-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13680817&dopt=Abstract
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Protective effects of zinc chelation in traumatic brain injury correlate with upregulation of neuroprotective genes in rat brain. Author(s): Hellmich HL, Frederickson CJ, DeWitt DS, Saban R, Parsley MO, Stephenson R, Velasco M, Uchida T, Shimamura M, Prough DS. Source: Neuroscience Letters. 2004 January 30; 355(3): 221-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14732471&dopt=Abstract
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Puromycin selectively increases mdr1a expression in immortalized rat brain endothelial cell lines. Author(s): Demeuse P, Fragner P, Leroy-Noury C, Mercier C, Payen L, Fardel O, Couraud PO, Roux F. Source: Journal of Neurochemistry. 2004 January; 88(1): 23-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14675146&dopt=Abstract
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Quality of Life Philosophy IV. The Brain and Consciousness. Author(s): Ventegodt S, Andersen NJ, Merrick J. Source: Scientificworldjournal. 2003 December 1; 3(12): 1199-209. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14646014&dopt=Abstract
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Recovery of brain docosahexaenoate leads to recovery of spatial task performance. Author(s): Moriguchi T, Salem N Jr. Source: Journal of Neurochemistry. 2003 October; 87(2): 297-309. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14511107&dopt=Abstract
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Review article: altered states of consciousness, theories of recovery, and assessment following a severe traumatic brain injury. Author(s): Duff D. Source: Axone. 2001 September; 23(1): 18-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14621499&dopt=Abstract
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Roles of the auditory midbrain and thalamus in selective phonotaxis in female gray treefrogs (Hyla versicolor). Author(s): Endepols H, Feng AS, Gerhardt HC, Schul J, Walkowiak W. Source: Behavioural Brain Research. 2003 October 17; 145(1-2): 63-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529806&dopt=Abstract
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Ruta 6 selectively induces cell death in brain cancer cells but proliferation in normal peripheral blood lymphocytes: A novel treatment for human brain cancer. Author(s): Pathak S, Multani AS, Banerji P, Banerji P. Source: International Journal of Oncology. 2003 October; 23(4): 975-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963976&dopt=Abstract
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S-adenosyl-L-methionine: effects on brain bioenergetic status and transverse relaxation time in healthy subjects. Author(s): Silveri MM, Parow AM, Villafuerte RA, Damico KE, Goren J, Stoll AL, Cohen BM, Renshaw PF. Source: Biological Psychiatry. 2003 October 15; 54(8): 833-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14550683&dopt=Abstract
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Stimulus complexity enhances auditory discrimination in patients with extremely severe brain injuries. Author(s): Kotchoubey B, Lang S, Herb E, Maurer P, Schmalohr D, Bostanov V, Birbaumer N. Source: Neuroscience Letters. 2003 December 4; 352(2): 129-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14625040&dopt=Abstract
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Sub-chronic treatment with an extract of Hypericum perforatum (St John's wort) significantly reduces cortisol and corticosterone in the rat brain. Author(s): Franklin M, Reed A, Murck H. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2004 January; 14(1): 7-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14659982&dopt=Abstract
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Synthesis and biological evaluation of GABA derivatives able to cross the bloodbrain barrier in rats. Author(s): Carelli V, Liberatore F, Scipione L, Giorgioni G, Di Stefano A, Impicciatore M, Ballabeni V, Calcina F, Magnanini F, Barocelli E. Source: Bioorganic & Medicinal Chemistry Letters. 2003 November 3; 13(21): 3765-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14552775&dopt=Abstract
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Temporal dynamics of brain anatomy. Author(s): Toga AW, Thompson PM.
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Source: Annual Review of Biomedical Engineering. 2003; 5: 119-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14527311&dopt=Abstract •
The brain an owner's manual. Author(s): Spiker T. Source: Fortune. 2003 October 6; 148(7): 117-9, 122, 124 Passim. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14571694&dopt=Abstract
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The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activity. Author(s): Yuan CS, Mehendale S, Xiao Y, Aung HH, Xie JT, Ang-Lee MK. Source: Anesthesia and Analgesia. 2004 February; 98(2): 353-8, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14742369&dopt=Abstract
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The impact of deafness to the survival of the newborn cells in the brain of juvenile white-rumped munia, Lonchura striata. Author(s): Bao C, Zeng L, Zuo M. Source: Zoological Science. 2003 September; 20(9): 1079-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14578567&dopt=Abstract
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The musician's brain: functional imaging of amateurs and professionals during performance and imagery. Author(s): Lotze M, Scheler G, Tan HR, Braun C, Birbaumer N. Source: Neuroimage. 2003 November; 20(3): 1817-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14642491&dopt=Abstract
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Thyroid, brain and mood modulation in affective disorder: insights from molecular research and functional brain imaging. Author(s): Bauer M, London ED, Silverman DH, Rasgon N, Kirchheiner J, Whybrow PC. Source: Pharmacopsychiatry. 2003 November; 36 Suppl 3: S215-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14677082&dopt=Abstract
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Trans-sodium crocetinate increases oxygen delivery to brain parenchyma in rats on oxygen supplementation. Author(s): Okonkwo DO, Wagner J, Melon DE, Alden T, Stone JR, Helm GA, Jane JA Sr. Source: Neuroscience Letters. 2003 December 4; 352(2): 97-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14625032&dopt=Abstract
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Zinc released from metallothionein-iii may contribute to hippocampal CA1 and thalamic neuronal death following acute brain injury. Author(s): Lee JY, Kim JH, Palmiter RD, Koh JY.
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Source: Experimental Neurology. 2003 November; 184(1): 337-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14637104&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; 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 Age-Related Cognitive Decline Source: Healthnotes, Inc.; www.healthnotes.com AIDS and HIV Source: Integrative Medicine Communications; www.drkoop.com Alzheimer's Disease Source: Healthnotes, Inc.; www.healthnotes.com Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com
Alternative Medicine
Amenorrhea Source: Healthnotes, Inc.; www.healthnotes.com Anxiety Source: Healthnotes, Inc.; www.healthnotes.com Anxiety Source: Integrative Medicine Communications; www.drkoop.com Anxiety and Panic Attacks Source: Prima Communications, Inc.www.personalhealthzone.com Ascariasis Source: Integrative Medicine Communications; www.drkoop.com Atherosclerosis Source: Healthnotes, Inc.; www.healthnotes.com Attention Deficit Hyperactivity Disorder Source: Integrative Medicine Communications; www.drkoop.com Autism Source: Healthnotes, Inc.; www.healthnotes.com Bipolar Disorder Source: Healthnotes, Inc.; www.healthnotes.com Birth Defects Prevention Source: Healthnotes, Inc.; www.healthnotes.com Brain Cancer Source: Integrative Medicine Communications; www.drkoop.com Breast Cancer Source: Healthnotes, Inc.; www.healthnotes.com Cancer Prevention and Diet Source: Healthnotes, Inc.; www.healthnotes.com Cataracts Source: Integrative Medicine Communications; www.drkoop.com Cirrhosis Source: Integrative Medicine Communications; www.drkoop.com Colon Cancer Source: Healthnotes, Inc.; www.healthnotes.com Congestive Heart Failure Source: Prima Communications, Inc.www.personalhealthzone.com
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Depression Source: Healthnotes, Inc.; www.healthnotes.com Depression Source: Integrative Medicine Communications; www.drkoop.com Depression (Mild to Moderate) Source: Prima Communications, Inc.www.personalhealthzone.com Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com Eating Disorders Source: Healthnotes, Inc.; www.healthnotes.com Edema Source: Integrative Medicine Communications; www.drkoop.com Epilepsy Source: Healthnotes, Inc.; www.healthnotes.com Epilepsy Source: Integrative Medicine Communications; www.drkoop.com Epstein-barr Virus Source: Integrative Medicine Communications; www.drkoop.com Fainting Source: Integrative Medicine Communications; www.drkoop.com Female Infertility Source: Healthnotes, Inc.; www.healthnotes.com Gout Source: Healthnotes, Inc.; www.healthnotes.com Guinea Worm Disease Source: Integrative Medicine Communications; www.drkoop.com Heat Exhaustion Source: Integrative Medicine Communications; www.drkoop.com Hemophilia Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com Histoplasmosis Source: Integrative Medicine Communications; www.drkoop.com
Alternative Medicine
HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com Hookworm Source: Integrative Medicine Communications; www.drkoop.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Hyperkalemia Source: Integrative Medicine Communications; www.drkoop.com Hypoglycemia Source: Integrative Medicine Communications; www.drkoop.com Hypothermia Source: Integrative Medicine Communications; www.drkoop.com Infantile Colic Source: Integrative Medicine Communications; www.drkoop.com Influenza Source: Healthnotes, Inc.; www.healthnotes.com Insomnia Source: Healthnotes, Inc.; www.healthnotes.com Insomnia Source: Integrative Medicine Communications; www.drkoop.com Insomnia Source: Prima Communications, Inc.www.personalhealthzone.com Leukemia Source: Integrative Medicine Communications; www.drkoop.com Liver Cirrhosis Source: Healthnotes, Inc.; www.healthnotes.com Liver Disease Source: Integrative Medicine Communications; www.drkoop.com Loiasis Source: Integrative Medicine Communications; www.drkoop.com Low Blood Sugar Source: Integrative Medicine Communications; www.drkoop.com Lung Cancer Source: Healthnotes, Inc.; www.healthnotes.com
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Lung Cancer Source: Integrative Medicine Communications; www.drkoop.com Lupus Source: Integrative Medicine Communications; www.drkoop.com Lyme Disease Source: Integrative Medicine Communications; www.drkoop.com Lymphatic Filariasis Source: Integrative Medicine Communications; www.drkoop.com Meningitis Source: Integrative Medicine Communications; www.drkoop.com Menkes' Disease Source: Healthnotes, Inc.; www.healthnotes.com Menopause Source: Healthnotes, Inc.; www.healthnotes.com Migraine Headaches Source: Healthnotes, Inc.; www.healthnotes.com Migraine Headaches Source: Prima Communications, Inc.www.personalhealthzone.com Mononucleosis Source: Integrative Medicine Communications; www.drkoop.com Motion Sickness Source: Integrative Medicine Communications; www.drkoop.com Multiple Sclerosis Source: Healthnotes, Inc.; www.healthnotes.com Multiple Sclerosis Source: Integrative Medicine Communications; www.drkoop.com Mumps Source: Integrative Medicine Communications; www.drkoop.com Obesity Source: Integrative Medicine Communications; www.drkoop.com Osteoarthritis Source: Healthnotes, Inc.; www.healthnotes.com Osteoporosis Source: Prima Communications, Inc.www.personalhealthzone.com
Alternative Medicine
Parkinson's Disease Source: Healthnotes, Inc.; www.healthnotes.com Parkinson's Disease Source: Integrative Medicine Communications; www.drkoop.com Phenylketonuria Source: Healthnotes, Inc.; www.healthnotes.com Pinworm Source: Integrative Medicine Communications; www.drkoop.com PMS Source: Integrative Medicine Communications; www.drkoop.com Post Traumatic Stress Disorder Source: Integrative Medicine Communications; www.drkoop.com Pregnancy and Postpartum Support Source: Healthnotes, Inc.; www.healthnotes.com Premenstrual Syndrome Source: Integrative Medicine Communications; www.drkoop.com Prostate Cancer Source: Healthnotes, Inc.; www.healthnotes.com Prostate Cancer Source: Integrative Medicine Communications; www.drkoop.com PTSD Source: Integrative Medicine Communications; www.drkoop.com Recurrent Ear Infections Source: Healthnotes, Inc.; www.healthnotes.com River Blindness Source: Integrative Medicine Communications; www.drkoop.com Roseola Source: Integrative Medicine Communications; www.drkoop.com Roundworms Source: Integrative Medicine Communications; www.drkoop.com Rubella Source: Integrative Medicine Communications; www.drkoop.com Sarcoidosis Source: Integrative Medicine Communications; www.drkoop.com
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Schizophrenia Source: Healthnotes, Inc.; www.healthnotes.com Seasonal Affective Disorder Source: Healthnotes, Inc.; www.healthnotes.com Seizure Disorders Source: Integrative Medicine Communications; www.drkoop.com Senile Dementia Source: Integrative Medicine Communications; www.drkoop.com Shock Source: Integrative Medicine Communications; www.drkoop.com Sleep Apnea Source: Integrative Medicine Communications; www.drkoop.com Sleeplessness Source: Integrative Medicine Communications; www.drkoop.com Stress Source: Integrative Medicine Communications; www.drkoop.com Stroke Source: Healthnotes, Inc.; www.healthnotes.com Stroke Source: Integrative Medicine Communications; www.drkoop.com Systemic Lupus Erythematosus Source: Integrative Medicine Communications; www.drkoop.com Tardive Dyskinesia Source: Healthnotes, Inc.; www.healthnotes.com Tension Headache Source: Integrative Medicine Communications; www.drkoop.com Threadworm 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 Trichinosis Source: Integrative Medicine Communications; www.drkoop.com
Alternative Medicine
Tuberculosis Source: Integrative Medicine Communications; www.drkoop.com Urinary Incontinence Source: Integrative Medicine Communications; www.drkoop.com Vertigo Source: Healthnotes, Inc.; www.healthnotes.com Visceral Larva Migrans Source: Integrative Medicine Communications; www.drkoop.com Water Retention Source: Integrative Medicine Communications; www.drkoop.com Whipworm Source: Integrative Medicine Communications; www.drkoop.com •
Alternative Therapy Acu-diet Alternative names: Dr. Bahr's acu-diet Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/a.html Acupuncture Source: Integrative Medicine Communications; www.drkoop.com Acupuncture Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,663,00.html Alphabiotics Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/a.html Applied Kinesiology Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,711,00.html Apraxia Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/a.html Aromatherapy Source: Integrative Medicine Communications; www.drkoop.com
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Aromatherapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,664,00.html Art Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,671,00.html Aurasomatherapy Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/a.html Biofeedback Source: Integrative Medicine Communications; www.drkoop.com Biofeedback Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,675,00.html Chelation Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,679,00.html Color Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,683,00.html Craniosacral Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,685,00.html Dance Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,687,00.html Guided Imagery Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,699,00.html Hemi-sync Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/h.html
Alternative Medicine
Human Energetic Assessment and Restorative Technic Alternative names: HEART Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/h.html Hypnotherapy Source: Integrative Medicine Communications; www.drkoop.com Iridology Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,709,00.html Joy Touch Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/j.html Light Therapy Source: Healthnotes, Inc.; www.healthnotes.com Light Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,713,00.html Magnet Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,715,00.html Meditation Source: Healthnotes, Inc.; www.healthnotes.com Meditation Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,717,00.html Neurobiofeedback Alternative names: NBF Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/n.html Omar's Touch Therapy Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/o.html
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One Brain Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/o.html Psychodynamic Chirology (pdc) Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/p.html Scalp Acupuncture Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/s.html Silva Mind Control Alternative names: Silva Mental Dynamics Silva Method Silva Method of mind development Silva Mind Control method Silva Mind Control Method of Mental Dynamics Silva Mind Control program of Mental Dynamics Silva Mind Control system Silva mind method Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/s.html Skydancing Tantra Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/s.html Spirituality Source: Integrative Medicine Communications; www.drkoop.com Tai Chi Source: Integrative Medicine Communications; www.drkoop.com Tomatis Method Alternative names: auditory stimulation auditory training listening therapy Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/t.html Wisdom Chi Kung Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/w.html Yoga Source: Integrative Medicine Communications; www.drkoop.com
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Zarlen Therapy Alternative names: Zarlen direct channelling Zarlen Therapy technique Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/z.html •
Chinese Medicine Heizhongcaozi Alternative names: Fennelflower Seed; Semen Nigellae Source: Chinese Materia Medica Naolejing Alternative names: Naolejing Syrup Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China
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Herbs and Supplements 5-htp Source: Integrative Medicine Communications; www.drkoop.com 5-hydroxytryptophan Source: Healthnotes, Inc.; www.healthnotes.com 5-hydroxytryptophan (5-htp) Source: Integrative Medicine Communications; www.drkoop.com ALA Source: Integrative Medicine Communications; www.drkoop.com Aloe Alternative names: Aloe vera L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Alpha-Linolenic Acid (ALA) Source: Integrative Medicine Communications; www.drkoop.com Alpha-Lipoic Acid Source: Integrative Medicine Communications; www.drkoop.com Alpha-Lipoic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10002,00.html American Ginseng Alternative names: Panax quinquefolium Source: Integrative Medicine Communications; www.drkoop.com
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Amino Acids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10003,00.html Aminoglycosides Source: Integrative Medicine Communications; www.drkoop.com Angelica Sinensis Source: Integrative Medicine Communications; www.drkoop.com Antibiotic Combination: Sulfa Drugs Source: Integrative Medicine Communications; www.drkoop.com Anticonvulsants Source: Healthnotes, Inc.; www.healthnotes.com Antidepressants Source: Healthnotes, Inc.; www.healthnotes.com Antioxidants Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10004,00.html Aralia Alternative names: Spikenard; Aralia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Aspirin Source: Healthnotes, Inc.; www.healthnotes.com Astragalus Source: Prima Communications, Inc.www.personalhealthzone.com Astragalus Mem Alternative names: Huang-Qi; Astragalus membranaceus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ava Source: Integrative Medicine Communications; www.drkoop.com Barbiturates Source: Healthnotes, Inc.; www.healthnotes.com Barbiturates Source: Integrative Medicine Communications; www.drkoop.com Betula Alternative names: Birch; Betula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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Biguanides Source: Integrative Medicine Communications; www.drkoop.com Bile Acid Sequestrants Source: Integrative Medicine Communications; www.drkoop.com Black Cohosh Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10009,00.html Borago Alternative names: Borage; Borago officinalis Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Bovine Colostrum Source: Healthnotes, Inc.; www.healthnotes.com Carbamazepine Alternative names: Atretol, Carbatrol, Epitol, Tegretol, Tegretol XR Source: Prima Communications, Inc.www.personalhealthzone.com Carbidopa/levodopa Source: Healthnotes, Inc.; www.healthnotes.com Carnosine Source: Healthnotes, Inc.; www.healthnotes.com Carotenoids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,763,00.html Cayenne Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,765,00.html Centella Alternative names: Gotu Kola; Centella asiatica (Linn.) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Cephalosporins Source: Integrative Medicine Communications; www.drkoop.com Chamomile Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,766,00.html Chasteberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com
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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,767,00.html Chinese Angelica Source: Integrative Medicine Communications; www.drkoop.com Chrysanthemum Parthenium Source: Integrative Medicine Communications; www.drkoop.com Clonidine Source: Healthnotes, Inc.; www.healthnotes.com Coenzyme Q10 Source: Integrative Medicine Communications; www.drkoop.com CoQ10 Source: Integrative Medicine Communications; www.drkoop.com Corydalis Alternative names: Corydalis turtschaninovii, Corydalis yanhusuo Source: Healthnotes, Inc.; www.healthnotes.com Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org 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 DHA Source: Integrative Medicine Communications; www.drkoop.com DMAE Source: Healthnotes, Inc.; www.healthnotes.com DMAE Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10023,00.html Docosahexaenoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Docosahexaenoic Acid (DHA) Source: Integrative Medicine Communications; www.drkoop.com
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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 Echinacea Alternative names: Echinacea angustifolia, Echinacea pallida, Echinacea purpurea, Purple Coneflower Source: Integrative Medicine Communications; www.drkoop.com Echinacea Angustifolia Source: Integrative Medicine Communications; www.drkoop.com Echinacea Pallida Source: Integrative Medicine Communications; www.drkoop.com Echinacea Purpurea Source: Integrative Medicine Communications; www.drkoop.com EDTA Source: Integrative Medicine Communications; www.drkoop.com Electrolytes Source: Integrative Medicine Communications; www.drkoop.com Ephedra Alternative names: Ephedra sinica, Ephedra intermedia, Ephedra equisetina Source: Healthnotes, Inc.; www.healthnotes.com Ethylenediaminetetraacetic Acid (EDTA) Source: Integrative Medicine Communications; www.drkoop.com Feverfew Alternative names: Tanacetum parthenium, Chrysanthemum parthenium Source: Integrative Medicine Communications; www.drkoop.com Feverfew Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,780,00.html Fluvoxamine Source: Healthnotes, Inc.; www.healthnotes.com GABA Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10027,00.html GABA (Gamma-Amino Butyric Acid) Source: Healthnotes, Inc.; www.healthnotes.com
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Gamma-Oryzanol Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10028,00.html Garcinia Cambogia Alternative names: Citrin, Gambooge Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ginger Source: Prima Communications, Inc.www.personalhealthzone.com Ginkgo Alternative names: Ginkgo biloba Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ginkgo Source: Prima Communications, Inc.www.personalhealthzone.com Ginkgo Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Ginkgo Biloba Source: Healthnotes, Inc.; www.healthnotes.com Ginkgo Biloba Source: Integrative Medicine Communications; www.drkoop.com Ginkgo Biloba Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,788,00.html Glandular Extracts Source: Healthnotes, Inc.; www.healthnotes.com Glutamine Source: Integrative Medicine Communications; www.drkoop.com Glutamine Source: Prima Communications, Inc.www.personalhealthzone.com Glutamine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10030,00.html Glycine Source: Healthnotes, Inc.; www.healthnotes.com
Alternative Medicine
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Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Gotu Kola Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10031,00.html Grape Seed Extract Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,793,00.html Gymnema Alternative names: Gurmar; Gymnema sylvestre Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Histamine H2 Antagonists Source: Integrative Medicine Communications; www.drkoop.com Horsetail Alternative names: Equisetum arvense Source: Healthnotes, Inc.; www.healthnotes.com Huperzia Source: Healthnotes, Inc.; www.healthnotes.com Huperzine A Source: Prima Communications, Inc.www.personalhealthzone.com Huperzine A Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10038,00.html Hydrastis Alternative names: Goldenseal; Hydrastis canadensis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Illicium Alternative names: Star Anise; Illicium verum (Hook, F.) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Inositol Source: Prima Communications, Inc.www.personalhealthzone.com Ipecac Alternative names: Cephaelis ipecacuanha Source: Healthnotes, Inc.; www.healthnotes.com
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Ispaghula Source: Integrative Medicine Communications; www.drkoop.com Juniperus Alternative names: Juniper; Juniperus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Kava Alternative names: Piper methysticum Source: Healthnotes, Inc.; www.healthnotes.com Kava Source: Prima Communications, Inc.www.personalhealthzone.com Kava Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,798,00.html Kava Kava Alternative names: Piper methysticum, Ava Source: Integrative Medicine Communications; www.drkoop.com Kudzu Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,858,00.html Lavender Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,799,00.html Lecithin Source: Prima Communications, Inc.www.personalhealthzone.com Lemon Balm Alternative names: Melissa officinalis Source: Healthnotes, Inc.; www.healthnotes.com Leonurus Alternative names: Motherwort; Leonurus cardiaca Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Levodopa Source: Healthnotes, Inc.; www.healthnotes.com Lithium Source: Healthnotes, Inc.; www.healthnotes.com
Alternative Medicine
Lobelia Alternative names: Lobelia inflata L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org L-tyrosine Source: Healthnotes, Inc.; www.healthnotes.com Macrolides Source: Integrative Medicine Communications; www.drkoop.com Maidenhair Tree Source: Integrative Medicine Communications; www.drkoop.com Matricaria Alternative names: Chamomile; Matricaria chamomilla Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Melatonin Source: Healthnotes, Inc.; www.healthnotes.com Melatonin Source: Integrative Medicine Communications; www.drkoop.com Melatonin Source: Prima Communications, Inc.www.personalhealthzone.com Melatonin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,804,00.html Methionine Source: Healthnotes, Inc.; www.healthnotes.com Methylsulfonylmethane Source: Healthnotes, Inc.; www.healthnotes.com Milk Thistle Source: Prima Communications, Inc.www.personalhealthzone.com Mixed Amphetamines Source: Healthnotes, Inc.; www.healthnotes.com Momordica Alternative names: Bitter Gourd, Karela; Momordica charantia Linn. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Musa Banana Alternative names: Plantain, Banana; Musa sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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NAC (N-AcetylCysteine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,809,00.html NADH Source: Healthnotes, Inc.; www.healthnotes.com NADH Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10047,00.html Ornithine Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Panax Quinquefolium Source: Integrative Medicine Communications; www.drkoop.com Penicillin Derivatives Source: Integrative Medicine Communications; www.drkoop.com Pennyroyal Alternative names: Hedeoma pulegoides, Mentha pulegium Source: Healthnotes, Inc.; www.healthnotes.com Phenobarbital Alternative names: Bellatal, Solfoton Source: Prima Communications, Inc.www.personalhealthzone.com Phenylalanine Source: Healthnotes, Inc.; www.healthnotes.com Phenylalanine Source: Integrative Medicine Communications; www.drkoop.com Phenylalanine Source: Prima Communications, Inc.www.personalhealthzone.com Phenylpropanolamine Source: Healthnotes, Inc.; www.healthnotes.com Phosphatidylserine Source: Healthnotes, Inc.; www.healthnotes.com Phosphatidylserine Source: Prima Communications, Inc.www.personalhealthzone.com
Alternative Medicine
Phosphatidylserine (PS) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,813,00.html Phytolacca Alternative names: Poke root, Endod; Phytolacca dodecandra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Piper Alternative names: Kava; Piper methysticum Forst.f Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Piper Methysticum Source: Integrative Medicine Communications; www.drkoop.com Piper Nigrum Alternative names: Black Pepper Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Plantago Isphagula Source: Integrative Medicine Communications; www.drkoop.com Pregnenolone Source: Healthnotes, Inc.; www.healthnotes.com Pregnenolone Source: Prima Communications, Inc.www.personalhealthzone.com Primidone Alternative names: Mysoline Source: Prima Communications, Inc.www.personalhealthzone.com Progesterone Source: Healthnotes, Inc.; www.healthnotes.com Proton Pump Inhibitors (Gastric Acid Secretion Inhibitors) Source: Integrative Medicine Communications; www.drkoop.com Psyllium Alternative names: Ispaghula,Plantago isphagula Source: Integrative Medicine Communications; www.drkoop.com Purple Coneflower Source: Integrative Medicine Communications; www.drkoop.com Quinolones Source: Integrative Medicine Communications; www.drkoop.com Rosemary Alternative names: Rosmarinus officinalis Source: Integrative Medicine Communications; www.drkoop.com
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Rosmarinus Officinalis Source: Integrative Medicine Communications; www.drkoop.com S-Adenosylmethionine (SAMe) Source: Integrative Medicine Communications; www.drkoop.com Sambucus Alternative names: Black Elderberry; Sambucus nigra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org SAMe Source: Healthnotes, Inc.; www.healthnotes.com SAMe Source: Integrative Medicine Communications; www.drkoop.com SAMe (S-Adenosylmethionine) Source: Prima Communications, Inc.www.personalhealthzone.com Sanguinaria Alternative names: Bloodroot; Sanguinaria canadensis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Sertraline Source: Healthnotes, Inc.; www.healthnotes.com St. John’s Wort Alternative names: Hypericum perforatum Source: Healthnotes, Inc.; www.healthnotes.com Sumatriptan Source: Healthnotes, Inc.; www.healthnotes.com Tanacetum Parthenium Source: Integrative Medicine Communications; www.drkoop.com Tang Kuei Source: Integrative Medicine Communications; www.drkoop.com Taurine Source: Healthnotes, Inc.; www.healthnotes.com Taurine Source: Prima Communications, Inc.www.personalhealthzone.com Tetracycline Derivatives Source: Integrative Medicine Communications; www.drkoop.com Thioridazine Source: Healthnotes, Inc.; www.healthnotes.com
Alternative Medicine
Thymus Alternative names: Thyme; Thymus vulgaris Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tocotrienols Source: Healthnotes, Inc.; www.healthnotes.com Tramadol Source: Healthnotes, Inc.; www.healthnotes.com Trazodone Source: Healthnotes, Inc.; www.healthnotes.com Tyrosine Source: Integrative Medicine Communications; www.drkoop.com Tyrosine Source: Prima Communications, Inc.www.personalhealthzone.com Uncaria Asian Alternative names: Asian species; Uncaria sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Uricosuric Agents Source: Integrative Medicine Communications; www.drkoop.com Vacciniumb Alternative names: Bilberry; Vaccinium myrtillus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Valerian Alternative names: Valeriana officinalis Source: Healthnotes, Inc.; www.healthnotes.com Valerian Source: Prima Communications, Inc.www.personalhealthzone.com Valerian Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Valeriana Alternative names: Valerian; Valeriana officinalis Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Valproic Acid Source: Healthnotes, Inc.; www.healthnotes.com Valproic Acid Source: Prima Communications, Inc.www.personalhealthzone.com
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Venlafaxine Source: Healthnotes, Inc.; www.healthnotes.com Viburnum Alternative names: Cramp Bark, Highbush Cranberry; Viburnum sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Wild Indigo Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Willow Bark Alternative names: There are several species of willow includingSalix alba, Salix nigra, Salix fragilis, Salix purpurea, Salix babylonica, White Willow, European Willow, Black Willow, Pussy Willow, Crack Willow, Purple Willow, Weeping Willow, Liu-zhi Source: Integrative Medicine Communications; www.drkoop.com Withania Ashwagandha Alternative names: Ashwagandha; Withania somnifera L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Wormwood Alternative names: Artemisia absinthium Source: Healthnotes, Inc.; www.healthnotes.com Yohimbe Source: Prima Communications, Inc.www.personalhealthzone.com Zizyphus Alternative names: Jujube; Ziziphus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Zolmitriptan Source: Healthnotes, Inc.; www.healthnotes.com Zolpidem 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. CLINICAL TRIALS AND BRAIN Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning brain.
Recent Trials on Brain The following is a list of recent trials dedicated to brain.8 Further information on a trial is available at the Web site indicated. •
Adjuvant Radiation Therapy in Treating Patients With Brain Metastases Condition(s): brain metastases Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Cooperative Group
Radiotherapy
Cooperative
Group;
EORTC
Brain
Tumor
Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Adjuvant radiation therapy may kill any remaining tumor cells following surgery or radiosurgery for brain metastases. PURPOSE: Randomized phase III trial to study the effectiveness of whole-brain radiation therapy after surgery or radiosurgery in treating patients with brain metastases from solid tumors. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002899 •
Antineoplaston Therapy in Treating Children With Brain Tumors Condition(s): childhood brain tumor Study Status: This study is currently recruiting patients.
8
These are listed at www.ClinicalTrials.gov.
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Sponsor(s): Burzynski Research Institute Purpose - Excerpt: RATIONALE: Antineoplastons are naturally-occurring substances found in urine. Antineoplastons may inhibit the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of antineoplaston therapy in treating children with brain tumors. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003458 •
Antineoplaston Therapy in Treating Children With Primary Malignant Brain Tumors Condition(s): childhood brain tumor; childhood meningioma Study Status: This study is currently recruiting patients. Sponsor(s): Burzynski Research Institute Purpose - Excerpt: RATIONALE: Antineoplastons are naturally occurring substances found in urine. Antineoplastons may inhibit the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of antineoplaston therapy in treating children who have primary malignant brain tumors. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003476
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Antineoplaston Therapy in Treating Patients With Brain Stem Glioma Condition(s): recurrent adult brain tumor; adult brain stem glioma; untreated childhood brain stem glioma; recurrent childhood brain stem glioma Study Status: This study is currently recruiting patients. Sponsor(s): Burzynski Research Institute Purpose - Excerpt: RATIONALE: Antineoplastons are naturally-occurring substances found in urine. Antineoplastons may inhibit the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of antineoplaston therapy in treating patients with brain stem glioma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003459
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Antineoplaston Therapy in Treating Patients With Brain Tumors Condition(s): ACTH-producing pituitary tumor; TSH producing pituitary tumor; adult brain tumor Study Status: This study is currently recruiting patients. Sponsor(s): Burzynski Research Institute
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Purpose - Excerpt: RATIONALE: Antineoplastons are naturally-occurring substances found in urine. Antineoplastons may inhibit the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of antineoplaston therapy in treating patients with brain tumors. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003457 •
Antineoplaston Therapy in Treating Patients With Germ Cell Tumors of the Brain Condition(s): recurrent childhood brain tumor; childhood central nervous system germ cell tumor; recurrent adult brain tumor; adult central nervous system germ cell tumor Study Status: This study is currently recruiting patients. Sponsor(s): Burzynski Research Institute Purpose - Excerpt: RATIONALE: Antineoplastons are naturally occurring substances found in urine. Antineoplastons may inhibit the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of antineoplaston therapy in treating patients with germ cell tumors of the brain. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003482
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Antineoplaston Therapy in Treating Patients With Primary Malignant Brain Tumors Condition(s): adult brain tumor Study Status: This study is currently recruiting patients. Sponsor(s): Burzynski Research Institute Purpose - Excerpt: RATIONALE: Antineoplastons are naturally occurring substances found in urine. Antineoplastons may inhibit the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of antineoplaston therapy in treating patients with primary malignant brain tumors. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003475
•
Cilengitide in Treating Children With Refractory Primary Brain Tumors Condition(s): childhood brain tumor; childhood meningioma; childhood spinal cord tumors Study Status: This study is currently recruiting patients. Sponsor(s): Pediatric Brain Tumor Consortium; National Cancer Institute (NCI)
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Purpose - Excerpt: RATIONALE: Cilengitide may slow the growth of brain cancer cells by stopping blood flow to the tumor. PURPOSE: Phase I trial to study the effectiveness of cilengitide in treating children who have recurrent, progressive, or refractory primary CNS tumors. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063973 •
Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation or Bone Marrow Transplantation in Treating Patients With Brain Cancer Condition(s): adult brain tumor; childhood central nervous system germ cell tumor; childhood ependymoma; Childhood Medulloblastoma; childhood supratentorial primitive neuroectodermal tumors Study Status: This study is currently recruiting patients. Sponsor(s): Kaplan Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining temozolomide, thiotepa, and carboplatin followed by peripheral stem cell transplantation or bone marrow transplantation in treating patients who have brain cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025558
•
Genotype Influence on Recovery After Traumatic Brain Injury Condition(s): Brain Injury Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: Genetic differences in response to brain injury may reasonably be expected to play a role in the initial consequences of traumatic brain injury and in the rate of recovery from such injury. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018499
•
Home Stimulation for Brain-Asphyxiated Infants Condition(s): Hypoxia, Brain; Hypoxia-Ischemia, Brain Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD)
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Purpose - Excerpt: This study examines the potential benefits of a home stimulation program to treat infants who have suffered from brain asphyxiation (lack of oxygen). The program involves one year of stimulatory activities. Progress will be evaluated through neurological and behavioral exams. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006516 •
Hypothermia to Treat Severe Brain Injury Condition(s): Brain Injuries; Hypothermia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The purpose of this trial is to determine if hypothermia (body cooling), administered very soon after a severe brain injury in patients who are hypothermic on admission, improves functional outcome. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040339
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Irinotecan and Whole-Brain Radiation Therapy in Treating Patients With Unresectable Brain Metastases From Non-Small Cell Lung Cancer Condition(s): recurrent non-small cell lung cancer; stage IV non-small cell lung cancer; brain metastases Study Status: This study is currently recruiting patients. Sponsor(s): Norris Cotton Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy and radiation therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining irinotecan with whole-brain radiation therapy in treating patients who have unresectable brain metastases from non-small cell lung cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00036803
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Magnesium Sulfate For Brain Injury Condition(s): Brain Injuries; Head Injury; Brain Concussion Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS)
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Purpose - Excerpt: The purpose of the study is to determine whether magnesium sulfate, given within 8 hours of a moderate or severe traumatic brain injury improves survival, decreases the number of people developing seizures, improves the survivors' mental and psychological functioning, including the ability to return to daily life, live independently, and return to work or school. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004730 •
Methylphenidate to Improve Quality of Life in Patients Undergoing Radiation Therapy for Brain Tumors Condition(s): adult brain tumor; brain metastases; cognitive and functional effects; Depression; Fatigue; Quality of Life Study Status: This study is currently recruiting patients. Sponsor(s): Comprehensive Cancer Center of Wake Forest University; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Methylphenidate may decrease side effects of radiation therapy. It is not yet known if methylphenidate is effective in improving quality of life in patients with primary or metastatic brain tumors. PURPOSE: Randomized phase III trial to determine the effectiveness of methylphenidate in improving quality of life in patients who have brain tumors and are undergoing radiation therapy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031798
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Modafinil in Treating Fatigue and Behavioral Change in Patients With Primary Brain Cancer Condition(s): adult brain tumor; Fatigue; cognitive/functional effects Study Status: This study is currently recruiting patients. Sponsor(s): Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Modafinil may be effective in relieving fatigue and improving behavioral changes such as memory loss in patients who have undergone treatment for primary brain cancer. The effectiveness of modafinil in relieving fatigue and improving behavioral change is not yet known. PURPOSE: Randomized clinical trial to determine the effectiveness of modafinil in treating fatigue and behavioral changes in patients who have undergone treatment for primary brain cancer. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00052286
Clinical Trials
•
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Photodynamic Therapy With Porfimer Sodium in Treating Patients With Refractory Brain Tumors Condition(s): adult brain tumor; brain metastases; childhood brain stem glioma; childhood brain tumor; childhood cerebellar astrocytoma; childhood visual pathway and hypothalamic glioma Study Status: This study is currently recruiting patients. Sponsor(s): Medical College of Wisconsin Purpose - Excerpt: RATIONALE: Photodynamic therapy uses light and photosensitizing drugs to kill tumor cells and may be an effective treatment for refractory brain tumors. PURPOSE: Phase I trial to study the effectiveness of photodynamic therapy using porfimer sodium in treating patients who have refractory brain tumors, including astrocytoma, ependymoma, and medulloblastoma. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002647
•
Radiation Therapy With or Without Thalidomide in Treating Patients With Brain Metastases Condition(s): brain metastases Study Status: This study is currently recruiting patients. Sponsor(s): Radiation Therapy Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as thalidomide may stop the growth of brain metastases by stopping blood flow to the tumor. It is not yet known whether radiation therapy is more effective with or without thalidomide in treating brain metastases. PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy with or without thalidomide in treating patients who have brain metastases. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033254
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Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Primary Brain Tumors Condition(s): adult brain tumor Study Status: This study is currently recruiting patients. Sponsor(s): Duke Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate tumor cells and deliver radioactive tumor-killing substances such as radioactive iodine to them without harming normal cells. PURPOSE: Randomized phase I/II trial to compare two methods of delivering radiolabeled monoclonal antibody therapy to patients with primary brain tumors. Phase(s): Phase I; Phase II
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003478 •
Radiosurgery With or Without Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases Condition(s): brain metastases Study Status: This study is currently recruiting patients. Sponsor(s): American College of Surgeons; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Radiosurgery may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue. It is not yet known if radiosurgery is more effective with or without whole-brain radiation therapy in treating brain metastases. PURPOSE: Randomized phase III trial to compare the effectiveness of radiosurgery with or without whole-brain radiation therapy in treating patients who have brain metastases. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00030628
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SCH 66336 in Treating Children With Recurrent or Progressive Brain Tumors Condition(s): childhood brain tumor; childhood meningioma; childhood rhabdoid tumor of the central nervous system; childhood spinal cord tumors Study Status: This study is currently recruiting patients. Sponsor(s): Pediatric Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: SCH 66336 may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. PURPOSE: Phase I trial to study the effectiveness of SCH 66336 in treating children who have recurrent or progressive brain tumors. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00015899
•
Study of Neurologic Progression with Motexafin Gadolinium and Radiation Therapy (SMART) Condition(s): Neoplasm
Brain
Neoplasms;
Carcinoma,
Non-Small-Cell
Lung;
Metastases,
Study Status: This study is currently recruiting patients. Sponsor(s): Pharmacyclics Purpose - Excerpt: The primary purpose of the study is to determine if patients with brain metastases from non-small cell lung cancer treated with Motexafin Gadolinium
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and whole brain radiation therapy retain their neurologic function and ability to think for a longer time compared to patients treated with whole brain radiation therapy alone. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054795 •
Study of Systemic and Spinal Chemotherapy Followed by Radiation for Infants with Brain Tumors Condition(s): Brain Tumors Study Status: This study is currently recruiting patients. Sponsor(s): Baylor College of Medicine; Texas Children's Hospital; Duke University; St. Jude Children's Research Hospital Purpose - Excerpt: The purposes of this study are to find the highest dose of mafosfamide that can be given without causing severe side effects, to see how well the combination of these chemotherapy drugs and lower doses of radiation work to delay or stop the growth of the tumor, and to evaluate the pharmacokinetics (how the body handles) of Mafosfamide. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042367
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Temozolomide and O6-Benzylguanine in Treating Children With Recurrent Brain Tumors Condition(s): childhood brain tumor; childhood meningioma; childhood spinal cord tumors Study Status: This study is currently recruiting patients. Sponsor(s): Pediatric Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. O6-benzylguanine may increase the effectiveness of temozolomide by making tumor cells more sensitive to the drug. PURPOSE: Phase I trial to study the effectiveness of combining O6-benzylguanine with temozolomide in treating children who have recurrent or refractory brain tumors. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00052780
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Temozolomide and Thalidomide in Treating Patients With Brain Metastases Secondary to Melanoma Condition(s): Stage IV Melanoma; brain metastases; Recurrent Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Cancer and Leukemia Group B; National Cancer Institute (NCI)
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Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy, such as temozolomide, use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Combining temozolomide with thalidomide may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining temozolomide with thalidomide in treating patients who have brain metastases secondary to melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00072163 •
Temozolomide and Vinorelbine in Treating Patients With Recurrent Brain Metastases Condition(s): brain metastases Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I/II trial to study the effectiveness of temozolomide and vinorelbine in treating patients who have recurrent brain metastases. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00026494
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Temozolomide for Treatment of Brain Metastases from Non-Small Cell Lung Cancer Condition(s): Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Brain Neoplasms Study Status: This study is currently recruiting patients. Sponsor(s): Schering-Plough Purpose - Excerpt: The purpose of this study is to demonstrate improvement in overall survival for the combination of whole brain radiation therapy (WBRT) plus temosolomide (TMZ) vs WBRT plus placebo. Secondary objective is to demonstrate an improvement in the time to radiological CNS progression with the addition of TMZ to WBRT. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00076856
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Tipifarnib in Treating Young Patients With Recurrent, Refractory, or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma Condition(s): childhood brain stem glioma; childhood brain tumor; childhood cerebellar astrocytoma; childhood cerebral astrocytoma and malignant glioma; Childhood Oligodendroglioma; childhood visual pathway and hypothalamic glioma Study Status: This study is currently recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. PURPOSE: Phase II trial to study the effectiveness of tipifarnib in treating young patients who have recurrent, refractory, or progressive high-grade glioma, medulloblastoma, primitive neuroectodermal tumor, or brain stem glioma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070525
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Vaccine Therapy and Sargramostim in Treating Patients With Sarcoma or Brain Tumor Condition(s): Brain Tumor; childhood brain tumor; childhood soft tissue sarcoma; gastrointestinal stromal tumor; Muscle Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Dana-Farber/Harvard Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim increase the number of immune cells found in bone marrow or peripheral blood. Combining vaccine therapy with sargramostim may cause a stronger immune response and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining vaccine therapy with sargramostim in treating patients who have advanced sarcoma or brain tumor. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069940
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Carmustine Followed By Surgery in Treating Patients With Recurrent Supratentorial Malignant Glioma or Metastatic Brain Neoplasm Condition(s): adult glioblastoma multiforme; brain metastases; adult anaplastic astrocytoma; adult malignant ependymoma; adult anaplastic oligodendroglioma Study Status: This study is no longer recruiting patients. Sponsor(s): Direct Therapeutics Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I/II trial to
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study the effectiveness of carmustine followed by surgery in treating patients who have recurrent supratentorial malignant glioma or metastatic brain neoplasm. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00009854 •
Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Brain Tumor Condition(s): childhood brain tumor; childhood rhabdomyosarcoma; Neuroblastoma; Retinoblastoma Study Status: This study is no longer recruiting patients. Sponsor(s): Kaplan Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of different regimens of combination chemotherapy followed by peripheral stem cell transplantation in treating children who have newly diagnosed brain tumor. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003273
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Evaluation of Factors in Human Brain Tumors Condition(s): Brain Neoplasm; Glioblastoma; Glioma; Pituitary Neoplasm Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: Presently, patients with primary malignant brain tumors have a life expectancy of 15 weeks following surgery unless they receive additional types of therapy (chemotherapy, radiotherapy, and/or immunotherapy). Patients that receive additional therapy can increase life expectancy to 50 weeks. The statistics on the life expectancy and survival have increased efforts among researchers to develop new treatments for primary malignant brain tumors. This research project involves the growth and study of human brain tumor cells outside the body in the laboratory as part of an attempt to better understand these tumors and to develop more effective treatments for them. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001171
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Gene Therapy for the Treatment of Brain Tumors Condition(s): Brain Neoplasm; Neoplasm Metastasis
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Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: Malignant brain tumors are responsible for a significant amount of deaths in children and adults. Even with advances in surgery, radiation therapy, and chemotherapy, many patients diagnosed with a malignant brain tumor survive only months to weeks. In an attempt to improve the prognosis for these patients, researchers have developed a new approach to brain tumor therapy. This approach makes use of DNA technology to transfer genes sensitive to therapy into the cells of the tumor. Infections with the herpes simplex virus can cause cold sores in the area of the mouth. A drug called ganciclovir (Cytovene) can kill the virus. Ganciclovir is effective because the herpes virus contains a gene (Herpes-Thymidine Kinase TK gene) that is sensitive to the drug. Researchers have been able to separate this gene from the virus. Using DNA technology, researchers hope to transfer and implant the TK gene into tumor cells making them sensitive to ganciclovir. In theory, giving patients ganciclovir will kill all tumor cells that have the TK gene incorporated into them. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001328 •
Magnesium Sulfate to Prevent Brain Injury in Premature Infants Condition(s): Brain Injuries; Cerebral Palsy Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Premature infants are at risk for acute brain injuries and long-term developmental problems such as cerebral palsy (CP). Research suggests that high levels of magnesium at and around the time of birth may decrease the risk of brain injuries. This study will evaluate the effects of giving magnesium to premature infants. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065949
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Melatonin and Radiation Therapy in Treating Patients With Brain Metastases Condition(s): unspecified adult solid tumor, protocol specific; brain metastases; radiation toxicity Study Status: This study is no longer recruiting patients. Sponsor(s): Radiation Therapy Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as melatonin may make tumor cells more sensitive to radiation therapy and may protect normal cells from the side effects of radiation therapy. PURPOSE: Randomized phase II trial to determine the effectiveness of combining melatonin with radiation therapy in treating patients who have brain metastases. Phase(s): Phase II
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031967 •
Phase II Randomized Study of Stereotactic Radiosurgery Plus Fractionated WholeBrain Radiotherapy vs Fractionated Whole-Brain Radiotherapy Alone for Multiple Primary or Metastatic Brain Tumors Condition(s): Brain Neoplasms Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS); University of Pittsburgh Purpose - Excerpt: Objectives: I. Evaluate whether stereotactic radiosurgery provides local control at multiple sites in patients with primary or metastatic brain tumors, controlled systemic disease, and preserved neurologic function. II. Examine survival, clinical outcome, and local tumor imaging response in these patients. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004659
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Radiation Therapy With or Without RSR13 in Treating Patients With Brain Metastases Condition(s): brain metastases Study Status: This study is no longer recruiting patients. Sponsor(s): Allos Therapeutics Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as RSR13 may make tumor cells more sensitive to radiation therapy. PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy to the brain with or without RSR13 in treating patients who have brain metastases. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005887
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Radiation Therapy With or Without Temozolomide in Treating Patients With NonSmall Cell Lung Cancer That is Metastatic to the Brain Condition(s): brain metastases Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy
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may kill more tumor cells. PURPOSE: Randomized phase II trial to compare the effectiveness of radiation therapy plus temozolomide to that of radiation therapy alone in treating patients who have non-small cell lung cancer that is metastatic to the brain. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00030836 •
Radiolabeled Monoclonal Antibody Therapy After Radiation Therapy in Treating Patients With Primary Brain Tumors Condition(s): Central Nervous System Tumor; Brain Tumor Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Duke Comprehensive Cancer Center Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate tumor cells and deliver tumor-killing substances, such as radioactive iodine, to them without harming normal cells. PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody after radiation therapy in treating patients with newly diagnosed primary brain tumors that can be surgically resected. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003484
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SU5416 in Treating Children With Recurrent or Progressive Brain Tumors Condition(s): recurrent childhood brain stem glioma; recurrent childhood visual pathway and hypothalamic glioma; childhood choroid plexus tumor; recurrent childhood cerebral astrocytoma; childhood craniopharyngioma; recurrent childhood cerebellar astrocytoma; childhood central nervous system germ cell tumor; recurrent childhood ependymoma; recurrent childhood supratentorial primitive neuroectodermal and pineal tumors; childhood meningioma; recurrent childhood medulloblastoma; Childhood Oligodendroglioma Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Pediatric Brain Tumor Consortium Purpose - Excerpt: RATIONALE: SU5416 may stop the growth of brain cancer cells by stopping blood flow to the tumor. PURPOSE: Phase I trial to study the effectiveness of SU5416 in treating children who have recurrent or progressive brain tumors. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006247
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Temozolomide in Treating Patients With Brain Metastases Condition(s): brain metastases
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Study Status: This study is no longer recruiting patients. Sponsor(s): Duke Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of temozolomide in treating patients who have brain metastases. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005954 •
Temozolomide With or Without Radiation Therapy to the Brain in Treating Patients With Stage IV Melanoma That Is Metastatic to the Brain Condition(s): Stage IV Melanoma; Recurrent Melanoma; brain metastases Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Melanoma Cooperative Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known if chemotherapy is more effective with or without radiation therapy in treating brain metastases. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy with or without radiation therapy to the brain in treating patients who have stage IV melanoma with asymptomatic brain metastases. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00020839
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A Pediatric Phase I Trial of RMP-7 and Carboplatin in Brain Tumors Condition(s): Brain Neoplasms; Glioma; Medulloblastoma Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: The presence of a highly selective blood-brain barrier (BBB) at the level of the brain capillary endothelium prevents chemotherapeutic agents from attaining therapeutic concentrations at the target site. RMP-7 is a synthetic bradykinin analog which specifically binds to B2 receptors expressed on the brain capillary endothelial cells and preferentially increases capillary permeability within CNS tumors. Carboplatin is an anticancer agent with preclinical and clinical antitumor activity against a variety of brain tumors. A pediatric phase I trial of the combination of RMP-7 and carboplatin will be conducted to determine the maximum tolerated dose of RMP-7 in children with refractory brain tumors. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below
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Web Site: http://clinicaltrials.gov/ct/show/NCT00001502 •
Carmustine Implants in Treating Patients With Brain Metastases Condition(s): unspecified adult solid tumor, protocol specific; brain metastases Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving the drugs in different ways may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of implanted carmustine wafers in treating patients who have brain metastases and who are undergoing surgery to remove the tumor. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003878
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Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Infants With Malignant Brain or Spinal Cord Tumors Condition(s): childhood brain tumor; childhood rhabdomyosarcoma; Neuroblastoma Study Status: This study is suspended. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctors to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating infants with malignant brain or spinal cord tumors. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003141
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Donepezil and EGb761 in Improving Neurocognitive Function in Patients Who Have Previously Undergone Radiation Therapy for Primary Brain Tumor or Brain Metastases Condition(s): adult brain tumor; brain metastases; radiation toxicity Study Status: This study is not yet open for patient recruitment. Sponsor(s): Comprehensive Cancer Center of Wake Forest University; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Donepezil and EGb761 may be effective in improving neurocognitive function (such as thinking, attention, concentration, and memory) and may improve quality of life in patients who have undergone radiation therapy to the brain. PURPOSE: Phase II trial to study the effectiveness of donepezil and EGb761 in
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improving neurocognitive function in patients who have undergone radiation therapy for primary brain tumor or brain metastases. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070161 •
PET Scan of Brain Metabolism in Relation to Age and Disease Condition(s): Alzheimer's Disease; Brain Neoplasm; Niemann Pick Disease Study Status: This study is completed. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The main source of energy for the brain comes from a combination of oxygen and glucose (sugar). For brain cells to function normally they must receive a constant supply of these nutrients. As areas of the brain become more active blood flow into and out of these areas increase. In addition to oxygen and glucose, the brain uses chemical compounds known as phospholipids. These phospholipids make up the covering of nerve cells that assist in the transfer of information from cell to cell. Without phospholipids brain cell activity may become abnormal and cause problems in the nervous system. Certain diseases like Alzheimer's disease and brain tumors can affect blood flow to the brain and change the way the brain metabolizes phospholipids. In addition to diseases, changes in the brain occur with normal healthy aging. This study is designed to use PET scan to measure changes in blood flow and changes in phospholipid metabolism. Using this technique, researchers can improve their understanding of how certain diseases change the shape and function of the brain. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001972
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Radiation Therapy Plus Thalidomide and Temozolomide in Treating Patients With Newly Diagnosed Brain Metastases Condition(s): brain metastases; unspecified adult solid tumor, protocol specific Study Status: This study is not yet open for patient recruitment. Sponsor(s): Comprehensive Cancer Center of Wake Forest University; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Combining whole-brain radiation therapy with thalidomide and temozolomide may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining whole-brain radiation therapy with thalidomide and temozolomide in treating patients who have newly diagnosed brain metastases. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below
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Web Site: http://clinicaltrials.gov/ct/show/NCT00049361 •
Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Primary or Metastatic Brain Tumors Condition(s): adult brain tumor; brain metastases; localized resectable neuroblastoma; Neuroblastoma Study Status: This study is suspended. Sponsor(s): Duke Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and deliver radioactive tumor-killing substances to them without harming normal cells. This may be effective treatment for primary or metastatic brain tumors. PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy in treating patients with primary or metastatic brain tumors. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003461
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Study of Temozolomide in the Treatment of Brain Metastasis from Non-small-cell Lung Cancer Condition(s): Neoplasms
Metastases,
Neoplasm;
Carcinoma,
Non-Small-Cell
Lung;
Brain
Study Status: This study is completed. Sponsor(s): Schering-Plough Purpose - Excerpt: Brain metastases from solid tumors are diagnosed in more than 300,000 patients annually. Nonsmall cell lung cancer accounts for the majority of CNS mets. Treatment with whole brain radiation and steroids will improve neurologic symptoms in about 50% of patients although survival is short. This study will test the safety and efficacy of temozolomide in combination with radiation therapy in the treatment of patients with brain mets form nonsmall cell lung cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034697
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately
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5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “brain” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 5. PATENTS ON BRAIN Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “brain” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on brain, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Brain By performing a patent search focusing on brain, 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
9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on brain: •
Brain cooling device and monitoring system Inventor(s): Corbett; Dale (14 Bryon, St. John's, Newfoundland, CA A1B 3B7), Fletcher; R. David (#117 16350 White Rock, British Columbia, CA V4A 8J8), Hillier; Tim F (Box 34, Suite 407, RR4, Saskatoon, Saskatchewan, CA S7K 3Z7), Ramsden; Vivian R. (409 Waterloo Crescent, Saskatoon, Sasktchewan, CA S7H 4L3), Thornhill; Jim (2336 Munroe Avenue South, Saskatoon, Saskatchewan, CA SJ7 1S5), White; Gill N. (4255 Argyle Street, Regina, Saskatchewan, CA S4S 3M1) Assignee(s): None Reported Patent Number: 6,682,552 Date filed: September 17, 2001 Abstract: A device and system designed for use in a pre-hospital setting to cool the brain after injury is described. The device incorporates a cold insert into an arch that fits around the neck of a subject, without obstructing the airway of the subject. A cold insert, such as a frozen fluid or endothermic packet, is disposed within one or both of the terminal ends of the arch, adjacent to one or both of the subject's carotid arteries. The cooling effect is specifically directed to cool the blood flowing through the carotid artery to the brain. A system incorporating the device with a temperature monitor is also disclosed. The system allows a health care professional to monitor and regulate cooling as required in the pre-hospital setting. Excerpt(s): The present invention relates generally to the field of medical devices. More particularly, the present invention relates to a device and monitoring system for use in localized cooling of the brain. Temperature is an important variable in determining the amount of neural damage resulting from an ischemic attack (Dietrich et al, 1990). Clinically, temperature is now deemed a significant, independent risk factor for stroke (Reith et al, 1996), as well as a contributing risk factor to other risk factors for stroke such as hypertension, cigarette smoking, atrial fibrillation, diabetes, and transient ischemic attacks etc. Therapeutically, the implementation of mild hypothermia (34-36.degree. C.) to stroke and head trauma patients is advocated as beneficial based on clinical studies (Kammersgaard et al, 2000; Schwab et al, 1997) and animal experiments indicating long term neural and behavioural benefits (Corbett & Thornhill, 2000; Colbourne & Corbett, 1994). Clinically, whole body cooling of stroke patients has been tested with forced air cooling with the Bair Hugger Wrap and anesthesics (Kammersgaard et al, 2000) or with cooling from fans and alcohol washes (Schwab et al, 1997). Pethidine anesthestic is given to prevent shivering activation. These whole body-cooling techniques are generally effective in reducing core temperature but long term stroke outcome analysis is not yet known. More regionalized head cooling of head trauma and stroke patients has been attempted. Cooling helmets (previously cooled or having cooled water or air circulating through them) attempt to decrease brain temperature via conductive changes through the skull (Klatz & Goldman, 1995 in U.S. Pat. No. 5,913,885; Gunn & Gunn 1998 in PCT Patent Application WO98/56310). Cooling pillows for the head and neck region have also been devised to decrease the body temperature of the patient (Tsutomu & Koji, 1998 in Japanese Patent Publication 09-072152; Katsumitsu & Shinichi, 2000 in Japanese Patent Publication 10-250455). These extracranial cooling devices may take some time to internally cool the brain via convective (air) or conductive processes. Another approach (Schwartz, 1997) is to cool the brain directly via cooling the carotid arterial blood by
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way of a water perfused neck collar, or alternatively, cooling the oral cavity by way of a water perfused endotracheal tube. Web site: http://www.delphion.com/details?pn=US06682552__ •
Composition and treatment method for brain and spinal cord injuries Inventor(s): Wang; Yanming (203 Summer St., Malden, MA 02148) Assignee(s): None Reported Patent Number: 6,683,066 Date filed: September 24, 2001 Abstract: After interruption of blood supply to central nervous system tissue, cerebral edema sets in. It has been shown that restoring blood flow to injured areas of the central nervous system after the onset of edema does not result in blood reperfusing the tissue. A composition and method for treating injured central nervous tissue, or preventing injury to central nervous system tissue is provided. The composition is generally an amphipathic lipid in an oil solution. The method provides for withdrawing cerebrospinal fluid from the subarachnoid spaces around the tissue to be treated or protected, and replacing that fluid with an approximately equivalent volume of the amphipathic lipid in oil composition. The treatment can be augmented with agents that suppress production of cerebrospinal fluid, or with other known agents. Excerpt(s): This invention is related to medical formulations used to treat and protect the central nervous system and methods of using those formulations. In particular, the invention relates to neuroprotective compositions and methods using those compositions to protect the brain or minimize lasting damage. Most Central Nervous System (CNS) injuries, including stroke, trauma, hypoxia-ischemia, multiple sclerosis, seizure, infection, and poisoning directly or indirectly involve a disruption of blood supply to the CNS, and share the same common pathologic process, that is: rapid cerebral edema leading to irreversible brain damage, and eventually to brain cell death. One common injury to the CNS is stroke, the destruction of brain tissue as a result of intracerebral hemorrhage or infarction. Stroke is a leading cause of death in the developed world. It may be caused by reduced blood flow or ischemia that results in deficient blood supply and death of tissues in one area of the brain (infarction). Causes of ischemic strokes include blood clots that form in the blood vessels in the brain (thrombus) and blood clots or pieces of atherosclerotic plaque or other material that travel to the brain from another location (emboli). Bleeding (hemorrhage) within the brain may also cause symptoms that mimic stroke. Web site: http://www.delphion.com/details?pn=US06683066__
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Compositions and methods for enhancing drug delivery across and into epithelial tissues Inventor(s): Kirschberg; Thorsten A. (Mountain View, CA), McGrane; P. Leo (Mountain View, CA), Rothbard; Jonathan B. (Cupertino, CA), Sista; Lalitha V. S. (Sunnyvale, CA), Wender; Paul A. (Menlo Park, CA) Assignee(s): Cellgate, Inc. (sunnyvale, Ca) Patent Number: 6,669,951 Date filed: February 23, 2001 Abstract: This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including the skin, gastrointestinal tract, pulmonary epithelium, ocular tissues and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length. Excerpt(s): This invention pertains to the field of compositions and methods that enhance the delivery of drugs and other compounds across the dermal and epithelial membranes, including, for example, skin, the gastrointestinal epithelium and the bronchial epithelium. Transdermal or transmucosal drug delivery is an attractive route of drug delivery for several reasons. Gastrointestinal drug degradation and the hepatic first-pass effect are avoided. In addition, transdermal and transmucosal drug delivery is well-suited to controlled, sustained delivery (see, e.g., Elias, In Percutaneous Absorption: Mechanisms-Methodology-Drug Delivery, Bronaugh & Maibach, Eds., pp 1-12, Marcel Dekker, New York, 1989.). For many applications, traditional methods of administering drugs are not optimal because of the very large initial concentration of the drug. Transdermal delivery could allow a more uniform, slower rate of delivery of a drug. Moreover, patient compliance is encouraged because such delivery methods are easy to use, comfortable, convenient and non-invasive. These advantages of transdermal and transmucosal delivery have not led to many clinical applications because of the low permeability of epithelial membranes, the skin in particular, to drugs. The difficulties in delivering drugs across the skin result from the barrier property of skin. Skin is a structurally complex thick membrane that represents the body's border to the external hostile environment. The skin is composed of the epidermis, the dermis, the hypodermis, and the adenexal structures (epidermal appendages). The epidermis, the outermost epithelial tissue of the skin, is itself composed of several layers--the stratum corneum, the stratum granulosum, the stratum spinosum, and the stratum basale. Web site: http://www.delphion.com/details?pn=US06669951__
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Delivery of therapeutic agents by gene therapy Inventor(s): McGarrity; Gerard J. (Gaithersburg, MD), Oldfield; Edward H. (Philomont, VA), Ram; Zvi (Tel Aviv, IL) Assignee(s): Genetic Therapy, Inc. (gaithersburg, Md), The United States of America AS Represented by the Department of Health and (washington, Dc) Patent Number: 6,669,935 Date filed: December 15, 1998 Abstract: A process for treating a disease or disorder of a host by delivery of a therapeutic agent to the brain of the host, which comprises transducing endothelial cells of blood vessels located in the brain of a host in vivo with a vector including a polynucleotide encoding a therapeutic agent. The vector is administered intravascularly to the host, and the vector produces the therapeutic agent in the endothelial cells. Excerpt(s): This invention relates to gene therapy for treatment of a disease or disorder by delivering therapeutic agents to the brain. More particularly, this invention relates to gene therapy through delivery of therapeutic agents to the brain by transducing endothelial cells of blood vessels located in the brain in vivo with a vector, wherein the vector is administered intravascularly. The invention further relates to treatment of tumors by transducing gene therapy wherein endothelial cells of blood vessels of the tumor are transduced with a polynucleotide expressing a therapeutic agent. This invention further relates to the treatment of brain tumors by gene therapy wherein endothelial cells of blood vessels located in a brain tumor are transduced with a vector which includes a polynucleotide encoding an agent which when expressed provides for inhibition, prevention or destruction of the tumor. The vector is administered intravascularly. The agent may be a negative selective marker. Upon administration of an interaction agent to the host, the growth of the brain tumor is inhibited, prevented, or destroyed, thereby leading to regression of the tumor. Gene therapy has been used to deliver a therapeutic agent to the brain by in vivo transduction of cells which involves direct injection of a suitable vector into cells located in the brain, e.g., injection of the vector into tumor cells located in the brain. Web site: http://www.delphion.com/details?pn=US06669935__
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Device for enhanced delivery of biologically active substances and compounds in an organism Inventor(s): Lerner; Eduard N. (Amsterdam, NL), Lerner; Leonid (Los Angeles, CA) Assignee(s): Intraabrain International NV (curacao, An) Patent Number: 6,678,553 Date filed: May 20, 1998 Abstract: A device and methods are described for a non-invasive transnasal and transocular drug delivery to the central nervous system using iontophoresis technology. By delivered through the olfactory nerve and the optical nerve, a biologically active substance of interest can be enhanced to be delivered into the CNS and CSF and bypassing the blood-brain barrier. Such drug delivery system can also be enhanced by using phonophoresis and other enhancement techniques. Excerpt(s): Most of the efforts currently under way to discover new therapeutic drugs for disorders of the central nervous system (CNS) will also face the problem of
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delivering them to the brain without impairing the activity or integrity of such substances or compounds, while minimizing systemic adverse effects. And that means finding a way around--or through--the blood brain barrier (BBB), a physiological barrier between bloodstream and brain. A National Institutes of Mental Health (NIMH) study showed that, in the United States, one out of three individuals suffers from a CNS disorder at some time in life. Approximately two million in the same country have suffered a stroke, which is the third leading cause of death in the United States. After the discovery of the electrical nature of nerve impulse by Galvani in 1791, attention focused on the possibility of using electricity as a mode of drug delivery. It has been long known that medicines could be introduced into the human body by way of the skin. The skin has a selective permeability to lipophilic (lipid soluble) substances and acts as a barrier to hydrophilic (water soluble) substances. In 1747, Veratti suggested that hydrophobic drugs might be Introduced to the subcutaneous tissue through human skin by the application of a direct current. This mode has become known as iontophoresis (meaning ion transfer). Web site: http://www.delphion.com/details?pn=US06678553__ •
Direct central nervous system catheter and temperature control system Inventor(s): Meythaler; Jay M. (Birmingham, AL), Miller; Landon C. (Tuscalosa, AL), Peduzzi; Jean (Clanton, AL) Assignee(s): Uab Research Foundation (birmingham, Al) Patent Number: 6,682,508 Date filed: December 3, 2001 Abstract: A central nervous system (CNS) catheter assembly (20) adapted for use as a ventriculostomy catheter and a spinal catheter includes a catheter body (28) defining at least one lumen (30) therethrough having a drug delivery branch (22) and a monitoring/sensing branch (24). The drug delivery branch (22) and the monitoring/sensing second branch (24) are in fluid communication with the lumen (30). The assembly further includes a filter assembly (36) disposed in fluid communication with the drug delivery branch (22) and a valve assembly (54) disposed in fluid communication with the monitoring/sensing branch (24). Also in accordance with the present invention, there is provided a temperature control system (170) for use in controlling the temperature of a location within the central nervous system such as the brain or the spinal cord. The system further includes a pump controller (180), a central processing unit or controller (194), a temperature sensing element (184), and a power supply (194) all operatively connected to the temperature control mechanism. Excerpt(s): The subject invention relates to a catheter assembly and, more specifically, to a direct central nervous system catheter assembly suitable for use for: the simultaneous measurement of intracranial pressure, draining of cerebrospinal fluid (CSF), delivery of therapeutic agents and/or drug(s) directly into the cerebrospinal fluid, and a temperature control system which can be coupled to the direct central nervous system catheter to prevent or reduce damage to the central nervous system. By way of background, ventriculostomy catheters are commonly used to facilitate the drainage of cerebrospinal fluid (CSF) to reduce intracerebral pressure and can also be connected to pressure transducers for the monitoring of intracranial pressure (ICP). The increased use of ventriculostomy catheters can be directly associated with the publication of Guidelines to the Management of Severe Head Injury (Bullock et al. (1995) Guidelines for the Management of Severe Head Injury. San Francisco: Brain Trauma Foundation,
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Inc.; Rosner et al. (1992) J. Neurosurgery 76:399A; Rosner et al. (1990) J. Trauma 30:93341; Rosner (1987) "Cerebral perfusion pressure: The link between intracranial pressure and systemic circulation". In Wood (ed.): Cerebral Flood Flow: Physiologic and Clinical Aspects. McGraw Hill, New York, N.Y., pp. 425-88, 1987). These Guidelines recommend the use of either a pressure bolt against the cerebral membranes or that a ventriculostomy be performed to directly measure ICP in all patients with a head injury and a Glascow coma score (GCS) of less than 10. Additionally, ventriculostomies are often utilized because of the added feature of allowing direct access to the CSF at the level of the brain. This is of particular importance as these catheters allow direct access to the CSF, which allows for direct withdrawal of CSF to control increased intracranial pressure, monitor drug levels or metabolites in the CSF (Kossman et al. (1996) J. Antimicrob. Chemother. 37(1):161-7), or to remove toxic substances from the CSF flow (Kristofet al. (1998) J. Neurol. Neurosurg. Psychiatry. 64(3):379-81). Similar to the present day ventriculostomy catheters, spinal catheters having an external port have been utilized for many years for the sampling of CSF and for the delivery of medications to the CSF in and around the spinal cord. These medications include anesthetics and acute pain medications. In animal models of induced CNS injury it has been suggested that intrathecal or intraventricular delivery may be of use to attenuate the amount of injury (Buki et al. (1999) J. Neurotrauma 16(6):511-21). Web site: http://www.delphion.com/details?pn=US06682508__ •
Drug delivery catheter assembly with inflatable balloon Inventor(s): Putz; David A. (Franksville, WI) Assignee(s): Ad-tech Medical Instrument Corp. (racine, Wi) Patent Number: 6,656,152 Date filed: November 16, 2001 Abstract: An improved assembly and method for accurately and safely delivering a drug to a selected intracranial site are disclosed. The assembly ensures delivery of the drug to the selected site by providing a barrier which prevents "backflow" or leakage of the drug. The assembly includes a guide catheter having an inflatable balloon which is able to seal or occlude the tract created by the insertion of the guide catheter into the brain. The guide catheter further includes a passageway which receives a delivery catheter through which the drug is administered to the selected site in the brain. Upon delivery of the drug to the selected site, the balloon may be deflated and the assembly removed. Excerpt(s): This invention is related generally to the delivery of drugs to a patient and, more particularly, to the intracranial delivery of drugs. The introduction of drugs or other therapeutic agents to sites in the brain is common in many neurosurgical procedures today. Such procedures include the delivery of chemotherapeutic agents such as protein toxins to brain tumors, delivery of genes used in genetic therapy, and the delivery of neural cell or tissue during transplantation surgeries. One area in which use of such procedures is particularly relevant is in drug delivery for treatment of epilepsy and other movement disorders. In the last twenty years, major advances have been made concerning the identification of specific epileptic syndromes which respond poorly to treatment by ingested drugs but may be successful treated by surgical intervention. Recent advances in diagnostic technology and surgical techniques have led to an increasing use of surgical treatment of epilepsy. In addition, through the discovery that particular seizures result from particular neuronal activity, the targeting of the
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causal neuronal activity for treatment by anti-epileptic drugs has achieved success. The neuronal cell populations responsible for such activity may be eliminated through the direct delivery of drugs such as excitotoxins. The elimination of specific epileptic disturbances has allowed people afflicted with epilepsy to be relieved of disabling seizures and the disturbing side-effects of treatment while avoiding the long-term psychosocial consequences of living with an uncontrolled epileptic disorder. Web site: http://www.delphion.com/details?pn=US06656152__ •
Embolectomy catheters and methods for treating stroke and other small vessel thromboembolic disorders Inventor(s): Chow; Sean L. (Tustin, CA), Cox; Brian J. (Laguna Niguel, CA), Green, Jr.; George R. (Costa Mesa, CA), Monetti; Richard R. (San Clemente, CA), Rosenbluth; Robert F. (Laguna Niguel, CA), Sternweiler; Thomas R. (Laguna Niguel, CA) Assignee(s): Microvention, Inc. (aliso Viejo, Ca) Patent Number: 6,685,722 Date filed: November 10, 1999 Abstract: Embolectomy catheters, rapid exchange microcatheters, systems and methods for removing clots or other obstructive matter (e.g., thrombus, thromboemboli, embolic fragments of atherosclerotic plaque, foreign objects, etc.) from blood vessels. This invention is particularly useable for percutaneous removal of thromboemboli or other obstructive matter from small blood vessels of the brain, during an evolving stroke or period of cerebral ischemia. In some embodiments, the embolectomy catheters of this invention are advanceable with or over a guidewire which has been pre-inserted through or around the clot. Also, in some embodiments, the embolectomy catheters include clot removal devices which are deployable from the catheter after the catheter has been advanced at least partially through the clot. The clot removal device may include a deployable wire nest that is designed to prevent a blood clot from passing therethrough. The delivery catheter may include telescoping inner and outer tubes, with the clot removal device being radially constrained by the outer tube. Retraction of the outer tube removes the constraint on the clot removal device and permits it to expand to its deployed configuration. An infusion guidewire is particularly useful in conjunction with the embolectomy catheter, and permits infusion of medicaments or visualization fluids distal to the clot. Excerpt(s): The present invention relates generally to medical methods and devices, and more particularly to thrombolectomy catheters, and methods for using such catheters, for removing blood clots or other matter from the lumens of blood vessels or other anatomical conduits. Various types of thromboembolic disorders, such as stroke, pulmonary embolism, peripheral thrombosis, atherosclerosis, and the like, are known to occur in human beings and other mammals. Such thromboembolic disorders are typically characterized by the presence of a thromboembolus (i.e., a viscoelastic blood clot comprised of platelets, fibrinogen and other clotting proteins) which has become lodged at a specific location in a blood vessel. In cases where the thromboembolism is located in a vein, the obstruction created by the thromboembolus may give rise to a condition of blood stasis, with the development of a condition known as thrombophlebitis within the vein. Moreover, peripheral venous embolisms may migrate to other areas of the body where even more serious untoward effects can result. For example, the majority of pulmonary embolisms are caused by emboli that originate in
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the peripheral venous system, and which subsequently migrate through the venous vasculature and become lodged with the lung. Web site: http://www.delphion.com/details?pn=US06685722__ •
Engraftable human neural stem cells Inventor(s): Kim; Seung U. (Vancouver, CA), Snyder; Evan Y. (Jamaica Plain, MA), Wolfe; John H. (Philadelphia, PA) Assignee(s): The Children's Medical Center Corporation (boston, Ma), University of British Columbia (vancouver, Gb), University of Pennsylvania (philadelphia, Pa) Patent Number: 6,680,198 Date filed: September 20, 1999 Abstract: Stable clones of neural stem cells (NSCs) have been isolated from the human fetal telencephalon. In vitro, these self-renewing clones (affirmed by retroviral insertion site) can spontaneously give rise to all 3 fundamental neural cell types (neurons, oligodendrocytes, astrocytes). Following transplantation into germinal zones of the developing newborn mouse brain, they, like their rodent counterparts, can participate in aspects of normal development, including migration along well-established migratory pathways to disseminated CNS regions, differentiation into multiple developmentallyand regionally-appropriate cell types in response to microenvironmental cues, and nondisruptive, non-tumorigenic interspersion with host progenitors and their progeny. Readily genetically engineered prior to transplantation, human NSCs are capable of expressing foreign transgenes in vivo in these disseminated locations. Further supporting their potential for gene therapeutic applications, the secretory products from these NSCs can cross-correct a prototypical genetic metabolic defect in abnormal neurons and glia in vitro as effectively as do murine NSCs. Finally, human cells appear capable of replacing specific deficient neuronal populations in a mouse model of neurodegeneration and impaired development, much as murine NSCs could. Human NSCs may be propagated by a variety of means--both epigenetic (e.g., chronic mitogen exposure) and genetic (transduction of the propagating gene vmyc)--that are comparably safe (vmyc is constitutively downregulated by normal developmental mechanisms and environmental cues) and effective in yielding engraftable, migratory clones, suggesting that investigators may choose the propagation technique that best serves the demands of a particular research or clinical problem. All clones can be cryopreserved and transplanted into multiple hosts in multiple settings. Excerpt(s): Neural stem cells (NSCs) are postulated to be relatively primordial, uncommitted cells that exist in the developing and even adult nervous system and are responsible for giving rise to the array of more specialized cells of the mature CNS.sup.1-12. They are operationally defined by their ability (a) to differentiate into cells of all neural lineages (neurons--ideally of multiple subtypes, oligodendroglia, astroglia) in multiple regional and developmental contexts (i.e., be multipotent); (b) to self-renew (i.e., also give rise to new NSCs with similar potential); (c) to populate developing and/or degenerating CNS regions. An unambiguous demonstration of monoclonal derivation is obligatory to the definition--i.e., a single cell must possess these attributes. With the earliest recognition that rodent neural cells with stem cell properties, propagated in culture, could be reimplanted into mammalian brain where they could reintegrate appropriately and stably express foreign genes.sup.13-16, gene therapists and restorative neurobiologists began to speculate how such a phenomenon might be harnessed for therapeutic advantage as well as for understanding
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developmental mechanisms. These, and the studies which they spawned (reviewed elsewhere.sup.2,9-11,17-21) provided hope that the use of NSCs--by virtue of their inherent biology--might circumvent some of the limitations of presently available graft material and gene transfer vehicles and make feasible a variety of novel therapeutic strategies.sup.20-22. Neural cells with stem cell properties have been isolated from the embryonic, neonatal and adult rodent CNS and propagated in vitro by a variety of equally effective and safe means--both epigenetic (e.g., with mitogens such as epidermal growth factor [EGF] or basic fibroblast growth factor [bFGF].sup.1,5,16,23-27 or with membrane substrates.sup.7) and genetic (e.g., with propagating genes such as vmyc or SV40 large T-antigen.sup.1,9-15,17-19,28-32). Maintaining such NSCs in a proliferative state in culture does not appear to subvert their ability to respond to normal developmental cues in vivo following transplantation--to withdraw from the cell cycle, interact with host cells, differentiate appropriately.sup.9-16,29-33. These extremely plastic cells migrate and differentiate in a temporally and regionally appropriate manner particularly following implantation into germinal zones throughout the brain. They participate in normal development along the murine neuraxis, intermingling nondisruptively with endogenous progenitors, responding similarly to local microenvironmental cues for their phenotypic determination and appropriately differentiating into diverse neuronal and glial cell types. In addition, they can express foreign genes (both reporter genes and therapeutic genes) in vivo.sup.9-21,29-32, and are capable of specific neural cell replacement in the setting of absence or degeneration of neurons and/or glia.sup.9,11,31,32. We present evidence that neural cells with rigorously defined stem cell features, may, indeed, be isolated from the human brain and may emulate the behavior of NSCs in lower mammals. Not only do these observations vouchsafe conservation of certain neurodevelopmental principles to the human CNS, but they suggest that this class of neural cells may ultimately be applied as well to research and clinical problems in the human. Indeed, not only might the actual human NSC clones described in this report serve that function, but our data suggest that other investigators may readily obtain and propagate such cells from other sources of human material through a variety of equally safe and effective methods (both epigenetic and genetic) with the expectation that such cells will fulfill the demands of multiple research and/or therapeutic problems. Web site: http://www.delphion.com/details?pn=US06680198__ •
Human glucocorticoid receptor 1A promoter and splice variants Inventor(s): Breslin; Mary B. (Kenner, LA), Vedeckis; Wayne V. (Metairie, LA) Assignee(s): Board of Supervisors of Louisiana State University and Agricultural and (baton Rouge, La) Patent Number: 6,649,341 Date filed: April 19, 2000 Abstract: A new sequence, hGR 1Ap/e, has been isolated from human DNA upstream from the previously known 2.7 kbp human GR promoter region. This new sequence was found to contain a new promoter (the 1A GR promoter) and a new untranslated exon sequence (GR exon 1A) for the human glucocorticoid receptor protein (hGR). Alternative splicing produces three different hGR 1A-containing transcripts, 1A1, 1A2, and 1A3. Exon 1A3-containing GR transcripts appear to be restricted to blood cell cancers and to the human brain. Glucocorticoid hormone treatment caused an upregulation of exon 1A3-containing GR transcripts in T-lymphoblast cells, and a down-
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regulation of exon 1A3-containing transcripts in B-lymphoblast cells. Thus detection of exon 1A3-containing transcripts can be used for the diagnosis of patients with blood cell cancers, including T-cell acute lymphoblastic leukemia (ALL), and to identify patients that would benefit from glucocorticoid hormone treatment. Excerpt(s): This invention pertains to the location of a human glucocorticoid receptor gene promoter region and to three splice variants of the human glucocorticoid receptor gene; and the use of the promoter region and of the splice variants to improve the diagnosis and treatment of leukemia. The use of naturally occurring substances, such as hormones, to treat cancer has certain advantages. Although side effects can occur, the effects are usually less severe than those caused by cytotoxic chemotherapy. Unfortunately most cancers are not effectively controlled by hormonal therapy, but exceptions include certain hormonally-dependent breast cancers that can be treated with the anti-estrogen tamoxifen, and acute promyelocytic leukemia that is responsive to alltrans retinoic acid. Additionally, some lymphoid malignancies can be effectively treated with glucocorticoid steroid hormones, hormones that control a variety of metabolic and developmental processes. See R. R. Denton et al., "Differential Autoregulation of Glucocorticoid Receptor Expression in Human T- and B-Cell Lines," Endocrinology, vol. 133, pp. 248-256 (1993). Certain types of B- and T-cell acute lymphoblastic leukemia ("ALL") are particularly sensitive to glucocorticoid hormonal therapy. Glucocorticoids affect lymphoid malignancies due to the induction of programmed cell death, or apoptosis, of immature lymphocytes. See C. W. Distelhorst, "Basic and Clinical Studies of Glucocorticosteroid Receptors in Lymphoid Malignancies," pp. 494-515 in W. V. Vedeckis (ed.) Hormones and Cancer (1996). The cytolytic effect of glucocorticoids is mediated by the glucocorticoid receptor (GR). Upon entering the cell, glucocorticoids bind to the soluble intracellular receptor protein GR, causing an alteration in GR structure. This alteration in structure converts the unactivated receptor to the activated form that both binds to specific DNA sequences and facilitates transcription of glucocorticoid-responsive genes. The transcribed glucocorticoid-induced mRNA messages are then transported into the cytoplasm and translated into specific proteins. The changes in concentration and types of the intracellular proteins modulate a variety of intracellular processes. GR concentration has been shown to correlate with sensitivity to steroid treatment in vitro. See J. N. Vanderbilt et al., "Intracellular Receptor Concentration Limits Glucocorticoid-Dependent Enhancer Activity," Mol. Endocrinol., vol. 1, pp. 68-74(198.sup.7). Additionally, an in vivo study of large numbers of patients with ALL found that a low GR level in lymphoblasts isolated at the initial diagnosis was significantly correlated with a poor response to therapy, shorter duration of remission, and a poor overall prognosis. Distelhorst (1996). Web site: http://www.delphion.com/details?pn=US06649341__ •
Matrix adhering to nasal mucosa Inventor(s): Akiyama; Yoko (Omihachiman, JP), Bando; Hiroto (Osaka, JP), Nagahara; Naoki (Kawabe-gun, JP) Assignee(s): Takeda Chemical Industries, Ltd. (osaka, Jp) Patent Number: 6,663,883 Date filed: February 21, 2002 Abstract: This invention provides a matrix adhering to the nasal mucosa which allows improved transfer into the brain of a drug exerting its effect in the brain and is capable
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of continuously supplying the drug into the brain. This matrix contains a polyglycerol fatty acid ester, the drug exerting its effect in the brain, and a viscogenic substance. Excerpt(s): The present invention relates to a matrix adhering to the nasal mucosa, which allows improved transfer, into the brain, of a drug exerting its effect in the brain and is capable of continuously supplying the drug into the brain. As those literatures that disclose pharmaceutical compositions adsorbed into mucosae, the followings are known. 1) WO-A 98/42323 describes "A pharmaceutical composition comprising an unease inhibitor and an oil base material", and there is an example of an agent adhering to mucosae on digestive tracts. Web site: http://www.delphion.com/details?pn=US06663883__ •
Method to increase cerebral blood flow in amyloid angiopathy Inventor(s): Schmidt; Ann Marie (Franklin Lakes, NJ), Stern; David M. (Great Neck, NY), Yan; Shi Du (New York, NY), Zlokovic; Berislav (Rochester, NY) Assignee(s): The Trustee of Columbia University in the City of New York (new York, Ny) Patent Number: 6,677,299 Date filed: November 5, 2001 Abstract: The present invention provides a method for decreasing cerebral vasoconstriction in a subject suffering from chronic or acute cerebral amyloid angiopathy which comprises administering to the subject an inhibitor of receptor for advanced glycation endproduct (RAGE) in an effective amount to inhibit transcytosis of amyloid.beta. peptides across the blood-brain barrier in the subject, thereby decreasing cerebral vasoconstriction in the subject. The invention further provides for a method for ameliorating neurovascular stress in a subject which comprises administering to the subject an effective amount of an inhibitor of receptor for advanced glycation endproduct (RAGE), so as to increase cerebral blood flow in the subject, thereby ameliorating neurovascular stress in the subject. Excerpt(s): Throughout this application, various publications are referenced by number. Full citations for these publications may be found listed at the end of the specification immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein. The pain of Alzheimer's disease results directly from the memory loss and cognitive deficits suffered by the patient. These eventually result in the patient's loss of identity, autonomy, and freedom. As a step toward curing this disease, alleviating its symptoms, or retarding its progression, it would be desirable to develop a transgenic animal model exhibiting the main debilitating phenotype of Alzheimer's disease, that is, memory loss, expressed concomitantly with the neuropathological correlates of Alzheimer's disease, for example, beta-amyloid accumulation, increased glial reactivity, and hippocampal cell loss. It is estimated that over 5% of the U.S. population over 65 and over 15% of the U.S. population over 85 are beset with some form of Alzheimer's disease (Cross, A. J., Eur J Pharmacol (1982) 82:7780; Terry, R. D., et al., Ann Neurol (1983) 14:497506). It is believed that the principal cause for confinement of the elderly in long term care facilities is due to this disease, and approximately 65% of those dying in skilled nursing facilities suffer from it. Web site: http://www.delphion.com/details?pn=US06677299__
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Methods for promoting weight gain using GPE-related compounds Inventor(s): Alexi; Tajrena (Auckland, NZ) Assignee(s): Neuronz Limited (auckland, Nz) Patent Number: 6,682,753 Date filed: March 13, 2002 Abstract: Weight gain in a mammal, especially a human, having a condition that leads to decreased weight gain or weight loss, such as AIDS, brain trauma, a chronic neurodegenerative disease such as Alzheimer's disease, Parkinson's disease, Huntington's disease, or multiple sclerosis, or other condition, is promoted by increasing the effective concentration of a GPE-related compound (GPE or a GPE analog) in the central nervous system of the mammal. This increase may be achieved by administration to the mammal of an effective amount of a GPE-related compound, a prodrug thereof, or an implant containing cells that express the GPE-related compound or prodrug. Excerpt(s): This invention relates to methods of promoting weight gain. Weight loss after head injury is a common side effect (Pepe et al. (1999), The metabolic response to acute traumatic brain injury and implications for nutritional support, Journal of Head Trauma and Rehabilitation, 5: 462-474; Borzotta et al. (1994), Enteral versus parenteral nutrition after severe closed head injury, Journal of Trauma, 37(3): 459-468; Flakoll et al. (1995), Protein and glucose metabolism during isolated closed-head injury, American Journal of Physiology, 269(4Pt1): E636-E641). There are also no treatments currently available to prevent the cell death that occurs in the brain as a consequence of head injury. Similarly, weight loss is a common symptom associated with chronic neurological diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and multiple sclerosis. Treatments available at present for such chronic neurological diseases only target symptoms. No drugs are currently available to intervene in the disease process. Web site: http://www.delphion.com/details?pn=US06682753__
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Monoclonal antibody recognizing C-terminus of hBNP Inventor(s): Igano; Ken'ichi (Nara, JP), Inouye; Ken (Hyogo, JP), Kono; Masao (Osaka, JP), Tsuji; Tetsuo (Nara, JP), Yamauchi; Akira (Osaka, JP) Assignee(s): Shionogi Seiyaku Kabushiki Kaisha (osaka, Jp) Patent Number: 6,677,124 Date filed: August 31, 2001 Abstract: A hybridoma producing a monoclonal antibody recognizing the C-terminus of human brain natriuretic peptide (hBNP) was cultivated in a medium or the abdominal cavity of a mouse to recover the monoclonal antibody from the medium or ascites accumulated in the abdominal cavity. An immunoassay for hBNP was established using the monoclonal antibody. The immunoassay for hBNP of the invention is so sensitive that the minimum detection limit is 1 pg/ml and can therefore determine the hBNP level in blood plasma directly, without the extraction of hBNP from blood plasma. It is useful for diagnosing diseases such as hypertension and the like, and states of the heart, kidney, and the like by using the increase/decrease of the hBNP level as an index.
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Excerpt(s): This invention relates to a monoclonal antibody recognizing the C-terminus of hBNP, a hybridoma producing the monoclonal antibody, a method of producing the monoclonal antibody comprising cultivating the hybridoma in a medium or an abdominal cavity of a mouse and recovering said monoclonal antibody from said medium or ascites in said abdominal cavity, and an immunoassay for hBNP with use of said monoclonal antibody. Brain natriuretic peptide (BNP) in the porcine brain was first reported by Matsuo et al, Nature 332, 78-81 (1988). There exist porcine (p) BNP-26 of 26 amino acid residues and pBNP-32 of 32 residues. These has peripheral and central actions similar to those of atrium natriuretic peptide (ANP) and play an important role in the homeostasis of body fluid and the control of blood pressure together with ANP. BNP was suggested to be produced in and secreted from the heart in human (Biochem. Biophys. Res. Commun. 159, 1427-1434 (1989)), and BNP in the human heart has recently be isolated and characterized (FEBS Lett. 259, 341-345 (1990)). Human BNP (hBNP) comprises 32 amino acid residues identical with the sequence 77-108 of hBNP precursor. As mentioned above, because BNP plays an important role in the homeostasis of body fluid and the control of blood pressure, the determination of hBNP in the blood by an immunoassay etc. seems useful for diagnosing diseases such as hypertension and the like and states of heart, kidney and the like with taking an increase/decrease of hBNP level as an index. However, an average level of hBNP in the blood of normal adults is 0.9.+-.0.07 fmol/ml (3.12.+-.0.24 pg/ml) (J. Clin. Invest. 87, 1402-1412 (1991)) and such a low level has made it impossible to directly assay hBNP in the blood plasma without an extraction. Web site: http://www.delphion.com/details?pn=US06677124__ •
Pharmaceutical combinations for the treatment of stroke and traumatic brain injury Inventor(s): Chenard; Bertrand L. (Waterford, CT), Menniti; Frank S. (Mystic, CT), Saltarelli; Mario D. (Mystic, CT) Assignee(s): Pfizer Inc (new York, Ny) Patent Number: 6,667,317 Date filed: September 6, 2001 Abstract: This invention relates to methods of treating traumatic brain injury (TBI) or hypoxic or ischemic stroke, comprising administering to a patient in need of such treatment an NR2B subtype selective N-methyl-D-aspartate (NMDA) receptor antagonist in combination with either: (a) a neutrophil inhibitory factor (NIF); (b) a sodium channel antagonist; (c) a nitric oxide synthase (NOS) inhibitor; (d) a glycine site antagonist; (e) a potassium channel opener; (f) an AMPA/kainate receptor antagonist; (g) a calcium channel antagonist; (h) a GABA-A receptor modulator (e.g., a GABA-A receptor agonist); or (i) an antiinflammatory agent. Excerpt(s): This invention relates to methods of treating traumatic brain injury (TBI), ischemic stroke, or hypoxic brain injury, comprising administering to a patient in need of such treatment an NR2B subtype selective N-methyl-D-aspartate (NMDA) receptor antagonist in combination with one or more other compounds that protect neurons from toxic insult, inhibit the inflammatory reaction after brain damage or promote cerebral reperfusion. More specifically, this invention relates to methods of treating traumatic brain injury (TBI) or hypoxic or ischemic stroke, comprising administering to a patient in need of such treatment an NR2B subtype selective N-methyl-D-aspartate (NMDA) receptor antagonist in combination with either: (a) a neutrophil inhibitory factor (NIF); (b) a sodium channel antagonist; (c) a nitric oxide synthase (NOS) inhibitor; (d) a glycine
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site antagonist; (e) a potassium channel opener; (f) an AMPA/kainate receptor antagonist; (g) a calcium channel antagonist; (h) a GABA-A receptor modulator (e.g., a GABA-A receptor agonist); (i) an antiinflammatory agent; or (j) a matrix metalloprotease (MMP) inhibitor. Brain and spinal cord injury caused by stroke, trauma or hypoxia often result in lifelong disability and premature death. The cause of disability and death is the disruption of function and frank death of neurons and other cells in the central nervous system. Therefore, a clear benefit is anticipated from therapies that reduce or prevent neuronal dysfunction and death after ischemic, hypoxic or traumatic CNS insult. Web site: http://www.delphion.com/details?pn=US06667317__ •
Stem cell growth factor-like polypeptide Inventor(s): Chao; Cheng-Chi (19980 Portal Plaza, Cupertino, CA 95014), Childs; John (611 Arcadia Ter. Unit #303, Sunnyvale, CA 94085), Drmanac; Radoje T. (850 E. Greenwich Pl., Palo Alto, CA 94303), Labat; Ivan (1006 Asbury Way, Mountain View, CA 94043), Mize; Nancy K. (662 Mountain View Ave., Mountain View, CA 94041), Tang; Y. Tom (4230 Ranwick Ct., San Jose, CA 95118) Assignee(s): None Reported Patent Number: 6,667,391 Date filed: January 16, 2001 Abstract: The invention provides novel polynucleotides and polypeptides encoded by such polynucleotides and mutants or variants thereof that correspond to a novel human stem cell growth factor-like protein. These polynucleotides comprise nucleic acid sequences isolated from cDNA libraries from human fetal liver spleen (Hyseq clone identification number 6118092), ovary (Hyseq clone identification number 8375786), adult brain (Hyseq clone identification numbers 701734, 15327638, 15741682, 15954941, 15955015), lung tumor (Hyseq clone identification number 11047146 and 10280328), spinal cord (Hyseq clone identification number 10102150), cervix (Hyseq clone identification numbers 10022437 and 14029194), ovary (Hyseq clone identification number 8319153), endothelial cells (Hyseq clone identification number 13815744), umbilical cord (Hyseq clone identification number 18568149), lymphocyte (Hyseq clone identification number 10257378), lung fibroblast (Hyseq clone identification number 17116257), fetal brain (Hyseq clone identification number 15266959), and testis. Other aspects of the invention include vectors containing processes for producing novel human stem cell growth factor-like polypeptides, and antibodies specific for such polypeptides. Excerpt(s): The present invention provides novel polynucleotides and proteins encoded by such polynucleotides, along with uses for these polynucleotides and proteins, for example in therapeutic, diagnostic and research methods. In particular, the invention relates to a novel human stem cell growth factor-like protein. Technology aimed at the discovery of protein factors (including e.g., cytokines, such as lymphokines, interferons, CSFs, chemokines, and interleukins) has matured rapidly over the past decade. The now routine hybridization cloning and expression cloning techniques clone novel polynucleotides "directly" in the sense that they rely on information directly related to the discovered protein (i.e., partial DNA/amino acid sequence of the protein in the case of hybridization cloning; activity of the protein in the case of expression cloning). More recent "indirect" cloning techniques such as signal sequence cloning, which isolates DNA sequences based on the presence of a now well-recognized secretory leader sequence motif, as well as various PCR-based or low stringency hybridization-based
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cloning techniques, have advanced the state of the art by making available large numbers of DNA/amino acid sequences for proteins that are known to have biological activity, for example, by virtue of their secreted nature in the case of leader sequence cloning, by virtue of their cell or tissue source in the case of PCR-based techniques, or by virtue of structural similarity to other genes of known biological activity. Identified polynucleotide and polypeptide sequences have numerous applications in, for example, diagnostics, forensics, gene mapping; identification of mutations responsible for genetic disorders or other traits, to assess biodiversity, and to produce many other types of data and products dependent on DNA and amino acid sequences. Web site: http://www.delphion.com/details?pn=US06667391__ •
Tryptophan source from plants and uses thereof Inventor(s): Hudson; Craig J. (253 Cambria Street, Stratford, Ontario, CA N5A 1H9), Hudson; Susan P. (253 Cambria Street, Stratford, Ontario, CA N5A 1H9) Assignee(s): None Reported Patent Number: 6,656,473 Date filed: July 11, 2001 Abstract: Compositions are described comprising at least partially defatted meal from a plant source containing protein-bound tryptophan, preferably squash seeds, and, optionally, a carbohydrate source provided in an amount capable of facilitating transport of in vivo generated tryptophan across the blood brain barrier. Also described are dietary supplements, foods and beverages comprising the composition of the invention to induce sleep or provide tryptophan supplementation to individuals in need thereof. Excerpt(s): This invention relates to compositions comprising natural sources of tryptophan, particularly protein-bound tryptophan from plants, processes for making said compositions; physical formulations of said compositions, and use of said compositions as dietary supplements, food, beverage, and as pharmaceutical compositions for inducing sleep, improving tryptophan metabolism, alleviating reduced levels of serotonin in a human, anxiety disorder, depression, obsessive compulsive, aggression, chronic paid and eating disorder. Tryptophan is an essential amino acid found in numerous naturally occurring plant proteins and which has a number of interesting medicinal qualities including treatment of insomnia as well as an adjunct in the treatment of a number of psychiatric disorders. After absorption, tryptophan circulates in the blood as approximately 80% bound to plasma albumin with the remaining 20% circulating as free tryptophan, and under appropriate conditions, tryptophan is transported into the brain. Once across the blood brain (BBB), tryptophan becomes available for metabolism into serotonin, a neurotransmitter implicated in mood and sleep regulation (Boman, 1988). Serotonin, in turn, is metabolized to melatonin; a sleep related hormone found in the pineal gland, a small cone-like structure in the epithalamus of the brain that regulates the 24-hour circadian rhythm in humans. Ingestion of a sufficient quantity of tryptophan per se consistently results in reduced sleep latency i.e. the time from "lights out" to sleep, and an improvement in overall quality of sleep through improved sleep architecture (Boman, 1988). Tryptophan metabolism to serotonin also serves well in conditions where depleted serotonin levels exists such as anxiety disorders, depression, obsessive-compulsive some pain disorders, aggression and eating disorders. The hypnotic effects of tryptophan are well studied and follow a fairly flat dose-response curve with a plateau at approximately 1000 mg
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(for review see Schneider-Helmut and Spinweber, 1986). When given alone, as little as 250 mg of tryptophan is sufficient to produce improved sleep in people with mild insomnia, or in those reporting longer-than-average sleep latency (Hartmann and Spinweber, 1976; Hartmann 1982). Dosages of 1000 mg are associated with more consistent results (Schneider-Helmut and Spinweber, 1986) but higher dosages (2,00012,000 mg) offer little extra benefit and, indeed, the highest dosages (12,000 mg) are associated with disrupted sleep architecture despite a reduction in sleep latency (Griffiths et al 1972). Web site: http://www.delphion.com/details?pn=US06656473__ •
Tumor necrosis related receptor, TR7 Inventor(s): Deen; Keith Charles (Glenmoore, PA), Hurle; Mark R. (Norristown, PA), Tan; Kong B. (Philadelphia, PA), Young; Peter (Lawrenceville, NJ) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,660,839 Date filed: May 19, 1999 Abstract: TR7 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing TR7 polypeptides and polynucleotides in the design of protocols for the treatment of chronic and acute inflammation, arthritis, septicemia, autoimmune diseases (such as inflammatory bowel disease and psoriasis), transplant rejection, graft versus host disease, infection, stroke, ischemia, acute respiratory disease syndrome, restenosis, brain injury, AIDS, bone diseases, cancer (such as lymphoproliferative disorders), atherosclerosis, and Alzheimers disease, among others and diagnostic assays for such conditions. Excerpt(s): This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to Tumor necrosis factor receptor (TNF-R) family, hereinafter referred to as TR7. The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. Many biological actions, such as responses to certain stimuli and natural biological processes, are controlled by factors such as cytokines. Cytokines generally act through receptors by engaging the receptor and producing an intracellular response. For example, tumor necrosis factors (TNF) alpha and beta are cytokines which act through TNF receptors to regulate numerous biological processes, including protection against infection and induction of shock and inflammatory disease. The TNF molecules belong to the "TNF-ligand" superfamily, and act together with their receptors or counter-ligands, the "TNF-receptor" superfamily. So far, nine members of the TNF-ligand superfamily have been identified and ten members of the TNF-receptor superfamily have been characterized. Identified ligands include TNF-.alpha., lymphotoxin-.alpha. (LT-.alpha., also known as TNF-.beta.), LT-.beta. (found in complex heterotrimer LT-.alpha.2-.beta.), FasL, CD40L, CD27L, CD30L, 4-1BBL, OX40L and nerve growth factor (NGF). The superfamily of TNF-receptors include the p55TNF receptor, p75TNF receptor, TNF receptor-related protein, FAS antigen or APO-1, CD40, CD27, CD30, 4-1BB, OX40, low a p75 and NGF-receptor (Meager, A., Biologicals, 22:291-295 (1994)). Web site: http://www.delphion.com/details?pn=US06660839__
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Patent Applications on Brain As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to brain: •
Anti-aging nutritional supplement Inventor(s): Giampapa, Vincent C.; (Montclair, NJ) Correspondence: Melvin K. Silverman; Suite 500; 500 West Cypress Creek Road; Fort Lauderdale; FL; 33309; US Patent Application Number: 20040001817 Date filed: May 13, 2003 Abstract: An anti-aging nutritional supplement composition includes vitamins, minerals, an inflammatory process support, a blood sugar/insulin support, a botanical antioxidants, a methylating factor, a DNA repair agent, a fat metabolizer, an absorption enhancer, a brain function support, whole foods, a cellular energizer, a nucleotide precursor, amino acids, a fatty acid complex, and digestive enzymes. The composition supplies nutritional supplements necessary for proper glycation, DNA methylation, anti-oxidation, and control of inflammatory processes. The composition and the method of use provide an effective anti-aging treatment by decreasing DNA damage, increasing DNA repair, and improving immune function of human body. Excerpt(s): This application is the non-provisional patent application of provisional patent application serial No. 60/378,160 filed May 14, 2002, which is herein incorporated by reference in its entirety. The instant invention relates to a program of oral supplementation to augment what is termed the cellular soup. The cellular soup constitutes extracellular and intra-cellular fluid which acts respectively to nourish the extracellular matrix, such as tissue and nerves, and the intra-cellular matrix which comprises the inner structure of the cells, this including the cell nucleus and the mitrocondria which are the energy producing elements within every living cell. The cell nucleus is where most genetic functions occur, including the aging process. Accordingly, proper nourishment to the cell nucleus and mitrocondria is an essential aspect of any anti-aging therapy. Within context of the instant invention, the term of cell represents both somatic cell and adult stem cell. Within the cellular soups are many organic compounds which affect the metabolic process, these including vitamins, minerals, enzymes, amino acids, pre-hormones (known as hormonal precursors), cofactors, antioxidants, anti-inflammatories, anti-glycation agents and DNA methylation control agents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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This has been a common practice outside the United States prior to December 2000.
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Aortic shunt for selective cerebral perfusion in stroke and cardiac arrest Inventor(s): Barbut, Denise R.; (New York, NY) Correspondence: O'melveny & Meyers; 114 Pacifica, Suite 100; Irvine; CA; 92618; US Patent Application Number: 20040006299 Date filed: July 1, 2003 Abstract: An aortic shunt comprising a second tubular member nested within a lumen of a first tubular member, wherein aortic blood flows through the lumen of the first tubular member and oxygenated and/or cooled blood is infused through a lumen and distal port(s) of the second tubular member to perfuse the cerebral vasculature. Alternatively, a cooling cylinder is nested within the first member, such that aortic blood is cooled through the cylinder before being delivered to the brain. A venous return catheter comprising an elongate tubular member is also provided to remove and isolate the cooled blood entering through jugular veins from the blood entering through the subclavian veins, when the cannula is positioned in the superior vena cava. Methods of using the aortic shunt and/or venous return cannula in providing selective cerebral perfusion in patients suffering from stroke and cardiac arrest are also disclosed. Excerpt(s): This is a divisional of U.S. application Ser. No. 09/658,482 filed Sep. 7, 2000, incorporated herein by reference in its entirety. The present invention relates generally to medical devices. More particularly, the invention relates to methods and devices for selectively diverting blood flow to the cerebral vasculature from the aorta in patients having stroke or cardiac arrest. More particularly, the invention relates to apparatus and methods which provide an aortic shunt and a venous return cannula for augmenting and/or cooling oxygenated blood to the brain. The devices and methods also provide mechanisms for variable blood flow through the aorta. Patients experiencing cerebral ischemia often suffer from disabilities ranging from transient neurological deficit to irreversible damage (stroke) or death. Cerebral ischemia, i.e., reduction or cessation of blood flow to the central nervous system, can be characterized as either global or focal. Global cerebral ischemia refers to reduction of blood flow within the cerebral vasculature resulting from systemic circulatory failure caused by, e.g., shock, cardiac failure, or cardiac arrest. Within minutes of circulatory failure, tissues become ischemic, particularly in the heart and brain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Assessing blood brain barrier dynamics or identifying or measuring selected substances, including ethanol or toxins, in a subject by analyzing Raman spectrum signals Inventor(s): Borchert, Mark S.; (La Canada, CA), Lambert, James L.; (Sunland, CA) Correspondence: Myers Bigel Sibley & Sajovec; PO Box 37428; Raleigh; NC; 27627; US Patent Application Number: 20040019283 Date filed: March 25, 2003 Abstract: A non-invasive method for analyzing the blood-brain barrier includes obtaining a Raman spectrum of a selected portion of the eye and monitoring the Raman spectrum to ascertain a change to the dynamics of the blood brain barrier.Also, noninvasive methods for determining the brain or blood level of an analyte of interest, such as glucose, drugs, alcohol, poisons, and the like, comprises: generating an excitation
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laser beam at a selected wavelength (e.g., at a wavelength of about 400 to 900 nanometers); focusing the excitation laser beam into the anterior chamber of an eye of the subject so that aqueous humor, vitreous humor, or one or more conjunctiva vessels in the eye is illuminated; detecting (preferably confocally detecting) a Raman spectrum from the illuminated portion of the eye; and then determining the blood level or brain level (intracranial or cerebral spinal fluid level) of an analyte of interest for the subject from the Raman spectrum. In certain embodiments, the detecting step may be followed by the step of subtracting a confounding fluorescence spectrum from the Raman spectrum to produce a difference spectrum; and determining the blood level and/or brain level of the analyte of interest for the subject from that difference spectrum, preferably using linear or nonlinear multivariate analysis such as partial least squares analysis. Apparatus for carrying out the foregoing methods are also disclosed. Excerpt(s): This application is a continuation-in-part of International Patent Application Serial No. PCT/US/02/00649, filed Jan. 9, 2002, which is a continuation-in-part of U.S. application Ser. No. 09/756,897, filed Jan. 9, 2001, which is a continuation-in-part of U.S. application Ser. No. 09/690,113, filed Oct. 16, 2000, which is a continuation of U.S. application Ser. No. 09/351,788, filed Jul. 12, 1999, now U.S. Pat. No. 6,181,957, which claims the benefit of priority to U.S. Provisional Application No. 60/092,545, filed Jul. 13, 1998, the disclosures of which are hereby incorporated by reference as if restated in their entirety herein. The present invention concerns methods and apparatus for measuring or identifying the presence of selected substances in the body and/or assessing blood brain dynamics of a subject via non-invasive spectrographic analysis of certain regions of the eye, such as the aqueous humor in the anterior chamber of the eye. Non-invasive measurement of physiological and foreign substances, including blood glucose, by optical spectroscopy techniques has remained an elusive target for at least two decades. Blood, tissue, and most excreted fluids contain numerous substances which confound many spectral signatures. On the other hand, the aqueous humor (AH), which fills the anterior chamber of the eye (between the lens and cornea), contains relatively few molecules capable of interfering with the spectroscopic detection of glucose. These are primarily lactate, ascorbate, and urea. This fact, along with its optically accessible location behind the cornea, makes the AH an attractive choice as a site on which to attempt non-invasive analysis of many substances present in a biological subject, including glucose. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Brain retraction sensor Inventor(s): Ayad, Michael; (Washington, DC) Correspondence: Daryl A. Basham; Roylance Abrams Berdo & Goodman; 1300 19th Street, N.W.; Washington; DC; 20036; US Patent Application Number: 20040010208 Date filed: July 9, 2002 Abstract: An electrode grid device is disclosed comprising a deformable envelope, further comprising non-polarizable electrodes and a pressure recording port. The device is designed to allow for monitoring of brain retraction pressure and local cortical electrical activity including DC potential, as well as to redistribute the force applied during retraction and thereby diminish the chance of focal brain injury during surgery. Retraction pressure recorded is equal over the full area of contact, providing a more meaningful measurement than simply at one point on the retractor. A means is
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disclosed for evacuation of air from the system to improve accuracy and fidelity of the pressure measurements. It is a further aspect of the device to allow for measurement of intracranial pressure, DC potential and EEG in epileptic and severe head trauma patients for management of edema and injury, respectively. Excerpt(s): This invention is related generally to intracranial sensors for prevention of retractor blade injury (i.e., "retraction injury") of the brain, and subdural monitoring devices. A retractor is an instrument used during surgery for, among other things, holding back structures adjacent to the immediate operative field (See, e.g., U.S. Pat. No. 5,769,781). During neurosurgical operations for aneurysms, tumors or other lesions located in the skull base, the surgeon must employ retracting devices in order to displace one or more lobes of the brain enough to gain adequate surgical exposure to the lesion. These retractors are adjusted by hand to optimize exposure. Unfortunately, it is very difficult for the surgeon to accurately gauge the amount of pressure actually applied to the brain during such placement of the retractor (see, e.g., Hongo et al., J Neurosurg 1987; 66:270-275). Moreover, it is also possible to inadvertently position the blade of the retractor such that a focal pressure point occurs at one particular area of the retractor blade pressing against the brain. Thus, injury to the brain can occur as a result of brain retraction when either the force applied is excessive or when the pressure is not adequately distributed to a large enough area of brain. This injury is thought to be the result of ischemia (inadequate blood flow) caused by the retraction, local trauma, or a combination of both. It has been estimated that brain retraction injury occurs in approximately 10% of major cranial base tumor procedures and 5% of intracranial aneurysm surgeries (Andrews et al., Neurosurgery 1993; 33:1052-64). Various attempts have been made to develop technology to help minimize the incidence of this type of injury, with limited success. For example, a strain gauge or gauges attached to the retractor blade has been employed (Hongo et al., 1987; Rosenorn J., Acta Neurochir (Wein) 1987; 85:17-22). This approach has limited utility because pressure can only be measured from the point or points where the strain gauges are situated. As mentioned above, sometimes the brunt of the force occurs at the tip of the retractor blade where no strain gauge is present. Certainly this technique does little, if anything, to distribute force on the brain more evenly. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and methods for treatment and detection of multiple cancers Inventor(s): Liau, Linda M.; (Los Angeles, CA) Correspondence: Gates & Cooper Llp; Howard Hughes Center; 6701 Center Drive West, Suite 1050; Los Angeles; CA; 90045; US Patent Application Number: 20040005642 Date filed: July 2, 2002 Abstract: The invention provides a method for inhibiting proliferation of cancer cells, as well as methods for detecting and treating various cancers, including cancer of the brain, lung, breast, prostate and colon. The method comprises contacting a cancer cell with a molecule that disrupts the biological activity of a GDOX molecule. In one embodiment, the molecule is an antibody directed against a GDOX peptide. In other embodiments, the molecule is an antisense nucleotide directed against a GDOX nucleic acid molecule, or a vaccine comprising a GDOX peptide or a polynucleotide encoding a GDOX peptide. The invention additionally provides methods for detecting and treating cancer using GDOX-related molecules.
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Excerpt(s): Throughout this application various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to describe more fully the state of the art to which this invention pertains. The present invention relates generally to detection and therapy of cancer. The invention is more specifically related to a novel gene, GDOX, and to GDOXrelated molecules as therapeutic and diagnostic targets. GDOX antibodies and antisense nucleotides can be used in vaccines and pharmaceutical compositions for the treatment of various cancers expressing GDOX, as well as in methods of detecting and assessing the malignancy of such cancers. The invention further provides methods for identifying molecules useful in the treatment and detection of cancer. Cancer and infectious disease are significant health problems throughout the world. Although advances have been made in detection and therapy of these diseases, no vaccine or other universally successful method for prevention or treatment is currently available. Current therapies, which are generally based on a combination of chemotherapy or surgery and radiation, continue to prove inadequate in many patients. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Enhanced brain function by gaba-ergic stimulation Inventor(s): Leventhal, Audie G.; (Salt Lake City, UT) Correspondence: Klarquist Sparkman, Llp; 121 SW Salmon Street; Suite 1600; Portland; OR; 97204; US Patent Application Number: 20040023952 Date filed: December 17, 2002 Abstract: Methods are disclosed for improving age-related decreases in cortical function by increasing the activity of inhibitory pathways, such as GABA-ergic pathways, in the central nervous system. In particular examples, subjects with age-related decreases in cortical function are treated by administering therapeutically effective amounts of a GABA-ergic agonist. The disclosed methods also enable screening for drugs that inhibit an age-related decline in cortical function, for example by exposing a subject to a test agent, and measuring an increase in GABA-ergic cortical inhibitory activity. Excerpt(s): This invention concerns treatments for improving age-related cortical function of a subject. Cognition is the ability of a subject to use information about and from the environment in an adaptive way. Unfortunately, cognitive and other cortical functions (such as auditory discrimination, somatosensory function, motor function, and language abilities) often decline in aging subjects. This decline is a common cause of incapacity, morbidity and even death in elderly animals and humans. These problems are expected to become more widespread as life span increases, and more individuals live into senescence. One of the great medical and social challenges of the coming decades is to develop approaches to deal with this often incapacitating problem. Gamma-aminobutyric acid (GABA) is regarded as one of the major inhibitory amino acid transmitters in the mammalian brain. Widely (although unequally) distributed through the mammalian brain, GABA is believed to be a transmitter at approximately 30% of the synapses in the brain. GABA mediates many of its actions through a complex of proteins (GABA receptors) localized both on cell bodies and nerve endings. Postsynaptic responses to GABA are mediated through alterations in chloride conductance that generally, although not invariably, lead to hyperpolarization of the cell. Drugs that interact at the GABAa receptor can possess a spectrum of pharmacological activities depending on their abilities to modify the action of GABA.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Gene and protein specific for excitable tissues Inventor(s): Jay, Gilbert; (North Bethesda, MD), Li, Xuan; (Silver Spring, MD), Shu, Youmin; (Potomac, MD) Correspondence: Origene Technologies, Incorporated; 6 Taft Court; Suite 100; Rockville; MD; 20850; US Patent Application Number: 20030235826 Date filed: June 24, 2002 Abstract: The present invention relates to OTB182, and all facets of novel polynucleotides encoded by it, the polypeptides they encode, antibodies and specific binding partners thereto, and their applications to research, diagnosis, drug discovery, therapy, clinical medicine, forensic science and medicine, etc. The polynucleotides are expressed in excitable tissues, such as heart, brain, and muscle, and are therefore useful in variety of ways, including, but not limited to, as molecular markers, as drug targets, and for detecting, diagnosing, staging, monitoring, prognosticating, preventing or treating, determining predisposition to, etc., diseases and conditions, such neuropathy, neuralgic amyotrophy (e.g., HNA), myopathy, sensorineural hearing loss (e.g., DFNA20), mental retardation, neuromuscular disorders, and other diseases especially relating to excitable tissues, such as heart, brain, and muscle. Excerpt(s): Polyadenylated mRNA was isolated from tissue samples, and used as a template for first-strand cDNA synthesis. The resulting cDNA samples were normalized using beta-actin as a standard. For the normalization procedure, PCR was performed on aliquots of the first-strand cDNA using beta-actin specific primers. The PCR products were visualized on an ethidium bromide stained agarose gel to estimate the quantity of beta-actin cDNA present in each sample. Based on these estimates, each sample was diluted with buffer until each contained the same quantity of beta-actin cDNA per unit volume. To detect gene expression, PCR was carried out on aliquots of the normalized tissue samples using a forward (SEQ ID NO 3) and reverse (SEQ ID NO 4) gene-specific primers. The reaction products were loaded on to an agarose (e.g., 1.5-2%) gel and separated electrophoretically. The present invention relates to all facets of OTB182, polypeptides encoded by it, antibodies and specific binding partners thereto, and their applications to research, diagnosis, drug discovery, therapy, clinical medicine, forensic science and medicine, etc. The polynucleotides and polypeptides are useful in variety of ways, including, but not limited to, as molecular markers, as drug targets, and for detecting, diagnosing, staging, monitoring, prognosticating, preventing or treating, determining predisposition to, etc., diseases and conditions relating to excitable tissues, such as heart, brain, and muscle. The identification of specific genes, and groups of genes, expressed in pathways physiologically relevant to such tissues permits the definition of functional and disease pathways, and the delineation of targets in these pathways which are useful in diagnostic, therapeutic, and clinical applications. The present invention also relates to methods of using the polynucleotides and related products (proteins, antibodies, etc.) in business and computer-related methods, e.g., advertising, displaying, offering, selling, etc., such products for sale, commercial use, licensing, etc. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Gpe analogs Inventor(s): Alexi, Tajrena; (Auckland, NZ), Gluckman, Peter; (Auckland, NZ) Correspondence: Fliesler Dubb Meyer & Lovejoy, Llp; Four Embarcadero Center; Suite 400; San Francisco; CA; 94111; US Patent Application Number: 20040014674 Date filed: June 11, 2003 Abstract: The invention relates to GPE analogs, particularly GPE analogs capable of inducing an equivalent physiological effect to GPE within a patient. Such GPE analogs include peptides where the Gly of Gly-Pro-Glu is replaced by any of Ala, Ser, Thr, or Pro; where the Pro of Gly-Pro-Glu is replaced by any of Ala, Ser, Thr, or Gly; and where the Glu of Gly-Pro-Glu is replaced by any of Asn, Asp, or Gln. The GPE analogs of the invention have application in any method of therapy or porphylaxis in which GPE has application. These applications include the treatment of acute brain injury and neurodegenerative disease, including but not limited to injury or disease in the CNS. The GPE analogs will normally be administered as part of a pharmaceutical composition or preparation. Excerpt(s): GPE is a tri-peptide consisting of amino acids Gly-Pro-Glu. It and its dipeptide derivatives Gly-Pro and Pro-Glu were first disclosed by Sara et al in EP 0366638. Sara et al disclosed that GPE is effective as a neuromodulator (able to affect the electrical properties of neurons). The applicants have also established that GPE has neuroprotective properties and that it therefore has utility in the prevention or inhibition of neural cell death (WO 95/17204). The nervous system contains neural cells and glial cells. Glial cells, including astrocytes, microglia, Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system, often aid neural cells and neural activity by providing support and assistance to neural cells through means including anatomical configuration, metabolic activity, and physiological function. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Immortalized lines of endothelial brain cells and therapeutic applications thereof Inventor(s): Chaverot, Nathalie; (Paris, FR), Couraud, Pierre-Olivier; (Auffargis, FR), Laterra, John J.; (Baltimore, MD), Quinonero, Jerome; (Noisiel, FR), Roux, Francoise; (Paris, FR), Strosberg, Arthur Donny; (Paris, FR), Tchelingerian, Jean-Leon; (Gif-SurYvette, FR), Vignais, Lionel; (Paris, FR) Correspondence: Mintz Levin Cohn Ferris Glovsky & Popeo; 666 Third Avenue; New York; NY; 10017; US Patent Application Number: 20040018619 Date filed: May 19, 2003 Abstract: The invention relates to optionally modified immortalized lines of endothelial brain cells of mammalians, as well as applications as preventive or curative drug and particularly for the treatment of primary and secondary, neurologic or psychiatric diseases, including brain tumor, and for stimulating the growth and reproduction of breeding animals. The invention also relates to the method for preparing said cell lines. The endothelial cell lines of mammalians disclosed are comprised of immortalized endothelial brain cells presenting at least one of the following characteristics of
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differentiated endothelial brain cells, in a stable way: the expression of endothelial markers, the secretion of vasoactive substances, the expression of molecules of the major histocompatilility complex (MHC), the expression of hormonal receptors, and the existence of tight junctions; said cell lines comprise a nucleic acid fragment having at least one immortalizing fragment of a viral or cellular oncogene, optionally associated with at least one selection gene, and an expression vector comprising a sequence coding for polypeptide, a protein or a viral vector, optionally associated with at least one selection gene and optionally at least one marker gene, and they are capable in vivo to integrate brain vessels of a host mammalian and produce said polypeptide, said protein or said viral vector. Excerpt(s): The present invention relates to immortalized lines of mammalian endothelial brain cells, where appropriate modified, as well as to their applications as a medicinal product for preventive or curative use, and in particular for the treatment of various primary and secondary neurological or psychiatric disorders or diseases, including brain tumours. For some years, new methods of treatment of a number of neurological disorders formerly considered to be refractory to all conventional treatments have made use of gene therapy. These new methods are linked, in particular, to the advances made in the field of the construction of effective expression vectors and of transporters of viral and cellular transgenes, and in the characterization of target cells suitable for gene therapy of the nervous system. Two different approaches are essentially proposed for carrying out the transfer of genes into the nervous system: a socalled in vivo approach which focuses on the direct transfer of the genetic material to the cells in vivo, using viral and chemical agents, and an ex vivo approach which is characterized in that the gene transfer is performed in cells in culture, which are then implanted into the host body. The latter approach comprises steps of molecular manipulations, of cloning and of cell implantation so as to permit the distribution of the active substances in the host (SUHR S. T. et al., Arch. Neurol., 1993, 50, 1252-1268). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Immunological control of beta-amyloid levels in vivo Inventor(s): Raso, Victor; (Brighton, MA) Correspondence: Kevin M. Farrell; Pierce Atwood; Suite 350; One New Hampshire Avenue; Portsmouth; NH; 03801; US Patent Application Number: 20030235897 Date filed: March 10, 2003 Abstract: The present invention provides an antibody which catalyzes hydrolysis of.beta.-amyloid at a predetermined amide linkage. The antibody preferentially binds a transition state analog which mimics the transition state adopted by.beta.-amyloid during hydrolysis at a predetermined amide linkage and also binds to natural.beta.amyloid with sufficient affinity to detect by ELISA. Alternatively, the antibody preferentially binds a transition state analog which mimics the transition state adopted by.beta.-amyloid during hydrolysis at a predetermined amide linkage, and does not bind natural.beta.-amyloid with sufficient affinity to detect by ELISA. Antibodies generated are characterized by the amide linkage which they hydrolyze. Specific antibodies provided include those which catalyze the hydrolysis at the amyloid linkages between residues 39 and 40, 40 and 41, and 41 and 42, of.beta.-amyloid. The present invention also provides a vectorized antibody which is characterized by the ability to cross the blood brain barrier and is also characterized by the ability to catalyze the
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hydrolysis of.beta.-amyloid at a predetermined amide linkage. The vectorized antibody can take the form of a bispecific antibody, which has a first specificity for the transferrin receptor and a second specificity for a transition state adopted by.beta.-amyloid during hydrolysis. The present invention also provides a method for sequestering free.beta.amyloid in the bloodstream of an animal by intravenously administering antibodies specific for.beta.-amyloid to the animal in an amount sufficient to increase retention of.beta.-amyloid in the circulation. In addition, the present invention provides a method for sequestering free.beta.-amyloid in the bloodstream of an animal by immunizing an animal with an antigen comprised of an epitope which is present on.beta.-amyloid endogenous to the animal under conditions appropriate for the generation of antibodies which bind endogenous.beta.-amyloid. Therapeutic applications of these methods include treating patients diagnosed with, or at risk for Alzheimer's disease. Methods for reducing levels of.beta.-amyloid in the brain of an animal, by intravenously administering antibodies specific for endogenous.beta.-amyloid to the animal, or by immunizing the animal with an antigen comprised of an epitope which is present on endogenous.beta.-amyloid are also provided. In one embodiment, the antigen used to generate the antibodies is a transition state analog which mimics the transition state adopted by.beta.-amyloid during hydrolysis at a predetermined amide linkage. Similar methods which utilize or generate antibodies which catalyze the hydrolysis of.beta.amyloid for reducing levels of circulating.beta.-amyloid in an animal, and also for preventing the formation of amyloid plaques in the brain of an animal, and also for disaggregating amyloid plaques present in the brain of an animal, are also provided. Also provided is a method for generating antibodies which catalyze hydrolysis of a protein or polypeptide by immunizing an animal with an antigen comprised of an epitope which has a statine analog which mimics the conformation of a predetermined hydrolysis transition state of the polypeptide. A similar method, which utilizes reduced peptide bond analogs to mimic the conformation of a hydrolysis transition state of a polypeptide, is also provided. Excerpt(s): Alzheimer's disease is a progressive and ultimately fatal form of dementia that affects a substantial portion of the elderly population. Definitive diagnosis at autopsy relies on the presence of neuropathological brain lesions marked by a high density of senile plaques. These extracellular deposits are found in the neo-cortex, hippocampus and amygdala as well as in the walls of the meningeal and cerebral blood vessels. The principal component of these plaques is a 39 to 43 residue.beta.-amyloid peptide. Each plaque contains approximately 20 fmole (80 picograms) of this 4 kDa peptide (Selkoe et al., J. of Neurochemistry 46: 1820 (1986)). Apolipoprotein E and neurofibrillary tangles formed by the microtubule-associated tau protein are also often associated with Alzheimer's disease.beta.-amyloid is proteolytically cleaved from an integral membrane protein called the.beta.-amyloid precursor protein. The gene which codes for this protein in humans is found on chromosome 21 (St George-Hyslop et al., Science 235: 885 (1987), Kang et al., Nature 325: 733 (1987)). Numerous cultured cells and tissues (eg. brain, heart, spleen, kidney and muscle) express this.beta.-amyloid precursor protein and also secrete the 4 kDa.beta.-amyloid fragment into culture media, apparently as part of a normal processing pathway. While it is difficult to establish an absolute causal relationship between.beta.-amyloid or the plaques it forms and Alzheimer's disease, there is ample evidence to support the pathogenic role of.beta.amyloid. For example, patients with Down's syndrome have an extra copy of the.beta.amyloid precursor protein gene due to trisomy of chromosome 21 (St George-Hyslop et al., Science 235: 885 (1987), Kang et al., Nature 325: 733 (1987)). They correspondingly develop an early-onset Alzheimer's disease neuropathology at 30-40 years of age. Moreover, early-onset familial Alzheimer's disease can result from mutations in
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the.beta.-amyloid precursor protein gene which fall within or adjacent to the.beta.amyloid sequence (Hardy, J., Nature Genetics 1: 233 (1992)). These observations are consistent with the notion that deposition of.beta.-amyloid as plaques in the brain are accelerated by an elevation in its extracellular concentration (Scheuner et al., Nature Med. 2: 864 (1996)). The finding that.beta.-amyloid is directly neurotoxic both in vitro and in vivo (Kowall et al., Proc. Natl. Acad. Sci. 88: 7247 (1991)), suggest that soluble aggregated.beta.-amyloid, not the plaques per se, may produce the pathology. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Magnetic head wear, hat, sweat band or eye glasses with thermo electric cooler or heater Inventor(s): Buckner, Lynn A.; (Chickamauga, GA) Correspondence: Lynn A. Buckner; P.O. Box 609; Chickamauga; GA; 30707; US Patent Application Number: 20040010178 Date filed: July 3, 2003 Abstract: A magnetic head wear to place a magnetic field in close proximity a persons head, brain and blood flow. A magnetized hat, sweatband, magnetic eyeglasses, scarf, earmuffs, hearing aid or head ornament places a magnetic field in proximity to the brain which has significant blood volume & flow. Thus the magnetism improves the health of the body. A thermal cooler/heater may be added to a head gear to cool or warm the head thus improving body health. Excerpt(s): Head bands, sweat band, caps or hats have not previously been equipped with magnetic means for the purpose of improving health. The objective of the magnetic head wear is to place a magnetic field in close proximity a persons head, brain and blood flow. Wearing a magnetized hat, sweatband, magnetic eyeglasses, scarf, earmuffs, hearing aid or head ornament places a magnetic field in proximity to the brain which has significant blood volume & flow. A magnetic field placed in close proximity to a human body for a period of time and or frequent intervals improves the health of the body. The above described devices, place a magnetic field in close proximity to the body of the person wearing the device and allows for frequent use of the device. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method and apparatus for stimulating the sphenopalatine ganglion to modify properties of the bbb and cerebral blood flow Inventor(s): Gross, Yossi; (Mazor, IL), Shalev, Alon; (Raanana, IL) Correspondence: Abelman Frayne & Schwab; 150 East 42nd Street; New York; NY; 10017-5612; US Patent Application Number: 20040015068 Date filed: January 22, 2003 Abstract: Apparatus for modifying a property of a brain of a patient is provided, including one or more electrodes (7), adapted to be applied to a site selected from a group of sites consisting of: a sphenopalatine ganglion (SPG) (6) of the patient and a neural tract originating in or leading to the SPG. A control unit (8) is adapted to drive the one or more electrodes to apply a current to the site capable of inducing (a) an
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increase in permeability of a blood-brain barrier (BBB) of the patient, (b) a change in cerebral blood flow of the patient, and/or (c) an inhibition of parasympathetic activity of the SPG. Excerpt(s): The present invention relates generally to medical procedures and electronic devices. More specifically, the invention relates to the use of electrical devices for implantation in the head, for example, in the nasal cavity. The invention also relates to apparatus and methods for administering drugs, for treating stroke and migraine, and for improving cerebral blood flow. The blood-brain barrier (BBB) is a unique feature of the central nervous system (CNS) which isolates the brain from the systemic blood circulation. To maintain the homeostasis of the CNS, the BBB prevents access to the brain of many substances circulating in the blood. The BBB is formed by a complex cellular system of endothelial cells, astroglia, pericytes, perivascular macrophages, and a basal lamina. Compared to other tissues, brain endothelia have the most intimate cellto-cell connections: endothelial cells adhere strongly to each other, forming structures specific to the CNS called "tight junctions" or zonula occludens. They involve two opposing plasma membranes which form a membrane fusion with cytoplasmic densities on either side. These tight junctions prevent cell migration or cell movement between endothelial cells. A continuous uniform basement membrane surrounds the brain capillaries. This basal lamina encloses contractile cells called pericytes, which form an intermittent layer and probably play some role in phagocytosis activity and defense if the BBB is breached. Astrocytic end feet, which cover the brain capillaries, build a continuous sleeve and maintain the integrity of the BBB by the synthesis and secretion of soluble growth factors (e.g., gamma-glutamyl transpeptidase) essential for the endothelial cells to develop their BBB characteristics. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and apparatus for taking cerebral laminograms for working up limbic system Inventor(s): Matsuzawa, Taiju; (Sendai-shi, JP) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20040015076 Date filed: May 23, 2003 Abstract: It is intended to establish a method for forming cerebral laminograms efficacious in working up mental diseases. Provided are a laminographic method for forming cerebral laminograms which involves the step of forming laminographic images of the hippocampus and the amygdala in the limbic system, the brain stem, and the cerebral cortex all in a single image plane: and an apparatus for the laminographic method as described above. Excerpt(s): The present invention relates to a novel method for forming cerebral laminograms and an apparatus for forming cerebral laminograms. In recent years, apparatuses for taking images for medical use have been widely developed ranging from those apparatuses that give images that can be directly seen after image taking to those apparatuses of the type in which computer-processed images are observed according to the development of digital image processing technology. Magnetic resonance imaging apparatus (MRI), an X-ray computer tomographic apparatus (CT) or a positron emission tomographic apparatus (PET) is one of them. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method and device for correcting or reducing the formation of facial lines Inventor(s): Chernyakhovsky, Anna; (Winnipeg, CA), Ioffe, Semyon; (Winnipeg, CA) Correspondence: Ogilvy Renault; 1981 Mcgill College Avenue; Suite 1600; Montreal; QC; H3a2y3; CA Patent Application Number: 20040024373 Date filed: March 27, 2003 Abstract: A method for reducing the formation of lines on the skin of a person's face and neck (and/or at least partly removing such lines) comprises applying pressure on the skin at locations where a reduction in the formation of lines (or a reduction of lines) is desired with this pressure being sufficient for at least partly impeding the development of these lines by causing the person in time to diminish his/her formation of facial expressions which cause the skin to wrinkle. If the pressure is applied for a prolonged period of time, biofeedback between the brain, muscles and skin subconsciously cause the person to reduce making such facial expressions. The device is a compression and face stabilising device which comprises a mask and/or one or more bands adapted to be positioned on the skin at the aforementioned locations, and an attachment mechanism to secure the mask to the head and/or neck of the person and which is adapted to apply sufficient pressure at such locations for at least partly impeding the development of lines thereat. Excerpt(s): This Application is a Continuation of U.S. Ser. No. 09/410,078 filed on Oct. 1, 1999, pending. The present invention relates to systems for improving facial aesthetics and, more particularly, for at least partly removing or reducing the formation of ageing lines on the face. With the ageing process, the skin loses its elasticity and cannot keep its original connection with the body's muscles. Therefore, when muscles repetitively contract to define different facial expressions, the associated skin contracts as well, but does not exactly return to its original position and shape thereby gradually creating fine lines and wrinkles. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method and use of extract of a member of Typhaceae's family Inventor(s): Zhou, Tong-Shui; (Shanghai, CN) Correspondence: Raymond Y. Chan; Suite 128; 108 N. Ynez AVE.; Monterey Park; CA; 91754; US Patent Application Number: 20040018261 Date filed: July 16, 2003 Abstract: An extract of Typhae Pollen which is a traditional Chinese medicine consisting of flavonoids as active components includes at least one member of the group selected from kaempferol, quercetin and isorhamnetin and the derivatives of these active components. The present invention also relates to the degraded form of flavonoids, the metal derivatives formed with sodium and potassium salts, and the metal complex formed with a predetermined metal ion. The extract of Typhae Pollen is prepared by a plurality of extraction processes and has a plurality of functions for promoting health including lowering blood lipid level, preventing arteriosclerosis, promoting tolerance of brain and heart tissue under anaerobic condition, preventing blood platelet coagulation, preventing thrombosis and stop bleeding. The extract of Typhae Pollen of the present
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invention is also used for preventing and treating diseases related to blood vessels in brain and heart, and poor blood circulation induced diseases selecting from the group consisting of chest pain, stomachache, physical injuries, puerperium pain and menstruation. Excerpt(s): The present invention relates to technology in medical and health science, and more particularly to an extract of a Typhae Pollen and its manufacture and application in medicine and health science. `Typhae Pollen` is a common traditional Chinese medicine, which is generally dried pollen of the family Typhaceae such as Typha angustifolia L. and Typha orientalis Presl. According to the principles of the tradition Chinese medicine, Typhae Pollen has the properties of stop bleeding, bruise heeling, and enhancing circulation of the lymphatic system and it has been widely used in the treatment of bleeding, apistaxis, hematemesis, external bleeding, painful menstruation, colic, abscess, painful lymphatic system's disease or discomfort. Recent scientific researches envisage that the extracted components of Typhae Pollen by water extraction or alcohol extraction is capable of substantially increasing the coronary blood flow, improving microcirculation, increasing the tolerance ability of brain and cardiac muscle under anaerobic condition, lowering the consumption of oxygen of brain and heart system, promoting blood vessel dilation, lowering the blood lipid level, preventing arteriosclerosis, and acting as anticoagulant. All the different species of Typhae Pollen comprises organic acid, flavonoids, sterol components, long chain aliphatic components and polysaccharides. The principles and applications of these chemical components were only once disclosed in a Chinese patent 1006015 in China wherein the active mechanism and application of lowering blood lipid level of sterol, long chain aliphatic compounds of Typhae Pollen were described. Since then, there is no related arts relating to Typhae Pollen's extract. A main object of the present invention is to provide an extract of Typhae Pollen and a manufacturing method thereof wherein one of the extract components is flavonol glycosides. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of endovascular brain mapping Inventor(s): Batich, Christopher D.; (Gainesville, FL), Burry, Matthew V.; (Gainesville, FL), Mericle, Robert A.; (Gainesville, FL), Richter, O. Erich; (Gainesville, FL), Santra, Swadeshmukul; (Gainesville, FL), Watkins, Courtney S.; (Gainesville, FL) Correspondence: Dennis P. Clarke; Miles & Stockbridge P.C.; Suite 500; 1751 Pinnacle Drive; Mclean; VA; 22102-3833; US Patent Application Number: 20030236457 Date filed: April 24, 2003 Abstract: Disclosed are the following strategies for endovascularly mapping the brain with a chemical agent capable of staining the preselected region of the brain to a color visibly contrasting with non-stained portions of the brain and of passing through the blood-brain barrier to the preselected region of the brain: 1) Passive transport: (a) prodrug, (b) Modification of mapping agent to mimic molecules that readily cross the BBB (e.g., amino acid, glucose, etc.); 2) Active transport; 3) Receptor-mediated transport (e.g., antibody mediated); 4) Blood brain barrier (BBB) manipulation; 5) Emulsification of agent (such as carotene, organic dye, etc.) to stain capillary endothelium; 6) Embolization of brain capillaries; 7) Grafted-nanoparticle systems for brain delivery of mapping agent.
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Excerpt(s): The present invention relates to a novel brain mapping system especially adapted for the enhancement of Craniotomy Guidance. Brain mapping is the attempt to specify in as much detail as possible the localization of function in the human brain (Savoy R L: History and future directions of human brain mapping and functional neuroimaging. Acta sychologica 07:9-42, 2001). A variety of brain-mapping techniques exist, ranging from the historic lesion studies to functional magnetic resonance imaging (fMRI) (Llins, R R: Mapping Brain Terrain. Neurobiology of Disease 7 499-500, 2000; Orison W W, Lewine J P, Sanders J A, Hartshorne M F: Functional Brain Imaging. St. Louis: Mosby, 1995. The oldest and simplest form of brain mapping is lesion studies (Corkin 5, Amaral D G, Johnson K A, Hyman B T: H.M's medial temporal lobe lesion: findings from MRI. Journal of Neuroscience 17:3964-3979, 1997; Kolb B, Whishaw I Q: Fundamentals of human neuropsychology (.sub.4th ed.). New York: Freeman, 1996; Tootell R B H, Iale A M, Sereno M I, Malach R: New images from human visual cortex. Trends in Neuroscience 19(11):481-489, 1996). The anatomic basis of neurological function has been inferred from the correlation of clinical findings with anatomical studies, whether by autopsy or radiology, in patients with known discrete brain lesions. This is the method by which the knowledge of localization was long advanced, but with marked limitations. Lesions are not controlled and often involve multiple areas with multiple functions. Gray matter subserving one function often overlies white matter carrying fibers subserving an unrelated function. Nevertheless, our basic understanding of neuroanatomy is largely based on these historic studies, and forms the basis for the crude form of preoperative brain mapping currently employed for many neurosurgical procedures the expectation of the neurosurgeon that a given resection has a certain probability of producing a given neurologic deficit. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of treating cancer using kinase inhibitors Inventor(s): Agus, David B.; (Beverly Hills, CA) Correspondence: Richard H. Zaitlen, ESQ.; Pillsbury Winthrop Llp; Suite 2800; 725 South Figueroa Street; Los Angeles; CA; 90017-5406; US Patent Application Number: 20040001833 Date filed: June 4, 2003 Abstract: Described herein are methods for treating cancer and other disease conditions in individuals who have either developed a resistance to conventional tyrosine kinase inhibitor (TKI) therapy or who are non-responsive ab initio to conventional TKI therapy. In various embodiments, the methods include administering to a patient a resistancesurmounting quantity of a TKI on a weekly or semi-weekly basis. Alternate embodiments of the present invention include a diagnostic method for assessing an individual's probability of being resistant to TKI therapy, based upon an expression level of epithelial membrane protein-1 (EMP-1); one of the genes believed to be responsible for TKI resistance. The methods of the present invention may be particularly useful in the treatment of lung, breast, prostate, ovarian, brain and colon cancers. The methods of the present invention may be effective in blocking the HER-2 kinase domain either in addition to or in lieu of blocking the EGFR kinase domain. Excerpt(s): This application claims the benefit of priority under 35 U.S.C.sctn. 119 of provisional U.S. application serial No. 60/386,622, filed Jun. 5, 2002, the contents of which are hereby incorporated by reference. Embodiments of the present invention are directed to methods for treating and preventing disease conditions, such as cancer,
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particularly in those individuals who have developed a resistance or who are not responsive ab initio to tyrosine kinase inhibitor (TKI) therapy. It is believed that cancer in humans is linked to the activity of non-viral, endogenous oncogenes, and that a substantial portion of these oncogenes code for protein tyrosine kinases. Ligandmediated receptor tyrosine kinase inhibitors (RTKs), in particular, form a significant subgroup of these oncogenes, and are believed to function as "master switches" for a coordinated cellular communication network that regulates the normal proliferation of eukaryotic cells. Approximately sixty such RTKs have been identified to date; their respective cell signaling pathways having been studied in detail. Moreover, misregulation of RTK signaling pathways has been observed in various types of human cancer, suggesting that signal transduction therapy may be a useful therapeutic modality for the treatment of cancer. Other disease conditions in which RTKs play a pivotal role might also benefit from such therapy. One noteworthy success in this area is imatinib mesylate (available from Novartis Pharmaceuticals Corporation under the tradename GLEEVEC; hereinafter "GLEEVEC"); it is effective in the treatment of Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) by inhibiting translocation of the fusion gene responsible for BCR-ABL tyrosine kinase. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for modulating the axonal outgrowth of central nervous system neurons Inventor(s): Benowitz, Larry I.; (Newton Centre, MA) Correspondence: Nixon Peabody Llp; 101 Federal ST; Boston; MA; 02110; US Patent Application Number: 20040014710 Date filed: March 10, 2003 Abstract: Methods for modulating the axonal outgrowth of central nervous system neurons are provided. Methods for stimulating the axonal outgrowth of central nervous system neurons following an injury (e.g., stroke, Traumatic Brain Injury, cerebral aneurism, spinal cord injury and the like) and methods for inhibiting the axonal outgrowth of central nervous system neurons are also provided. Finally, a packed formulation comprising a pharmaceutical composition comprising an inosine nucleoside and a pharmaceutically acceptable carrier packed with instructions for use of the pharmaceutical composition for treatment of a central nervous system disorder is provided. Excerpt(s): Past early childhood, injury to the central nervous system (CNS) results in functional impairments that are largely irreversible. Within the brain or spinal cord, damage resulting from stroke, trauma, or other causes can result in life-long losses in cognitive, sensory and motor functions, and even maintenance of vital functions. Nerve cells that are lost are not replaced, and those that are spared are generally unable to regrow severed connections, although a limited amount of local synaptic reorganization can occur close to the site of injury. Functions that are lost are currently untreatable. Regenerative failure in the CNS has been attributed to a number of factors, which include the presence of inhibitory molecules on the surface of glial cells that suppress axonal growth; absence of appropriate substrate molecules such as laminin to foster growth and an absence of the appropriate trophic factors needed to activate programs of gene expression required for cell survival and differentiation. By contrast, within the peripheral nervous system (PNS), injured nerve fibers can regrow over long distances, with eventual excellent recovery of function. Within the past 15 years, neuroscientists have come to realize that this is not a consequence of intrinsic differences between the
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nerve cells of the peripheral and central nervous system; remarkably, neurons of the CNS will extend their axons over great distances if given the opportunity to grow through a grafted segment of PNS (e.g., sciatic nerve). Therefore, neurons of the CNS retain a capacity to grow if given the right signals from the extracellular environment. Factors which contribute to the differing growth potentials of the CNS and PNS include partially characterized, growth-inhibiting molecules on the surface of the oligodendrocytes that surround nerve fibers in the CNS, but which are less abundant in the comparable cell population of the PNS (Schwann cells); molecules of the basal lamina and other surfaces that foster growth in the PNS but which are absent in the CNS (e.g., laminin); and trophic factors, soluble polypeptides which activate programs of gene expression that underlie cell survival and differentiation. Although such trophic factors are regarded as essential for maintaining the viability and differentiation of nerve cells, the particular ones that are responsible for inducing axonal regeneration in the CNS remain uncertain. As a result, to date, effective treatments for CNS injuries have not been developed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for the prevention and/or the treatment of neurological disorders Inventor(s): Neuville, Pascal; (La Wantzenau, FR) Correspondence: Burns Doane Swecker & Mathis L L P; Post Office Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20040014648 Date filed: May 16, 2003 Excerpt(s): The present invention relates to the use of substrates of an UDPglucuronosyltransferase (UGT) and salts thereof, for the prevention and/or the treatment of neurological disorders. In preferred embodiment, the present invention relates to the use of substrates of at least an UDP-glucuronosyltransferase (UGT) expressed in brain and salts thereof, for the prevention and/or the treatment of neurological disorders, It further relates to the use of said substrates, and salts thereof, for preventing and/or treating glutamate cytotoxicity, and more specifically of glutamate induced neurological disorders. Additionally, it concerns the use of said substrates, and salts thereof, for making drugs exerting an inhibitory effect on the release of glutamate. A large number of studies have established that cellular communication using excitatory amino acids can be transformed into a mechanism of cell destruction. Glutamate, for example, is the main excitatory neurotransmitter in the nervous system, especially brain and spinal cord, of mammals wherein it is working at a variety of excitatory synapses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Peptides which enhance transport across tissues and methods of identifying and using the same Inventor(s): Alvarez, Vernon L.; (Morrisville, PA), O'Mahony, Daniel Joseph; (Dublin, IE), Seveso, Michela; (Dublin, IE) Correspondence: Caesar, Rivise, Bernstein, Cohen & Pokotilow, LTD.; Attn: Elan; 12th Floor, Seven Penn Center; 1635 Market Street; Philadelphia; PA; 19103-2212; US Patent Application Number: 20040023204 Date filed: March 22, 2002 Abstract: A method of identifying a peptide which permits or facilitates the transport of an active agent through a human or animal tissue. A predetermined amount of phage from a random phage library or a preselected phage library is administered in vivo or in situ to a site in an animal, such as into the gastro-intestinal tract. At a predetermined time, the phage which is transported across a tissue barrier is harvested at a harvesting site, such as in portal or systemic blood or brain tissue, which is separated from the site of administration by the tissue barrier to select transported phage. This transported phage is amplified in a host. This cycle of events is repeated (using the transported phage produced in the most recent cycle) a predetermined number of times to obtain a selected phage library containing phage which can be transported from the site of administration to the harvesting site. The identity of at least one peptide coded by phage in the selected phage library is determined to identify a peptide which permits or facilitates the transport of an active agent through a human or animal tissue. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 08/46,411, filed Nov. 8, 1996. This invention relates to the identification of peptide sequences which permit or facilitate the transport of drugs, macromolecules, or particles, such as biodegradable nano- and microparticles, through human or animal tissues. In particular, this invention relates to the use of phage display libraries in a screening assay in order to determine the identity of peptides sequences which enhance the delivery of the bacteriophage through tissue, such as epithelial cells lining the lumenal side of the gastro-intestinal tract (GIT). The epithelial cells lining the lumenal side of the GIT are a major barrier to drug delivery following oral administration. However, there are four recognized transport pathways which can be exploited to facilitate drug delivery and transport: the transcellular, paracellular, carrier-mediated and transcytotic transport pathways. The ability of a conventional drug, peptide, protein, macromolecule or nanoor microparticulate system to "interact" with one of these transport pathways may result in increased delivery of that drug or particle from the GIT to the underlying circulation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Porphyron based neuton capture agents for cancer therapy Inventor(s): Jaquinod, L.; (Davis, CA), Shetty, S.J.; (Bornbay, IN), Smith, K.M.; (Baton Rogue, LA), Vicente, M. G. H.; (Baton Rouge, LA) Correspondence: Fulbright And Jaworski L L P; Patent Docketing 29th Floor; 865 South Figueroa Street; Los Angeles; CA; 900172576 Patent Application Number: 20040014737 Date filed: April 2, 2003
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Abstract: The invention describes the synthesis of a panel of novel carbon-carbon linked carboranyl-containng 5,10,15,20-tetraphenylporphyrins bearing 25-44% boron by weight. Preliminary in vitro evaluation of several of these compounds, using both rat and human brain tumor cell lines, shows that these compounds display very low cytotoxicities, are capable of delivering substantial amounts of boron intracellularly, and are retained for long periods of time. Excerpt(s): The field of the invention is cancer therapy. Boron neutron capture therapy (BNCT) is a bimodal modality for cancer treatment consisting on the irradiation of.sup.10B-rich tumors with low-energy (thermal) neutrons, with subsequent production of high linear energy transfer particles,.sup.4He.sup.2+ (alpha-particle) and.sup.7Li.sup.3+, which cause severe damage to tumor cells through ionization processes; see Barth, Soloway, Fairchild et al., infra; Barth, Soloway, Goodman et al., infra. Because the cytotoxic ions produced in the nuclear reaction have a limited distance of travel in tissue (approximately one cell diameter, 5-9.mu.m), the success of this modality for cancer therapy depends on the selective uptake of boron in the tumor cells; see Hawthorne, (1998), infra; Hawthorne, (1993). infra. Malignant brain tumors are responsible for more than 10,000 deaths per year in the United States, and BNCT is specially attractive as the treatment because it potentially targets and destroys malignant cells in the presence of normal cells, thus, preventing undesirable side effects common in other types of treatments. In addition, BNCT has advantages over photoradiation therapy in that neutron beams can penetrate upwards of ten times deeper, to reach deep-seated tumor sites (6-7 cm). In recent years, several research groups have developed a variety of new.sup.10B carriers with improved tumor selectivity over the two boron neutron capture agents currently undergoing clinical trials in the U.S., Europe, and Japan, for the treatment of patients with glioblastomas and melanomas disodium mercapto-closo-dodecaborate (BSH) and L-4-dihydroxyborylphenylalanine (BPA). See Kageji, et al., infra. Pignol, et al., infra; Elowitz, et al., infra. To date, of all the new boron-delivery agents, porphyrins are particularly promising tumor-selective compounds because of their natural tendency to accumulate in neoplastic tissue; see Bonnett, infra. This property of porphyrins provides the basis for their use in another therapeutic method, the photodynamic therapy (PDT) of tumors; see Schnitmaker, et al., infra; Dougherty, et al., infra. PDT relies on the selective uptake of a photosensitizer in tumor tissues, followed by generation of singlet oxygen and other cytotoxic species upon irradiation with red light. Photofrin.RTM., a porphyrin derivative and only FDA-approved PDT drug has been used to treat thousands of patients in Canada, Europe, Japan and U.S. with early and advanced stage cancer of the lung, digestive tract, and genitourinary tract. In addition to necrosis as the result of oxidative damage, it has been recently shown that some porphyrins also induce apoptosis (programmed cell death), either upon irradiation with light (particularly at low light doses), or by accumulation of high drug levels in tissues, in the dark.; see Luo, Chang, et al., infra; Luo, Ke, et al., infra. The ability of porphyrin-PDT to induce apoptosis may also be an important element for the success of both PDT and BNCT modalities for cancer treatment. Photofrin.RTM. presents the disadvantages of being a complex mixture of compounds of variable composition. Thus, active research in the area of development of new and highly efficient PDT photosensitizers is underway. Also, boron-containing porphyrin derivatives that selectively localize in tumor cells have potential PDT applications; see Hill, Kahl, Stylli et al., infra. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Precision brain blood flow assessment remotely in real time using nanotechnology ultrasound Inventor(s): Crutchfield, Kevin E.; (Potomac, MD), Davidson, John B.; (Laytonsville, MD), Fitall, Simon; (Bethesda, MD), Mozayeni, B. Robert; (Rockville, MD) Correspondence: Hogan & Hartson Llp; IP Group, Columbia Square; 555 Thirteenth Street, N.W.; Washington; DC; 20004; US Patent Application Number: 20040002654 Date filed: February 6, 2003 Abstract: The present invention relates generally to systems and methods for assessing blood flow in blood vessels, for assessing vascular health, for conducting clinical trials, for screening therapeutic interventions for adverse effects, and for assessing the effects of risk factors, therapies and substances, including therapeutic substances, on blood vessels, especially cerebral blood vessels, all achieved by measuring various parameters of blood flow in one or more vessels and analyzing the results in a defined matter. The relevant parameters of blood flow include mean flow velocity, systolic acceleration, and pulsatility index. By measuring and analyzing these parameters, one can ascertain the vascular health of a particular vessel, multiple vessels and an individual. Such measurements can also determine whether a substance has an effect, either deleterious or advantageous, on vascular health. In one of many embodiments, the present invention further provides an expert system for achieving the above. Excerpt(s): The present application is a Continuation-in-Part application of U.S. patent application Ser. No. 09/966,368, filed Oct. 1, 2001 and claiming priority from U.S. Provisional Patent Application Serial Nos. 60/236,661, 60/236,662, 60/236,663, 60/236,875, and 60/236,876, each filed Sep. 29, 2000, and from Serial Nos. 60/263,165 and 60/263,221, both filed Jan. 23, 2001. The present application further claims priority under 35 U.S.C.sctn.119(e) to U.S. Provisional Patent Application Serial No. 60/354,227, filed Feb. 6, 2002 and incorporated herein by reference. The present invention relates generally to systems and methods for assessing vascular health and for assessing the effects of treatments, risk factors and substances, including therapeutic substances, on blood vessels, especially cerebral blood vessels, all achieved by measuring various parameters of blood flow in one or more vessels and analyzing the results in a defined matter. In addition, the present invention further pertains to collecting, analyzing, and using the measurement of various parameters of blood flow in one or more vessels to establish protocols for and to monitor clinical trials. Further, the present invention relates to an automated decision support system for interpreting the values of various parameters of blood flow in one or more vessels in assessing the vascular health of an individual. Proper functioning of the vascular system is essential for the health and fitness of living organisms. The vascular system carries essential nutrients and blood gases to all living tissues and removes waste products for excretion. The vasculature is divided into different regions depending on the organ systems served. If vessels feeding a specific organ or group of organs are compromised, the organs and tissues supplied by those vessels are deleteriously affected and may even fail completely. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Treatment of neuropathic pain Inventor(s): Kohlhaas, Kathy L.; (Lake Zurich, IL), Rueter, Lynne E.; (Round Lake Beach, IL) Correspondence: Steven F. Weinstock; Abbott Laboratories; 100 Abbott Park Road; DEPT. 377/ap6a; Abbott Park; IL; 60064-6008; US Patent Application Number: 20040010018 Date filed: May 15, 2003 Abstract: A method for treating a patient suffering from neuropathic pain, comprising administering to a patient in need of such treatment an effective amount of an agonist drug capable of binding to the neuronal nicotinic receptor (NNR) but which does not readily cross the blood-brain barrier. Excerpt(s): This application claims priority to U.S. Provisional Application Serial No. 60/378,039 filed May 15, 2002 and U.S. Provisional Application Serial No. 60/439,687, filed Jan. 13, 2003. The present invention relates to a novel treatment of neuropathic pain. Specifically, the invention relates to a method for treating a patient suffering from neuropathic pain, including allodynia and to the reduction of side effects associated with agonist activation of central neuronal nicotinic receptors. Pain is a sensation and a perception that is comprised of a complex series of mechanisms. In its most simple construction, it is a signal from the firing of nociception, touch and pressure receptors in the periphery that is transmitted to the spinal cord and finally to lower and higher centers of the brain. However, this signal can be modified in a multitude of ways at each level of the pain pathway. (See e.g Millan, M. J. (1999) The Induction of Pain: An Integrative Review, Progress in Neurobiology, 57, 1-164 (Pergamon Press) for an in depth review). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of Epothilones in the treatment of brain diseases associated with proliferative processes Inventor(s): Buchmann, Bernd; (Neuendorf, DE), Hoffmann, Jens; (Muehlenbeck, DE), Klar, Ulrich; (Berlin, DE), Lichtner, Rosemarie; (Berlin, DE), Rotgeri, Andrea; (Berlin, DE), Schwede, Wolfgang; (Berlin, DE), Skuballa, Werner; (Berlin, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20040019088 Date filed: February 28, 2003 Abstract: This invention provides the use of an Epothilone, which shows an average distribution coefficient between plasma and brain of 0.3 to 1.5 in the mouse intravenous bolus injection assay, for the preparation of a medicament for the treatment of a brain disease associated with proliferative processes. Excerpt(s): This application claims the benefit of the filing date of U.S. Provisional Application Serial No. 60/361,062 filed Mar. 1, 2002. The present invention relates to the use of Epothilones in the treatment of brain diseases associated with proliferative processes, especially primary or secondary brain tumors, multiple sclerosis, and Alzheimer's disease. The possibilities of medicamentous treatment of brain diseases are strongly limited by the existence of the so-called blood-brain-barrier (BBB). While the
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BBB serves as a protective mechanism for preventing exogenous substances to enter the brain tissue, unfortunately, it also prevents the entry of drugs administered by a conventional mode (orally, parenterally, etc.) (A. Maelicke, Nachr. Chem Tech. Lab. 1989, 37, 32-34). 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, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “brain” (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. You can also use this procedure to view pending patent applications concerning brain. 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 Overview This chapter provides bibliographic book references relating to brain. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on brain 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” (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: •
Your Brain Is Younger Than You Think: A Guide to Mental Aging Source: Chicago, IL: Nelson-Hall Publishers. 1981. 164 p. Contact: Available from Nelson-Hall Publishers. 111 North Canal Street, Chicago, IL 60606. PRICE: $14.95 (hardcover); $7.95 (paperback). Summary: Mental illness need not be considered incurable when it strikes the elderly. Emotional problems can usually be successfully treated, and even the brain deterioration of senility may some day respond to treatment. Memory loss and confusion do not necessarily indicate a serious breakdown of mental functioning. Memory loss can be alleviated through simple memory devices, and confusion in familiar surroundings can be treated in many cases with simple therapy. The author argues that hardening of the arteries and simple aging do not provide valid explanations for the incidence of senility.
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Alzheimer's Disease: Senile Dementia of Alzheimer's Type. Aging of the Brain Source: Danish Medical Bulletin. 32(Supplement 1): 1-111. February 1985. Contact: Available from Kellogg International Health and Aging Program. School of Social Work, University of Michigan, Office of Agency and Community Relations, 1065 Frieze Building, Ann Arbor, MI 48109-1285. (313) 747-4281. PRICE: $12.00. Summary: The 20 papers contained in this supplement were presented at an international conference held in Copenhagen, Denmark, under the auspices of the World Health Organization, and at a series of international symposia held in the United States. Presentations included the following topics: Unanswered questions about the mechanisms and etiology of Alzheimer's disease; the structural development of the disease; neuropathological and neurochemical correlates; neurotransmitters in the brains of patients; determinations of cerebral glucose utilization; differential diagnosis; psychological evaluation; institutionalization; epidemiological aspects; dementia and the family; and some strategies for tackling the problems of dementia in the next decade.
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Directory of California Respite Resources: For Caregivers of Brain-Impaired Adults Source: San Francisco, CA: Family Caregiver Alliance. 1994. 123 p. Contact: Family Caregiver Alliance. 425 Bush Street, Suite 500, San Francisco, CA 94108. (415) 434-3388. PRICE: $15.00. Summary: This annually-updated directory lists over 1,275 respite resources in California for caregivers of adults with brain injuries (e.g., Alzheimer's disease, Parkinson's disease, stroke, traumatic brain injury). It is organized by country (58 counties) and includes the following service categories: agencies/organizations that list attendants who provide respite to caregivers, center-based adult day care program/centers, agencies and people who provide home care (includes home health agencies and hospices), facilities that provide short-term, overnight respite to caregivers, and agencies/organizations that provide subsidized respite and volunteer respite programs (includes California Caregiver Resource Centers, and church-based volunteer programs). Each entry provides the organization's address, telephone numbers, and principal contact. It also briefly describes the service areas of each of the 11 California Caregiver Resource Centers, which are responsible for gathering information about the respite resources in their service region.
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Brain Facts: A Primer on the Brain and Nervous System Source: Washington, DC: Society for Neuroscience. 1993. 52 p. Contact: Society for Neuroscience. 11 Dupont Circle, NW, Suite 500, Washington, DC 20036. (202) 462-6688. PRICE: $6.00. Summary: This book briefly describes what is known about the brain and nervous system, brain disorders, and avenues of research that promise new therapies for many of the most devastating neurological and psychiatric diseases. Topics include brain development; what a neuron is and its function; and the brain's involvement in sensation and perception, learning and memory, movement, sleep, stress, and aging. This book examines advances in research on Parkinson's disease, pain, epilepsy, major depression, and manic-depressive illness in addition to neurological disorders such as addiction, Alzheimer's disease, Down syndrome, Gilles de la Tourette's syndrome, brain tumors, and multiple sclerosis. It explores recent advances in diagnostic methods such as positron emission tomography, magnetic resonance imaging, magnetic source
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imaging, and gene diagnosis; and discusses potential therapies using drugs and transplants. •
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 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.
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What to Do About Your Brain-Injured Child or Your Brain-Damaged, Mentally Retarded, Mentally Deficient, Cerebral-Palsied, Spastic, Flaccid, Rigid, Epileptic, Autistic, Athetoid, Hyperactive, Down's Source: Garden City, NY: Avery Publishing Group. 1994. 316 p. Contact: Available from Avery Publishing Group. 120 Old Broadway, Garden City, NY 11040. (800) 548-5757 or (516) 741-2155. Fax (516) 742-1892. PRICE: $11.95 plus shipping and handling. ISBN: 0895295989. Summary: This book describes the philosophies and treatment approaches of The Institutes for the Achievement of Human Potential (Philadelphia, PA), founded by Glenn Doman. The book describes the Institutes' work with brain-injured children and focuses on why old theories and techniques fail with this population. The author first tells the story of the Institutes worldwide research, setbacks and breakthroughs, and efforts to refine the treatment of brain injury. The author describes the tools used to measure and improve visual, auditory, tactile, mobility, language, and manual development. The author then describes the program with which parents are able to treat their own children at home in a familiar and loving environment. Included throughout the book are case histories, drawings, charts, and diagrams. A subject index concludes the book.
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A good start in life: Understanding your child's brain and behavior Source: Washington, DC: Joseph Henry Press. 2002. 283 pp. Contact: Available from National Academies Press, 2101 Constitution Avenue, N.W., Lockbox 285, Washington, DC 20002. Telephone: (202) 334-3313 or (888) 624-8422 / fax: (202) 334-2451 / e-mail:
[email protected] / Web site: http://www.nap.edu. $22.95, plus shipping and handling. Summary: This book discusses child brain and behavior development during pregnancy and the first six years. It is divided into four parts covering life in the womb and birth;
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the first year; the second year; and years three to six. Topics include brain development in the womb; birth; exploring; comfort and communications; regions of the brain; motor, language, play, and daily life milestones; discovery; toddlers and temperament; gaining competence; living together; and paths to personality. The book also provides ten guideposts for parents, a glossary, references, and an index. •
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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Keep Your Brain Young: The Complete Guide to Physical and Emotional Health and Longevity Source: New York, NY: John Wiley and Sons, Inc. 2002. 296 p. Contact: Available from John Wiley and Sons, Inc. 111 River Street, Hoboken, NJ 07030. (201) 748-6000 or FAX: (201) 748-6088. E-mail: www.wiley.com/cda/contact_us/. Website: www.wiley.com. PRICE: $24.95 for paperback, ISBN: 0471407925; PRICE: $24.95 for E-book, ISBN: 0471271101. Summary: This book explains methods which may keep your brain working at the highest possible level for the longest possible time. It is based on current research findings and supplemented with case examples from the authors' patient files. It describes the normal changes that occur in the aging brain and shows how to minimize them while enhancing mental and physical functioning. It discusses the steps a person can take that may reduce the risk for serious diseases such as Alzheimer's and Parkinsons's, and explains how to recognize the symptoms of these diseases, should they occur. It also discusses the brain-body link for other diseases, including heart disease and cancer. It highlights the progress being made in the treatment of brain disorders and explains the latest techniques for maintaining memory, managing stress, and coping with sleep disorders. In addition, it explains which foods provide the best nutrition for the brain and protect it from illness, how alcohol affects the brain, and how to recognize and deal with the symptoms of depression. It includes a list of organizations, books, and websites for further information.
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What's going on in there?: How the brain and mind develop in the first five years of life Source: New York: Bantam Books, Random House. 1999. 533 pp.
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Contact: Available from Random House, Bantam Books, 1540 Broadway, New York, NY 10036 / Web site: http://www.randomhouse.com. $26.95. Summary: This book explores neural and psychological development from conception to age five. It covers topics such as critical prenatal influences, infant stimulation, sex linked developmental differences, and the nature nurture controversy. The author devotes a chapter each to the development of touch, balance and motion, smell, taste, vision, hearing, motor skills, social and emotional growth, and the emergence of memory. The final chapter is suggestions for raising a smarter child. •
Psychiatric Consequences of Brain Disease in the Elderly: A Focus on Management Source: New York, NY: Plenum Press. 1989. 211 p. Contact: Available from Plenum Press. 233 Spring Street, New York, NY 10013. (212) 620-8000 or (800) 221-9369. PRICE: $65.00. ISBN: 0306432161. Summary: This book for psychiatrists, neurologists, geriatricians, and related health professionals was developed from a 1987 international symposium on brain disease in the elderly. The book discusses specific approaches to the management of neuropsychiatric disorders in the elderly. Nine chapters prepared by experts in their respective fields cover the nature of neuropsychiatric syndromes in the elderly and their pharmacological management; studies of neuropsychiatric disorders; psychodynamic perspectives in the clinical approach to brain disease in the elderly; psychotherapy and the cognitively impaired elderly; guidelines for helping the family of such patients; the utility of combined neuropsychological and behavior approaches in the management of disruptive behaviors in the cognitively impaired elderly; issues related to long-term care settings; and a practical integrated approach for psychiatric care of the elderly. Information about Alzheimer's disease includes the presentation of a case study, discussions of the cause of dementia in Alzheimer's disease, a diagnostic scoring system for Alzheimer's disease, the involvement of the frontal convexity region, neurochemistry in Alzheimer's disease, neuropathological comparison to Parkinson's disease, personality changes in Alzheimer's disease, the public health issues related to Alzheimer's disease, and the theoretical relationship of Alzheimer's disease to the normal aging process.
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Mild Traumatic Brain Injury: A Therapy and Resource Manual Source: San Diego, CA: Singular Publishing Group, Inc. 1998. 260 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) 238-6789. E-mail:
[email protected]. Website: www.singpub.com. PRICE: $49.95 plus shipping and handling. ISBN: 1565938275. Summary: This book is a therapy and reference manual created in response to the unique needs of adolescents and adults who have sustained mild to moderate traumatic brain injuries (MTBI). The authors focus on providing practical suggestions for developing individualized therapy tasks to promote a client's successful return to the demands of the home, school, or work environment. Nine chapters cover the diversified roles of the speech language pathologist, the assessment of MTBI, treatment options (including establishing a positive therapeutic relationship), treating complex attention impairments, treating functional and prospective memory impairments, treating word retrieval and thought formulation impairments, treating information processing impairments (auditory and visual), treating executive functioning impairments, and
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therapy documentation, transition, and discharge. Each chapter includes therapy tasks, home practice tasks, and suggestions for families (including patient and family handouts). The text concludes with a reference list and subject index. 26 references. •
Pediatric Traumatic Brain Injury: Proactive Intervention Source: San Diego, CA: Singular Publishing Group, Inc. 1994. 281 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) 238-6789. E-mail:
[email protected]. Website: www.singpub.com. PRICE: $42.50 plus shipping and handling. ISBN: 1565931688. Summary: This book is designed for professionals from a variety of disciplines who are challenged daily by children and adolescents with traumatic brain injury (TBI). The authors explain their philosophy for planning and implementing programming for this group of youngsters. The book is divided into four major parts: Part I provides an overview of TBI in the pediatric population; Part II describes how to use problemsolving techniques to conduct functional assessments; Part III suggests treatment approaches based on a proactive, problem-solving approach; and, using a case study, Part IV illustrates this approach to intervention. Each chapter begins with an introduction and list of objectives for the reader and ends with several summary guidelines and a reference list. A brief subject index concludes the volume.
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Handbook of the Aging Brain Source: San Diego, CA: Academic Press. 1998. 263 p. Contact: Available from Academic Press. 525 B Street, Suite 1900, San Diego, CA 921014495. (800) 321-5068, (619) 231-0926; FAX: (800) 874- 6418. Internet: http://www.apnet.com. PRICE: $79.95. ISBN: 0127346104. Summary: This book presents 16 papers highlighting recent research findings on the aging brain. The papers include: Normal and Abnormal Memory: Aging and Alzheimer's Disease (AD); Stress, Glucocorticoids, and Hippocampal Aging in Rat and Human; Spatial Cognition and Functional Alterations of Aged Rat Hippocampus; Identification of Molecular and Cellular Mechanisms of Learning and Memory: The Impact of Gene Targeting; Normal Aging and AD; Transgenic Mouse Models with Neurofilament-induced Pathologies; Transgenic Models of Amyotrophic Lateral Sclerosis and AD; Toward a Genetic Analysis of Unusually Successful Neural Aging; the Role of the Presenilins in AD; Mechanisms of Neuron Death in Neurodegenerative Disease of the Elderly: Role of the Lewy Body; Microtubule-associated Protein Tau: Biochemical Modifications, Degradation, and AD; A Novel Gene in the Armadillo Family Interacts with Presenilin 1; Putative Links between Some of the Key Pathological Features of the Alzheimer's Brain; Unraveling the Controversy of Human Prion Protein Diseases; Translational Control, Apoptosis, and the Aging Brain; and Astrocyte Senescence and the Pathogenesis of Parkinson's Disease. Each chapter contains references.
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Coping with Mild Traumatic Brain Injury Source: Garden City Park, NY: Avery Publishing Group, Inc. 1998. 352 p. Contact: Available from Avery Publishing Group, Inc. 120 Old Broadway, Garden City Park, NY 11040. (800) 548-5757. PRICE: $14.95 (retail price); bulk rates available. ISBN: 0895297914.
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Summary: This book presents a guide to coping with mild traumatic brain injury (MTBI), a problem resulting from car accidents, falls, sports injuries, work-related accidents, and physical assault. The authors note that MTBI is commonly misdiagnosed because the symptoms are unpredictable and can be mistaken for those of many other conditions. The authors first review how the brain works and how it can be injured, the procedures used to diagnose brain injury, and the different treatments available. They then examine the most common physical, mental, and psychological symptoms of brain injury, explaining why each occurs and what can be done about it, and offering practical suggestions for coping with the problem. Also covered are financial, insurance, and family issues; the rehabilitation process; and eventual outcomes. Most of the chapters deal with one particular aftereffect of MTBI and provide a real-life story, an explanation of why the symptom or problem occurs, information about treatment, and practical suggestions for coping with the problem. Chapters cover specific problems including fatigue, headaches, dizziness, problems with sexuality, vision problems, hearing problems, sensory and metabolic disturbances, muscular and motor problems, and seizures. Other problems relate to attention and concentration, memory, reasoning and understanding, speech and language, academic performance, moods and behaviors, psychiatric disorders, and grieving. The book concludes with an extensive resource section that provides additional guidance and sources of support. •
Memory Cure: How to Protect Your Brain Against Memory Loss and Alzheimer's Disease Source: New York, NY: McGraw-Hill. 2003. 240 p. Contact: Available from McGraw-Hill Companies, P.O. Box 182604, Columbus, OH 43272. (877) 833-5524; FAX: (614) 759-3759. E-mail:
[email protected]. Website: www.books.mcgraw-hill.com. PRICE: $21.95. ISBN: 0071409246. Summary: This book presents a plan for improving memory, preventing memory loss, and protecting the brain against Alzheimer's disease (AD). Part I explains how memory works, what happens in the aging brain, the difference between normal forgetfulness and AD, what goes wrong in the AD brain, and other possible causes of memory loss. Part II presents a 10-step plan for protecting the brain from AD and memory loss and reviews new medications for the prevention and treatment of AD. Part III explains how AD is diagnosed and summarizes what is known about heredity and AD. The book also provides tips for enhancing memory and a comprehensive resource section that includes information about organizations, government agencies, professional associations, clinical trials, and Alzheimer's Disease Research Centers.
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Cognitive-Communicative Abilities Following Brain Injury: A Functional Approach Source: San Diego, CA: Singular Publishing Group, Inc. 1994. 303 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) 238-6789. E-mail:
[email protected]. Website: www.singpub.com. PRICE: $45.00 plus shipping and handling. ISBN: 1565931025. Summary: This book presents a systematic approach for addressing the cognitivecommunicative needs of individuals with traumatic brain injury, at the postacute stage of rehabilitation. The author emphasizes the communication aspect of cognitivecommunicative functioning. Five chapters discuss developing a functional perspective; a model for understanding social communication following brain injury; functional approaches to the assessment of cognitive-communicative abilities; and rebuilding
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cognitive-communicative competence and community integration. Numerous appendices provide materials with which to implement the communication model. 473 references. •
Screening for Brain Impairment: A Manual for Mental Health Practice. 2nd Ed Source: New York, NY: Springer Publishing Co. 1994. 242 p. Contact: Available from Springer Publishing Co. 536 Broadway, New York, NY 10012. (212) 431-4370. PRICE: $33.95 plus $3.95 shipping and handling. ISBN: 0826157416. Summary: This book provides general clinicians with an outline for the evaluation of patients with suspected central nervous system dysfunction. This second edition reflects the recent increase in the number of neuropsychological assessment devices. Chapters examine neurological disorders (including Alzheimer's disease and related dementias) and psychiatric disorders with neurological implications; some approaches to neurological assessment; the history of neuropsychology; the mental status examination; and screening tests for perceptual and motor functions, verbal functions, memory functions, higher cognitive functions, and neuropsychological conditions. This book discusses the major causes of dementia common reversible causes of it, and assessments for neuropsychological screening. The batteries described are effective in assisting the clinician in differential diagnosis. These batteries include the Wysocki and Sweet Screening Battery, the Wechsler Adult Intelligence Scale, the Barry Rehabilitation Inpatient Screening of Cognition, and the Mini-Inventory of Right Brain Injury. The book concludes with a glossary of terms. 376 references.
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Rethinking the brain: New insights into early development Source: New York, NY: Families and Work Institute. 1997. 92 pp., exec. summ. (32 pp.). Contact: Available from Publications Department, Families and Work Institute, 330 Seventh Avenue, Fourteenth Floor, New York, NY 10001. Telephone: (212) 465-2044 / fax: (212) 465-8637 / Web site: http://www.familiesandwork.org. Summary: This book was inspired by the conference, Brain Development in Young Children: New Frontiers for Research, Policy and Practice held June 13-14, 1996 at the University of Chicago. It focused on recent developments in neuroscience and considered the significance of these findings in the development of public policies to assure the healthy development of children and to enhance their ability to learn. The conference was held in conjunction with the I Am Your Child campaign. The book summarizes the main findings of the conference, considers why major breakthroughs are being made now, examines the lessons learned, and discusses their implications. The book includes a glossary, two appendices listing the conference participants and giving examples of early intervention programs, and a bibliography.
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Pediatric Brain Injury: A Practical Resource Source: San Antonio, TX: Communication Skill Builders, Inc. 1993. 192 p. Contact: Available from Communication Skill Builders. Psychological Corporation, Order Service Center, P.O. Box 839954, San Antonio, TX 78283-3954. Voice (800) 2118378; TTY (800) 723-1318; Fax (800) 232-1223. PRICE: $52.00 plus shipping and handling. ISBN: 0884506436. Summary: This book, intended for speech-language pathologists, parents, teachers, and students, presents information on treatment of children who experience brain injury
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after a history of normal development. The authors discuss the nature and incidence of brain injury in children, the philosophy of therapy, suggestions for working with parents and family members, and current research on brain injury in children. Factors in the prevention of injury to children are also discussed. Specific topics include closed head injury, open head injury, anoxia, infection, the structure of the brain, diagnostic tests used to confirm or classify brain injuries, the neuropathology of brain injury in children, the implications of normal development stages in recovery, coma, the multidisciplinary care team involved in treating patients with brain injury, the family's role, philosophies of therapy, the functionally comatose child, the structure-dependent child, the concrete processor, issues of feeding, the continuum of care, and caring for the caregivers. For each of classification of brain injury, the authors discuss symptoms and specific therapeutic recommendations. The book concludes with a bibliography and appendices on levels of consciousness, suggested tests and assessment tools, and suggested language and cognitive activities. 73 references. (AA-M). •
Aging of the Brain and Alzheimer's Disease Source: Amsterdam, The Netherlands: Elsevier Science Publishers B.V. (Biomedical Division). 1986. 525 p. Contact: Available from Elsevier Science Publishing Company. 52 Vanderbilt Avenue, New York, NY 10017. (212) 633-3651. PRICE: $240.00. ISBN: 0444807934. Summary: This book, which contains the proceedings of the 14th International Summer School of Brain Research held in August 1985 in Amsterdam, presents topics relevant to neurobiologists as well as medical practitioners such as psychologists, neurologists, psychiatrists, and geriatrists in the field of Alzheimer's disease. The primary areas of discussion include clinical diagnosis of dementias; neurochemical status of healthy individuals, of the elderly, and of individuals who have multi-infarct dementia or Alzheimer's, Huntington's, or Parkinson's disease; the possible genetic/molecular, biochemical, and environmental causes of dementia including Alzheimer's disease; and therapeutic strategies such as diet and manipulation of dopaminergic and cholinergic systems to treat cognitive deficits in old age. The application of experimental techniques such as immunocytochemistry, deoxyglucose, mRNA, and event-related potentials is discussed in terms of gaining insight into the aging or disease process of the brain under various conditions. Data are related to functional and morphological studies, human trials, and animal experiments where possible.
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Communication Problems After a Brain Injury or Stroke Source: Washington, DC: American Association of Retired Persons (AARP). 1994. 12 p. Contact: Available from Pritchett and Hull Associates, Inc. 3440 Oakcliff Road, N.E., Suite 110, Atlanta, GA 30340-3079. (800) 241-4925. PRICE: $3.20 for health professionals; $6.25 retail; plus shipping and handling. ISBN: 0939838443. Summary: This booklet is written to help patients and their families and caregivers understand common communication problems that can occur after a brain injury or stroke. Topics include communication and the brain, what happens to the brain during a stroke, the symptoms of communication disorders, using gestures as a basic way to communicate, the role of the speech language pathologist or therapist, aphasia, dysarthria, apraxia, cognitive problems, writing, understanding speech, memory problems, and getting respite. For each of the common communication problems, the authors provide communication strategies to address the disorder. The booklet is illustrated with cartoon-like line drawings depicting a variety of ethnic groups.
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Traumatic Brain Injury in Children and Adolescents: A Sourcebook for Teachers and Other School Personnel, Second Edition Source: Austin, TX: PRO-ED, Inc. 1999. 149 pp. ISBN: 0-89079-805-2. Contact: Available from PRO-ED, Inc. 8700 Shoal Creek Boulevard, Austin, TX 787576897. (800) 897-3202; Fax (800) 397-7633. Web site: http://www.proedinc.com. PRICE: $30.00 plus shipping and handling. Summary: This guide provides new and updated information for all educators who are serving students with traumatic brain injury (TBI.) The text is easy to read and offers an overview of the entire spectrum of issues related to TBI. In addition to describing the short-and long-term causes and consequences of TBI, this sourcebook presents techniques and procedures to successfully return the child to school following an injury. Additionally, this sourcebook provides practical suggestions that will help teachers develop appropriate educational programs for students in the years following TBI. Annotated bibliography, glossary, references, and index included.
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HIV, AIDS, and the Brain Contact: Raven Press, 1185 Ave of the Americas, New York, NY, 10036, (212) 930-9500. Summary: This monograph reviews findings on the neurological and psychiatric complications of HIV type 1 (HIV-1) infection and AIDS. It focuses chiefly on the pathogenesis and clinical aspects of a primary neurological disorder -- known variously as AIDS dementia complex (ADC), HIV cognitive-motor complex, HIV dementia, and, in children, HIV encephalopathy -- which is caused by HIV-1 itself rather than an opportunistic infection. The studies presented shed light on the interactions of HIV-1 with the brain, and on the pathogenesis of viral and immunological diseases of the central nervous system. Coverage begins with background information on the principal pathogenic forces involved in causing brain dysfunction in ADC; i.e., HIV-1 neurotropism, immune system interactions with viruses, and cytokine circuits in the brain. A major portion of the book examines the neuropathology and pathogenesis of ADC and identifies targets for novel therapeutic strategies. This section includes studies on the role of macrophages and microglia in HIV-related neuropathology; the changes observed in HIV encephalitis; the relationship of cytokine expression to ADC pathogenesis; and the role of amino acid excitotoxicity in mediating neuronal injury. Two chapters highlight relevant experimental findings on neuropathology and viral neurotropism in simian immunodeficiency virus infection, an animal model of HIV-1 infection. Also included are extensive discussions of clinical aspects of HIV-related neurological and psychiatric disorders. Psychiatrists review their experience with depression and other psychiatric disorders in HIV-infected patients and offer guidelines for evaluation and treatment. Other contributors examine the epidemiology, risk factors, and natural history of ADC, and describe current methods for evaluating ADC in adults. Close attention is also given to the pathogenesis, clinical features, diagnosis, and management of HIV encephalopathy in infants and children.
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Children with Traumatic Brain Injury: A Parent's Guide Source: Bethesda, MD. Woodbine House Special Needs Collection. Contact: Available from Woodbine House. 6510 Bells Mill Rd., Bethesda, MD 20817. 301897-3570; 800-843-7323. Web site: www.woodbinehouse.com. PRICE: $17.95 plus shipping and handling. ISBN: 0-933149-99-9 (paperback). 482pp.
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Summary: This reference book provides parents of children with traumatic brain injury (TBI) with support, information, and coping skills to help with their child's recovery process. Written by a team of professionals and experts, the guide covers diagnosis, medical and rehabilitation issues, cognitive and behavioral effects, emotional adjustment, education, and prevention. Includes 40 photographs, a glossary, and reading and resource lists. •
Aging and the Brain Source: New York, NY: Raven Press. 1988. 314 p. Contact: Available from Raven Press. 1185 Avenue of the Americas, New York, NY 10036. (212) 930-9541 or (212) 930-9500. PRICE: $85.00. ISBN: 0881673293 (Order Code 1795). Summary: This reference text for gerontologists, geriatricians, clinical psychologists, neuropathologists, and neurologists describes the current understanding and research findings concerning the underlying causes and diagnosis of Alzheimer's disease (AD) and related disorders. The 16 papers comprising the text were prepared by neurologists, pathologists, and other health professionals. Topics addressed include: the genetics of aging and disease models; advances in the diagnosis of dementia; functional differences in memory characteristics between AD and Huntington's disease; cerebral imaging and function in dementias; morphometric and neurotransmitter aspects in normal aging and in AD; the role of neurotoxins; the protein chemistry of neurofibrillary tangles and amyloid plaques in AD; the possible role of amyloidogenic A4 protein in the pathogenesis of AD; prion diseases and brain dysfunction; the role of neuronotrophic factors in the adult central nervous system; and cholinergic trophic factors in AD. Literature citations are appended to each paper, and numerous illustrations and data are presented throughout 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: When following the link below, you may discover non-medical books that use the generic term “brain” (or a synonym) in their titles. •
Amazon.com: http://www.amazon.com/exec/obidos/externalsearch?tag=icongroupinterna&keyword=brain&mode=books
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” (or synonyms) into the search box, and select “books only.” From
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there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •
Abnormal postural reflex activity caused by brain lesions. Author: Bobath, Berta.; Year: 2000; London, Heinemann [1965]
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An anatomical analysis of the white matter in the brain stem of the cat. Author: Busch, H. F. M. (Hermanus Franciscus Maria),; Year: 2003; Assen [1961]
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Atlas of the canine brain, by O. S. Adrianov and T. A. Mering. [Translation]ed. by E. F. Domino. Author: Adrianov, O. S. (Oleg Sergeevich); Year: 2003; [Ann Arbor, Mich., c1964] http://www.amazon.com/exec/obidos/ASIN/0124657419/icongroupinterna
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Atlases of the brain [electronic resource] Author: Stensaas, Suzanne S.; Year: 2004; Salt Lake City: Knowledge Weavers, Spencer S. Eccles Health Sciences Library, University of Utah, [2000?]
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Back from the brink: how crises spur doctors to new discoveries about the brain Author: Sylvester, Edward J.; Year: 2002; New York: Dana Press, c2004; ISBN: 0972383042 http://www.amazon.com/exec/obidos/ASIN/0972383042/icongroupinterna
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Brain gender Author: Hines, Melissa.; Year: 2001; New York, N.Y.: Oxford University Press, 2004; ISBN: 0195084101 http://www.amazon.com/exec/obidos/ASIN/0195084101/icongroupinterna
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Brain hypothermia treatment Author: Hayashi, Nariyuki.; Year: 1999; Tokyo; New York: Springer-Verlag, c2004; ISBN: 4431404465 http://www.amazon.com/exec/obidos/ASIN/4431404465/icongroupinterna
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Brain warping Author: Toga, Arthur W.; Year: 2002; San Diego: Academic Press, c1999; ISBN: 0126925356 http://www.amazon.com/exec/obidos/ASIN/0126925356/icongroupinterna
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Deep brain stimulation and epilepsy Author: Lüders, Hans.; Year: 2004; London; New York: Martin Dunitz; Independence, KY: Distributed in the USA by Fullfilment Center, Taylor; Francis, 2004; ISBN: 1841842591 http://www.amazon.com/exec/obidos/ASIN/1841842591/icongroupinterna
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Forensic neuropathology; lesions of the brain and spinal cord of medicolegal importance. Author: Courville, Cyril B. (Cyril Brian),; Year: 2004; Mundelein, Ill., Callaghan [c1964]
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Hyperbaric oxygen therapy for brain injury, cerebral palsy, and stroke: summary. Author: United States. Agency for Healthcare Research and Quality.; Year: 2004; [Rockville, Md.]: U.S. Dept. of Health and Human Services, Public Health Service, Agency for Healthcare Research and Quality, [2003]
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Microcosms of the brain: what sensorimotor systems reveal about the mind Author: Tweed, Douglas.; Year: 1881; Oxford; New York: Oxford University Press, 2003; ISBN: 0198507356
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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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http://www.amazon.com/exec/obidos/ASIN/0198507356/icongroupinterna •
Neoplasms of the reticuloendothelial system of the brain. Author: Burstein, Stephen David,; Year: 2004; [Minneapolis] 1962
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Pediatric brain injury: a practical resource Author: Sellars, Carole Wedel.; Year: 2003; Austin, Tex.: Pro-Ed, c2004; ISBN: 0890799628 http://www.amazon.com/exec/obidos/ASIN/0890799628/icongroupinterna
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Soul made flesh: the discovery of the brain-- and how it changed the world Author: Zimmer, Carl,; Year: 2003; New York: Free Press, c2004; ISBN: 0743230388 http://www.amazon.com/exec/obidos/ASIN/0743230388/icongroupinterna
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The ageing brain: the neurobiology and neuropsychiatry of ageing Author: Sachdev, Perminder.; Year: 1999; Lisse; Exton, PA: Swets; Zeitlinger Publishers, c2003; ISBN: 9026519435 http://www.amazon.com/exec/obidos/ASIN/9026519435/icongroupinterna
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The synaptic organization of the brain Author: Shepherd, Gordon M.,; Year: 2002; New York: Oxford University Press, 2004; ISBN: 0195159551 http://www.amazon.com/exec/obidos/ASIN/0195159551/icongroupinterna
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Traumatic brain injury: rehabilitative treatment and case management Author: Ashley, Mark J.; Year: 2004; Boca Raton: CRC Press, 2003; ISBN: 0849313627 http://www.amazon.com/exec/obidos/ASIN/0849313627/icongroupinterna
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Your brain, master computer. Author: Hyde, Margaret O. (Margaret Oldroyd),; Year: 2003; New York, McGraw-Hill [c1964]
Chapters on Brain In order to find chapters that specifically relate to brain, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and brain 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” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on brain: •
Association of Aluminum and Silicon With Neuropathological Changes in the Ageing Brain Source: in Ulrich, J., ed. Histology and Histopathology of the Aging Brain. Basel, Switzerland: S. Karger AG. 1988. p. 140-155. Contact: Available from S. Karger AG. 26 West Avon Road, Box 529, Farmington, CT 06085. (203) 675-7834. PRICE: $148.00. ISBN: 3805547714. Summary: Aluminum (Al) produces, in susceptible animal species, disruption of shortterm memory, focal neurological deficits, and seizures, and also induces neurofibrillary tangles in several neuronal types which resemble, at the light microscopic level, the neurofibrillary tangles in Alzheimer's disease. This chapter focuses attention on the distribution of Al and silicon revealed using advanced microanalytical techniques (electron and proton microprobe X-ray microanalysis and secondary ion mass spectrometry) in relation to the pathogenesis of neurofibrillary tangles and senile
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plaques. Scanning electron micrographs and X-ray energy spectra are presented and discussed. 75 references. •
Language Disorders in Children Treated for Brain Tumours Source: in Murdoch, B.E. Communication Disorders and Childhood Cancer. London, United Kingdom: Whurr Publishers Ltd. 1999. p. 55-75. Contact: Available from Taylor and Francis, Inc. 7625 Empire Drive, Florence, KY 41042. (800) 634-7064. Fax (800) 248-4724. PRICE: $47.95 plus shipping and handling. ISBN: 1861561156. Summary: As the treatments become more effective, an increasing number of children displaying communication deficits as a consequence of treatment for childhood cancer have begun to appear in the caseloads of speech pathologists and other health professionals. This chapter on language disorders is from a book that offers an overview of the communication impairments that occur in association with the two most common forms of childhood cancer, namely leukemia and brain tumor. The authors discuss a number of factors occurring secondary to the presence and removal of posterior fossa tumors that could conceivably lead to disturbances in language function. The authors review a number of case studies that demonstrate these postoperative complications in language. As yet, no characteristic language pattern has arise that could offer clinicians a starting point for patient management, or alert them to specific areas of language deficit. Rather, the data available to date indicate the presence of variable language abilities within the tumor population thereby necessitating the need for development and implementation of individualized therapy programs. The authors caution that neurological deterioration can occur in these children from months to years after the completion of treatment of brain tumors; postoperative baseline measurements of language abilities are highly recommended. 4 figures. 60 references.
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EEG Brain Mapping in Patients With SDAT and Vascular Dementia: Results and Correlations With MRI, SPECT and TCD Source: in Battistin, L.; Gerstenbrand, F., eds. Aging Brain and Dementia: New Trends in Diagnosis and Therapy. Proceedings of A Symposium held in Padova, Italy, September 22-24, 1988. New York, NY: Alan R. Liss, Inc. 1990. p. 337-348. Contact: Available from Alan R. Liss, Inc. 41 East 11th Street, New York, NY 10003. (212) 741-2515. ISBN: 0471562114. Summary: Besides exact psychometric testing, clinical assessment, and neuroimaging techniques (e.g.: MRI; SPECT; ultrasound), topographic EEG brain mapping is of increasing interest for the study and differential diagnosis of dementia. Using computerized data analysis, the amplitudes and topographic distribution of EEG frequencies are imaged and the averaged values of different patient groups may be compared statistically. In the present study, patients with vascular dementia showed significantly higher amplitudes in the delta and theta bands, while the alpha frequencies and amplitudes were significantly lower in those patients with senile dementia of the Alzheimer's type. These results emphasize the utility of EEG brain mapping in the differential diagnosis of dementia. 16 references.
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Brain Imaging Techniques in Alzheimer's Disease (CT, NMR, SPECT and PET) Source: in Crawford, J.R. and Parker, D.M., eds. Developments in Clinical and Experimental Neuropsychology. New York, NY: Plenum Press. 1989. p. 1-13.
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Contact: This publication may be available from your local medical library. Call for information. ISBN: 0306432447. Summary: Brain imaging techniques described in this chapter allow direct examination of brain structure and function in health and disease states in vivo, as in Alzheimer's disease (AD). AD dementias are, for the most part, age-related conditions; hence, the importance of aging effects on brain structure and function must be taken into account in interpreting changes in patients with dementing conditions. Further, the ultimate classification of dementia must rely on postmortem corroboration of macroscopic and microscopic changes in order to be definitive, and ultimately, pathological criteria should be used to confirm the clinical and imaging findings. 36 references. •
Brain Sampling and Preservation of Specimens From Alzheimer Patients and Controls for Morphology Source: in Courtois, Y., Faucheux, B., Forette, B., Knook, D.L., and Treton, J.A., eds. Modern Trends in Aging Research. London, England: John Libbey and Company, Limited. 1986. p. 413-420. Contact: Available from John Libbey and Company, Limited. 80/84 Bondway, London SW8 1SF, UNITED KINGDOM. (01) 582-5266. ISBN: 086916103X. Summary: Controls for research on Alzheimer's disease (AD) using brain tissue specimens should be matched not only with respect to age, but also for sex, hand preference, laterality, alcohol and medication intakes, seasonal influences, clock time of death, agonal state, postmortem delay, and the mode and time of storage, since each of these factors is known to influence brain morphology. This book chapter shows the advantages of combining immunocytochemistry with morphometry in the brain. It has been shown that cell density, a measure used so far in neuropathology, is a highly insensitive parameter for cell loss. Preference should be given to describing the volume and cell number of the brain structures in order to arrive at an accurate description of the changes that occur in the human brain during aging and dementia. Results obtained with these techniques in AD brains should be checked for regional specificity. Some problems involving disease controls and brain biopsies are discussed. 31 References.
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Pharmacological Aspects of Brain Aging and Dementia Source: in Courtois, Y., et al., eds. Modern Trends in Aging Research: Proceedings of the International INSERM-EURAGE Symposium 'Modern Trends in Aging, Research, Gerontology and Geriatrics' held in Paris, March 1986. London, England: John Libbey and Company. 1986. p. 473-484. Contact: Available from John Libbey and Company. 80/84 Bondway, London SW8 1SF, ENGLAND. (71) 582-5266. ISBN: 086916103X. PRICE: Call for information. Summary: Development of medications capable of treating Alzheimer's disease (AD) and senile dementias has encountered several difficulties: (a) the absence of AD in test animals; (b) the need to resort to experimental models, all of which are open to criticism; and (c) the multiplicity of neurochemical and histopathological disorders, potential targets for such medications. A review of the types of pharmaceuticals presently available is presented, stressing their action on neurotransmission, the free radical mechanism, and cerebral energetic metabolism. 23 references. (AA-M).
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The Educational Needs of Children with Traumatic Brain Injury Source: Children with Traumatic Brain Injury: A Parent's Guide. Bethesda, MD. Woodbine House Special Needs Collection. Contact: Available from Woodbine House. 6510 Bells Mill Rd., Bethesda, MD 20817. 301897-3570; 800-843-7323. Web site: www.woodbinehouse.com. ISBN: 0-933149-99-9. pp 294-349. PRICE: full text available at $17.95 plus shipping and handling. Summary: In this chapter of Children with Traumatic Brain Injury: A Parent's Guide, the authors discuss how the effects of traumatic brain injury (TBI), including psychosocial, emotional, and cognitive functioning impacts a child's ability to succeed in school. The chapter discusses the laws that govern special educational services (IDEA and ADA), private and public assessment and interpretation, parent and educator roles, and assistance for children who may not be eligible under IDEA.
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Morphological Aspects of Rat Brain After Intracerebral Administration of Alzheimer Brain Homogenates Source: in Courtois, Y., et al., eds. Modern Trends in Aging Research: Proceedings of the International INSERM-EURAGE Symposium 'Modern Trends in Aging, Research, Gerontology and Geriatrics' held in Paris, March 1986. London, England: John Libbey and Company. 1986. p. 533-539. Contact: Available from John Libbey and Company. 80/84 Bondway, London SW8 1SF, ENGLAND. (71) 582-5266. ISBN: 086916103X. PRICE: Call for information. Summary: Reaction of rat brain to young, elderly, and senile dementia Alzheimer type (SDAT) brain tissue was studied by two approaches: (a) implantation of human brain fragments in the rat cortex; and (b) intraventricular injection of human brain homogenates. Implantation of SDAT brain tissue induced the appearance of twisted filaments among the normal straight filaments; injection induced cellular necrosis in the host cortex and hippocampus, giving a spongiform appearance to the rat brain. The results suggest that different impairing activities develop during aging and SDAT. The close morphological similarity between the altered rat brain and the human brain supports the assertion that this experimental model could provide a valuable approach to studies of the pathogenesis of SDAT and identification of its inducing factors. 13 references. (AA-M).
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Disease Models of Aging: Brain and Behavior Considerations Source: in Birren, J.E. and Bengtson, V.L., eds. Emergent Theories of Aging. New York, NY: Springer Publishing Company, Inc. 1988. p. 83-89. Contact: This publication may be available from your local medical library. Call for information. ISBN: 0826162509. Summary: The author argues that attention to diseases of the brain and mind in later life may provide new information concerning the influence of the brain on normal aging. Disease models of brain changes altering behavior in later life focus attention on the potential modifiability of behavior with aging, in general. Alzheimer's disease is considered as a paradigm for studying relationships between the brain and behavior. This book chapter gives specific attention to the relationship between behavior and brain plasticity, behavioral disorder and brain changes, and new information for behavioral and psychosocial theories of aging. 11 references.
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Neurochemistry of the Aging Human Brain Source: in Hazzard, W.R., et al., eds. Principles of Geriatric Medicine and Gerontology. 2nd ed. New York, NY: McGraw-Hill, Inc. 1990. p. 905-912. Contact: This publication may be available from your local medical library. Call for information. ISBN: 0070275009. Summary: The authors of this chapter suggest that, while there is some significant agerelated loss of neurons, dendritic arborization, and enzymes and receptors involved in the neurotransmission function of the brain, these losses should not be considered as a general or necessary phenomena of aging. In contrast, loss of function is usually associated with specific areas of the brain. It is emphasized that the reported changes described in the biochemistry and structure of the aging human brain do not necessarily affect the ordinary activities of living or occupational performance, generally, until 75 years of age. Hence, this report outlines and discusses: (1) morphological and biochemical changes during normal aging of the human brain; (2) biochemical aspects of conduction and neurotransmission (considering catecholamines, serotonin, acetylcholine, and neuropeptides); and (3) age-related diseases of the aging brain, including the biochemical abnormalities and characteristics of Parkinson's and Alzheimer's diseases. 50 references.
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AAC and Traumatic Brain Injury: Influence of Cognition on System Design and Use Source: in Beukelman, D.R.; Yorkston, K.M.; Reichle, J., eds. Augmentative and Alternative Communication for Adults with Acquired Neurologic Disorders. Baltimore, MD: Paul H. Brookes Publishing Co. 2000. p. 271-304. Contact: Available from Paul H. Brookes Publishing Co. P.O. Box 10624, Baltimore, MD 21285. (800) 638-3775. Fax (410) 337-8539. Website: www.brookespublishing.com. PRICE: $42.00 plus shipping and handling. ISBN: 1557664730. Summary: The loss of speech in adulthood due to acquired neurologic disorders causes a person to confront enormous life changes. This chapter on the use of augmentative and alternative communication (AAC) strategies for people with traumatic brain injury (TBI) is from a textbook that explores the challenges these adults face during their transition, whether gradual or immediate, from speaking to using AAC. People with a TBI may experience such severe neurogenic communication disorders that they are unable to meet their communication needs through natural speech alone. Many people use AAC systems sometime during the recovery process. In this chapter, the authors review the neuropathology of TBI, discuss the cognitive impairments and behavior issues that are commonly associated with TBI, present a theoretical framework that assists in the rehabilitation of people with TBI using AAC systems, and discuss the influence of cognition on the selection, design, and use of AAC systems. The authors discuss different types of AAC systems, assessing and remediating impairments, functional limitations, factors to consider in the configuration of AAC display, and symbol use and message formulation. The authors conclude by noting that AAC devices are getting smaller and more powerful, and they perform a variety of functions. Speech language pathologists and other rehabilitation professionals are increasingly aware of the benefits of AAC for people with TBI and are incorporating AAC into treatment plans for individuals at all stages of recovery. 2 tables. 70 references.
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Calcium Homeostasis in Brain Aging and Alzheimer's Disease Source: in Bergener, M.; Reisberg, B., eds. Diagnosis and Treatment of Senile Dementia. New York, NY: Springer-Verlag. 1989. p. 276-287. Contact: Available from Springer-Verlag. 175 Fifth Avenue, New York, NY 10010. (212) 460-1500. PRICE: $76.20. ISBN: 0387508007. Summary: There is growing evidence that age-related changes in calcium (Ca) homeostasis occur and may be present in key physiological processes in excitable tissues. This chapter discusses two apparently conflicting lines of evidence concerning age-dependent alterations in Ca homeostasis that have developed in the past several years: (1) that Ca availability or flux into excitable cells may be decreased in aged animals; and (2) that Ca influx may be increased in aged brain cells. Experimental evidence concerning these two views is presented and discussed. A mechanistic hypothesis on the role of altered membrane Ca conductance in Alzheimer's disease also is proposed. Currently the data implicate mechanisms that regulate voltage-dependent Ca influx, but it is not clear whether this is the only or the essential aspect of altered Ca homeostasis. It is concluded that, while there are new and interesting data on the possible age-related alteration of a key Ca regulatory mechanism, much remains to be done in defining the specific putative mechanism that underlies this alteration, and in definitively testing the degree of its contribution to brain aging. 44 references.
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Changes in the Integrated Activity of the Brain With Healthy Aging and Dementia of the Alzheimer Type Source: in Battistin, L.; Gerstenbrand, F., eds. Aging Brain and Dementia: New Trends in Diagnosis and Therapy. Proceedings of a Symposium Held in Padova, Italy, September 22-24, 1988. New York, NY: Alan R. Liss, Inc. 1990. p. 355-369. Contact: Available from Alan R. Liss, Inc. 41 East 11th Street, New York, NY 10003. (800) 225-5945 or (212) 475-7700. PRICE: $140.00. ISBN: 0471562114. Summary: This article summarizes and discusses studies conducted by the authors with optimally healthy subjects to determine the effects of aging in the absence of diseases that are common in the elderly. Initial studies examined 40 healthy adult males (ages 2183), with the finding that there was no significant correlation between age and measures of cerebral metabolism, either global or regional. The percent decrease in global gray matter metabolism over the age range was 2 percent. Regional metabolic values were obtained using positron emission tomography (PET). The authors also compared regional intercorrelations of glucose metabolic rates in a group of 15 young subjects (ages 20-32) and a group of 15 older subjects (ages 64-83). The younger group showed many correlations within and between the frontal and parietal lobes, a smaller number of correlations within and between the temporal and occipital lobes, and few correlations between the frontal-parietal and temporal-occipital domains. The older group had the same general pattern of intercorrelations, but there were significantly fewer correlations between metabolic rates in the frontal and parietal regions and between regions within the parietal areas bilaterally. The reduced number of correlations within the parietal lobes and between the frontal and parietal areas may be associated with some of the neuropsychological deficits that are seen in the elderly. This correlates with lower cognitive test scores obtained in elderly subjects than in younger subjects. Hence, reduction in mental performance in older subjects may be a reflection of the reduced functional coupling between the anterior and posterior brain regions, as revealed by PET analyses. It is concluded that PET is useful in identifying aspects of cerebral metabolism that are affected in aging and dementia. 41 references.
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Aging Brain Source: in Secret Life of the Brain. Washington, DC: Dana Press and Joseph Henry Press. 2001. p. 153-191. Contact: National Academy Press, 500 Fifth Street, Lockbox 285, N.W. Washington, DC 20055. (888) 624-8373; (202) 334- 3313; FAX: (202) 334-2451. Website: www.jhpress.org or www.nap.edu. PRICE: $35.00. ISBN: 0309074355. Summary: This book chapter examines the changes that occur in the aging brain and their effects on memory and thinking. First, it discusses normal memory function and the age-related changes that can affect how we process and remember information. Then, it describes the brain changes that occur in Alzheimer's disease (AD) and the effects these changes have on a person's ability to think and function. It discusses the genetic aspects of AD, the differences between AD and age-related memory changes, the role of beta-amyloid in the development of AD, efforts to develop a vaccine against AD, and lifestyle changes that may help prevent AD. The chapter also discusses stroke and the possibility of using stem cells to replace damaged brain cells and reverse the effects of stroke, AD, and other degenerative brain disorders. 23 color illustrations and photos, index.
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Brain and Age-Related Dementing Diseases Source: in Bayles, K.A.; Kaszniak, A.W. Communication and Cognition in Normal Aging and Dementia. Boston, MA: College-Hill Press. 1987. p. 1-45. Contact: This publication may be available from your local medical library. Call for information. ISBN: 0316083976. Summary: This book chapter is presented as an introduction to the most common causes of irreversible dementia, including Alzheimer's, Parkinson's, and Huntington's diseases and vascular disease resulting in multiple infarctions. This information is intended to provide a foundation for the interpretation of data obtained in behavioral studies of persons with dementia. Sources listed in the bibliography to the chapter provide more comprehensive descriptions of the neuropathology and neurochemistry of specific dementing diseases. Several of the 21 figures presented detailed neuroanatomic structures and brain regions that aid in identifying the important structures affected by the pathologic processes discussed in this chapter. Attention is given to the characteristics of dementia, its causes, epidemiology, costs, clinical presentation, diagnosis, and treatments. 339 references.
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Brain in Aging and Dementia Source: in Bair, F.E., ed. Alzheimer's, Strokes, and 29 Other Neurological Disorders Sourcebook. Detroit, MI: Omnigraphics, Inc. 1993. p. 525-544. Contact: Available from Omnigraphics, Inc. Penobscot Building, Detroit, MI 48226. (313) 961-1340 or (800) 234-1340 or FAX (313) 961-1383. PRICE: $80.00. Summary: This book chapter provides information for patients, families, and nonprofessional caregivers about the brain in aging and dementia. It is part of a reference book on neurological disorders that is based on data from the National Institute of Neurological and Communicative Disorders and Stroke. This chapter describes the normal anatomy, physiology, and function of the brain in youth and the changes that occur with normal aging and in dementia. The chapter also discusses such topics as the behavioral characteristics of dementia and the affected population, types of
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dementias, possible causes of Alzheimer's disease, reversible dementias, and directions in dementia research. A question and answer section is included at the end of the chapter. See AZBK04168 for a chapter on Alzheimer's disease and AZBK04169 for a chapter on the dementias. •
Illnesses of the Older Brain Source: in Giaquinto, S. Aging and the Nervous System. New York, NY: John Wiley and Sons, Ltd. 1988. p. 159-179. Contact: This publication may be available from your local medical library. Call for information. ISBN: 0471918350. Summary: This chapter describes and discusses 13 common diseases of old age. These include: senile dementia of the Alzheimer's disease type; multi-infarct dementia; mixed dementia; Pick's dementia; Binswanger's subcortical encephalopathy; Parkinson's disease; hyperkinesias of various origins; idiopathic hydrocephalus; progressive supranuclear palsy; Creutzfeld-Jakob's disease; depression; neurosis; and psychosis and confusional states. Data on the increased incidence of Alzheimer's disease in the U.S. are included. 63 references.
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Brain Changes in Alzheimer's Disease Source: in Jorm, A.F. Understanding Senile Dementia. Kent, England: Croom Helm Ltd. 1987. p. 21-34. Contact: This publication may be available from your local medical library. Call for information. ISBN: 0412437406 (paperback). Summary: This chapter examines the most common cause of dementia in the elderly, Alzheimer's disease. Particular attention is given to: senile plaques and neurofibrillary tangles; regions of the brain that are most affected (the hippocampus and the cerebral cortex); the role of neurotransmitters in Alzheimer's disease; the utility of brain imaging in the diagnosis of Alzheimer's disease; differences in two types of Alzheimer's disease as a function of age (before about 70, and very late in life, after about 80); and differences between Alzheimer's disease and normal aging. Selected photomicrographs, drawings, and tabular data are included.
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Organic Brain Syndromes Presenting With Global Cognitive Impairment: Delirium and Dementia Source: in Winokur, G. and Clayton, P., eds. Medical Basis of Psychiatry. Philadelphia, PA: W.B. Saunders Company. 1986. p. 3-19. Contact: Available from W.B. Saunders Company. West Washington Square, Philadelphia, PA 19105. (800) 545-2522. PRICE: $69.00. ISBN: 0721613063. Summary: This chapter examines two types of organic brain disturbances in detail: delirium and dementia. Aspects of delirium discussed include its definition, etiology, pathogenesis, epidemiology, pathology, clinical presentation, clinical course, laboratory findings, differential diagnosis, and treatment. Aspects of dementia include its definition, the etiology and pathogenesis of different types of dementia (primary degenerative; multi-infarct; other), the epidemiology of each of the various dementia types, the pathology of each these types, clinical features, clinical course, laboratory findings, differential diagnosis, and treatment. 66 references.
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Assessment of Mild-to-Moderate Traumatic Brain Injury Source: in Green, B.S.; Sevens, K.M.; Wolfe, T.D.W. Mild Traumatic Brain Injury: A Therapy and Resource Manual. San Diego, CA: Singular Publishing Group, Inc. 1998. p. 19-60. 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) 238-6789. E-mail:
[email protected]. Website: www.singpub.com. PRICE: $49.95 plus shipping and handling. ISBN: 1565938275. Summary: This chapter is from a therapy and reference manual created in response to the unique needs of adolescents and adults who have sustained mild to moderate traumatic brain injuries (MTBI). The authors focus on providing practical suggestions for developing individualized therapy tasks to promote a client's successful return to the demands of the home, school, or work environment. This chapter addresses the assessment of MTBI. Topics include neuropsychological evaluation and assessment considerations, the importance of an integrated assessment, test administration, complex attention, memory skills, verbal communication skills, written communication skills, verbal information processing skills, written information processing skills, executive functioning skills, reasoning skills, and mathematical skills. A final section covers preparing the cognitive language evaluation report, including analyzing test scores, interpreting supplemental information, and sharing assessment results. The chapter concludes with extensive appendices, including client interview questionnaires, sample evaluation segments, vocational recommendations, and publisher and purchasing information for standardized tests. 10 references.
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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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Clinical Trials with the Auditory Brain Stem Implant Source: in Waltzman, S.B. and Cohen, N.L., eds. Cochlear Implants. New York, NY: Thieme. 2000. p. 357-377. Contact: Available from Thieme. 333 Seventh Avenue, New York, NY 10001. (800) 7823488. Fax (212) 947-0108. E-mail:
[email protected]. PRICE: $89.00 plus shipping and handling. ISBN: 0865778825. Summary: This chapter on clinical trials with the auditory brainstem implant is from a book that incorporates original chapters on relevant topics with related papers. The papers were presented at the Fifth International Cochlear Implant Conference held in New York, in May, 1997. The book provides professionals involved in the field of cochlear implants with a comprehensive reference text. All aspects of implantation are covered including the effects of electrical stimulation, processing capabilities, preoperative criteria, medical, surgical and radiological issues, results and postoperative programming, rehabilitation, and education. This chapter reviews the development, use, programming, and results with the multichannel auditory brain stem implant (ABI). The data reported is from the clinical trial conducted in the United States. The results section covers demographics, psychophysics, speech processor programming, and speech recognition. Accompanying the chapter are five related articles: cochlear implantation in neurofibromatosis Type 2; a new electrode design for the stable placing of a brainstem electrode; the Digisonic auditory brain stem implant (report of the first three cases); a new method to find the optimal location for an auditory brainstem electrode on the cochlear nucleus; and a bipolar stimulating probe for cochlear nucleus localization in auditory brainstem implant surgery. 7 figures. 4 tables. 44 references.
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Disorders of the Auditory Nerve and Brain Stem Source: in Mencher, G.T.; Gerber, S.E.; McCombe, A. Audiology and Auditory Dysfunction. Needham Heights, MA: Allyn and Bacon. 1997. p. 207-219. Contact: Available from Allyn and Bacon. 160 Gould Street, Needham Heights, MA 02194-2310. (800) 278-3525; Fax (617) 455-7024; E-mail:
[email protected]; http://www.abacon.com. PRICE: $46.95 plus shipping and handling. ISBN: 0205161014. Summary: This chapter on disorders of the auditory nerve and brain stem is from an audiology textbook on auditory dysfunction. There are a number of disorders affecting the auditory nerve and its connections to the central nervous system; they can be categorized as congenital, infective, inflammatory, traumatic, degenerative, etc. Most of these processes have already been discussed in earlier chapters in this book. In this chapter, the author focuses on the neoplasm or tumor pathology of auditory nerve disorders. This group of disorders is a relatively uncommon cause of auditory nerve dysfunction and is represented almost exclusively by the diagnosis of acoustic neuroma. The author discusses acoustic neuromas in some detail, covering pathology, clinical features, audiological considerations, and medical considerations. Two additional sections address von Recklinghausen disease and brain stem lesions. The author stresses that patients with eighth cranial nerve pathology (acoustic tumors) need audiological counseling, information on localization and making maximum use of residual hearing, amplification, protection of the ear and hearing, and in some cases, assistive devices, auditory training, speech reading, etc. 6 figures. 1 table.
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Neuropathological Aspects of Brain Aging and SDAT Source: in Courtois, Y., et al., eds. Modern Trends in Aging Research: Proceedings of the International INSERM-EURAGE Symposium 'Modern Trends in Aging, Research, Gerontology and Geriatrics' held in Paris, March 1986. London, England: John Libbey and Company. 1986. p. 435-441. Contact: Available from John Libbey and Company. 80/84 Bondway, London SW8 1SF, ENGLAND. (71) 582-5266. ISBN: 086916103X. PRICE: Call for information. Summary: This chapter presents some of the neuropathological features of senile dementia of the Alzheimer type (SDAT). Emphasis is placed on: (a) cortical atrophy due mainly to a 'shrinkage' of the length of the cortical ribbon, with its thickness remaining constant; (b) the location of senile plaques, mainly in layers II and III of the neocortex; and (c) recent data concerning the formation of neurofibrillary tangles. The aim of this chapter is not to serve as a review of the neuropathology of SDAT, but rather to pinpoint what currently seems to be the most salient pathological features of the disease. 31 references. (AA-M).
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Basal Forebrain Cholinergic Neurons and Alzheimer's Disease Source: in Iversen, L.L.; Iversen, S.D.; and Snyder, S.H., eds. Psychopharmacology of the Aging Nervous System, Volume 20. New York, NY: Plenum Press. 1988. p. 69-106. Contact: Available from Plenum Press. 233 Spring Street, New York, NY 10013. (800) 221-9369. PRICE: $85.00. ISBN: 0306427443. Summary: This chapter reviews the current state of knowledge on the involvement of forebrain cholinergic systems in Alzheimer's disease (AD). This is carried out in the context of current knowledge of the neuroanatomy and the pharmacology of this neuronal system. Finally, the efficacy of cholinergic replacement strategies in managing AD is addressed. This chapter addresses three principal themes: basic forebrain cholinergic systems; cholinergic alterations in AD; and cholinergic physiology. Five principal findings (for which there is broad experimental validity) are described that were derived from research on the role of basal forebrain cholinergic pathways in AD pathophysiology over the past 10 years. 235 references.
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Alzheimer's Disease Causes Metabolic Uncoupling of Associative Brain Regions Beyond That Seen in the Healthy Elderly Source: in Govoni, S.; Battaini, F., eds. Modification of Cell to Cell Signals During Normal and Pathological Aging. New York, NY: Springer-Verlag. 1987. p. 47-61. Contact: Available from Springer-Verlag. 175 Fifth Avenue, New York, NY 10010. (212) 460-1500. PRICE: $90.00. ISBN: 0387178864. Summary: This chapter summarizes the positron emission tomography (PET) data obtained by the authors that describe regional cerebral glucose metabolic rates in relation to healthy aging and early and progressive metabolic abnormalities in associative neocortical structures in Alzheimer's disease (AD) patients. Information is included on neuropsychological deficits that correlate with these metabolic abnormalities. Results with reference to the associational organization of the human brain also are discussed. In mildly demented AD patients without measurable neocortically mediated cognitive abnormalities, PET demonstrates reduced parietal and temporal lobe glucose metabolism and left/right metabolic asymmetries in neocortical association areas. Similar metabolic abnormalities occur in moderately demented
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patients, but are accompanied by appropriate language and visuospatial discrepancies. Left/right metabolic asymmetries correspond with reduced numbers of partial correlations between metabolic rates in homologous right and left regions, and in the frontal and parietal cortices, indicating metabolic uncoupling among these regions. The affected association regions are those which demonstrate AD-type neuropathology postmortem. 41 references. •
Psychosocial Effects of Traumatic Brain Injury Source: Austin, TX: PRO-ED, Inc. 1999. Traumatic Brain Injury in Children and Adolescents: A Sourcebook for Teachers and Other School Personnel, Second Edition. ISBN:0-89079-805-2. (5)29-38. Contact: Available from PRO-ED, Inc. 8700 Shoal Creek Boulevard, Austin, TX 787576897. (800) 897-3202; Fax (800) 397-7633. Web site: http://www.proedinc.com. PRICE: $30.00 plus shipping and handling for full text. Summary: This fifth chapter of the second edition of the teacher's sourcebook, Traumatic Brain Injury in Children and Adolescents, discusses types of psychosocial problems; age considerations; issues in adolescent TBI, and the school's role in psychosocial outcome.
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Immediate and Long-Term Effects of Traumatic Brain Injury Source: Austin, TX: PRO-ED, Inc. 1999. Traumatic Brain Injury in Children and Adolescents: A Sourcebook for Teachers and Other School Personnel, Second Edition. ISBN:0-89079-805-2. (4)15-28. Contact: Available from PRO-ED, Inc. 8700 Shoal Creek Boulevard, Austin, TX 787576897. (800) 897-3202; Fax (800) 397-7633. Web site: http://www.proedinc.com. PRICE: $30.00 plus shipping and handling for full text. Summary: This fourth chapter of the second edition of the teacher's sourcebook, Traumatic Brain Injury in Children and Adolescents, discusses the neuropathology; initial and long- term effects, including language, cognitive, sensory, and emotional; and characteristics of traumatic brain injury (TBI). A case study is included.
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Facts About Traumatic Brain Injury in Children and Adolescents Source: Austin, TX: PRO-ED, Inc. 1999. Traumatic Brain Injury in Children and Adolescents: A Sourcebook for Teachers and Other School Personnel, Second Edition. ISBN:0-89079-805-2. (2)3-8. Contact: Available from PRO-ED, Inc. 8700 Shoal Creek Boulevard, Austin, TX 787576897. (800) 897-3202; Fax (800) 397-7633. Web site: http://www.proedinc.com. PRICE: $30.00 plus shipping and handling for full text. Summary: This second chapter of the second edition of the teacher's sourcebook, Traumatic Brain Injury in Children and Adolescents, discusses incidents of traumatic brain injury (TBI) among children; levels of severity of TBI; and causes and risk factors of TBI.
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Animal Models in Dementia Research: Metabolic Changes After Intracerebroventricular Injections of Bromopyruvate, AF64A, and Alzheimer Brain Homogenates Source: in Courtois, Y., et al., eds. Modern Trends in Aging Research: Proceedings of the International INSERM-EURAGE Symposium 'Modern Trends in Aging, Research,
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Gerontology and Geriatrics' held in Paris, March 1986. London, England: John Libbey and Company. 1986. p. 541-548. Contact: Available from John Libbey and Company. 80/84 Bondway, London SW8 1SF, ENGLAND. (71) 582-5266. ISBN: 086916103X. PRICE: Call for information. Summary: Three different approaches were tested to produce 'dementia' symptoms such as deficits in learning and memory associated with senile dementia of the Alzheimer's type (SDAT) and to relate them to changes in oxidative and energy metabolism of brain cortex and hippocampus, by injection of bromopyruvate (BP), a substrate analog of pyruvate, into experimental rats. BP functions as an inhibitor of the multi-enzyme complex, pyruvate dehydrogenase. Inhibition of pyruvate oxidation was associated with deficits in learning and memory. Administration of brain homogenate from elderly and SDAT cases, respectively, produced learning deficits which could not be related to biochemical abnormalities in either the cortex or the hippocampus. It is concluded that the approaches used in these studies may be useful tools for further research on morphological, metabolic, and behavioral aspects of dementia in experimental animals. 23 references. (AA-M).
Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to brain have been published that consolidate information across various sources. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:12 •
Brain Connections: Your Source Guide to Information on Brain Diseases and Disorders. 5th ed Source: New York, NY: Dana Alliance for Brain Initiatives. 2000. 49 p. Contact: Available from Dana Press. Charles A. Dana Foundation, 745 Fifth Avenue, Suite 700, New York, NY 10151. Fax (212) 593-7623. Website: www.dana.org. PRICE: Single copy free. Summary: This guide lists organizations that assist people with a brain-related disorder or disease as well as those organizations that assist caregivers and health care providers in these areas. The guide lists more than 275 organizations alphabetically by disease or disorder. Listings of particular relevance to communication disorders include: acoustic neuroma, aphasia, ataxia, attention deficit hyperactivity disorder, autism, deafness and hearing loss, disability and rehabilitation, dizziness, dyslexia, dystonia, head injury, learning disabilities, neurofibromatosis, smell and taste (chemosensory) disorders, spasmodic dysphonia, stuttering, tinnitus, Tourette syndrome, and vestibular disorders. Emphasis is placed on organizations that have a national focus, however, many of these groups sponsor local chapters or affiliates and make referrals to local medical professionals and organizations. For each organization listed, the guide notes mailing address, telephone numbers, e-mail and web sites; also provided are symbols which indicate that the organization offers support groups, referrals to doctors, referrals to
12 You will need to limit your search to “Directory” and “brain” using the "Detailed Search" option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Select your preferred language and the format option “Directory.” Type “brain” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months.
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other sources of information, regional chapters, availability of literature, availability of speakers, and volunteer opportunities. The guide also describes the publishing body, the Dana Alliance for Brain Initiatives, and provides a list of ways in which readers can support and further brain research. •
Brain Connections: Your Guide to Information on Brain Diseases and Disorders. Fifth Edition 2000-2002 Source: New York, NY: Dana Alliance for Brain Initiatives. 2000. 49 p. Contact: Available from Dana Alliance for Brain Initiatives. 745 Fifth Avenue, Suite 700, New York, NY 10151. (212) 223-4040; FAX: (212) 317- 8721. Internet: http://www.dana.org. PRICE: Free. Summary: This resource guide lists organizations that assist people with brain diseases and disorders, and those responsible for their care. It includes over 275 organizations, listed alphabetically by the disease or disorder. It emphasizes organizations that are national in scope. The guide offers telephone numbers, postal and email addresses, web sites, and services available. The guide concludes with information about the Dana Press and ways that the reader can support brain research.
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CHAPTER 7. MULTIMEDIA ON BRAIN Overview In this chapter, we show you how to keep current on multimedia sources of information on brain. 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 is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “brain” 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” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on brain: •
Speech Production Disorders Following Traumatic Brain Injury Source: Tucson, AZ: National Center for Neurogenic Communication Disorders. 1993. (videocassette and handout). Contact: Available from National Center for Neurogenic Communication Disorders. Telerounds Coordinator, Building 71, Room 500, University of Arizona, Tucson, AZ 85721. (520) 621-1819 or (520) 621-1472. PRICE: $25.00. Summary: In this telerounds program, speech production disorders and neural lesions are described for a group of individuals with traumatic brain injury (TBI). The neural lesions are interpreted in terms of their possible relations to the speech disorders and the proposed neural mechanisms of speech production. The program also discusses the associated research and clinical implications. The handout provided with the videotape includes an abstract, a list of objectives, a brief outline of the program, a reference list, and an evaluation form for viewers to complete and return. 31 references. (AA-M).
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Module 4. Alzheimer Journey: Understanding Alzheimer Disease: The Link Between Brain and Behavior Source: Toronto, Ontario: Alzheimer Society of Canada. 2002. [videocassette and workbook, 15 p.]. Contact: Alzheimer Society of Canada. 20 Eglinton Avenue West, Suite 1200. Toronto, Ontario, Canada M4R 1K8. (800) 616-8816; (416) 488-8772. FAX: (416) 488-3778. E-mail:
[email protected]. Website: www.alzheimer.ca. PRICE: $25.00 ($100.00 for all 4 videocassetes in series). Summary: This video and accompanying workbook explain how the brain works and what happens when different areas of the brain are affected by Alzheimer's disease. First, it describes the normal functions of different parts of the brain. Then, it explains which functions or abilities may be impaired as the disease progresses and affects different parts of the brain. It outlines the symptoms and behavioral changes associated with damage to each brain area, coping strategies for the patient, and management tips for caregivers. It concludes with general suggestions to help the patient and caregiver maintain a healthy lifestyle and improve communications.
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Exploring Your Brain: Memory Source: New York, NY: Dana Foundation. 1998. Contact: Available from Films for the Humanities and Sciences. PO Box 2053, Princeton, NJ 08543-2053. (800) 257-5126, (609) 275-1400; FAX: (609) 275-3767. Internet: http://www.films.com. PRICE: $89.95. Item number: BVL8644. Summary: This video is one in a series about the brain, broadcast by the Public Broadcasting System. This show discussed the biology of memory and memory loss. The first segment of the program discussed types of memory such as explicit and implicit, and short and long term memory. The panelists then discussed the aging brain and the prospect of losing memory. Factors which can prevent or slow memory loss may include education, physical and mental activity, and a feeling of control over one's life. Current research into treating memory loss includes cholinesterase inhibitors, Vitamin E, and hormone replacement therapy. The next section of the show discussed memory distortion and recovered memory. Following a question and answer time with the audience, the panelists expressed their thoughts on future research into memory and the brain.
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Alzheimer's Disease: Silent Changes in the Brain Source: Los Angeles, CA: University of Southern California, School of Medicine. 1985. (videocassette). Contact: Available from Office of Instructional Medical Services. Keith Administration Building, Room B-16, University of California. 2025 Zonal Avenue, Los Angeles, CA 90033. (213) 224-7041. PRICE: $195.00 (purchase), $95.00 (rental). Summary: This videotape is designed for caregivers, patients diagnosed with Alzheimer's disease, and their family members. The program addresses issues such as diagnosis of Alzheimer's disease, patient management, the disease process, research, and other practical matters.
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Brain and Behaviour Source: Ryde, New South Wales, Australia: Alzheimer's Disease and Related Disorders Association. 1988. (videocassette). Contact: Available from University of Sydney. Television Service, 6th Floor, Carslaw Building, Sydney, New South Wales, 2006 AUSTRALIA. (02) 692-3005. PRICE: US $39.00 for VHS, Beta; US $52.00 for U-Matic. Summary: This videotape on Alzheimer's disease was produced for the Alzheimer's Disease and Related Disorders Society of New South Wales, Australia, and is directed toward a wide audience, including family members, support personnel, and medical and paramedical professionals. The video uses an informal group setting to describe changes in brain function and behavior that occur in people with Alzheimer's disease. It discusses the parts of the brain that are affected by Alzheimer's disease and related dementias, including the temporal, parietal, and frontal lobes and the limbic system; the functions of these parts, and how the brain changes as the disease follows its course. The video then presents how these physical changes affect behavior and personality. Included are filmed interviews to demonstrate techniques that can be used to help persons with Alzheimer's disease and to help others in understanding and coping with the affected person's disabilities.
Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio 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 “Sound Recordings.” Type “brain” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on brain: •
AIDS Update: ED Management, Part 1 Contact: California Medical Association, Audio Digest Foundation, 1577 E Chevy Chase Dr, Glendale, CA, 91206, (213) 245-8505. Summary: This sound recording, along with accompanying pre-test and post-test questions, is part on an ongoing series of educational activities. The first speaker, David F. Dreis, from the Section of Chest and Infectious Diseases at the Virginia Mason Medical Center in Seattle, discusses prevalence and detection of Acquired immunodeficiency syndrome (AIDS). He explains the risks involved in blood transfusions, routes of Human immunodeficiency virus (HIV) transmission, the HIVantibody test, and the potential for development of AIDS. David A. Talan, assistant professor of medicine at the University of California Los Angeles School of Medicine, looks at physicians' fear of infection. His presentation deals with the risks of infection for emergency personenel, the possibility of transmission through casual contact, and the risks of transmission in the emergency room. He then presents Centers for Disease Control and Prevention (CDC) recommendations for infection control and occupational safety, and procedures for handling a needlestick. The final speaker, George F. Risi Jr., assistant professor of Medicine at Lousiana State University School of Medicine in New Orleans, looks at opportunistic infections in the lung, gut, and brain. His presentation deals with pneumocystis carinii pneumonia (PCP), common respiratory pathogens, gastrointestinal mainfestations, and neurologic manifestations.
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Bibliography: Multimedia on Brain 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 (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: •
Atlas of the human brain Source: Jürgen K. Mai, Joseph Assheuer, George Paxinos; Year: 2004; San Diego, Calif.: Elsevier Academic Press, c2004
•
Atlases of the brain [electronic resource] Source: Suzanne S. Stensaas. [et al.]; Year: 2000; Format: Electronic resource; Salt Lake City: Knowledge Weavers, Spencer S. Eccles Health Sciences Library, University of Utah, [2000?]
•
Exposure and removal of the brain [videorecording] Source: Department of Anatomy, University of Texas Medical School at San Antonio; Year: 1971; Format: Videorecording; San Antonio: The Dept.; [for sale by Univ. of Texas Health Science Center at San Antonio, Dept. of Anatomy, 1971?]
•
MRI of the brain and spine [electronic resource] Source: Scott W. Atlas [editor]; Year: 2003; Format: Electronic resource; Philadelphia, PA: Lippincott Williams & Wilkins, [2003]
•
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]
•
Topography: detailed topography of the major divisions and subdivisions of the brain [videorecording] Source: National Medical Audiovisual Center; Year: 1972; Format: Videorecording; [Atlanta]: The Center, [1972]
•
Topography: major division of the brain and their relation to the embryonic brain [videorecording] Source: National Medical Audiovisual Center; Year: 1972; Format: Videorecording; [Atlanta]: The Center, [1972]
•
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. 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. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with brain. 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 following
270 Brain
drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to brain: Acyclovir •
Systemic - U.S. Brands: Zovirax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202008.html
Amlodipine •
Systemic - U.S. Brands: Norvasc http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202670.html
Amlodipine and Benazepril •
Systemic - U.S. Brands: Lotrel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203634.html
Anesthetics, General •
Systemic - U.S. Brands: Amidate; Brevital; Diprivan; Ethrane; Fluothane; Forane; Ketalar; Penthrane; Pentothal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203043.html
Angiotensin-Converting Enzyme (Ace) Inhibitors •
Systemic - U.S. Brands: Accupril; Aceon; Altace; Capoten; Lotensin; Mavik; Monopril; Prinivil; Univasc; Vasotec 4; Zestril http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202044.html
Angiotensin-Converting Enzyme (Ace) Inhibitors and Hydrochlorothiazide •
Systemic - U.S. Brands: Accuretic; Capozide; Lotensin HCT; Prinzide; Uniretic; Vaseretic; Zestoretic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202045.html
Benzonatate •
Systemic - U.S. Brands: Tessalon http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202085.html
Beta-Adrenergic Blocking Agents and Thiazide Diuretics •
Systemic - U.S. Brands: Corzide 40/5; Corzide 80/5; Inderide; Inderide LA; Lopressor HCT; Tenoretic 100; Tenoretic 50; Timolide 10-25; Ziac http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202088.html
Botulinum Toxin Type A •
Parenteral-Local - U.S. Brands: Botox http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202608.html
Bromocriptine •
Systemic - U.S. Brands: Parlodel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202094.html
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Buspirone •
Systemic - U.S. Brands: BuSpar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202100.html
Cabergoline •
Systemic - U.S. Brands: Dostinex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203584.html
Calcium Channel Blocking Agents •
Systemic - U.S. Brands: Adalat; Adalat CC; Calan; Calan SR; Cardene; Cardizem; Cardizem CD; Cardizem SR; Dilacor-XR; DynaCirc; Isoptin; Isoptin SR; Nimotop; Plendil; Procardia; Procardia XL; Vascor; Verelan http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202107.html
Candesartan •
Systemic - U.S. Brands: Atacand http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203598.html
Carboplatin •
Systemic - U.S. Brands: Paraplatin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202115.html
Carmustine •
Systemic - U.S. Brands: BiCNU http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202117.html
Carvedilol •
Systemic - U.S. Brands: Coreg http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203636.html
Citalopram •
Systemic - U.S. Brands: Celexa http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203653.html
Clonidine •
Systemic - U.S. Brands: Catapres; Catapres-TTS http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202152.html
Clonidine and Chlorthalidone •
Systemic - U.S. Brands: Combipres http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202153.html
Clopidogrel •
Systemic - U.S. Brands: Plavix http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203403.html
Cyclophosphamide •
Systemic - U.S. Brands: Cytoxan; Neosar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202174.html
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Cytarabine •
Systemic - U.S. Brands: Cytosar-U http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202177.html
Cytarabine, Liposomal •
Intrathecal - U.S. Brands: DepoCyt http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500008.html
Dextromethorphan •
Systemic - U.S. Brands: Cough-X; Creo-Terpin; Trocal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202187.html
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
Dipyridamole and Aspirin •
Systemic - U.S. Brands: Aggrenox http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500072.html
Diuretics, Loop •
Systemic - U.S. Brands: Bumex; Edecrin; Lasix; Myrosemide http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202205.html
Diuretics, Potassium-Sparing •
Systemic - U.S. Brands: Aldactone; Dyrenium; Midamor http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202206.html
Diuretics, Potassium-Sparing, and Hydrochlorothiazide •
Systemic - U.S. Brands: Aldactazide; Dyazide; Maxzide; Moduretic; Spirozide http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202207.html
Diuretics, Thiazide •
Systemic - U.S. Brands: Aquatensen; Diucardin; Diulo; Diuril; Enduron; Esidrix; Hydro-chlor; Hydro-D; HydroDIURIL; Hydromox; Hygroton; Metahydrin; Microzide; Mykrox; Naqua; Naturetin; Oretic; Renese; Saluron; Thalitone; Trichlorex 10; Zaroxolyn http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202208.html
Doxazosin •
Systemic - U.S. Brands: Cardura http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202629.html
Researching Medications
Enalapril and Felodipine •
Systemic - U.S. Brands: Lexxel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203638.html
Eprosartan •
Systemic - U.S. Brands: Teveten http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500044.html
Ergoloid Mesylates •
Systemic - U.S. Brands: Gerimal; Hydergine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202215.html
Etoposide •
Systemic - U.S. Brands: Etopophos; Toposar; VePesid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202234.html
Fluoxetine •
Systemic - U.S. Brands: Prozac; Sarafem http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202247.html
Fluvoxamine •
Systemic - U.S. Brands: Luvox http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202919.html
Galantamine •
Systemic - U.S. Brands: Reminyl http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500281.html
Glycerin •
Systemic - U.S. Brands: Glyrol; Osmoglyn http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202263.html
Goserelin •
Systemic - U.S. Brands: Zoladex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202267.html
Guanabenz •
Systemic - U.S. Brands: Wytensin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202271.html
Guanadrel •
Systemic - U.S. Brands: Hylorel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202272.html
Guanethidine •
Systemic - U.S. Brands: Ismelin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202273.html
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Guanfacine •
Systemic - U.S. Brands: Tenex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202275.html
Histrelin •
Systemic - U.S. Brands: Supprelin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203510.html
Hydralazine and Hydrochlorothiazide •
Systemic - U.S. Brands: Apresazide http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202286.html
Ifosfamide •
Systemic - U.S. Brands: IFEX http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202293.html
Indapamide •
Systemic - U.S. Brands: Lozol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202296.html
Irbesartan •
Systemic - U.S. Brands: Avapro http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203379.html
Losartan •
Systemic - U.S. Brands: Cozaar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202767.html
Losartan and Hydrochlorothiazide •
Systemic - U.S. Brands: Hyzaar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203639.html
Measles Virus Vaccine Live •
Systemic - U.S. Brands: Attenuvax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202338.html
Mecamylamine •
Systemic - U.S. Brands: Inversine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202340.html
Methyldopa •
Systemic - U.S. Brands: Aldomet http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202359.html
Methyldopa and Thiazide Diuretics •
Systemic - U.S. Brands: Aldoclor; Aldoril http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202360.html
Researching Medications
Minoxidil •
Systemic - U.S. Brands: Loniten http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202373.html
Mumps Virus Vaccine Live •
Systemic - U.S. Brands: Mumpsvax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202382.html
Nafarelin •
Systemic - U.S. Brands: Synarel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202646.html
Nisoldipine •
Systemic - U.S. Brands: Sular http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203431.html
Paroxetine •
Systemic - U.S. Brands: Paxil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202717.html
Pneumococcal Conjugate Vaccine •
Systemic - U.S. Brands: Prevnar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500121.html
Prazosin •
Systemic - U.S. Brands: Minipress http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202475.html
Prazosin and Polythiazide •
Systemic - U.S. Brands: Minizide http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202476.html
Primidone •
Systemic - U.S. Brands: Myidone; Mysoline http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202479.html
Rauwolfia Alkaloids •
Systemic - U.S. Brands: Harmonyl; Raudixin; Rauval; Rauverid; Serpalan; Wolfina http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202503.html
Rauwolfia Alkaloids and Thiazide Diuretics •
Systemic - U.S. Brands: Demi-Regroton; Diupres; Diurigen with Reserpine; Diutensen-R; Enduronyl; Enduronyl Forte; Oreticyl; Oreticyl Forte; Rauzide; Regroton http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202504.html
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276 Brain
Reserpine, Hydralazine, and Hydrochlorothiazide •
Systemic - U.S. Brands: Cam-Ap-Es; Cherapas; Ser-A-Gen; Seralazide; Ser-ApEs; Serpazide; Tri-Hydroserpine; Unipres http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202506.html
Rivastigmine •
Systemic - U.S. Brands: Exelon http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500151.html
Sertraline •
Systemic - U.S. Brands: Zoloft http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202651.html
Sibutramine •
Systemic - U.S. Brands: Meridia http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203725.html
Sulfasalazine •
Systemic - U.S. Brands: Azulfidine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202537.html
Tacrine •
Systemic - U.S. Brands: Cognex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202722.html
Telmisartan •
Systemic - U.S. Brands: Micardis http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203710.html
Temozolomide •
Systemic - U.S. Brands: Temodar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500076.html
Terazosin •
Systemic - U.S. Brands: Hytrin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202546.html
Thioxanthenes •
Systemic - U.S. Brands: Navane; Taractan; Thiothixene HCl Intensol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202564.html
Ticlopidine •
Systemic - U.S. Brands: Ticlid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202637.html
Torsemide •
Systemic - U.S. Brands: Demadex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202740.html
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Trandolapril and Verapamil •
Systemic - U.S. Brands: Tarka http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203641.html
Trientine •
Systemic - U.S. Brands: Syprine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202575.html
Valsartan •
Systemic - U.S. Brands: Diovan http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203478.html
Varicella Virus Vaccine Live •
Systemic - U.S. Brands: Varivax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202998.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.
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Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to brain by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “brain” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for brain: •
Dimethyl sulfoxide http://www.rarediseases.org/nord/search/nodd_full?code=238
•
Liposome encapsulated recombinant interleukin-2 http://www.rarediseases.org/nord/search/nodd_full?code=258
•
Serratia marcescens extract (polyribosomes) (trade name: Imuvert) http://www.rarediseases.org/nord/search/nodd_full?code=46
•
Bromodeoxyuridine http://www.rarediseases.org/nord/search/nodd_full?code=681
•
Herpes simplex virus gene http://www.rarediseases.org/nord/search/nodd_full?code=736
•
Poly-ICLC http://www.rarediseases.org/nord/search/nodd_full?code=835
•
Busulfan (trade name: Spartaject) http://www.rarediseases.org/nord/search/nodd_full?code=838
•
Mitolactol http://www.rarediseases.org/nord/search/nodd_full?code=85
•
Thalidomide http://www.rarediseases.org/nord/search/nodd_full?code=908
•
Corticotropin-releasing factor, human (trade name: Xerecept) http://www.rarediseases.org/nord/search/nodd_full?code=909
•
Interferon beta (recombinant human) http://www.rarediseases.org/nord/search/nodd_full?code=99
Researching Medications
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If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
283
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 Institute13: •
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/
13
These publications are typically written by one or more of the various NIH Institutes.
284 Brain
•
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/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.14 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:15 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
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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). 15 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The 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” 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” (or synonyms) into the “For these words:” box. The following is a sample result: •
Annual Report: Sixth Year Progress of Programs Under the Comprehensive Act for Families and Caregivers of Brain-Impaired Adults Source: San Francisco, CA: Family Survival Project. 1991. [40 p.]. Contact: Available from Family Survival Project. 425 Bush Street, Suite 500, San Francisco, CA 94108. (415) 434-3388. PRICE: Free. Summary: This annual report describes the progress during fiscal year 1990-91 of programs developed under the California Comprehensive Act for Families and Caregivers of Brain-Impaired Adults. This act established a statewide system of Caregiver Resource Centers (CRCs) to assist families providing long term care for persons with Alzheimer's disease and other chronic or degenerative brain disorders. The report provides background information about the development and implementation of the statewide program and the service components provided by the CRCs. It describes the methodology used to collect data for the report and presents findings in the following areas: profiles of the family clients and patient population; the costs and amount of each service provided; the demand for respite services and success in meeting this demand; success in helping families avoid institutional placement; and identification of the unmet needs of brain impaired persons and their families and progress in developing programs and services to meet these needs. The report includes recommendations for future efforts to identify and address caregiver needs.
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Funding traumatic brain injury services Source: Denver, CO: National Conference of State Legislatures. 2001. 33 pp. Contact: Available from National Conference of State Legislatures, 1560 Broadway, Suite 700, Denver, CO 80202. Telephone: (303) 830-2200 or (303) 830-2054 book order line / fax: (303) 863-8003 / e-mail:
[email protected] / Web site: http://www.ncsl.org. $15.00, plus shipping and handling. Summary: This brief offers an overview of traumatic brain injury (TBI) and its effect on individuals and society, particularly in the need for and use of a variety of health and assistive services. It is designed to serve as a guide for states to identify resources and funding streams to help address the range of associated issues. Topics discussed include
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defining TBI; outlining legislative concerns; determining how prevalent TBI is in the United States in relation to other chronic illnesses and conditions; and identifying legislation and funding sources covering TBI. The appendix contains state-by-state information about federal and state spending on TBI, data collected in a study conducted by the Brain Injury Association of America Inc. in 1999. Statistical information is presented in charts, graphs, and tables throughout the report. [Funded by the Maternal and Child Health Bureau]. •
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.
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Report of the NIH Consensus Development Conference on the Rehabilitation of Persons With Traumatic Brain Injury Source: Rockville, MD: National Institute of Child Health and Human Development. 1999. 530 pp. Contact: Available from National Institute of Child Health and Human Development Clearinghouse, P.O. Box 3006, Rockville, MD 20847. Telephone: (800) 370-2943 TTY: (888) 320-6942 / fax: (301) 984-1473 / e-mail:
[email protected] / Web site: http://www.nichd.nih.gov/publications/info.htm. Available at no charge. Summary: This consensus development statement is meant to inform the biomedical research and clinical practice communities of the results of the National Institutes of Health Consensus Development Conference on Rehabilitation of Persons with Traumatic Brain Injury, held October 26- 28, 1998 in Bethesda, Maryland. The statement provides information on effective rehabilitation measures for persons who have suffered a traumatic brain injury as well as conclusions and recommendations of the consensus panel. Additional topics include epidemiology of brain injury, hospitalization trends, family consequences, the economics of rehabilitation, research in cognitive rehabilitation, models of care, access to services, and ethical considerations in traumatic brain injury research. Report sections include the consensus statement, a list of consensus development panel, speakers, planning committee, the conference abstracts, and the consensus panel report. Also included is a listing of acronyms/abbreviations and three appendices containing three studies on traumatic brain injury.
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Who's Taking Care?: A Profile of California's Family Caregivers of Brain-Impaired Adults Source: San Francisco, CA: Family Survival Project. March 1990. 114 p. Contact: Available from Family Survival Project. 425 Bush Street, Suite 500, San Francisco, CA 94108. (800) 445-8106 or (415) 434-3388. PRICE: $20.00. Summary: This detailed report presents the findings from the first statewide California database on caregivers and brain-impaired adults, collected through a uniform assessment process by a network of 11 Regional Resource Centers (RRC's). The report is comprised of 4 chapters. The first provides a review of the current literature on the functional problems of brain-impaired adults and the impact on caregivers. The second describes the study methodology, including a review of the assessment instrument and measures used in this research. The third chapter presents the study findings in 7 categorical sections (patient characteristics; caregiver characteristics; patient problem behaviors; caregiver well-being (i.e., stress and burden, physical and mental health); caregiver social support; service needs and utilization; and a presentation of a preliminary look at the impact of caregiving 6 months after the baseline assessment). The last chapter provides a summary of findings and conclusions. A list of references and appendices containing summary data tables and a map of the statewide network of RRC's in California are included. 55 references.
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TBI: Traumatic Brain Injury State Demonstration Grant Program: Project abstracts, FY__ Source: Silver Spring, MD: TBI Technical Assistance Center. 1998. annual. Contact: Available from TBI Technical Assistance Center, 8737 Colesville Road, Suite 950, Silver Spring, MD 20910. Telephone: (301) 650-8080 / fax: (301) 650-8045. Summary: This report begins with background information on the Traumatic Brain Injury State Demonstration Grant Program. Part II of the report is a tabular state-bystate summary of objectives. Part III contains project abstracts for planning grants and implementation grants, each section arranged alphabetically by state name. Part IV is the grantee contact list. [Funded by the Maternal and Child Health Bureau].
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Traumatic brain injury in Massachusetts: Incidence and prevention Source: Boston, MA: Injury Prevention and Control Program, Massachusetts Department of Public Health. 1994. 44 pp. Contact: Available from Cindy Rodgers, Massachusetts Department of Public Health, Injury Prevention and Control Program, 250 Washington Street, Fourth Floor, Boston, MA 02108-4619. Telephone: (617) 624-5070 / fax: (617) 624-5075 / e-mail:
[email protected]. Available at no charge. Summary: This report describes the extent of traumatic brain injury in Massachusetts, including the frequency of brain injury by cause, and estimates the lifetime costs of health care and lost earnings. Clinical patterns of these injuries, sample cases from one emergency department, and prevention strategies targeted at the three leading causes of brain injuries: motor vehicles, falls and firearms, are also described.
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Rehabilitation for Traumatic Brain Injury in Children and Adolescents Source: Rockville, MD: Agency for Healthcare Research and Quality (AHRQ), Department of Health and Human Services. September 1999. 120 p.
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Contact: Available from Agency for Healthcare Research and Quality (AHRQ). P.O. Box 8547, Silver Spring, MD 20907-8547. (800) 358-9295. Website: www.ahrq.gov. PRICE: Single copy free. AHCPR Publication Number 00-E001. Summary: This report focuses on the results of a systematic review of the literature about child and adolescent traumatic brain injury (TBI). With the assistance of technical experts, key questions were formulated in five areas: the effectiveness of early, intensive rehabilitation; referral of children with TBI to special education; the effectiveness of special education for children with TBI; the effect of developmental phase on prediction and outcome; and the effect of support for families. Patient populations, interventions, and outcome measures were defined, and literature was compiled and categorized from seven databases: medical, educational, and psychological. The initial search strategy yielded 1,464 abstracts of potentially relevant studies; of these, 356 articles were relevant to one of the five research questions. No randomized controlled trials and very few comparative studies were found that addressed the key research questions. One study suggests that the early introduction of physiatry during the acute care phase of treatment aids in detecting musculoskeletal trauma that may otherwise be missed. No literature was found that accurately documents rates of referral for children with TBI to special services. A large body of literature documents the utility of patients' developmental information in predicting deficits and outcomes. Correlational studies associate family support with better family functioning. This report reviews the findings of the literature review and includes discussions and recommendations for future research. Appendices list the technical expert panels, key questions, search strategies, categorization and code system for bibliography, and an evidence table template. The report concludes with the bibliography of the studies reviewed. 2 figures. 4 tables. 563 references. •
Traumatic brain injury in the United States: Assessing outcomes in children: Summary and recommendations from the Expert Working Group, Atlanta, GA, October 26-27, 2000 Source: [Atlanta, GA]: National Center for Injury Prevention and Control. [2001]. 50 pp. Contact: Available from HRSA Information Center, 2070 Chain Bridge Road, Suite 450, Vienna, VA 22182-2536. Telephone: (888) ASK-HRSA or (877) 474-4772 TTY / fax: (703) 821-2098 / e-mail:
[email protected] / Web site: http://www.ask.hrsa.gov. Summary: This report is intended for researchers, public health professional including those from state health departments, and advocates interested in furthering research on outcomes of traumatic brain injury (TBI) in children. This report summarizes the comments, suggestions, and recommendations of a working group convened by the Centers for Disease Control and Prevention (CDC) on assessment of TBI outcomes in children and youth. Meeting participants identified (1) key research topics and variables to measure in assessing longer-term outcomes; (2) reviewed conceptual models of disability that could provide a framework for designing appropriate studies of TBI outcomes; (3) discussed the advantages and shortcomings for assessing these outcomes; and (4) described the challenges in designing and implementing studies on TBI and recommended ways to address those challenges. The appendices include an overview of available outcome assessments; presentation slides; surveillance data from South Carolina; resources to guide selection of research topics; and an overview of TBI surveillance activities funded by the CDC.
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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 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].
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Good Beginnings for All Children: From Brain Research to Action Source: St. Louis, MO: Parents as Teachers National Center. [1998]. 31 pp. Contact: Available from Parents as Teachers National Center, 10176 Corporate Square Drive, Suite 230, St. Louis, MO 63132. Telephone: (314) 432-4330 / fax: (314) 432-8963 / e-mail:
[email protected] / Web site: http://www.patnc.org. $7.50 including shipping and handling. Summary: This report summarizes the presentations and discussions held during a national forum, titled Good Beginnings for All Children: From Brain Research to Action, on how to apply neuroscience research to the field of education. The forum focused primarily on language acquisition in young children. The report includes the potential role of neuroscience research in education reform, how the brain develops, how children learn language, how this information can best inform policy and practice, case studies, of statewide and community collaborative efforts, Rob Reiner's 'I am Your Child' Campaign, and points of commonality and controversy.
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Family Matter: A Longitudinal Study of California Caregivers of Brain-Impaired Adults Source: San Francisco, CA: Family Survival Project. November 1991. 116 p. Contact: Available from Family Survival Project. 425 Bush Street, Suite 500, San Francisco, CA 94108 (415) 434-3388. PRICE: $20.00. Summary: This research report describes a longitudinal study conducted between April 1988 and June 1990 in San Francisco, California, to examine changes over time in the well being, social support, service needs, and service utilization of caregivers of brain impaired persons. The report first reviews the literature, highlighting prior research on caregivers for the three diagnostic groups examined in the study: dementia (among dementias, Alzheimer's disease was the most common diagnosis); stroke; and traumatic brain injury. The report then describes the study instruments and methodology and presents findings in the following areas: 1) caregiver and patient status over time; 2) caregiver and patient characteristics and patient problem behaviors at baseline; 3) changes in caregiver well being such as stress and burden, physical health, and mental health; and 4) changes in social support and in service needs and utilization. The authors note that perhaps the most important finding of the study is that caregiver well
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being can improve over time in a caregiving population with relatively high baseline burden and depression levels. The authors state that the findings provide important implications for future policy, service, and research initiatives to assist family caregivers of brain-impaired adults. 93 references. •
Employed Caregivers of Brain-Impaired Adults: An Assessment of the Dual Role Source: San Francisco, CA: Family Survival Project. February 1987. 96 p. Contact: Available from Family Survival Project. 425 Bush Street, Suite 500, San Francisco, CA 94108. (800) 445-8106 or (415) 434-3388. PRICE: $10.00. Summary: This research report examines the joint demands of caregiving and employment for family members caring for brain-impaired adults by comparing employed and non-employed caregivers. The goals of the research were to develop a profile of employed caregivers of brain-impaired adults, to examine the social and psychological impact of the dual roles of caregiving and working outside the home, and to examine the impact of caregiving on employment. While employed caregivers have jobs, they spend an average of 35 hours per week in caregiving; however, caregivers not employed spend almost 2.5 times as many hours caring for their relatives (on the average, 12 hours per day). There was no evidence that employment adversely affected the caregiver's perception of the quality of care or the quality of the caregiver's relationship to the brain-impaired adult. Both employed and not employed caregivers had more harmonious relationships with their brain-impaired relatives following their placement in a nursing home or other care facility. Caregivers who worked at their jobs less than 20 hours per week experienced more stress and burden than those who were employed for longer hours per week. The results of this study are statistically summarized (44 tables) and discussed. 21 references.
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Homecare Versus Institutionalization: Family Caregiving and Senile Brain Disease Source: International Journal of Nursing Studies. 20(1): 23-32. 1983. Summary: This study explored the factors influencing a caregiver to continue living with an old person with irreversible senile brain disease, versus those leading a family to consider institutionalization. The non-random sample consisted of 30 elderly persons with dementia and their family caregivers. Mutuality between the supportive and the impaired family members emerged as the major parameter for families managing life with senile brain disease. Components of mutuality include the caregiver's ability to find gratification in the relationship and to perceive the impaired person as reciprocating by virtue of his or her existence. Health visiting services for preventive, maintenance, and curative home care for both cognitively impaired persons and their caregivers would answer a large need. 23 references.
The NLM Gateway16 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.17 To 16 17
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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use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “brain” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 856236 10000 1996 1282 5007 874521
HSTAT18 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.19 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.20 Simply search by “brain” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists21 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.22 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.23 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for
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Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.
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The HSTAT URL is http://hstat.nlm.nih.gov/.
20 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. 21 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 22
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. 23 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/.
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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Brain In the following section, we will discuss databases and references which relate to the Genome Project and brain. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).24 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “brain” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for brain: •
Deleted in Malignant Brain Tumors 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601969
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Arteriovenous Malformations of the Brain Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?108010
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Band Heterotopia of Brain Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600348
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Brain and Acute Leukemia Gene, Cytoplasmic Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606602
24 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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Brain Anomalies, Retardation, Ectodermal Dysplasia, Skeletal Malformations, Hirschsprung Disease, Ear/eye Anomalies, Cleft Palate/cryptorchidism, and Kidney Dysplasia/hypoplasia Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300404
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Brain Cytoplasmic Rna 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606089
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Brain-abundant Signal Protein, Membrane-attached, 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605940
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Brain-derived Neurotrophic Factor Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?113505
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Brain-specific Angiogenesis Inhibitor 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602682
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Brain-specific Angiogenesis Inhibitor 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602683
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Brain-specific Angiogenesis Inhibitor 3 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602684
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Brain-specific Protein Pc-1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?113510
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Creatine Kinase, Brain Type Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?123280
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Creatine Kinase, Brain Type, Ectopic Expression of Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?123270
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Gastrulation Brain Homeo Box 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603354
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Gastrulation Brain Homeo Box 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601135
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Glioma of Brain, Familial Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?137800
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Glucose Transport Defect, Blood-brain Barrier Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606777
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Glutamic Acid Decarboxylase, Brain, Membrane Form Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138277
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Glycogen Phosphorylase, Brain Type Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138550
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Hair-Brain Syndrome Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?234050
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Hypotonia, Congenital Nystagmus, Ataxia, and Abnormal Auditory Brain Stem Responses Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300184
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Muscle-Eye-Brain Disease Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?253280
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Navajo Brain Stem Syndrome Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601536
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Peripheral Neuropathy, Ataxia, Focal Necrotizing Encephalopathy, and Spongy Degeneration of Brain Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?260970
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Pick Disease of Brain Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?172700
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Prostaglandin D2 Synthase, Brain Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?176803
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Prostate Cancer/Brain Cancer Susceptibility Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603688
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Ras Homolog Enriched in Brain 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601293
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Solute Carrier Family 25 (Mitochondrial Carrier, Brain), Member 14 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300242
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Superconserved Receptor Expressed in Brain 3 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300253
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T-Box, Brain, 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?604616
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Tubulin, Alpha, Brain-Specific Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602529 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
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Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
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Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
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Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
Physician Resources
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
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To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “brain” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database25 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database26 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “brain” (or synonyms) into the search box, and 25
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 26 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
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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 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. 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. 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”:
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Guides on brain Brain Cancer http://www.nlm.nih.gov/medlineplus/braincancer.html Brain Cancer http://www.nlm.nih.gov/medlineplus/tutorials/braincancerloader.html Brain Diseases http://www.nlm.nih.gov/medlineplus/braindiseases.html
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Other guides Anatomy http://www.nlm.nih.gov/medlineplus/anatomy.html Aneurysms http://www.nlm.nih.gov/medlineplus/aneurysms.html Head and Brain Injuries http://www.nlm.nih.gov/medlineplus/headandbraininjuries.html Parkinson's Disease http://www.nlm.nih.gov/medlineplus/parkinsonsdisease.html
Within the health topic page dedicated to brain, the following was listed: •
General/Overviews Facts about Concussion and Brain Injury and Where to Get Help Source: National Center for Injury Prevention and Control http://www.cdc.gov/doc.do?id=0900f3ec8006c289 Head Injuries: What to Watch for Afterward Source: American Academy of Family Physicians http://familydoctor.org/084.xml
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Diagnosis/Symptoms Computed Tomography (CT)-Head Source: American College of Radiology, Radiological Society of North America http://www.radiologyinfo.org/content/ct_of_the_head.htm Functional MR Imaging (fMRI) - Brain Source: American College of Radiology, Radiological Society of North America http://www.radiologyinfo.org/content/functional_mr.htm Head Trauma Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=FA00008
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Treatment First Aid for Head Injuries Source: National Institute for Occupational Safety and Health http://www.cdc.gov/nasd/docs/d000801-d000900/d000815/d000815.html
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What Is Neurosurgery? http://www.nlm.nih.gov/medlineplus/tutorials/whatisneurosurgeryloader.html •
Specific Conditions/Aspects Brain Injuries and Mass Trauma Events Source: National Center for Injury Prevention and Control http://www.cdc.gov/masstrauma/factsheets/public/brain_injuries.htm Brain Pain: Recognizing a Subdural Hematoma Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=BN00015 Cerebral Hypoxia (Anoxia) Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/anoxia_doc.htm Coma, Including Persistent Vegetative State Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/coma_doc.htm Concussion Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00320 Intracranial Hematoma Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00330 JAMA Patient Page: Concussion in Sports Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZMFGAA9ND &sub_cat=187 Traumatic Brain Injury: Cognitive and Communication Disorders Source: National Institute on Deafness and Other Communication Disorders http://www.nidcd.nih.gov/health/voice/tbrain.asp Traumatic Brain Injury: No One Pathway to Recovery Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=BN00005
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Children Bump on the Head: When Is It Serious? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00763 Concussions Source: Nemours Foundation http://kidshealth.org/kid/ill_injure/aches/concussion.html Head Injuries Source: Nemours Foundation http://kidshealth.org/parent/firstaid_safe/emergencies/head_injury.html
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JAMA Patient Page: Inflicted Brain Injury in Children Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZ4SS4F0JD&s ub_cat=187 Shaken Baby Syndrome Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/shakenbaby.htm •
From the National Institutes of Health Traumatic Brain Injury: Hope Through Research Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/pubs/TBI.htm
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Law and Policy Bicycle Helmet Use Laws Source: National Highway Traffic Safety Administration http://www.nhtsa.dot.gov/people/injury/New-factsheet03/BicycleHelmetUse.pdf
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Organizations Brain Injury Association http://www.biausa.org/Pages/home.html National Center for Injury Prevention and Control http://www.cdc.gov/ncipc/ National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/
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Pictures/Diagrams Atlas of the Body: The Brain -- Lobes Source: American Medical Association http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZR9WH46JC &sub_cat=185 Atlas of the Body: The Brain -- Side View Source: American Medical Association http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZYUAM46JC &sub_cat=185 Atlas of the Body: The Skull Source: American Medical Association http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZCIHWBGJC &sub_cat=523
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Prevention/Screening Heads Up: Preventing Brain Injuries Source: National Center for Injury Prevention and Control http://www.cdc.gov/ncipc/pub-res/tbi_toolkit/patients/preventing.htm
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JAMA Patient Page: Protecting against Head Injuries Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZ8ZI10NAC& sub_cat=366 •
Research Knocking Noggins Source: Society for Neuroscience http://web.sfn.org/content/Publications/BrainBriefings/knocking.html Life and Death of a Neuron Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/pubs/NINDS_Neuron.htm
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Statistics Traumatic Brain Injury Facts and Statistics Source: National Center for Injury Prevention and Control http://www.cdc.gov/doc.do?id=0900f3ec800081d7
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Teenagers Concussions Source: Nemours Foundation http://kidshealth.org/teen/safety/first_aid/concussions.html Pre-Season Testing Can Lead to Better Management of Injured High School Athletes Source: American Association of Neurological Surgeons http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZPT89GR9C& sub_cat=405
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. 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: •
Facts About Concussion and Brain Injury Source: Atlanta, GA: National Center for Injury Prevention and Control. 199x. 18 p.
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Contact: Available from National Center for Injury Prevention and Control. Mailstop F41, 4770 Buford Highway, Atlanta, GA 30341. (770) 488-4642. Also available from www.cdc.gov/ncipc.tbi. PRICE: Single copy free. Summary: A blow or jolt to the head can disrupt the normal function of the brain. Doctors often call this type of brain injury a concussion or closed head injury. This brochure explains what can happen after a concussion, how to get better, and where to go for more information and help when needed. The brochure was written to help people who are treated for less severe brain injuries, either in hospital emergency departments or with brief hospital admission. The brochure reviews the health care provided to people with concussion, the danger signs of concussion in adults and in children, the symptoms of brain injury in adults, children, and in older adults, tips for healing (for adults and for children), and where to get help, including help for families and caregivers. Symptoms of brain injury related to communication disorders can include having trouble remembering things, experiencing slowness in thinking, acting, speaking or reading, having trouble with balance or feeling dizzy, or experiencing a ringing in the ears (tinnitus). The brochure concludes with a list of resources for additional information, including the help line and web site of the Brain Injury Association (BIA). •
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 fractures can result in facial paralysis, deafness, muscle disorders, and loss of sensory function. 8 references.
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Traumatic Brain Injury: Every Parent's Fear Source: in DeFeo, A.B., ed. Parent Articles 2. San Antonio, TX: Communication Skill Builders. 1995. p. 179-180. Contact: Available from Communication Skill Builders. Customer Service, 555 Academic Court, San Antonio, TX 78204-2498. (800) 211-8378; Fax (800) 232-1223. PRICE: $55.00 plus shipping and handling. Order Number 076-163-0732. Summary: In this fact sheet, from a communication skills book for parents, a parent of a child with a traumatic brain injury (TBI) discusses the emotions and psychological factors that may affect the parents of children with TBI. Topics covered include the author's family's story, coping immediately after the trauma occurs, later recovery,
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speech and language re-development, psychosocial concerns as the child progresses, the role of speech language therapy, dealing with the rehabilitation and insurance communities, and the need for parents to find their own support network. The author encourages parents to educate themselves, to draw on other parents for support, and to act as their child's advocate. •
National Alzheimer's Disease Autopsy and Brain Bank Source: La Jolla, CA: University of California, San Diego. [4 p.]. Contact: Available from University of California, San Diego. Department of Pathology, M-012, School of Medicine, La Jolla, CA 92093. (619) 534-6858 or (619) 534-1889; or Alzheimer's Association of San Diego, Inc. P.O. Box 99037, San Diego, CA 92109. Summary: The University of California, San Diego, School of Medicine has established the world's first Brain Bank devoted solely to research into the cause and treatment of Alzheimer's disease. There is no animal model for the disease so fresh human tissue is urgently needed for research. An autopsy will provide a family with a definitive statement as to whether the deceased did indeed have Alzheimer's disease. It is a service available to all Alzheimer's families and there is no charge except for transportation or shipping.
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Statewide Information Clearinghouse on Brain Impairment: National HeadquartersAssociations Source: San Francisco, CA: Family Survival Project. July 1992. 9 p. Contact: Family Survival Project. 425 Bush Street, Suite 500, San Francisco, CA 94108. (415) 434-3388 or (800) 445-8106 (in California). PRICE: Free. Summary: This alphabetical list provides the names, addresses, and phone numbers of 144 national headquarters and associations concerned with the needs of brain-impaired adults and their families.
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Patients With Brain Injury: A Family Guide to Assisting in Speech, Language and Cognitive Rehabilitation. 2nd ed Source: Austin, TX: Pro-Ed. 1995. 32 p. Contact: Available from Pro-Ed. 8700 Shoal Creek Boulevard, Austin, TX 78757. (512) 451-3246; Fax (512) 451-8542. PRICE: $6.00 plus shipping and handling. Item Number 6884. Summary: This booklet about recovery from brain injury and the rehabilitation process serves as a general guide for families. The authors emphasize that when family members better understand the process of recovery, they will be more confident about their role in the rehabilitation process. The authors include brief descriptions and suggestions on these topics: the family's role in early treatment; levels of cognitive functioning; and suggested goals and activities for improved speech, language, and cognition. Family members can help the patient reach various levels of recovery and improvement by actively participating during therapy. A glossary describing the rehabilitation team members and their roles concludes the booklet. A blank chart for recording progress in each of the areas discussed in also included. 1 table.
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Alzheimer's: A Broken Brain Source: Tuscalousa, AL: Dementia Education and Training Program. 1995. 10 p.
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Contact: Dementia Education and Training Program. 200 University Boulevard, Tuscalousa, AL 35401. (800) 457-5679. PRICE: $2.25 plus shipping. Summary: This booklet for caregivers illustrates the effects of Alzheimer's disease (AD) on the brain using color photographs of the brain and brain sections. The booklet presents side-by-side photographs of normal brains and AD brains to show the changes that occur as brain cells die in AD. Each set of photographs is accompanied by a brief description of the effect of those cellular changes on functions such as memory, language, thinking, emotions, and behavior. The booklet emphasizes that because AD patients' brains are dying, they have trouble remembering things; they have difficulty understanding words; they forget how to do ordinary things like dressing or shaving; they may forget familiar faces; they may have false ideas; they may see and hear things that are not real; they may get angry when they do not mean to; they can get frustrated easily; and they are still human and love their families. •
Vascular Dementia: An Explanation of Dementia Caused by Multiple Brain Strokes Source: Tuscaloosa, AL: Dementia Education and Training Program. 1995. 10 p. Contact: University Supply Store. Attn: Jef Smith, PO Box 870291, Ferguson Center, Tuscaloosa, AL 35487. (800) 825-6802. PRICE: $2.25. Summary: This booklet for families and other lay caregivers is designed to explain dementia caused by multiple small strokes (vascular dementia). It discusses how a stroke can be caused by the hardening of arteries that supply blood to the brain; and how the resulting damage can affect the patient's memory and speech, temper and personality, and ability to understand words. The text is accompanied by color photographs of normal and clogged blood vessels, and normal and stroke-damaged brains. Ten facts about vascular dementia are listed.
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Understanding Brain Death Source: New York, NY: National Kidney Foundation, Inc. 1996. 4 p. Contact: Available from National Kidney Foundation. U.S. Materials Orders, 30 East 33rd Street, New York, NY 10016. (212) 889-2210. Fax (212) 689-9261. PRICE: $15.00 for 100 copies. Item number: 06-20. Summary: This booklet helps define and explain brain death and provides information for family members of patients who have been declared brain dead. The diagnosis of brain death is defined as 'death based on the absence of all neurologic function.' The booklet, prepared by other families who have had a loved one declared brain dead, is designed to answer questions about brain death. Topics covered include a full definition of brain death, how brain death is determined (the tests undertaken), what happens to the patient during these tests, the role of drugs that can stop the brain from working and give a false diagnosis, why the heart still beats even during brain death, the difference between coma and brain death, what happens when the patient is declared brain dead, saying goodbye to a loved one who is brain dead, and making decisions about ventilator removal and the possibility of organ or tissue donation. The booklet emphasizes that brain death is permanent and irreversible. Information is provided to help the survivors through their time of grieving.
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After Traumatic Brain Injury: Helping Someone You Love During Early Rehabilitation Source: San Bruno, CA: Krames-Staywell. 1997. 16 p.
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Contact: Available from Krames-Staywell. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 244-4512. Website: www.krames.com. PRICE: $1.50 each; bulk copies available. Order number 1812-TXDT. Summary: This booklet helps families and caregivers understand their role as a family member undergoes rehabilitation after traumatic brain injury (TBI). The booklet emphasizes that recovering from brain injury is a lifelong process. Topics covered include the members of the patient rehabilitation team, the role of the family member, the physiology of the brain, how brain injury happens, the different types of brain injury (tearing, bleeding, swelling), how thinking skills are affected, strategies for helping patients with their thinking skills (to improve memory, link ideas, relearn language), strategies for help with the patient's senses (to regain balance, address problems with sight or sound, and deal with time), behavioral changes that may accompany brain injury and how to deal with them (to handle feelings, control agitation, and regain social skills), how to handle other physical problems (to improve posture and motion, reduce muscle and joint problems, reduce swallowing problems, and control seizures), and strategies to support family relationships. The booklet offers practical strategies for family members to apply in everyday activities. The brochure is filled with line drawings of families in various settings. The tollfree number of the National Brain Injury Association (800-444-6443) is provided as a resource. •
Traumatic Brain Injury: A Guide for the Patient and Family Source: Stow, OH: Interactive Therapeutics, Inc. 1993. 61 p. Contact: Available from Interactive Therapeutics, Inc. P.O. Box 1805, Stow, OH 44224. (800) 253-5111 or (216) 688-1371; Fax (330) 923-3030; E-mail:
[email protected]. PRICE: $4.50 each for 1 to 25 copies; bulk rates available. Summary: This booklet is intended to serve as an introduction to traumatic brain injury (TBI) and as a reference to other sources of information to guide patients and their families as they learn about TBI. Four sections cover brain function, TBI and how it affects the brain, what to expect during recovery and rehabilitation, and living and coping with TBI. The chapter on possible impairments from TBI includes a section on speech and language disorders, covering aphasia, communication problems, dysarthria, and apraxia of speech. The booklet concludes with an extensive glossary of terms.
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AIDS Dementia and HIV Brain Impairment Contact: AVERT, 4 Brighton Rd, Horsham, http://www.avert.org. Summary: This brochure about brain impairment related to the human immunodeficiency virus (HIV) is primarily for professionals working with persons with HIV-related brain impairment, but may be of interest to persons with HIV/AIDS and their families. The first section of the brochure provides an overview of the definition, diagnosis, and drug treatment of HIV-related brain impairment. Specific topics include the effect of HIV on the brain, opportunistic brain disease in HIV (e.g., cerebral toxoplasmosis, cryptococcal cytomegalovirus, progressive multifocal leucoencephalopathy, and brain lymphomas), the presentation of HIV brain impairment, the nature of HIV-related brain impairment (cognitive difficulties), general guidelines for providing help for someone with cognitive difficulties, and treatment and compliance issues in out- and inpatient settings. The second section describes assessment and management approaches that can be adopted as part of an approach to good service delivery. Specific topics include initiating assessments, the consequences of a diagnosis of HIV brain impairment, the aims of service provision, psychiatric liaison,
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the planning of care packages for people with HIV brain impairment, community provisions, maintenance of autonomy and decision-making by HIV brain-impaired persons, home care issues, the purpose and organization of day occupation, and multiple-problem patients. Sources of additional information are provided. •
Give the Greatest Gift.Brain Tissue for Alzheimer's Disease Source: Durham, NC: Consortium to Establish a Registry for Alzheimer's Disease. 1994. 2 p. Contact: Consortium to Establish a Registry for Alzheimer's Disease. Box 3203, Duke University Medical Center, Durham, NC 27710. (919) 286-6406. PRICE: $0.50 each for 1099 copies; $0.40 each for 100 or more copies. Summary: This brochure answers commonly asked questions about the donation of brain tissue for Alzheimer's disease research. It explains that brain tissue is needed to understand better the causes of memory loss and other mental or behavioral problems. There is no cost to the family for donation of brain tissue in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) program. The donation does not affect funeral arrangements for the patient. Procedures for providing consent, reasons why normal brain tissue also is needed for research, and ways information obtained from brain examinations benefits the family are explained.
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Brain Donation Program for Alzheimer's Disease and Healthy Volunteers: A Gift for the Future Source: Houston, TX: Alzheimer's Disease Research Center, Baylor College of Medicine. 1993. 4 p. Contact: Available from Alzheimer's Disease Research Center, Baylor College of Medicine. Department of Neurology, 6550 Fannin, Suite 1801, Houston, TX 77030. (713) 798-6660. PRICE: Free. Summary: This brochure describes the Brain Donation Program at the Baylor College of Medicine Alzheimer's Disease Research Center. The program seeks volunteers with Alzheimer's disease and healthy volunteers to donate brains for autopsy. The donations will contribute to research about the pathology, etiology, and genetics of Alzheimer's disease. The brochure includes an accompanying letter and permission form, and outlines reasons for participating in the program, steps to be taken upon deciding to participate, and steps to be taken when the participant dies. Also included is a notification sticker to be placed on the patient's file upon hospitalization or institutionalization.
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Join the NeuroExplorers in. BrainLink: A Project of Baylor College of Medicine Source: Houston, TX: Baylor College of Medicine. 1994. 6 p. Contact: Available from BrainLink Materials. 1709 Dryden, Suite 545, Houston, TX 77030. (713) 798-8200; FAX (713) 798-8201. PRICE: Free. Summary: This brochure describes the BrainLink educational project of the Baylor College of Medicine in Houston, Texas. BrainLink is designed to help elementary school and middle school students discover how their brains make them unique. The project uses special activities that help students explore concepts about the brain, the nervous system, and cutting- edge research and health issues. The project emphasizes natural
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links between science and other educational disciplines. Each topical unit contains activities that integrate science, literature, mathematics, health, and social studies. •
Del Oro Caregiver Resource Center for Caregivers of Brain Impaired Adults Source: Carmichael, CA: Del Oro Caregiver Resource Center. 6 p. Contact: Available from Del Oro Caregiver Resource Center. 5713A Marconi Avenue, Suite 300, Carmichael, CA 95608. (800) 635-0220 or (916) 971-0893. PRICE: Free. Summary: This brochure describes the goals, services, and eligibility requirements of a program provided by a California Regional Resource Center to aid adults who suffer from brain impairment due to various causes (Alzheimer's, Parkinson's, Huntington's and other degenerative diseases of the brain; stroke; traumatic brain injury; brain tumors). The Center was founded in 1984 to establish a coordinated resource system to meet the needs of brain impaired adults through assistance to their families, professionals, and other caregivers. The Center supplies information and referral services to caregivers of brain impaired adults, and provides contractual services for legal and financial advice, family counseling, respite care, and diagnostic assessment.
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Los Angeles Caregiver Resource Center: Part of a Statewide System of Regional Resource Centers Serving Families and Care Givers of Brain Impaired Adults Source: Los Angeles, CA: Los Angeles Caregiver Resource Center. 1991. [6 p.]. Contact: Available from Los Angeles Caregiver Resource Center. 3715 McClintock Avenue, Los Angeles, CA 90089-0191. (213) 740-8711 or (800) 540-4442. PRICE: Free. Summary: This brochure describes the Los Angeles Caregiver Resource Center, a program of the Andrus Older Adult Center at the University of California. The Center is part of a statewide system of regional resource centers serving families and caregivers of adults with permanent brain impairment due to Alzheimer's disease and other dementing illnesses, stroke and other cerebrovascular accidents, traumatic brain injury, brain tumors, and other conditions. The Center assists these caregivers directly by providing the following services: information and community resources, support groups, family consultations, respite care, legal and financial consultations, and workshops on issues related to caregiving. Families who reside in Los Angeles County are eligible for some or all of the services. The brochure describes these services and provides contact information for further inquiries.
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Brain Bank Source: Augusta, GA: Medical College of Georgia. 1991. [6 p.]. Contact: Available from Dr. Manuel Casanova, Medical College of Georgia. Department of Psychiatry and Health Behavior, 1515 Pope Avenue, Augusta, GA 30912-3800. (404) 721-3893 or (800) 733-1828. PRICE: Free. Summary: This brochure describes the tissue donation program of the Medical College of Georgia. The college accepts brain tissue from healthy individuals as well as persons who have neurological conditions such as Alzheimer's disease. Donated tissue is used for research and education on neurological disorders, including research to develop better treatments for these conditions.
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Religious Perspectives: Tissue Donation and Postmortem Human Brain Research Source: Belmont, MA: Harvard Brain Tissue Resource Center, McLean Hospital. 2000. 2 p. Contact: Harvard Brain Tissue Resource Center. McLean Hospital. 115 Mill Street, Belmont, MA 02478-9106. (800) 272-4622. FAX: (617) 855-3199. Website: www.brainbank.mclean.org:8080. PRICE: free. Publication number: HBTRC4/00. Summary: This brochure presents selected religious perspectives on tissue donation and postmortem human brain research. Although positions vary from one denomination to another, the majority of religions appear to support postmortem brain tissue donation and research. While some faiths have very particular laws governing the circumstances of donation, the mandate to heal and the call to compassion are recognized as fundamental to all religions. This brochure summarizes the perspectives of Protestant Christianity, Catholicism, Judaism, Greek Orthodox, Islam, Buddhism, Hinduism, Jehovah's Witness, and Christian Scientists. (See AZBR09166 for a brochure on brain donation to the Harvard Brain Tissue Resource Center.).
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Brain Donation Information for Neurological Diseases Source: Belmont, MA: Harvard Brain Tissue Resource Center, McLean Hospital. 2000. 2 p. Contact: Harvard Brain Tissue Resource Center. McLean Hospital. 115 Mill Street. Belmont, MA 02478-9896. (800) 272-4622. PRICE: free. Publication number HBTRC1/00. Summary: This brochure provides information about brain donation to the Harvard Brain Tissue Resource Center. The Center has been established as a centralized resource for the collection and distribution of human brain specimens for research in a broad range of neurological disorders, including Huntington's disease, Parkinson's disease, and progressive supranuclear palsy. It explains donation eligibility and restrictions, types of tissue donation, how to initiate the brain donation process, general information about the donation procedure, and steps for a successful brain donation. A brain donation registration form is included. (See AZBR09167 for a brochure summarizing selected religious perspectives on tissue donation.).
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Glimpse of the Brain: The Acoustic Neuroma Connection Source: Atlanta, GA: Acoustic Neuroma Association. March 1998. 15 p. Contact: Available from Acoustic Neuroma Association (ANA). 600 Peachtree Parkway, Suite 108, Cumming, GA 30041-8211. (770) 205-8211. Fax (770 www.ANAUSA.org. PRICE: $1.50 plus shipping and handling. Summary: This brochure reprints an article from the quarterly newsletter of the Acoustic Neuroma Association on the nervous system and acoustic neuromas. Topics covered include the structure and function of the parts of the brain; the anatomic location of the cranial nerves; the anatomic basic for acoustic neuroma symptoms; auditory symptoms; unsteadiness and vertigo; facial weakness and eye tearing; facial numbness; facial pain; incoordination in extremities; double vision; difficulty swallowing; weakness or loss of sensation in extremities; and headaches. The brochure includes space for readers to record notes. 6 figures.
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Brain Autopsy: A Guide for Funeral Directors Source: Chicago, IL: Alzheimer's Association. 1999. 2 p.
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Contact: Alzheimer's Association. 919 North Michigan Avenue, Suite 1100, Chicago, IL 60611-1676. (800) 272-3900. Internet: http://www.alz.org. PRICE: 1 copy free. $8 per 100. Contact your local Alzheimer's Association chapter. Item Number: PF211Z. Summary: This document is designed to help funeral directors work with families who request a brain autopsy for a loved one with Alzheimer's disease. First, it outlines the reasons why families may request a brain autopsy, including confirmation of diagnosis, research advancement, and accurate reporting. Then, it answers some of the questions families may have about whether brain autopsy causes disfigurement, whether it will delay funeral arrangements, how long it will take to get the results, how much it costs, and whether the loved one's organs can be donated. Finally, it suggests ways the funeral director can support families, both when the necessary pre-arrangements have been made, and when they have not been made. •
Brain Development Source: [St. Paul, MN]: Minnesota Coalition for Family Policy. [ca. 1999]. 2 pp. Contact: Available from Minnesota Coalition for Family Policy, 1295 Bandana Boulevard, North, Suite 210, St. Paul, MN 55108. Telephone: (651) 637- 2470 / fax: (651) 647-4623 / e-mail:
[email protected] / Web site: http://www.cyfc.umn.edu/mcfp/. Available from the Web site at no charge. Summary: This fact sheet discusses how children's early experiences affect how their brains develop, and how a variety of factors, including unresponsive or inconsistent care, can affect this development.
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Brain Concepts: How the Brain Ages Source: Washington, DC: Society for Neuroscience. 1992. 4 p. Contact: Society for Neuroscience. 11 Dupont Circle, NW, Suite 500, Washington, DC 20036. (202) 462-6688. PRICE: 50 cents each; sent in eight title bundles, $4.00. Summary: This fact sheet discusses normal changes in the brain due to aging and the effect of these changes on reasoning and other intellectual activities. Following an examination of brain structure and function and the effects of aging on neurons, this fact sheet addresses potential therapies for cognitive decline and the dementias. It also discusses the use of mental exercises to keep the brain active, and examines intellectual capacity during the aging process. It shows the ability of the brain to expand its capacity to learn when it is stimulated by the surrounding environment. It concludes by highlighting several common sense approaches to keeping mentally fit.
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Brain Concepts: Genes and the Brain Source: Washington, DC: Society for Neuroscience. 1992. 4 p. Contact: Society for Neuroscience. 11 Dupont Circle, NW, Suite 500, Washington, DC 20036. (202) 462-6688. PRICE: 50 cents each, sent in eight title bundles, $4.00. Summary: This fact sheet discusses the role of genetic research in the identification and development of potential therapies for brain diseases and explains the Human Genome Project. Scientists have identified 20 neurological disorders and the chromosomal location of the defect in 50 to 100 of them. Gene mapping has led to the localization on chromosome 21 of the gene coding the beta amyloid precursor, the protein that is cut abnormally to form the smaller peptide, beta amyloid. It is this peptide that accumulates in plaques in Alzheimer's disease. New molecular genetic technology has allowed the
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development of animal models of genetic diseases that help scientists better understand many brain disorders. Potential therapies to the brain are being generated through genetic engineering techniques. This fact sheet highlights additional scientific advancements, such as the development of immortalized neurons and the cloning and sequencing of genes resulting in new treatments such as the rational drug design. •
Prevalence of Traumatic Brain Injury in the United States Source: Rockville, MD: American Speech-Language-Hearing Association (ASHA), Science and Research Department. 1995. 1 p. Contact: Available from American Speech-Language-Hearing Association (ASHA). Science and Research Department. 10801 Rockville Pike, Rockville, MD 20852. (301) 8975700. PRICE: Single copy free. Summary: This fact sheet from the American Speech-Language Hearing Association (ASHA) provides information on the prevalence of traumatic brain injury in the United States. Topics covered include communication disorders resulting from traumatic brain injury, statistics on head trauma, the most common causes of head injuries and the most common victims, survival rates, language function and brain hemisphere, hematomas, and prognostic considerations. 5 references.
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Evaluating Research Findings on Brain-Impairing Conditions Source: San Francisco, CA: Family Survival Project. 1989. 2 p. Contact: Available from Family Survival Project. 425 Bush Street, Suite 500, San Francisco, CA 94108. (415) 434-3388. PRICE: Single copy free. Summary: This fact sheet offers guidelines to help families of persons with brain impairing conditions evaluate research findings on possible treatments. The purpose is to help family members sort through the information presented in newspapers, magazines, and television and radio news stories and to distinguish fact from speculation. The guidelines can help families evaluate reports of new treatments for Alzheimer's disease. The fact sheet urges the reader to locate and thoroughly examine the original research article. It also outlines the key points to consider when evaluating the research and determining its applicability to individual situations.
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How to Form a Support Group for Families of Brain-Impaired Adults Source: San Francisco, CA: Family Survival Project. 1989. 3 p. Contact: Available from Family Survival Project. 425 Bush Street, Suite 500, San Francisco, CA 94108. (415) 434-3388. PRICE: Single copy free. Summary: This fact sheet offers suggestions to help families of brain impaired adults develop a support group. The information can be useful for families of persons with Alzheimer's disease who would like to share information and support with other people in a similar situation. The fact sheet offers tips for getting started and for planning the group structure, goals, and agendas. It includes a list of recommended readings and resources for additional information.
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Know Your Brain Source: Bethesda, MD: Neurological Institute. 1992. 8 p.
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Contact: Neurological Institute. P.O. Box 5801, Bethesda, MD 20824. (301) 496-5751 or (800) 352-9424. Summary: This fact sheet presents basic introductory material on the human brain. It describes how the healthy brain works, how to keep it healthy, and what happens when the brain is diseased or dysfunctional. The brain is divided into the forebrain, midbrain, and hindbrain. The hindbrain, including the cerebellum, the brain stem, and the upper part of the spinal cord, controls the body's vital functions, such as respiration and heart rate, as well as movements learned by rote. The midbrain controls some reflex actions and voluntary movements, and the forebrain enables thought and memory storage. The portions of the brain responsible for thoughts, sensations, and voluntary movements comprise the frontal, parietal, occipital, and temporal lobes. The cerebral cortex, or coating of the brain, is where information processing occurs. The inner brain, including the hypothalamus, thalamus, hippocampus, and basal ganglia, controls emotional states and perceptions. Structures connecting these major parts of the brain are the dendrites, axons, and axonal sheath, which acts as an insulator. Neurotransmitters help signals move from nerve cell to nerve cell and are secreted by sacs at the ends of axons. Common neurotransmitters are acetylcholine, gamma- aminobutyric acid, serotonin, and dopamine. Neurological disorders, including Alzheimer's disease, are listed that alter the brain's ability to function properly. 7 figures. •
Traumatic Brain Injury: Cognitive and Communication Disorders Source: Bethesda, MD: National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH). July 1998. [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. NIH Publication Number 98-4315. Summary: This fact sheet provides basic information about traumatic brain injury (TBI), defined as sudden physical damage to the brain. The fact sheet outlines the possible causes of TBI, and the resulting brain injuries. The author notes that major speech and language areas often receive damage in TBI, resulting in communication difficulties. Other problems due to TBI can be voice, swallowing, walking, balance, and coordination difficulties, as well as changes in the ability to smell and in memory and cognitive (thinking) skills. The fact sheet reports some statistics about who suffers from TBI, and outlines more specifically the cognitive and communication problems that can result from TBI. The fact sheet also briefly considers assessment of these cognitive and communication problems, as well as treatment options. Therapy usually focuses on regaining lost skills as well as on learning ways to compensate for abilities that have been permanently changed because of the brain injury. The fact sheet concludes with a brief description of current research efforts in this area, and a listing of organizations through which readers can get additional information. 1 figure.
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Brain MRI in Children with Large Cutaneous Melanotic Nevi Source: Bartlesville, OK: Nevus Outreach, Inc. 2002. 1 p. Contact: Available from Nevus Outreach, Inc. 1601 Madison Boulevard, Bartlesville, OK 74006. (877) 426-3887 or (918) 331-0595. E-mail:
[email protected]. Website: www.nevus.org. PRICE: Single copy free.
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Summary: This fact sheet provides health professionals with information on brain magnetic resonance imaging (MRI) in children with large cutaneous melanotic nevi. The main reason for an MRI in these children is to look for the presence of melanin in the brain. The fact sheet explains what an MRI is and describes the magnetic resonance techniques used to find melanin. In addition, the fact sheet explains the meaning of findings for T1 and T2 weighted images. 1 figure. •
The Comprehensive Act for Families and Caregivers of Brain-Impaired Adults Source: San Francisco, CA: Family Caregiver Alliance. 1994. 1 p. Contact: Family Caregiver Alliance. 425 Bush Street, Suite 500, San Francisco, CA 94108. (415) 434-3388; (800) 445-8106; (415) 434-9508. PRICE: Free. Summary: This fact sheet provides the legislative history and details of the Comprehensive Act for Families and Caregivers of Brain-Impaired Adults (Chapter 1658). The Act was designed to enable regions within California to develop programs that provide assistance to families, document their needs, conduct training for caregivers and professionals, and recommend statewide solutions to the problems families and caregivers face when caring for someone who is brain impaired. The law defines brain impairment as significant destruction of brain tissue with resultant loss of brain function, that includes Alzheimer's disease. Service eligibility is not based on a client's income. Current funding for Chapter 1658 involves $5.25 million for 11 Caregiver Resource Centers, the Statewide Resources Consultant, and the Department of Mental Health. (See AZBR05016).
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Visceral Sensations and Brain-Gut Mechanisms Source: Milwaukee, WI: International Foundation for Functional Gastrointestinal Disorders. 1996. 2 p. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217. (888) 964-2001 or (414) 9641799. Fax (414) 964-7176. E-mail:
[email protected]. Website: www.iffgd.org. PRICE: $0.50. Summary: This fact sheet reports on research that investigates visceral (physical or bodily) sensations and brain-gut mechanisms and their role in functional bowel disorders (FBD). The most common symptoms of patients with FBD are related to altered perception of sensations arising from the gastrointestinal tract. Sensations of bloating, fullness, gas, incomplete rectal evacuation, and crampy abdominal pain are the most common symptoms. The author explores the features which are unique to the sensory stimulation of the gastrointestinal tract (different from the sensory stimulation of the rest of the body). The brain has mechanisms to prevent the conscious mind from being aware of many things going on in the body. The author of this fact sheet hypothesizes that for people with FBD, this mechanism may not work well, resulting in a heightened awareness of stimuli from the gastrointestinal tract. The author also discusses the interaction between stimulation and the development of hypersensitivity and how this differs in people with FBD compared to those without FBD. The author ponders whether some of the visceral sensations (including abdominal pain and discomfort) may be recalled from memory banks within the limbic system in a way that is somehow related to emotional experience earlier in life, or linked in a nonspecific way to the general stress response. (AA-M).
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Traumatic Brain Injury Source: in DeFeo, A.B., ed. Parent Articles 2. San Antonio, TX: Communication Skill Builders. 1995. p. 145-148. Contact: Available from Communication Skill Builders. Customer Service, 555 Academic Court, San Antonio, TX 78204-2498. (800) 211-8378; Fax (800) 232-1223. PRICE: $55.00 plus shipping and handling. Order Number 076-163-0732. Summary: This fact sheet, from a communication skills book for parents, provides information on traumatic brain injury (TBI). The authors outline the cognitivecommunicative problems that can result from TBI, including attention problems, information-processing problems, the lack of vocabulary development, hyperverbal speech, tangential speech, word-finding problems, poor social language skills, nonverbal or motor speech problems, delayed language development, and memory problems. The authors also provides specific suggestions for families who want to help their child who is struggling with TBI-related communication problems. The authors encourage parents to incorporate these suggestions into everyday routines and to act as their child's advocate. 1 reference.
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National Alzheimer's Disease Autopsy-Brain Bank Research Instructions Source: La Jolla, CA: University of California, San Diego. 1987. [4 p.]. Contact: Available from University of California, San Diego. Department of Pathology, 0612, School of Medicine, La Jolla, CA 92093. (619) 534-6858. Summary: This factsheet provides instructions on how families with Alzheimer's disease can participate in the National Alzheimer's Disease Brain Bank and Research Program. An autopsy consent form is included, along with a questionnaire on patient characteristics.
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Brain Pack: An Interactive, Three-dimensional Exploration of the Mysteries of the Mind Source: Philadelphia, PA: Running Press Book Publishers. 1996. Datchet, Berkshire, England: Van der Meer Publishing. 1996. Contact: Available from online book dealers, such as Amazon.com. No longer available from publisher. PRICE: Ranges from $23.95 to $40.00, new and used. ISBN: 1561387460. Summary: This information pack is an interactive, three-dimensional exploration of the human brain. Seven pop-up spreads with more than 100 color illustrations provide a tour of basic brain anatomy, emotions, the senses, consciousness, differences in male and female brains, intelligence and language, and memory. Hands-on features include pop-up charts, pull-out flaps, fact-or-fiction games, memory exercises, pull-out pamphlets, experiments, brain teasers, puzzles, and optical illusions. The pack includes a 15-minute audiocassette tour of the brain, a set of cards for testing psychic ability, and tests for evaluating IQ and short-term memory skills.
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National Alzheimer's Disease Autopsy Brain Bank and Research Source: San Diego, CA: University of California at San Diego. National Alzheimer's Disease Brain Bank and Research. Spring 1991. 5 p.
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Contact: Available from University of California at San Diego. National Alzheimer's Disease Brain Bank and Research Program. 9500 Gillman Drive, La Jolla, CA 92093-0612. (619) 534-6858 or (619) 534-8852. PRICE: Single copy free. Summary: This information packet provides instructions for anyone outside of San Diego County, California, who wishes to participate in the University of California, San Diego, National Alzheimer's Disease Autopsy Brain Bank and Research Program. It tells what should be done both prior to death and at the time of death to donate tissue to the brain bank and to have an autopsy performed. The packet also includes instructions for the necessary postmortem procedures and for the shipping of the brain and brain tissue to the brain bank, and a sample form for researchers requesting tissue or fluids from the brain bank. •
SIDS and the Brain Stem Source: Minneapolis, MN: Minnesota Sudden Infant Death Center. 1993. 1 pp. Contact: Available from Minnesota Sudden Infant Death Center, Children's Hospitals and Clinics, 2525 Chicago Avenue South, Minneapolis, MN 55404. (612) 813-6285, (800) 732-3812 (in MN), (612) 813-7344 (Fax). Free to SIDS families. Summary: This information sheet presents the hypothesis that a brain stem maturation defect may be present in some sudden infant death syndrome (SIDS) victims. The publication summarizes the research that supports this hypothesis, emphasizes the importance of research on brain stem abnormalities as a possible cause of SIDS, and explains the difficulties involved in such research.
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Starting smart: How early experiences affect brain development Source: Chicago, IL: Ounce of Prevention Fund. 1996. 6 pp. Contact: Available from Ounce of Prevention Fund, 122 South Michigan Avenue, Suite 2050, Chicago, IL 60603. Telephone: (312) 922-3863 / fax: (312) 922-3337 / e-mail:
[email protected]. Summary: This pamphlet describes how good infant care must include talking to, stimulating, and responding to the baby in order to promote the development of intelligence and emotional stability. Research examples support the discussion. The text clarifies the relationship between cognitive development and developing emotional trust in others, self-confidence and self-control.
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Medicine for the Layman: Brain in Aging and Dementia Source: Bethesda, MD: National Institutes of Health. 33 p. Contact: Alzheimer's Disease Education and Referral (ADEAR) Center. PO Box 8250, Silver Spring, MD 20907-8250. (800) 438-4380; (301) 495-3311; FAX (301) 495-3334. Internet access: http://www.alzheimers.org. PRICE: Single copy free. Order Number Z04. Summary: This pamphlet explains brain anatomy and physiology to the layperson and discusses changes to the brain which occur in aging. It also informs the reader about various kinds of dementia and explains new directions in dementia research.
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Incidence and Prevalence of the Major Causes of Adult-Onset Brain Impairment in the United States and California Source: San Francisco, CA: Family Survival Project. 1992. [7 p.]. Contact: Available from Family Survival Project. 425 Bush Street, Suite 500, San Francisco, CA 94108. (415) 434-3388, (800) 455-8106 (in California), or FAX (415) 4343508. PRICE: Free. Summary: This statistical summary provides data estimating the incidence and prevalence of the major causes of brain impairment in adults throughout the United States, with specific statistics provided for California. The data show that between 10.7 and 14.9 million Americans aged 18 and over have some type of adult-onset brain impairment. The first table lists the estimated prevalence and high estimate prevalence for Alzheimer's disease and dementias, amyotrophic lateral sclerosis, brain tumor, epilepsy, HIV (AIDS) dementia, Huntington's disease, multiple sclerosis, Parkinson's disease, stroke, and traumatic brain injury. The second table shows the incidence rate per year for each of the above diagnoses. The third table shows demographic statistics for brain-impaired adults, including age, number affected, and average family size and compares those numbers to the total United States and California populations. References are provided for each table.
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Wherever You Live, There's Help: Resources for the Families and Caregivers of BrainImpaired Adults Source: San Francisco, CA: Family Caregiver Alliance. 1994. 1 p. Contact: Family Caregiver Alliance. 425 Bush Street Suite 500, San Francisco, CA 94108. (415) 434-3388; (800) 445-8106. PRICE: Free. Summary: Under a State law, Chapter 1658, the California Department of Mental Health was directed to establish and fund an information network accompanied by an array of appropriate programs and services for brain-impaired adults and their families. This brochure describes the California Caregiver Resource Center System designed to serve families and caregivers of persons with adult-onset chronic and disabling brain diseases and disorders including Alzheimer's disease. Resource Center services are described and 11 locations are listed along with their addresses and phone numbers. (see AZDC05015). The National Guideline Clearinghouse™
The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “brain” (or synonyms). The following was recently posted: •
(1) Part I. Guidelines for the management of severe traumatic brain injury. In: Management and prognosis of severe traumatic brain injury. (2) Update notice. Guidelines for the management of severe traumatic brain injury: cerebral perfusion pressure Source: American Association of Neurological Surgeons - Medical Specialty Society; 2000 (revised 2003); 165 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3794&nbr=3020&a mp;string=brain
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ACR Appropriateness Criteria for multiple brain metastases Source: American College of Radiology - Medical Specialty Society; 1999; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2504&nbr=1730&a mp;string=brain
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ACR Appropriateness Criteria for pre-irradiation evaluation and management of brain metastasis Source: American College of Radiology - Medical Specialty Society; 1999; 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2502&nbr=1728&a mp;string=brain
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ACR Appropriateness Criteria for solitary brain metastasis Source: American College of Radiology - Medical Specialty Society; 1999; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2503&nbr=1729&a mp;string=brain
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Guidelines for prehospital management of traumatic brain injury Source: Brain Trauma Foundation - Disease Specific Society; 2000; 81 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3288&nbr=2514&a mp;string=brain
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Part II. Early indicators of prognosis in severe traumatic brain injury. In: Management and prognosis of severe traumatic brain injury Source: American Association of Neurological Surgeons - Medical Specialty Society; 2000; 116 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3122&nbr=2348&a mp;string=brain
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Practice management guidelines for the management of mild traumatic brain injury Source: Eastern Association for the Surgery of Trauma - Professional Association; 2000; 29 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2793&nbr=2019&a mp;string=brain
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Practice parameter: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Source: American Academy of Neurology - Medical Specialty Society; 2000 May; 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2823&nbr=2049&a mp;string=brain
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Procedure guideline for brain perfusion single photon computed tomography (SPECT) using Tc-99m radiopharmaceuticals Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 1999 February; 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1334&nbr=602&am p;string=brain
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Universe of Florida patients with acute ischemic brain attack Source: Florida Agency for Health Care Administration - State/Local Government Agency [U.S.]; 1999 March 5; 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1801&nbr=1027&a mp;string=brain 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: •
A Guide to Selecting and Monitoring Brain Injury Rehabilitation Services Summary: This document provides information that's designed to assist the person with a brain injury and their family in choosing rehabilitation services which best meet all of their needs. Source: Brain Injury Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4884
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Adult Aphasia: Recent Research Summary: This consumer health education brochure provides basic information about aphasia, a language disorder that results from damage to portions of the brain that are responsible for language. Source: National Institute on Deafness and Other Communication Disorders Information Clearinghouse http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=31
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Adult Brain Tumors (PDQ®): Treatment Information for Patients Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4820
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Alzheimer's Disease Research Summary: Alzheimer's disease is a progressive, irreversible brain disorder with no known cause or cure. It attacks and slowly steals the minds of its victims. Source: American Health Assistance Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6683
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Brain and Spinal Cord Tumors -- Hope Through Research Summary: This brochure is designed to convey to patients and their families the latest research information on the diagnosis, course, and treatment options of various brain and spinal cord tumors. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=774
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Brain Basics - Preventing Stroke Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5431
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Brain Basics: Sleep Summary: This brochure presents a general overview of sleep and the effects of sleep on our daily functioning and our physical and mental health. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=791
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Brain Sprain Summary: Fun and games site for kids with diabetes or for children interested in learning about diabetes. Play air hockey or solve a crossword puzzle. Source: American Diabetes Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5909
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Brain's Response to Drugs: Teacher's Guide Summary: This is the teacher's guide for the Source: National Institute on Drug Abuse, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6434
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Brainteasers & Riddles!, National Institute of Environmental Health Sciences Summary: Get hundreds of brainteasers and riddles about the environment and health for kids to solve. Source: National Institute of Environmental Health Sciences, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5701
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Childhood Brain Tumors (PDQ®): Treatment Information for Patients Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4821
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Depression and Parkinson's Disease Summary: Depression can strike anyone, but people with Parkinson's disease, a progressive brain disorder affecting more than 500,000 Americans, may be at greater risk. Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6898
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Dictionary for Brain Tumor Patients Summary: Browse this site for online assistance in finding basic definitions for some general or specific medical and scientific terms, symbols and acronyms related to brain tumors. Source: American Brain Tumor Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=1984
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DreamLine: Free Travel for Children Coping With Serious Illness Summary: This is the web site of an organization that provides free vacation travel for children currently undergoing treatment for (or recovering from) a brain tumor, cancer, or leukemia. Source: Commercial Entity--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4763
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Facts About Progressive Supranuclear Palsy.PSP Summary: PSP is a rare, degenerative brain disorder related to Parkinson's disease. It strikes middle aged adults and the elderly, slightly more men than women and affects 6.4 in 100,000. Source: Society for Progressive Supranuclear Palsy http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7729
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Going to Extremes: Bipolar Disorder Summary: Bipolar disorder, also known as manic-depressive illness, is a serious brain disease that causes extreme shifts in mood, energy, and functioning. It affects approximately 2. Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6599
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Hydrocephalus Fact Sheet Summary: This consumer information fact sheet provides basic information about this neurological disorder--the abnormal accumulation of fluid, (cerebrospinal fluid, or CSF), within cavities of the brain. Source: Hydrocephalus Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2594
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Interactive Tour of the Brain Summary: Features eight views of the brain, brain anatomy, and brain function. Source: National Brain Tumor Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6524
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Juvenile Hemochromatosis & non-HFE related iron overload in youths Summary: Hemochromatosis is a genetic metabolic disorder where a person absorbs too much iron and can result in dangerously high accumulation of iron in vital organs such as liver, heart, joints and brain Source: Iron Disorders Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7786
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Keep Your Brain Healthy: Don't Use Drugs Summary: A National Institute on Drug Abuse (NIDA) nation wide public service campaign designed to help America's youth understand the risks associated with drug use. Source: National Institute on Drug Abuse, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5503
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Mind Over Matter Series Index Summary: The Mind Over Matter series is designed to encourage young people in grades five through nine to learn about the effects of drug abuse on the body and the brain. Source: National Institute on Drug Abuse, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3804
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Occupational Therapy And People With Alzheimer's Disease Summary: Alzheimer's disease, a condition that affects the brain, occurs in middle or late life, striking men and women of all races, cultures, and backgrounds. Source: American Occupational Therapy Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7305
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Primer of Brain Tumors Summary: The Primer of Brain Tumors is a reference manual for learning about, and better understanding, brain tumors. Source: American Brain Tumor Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6554
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Research Training And Career Development Grants -- National Institute of Neurological Disorders and Stroke Summary: Researchers can browse this site for information about federal grants, funding and contracts related to biomedical research on disorders of the brain and nervous system. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3795
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Sara's Quest Summary: Sara's Quest is a science-based drug abuse educational game. Players search out the correct answers to questions about how marijuana affects the brain. Source: National Institute on Drug Abuse, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5668
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Teenage Brain: A Work in Progress Summary: New imaging studies are revealing—for the first time—patterns of brain development that extend into the teenage years. Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6653
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Traumatic Brain Injury Source: National Information Center for Children and Youth with Disabilities, U.S. Department of Education http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3418
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Traumatic Brain Injury (TBI)-Effects and Intervention Summary: healthfinder® — your guide to reliable health information health library just for you health care organizations search: go help | about healthfinder® Traumatic Brain Source: American Occupational Therapy Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7342
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Traumatic Brain Injury Information Page Summary: A general overview of traumatic brain injury that includes a description of the disorder, treatment, prognosis and research information. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3042
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Traumatic Brain Injury: Hope Through Research Summary: Traumatic brain injury (TBI) is a major public health problem, especially among male adolescents and young adults ages 15 to 24, and among elderly people of both sexes 75 years and older. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7201
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Understanding Autism Summary: Autism is a developmental disability that affects how the brain functions, specifically those areas of the brain that control social ability and communication skills. Source: American Occupational Therapy Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7292
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What We Learned From Songbirds: The Adult Brain Can Generate New Nerve Cells Summary: This 2-page fact sheet describes the process of neurogenesis and the implications for therapeutic interventions. Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6632
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What You Need To Know About™ Brain Tumors Summary: This booklet describes the symptoms, diagnosis, and treatment of brain tumors. Source: Cancer Information Service, National Cancer Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7119 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. 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
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMD®Health: http://my.webmd.com/health_topics
News Services and Press Releases One of the simplest ways of tracking press releases on brain 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” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days.
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Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to brain. 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” (or synonyms). 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” (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” (or synonyms). If you know the name of a company that is relevant to brain, 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” (or synonyms).
Newsletters on Brain Find newsletters on brain using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “brain.” 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.” Type “brain” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •
Brain in the News Source: New York, NY: Dana Alliance for Brain Initiatives. 1994. [30 p. average]. Contact: Dana Alliance for Brain Initiatives. 745 Fifth Avenue, Suite 700, New York NY 10151. (212) 223-4040; FAX (212) 593-7623. PRICE: Free. Summary: This newsletter clipping service, published monthly, provides a collection of news articles and book reviews that deal with the subject of the brain. Articles cover such areas as dementia and Alzheimer's disease, brain research, AIDS and its effects on the brain, brain chemistry, psychological disorders, genetics, hormone imbalances, and drug therapy.
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BrainWork: The Neuroscience Newsletter Source: Washington, DC: Charles A. Dana Foundation. 1991-. Bimonthly. [8 p. average]. Contact: Charles A. Dana Foundation. 1001 G Street, NW, Suite 1025, Washington, DC 20001. (202) 737-9200. PRICE: Free. Summary: This newsletter is designed to provide information on neuroscience research and other issues related to brain function to researchers, physicians, and those interested in cognitive function and impairment. Typical topics explore issues related to Alzheimer's disease and other brain impairment due to aging, research advances in studying brain function, selected comments on drug therapies or misuse, and annotated bibliographies of related publications.
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Brain Briefings Source: Washington, DC: Society for Neuroscience. 1994-. [2 p. average]. Contact: Society for Neuroscience. 11 Dupont Circle, NW, Suite 500, Washington, DC 20036. (202) 462-6688. PRICE: $1.00 each, single copy free to members. Summary: This newsletter on the brain describes the progress of science, provides information about the diseased brain, and explains potential treatment. It also describes with basic discoveries that usually do not have a specific clinical application, but eventually may lead toward a human benefit. Sample newsletters discuss neurotrophic factors, which are responsible for the growth and survival of neurons during
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development and for maintaining adult nerve cells (neurons). This could be useful in the treatment of Alzheimer's disease. Other proteins include a signalling chemical called glutamate that can build up through oxygen deprivation in the brain and kill neurons by overstimulating them. Sample newsletters also describe a group of neurons within the visual cortex that selectively respond to visual information from one eye or the other; opiate receptors, their effects on the body, and possible uses in pain relief; neuroscience; and rapid eye movement and the study of sleeping disorders. •
Noteworthy Brains Source: Durham, NC: Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropathology Task Force. 1991. 2 p. (approximately). Contact: Available from Arthur Clark, Editor. Department of Pathology, University of Calgary, 3330 Hospital Drive, NW, Calgary, Alberta T2N 4N1, CANADA. (403) 6704761. PRICE: Call for price information. Summary: This newsletter was established by a group of neuropathologists with the goal of creating a forum to report interesting phenomena in patients with dementia, including Alzheimer's disease; to request and exchange tissue samples; and to support professional communication on the neuropathology of dementia, particularly Alzheimer's disease. The newsletter includes case reports and requests for tissue samples for research.
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” (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: •
TorsinA Immunostaining in the Normal Human Brain and in DYT1 Dystonia Brain Source: Dystonia Dialogue. 23(4): 6-7. December 2000-January 2001. Contact: Available from Dystonia Medical Research Foundation. One East Wacker Drive, Suite 2430, Chicago, IL 60601-1905. (312) 755-0198. Fax (312) 803-0138. E-mail:
[email protected]. Website: www.dystonia-foundation.org. Summary: Dystonia refers to the continuous involuntary contraction of muscles in one or more parts of the body, resulting in twisted and distorted postures. Recently, the genetic defect responsible for one of the primary generalized dystonias, early onset torsion dystonia (DYT1 dystonia), has been identified. This article discusses the use of torsinA immunostaining in the normal human brain and in DYT1 dystonia brains. This devastating disorder first appears in patients between 5 and 27 years of age. It is the most frequent genetic form of dystonia and is caused by the deletion of an amino acid (glutamic acid) within a protein called torsinA. The authors describe their research in this area, reporting on the distribution of torsinA immunostaining in the brains of four genetically confirmed cases of DYT1 dystonia. In all four of these cases, torsinA staining
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is detected, demonstrating that the genetic mutation in the DYT1 gene is not associated with an absence of torsinA protein. The authors note that this is the first demonstration of torsinA protein in the DYT1 dystonia brain. The article concludes by noting the rarity of this disorder, and the ongoing need for human brains donated for medical research. Readers are encouraged to contact the University of Maryland Brain Bank for Developmental Disorders to obtain further information about brain donations. Through these brain donations, coupled with the dedication of the clinical and medical research community, the authors hope to gain insight into the pathophysiology of this disorder and ultimately to identify new therapies. •
Neuroimaging in Alzheimer's Disease: New Brain Scanning Techniques for Diagnosis and Research Source: Alzheimer's Disease and Related Disorders Association, Inc., Greater San Francisco Bay Area. [Newsletter] 7(3): 2. Summer 1988. Contact: Available from Alzheimer's Association, Greater San Francisco Bay Area Newsletter. 800 San Antonio Road, Palo Alto, CA 94303. (415) 856-1333. (800) 942-1333. Summary: This article describes recent developments in imaging the brain in the diagnosis of Alzheimer's disease. It describes the anatomy of the brain and explains positron emission tomography scanning and single photon emission computed tomography scanning. The author cautions that neither technique is proven as a diagnostic test, although they are the only sorts of scans which show abnormalities in the disease.
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Caring Touch: Working With the Brain That Remains Source: Wiser Now. 3(9):1-4. September 1994. Summary: This article tells how touch benefits people with Alzheimer's disease (AD). Benefits of massage are relaxation, which leads to greater ease in breathing, greater mobility, increased appetite, decreased muscle contraction, increased circulation, and lower heart rate and blood pressure. Touch may be a means for regaining contact with withdrawn people. Professional massage therapy is feasible in residential and daycare facilities and supplements compassionate touch provided by family members. Ways to instigate touch for those with barriers, either physical or emotional, include starting with a handshake or a pat on the back. This article also provides techniques for performing massage and applying lotions and examples on how massage therapy can help relieve physical and emotional symptoms, often leading to catastrophic outbursts.
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Language and the Brain Source: On the Brain. 4(4): 1-3, 6. Fall 1995. Contact: Available from Harvard Mahoney Neuroscience Institute. Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115. (617) 432-1000. Summary: This newsletter article discusses language and the brain. Topics covered include the role of language as a part of human culture; modern linguistics and the language code; language processing; techniques that allow researchers to 'watch' the brain speak and listen; left-brain versus right-brain and brain specializations for language; how the brain's language system is connected to other intellectual and motor systems; and diseases affecting language. The author stresses that it is now possible to make highly specific diagnoses of what language processes are affected in a particular
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language disorder, and recent work has begun to demonstrate that targeting these specific impairments can improve language functioning. •
Organ Study Focuses on Abnormal Brain Proteins Source: Alzheimer's Research Review. [Newsletter] p. 2. Summer 1989. Contact: Available from Alzheimer's Disease Research, American Health Assistance Foundation. 15825 Shady Grove Road, Suite 140, Rockville, MD 20850. (301) 948-3244 or (800) 437-2423. PRICE: Single copy free. Summary: This newsletter article discusses research at the Oregon Health Sciences University that explores why proteins present in normally healthy individuals form abnormal conditions in Alzheimer's patients. Specifically, the article addresses degenerating brain tissue, nerve tangles and plaques. Amyloid precursor protein (APP) is being studied to find out how it is synthesized and degraded, leading to the formation of abnormal nerve tissue in Alzheimer's disease. Findings that indicate which brain cells create APP and what regulates its breakdown in those cells may help to identify more effective methods of treatment in the future.
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Stopping the Brain Drain Source: Harvard Health Letter. 16(12): 6-8. [Newsletter] October 1991. Contact: Available from Harvard Health Letter. P.O. Box 420300, Palm Coast, FL 321420300. (617) 432-1485. PRICE: $24.00 for yearly subscription of 12 issues; single copies $4.00 each. Summary: This newsletter article discusses the Assessment of Cognitive Skills (ACS) test, a new, computerized test designed to measure the cognitive capabilities of older people. Over 1,000 physicians aged 28 to 92 took the test and results reinforced the belief that mental capacity diminishes with age. The test should enable researchers gain insight into the aging brain, test results may eventually help to pinpoint cognitive disorders such as Alzheimer's disease. The article also discusses anatomical and cognitive changes in the brain and cites environment, disease, and drug or alcohol dependence as factors that influence the 'normal' aging of a brain. The importance of acetylcholinesterase in neuron function is also explained. According to the author, several experimental cognitive-enhancing drugs are being studied. One researcher cites the increase of glucose delivery to the brain as an important feature in any cognitiveenhancing drug. Research into the interplay of brain chemicals is critical to the development of cognitive enhancers and improving brain function in older people.
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Depression in the Patient With Lupus: Is It Primary Depression or Is It Lupus Involving the Brain? Source: Happenings. 24(4):1; April 1997. Contact: Lupus Foundation of America, Connecticut Chapter, Inc., 45 South Main Street, Room 111, West Hartford, CT 06107. Summary: This newsletter article for health professionals offers advice for the treatment and management of depression in the lupus patient. Depression can result from the stress of dealing with lupus, but it can also be caused by the affect of lupus on the neurologic system. Subtle and obvious signs of depression are identified. The article identifies blood and other medical tests that may help the rheumatologist determine if the patient is having a lupus flare so that he or she may decide if the patient's depression
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is the result of a lupus flare. In addition, medications that may be helpful in treating a flare and depression are highlighted. •
Brain Chemical May Hold Clues to Alzheimer's Treatment Source: NIH Record. 44(22): 5. October 27, 1992. Summary: This newsletter article reports on the discovery of a link between acetylcholine and the body's ability to metabolize amyloid, a protein that causes harmful deposits in the brains of people with Alzheimer's disease. This research, supported by the National Institute of Mental Health and the National Institute on Aging, suggests that treatment with acetylcholine-acting drugs can slow the buildup of amyloid, possibly delaying the onset of Alzheimer's disease. The article discusses the physiological effects of amyloid on the brain and how the researchers conducted their investigation into this phenomenon. The researchers cite this connection between acetylcholine and delayed amyloid buildup as an important step in eventually finding a treatment for Alzheimer's disease.
Associations and Brain The following is a list of associations that provide information on and resources relating to brain: •
American Brain Tumor Association Telephone: (847) 827-9910 Toll-free: (800) 886-2282 Fax: (847) 827-9918 Email:
[email protected] Web Site: http://www.abta.org Background: The American Brain Tumor Association (ABTA) is an independent, notfor-profit organization founded in 1973. Services include more than 20 publications that address brain tumors, their treatment, and coping with the disease. These publications are written in easy-to-understand language. The materials address brain tumors in all age groups. The Association provides free social service consultations by telephone; a mentorship program for new brain tumor support group leaders; a nationwide database of established support groups; a rescue listing of physicians offering investigative treatments; the 'Connections' pen pal program; and an award-winning Internet site. The American Brain Tumor Association conducts national symposia and sponsors regional Town Hall meetings for patients and their families.
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Brain and Tissue Bank for Developmental Disorders at the University of Miami Telephone: (305) 243-6834 Toll-free: (800) 592-7246 Fax: (305) 243-6970 Email:
[email protected] Web Site: www.miami.edu/braintissue-bank/ Background: The Brain and Tissue Bank for Developmental Disorders at the University of Miami is a not-for-profit research organization dedicated to advancing meaningful research regarding developmental disorders. Established in 1993, the facility is committed to collecting, preserving, and distributing human tissues to qualified
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scientific investigators dedicated to the improved understanding, care, and treatment of developmental disorders. The Brain and Tissue Bank for Developmental Disorders reaches out to individuals and organizations across the United States to encourage donor registration. All donor information remains anonymous. Educational materials include reports, brochures, and audiovisual aids. The organization is funded by the National Institute of Child Health and Human Development. •
Brain Injury Association, Inc Telephone: (703) 236-6000 Toll-free: (800) 444-6443 Fax: (703) 236-6001 Email:
[email protected] Web Site: http://www.biausa.org Background: The Brain Injury Association of America is a national health organization dedicated to creating a better future through brain injury prevention, research, education and advocacy. Established in 1980, the Brain Injury Association provides information, assistance, and a variety of programs and services to people with brain injuries and their families, health care professionals, and the general public. The BIAA networks with and provides guidance to state associations as well as hundreds of chapters and support groups that offer a range of services including care/case management, respite care, recreational opportunities, and, in some cases, housing, transportation, and emergency financial assistance. The BIAA also lobbies before Congress and the Administration; encourages state agencies to develop and fund appropriate services for people with brain injuries; offers a toll-free Family Helpline; provides emergency financial assistance through its 'Thumbs Up Fund'; and offers the 'Brain Injury Resource Center,' an interactive multimedia computer system with comprehensive brain injury information that is available at rehabilitation facilities, trauma centers, and hospitals across the country. The BIAA publishes manuals, directories, magazines, and books.
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Brain Injury Resource Center Telephone: (206) 621-8558 Fax: (206) 329-0912 Email:
[email protected] Web Site: http://www.headinjury.com/ Background: Brain Injury Resource Center is a nonprofit clearinghouse founded and operated by head injury activists in1985. Visitors get information, join a discussion group, build advocacy skills, and self-care skills. Catalogues resources from diverse organizations including support groups, rehabilitation, and research sites, as well as lay and professional journals and more.
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Brain Tumor Foundation for Children, Inc Telephone: (770) 458-5554 Fax: (770) 458-5467 Email:
[email protected] Web Site: www.braintumorkids.org
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Background: The Brain Tumor Foundation for Children, Inc. (BTFC) is a national voluntary organization dedicated to providing emotional and informational support to families of children with brain tumors. Established in 1983 and currently consisting of approximately 1,400 members, BTFC is also committed to promoting public awareness of pediatric brain tumors and raising funds to support research that may discover potential cures and improve the treatment and quality of life of those affected by pediatric brain tumor disease. In addition, the Brain Tumor Foundation for Children has support groups, offers family networking services, and engages in patient education. Educational materials includes brochures, pamphlets, and a regular newsletter. •
Brain Tumor Foundation of Canada Telephone: (519) 642-7755 Toll-free: (800) 265-5106 Fax: (519) 642-7192 Email:
[email protected] Web Site: http://www.btfc.org Background: The Brain Tumour Foundation of Canada is a not-for-profit organization dedicated to reaching every person in Canada affected by a brain tumour with support, education and information, and to fund brain tumour research. Established in 1982, the Brain Tumor Foundation of Canada is committed to raising public awareness about the causes, effects, and treatment of brain tumors; working to support and improve the quality of life of those affected by brain tumors; and striving to find a cure for brain tumors. The Foundation s primary educational objective is to meet the information needs of individuals with brain tumors and their families. Educational materials include comprehensive and easy-to-read patient resource handbooks in adult and pediatric versions. Other materials include pamphlets designed to alert individuals, parents, educators, and health care professionals to the early warning signs and symptoms of brain tumors; a quarterly newsletter entitled 'Brainstorm'; and many books, publications, videos, and audio cassettes. Program activities include support group meetings; a national telephone support system; home and hospital visits; and an annual Adult and Pediatric Brain Tumor Information Day.
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Brain Tumor Society Telephone: (617) 924-9997 Toll-free: (800) 770-8287 Fax: (617) 924-9998 Email:
[email protected] Web Site: http://www.tbts.org Background: The Brain Tumor Society (TBTS) is a national voluntary not-for-profit organization dedicated to finding a cure for brain tumors, improving affected individuals quality of life, disseminating educational information on brain tumors, and providing psychosocial support to affected individuals and their families. The Society raises funds and makes grants to advance carefully selected scientific research projects, improve clinical care, and find a cure. The Society encourages participation in support groups and offers a wide range of services to help individuals cope with and manage the problems associated with brain tumors. TBTS offers a variety of educational programs to raise public awareness, facilitate early diagnosis and treatment, and to educate professionals about psychosocial issues associated with rare diagnoses.
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Educational materials include a newsletter entitled 'Heads Up,' a booklet on resources, brochures, and special resources for persons with rare brain tumors. •
Carter Centers for Brain Research in Holoprosencephaly and RelatedMalformations Telephone: (214) 559-8411 Toll-free: (800) 421-1121 Fax: (214) 559-8383 Email:
[email protected] Web Site: http://www.stanford.edu/group/hpe Background: The Carter Centers for Brain Research in Holoprosencephaly represent the most concentrated study of holoprosencephaly in the world. The Centers were created to gather, store, organize, analyze and share information about HPE, but most importantly, to help families find hope. Holoprosencephaly (HPE) is a neurological birth defect in which the fetal brain does not grow and divide as it should during early pregnancy. The effects of this brain malformation can range from mild to severe. Specific chromosomal abnormalities and gene mutations have been identified in some patients and there is evidence that in some families, HPE is inherited. The Carter Centers are a collaborative initiative among sponsored Centers of Excellence in the field of HPE: The Texas Scottish Rite Hospital for Children in Texas; the Kennedy Krieger Institute in Maryland; Stanford University and UCSF in California; and National Institutes of Health in Maryland.
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Central Brain Tumor Registry of the United States Telephone: (630) 655-4786 Fax: (630) 655-1756 Email:
[email protected] Web Site: www.cbtrus.org Background: The Central Brain Tumor Registry of the United States (CBTRUS) is a voluntary not-for-profit organization dedicated to collecting and disseminating statistical data on all primary benign and malignant brain tumors. Such data collection and dissemination is for the purposes of accurately describing incidence rates and survival patterns, evaluating diagnosis and treatment, facilitating studies concerning causes (etiology), promoting professional and public awareness, and, ultimately, working toward the possible prevention of such brain tumors. CBTRUS was incorporated in 1992 following a two-year study by the American Brain Tumor Association to determine the feasibility of a central registry for all brain tumor cases. In the past, standard data collection in the United States had been limited to malignant brain tumor cases. The Central Brain Tumor Registry has since developed a populationbased brain tumor registry including data on both malignant and non-malignant brain tumors through centralizing and compiling information on newly diagnosed cases from 13 participating state cancer registries. The CBTRUS database summarizes collaborators' data and generates statistics that are published in the form of an Annual Report. The Annual Report is mailed free of charge to over 2,000 members of the neuroscience community as well as to affected individuals, family members, and businesses upon request. In addition to data collection and dissemination, CBTRUS is dedicated to conducting special studies aimed at broadening the scope of data concerning the incidence and prevalence of brain tumors in certain populations. CBTRUS also encourages and promotes interdisciplinary dialogue with other professional and
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volunteer organizations, believing that only through collaboration and cooperation will brain tumors be understood and overcome. •
Children's Brain Diseases Foundation Telephone: (415) 566-5402 Fax: (415) 863-3452 Email:
[email protected] Background: The Children s Brain Diseases Foundation is a national not-for-profit organization that raises funds for medical research into the causes and treatments of Batten disease. Batten disease, also known as Neuronal Ceroid Lipofuscinosis, is a rare progressive degenerative neurometabolic disorder characterized by gradual intellectual deterioration, seizure episodes, progressive motor impairment, and progressive visual impairment. Symptoms may begin in infancy, very early childhood, or late childhood depending on the specific type. There is also an adult form called Kuf s disease. Founded in 1968, the Foundation provides information on Batten Disease to affected families and their physicians and promotes public understanding of the disease. Research funds are provided to investigators to help maintain the momentum of research on Batten Disease; pursue new scientific opportunities in this area of study; and promote early diagnosis, effective treatment, and prevention of Batten Disease. The Foundation produces educational brochures including 'Help To Keep the Color In a Child s Life: Erase Batten Disease.'.
•
Children's Brain Tumor Foundation Telephone: (212) 448-9494 Toll-free: (866) 228-4673 Fax: (212) 448-1022 Email:
[email protected] Web Site: www.cbtf.org Background: The Children's Brain Tumor Foundation (CBTF), founded in 1988, funds scientific research on the causes of, and improved treatments for, pediatric brain and spinal cord tumors and provides support and educational services to families and survivors. CBTF distributes 'A Resource Guide for Parents of Children with Brain and Spinal Cord Tumors' at no charge to families in English and Spanish, co-sponsors educational seminars and teleconferences, and provides online information through its Web site at www.cbtf.org. Each year, CBTF provides information and referrals to critical services to hundreds of families from all over the world. The Parent-to-Parent Network provides support to newly diagnose families from experienced parents who have been trained as volunteers. A newsletter, The Challenge, is published twice a year.
•
Dana Alliance for Brain Initiatives Telephone: (212) 223-4040 Fax: (212) 593-7623 Email:
[email protected] Web Site: http://www.dana.org Background: The Dana Alliance for Brain Initiatives, a nonprofit organization supported by the Charles A. Dana Foundation, was established as an alliance of neuroscientists
336 Brain
dedicated to providing information and promoting understanding concerning the personal and public benefits of brain research. (The Charles A. Dana Foundation is a private philanthropic foundation with grant programs in health and education.) According to the Alliance, approximately one in five Americans is affected by a brain disease or disorder, ranging from learning disabilities to Parkinson s Disease from epilepsy to spinal cord injuries. The Dana Alliance for Brain Initiatives is dedicated to answering questions concerning brain-related research and providing information concerning new developments. The Alliance offers a variety of periodicals, newsletters, reports, reference works, and books. •
Harvard Brain Tissue Resource Center Telephone: (617) 855-2400 Toll-free: (800) 272-4622 Fax: (617) 855-3199 Email:
[email protected] Web Site: http://www.brainbank.mclean.org:8080 Background: The Harvard Brain Tissue Resource Center is a federally funded, not-forprofit organization, dedicated to serving as a national resource for the collection and distribution of postmortem brain tissues for medical research into the causes of neurological and psychiatric disorders. The Brain Bank is interested in the study of Huntington s, Alzheimer s, and Parkinson s diseases, Tourette and Rett syndromes, and autism, as well as schizophrenia and manic depressive illnesses. The Center distributes brain tissue samples, at no charge, to qualified investigators in the United States who are involved in studying the neurobiology of these disorders.
•
Healing Exchange Brain Trust Telephone: (617) 876-2002 Fax: (617) 876-2332 Email:
[email protected] Web Site: http://www.braintrust.org Background: The Healing Exchange Brain Trust is a nonprofit organization dedicated to providing, promoting, and improving communication opportunities for individuals who are personally affected by or who professionally treat or study localized neurologic disorders (e.g., brain tumors) and subsequent or related health care concerns. In 1993, the e-mail discussion list known as the 'BRAINTMR mailing list' was founded by a brain tumor survivor. The Healing Exchange Brain Trust was later established in 1997 in order to expand on the purpose and objectives of the BRAINTMR mailing list, utilize new technology, and address new topics. The Trust is dedicated to creating, maintaining, offering, or endorsing communication vehicles to promote national and international networking among affected individuals, family members, friends, health professionals, and researchers. In addition, the Trust is committed to conveying its knowledge, experiences, and resources to the broader health care community and the public to foster acceptance, understanding, and aid for individuals affected by neurologic conditions; to increase public awareness; and to further develop innovative resources. The Healing Exchange Brain Trust also seeks to emphasize ways in which affected individuals, family members, and health care professionals may work together to achieve healing and well-being. The Trust's programs and services include offering the BRAINTMR mailing list, which serves as an online forum for discussion of topics
Patient Resources 337
related to all types of brain tumors; maintaining a web site that includes a 'virtual space' known as the 'Healing Exchange' where people may exchange information and mutual support concerning brain disorders; and attending national and international conferences to show affected individuals, families, health professionals, and researchers the benefits of online communication and resources. The Trust's web site includes instructions discussing how to join the BRAINTMR mailing list; information concerning the Trust's mission, goals, programs, and services; and guestbook, events, and news areas. •
National Brain Tumor Foundation Telephone: (510) 839-9777 Toll-free: (800) 934-2873 Fax: (510) 839-9779 Email:
[email protected] Web Site: http://www.braintumor.org Background: The National Brain Tumor Foundation is a national not-for-profit voluntary organization that serves as a comprehensive center for information regarding resources and support services for people whose lives are affected by brain tumor disease. Established in 1981, the National Brain Tumor Foundation also provides financial support for investigational studies into the causes, prevention, and treatments of brain tumors. To these ends, the National Brain Tumor Foundation has funded basic and applied laboratory research and clinical trials of new treatments at major institutions in the United States. The organization has also supported research into quality of life issues that regularly confront people with brain tumors. A comprehensive guide is available for affected individuals and their families who want to learn more about brain tumors. The National Brain Tumor Foundation also produces a variety of educational materials including a newsletter entitled 'Search.' Affected individuals and family members may also receive referrals to a network of support groups throughout the United States.
•
Pediatric Brain Tumors Telephone: (809) 523-8311 Fax: (809) 523-8400 Email:
[email protected] Web Site: http://health.groups.yahoo.com/group/Pediatricbraintumors/ Background: Pediatric Brain Tumors is an on-line support group for parents of children with brain tumors. Brain tumors are abnormal growths in the brain that can be either cancerous (malignant) or noncancerous (benign). The effects on the brain of malignant and benign brain tumors can be similar and may cause the same types of problems, depending upon the type of tumor and where it is located in the brain. Pediatric Brain Tumors is mostly for parents and family members. However, medical professionals are welcome, too. Pediatric Brain Tumors is a support group and a center for networking and education for those families affected by pediatric brain tumors.
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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to brain. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with brain. 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. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “brain” (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”. 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” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.
Patient Resources 339
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” (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.27
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
27
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)28: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
28
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on brain: •
Basic Guidelines for Brain Brain herniation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001421.htm Brain surgery Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003018.htm
•
Signs & Symptoms for Brain Cardiac arrest Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003078.htm Coma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Decreased alertness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm
348 Brain
Decreased consciousness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Eyelid drooping Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003035.htm Eyes, pupils different size Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003314.htm Facial pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003027.htm Hematomas Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003235.htm Hyperventilation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003071.htm Irregular pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003081.htm Loss of consciousness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm No breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003069.htm No pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003078.htm Palpitations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003081.htm Paralysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003190.htm Problems breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Reduced alertness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Respiratory arrest Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003069.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm
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•
Diagnostics and Tests for Brain Endotracheal intubation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003449.htm
•
Background Topics for Brain Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Blood clots Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001124.htm Head injury Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000028.htm Irregular breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000007.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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BRAIN DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] 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]
Acetylcarnitine: An acetic acid ester of carnitine that facilitates movement of acetyl CoA into the matrices of mammalian mitochondria during the oxidation of fatty acids. [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] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acoustic: Having to do with sound or hearing. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical
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manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Actin: Essential component of the cell skeleton. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Actualization: Possibilities of realizing fully one's personal (e. g. intellectual) potential. [NIH] Acupuncture Therapy: Treatment of disease by inserting needles along specific pathways or meridians. The placement varies with the disease being treated. Heat or moxibustion and acupressure may be used in conjunction. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] 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] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH]
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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] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [NIH] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH]
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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] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Alexia: The inability to recognize or comprehend written or printed words. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] 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] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Allogeneic: Taken from different individuals of the same species. [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] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH]
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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-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [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] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyotrophy: A type of diabetic neuropathy that causes muscle weakness and wasting. [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] 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] 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] Anaplastic: A term used to describe cancer cells that divide rapidly and bear little or no resemblance to normal cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH]
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Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergy: Absence of immune response to particular substances. [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] Aneurism: A localized abnormal dilatation of a blood vessel filled with fluid or clotted blood, forming a pulsating tumor, and resulting from disease of the vessel wall. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] 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] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [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] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anophthalmia: Absence of an eye or eyes in the newborn due to failure of development of the optic cup or to disappearance of the eyes after partial development. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] 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
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supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
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] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [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
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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] Antispasmodic: An agent that relieves spasm. [EU] Antitumour: Counteracting tumour formation. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [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] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] 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] Aqueous humor: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [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
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phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]
Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Articulation: The relationship of two bodies by means of a moveable joint. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspartate: A synthetic amino acid. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] 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
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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] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [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] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrial Natriuretic Factor: A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight peptides derived from a common precursor and secreted by the heart atria. All these peptides share a sequence of about 20 amino acids. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Audiology: The study of hearing and hearing impairment. [NIH] Audiovisual Aids: Auditory and visual instructional materials. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Auditory Cortex: Area of the temporal lobe concerned with hearing. [NIH] Auditory nerve: The eight cranial nerve; also called vestibulocochlear nerve or acoustic nerve. [NIH] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with
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autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [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] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]
Axillary Vein: The venous trunk of the upper limb; a continuation of the basilar and brachial veins running from the lower border of the teres major muscle to the outer border of the first rib where it becomes the subclavian vein. [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] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [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] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] 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] Behavioral Symptoms: Observable manifestions of impaired psychological functioning. [NIH]
Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] 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] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH]
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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] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [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 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] Body Fluids: Liquid components of living organisms. [NIH] Body Regions: Anatomical areas of the body. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bolus injection: The injection of a drug (or drugs) in a high quantity (called a bolus) at once, the opposite of gradual administration (as in intravenous infusion). [EU] 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 Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [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
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therapy. [NIH] Boron Neutron Capture Therapy: A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachiocephalic Veins: Large veins on either side of the root of the neck formed by the junction of the internal jugular and subclavian veins. They drain blood from the head, neck, and upper extremities, and unite to form the superior vena cava. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary 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 metastases: Cancer that has spread from the original (primary) tumor to 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] Brain stem glioma: A tumor located in the part of the brain that connects to the spinal cord (the brain stem). It may grow rapidly or slowly, depending on the grade of the tumor. [NIH] Brain Stem Infarctions: Infarctions that occur in the brain stem which is comprised of the midbrain, pons, and medulla. There are several named syndromes characterized by their distinctive clinical manifestations and specific sites of ischemic injury. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH]
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Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broadband: A wide frequency range. Sound whose energy is distributed over a broad range of frequency (generally, more than one octave). [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] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [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] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] Cannula: A tube for insertion into a duct or cavity; during insertion its lumen is usually occupied by a trocar. [EU] 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] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen
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are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carboxy: Cannabinoid. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH]
Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carmustine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH]
Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] 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] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] 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]
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Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [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] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] 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 Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Fusion: Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization. [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 Movement: The movement of cells from one location to another. [NIH] 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 Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [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
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adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellular metabolism: The sum of all chemical changes that take place in a cell through which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]
Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrovascular Disorders: A broad category of disorders characterized by impairment of blood flow in the arteries and veins which supply the brain. These include cerebral infarction; brain ischemia; hypoxia, brain; intracranial embolism and thrombosis; intracranial arteriovenous malformations; and vasculitis, central nervous system. In common usage, the term cerebrovascular disorders is not limited to conditions that affect the cerebrum, but refers to vascular disorders of the entire brain including the diencephalon; brain stem; and cerebellum. [NIH]
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Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chelation Therapy: Therapy of heavy metal poisoning using agents which sequester the metal from organs or tissues and bind it firmly within the ring structure of a new compound which can be eliminated from the body. [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] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [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] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH]
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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] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Choroid Plexus: A villous structure of tangled masses of blood vessels contained within the third, lateral, and fourth ventricles of the brain. It regulates part of the production and composition of cerebrospinal fluid. [NIH] Choroid plexus tumor: A rare type of cancer that occurs in the ventricles of the brain. It usually occurs in children younger than 2 years. [NIH] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Abnormalities: Defects in the structure or number of chromosomes resulting in structural aberrations or manifesting as disease. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [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
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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] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Cleft Lip: Congenital defect in the upper lip where the maxillary prominence fails to merge with the merged medial nasal prominences. It is thought to be caused by faulty migration of the mesoderm in the head region. [NIH] Cleft Palate: Congenital fissure of the soft and/or hard palate, due to faulty fusion. [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] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [NIH] 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
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amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]
Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Cochlear Implantation: Surgical insertion of an electronic device implanted beneath the skin with electrodes to the cochlear nerve to create sound sensation in persons with sensorineural deafness. [NIH] Cochlear Implants: Electronic devices implanted beneath the skin with electrodes to the cochlear nerve to create sound sensation in persons with sensorineural deafness. [NIH] Cochlear Nerve: The cochlear part of the 8th cranial nerve (vestibulocochlear nerve). The cochlear nerve fibers originate from neurons of the spiral ganglion and project peripherally to cochlear hair cells and centrally to the cochlear nuclei (cochlear nucleus) of the brain stem. They mediate the sense of hearing. [NIH] Cochlear Nucleus: The brain stem nucleus that receives the central input from the cochlear nerve. The cochlear nucleus is located lateral and dorsolateral to the inferior cerebellar peduncles and is functionally divided into dorsal and ventral parts. It is tonotopically organized, performs the first stage of central auditory processing, and projects (directly or indirectly) to higher auditory areas including the superior olivary nuclei, the medial geniculi, the inferior colliculi, and the auditory cortex. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Coliphages: Viruses whose host is Escherichia coli. [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] Coloboma: Congenital anomaly in which some of the structures of the eye are absent due to
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incomplete fusion of the fetal intraocular fissure during gestation. [NIH] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Comatose: Pertaining to or affected with coma. [EU] Combination chemotherapy: Treatment using more than one anticancer drug. [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] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Compassionate: A process for providing experimental drugs to very sick patients who have no treatment options. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH]
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Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Compulsions: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conditioned stimulus: A situation in which one signal, or stimulus, is given just before another signal. After this happens several times, the first signal alone can cause the response that would usually need the second signal. [NIH] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective
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tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH] 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]
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] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Contusion: A bruise; an injury of a part without a break in the skin. [EU] Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [NIH] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [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] Cooperative group: A group of physicians, hospitals, or both formed to treat a large number of persons in the same way so that new treatment can be evaluated quickly. Clinical trials of new cancer treatments often require many more people than a single physician or hospital can care for. [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] Coreceptors: Invariant receptor of the helper T-cells. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH]
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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 Striatum: Striped gray and white matter consisting of the neostriatum and paleostriatum (globus pallidus). It is located in front of and lateral to the thalamus in each cerebral hemisphere. The gray substance is made up of the caudate nucleus and the lentiform nucleus (the latter consisting of the globus pallidus and putamen). The white matter is the internal capsule. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortices: The outer layer of an organ; used especially of the cerebrum and cerebellum. [NIH] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [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] Craniopharyngioma: A benign brain tumor that may be considered malignant because it can damage the hypothalamus, the area of the brain that controls body temperature, hunger, and thirst. [NIH] Cryoglobulinemia: A condition characterized by the presence of abnormal or abnormal quantities of cryoglobulins in the blood. They are precipitated into the microvasculature on exposure to cold and cause restricted blood flow in exposed areas. [NIH] Cryptococcosis: Infection with a fungus of the species Cryptococcus neoformans. [NIH] Cryptorchidism: A condition in which one or both testicles fail to move from the abdomen, where they develop before birth, into the scrotum. Cryptorchidism may increase the risk for development of testicular cancer. Also called undescended testicles. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for
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the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] 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] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge. [NIH]
Cutaneous: Having to do with the skin. [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] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclopia: Elements of the two eyes fused into one median eye in the center of the forehead of a fetal monster. [NIH] Cysteinyl: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a
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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] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [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] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
Day Care: Institutional health care of patients during the day. The patients return home at night. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] 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
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is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [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] Deoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity. [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] Dermal: Pertaining to or coming from the skin. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism. [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] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH]
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Diastolic heart failure: Inability of the heart to relax properly and fill with blood as a result of stiffening of the heart muscle. [NIH] Dichlorvos: An organophosphorus insecticide that inhibits acetylcholinesterase. [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]
Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [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] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] 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] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissection: Cutting up of an organism for study. [NIH] 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]
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Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Donepezil: A drug used in the treatment of Alzheimer's disease. It belongs to the family of drugs called cholinesterase inhibitors. It is being studied as a treatment for side effects caused by radiation therapy to the brain. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] 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] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [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 Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH]
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Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Ductus Arteriosus: A fetal blood vessel connecting the pulmonary artery with the descending aorta. [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] Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (receptors, opioid, kappa) and have been shown to play a role as central nervous system transmitters. [NIH] Dysarthria: Imperfect articulation of speech due to disturbances of muscular control which result from damage to the central or peripheral nervous system. [EU] Dyskinesias: Abnormal involuntary movements which primarily affect the extremities, trunk, or jaw that occur as a manifestation of an underlying disease process. Conditions which feature recurrent or persistent episodes of dyskinesia as a primary manifestation of disease may be referred to as dyskinesia syndromes (movement disorders). Dyskinesias are also a relatively common manifestation of basal ganglia diseases. [NIH] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [NIH] Dysphonia: Difficulty or pain in speaking; impairment of the voice. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [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] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is
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based on the results of a randomized control trial. [NIH] Ejaculation: The release of semen through the penis during orgasm. [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] Electroacupuncture: A form of acupuncture using low frequency electrically stimulated needles to produce analgesia and anesthesia and to treat disease. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [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] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embolectomy: Surgical removal of an obstructing clot or foreign material which has been transported from a distant vessel by the bloodstream. Removal of a clot at its original site is called thrombectomy. [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] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH]
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Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]
Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [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] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [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] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endostatin: A drug that is being studied for its ability to prevent the growth of new blood
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vessels into a solid tumor. Endostatin belongs to the family of drugs called angiogenesis inhibitors. [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 it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energetic: Exhibiting energy : strenuous; operating with force, vigour, or effect. [EU] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] 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] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU]
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Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [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] Epithalamus: The dorsal posterior subdivision of the diencephalon. The epithalamus is generally considered to include the habenular nuclei (habenula) and associated fiber bundles, the pineal body, and the epithelial roof of the third ventricle. The anterior and posterior paraventricular nuclei of the thalamus are included with the thalamic nuclei although they develop from the same pronuclear mass as the epithalamic nuclei and are sometimes considered part of the epithalamus. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Estrone: 3-Hydroxyestra-1,3,5(10)-trien-17-one. A metabolite of estradiol but possessing less biological activity. It is found in the urine of pregnant women and mares, in the human placenta, and in the urine of bulls and stallions. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), estrone may reasonably be anticipated to be a carcinogen
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(Merck, 11th ed). [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] Ethanolamine: A viscous, hygroscopic amino alcohol with an ammoniacal odor. It is widely distributed in biological tissue and is a component of lecithin. It is used as a surfactant, fluorimetric reagent, and to remove CO2 and H2S from natural gas and other gases. [NIH] Ethidium: A trypanocidal agent and possible antiviral agent that is widely used in experimental cell biology and biochemistry. Ethidium has several experimentally useful properties including binding to nucleic acids, noncompetitive inhibition of nicotinic acetylcholine receptors, and fluorescence among others. It is most commonly used as the bromide. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] 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] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH]
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Expiratory Reserve Volume: The extra volume of air that can be expired with maximum effort beyond the level reached at the end of a normal, quiet expiration. Common abbreviation is ERV. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular 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] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] Facial Pain: Pain in the facial region including orofacial pain and craniofacial pain. Associated conditions include local inflammatory and neoplastic disorders and neuralgic syndromes involving the trigeminal, facial, and glossopharyngeal nerves. Conditions which feature recurrent or persistent facial pain as the primary manifestation of disease are referred to as facial pain syndromes. [NIH] 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] Factor V: Heat- and storage-labile plasma glycoprotein which accelerates the conversion of prothrombin to thrombin in blood coagulation. Factor V accomplishes this by forming a complex with factor Xa, phospholipid, and calcium (prothrombinase complex). Deficiency of factor V leads to Owren's disease. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH]
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Family Relations: Behavioral, psychological, and social relations among various members of the nuclear family and the extended family. [NIH] Fast Neutrons: Neutrons, the energy of which exceeds some arbitrary level, usually around one million electron volts. [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] Febrile: Pertaining to or characterized by fever. [EU] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] 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 other enzymes yields different fibrinogen degradation products. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Firearms: Small-arms weapons, including handguns, pistols, revolvers, rifles, shotguns, etc. [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] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering,
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the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [NIH] 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] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]
Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Forskolin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant Coleus forskohlii. Has antihypertensive, positive ionotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fourth Ventricle: An irregularly shaped cavity in the rhombencephalon, between the medulla oblongata, the pons, and the isthmus in front, and the cerebellum behind. It is continuous with the central canal of the cord below and with the cerebral aqueduct above, and through its lateral and median apertures it communicates with the subarachnoid space. [NIH]
Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [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.
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[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] GABA: The most common inhibitory neurotransmitter in the central nervous system. [NIH] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Gait: Manner or style of walking. [NIH] Galactitol: A naturally occurring product of plants obtained following reduction of galactose. It appears as a white crystalline powder with a slight sweet taste. It may form in excess in the lens of the eye in galactosemia, a deficiency of galactokinase. [NIH] Galactokinase: An enzyme that catalyzes reversibly the formation of galactose 1-phosphate and ADP from ATP and D-galactose. Galactosamine can also act as the acceptor. A deficiency of this enzyme results in galactosemia. EC 2.7.1.6. [NIH] Galactosemia: Buildup of galactose in the blood. Caused by lack of one of the enzymes needed to break down galactose into glucose. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Gamma-interferon: Interferon produced by T-lymphocytes in response to various mitogens and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [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]
Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH]
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Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal stromal tumor: GIST. A type of tumor that usually begins in cells in the wall of the gastrointestinal tract. It can be benign or malignant. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH]
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Germ cell tumors: Tumors that begin in the cells that give rise to sperm or eggs. They can occur virtually anywhere in the body and can be either benign or malignant. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germinoma: The most frequent type of germ-cell tumor in the brain. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestures: Movement of a part of the body for the purpose of communication. [NIH] Ginkgo biloba: Exclusive species of the genus Ginkgo, family Ginkgoacea. It produces extracts of medicinal interest. Ginkgo may refer to the genus or species. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glasgow Coma Scale: A scale that assesses the response to stimuli in patients with craniocerebral injuries. The parameters are eye opening, motor reponse, and verbal response. [NIH] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glioblastoma multiforme: A type of brain tumor that forms from glial (supportive) tissue of the brain. It grows very quickly and has cells that look very different from normal cells. Also called grade IV astrocytoma. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Globus Pallidus: The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus. [NIH] Glossopharyngeal Nerve: The 9th cranial nerve. The glossopharyngeal nerve is a mixed motor and sensory nerve; it conveys somatic and autonomic efferents as well as general, special, and visceral afferents. Among the connections are motor fibers to the stylopharyngeus muscle, parasympathetic fibers to the parotid glands, general and taste afferents from the posterior third of the tongue, the nasopharynx, and the palate, and afferents from baroreceptors and chemoreceptors of the carotid sinus. [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] Glucokinase: A group of enzymes that catalyzes the conversion of ATP and D-glucose to ADP and D-glucose 6-phosphate. They are found in invertebrates and microorganisms and are highly specific for glucose. (Enzyme Nomenclature, 1992) EC 2.7.1.2. [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
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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] Glucuronosyltransferase: A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamate Decarboxylase: A pyridoxal-phosphate protein that catalyzes the alphadecarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining gaba levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC 4.1.1.15. [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]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [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] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Government Agencies: Administrative units of government responsible for policy making and management of governmental activities in the U.S. and abroad. [NIH]
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Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] 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] Group Structure: The informal or formal organization of a group of people based on a network of personal relationships which is influenced by the size and composition, etc., of the group. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gyrus Cinguli: One of the convolutions on the medial surface of the cerebral hemisphere. It surrounds the rostral part of the brain and interhemispheric commissure and forms part of the limbic system. [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] 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] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Hallucination: A sense perception without a source in the external world; a perception of an external stimulus object in the absence of such an object. [EU] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH]
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Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health 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] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Physics: The science concerned with problems of radiation protection relevant to reducing or preventing radiation exposure, and the effects of ionizing radiation on humans and their environment. [NIH] Hearing aid: A miniature, portable sound amplifier for persons with impaired hearing, consisting of a microphone, audio amplifier, earphone, and battery. [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 failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart Transplantation: The transference of a heart from one human or animal to another. [NIH]
Heartbeat: One complete contraction of the heart. [NIH] Hematemesis: Vomiting of blood. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [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] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH]
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Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [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] 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] 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] 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 virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Hexokinase: An enzyme that catalyzes the conversion of ATP and a D-hexose to ADP and a D-hexose 6-phosphate. D-Glucose, D-mannose, D-fructose, sorbitol, and D-glucosamine can act as acceptors; ITP and dATP can act as donors. The liver isoenzyme has sometimes been called glucokinase. (From Enzyme Nomenclature, 1992) EC 2.7.1.1. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Holistic Health: Health as viewed from the perspective that man and other organisms function as complete, integrated units rather than as aggregates of separate parts. [NIH] Holoprosencephaly: Anterior midline brain, cranial, and facial malformations resulting from the failure of the embryonic prosencephalon to undergo segmentation and cleavage. Alobar prosencephaly is the most severe form and features anophthalmia; cyclopia; severe mental retardation; cleft lip; cleft palate; seizures; and microcephaly. Semilobar holoprosencepaly is characterized by hypotelorism, microphthalmia, coloboma, nasal malformations, and variable degrees of mental retardation. Lobar holoprosencephaly is associated with mild (or absent) facial malformations and intellectual abilities that range from mild mental retardation to normal. Holoprosencephlay is associated with chromosome abnormalities. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH]
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Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]
Homogenate: A suspension of animal tissue that is ground in the all-glass "homogenizer" described by Potter and Elvehjem in 1936. [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] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Hospices: Facilities or services which are especially devoted to providing palliative and supportive care to the patient with a terminal illness and to the patient's family. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [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] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH]
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Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperoxia: An abnormal increase in the amount of oxygen in the tissues and organs. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertensive Encephalopathy: Brain dysfunction or damage resulting from malignant hypertension, usually associated with a diastolic blood pressure in excess of 125 mmHg. Clinical manifestations include headache, nausea, emesis, seizures, altered mental status (in some cases progressing to coma), papilledema, and retinal hemorrhage. Focal neurologic signs may develop. Pathologically, this condition may be associated with the formation of ischemic lesions in the brain (brain ischemia). [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperventilation: A pulmonary ventilation rate faster than is metabolically necessary for the exchange of gases. It is the result of an increased frequency of breathing, an increased tidal volume, or a combination of both. It causes an excess intake of oxygen and the blowing off of carbon dioxide. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] 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] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]
Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [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] Hypoxic: Having too little oxygen. [NIH]
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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] Ileum: The lower end of the small intestine. [NIH] Illusion: A false interpretation of a genuine percept. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]
Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]
Immunodominant Epitopes: Subunits of the antigenic determinant that are most easily recognized by the immune system and thus most influence the specificity of the induced antibody. [NIH] Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] 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] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH]
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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] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant Care: Care of infants in the home or institution. [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]
Infection Control: Programs of disease surveillance, generally within health care facilities, designed to investigate, prevent, and control the spread of infections and their causative microorganisms. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it
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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] 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] 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] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule. Insertion interrupts the gene's sequence such that its original function is no longer expressed. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Institutionalization: The caring for individuals in institutions and their adaptation to routines characteristic of the institutional environment, and/or their loss of adaptation to life outside the institution. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family
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contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] 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]
Intercellular Adhesion Molecule-1: A cell-surface ligand with a role in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] 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] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] 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] Intervention Studies: Epidemiologic investigations designed to test a hypothesized cause-
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effect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Aneurysm: A saclike dilatation of the walls of a blood vessel, usually an artery. [NIH]
Intracranial Embolism: The sudden obstruction of a blood vessel by an embolus. [NIH] Intracranial Embolism and Thrombosis: Embolism or thrombosis involving blood vessels which supply intracranial structures. Emboli may originate from extracranial or intracranial sources. Thrombosis may occur in arterial or venous structures. [NIH] 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] Intraindividual: Being or occurring within the individual. [EU] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intrathecal chemotherapy: Anticancer drugs that are injected into the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin,
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and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iontophoresis: Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ion exchange, air ionization nor phonophoresis, none of which requires current. [NIH] Ipsilateral: Having to do with the same side of the body. [NIH] Irinotecan: An anticancer drug that belongs to a family of anticancer drugs called topoisomerase inhibitors. It is a camptothecin analogue. Also called CPT 11. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] 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
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isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Jugular Veins: Veins in the neck which drain the brain, face, and neck into the brachiocephalic or subclavian veins. [NIH] Kainate: Glutamate receptor. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [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] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kidney Cortex: The outer zone of the kidney, beneath the capsule, consisting of kidney glomerulus; kidney tubules, distal; and kidney tubules, proximal. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetic: Pertaining to or producing motion. [EU] 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] Lactation: The period of the secretion of milk. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] 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 Therapy: Rehabilitation of persons with language disorders or training of children with language development disorders. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH]
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Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lateral Ventricles: Cavity in each of the cerebral hemispheres derived from the cavity of the embryonic neural tube. They are separated from each other by the septum pellucidum, and each communicates with the third ventricle by the foramen of Monro, through which also the choroid plexuses of the lateral ventricles become continuous with that of the third ventricle. [NIH] Laterality: Behavioral manifestations of cerebral dominance in which there is preferential use and superior functioning of either the left or the right side, as in the preferred use of the right hand or right foot. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] 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] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU]
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Ligands: A RNA simulation method developed by the MIT. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [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] Linear Energy Transfer: Rate of energy dissipation along the path of charged particles. In radiobiology and health physics, exposure is measured in kiloelectron volts per micrometer of tissue (keV/micrometer T). [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipectomy: Removal of localized subcutaneous fat deposits by suction curettage or blunt cannulization in the cosmetic correction of obesity and other esthetic contour defects. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] 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]
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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] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. [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] Lordosis: The anterior concavity in the curvature of the lumbar and cervical spine as viewed from the side. The term usually refers to abnormally increased curvature (hollow back, saddle back, swayback). It does not include lordosis as normal mating posture in certain animals ( = posture + sex behavior, animal). [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH]
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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] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [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] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lymphoproliferative Disorders: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lymphotoxin: Soluble substance released by lymphocytes activated by antigens or T-cell mitogens, that is cytotoxic to other cells. It is involved in allergies and chronic inflammatory diseases. Lymphotoxin is antigenically distinct from tumor necrosis factor-alpha (tumor necrosis factor), though they both share a common receptor, biological activities, and significant amino acid sequences. [NIH] Macroglia: A type of neuroglia composed of astrocytes. [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] Mafosfamide: A form of cyclophosphamide that can be administered as an intrathecal infusion. Mafosfamide is being studied as an anticancer drug; it belongs to the family of drugs called alkylating agents. [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] Magnetoencephalography: The measurement of magnetic fields over the head generated by electric currents in the brain. As in any electrical conductor, electric fields in the brain are accompanied by orthogonal magnetic fields. The measurement of these fields provides
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information about the localization of brain activity which is complementary to that provided by electroencephalography. Magnetoencephalography may be used alone or together with electroencephalography, for measurement of spontaneous or evoked activity, and for research or clinical purposes. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malformation: A morphologic developmental process. [EU]
defect
resulting
from
an
intrinsically
abnormal
Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Malondialdehyde: The dialdehyde of malonic acid. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Maple Syrup Urine Disease: A genetic disorder involving deficiency of an enzyme necessary in the metabolism of branched-chain amino acids, and named for the characteristic odor of the urine. [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] Maximum Tolerated Dose: The highest dose level eliciting signs of toxicity without having
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major effects on survival relative to the test in which it is used. [NIH] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Oncology: A subspecialty of internal medicine concerned with the study of neoplasms. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Medulloblastoma: A malignant brain tumor that begins in the lower part of the brain and can spread to the spine or to other parts of the body. Medulloblastomas are sometimes called primitive neuroectodermal tumors (PNET). [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning,
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(2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meningeal: Refers to the meninges, the tissue covering the brain and spinal cord. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningioma: A type of tumor that occurs in the meninges, the membranes that cover and protect the brain and spinal cord. Meningiomas usually grow slowly. [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] Meningoencephalitis: An inflammatory process involving the brain (encephalitis) and meninges (meningitis), most often produced by pathogenic organisms which invade the central nervous system, and occasionally by toxins, autoimmune disorders, and other conditions. [NIH] Menopause: Permanent cessation of menstruation. [NIH] 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] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [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] Metallothionein: A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH]
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Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [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] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] 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] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]
labeled
with
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] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH]
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Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] 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] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] 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] Morbillivirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. MEASLES VIRUS is the type species. [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]
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Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Skills: Performance of complex motor acts. [NIH] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Diseases: Acquired, familial, and congenital disorders of skeletal muscle and smooth muscle. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Music Therapy: The use of music as an adjunctive therapy in the treatment of neurological, mental, or behavioral disorders. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelin Sheath: The lipid-rich sheath investing many axons in both the central and peripheral nervous systems. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (Schwann cells in the peripheral and oligodendroglia in the central nervous system). Deterioration of the sheath in demyelinating diseases is a serious clinical problem. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH]
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Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]
Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [NIH] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] N-acetyl: Analgesic agent. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasal Septum: The partition separating the two nasal cavities in the midplane, composed of cartilaginous, membranous and bony parts. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis,
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prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [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] Neurites: In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell. [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 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]
Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized
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by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroectodermal tumor: A tumor of the central or peripheral nervous system. [NIH] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells. [NIH] Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurologic Manifestations: Clinical signs and symptoms caused by nervous system injury or dysfunction. [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] Neuroma: A tumor that arises in nerve cells. [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] Neuronal atrophy: Nerve cell death and functional loss. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH]
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Neuropil: A dense intricate feltwork of interwoven fine glial processes, fibrils, synaptic terminals, axons, and dendrites interspersed among the nerve cells in the gray matter of the central nervous system. [NIH] Neuropil Threads: Abnormal structures located chiefly in distal dendrites and, along with neurofibrillary tangles and senile plaques, constitute the three morphological hallmarks of Alzheimer disease. Neuropil threads are made up of straight and paired helical filaments which consist of abnormally phosphorylated microtubule-associated tau proteins. It has been suggested that the threads have a major role in the cognitive impairment seen in Alzheimer disease. [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] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurosurgeon: A doctor who specializes in surgery on the brain, spine, and other parts of the nervous system. [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] Neurosurgical Procedures: Surgery performed on the nervous system or its parts. [NIH] Neurotensin: A biologically active tridecapeptide isolated from the hypothalamus. It has been shown to induce hypotension in the rat, to stimulate contraction of guinea pig ileum and rat uterus, and to cause relaxation of rat duodenum. There is also evidence that it acts as both a peripheral and a central nervous system neurotransmitter. [NIH] Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis. [EU]
Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutron Capture Therapy: A technique for the treatment of neoplasms in which an isotope
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is introduced into target cells followed by irradiation with thermal neutrons. [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] Neutrophil: A type of white blood cell. [NIH] Nevus: A benign growth on the skin, such as a mole. A mole is a cluster of melanocytes and surrounding supportive tissue that usually appears as a tan, brown, or flesh-colored spot on the skin. The plural of nevus is nevi (NEE-vye). [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [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] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [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] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [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] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Family: A family composed of spouses and their children. [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
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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] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension. [NIH] Occipital Lobe: Posterior part of the cerebral hemisphere. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [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] Olfactory Bulb: Ovoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the vomeronasal organ via the vomeronasal nerve, is also included here. [NIH] Olfactory Nerve: The 1st cranial nerve. The olfactory nerve conveys the sense of smell. It is formed by the axons of olfactory receptor neurons which project from the olfactory epithelium (in the nasal epithelium) to the olfactory bulb. [NIH] Oligodendroglia: A class of neuroglial (macroglial) cells in the central nervous system. Oligodendroglia may be called interfascicular, perivascular, or perineuronal satellite cells
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according to their location. The most important recognized function of these cells is the formation of the insulating myelin sheaths of axons in the central nervous system. [NIH] Oligodendroglial: A cell that lays down myelin. [NIH] Oligodendroglioma: A rare, slow-growing tumor that begins in brain cells called oligodendrocytes, which provide support and nourishment for cells that transmit nerve impulses. Also called oligodendroglial tumor. [NIH] Oligoelement: A chemical substance, minute amounts of which can be found in living organisms. [EU] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncology: The study of cancer. [NIH] Oncolysis: The destruction of or disposal by absorption of any neoplastic cells. [NIH] Oncolytic: Pertaining to, characterized by, or causing oncolysis (= the lysis or destruction of tumour cells). [EU] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [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] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [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] Optical Illusions: An illusion of vision usually affecting spatial relations. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU]
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Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [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] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overall survival: The percentage of subjects in a study who have survived for a defined period of time. Usually reported as time since diagnosis or treatment. Often called the survival rate. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxaliplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative Phosphorylation: Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus
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brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Papilledema: Swelling around the optic disk. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] 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] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Parturition: The act or process of given birth to a child. [EU] Passive transport: The transport that occurs through the membrane at non-specific sites. [NIH]
Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of
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tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathologist: A doctor who identifies diseases by studying cells and tissues under a microscope. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [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] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] 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] Pericytes: Smooth muscle cell that wraps around normal blood 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 blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral stem cell transplantation: A method of replacing blood-forming cells destroyed by cancer treatment. Immature blood cells (stem cells) in the circulating blood that are similar to those in the bone marrow are given after treatment to help the bone marrow recover and continue producing healthy blood cells. Transplantation may be autologous (an individual's own blood cells saved earlier), allogeneic (blood cells donated by someone else), or syngeneic (blood cells donated by an identical twin). Also called peripheral stem cell
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support. [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] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Perivascular: Situated around a vessel. [EU] Peroneal Nerve: The lateral of the two terminal branches of the sciatic nerve. The peroneal (or fibular) nerve provides motor and sensory innervation to parts of the leg and foot. [NIH] Petechiae: Pinpoint, unraised, round red spots under the skin caused by bleeding. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] 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] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phonophoresis: Use of ultrasound to increase the percutaneous adsorption of drugs. [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]
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Phosphorylates: Attached to a phosphate group. [NIH] Phosphorylating: 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] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photoperiod: The time period of daily exposure that an organism receives from daylight or artificial light. It is believed that photoperiodic responses may affect the control of energy balance and thermoregulation. [NIH] Photosensitizer: A drug used in photodynamic therapy. When absorbed by cancer cells and exposed to light, the drug becomes active and kills the cancer cells. [NIH] Photosensitizing Agents: Drugs that are pharmacologically inactive but when exposed to ultraviolet radiation or sunlight are converted to their active metabolite to produce a beneficial reaction affecting the diseased tissue. These compounds can be administered topically or systemically and have been used therapeutically to treat psoriasis and various types of neoplasms. [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] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]
Pilot study: The initial study examining a new method or treatment. [NIH] Pineal Body: A small conical midline body attached to the posterior part of the third ventricle and lying between the superior colliculi, below the splenium of the corpus callosum. [NIH] Pineal gland: A tiny organ located in the cerebrum that produces melatonin. Also called pineal body or pineal organ. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [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] Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which vegetable proteins is available. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a
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fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] 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] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Platinum Compounds: Inorganic compounds which contain platinum as the central atom. [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] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or
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veins. [EU] Pneumonia: Inflammation of the lungs. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [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] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [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] Porfimer sodium: An anticancer drug that is also used in cancer prevention. It belongs to the family of drugs called photosensitizing agents. [NIH] Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Port: An implanted device through which blood may be withdrawn and drugs may be
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infused without repeated needle sticks. Also called a port-a-cath. [NIH] Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [NIH] Positron emission tomography scan: PET scan. A computerized image of the metabolic activity of body tissues used to determine the presence of disease. [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] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Postural: Pertaining to posture or position. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Pre-eclamptic: A syndrome characterized by hypertension, albuminuria, and generalized
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oedema, occurring only in pregnancy. [NIH] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] 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] Preoperative: Preceding an operation. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] 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] Primitive neuroectodermal tumors: PNET. A type of bone cancer that forms in the middle (shaft) of large bones. Also called Ewing's sarcoma/primitive neuroectodermal tumor. [NIH] Prion: Small proteinaceous infectious particles that resist inactivation by procedures modifying nucleic acids and contain an abnormal isoform of a cellular protein which is a major and necessary component. [NIH] 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] Probenecid: The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [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]
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Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promyelocytic leukemia: A type of acute myeloid leukemia, a quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. [NIH]
Prone: Having the front portion of the body downwards. [NIH] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prosencephalon: The part of the brain developed from the most rostral of the three primary vesicles of the embryonic neural tube and consisting of the diencephalon and telencephalon. [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] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH]
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Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [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] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa;
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protozoal. [EU] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Pseudotumor Cerebri: A condition marked by raised intracranial pressure and characterized clinically by headaches; nausea; papilledema, peripheral constriction of the visual fields, transient visual obscurations, and pulsatile tinnitus. Obesity is frequently associated with this condition, which primarily affects women between 20 and 44 years of age. Chronic papilledema may lead to optic nerve injury (optic nerve diseases) and visual loss (blindness). [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease 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] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychometric testing: Psychological and mental testing and quantitative analysis of an individual's psychological traits or attitudes or mental processes. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychoneuroimmunology: The field concerned with the interrelationship between the brain, behavior and the immune system. Neuropsychologic, neuroanatomic and psychosocial studies have demonstrated their role in accentuating or diminishing immune/allergic responses. [NIH] Psychophysics: The science dealing with the correlation of the physical characteristics of a stimulus, e.g., frequency or intensity, with the response to the stimulus, in order to assess the psychologic factors involved in the relationship. [NIH] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]
Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH]
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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] Puerperium: Period from delivery of the placenta until return of the reproductive organs to their normal nonpregnant morphologic state. In humans, the puerperium generally lasts for six to eight weeks. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary Gas Exchange: The exchange of oxygen and carbon dioxide between alveolar air and pulmonary capillary blood. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pupil: The aperture in the iris through which light passes. [NIH] Pupillary Reflex: Constriction of the pupil in response to light stimulation of the retina. [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] Putamen: The largest and most lateral of the basal ganglia lying between the lateral medullary lamina of the globus pallidus and the external capsule. It is part of the neostriatum and forms part of the lentiform nucleus along with the globus pallidus. [NIH] Pyramidal 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] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] 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]
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Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [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 Oncology: A subspecialty of medical oncology and radiology concerned with the radiotherapy of cancer. [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] Radioactive iodine: A radioactive form of the chemical element iodine, often used for imaging tests or as a treatment for cancer. [NIH] Radiobiology: That part of biology which deals with the effects of radiation on living organisms. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [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] Radiopharmaceuticals: Drugs containing a radioactive substance that are used in the diagnosis and treatment of cancer and in pain management of bone metastases. Also called radioactive drugs. [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] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even
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numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Ras gene: A gene that has been found to cause cancer when it is altered (mutated). Agents that block its activity may stop the growth of cancer. A ras peptide is a protein fragment produced by the ras gene. [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] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] 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] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [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] 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]
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Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]
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] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [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] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Research Support: Financial support of research activities. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into
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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] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Respite Care: Patient care provided in the home or institution intermittently in order to provide temporary relief to the family home care giver. [NIH] Restitution: The restoration to a normal state. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Hemorrhage: Bleeding from the vessels of the retina. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retractor: An instrument designed for pulling aside tissues to improve exposure at operation; an instrument for drawing back the edge of a wound. [NIH] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhabdoid tumor: A malignant tumor of either the central nervous system (CNS) or the kidney. Malignant rhabdoid tumors of the CNS often have an abnormality of chromosome 22. These tumors usually occur in children younger than 2 years. [NIH] Rhabdomyosarcoma: A malignant tumor of muscle tissue. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of
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developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Saquinavir: An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Sargramostim: A colony-stimulating factor that stimulates the production of blood cells, especially platelets, during chemotherapy. It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called GM-CSF. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH]
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Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] 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] Scrapie: A fatal disease of the nervous system in sheep and goats, characterized by pruritus, debility, and locomotor incoordination. It is caused by proteinaceous infectious particles called prions. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Scrotum: In males, the external sac that contains the testicles. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [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] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [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] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semantics: The relationships between symbols and their meanings. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU]
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Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Senile Plaques: Spherical masses consisting of amyloid fibrils and neuronal processes. [NIH] Senility: Old age; the physical and mental deterioration associated with old age. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septal Nuclei: Neural nuclei situated in the septal region. They have afferent and cholinergic efferent connections with a variety of forebrain and brainstem areas including the hippocampus, the lateral hypothalamus, the tegmentum, and the amygdala. Included are the dorsal, lateral, medial, and triangular septal nuclei, septofimbrial nucleus, nucleus of diagonal band, nucleus of anterior commissure, and the nucleus of stria terminalis. [NIH] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU] Septum Pellucidum: A triangular double membrane separating the anterior horns of the lateral ventricles of the brain. It is situated in the median plane and bounded by the corpus callosum and the body and columns of the fornix. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] 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]
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Sex Behavior: Sexual activities of humans. [NIH] Sex Behavior, Animal: Sexual activities of animals. [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] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shivering: Involuntary contraction or twitching of the muscles. It is a physiologic method of heat production in man and other mammals. [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]
Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoid Colon: The lower part of the colon that empties into the rectum. [NIH] 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] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [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] Skilled Nursing Facilities: Extended care facilities which provide skilled nursing care or
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rehabilitation services for inpatients on a daily basis. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Skull Base: The inferior region of the skull consisting of an internal (cerebral), and an external (basilar) surface. [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] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Security: Government sponsored social insurance programs. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soft tissue sarcoma: A sarcoma that begins in the muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU]
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Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somatic mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. [NIH] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] 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] 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] Spectroscopic: The recognition of elements through their emission spectra. [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 Disorders: Acquired or developmental conditions marked by an impaired ability to comprehend or generate spoken forms of language. [NIH] Speech pathologist: A specialist who evaluates and treats people with communication and swallowing problems. Also called a speech therapist. [NIH] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal
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roots are also included. [NIH] Spinous: Like a spine or thorn in shape; having spines. [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] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] 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 transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stereotactic: Radiotherapy that treats brain tumors by using a special frame affixed directly to the patient's cranium. By aiming the X-ray source with respect to the rigid frame, technicians can position the beam extremely precisely during each treatment. [NIH] Stereotactic radiosurgery: A radiation therapy technique involving a rigid head frame that is attached to the skull; high-dose radiation is administered through openings in the head frame to the tumor while decreasing the amount of radiation given to normal brain tissue. This procedure does not involve surgery. Also called stereotaxic radiosurgery and stereotactic radiation therapy. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on
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muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stria: 1. A streak, or line. 2. A narrow bandlike structure; a general term for such longitudinal collections of nerve fibres in the brain. [EU] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stringency: Experimental conditions (e. g. temperature, salt concentration) used during the hybridization of nucleic acids. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclavian: The direct continuation of the axillary vein at the lateral border of the first rib. It passes medially to join the internal jugular vein and form the brachiocephalic vein on each side. [NIH] Subclavian Artery: Artery arising from the brachiocephalic trunk on the right side and from the arch of the aorta on the left side. It distributes to the neck, thoracic wall, spinal cord, brain, meninges, and upper limb. [NIH] Subclavian Vein: The continuation of the axillary vein which follows the subclavian artery and then joins the internal jugular vein to form the brachiocephalic vein. [NIH] 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] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [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]
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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] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Superior vena cava: Vein which returns blood from the head and neck, upper limbs, and thorax. It is formed by the union of the two brachiocephalic veins. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Supratentorial: Located in the upper part of the brain. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [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
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the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron 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] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Tau Proteins: One of the two major classes of microtubule-associated proteins isolated from the brain. The proteins have two domains: one that binds to microtubules and a second that binds to other cell components. By binding to several unpolymerized tubulin molecules simultaneously, tau proteins speed up the nucleation process in tubulin polymerization. Chemically modified tau proteins also appear to be involved in the formation and/or composition of the neurofibrillary tangles and neuropil threads found in Alzheimer disease. [NIH]
Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH]
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Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temozolomide: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Temperament: Predisposition to react to one's environment in a certain way; usually refers to mood changes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [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] Thalamic Nuclei: Several groups of nuclei in the thalamus that serve as the major relay centers for sensory impulses in the brain. [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]
Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH]
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Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thermoregulation: Heat regulation. [EU] Thiotepa: A very toxic alkylating antineoplastic agent also used as an insect sterilant. It causes skin, gastrointestinal, CNS, and bone marrow damage. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), thiotepa may reasonably be anticipated to be a carcinogen (Merck Index, 11th ed). [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] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombectomy: Surgical removal of an obstructing clot or foreign material from a blood vessel at the point of its formation. Removal of a clot arising from a distant site is called embolectomy. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] 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]
Thrombophlebitis: Inflammation of a vein associated with thrombus formation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH]
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Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tibial Nerve: The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory innervation to parts of the calf and foot. [NIH] Tidal Volume: The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are TV or V with subscript T. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonicity: The normal state of muscular tension. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances
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usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]
Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Tractus: A part of some structure, usually that part along which something passes. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [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] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]
Transient Ischemic Attacks: Focal neurologic abnormalities of sudden onset and brief duration that reflect dysfunction in the distribution of the internal carotid-middle cerebral or the vertebrobasilar arterial system. [NIH] Translating: Conversion from one language to another language. [NIH]
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Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, 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 Centers: Specialized hospital facilities which provide diagnostic and therapeutic services for trauma patients. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]
Trophic: Of or pertaining to nutrition. [EU] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor model: A type of animal model which can be 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] 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] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]
Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive;
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called also neoplasm. [EU] Turpentine: The concrete oleoresin obtained from Pinus palustris Mill. (Pinaceae) and other species of Pinus. It contains a volatile oil, to which its properties are due, and to which form it is generally used. (Dorland, 28th ed) Turpentine is used as a solvent and an experimental irritant in biomedical research. Turpentine toxicity is of medical interest. [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] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Unresectable: Unable to be surgically removed. [NIH] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uricosuric: 1. Pertaining to, characterized by, or promoting uricosuria (= the excretion of uric acid in the urine). 2. An agent that promotes uricosuria. [EU] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] 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] Vagotomy: The interruption or removal of any part of the vagus (10th cranial) nerve. Vagotomy may be performed for research or for therapeutic purposes. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents
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(from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Valerian: Valeriana officinale, an ancient, sedative herb of the large family Valerianaceae. The roots were formerly used to treat hysterias and other neurotic states and are presently used to treat sleep disorders. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] 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] 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] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetable Proteins: Proteins which are present in or isolated from vegetables or vegetable products used as food. The concept is distinguished from plant proteins which refers to nondietary proteins from plants. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Vena: A vessel conducting blood from the capillary bed to the heart. [NIH] Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venter: Belly. [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] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] 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
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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 Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Ventriculostomy: Surgical creation of an opening in a cerebral ventricle. [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] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] 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] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vinorelbine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH]
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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] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Visual Cortex: Area of the occipital lobe concerned with vision. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitreous Humor: The transparent, colorless mass of gel that lies behind the lens and in front of the retina and fills the center of the eyeball. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to
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treat cancer. [NIH] 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] Zebrafish: A species of North American fishes of the family Cyprinidae. They are used in embryological studies and to study the effects of certain chemicals on development. [NIH] Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIVinduced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
461
INDEX 1 1-Methyl-4-phenyl-1,2,3,6tetrahydropyridine, 75, 351 A Abdomen, 351, 363, 364, 376, 404, 408, 425, 427, 447, 448, 452, 457 Abdominal, 213, 214, 314, 351, 372, 425, 427 Abdominal Pain, 314, 351 Aberrant, 18, 38, 351 Ablation, 12, 351 Abscess, 85, 89, 230, 259, 351, 443 Absenteeism, 351, 376 Acatalasia, 351, 366 Acceptor, 351, 391, 408, 424, 452 ACE, 78, 351 Acetylcarnitine, 133, 351 Acetylcholine, 24, 66, 79, 82, 87, 110, 255, 313, 331, 351, 370, 387, 420, 421 Acetylcholinesterase, 102, 150, 330, 351, 380 Acetylcysteine, 351 Acidity, 351, 427 Acoustic, 151, 260, 263, 310, 351, 360, 458 Acquired Immunodeficiency Syndrome, 49, 351 Actin, 223, 352, 416, 417, 419 Activities of Daily Living, 45, 352 Actualization, 125, 352 Acupuncture Therapy, 22, 352 Acute lymphoblastic leukemia, 211, 352 Acute lymphocytic leukemia, 352 Acute myeloid leukemia, 352, 433 Adaptability, 352, 367, 368 Adaptation, 20, 66, 128, 352, 402, 429 Adenine, 352, 436 Adenocarcinoma, 352, 421 Adenosine, 16, 352, 360, 427 Adenylate Cyclase, 134, 352, 390 Adjunctive Therapy, 352, 416 Adjustment, 64, 128, 249, 352 Adjuvant, 61, 181, 352, 392 Adolescence, 113, 352 Adrenal Cortex, 352, 376, 386, 432, 439 Adrenergic, 6, 85, 270, 353, 358, 381, 386, 450, 456 Adsorption, 353, 427 Adverse Effect, 206, 236, 353, 371, 444
Aerobic, 353, 414 Afferent, 353, 376, 432, 443 Affinity, 225, 353, 360, 371, 408, 413, 445 Agar, 78, 353, 377, 400, 428 Agarose, 223, 353, 400 Age Groups, 331, 353 Age of Onset, 10, 93, 353 Aged, 80 and Over, 353 Ageing, 10, 229, 251, 353 Agonist, 35, 88, 214, 215, 222, 237, 353, 381, 421, 450 Airway, 202, 353 Alanine, 100, 353 Albumin, 216, 354, 429 Alertness, 347, 348, 354 Alexia, 354, 382 Algorithms, 32, 354, 362 Alimentary, 354, 425 Alkaline, 354, 355, 365 Alkaloid, 354, 360, 365, 371, 421, 442 Alkylating Agents, 354, 366, 410, 451 Allogeneic, 354, 395, 426 Alpha Particles, 354, 437 Alternative medicine, 326, 354 Aluminum, 76, 78, 133, 251, 354 Alveoli, 354, 457 Ameliorating, 38, 212, 354 Amino Acid Sequence, 75, 80, 215, 354, 357, 387, 392, 410, 433 Amino Acid Substitution, 355, 396 Amino-terminal, 23, 81, 112, 355 Ammonia, 89, 355, 394, 449, 456 Amnestic, 150, 355 Amphetamines, 175, 355, 372 Amplification, 6, 45, 260, 355 Amygdala, 4, 7, 67, 226, 228, 355, 361, 408, 443, 451 Amyloid, 5, 10, 28, 38, 79, 84, 104, 212, 225, 226, 249, 257, 311, 330, 331, 355, 443 Amyotrophy, 223, 355 Anaerobic, 20, 229, 230, 355 Anaesthesia, 355, 401 Anal, 355, 409, 416 Analog, 23, 26, 196, 213, 225, 263, 355, 391, 441 Analogous, 43, 355, 381, 430, 454 Anaphylatoxins, 355, 373 Anaplastic, 191, 355
462 Brain
Androgens, 31, 73, 352, 355, 359 Anemia, 296, 356, 365, 390, 411, 460 Anergy, 50, 356 Anesthesia, 68, 134, 155, 353, 356, 383, 384, 432 Anesthetics, 207, 270, 356, 361, 386 Aneurism, 232, 356 Anginal, 356, 421 Angiogenesis, 15, 39, 61, 68, 294, 356, 385, 411 Angiogenesis inhibitor, 356, 385 Angiography, 31, 356 Angioplasty, 95, 356, 417 Angiotensinogen, 356, 439 Animal model, 25, 41, 49, 57, 68, 94, 207, 212, 248, 305, 312, 356, 455 Anions, 74, 354, 356, 405, 432, 443, 449 Annealing, 356, 430 Anode, 356 Anomalies, 43, 294, 356 Anophthalmia, 356, 397 Anorexia, 58, 355, 356 Anoxia, 247, 301, 356 Antagonism, 24, 356, 371 Anterior chamber, 220, 357, 405 Antibacterial, 357, 432, 446 Antibiotic, 168, 357, 378, 381, 426, 432, 446 Antibodies, 7, 50, 75, 76, 215, 222, 223, 225, 357, 360, 395, 400, 410, 415, 429, 437 Antibody therapy, 187, 199, 357 Anticoagulant, 230, 357, 434 Anticonvulsant, 83, 319, 357 Antigen, 25, 80, 124, 210, 217, 226, 353, 357, 373, 398, 399, 400, 401, 402, 412, 414 Antigen-Antibody Complex, 357, 373 Antihypertensive, 357, 390 Anti-infective, 357, 398, 404 Anti-inflammatory, 28, 36, 52, 357, 393, 401 Antimetabolite, 357, 379 Antineoplastic, 35, 354, 357, 366, 377, 381, 391, 392, 424, 430, 452, 458 Antineoplastic Agents, 35, 354, 357, 458 Antioxidant, 72, 101, 134, 137, 150, 357, 359, 424 Antipsychotic, 357, 371, 419 Antispasmodic, 358, 423, 442 Antitumour, 114, 358 Antiviral, 351, 358, 379, 387, 391, 403, 426 Anus, 355, 358, 364, 373, 438 Anxiety, 23, 157, 216, 358, 422, 432 Anxiety Disorders, 216, 358
Aorta, 219, 358, 382, 448, 458 Aphasia, 247, 259, 263, 304, 307, 319, 355, 358 Apolipoproteins, 358, 408 Aponeurosis, 358, 391 Apoptosis, 12, 14, 39, 62, 73, 111, 211, 235, 244, 358, 366, 377 Applicability, 312, 358 Apraxia, 163, 247, 307, 358 Aqueous, 220, 358, 362, 370, 378, 384, 398, 407 Aqueous humor, 220, 358, 370 Arachidonic Acid, 358, 433 Arginine, 74, 204, 355, 359, 421 Aromatase, 109, 359 Aromatic, 359, 413, 427 Arterial, 37, 117, 202, 359, 364, 368, 369, 399, 404, 434, 450, 454 Arteries, 31, 85, 239, 306, 358, 359, 363, 366, 368, 375, 405, 409, 414, 417, 456 Arteriolar, 359, 364, 439 Arterioles, 359, 363, 365, 414 Arteriolosclerosis, 359 Arteriosclerosis, 229, 230, 359 Arteriosus, 359, 436 Arteriovenous, 68, 293, 359, 368, 414 Articular, 359, 424 Articulation, 359, 382 Ascorbic Acid, 359, 398 Aspartate, 62, 79, 81, 91, 214, 359, 394 Assay, 214, 234, 237, 359, 400 Astringents, 359, 413 Astrocytes, 35, 36, 38, 59, 111, 209, 224, 359, 360, 410, 414, 415 Astrocytoma, 53, 102, 187, 191, 195, 360, 393 Asymptomatic, 196, 351, 360 Ataxia, 46, 263, 294, 295, 296, 360, 368, 451 ATP, 35, 149, 352, 360, 381, 391, 392, 393, 394, 397, 405, 409, 427, 434, 452 Atrial, 83, 87, 106, 202, 360 Atrial Fibrillation, 202, 360 Atrial Natriuretic Factor, 83, 360 Atrium, 214, 360, 457 Atrophy, 4, 7, 8, 9, 22, 39, 85, 115, 119, 261, 295, 296, 360, 419 Atropine, 360, 442 Attenuation, 125, 133, 360 Atypical, 360, 371 Audiology, 260, 360 Audiovisual Aids, 332, 360 Auditory Cortex, 360, 372
Index 463
Auditory nerve, 260, 360, 412 Autacoids, 360, 401 Autoantibodies, 75, 79, 360, 361 Autoantigens, 360 Autoimmune disease, 217, 361, 416 Autologous, 361, 426 Autonomic, 351, 358, 361, 376, 393, 421, 426, 449 Autonomic Nervous System, 361, 426, 449 Autopsy, 4, 9, 28, 226, 231, 305, 308, 310, 311, 315, 316, 361 Autoradiography, 81, 82, 87, 361 Axillary, 361, 448 Axillary Vein, 361, 448 Axonal, 15, 29, 62, 79, 232, 313, 361 Axons, 233, 313, 361, 379, 380, 403, 416, 418, 420, 422, 423, 432, 436 B Bacillus, 25, 361 Bacteria, 353, 357, 361, 374, 383, 385, 394, 409, 414, 438, 446, 454, 456 Bacterial Physiology, 352, 361 Bactericidal, 361, 387 Bacteriophage, 234, 361, 428, 454 Barbiturate, 361, 451 Basal Ganglia, 73, 79, 115, 136, 313, 358, 360, 361, 364, 382, 391, 393, 399, 408, 422, 436 Basal Ganglia Diseases, 360, 361, 382, 399 Base, 61, 212, 221, 352, 361, 378, 379, 392, 406, 436, 451 Basement Membrane, 228, 362, 388, 406 Basophils, 362, 395, 407 Behavioral Symptoms, 11, 362 Benign, 334, 337, 359, 362, 376, 391, 392, 393, 396, 418, 421, 437 Beta-pleated, 355, 362 Bilateral, 7, 362, 425 Bile, 169, 362, 391, 408, 447, 450 Bile Acids, 362, 447, 450 Bilirubin, 354, 362 Binding Sites, 38, 82, 362 Biochemical, 13, 14, 35, 44, 62, 66, 71, 72, 85, 130, 244, 247, 255, 263, 357, 362, 389, 424, 443 Biological response modifier, 362, 403 Biological therapy, 362, 395 Biopsy, 9, 103, 144, 362, 426 Biotechnology, 72, 84, 250, 285, 293, 295, 296, 297, 326, 362 Biotransformation, 362 Bivalent, 362, 413
Bladder, 363, 370, 374, 401, 416, 419, 434, 456 Blastocyst, 363, 374, 428 Bloating, 314, 363 Blood Coagulation, 363, 365, 388, 452 Blood Glucose, 127, 220, 363, 396, 399, 402 Blood Platelets, 363, 443 Blood pressure, 86, 88, 89, 148, 214, 329, 357, 363, 399, 415, 421, 445 Blood transfusion, 267, 363 Blood Volume, 37, 58, 227, 363, 457 Body Fluids, 363, 382, 390, 422, 445 Body Regions, 363, 372 Bolus, 58, 237, 363 Bolus infusion, 363 Bolus injection, 237, 363 Bone Marrow Transplantation, 184, 363 Bone metastases, 363, 437 Bone scan, 363, 441 Boron, 235, 363, 364, 377 Boron Neutron Capture Therapy, 364 Bowel, 314, 355, 364, 380, 402, 404, 407, 427, 448 Bowel Movement, 364, 380, 448 Brachiocephalic Veins, 364, 449 Brachytherapy, 53, 55, 115, 364, 403, 405, 437, 460 Bradykinin, 196, 364, 406, 421, 429 Brain Diseases, 21, 130, 237, 241, 242, 263, 264, 300, 311, 317, 335, 364, 406 Brain Hypoxia, 364, 451 Brain Infarction, 105, 117, 364 Brain Ischemia, 64, 66, 83, 151, 152, 153, 364, 368, 399 Brain stem glioma, 39, 182, 187, 191, 195, 364 Brain Stem Infarctions, 364 Branch, 206, 345, 364, 383, 410, 412, 420, 425, 436, 446, 450, 452, 453 Breakdown, 39, 62, 66, 239, 330, 364, 368, 380, 391 Breeding, 224, 365 Broadband, 21, 365 Bronchi, 365, 386, 454 Bronchial, 204, 365 Buccal, 365, 409 C Cadmium, 134, 365 Cadmium Poisoning, 365 Calcification, 359, 365 Callus, 365, 383 Calmodulin, 76, 78, 81, 83, 365
464 Brain
Camptothecin, 365, 405 Cannula, 219, 365 Capillary, 35, 61, 196, 230, 364, 365, 436, 441, 457, 458 Capillary Permeability, 196, 364, 365 Carbohydrate, 130, 216, 365, 394, 430 Carbon Dioxide, 17, 365, 366, 378, 391, 394, 399, 428, 436, 440, 457 Carboplatin, 184, 196, 271, 366 Carboxy, 23, 366 Carboxy-terminal, 23, 366 Carcinogen, 366, 386, 452 Carcinogenic, 354, 366, 402, 423, 433, 447, 455 Carcinoma, 108, 188, 190, 199, 366, 421, 447 Cardiac, 41, 43, 64, 87, 219, 230, 347, 360, 366, 383, 386, 417, 447, 449 Cardiac arrest, 64, 219, 347, 366, 449 Cardiorespiratory, 115, 366 Cardiovascular, 366, 443 Carmustine, 191, 192, 197, 271, 366 Carnitine, 139, 140, 351, 366 Carotene, 230, 366, 440 Carotid Arteries, 202, 366 Case report, 98, 115, 328, 366, 371 Case series, 366, 371 Caspase, 14, 366 Catabolism, 38, 366 Catalase, 83, 351, 366 Catecholamine, 366, 381 Catheter, 206, 207, 208, 219, 367, 384, 404 Catheterization, 356, 367, 404, 417 Cations, 367, 405 Caudal, 367, 380, 399, 422, 431 Caudate Nucleus, 361, 367, 376, 418, 422 Causal, 208, 226, 367, 404 Causality, 6, 367 Cause of Death, 68, 203, 206, 367 Cell Adhesion, 81, 367, 403 Cell Count, 51, 367 Cell Differentiation, 68, 367, 444 Cell Division, 14, 295, 361, 367, 387, 395, 412, 415, 428, 433 Cell Fusion, 69, 367 Cell membrane, 35, 367, 379, 405, 412, 416, 427, 445 Cell Movement, 228, 367 Cell proliferation, 68, 70, 83, 359, 367, 403, 444 Cell Respiration, 367, 414, 440 Cell Size, 367, 390
Cell Survival, 232, 367, 395 Cell Transplantation, 184, 192, 197, 368 Cellular metabolism, 44, 368 Cellulose, 368, 391, 428 Ceramide, 136, 368 Cerebellar, 34, 75, 126, 187, 191, 195, 360, 368, 372, 438, 455 Cerebellar Diseases, 360, 368, 455 Cerebellum, 7, 23, 50, 62, 120, 149, 313, 364, 368, 376, 390, 430, 438 Cerebral Arteries, 368, 414 Cerebral Cortex, 228, 258, 313, 360, 364, 368, 387, 388, 389, 418, 436 Cerebral hemispheres, 361, 364, 368, 369, 393, 407, 451 Cerebral Infarction, 364, 368 Cerebral Palsy, 16, 193, 250, 368 Cerebrospinal, 24, 37, 41, 84, 124, 203, 206, 322, 368, 370, 444 Cerebrospinal fluid, 24, 41, 84, 203, 206, 322, 368, 370, 444 Cerebrovascular, 3, 68, 309, 361, 368, 451 Cerebrovascular Disorders, 68, 368, 451 Cerebrum, 368, 369, 376, 428, 451, 455 Cervical, 98, 120, 369, 409 Cervix, 215, 369 Character, 241, 369, 378 Chelation, 46, 153, 164, 369 Chelation Therapy, 46, 164, 369 Chemokines, 25, 50, 95, 215, 369 Chemotactic Factors, 369, 373 Chemotaxis, 50, 369 Chemotherapeutic agent, 196, 207, 369 Chest Pain, 230, 369 Chin, 91, 133, 149, 369, 413 Chlorine, 90, 369 Cholecystokinin, 74, 130, 369 Cholesterol, 78, 158, 362, 369, 370, 408, 409, 412, 447, 450 Cholesterol Esters, 369, 408 Choline, 9, 13, 26, 62, 132, 140, 351, 370 Cholinergic, 6, 9, 10, 23, 42, 109, 137, 146, 247, 249, 261, 358, 370, 421, 443 Cholinesterase Inhibitors, 10, 266, 370, 381 Chondrocytes, 370, 389 Choroid, 18, 195, 370, 375, 407, 440 Choroid Plexus, 18, 195, 370, 407 Choroid plexus tumor, 195, 370 Chromaffin System, 370, 384 Chromatin, 358, 370, 385 Chromosomal, 311, 334, 355, 370, 441
Index 465
Chromosome, 226, 232, 311, 370, 374, 395, 397, 408, 440, 441, 455 Chromosome Abnormalities, 370, 397 Chronic Disease, 370, 376 Chronic Fatigue Syndrome, 52, 370 Chronic renal, 370, 430 Chylomicrons, 370, 408 Ciliary, 358, 359, 370 Ciliary processes, 358, 370 Circadian, 216, 370 Circadian Rhythm, 216, 370 Circulatory system, 143, 371, 384, 404 Citrus, 359, 371 Clamp, 29, 371 Clear cell carcinoma, 371, 379 Cleft Lip, 371, 397 Cleft Palate, 294, 371, 397 Clinical Medicine, 101, 223, 371, 431 Clinical study, 31, 34, 371 Clone, 74, 215, 371 Cloning, 24, 75, 76, 78, 81, 84, 95, 96, 109, 215, 225, 312, 362, 371, 402 Clozapine, 86, 145, 371 Coagulation, 229, 363, 371, 397, 429, 452 Coca, 371 Cocaine, 102, 371 Cochlea, 74, 372 Cochlear, 260, 372, 453, 458 Cochlear Diseases, 372, 453 Cochlear Implantation, 260, 372 Cochlear Implants, 260, 372 Cochlear Nerve, 372, 458 Cochlear Nucleus, 260, 372, 458 Coenzyme, 170, 359, 372 Cofactor, 372, 434, 452 Colic, 159, 230, 372 Coliphages, 361, 372 Colitis, 372, 402 Collagen, 354, 362, 372, 388, 389, 392, 411, 429 Collapse, 364, 372 Colloidal, 354, 372, 443 Coloboma, 372, 397 Colon, 157, 221, 231, 295, 372, 373, 402, 406, 444 Comatose, 247, 373 Combination chemotherapy, 192, 197, 373 Communication Disorders, 200, 247, 252, 255, 263, 265, 284, 301, 304, 312, 313, 319, 373 Comorbidity, 22, 373 Compassionate, 329, 373
Complement, 25, 29, 355, 373, 392, 402, 429 Complementary and alternative medicine, 143, 144, 180, 373 Complementary medicine, 144, 373 Complete remission, 374, 439 Compliance, 6, 307, 374 Compulsions, 374, 422 Computational Biology, 285, 293, 374 Computed tomography, 5, 11, 22, 97, 319, 329, 374, 441 Computerized tomography, 374 Conception, 243, 374, 389, 446 Concomitant, 14, 65, 100, 374 Conditioned stimulus, 13, 374 Conduction, 66, 255, 374, 416 Cone, 216, 374 Confounding, 6, 67, 220, 374 Conjugated, 8, 204, 374, 377, 417 Conjugation, 127, 362, 374, 394 Conjunctiva, 220, 374, 455 Connective Tissue, 359, 363, 372, 374, 375, 379, 389, 391, 392, 410, 413, 441, 448, 451 Consciousness, 45, 109, 115, 153, 247, 315, 348, 375, 378, 379, 380, 435 Constriction, 375, 405, 435, 436, 441, 457 Constriction, Pathologic, 375, 457 Consumption, 9, 133, 230, 375, 424 Continuum, 247, 375 Contraindications, ii, 375 Contralateral, 107, 375, 423, 438 Contrast medium, 356, 375 Control group, 4, 7, 22, 30, 375 Contusion, 49, 122, 375 Conus, 375, 436 Conventional therapy, 375 Conventional treatment, 225, 375 Convulsions, 357, 361, 375, 382, 399, 431 Cooperative group, 55, 375 Coordination, 55, 313, 368, 375, 416 Coreceptors, 106, 375 Cornea, 220, 357, 358, 375, 442 Corneum, 204, 375, 386 Coronary, 95, 111, 121, 230, 375, 414, 417 Coronary Thrombosis, 375, 414, 417 Corpus, 23, 62, 376, 393, 409, 418, 426, 428, 432, 443, 452, 459 Corpus Callosum, 23, 62, 376, 428, 443, 452 Corpus Striatum, 376, 393, 418 Cortex, 7, 45, 49, 81, 107, 226, 254, 263, 358, 376, 385, 414, 432, 438
466 Brain
Cortices, 32, 262, 376, 396 Corticosteroids, 376, 393 Cortisol, 20, 154, 354, 376 Cost of Illness, 287, 376 Cranial Nerves, 121, 310, 376 Craniocerebral Trauma, 361, 376, 396, 451, 453 Craniopharyngioma, 195, 376 Cryoglobulinemia, 91, 376 Cryptococcosis, 50, 376 Cryptorchidism, 294, 376 Cues, 209, 210, 376 Culture Media, 226, 353, 376 Cultured cells, 226, 377 Curative, 224, 225, 291, 377, 421, 452 Curcumin, 136, 377 Curettage, 377, 408 Cutaneous, 313, 314, 377, 409 Cyanosis, 377, 396 Cyclic, 61, 76, 352, 365, 377, 390, 395, 421, 427, 430, 433 Cyclophosphamide, 271, 377, 410 Cyclopia, 377, 397 Cysteinyl, 377, 413 Cytochrome, 359, 377, 424 Cytokine, 25, 52, 58, 67, 100, 124, 248, 377, 441, 451 Cytomegalovirus, 29, 307, 377, 391 Cytomegalovirus Infections, 377, 391 Cytoplasm, 211, 358, 362, 367, 377, 378, 385, 395, 413, 415, 419, 440 Cytoskeleton, 378, 402, 414 Cytotoxic, 50, 53, 211, 235, 378, 410, 437, 444 Cytotoxic chemotherapy, 211, 378 Cytotoxicity, 104, 233, 378 D Data Collection, 287, 334, 378 Daunorubicin, 378, 381 Day Care, 240, 378 Deamination, 378, 415, 456 Decarboxylation, 378, 394 Defense Mechanisms, 378, 403 Degenerative, 11, 40, 44, 242, 257, 258, 260, 286, 287, 309, 322, 335, 375, 378, 397, 416, 424 Dehydroepiandrosterone, 59, 378 Deletion, 328, 358, 378 Delirium, 258, 357, 378 Delivery of Health Care, 376, 378, 396 Delusions, 378, 435 Denaturation, 379, 430
Dendrites, 313, 379, 418, 419, 420, 422, 436 Dendritic, 15, 62, 255, 379, 412 Density, 16, 28, 46, 81, 226, 253, 379, 390, 408, 423, 446 Dentate Gyrus, 15, 379, 397 Deoxyglucose, 247, 379 Depolarization, 379, 444 Depressive Disorder, 30, 95, 379 Deprivation, 12, 328, 379 Dermal, 204, 379 Dermis, 204, 379, 449, 454 DES, 355, 379 Detoxification, 131, 379 Developmental Biology, 24, 133, 379 Dextroamphetamine, 379, 414 Diabetes Mellitus, 144, 158, 379, 394, 396 Diagnostic procedure, 201, 326, 379 Diastole, 379 Diastolic, 101, 379, 380, 399 Diastolic blood pressure, 379, 399 Diastolic heart failure, 101, 380 Dichlorvos, 150, 380 Diencephalon, 368, 380, 386, 399, 419, 432, 433, 451, 452 Diffuse Axonal Injury, 364, 380 Digestion, 354, 362, 364, 380, 404, 408, 448 Digestive system, 200, 380, 416 Digestive tract, 212, 235, 380, 445, 447 Dihydroxy, 235, 380, 441 Dilatation, 356, 380, 404, 432 Dilation, 230, 364, 380 Dilution, 45, 380, 386 Diploid, 380, 428, 455 Discrete, 231, 380, 409, 451 Discrimination, 118, 119, 154, 222, 380 Disease Progression, 7, 380, 458 Disinfectant, 380, 387 Disorientation, 378, 380 Dissection, 28, 380 Dissociation, 353, 380, 405 Distal, 208, 219, 361, 381, 383, 406, 420, 432, 435 Dizziness, 245, 263, 381, 458 DNA Topoisomerase, 381, 392 Dominance, 125, 126, 381, 407 Donepezil, 197, 381 Dopa, 381, 407 Dopamine, 26, 59, 77, 79, 80, 313, 358, 371, 372, 379, 381, 407, 415, 420, 427 Dorsal, 372, 381, 386, 431, 443, 446 Dose-dependent, 381, 460 Double-blind, 8, 27, 59, 381
Index 467
Doxorubicin, 65, 381 Drive, ii, vi, 83, 129, 227, 252, 290, 316, 328, 381, 405, 407 Drug Design, 278, 312, 381 Drug Interactions, 277, 381 Drug Tolerance, 382, 453 Duct, 365, 367, 382, 387, 441, 447, 449 Ductus Arteriosus, 101, 382 Duodenum, 362, 382, 420, 448 Dura mater, 382, 413, 424, 445 Dyes, 355, 362, 382, 390 Dynorphins, 382, 423 Dysarthria, 247, 307, 382 Dyskinesias, 361, 382, 416 Dyslexia, 19, 48, 263, 382 Dysphonia, 263, 382 Dysphoric, 379, 382 Dysplasia, 294, 296, 382 Dystonia, 98, 263, 328, 358, 382 Dystrophic, 7, 382 Dystrophy, 296, 382 E Eating Disorders, 158, 216, 382 Eclampsia, 100, 382, 431 Edema, 17, 19, 37, 58, 66, 158, 203, 221, 382, 404, 417, 422, 431 Effector, 86, 351, 373, 382, 419, 427 Efferent, 376, 382, 443 Efficacy, 20, 22, 23, 46, 55, 58, 91, 96, 199, 261, 381, 382, 409 Ejaculation, 119, 383, 442 Elasticity, 229, 359, 383 Elective, 383 Electroacupuncture, 149, 150, 383 Electrocoagulation, 371, 383 Electrode, 220, 260, 356, 383 Electroencephalography, 46, 383, 411 Electrolysis, 356, 367, 383 Electrolyte, 66, 378, 383, 390, 422, 431, 445 Electrophysiological, 13, 23, 29, 77, 83, 383 Elementary Particles, 383, 410, 421, 434 Emaciation, 352, 383 Embolectomy, 208, 383, 452 Emboli, 203, 208, 230, 383, 404 Embolism, 259, 383, 404, 436 Embolus, 383, 401, 404 Embryo, 363, 367, 383, 401, 430, 456 Embryogenesis, 13, 383 Embryology, 383, 420 Emesis, 384, 399 Empirical, 90, 146, 384 Emulsion, 361, 384
Encapsulated, 49, 278, 384 Encephalitis, 39, 80, 94, 106, 109, 248, 384, 413 Encephalitis, Viral, 384 Encephalomyelitis, 25, 384 Encephalopathy, 248, 258, 295, 384 Endarterectomy, 117, 356, 384 Endemic, 384, 411, 447 Endocrine Glands, 384 Endocrine System, 151, 384 Endogenous, 6, 22, 69, 70, 101, 210, 226, 232, 360, 381, 384, 385, 387, 394, 423, 454 Endometrium, 384, 413 Endorphins, 384, 420, 423, 433 Endostatin, 39, 384 Endothelium, 18, 35, 39, 66, 196, 230, 385, 421, 429 Endothelium, Lymphatic, 385 Endothelium, Vascular, 385 Endothelium-derived, 385, 421 Endotoxin, 385, 455 End-stage renal, 370, 385, 430 Energetic, 165, 253, 385 Energy balance, 103, 385, 428 Enhancer, 59, 211, 218, 385 Enkephalins, 385, 420, 423 Entorhinal Cortex, 385, 397 Environmental Exposure, 385, 423 Environmental Health, 284, 286, 321, 385 Enzymatic, 23, 111, 354, 365, 366, 373, 385, 412, 430, 440 Enzyme, 40, 144, 263, 270, 351, 352, 355, 359, 365, 366, 372, 377, 381, 382, 385, 391, 392, 393, 394, 395, 397, 401, 405, 406, 409, 411, 413, 415, 417, 427, 429, 430, 434, 438, 439, 444, 449, 452, 459, 460 Eosinophils, 385, 395, 407 Epidemic, 385, 447 Epidemiological, 36, 49, 240, 385 Epidermal, 204, 210, 385, 386, 412 Epidermal Growth Factor, 210, 386 Epidermis, 204, 375, 379, 385, 386, 398, 436 Epinephrine, 353, 381, 386, 420, 421, 456 Epithalamus, 216, 380, 386, 408 Epithelial, 204, 231, 234, 352, 386, 397, 406 Epithelial Cells, 234, 386, 397, 406 Epithelium, 204, 362, 385, 386, 405, 422 Epitope, 226, 386 ERV, 250, 268, 288, 290, 386, 388 Erythrocyte Volume, 363, 386 Erythrocytes, 356, 363, 386 Esophagus, 380, 386, 427, 448
468 Brain
Essential Tremor, 296, 386 Estradiol, 6, 77, 134, 386 Estrogen, 6, 8, 36, 74, 77, 101, 211, 359, 386, 433, 442, 450 Estrogen receptor, 37, 77, 386 Estrone, 6, 386 Ethanol, 124, 219, 387 Ethanolamine, 136, 387 Ethidium, 223, 387 Ethnic Groups, 247, 387 Etoposide, 149, 273, 387 Eukaryotic Cells, 232, 387, 401, 424, 456 Evacuation, 221, 314, 387, 407 Evoke, 387, 448 Excitation, 47, 219, 355, 387, 389, 420 Excitatory, 33, 73, 233, 387, 394 Excitatory Amino Acids, 233, 387 Excitotoxicity, 152, 248, 387 Exhaustion, 158, 356, 387, 411 Exocrine, 77, 369, 387, 425 Exogenous, 70, 238, 353, 362, 384, 387, 392, 394 Exon, 210, 387 Exotoxin, 113, 387 Expiration, 387, 388, 440 Expiratory, 386, 387, 388 Expiratory Reserve Volume, 386, 388 Extensor, 388, 435 External-beam radiation, 388, 405, 437, 460 Extracellular, 29, 37, 66, 79, 218, 226, 233, 355, 360, 375, 388, 389, 402, 411, 414, 445 Extracellular Matrix, 218, 375, 388, 389, 402, 411 Extracellular Matrix Proteins, 388, 411 Extracellular Space, 388, 414 Extraction, 213, 214, 229, 230, 388 Extrapyramidal, 358, 381, 388 Extravasation, 388, 396 Extremity, 388, 425, 441 F Facial, 229, 304, 310, 348, 388, 397, 412 Facial Expression, 229, 388 Facial Pain, 310, 388 Facial Paralysis, 304, 388 Factor V, 13, 388 Family Planning, 285, 388 Family Relations, 307, 389 Fast Neutrons, 389, 421 Fat, 57, 134, 135, 218, 358, 363, 366, 368, 383, 389, 408, 416, 445, 449 Fatigue, 133, 186, 245, 370, 389, 396
Fatty acids, 132, 148, 351, 354, 389, 394, 433 Febrile, 36, 44, 389, 411 Ferritin, 59, 78, 389 Fetal Blood, 382, 389 Fetus, 17, 34, 50, 389, 428, 432, 456 Fibrin, 135, 363, 389, 429, 452 Fibrinogen, 208, 389, 429, 452 Fibroblast Growth Factor, 15, 81, 210, 389 Fibroblasts, 389, 403 Fibrosarcoma, 115, 389 Fibrosis, 144, 296, 389, 442 Firearms, 288, 389 Fissure, 371, 373, 376, 379, 389, 432 Flatus, 389, 391 Flow Cytometry, 59, 389 Fluid Therapy, 390, 422 Fluorescence, 33, 71, 220, 387, 389, 390 Fluorescent Dyes, 389, 390 Folate, 13, 139, 140, 390 Fold, 31, 35, 37, 43, 62, 389, 390 Folic Acid, 13, 138, 139, 390 Follow-Up Studies, 26, 390 Foramen, 369, 390, 407, 412, 427 Forearm, 363, 390 Forskolin, 74, 390 Fossa, 252, 368, 390 Fourth Ventricle, 370, 390, 452 Free Radicals, 357, 380, 390, 417 Frontal Lobe, 126, 267, 368, 390, 432 Fructose, 390, 397 Functional magnetic resonance imaging, 5, 8, 10, 22, 32, 33, 47, 60, 64, 71, 89, 102, 149, 231, 390 Fungus, 376, 391 G GABA, 21, 34, 76, 103, 133, 135, 154, 214, 215, 222, 391, 394, 444 Gadolinium, 110, 188, 391 Gait, 23, 32, 116, 368, 391 Galactitol, 21, 391 Galactokinase, 391 Galactosemia, 21, 391 Gallbladder, 351, 369, 380, 391 Gamma Rays, 391, 437 Gamma-interferon, 391, 403 Ganciclovir, 87, 193, 391 Ganglia, 351, 361, 391, 418, 426, 449 Ganglion, 227, 372, 391, 423, 458 Ganglioside, 39, 146, 391 Gas, 314, 355, 366, 369, 386, 387, 389, 391, 398, 421, 436, 440, 449, 457
Index 469
Gas exchange, 391, 440, 457 Gastric, 177, 366, 386, 391 Gastrin, 392, 398 Gastrointestinal stromal tumor, 191, 392 Gastrointestinal tract, 117, 204, 314, 370, 387, 392, 443, 446 Gelatin, 377, 392, 394, 452 Gene Expression, 12, 13, 42, 56, 58, 75, 85, 151, 223, 232, 296, 392 Gene Targeting, 116, 244, 392 Gene Therapy, 39, 49, 53, 55, 95, 192, 205, 225, 392 Genetic Code, 392, 422 Genetic Engineering, 312, 362, 371, 392 Genetic testing, 10, 392, 430 Genetics, 3, 13, 135, 227, 249, 308, 327, 374, 381, 392 Genistein, 148, 151, 392 Genital, 371, 392, 456 Genitourinary, 235, 392, 456 Genomics, 92, 110, 392 Genotype, 184, 392, 427 Germ cell tumors, 183, 393 Germ Cells, 393, 412, 424, 445, 446, 451 Germinoma, 98, 393 Gestation, 17, 51, 373, 393, 426, 428 Gestures, 247, 393 Ginkgo biloba, 143, 150, 152, 172, 393 Ginseng, 167, 176, 393 Gland, 352, 370, 393, 410, 425, 428, 434, 442, 448, 449, 452, 453 Glasgow Coma Scale, 97, 112, 393 Glioblastoma, 191, 192, 393 Glioblastoma multiforme, 191, 393 Glioma, 35, 52, 53, 55, 95, 98, 182, 187, 191, 192, 195, 196, 294, 393 Globus Pallidus, 103, 361, 376, 393, 436 Glossopharyngeal Nerve, 388, 393 Glucocorticoid, 210, 211, 393 Glucokinase, 393, 397 Glucose, 17, 20, 26, 97, 131, 132, 151, 198, 213, 219, 220, 230, 240, 256, 261, 294, 295, 330, 359, 363, 368, 379, 391, 393, 394, 396, 397, 399, 402, 441, 446 Glucose Intolerance, 379, 393 Glucuronosyltransferase, 233, 394 Glutamate, 18, 20, 74, 76, 82, 116, 122, 133, 233, 328, 387, 394, 406 Glutamate Decarboxylase, 74, 394 Glutamic Acid, 294, 328, 390, 394, 420 Glutamine, 18, 172, 394 Glutathione Peroxidase, 149, 394
Glycerol, 394, 427 Glycerophospholipids, 394, 427 Glycine, 73, 172, 214, 354, 394, 420, 443 Glycolysis, 20, 394 Glycoprotein, 18, 65, 75, 78, 81, 146, 388, 389, 394, 395, 406, 416, 452, 455 Goats, 394, 442 Gonad, 394 Gonadal, 8, 31, 394, 447 Gonadotropin, 134, 394 Governing Board, 394, 431 Government Agencies, 245, 394, 431 Gp120, 39, 106, 395, 426 Grade, 52, 98, 191, 364, 393, 395 Graft, 210, 217, 395, 398, 401, 417 Graft Rejection, 395, 401 Grafting, 395, 401 Granule, 379, 395, 440 Granulocytes, 395, 407, 444, 459 Grasses, 390, 395 Group Structure, 312, 395 Growth factors, 10, 69, 228, 395, 414, 418 Guanylate Cyclase, 395, 421 Gyrus Cinguli, 395, 408 H Habitual, 369, 395 Haematoma, 395 Haemorrhage, 91, 395 Hair follicles, 379, 395, 459 Hallucination, 91, 395 Haploid, 395, 428 Haptens, 353, 395 Headache, 162, 396, 399 Health Care Costs, 376, 396 Health Education, 319, 396 Health Physics, 396, 408 Hearing aid, 227, 396 Hearing Disorders, 373, 396 Heart failure, 92, 396, 422 Heart Transplantation, 105, 119, 396 Heartbeat, 396, 449 Hematemesis, 230, 396 Hematoma, 19, 301, 396 Heme, 362, 377, 396, 417, 430 Hemiparesis, 364, 396 Hemoglobin, 31, 356, 377, 386, 396, 397, 430 Hemoglobin A, 396, 430 Hemoglobin M, 31, 377, 396 Hemoglobinopathies, 392, 396 Hemoglobinuria, 295, 397
470 Brain
Hemorrhage, 19, 47, 56, 91, 93, 137, 203, 259, 376, 383, 396, 397, 417, 436, 448 Hemostasis, 397, 403, 443 Hepatic, 204, 354, 378, 397, 415 Hepatitis, 144, 397 Hepatocytes, 397 Hereditary, 397, 416, 418, 440 Heredity, 245, 392, 397 Herpes, 6, 11, 87, 193, 278, 397 Herpes virus, 193, 397 Herpes Zoster, 397 Heterodimers, 397, 402, 454 Heterogeneity, 11, 112, 353, 397 Hexokinase, 75, 397 Histology, 133, 251, 397, 419 Holistic Health, 144, 397 Holoprosencephaly, 334, 397 Homeostasis, 66, 72, 214, 228, 256, 397 Homodimer, 398, 454 Homogenate, 263, 398 Homogeneous, 359, 375, 398 Homologous, 262, 362, 392, 398, 450 Hormonal, 211, 218, 225, 360, 398 Hormonal therapy, 211, 398 Hormone, 11, 20, 23, 76, 84, 103, 117, 135, 210, 216, 266, 327, 370, 376, 379, 386, 392, 398, 402, 404, 432, 433, 444, 446, 451, 452, 454 Hormone Replacement Therapy, 11, 266, 398 Hormone therapy, 398 Horny layer, 386, 398 Hospices, 240, 398 Host, 6, 29, 41, 49, 83, 205, 209, 210, 217, 225, 234, 254, 361, 372, 398, 400, 401, 459 Hybrid, 371, 398 Hybridization, 76, 215, 367, 398, 448 Hybridoma, 213, 214, 398 Hydrogen, 351, 362, 365, 366, 379, 388, 394, 398, 408, 415, 421, 422, 424, 427, 434, 449 Hydrogen Peroxide, 366, 394, 398, 408, 449 Hydrolysis, 136, 225, 351, 362, 398, 405, 427, 434 Hydrophilic, 65, 206, 398 Hydrophobic, 65, 206, 394, 398, 408 Hydroxyproline, 354, 372, 398 Hyperglycemia, 30, 104, 399 Hyperoxia, 72, 399 Hypersensitivity, 25, 50, 314, 399
Hypertension, 111, 117, 202, 213, 214, 359, 399, 404, 431 Hypertensive Encephalopathy, 56, 399 Hyperthermia, 133, 399 Hypertrophy, 101, 399 Hyperventilation, 112, 348, 399 Hypnotic, 144, 216, 361, 399, 451 Hypoglycaemia, 378, 399 Hypoglycemia, 20, 30, 159, 399 Hypoglycemic, 30, 399 Hypokinesia, 399, 425 Hypoplasia, 294, 399 Hypotension, 107, 358, 375, 399, 420 Hypothalamic, 187, 191, 195, 399 Hypothalamus, 313, 361, 364, 376, 380, 399, 408, 420, 428, 433, 443, 446, 452 Hypothermia, 113, 159, 185, 202, 250, 399 Hypoxemia, 17, 399 Hypoxia, 16, 17, 37, 137, 145, 184, 203, 215, 301, 368, 378, 399 Hypoxic, 14, 16, 93, 127, 149, 214, 399 I Id, 138, 156, 300, 301, 303, 317, 318, 319, 325, 344, 346, 400 Idiopathic, 10, 99, 258, 400 Ileum, 400, 420 Illusion, 400, 423, 458 Immune function, 145, 218, 400, 454 Immune response, 50, 63, 191, 352, 356, 357, 361, 395, 400, 449, 458, 459 Immune system, 50, 63, 67, 144, 248, 357, 362, 400, 401, 410, 416, 417, 435, 456, 459 Immunity, 29, 50, 144, 351, 353, 400, 410 Immunization, 400, 401 Immunoassay, 213, 214, 400 Immunodeficiency, 39, 78, 79, 80, 104, 248, 267, 295, 307, 351, 400 Immunodeficiency syndrome, 267, 400 Immunodiffusion, 353, 400 Immunodominant Epitopes, 50, 400 Immunoelectrophoresis, 353, 400 Immunofluorescence, 39, 400 Immunoglobulin, 73, 357, 400, 415 Immunohistochemistry, 42, 59, 400 Immunologic, 369, 400, 437, 460 Immunology, 352, 353, 390, 400 Immunosuppressive, 50, 377, 393, 400, 401, 450 Immunosuppressive therapy, 400, 401 Immunotherapy, 53, 192, 362, 401 Implant radiation, 401, 403, 405, 437, 460
Index 471
Implantation, 9, 11, 210, 225, 228, 254, 260, 374, 401 In situ, 15, 17, 26, 28, 42, 59, 74, 76, 80, 95, 104, 234, 401 In Situ Hybridization, 28, 42, 59, 74, 80, 95, 401 Incision, 401, 404 Incontinence, 163, 401, 442 Indicative, 401, 425, 457 Indomethacin, 101, 401 Induction, 12, 52, 62, 79, 83, 106, 124, 211, 217, 237, 355, 358, 401, 433 Infancy, 132, 335, 401 Infant Care, 316, 401 Infant, Newborn, 353, 401 Infarction, 71, 107, 149, 203, 368, 401, 439 Infection Control, 267, 401 Infiltration, 25, 52, 67, 401, 432 Inflammatory bowel disease, 217, 402 Infusion, 59, 208, 363, 402, 410, 417, 454 Ingestion, 130, 216, 365, 402, 430 Inhalation, 133, 402, 430 Initiation, 21, 64, 402, 454 Innervation, 81, 402, 427, 441, 453 Inositol, 18, 62, 173, 402 Inotropic, 381, 402 Inpatients, 402, 445 Insertional, 24, 402 Insight, 46, 57, 69, 247, 329, 330, 402 Insomnia, 159, 216, 402 Institutionalization, 240, 291, 308, 402 Insulator, 313, 402, 416 Insulin, 126, 218, 402 Insulin-dependent diabetes mellitus, 402 Integrins, 61, 402 Intensive Care, 110, 403 Intercellular Adhesion Molecule-1, 106, 403 Interferon, 111, 278, 391, 403, 410 Interferon-alpha, 403 Interleukin-1, 38, 79, 113, 403 Interleukin-2, 278, 403 Interleukin-6, 58, 403 Interleukins, 215, 403 Intermediate Filaments, 403, 419 Intermittent, 228, 390, 403, 409 Internal radiation, 403, 405, 437, 460 Interneurons, 34, 403 Interstitial, 53, 364, 388, 403, 405, 412, 439, 460 Intervention Studies, 144, 403 Intestinal, 234, 366, 369, 404, 411
Intestinal Mucosa, 369, 404 Intestine, 130, 364, 404, 406 Intoxication, 378, 404, 459 Intracellular, 29, 33, 211, 217, 401, 402, 404, 412, 421, 431, 433, 438, 444 Intracellular Membranes, 404, 412 Intracranial Aneurysm, 221, 404 Intracranial Embolism, 368, 404 Intracranial Embolism and Thrombosis, 368, 404 Intracranial Hypertension, 99, 396, 404, 453 Intracranial Pressure, 37, 206, 221, 404, 435 Intraindividual, 113, 404 Intramuscular, 404, 425 Intraocular, 373, 390, 404 Intraocular pressure, 390, 404 Intrathecal chemotherapy, 55, 404 Intravenous, 59, 69, 237, 363, 402, 404, 425 Intrinsic, 16, 24, 232, 353, 362, 404 Intubation, 115, 349, 367, 404 Invasive, 27, 63, 72, 111, 152, 204, 205, 219, 220, 400, 404, 410 Involuntary, 328, 361, 382, 386, 404, 417, 438, 444, 446 Iodine, 404, 437 Ion Channels, 360, 404, 450 Ion Exchange, 368, 404, 405 Ion Transport, 17, 66, 405 Ionization, 235, 405 Ionizing, 354, 385, 396, 405, 437 Ions, 33, 66, 235, 351, 362, 365, 380, 383, 398, 405, 434, 445 Iontophoresis, 205, 206, 405 Ipsilateral, 71, 405, 438 Irinotecan, 185, 405 Iris, 357, 359, 375, 405, 436 Irradiation, 235, 318, 364, 405, 421, 460 Ischemic stroke, 19, 203, 214, 405 Isoenzyme, 397, 405 Isozymes, 74, 82, 406 J Joint, 291, 307, 359, 406, 424, 450 Jugular Veins, 219, 406 K Kainate, 214, 215, 380, 406 Kallidin, 364, 406 Kb, 38, 284, 406 Keto, 21, 106, 406 Kidney Cortex, 406, 413 Kidney Disease, 200, 284, 296, 406 Kinetic, 20, 405, 406
472 Brain
L Labile, 373, 388, 406 Labyrinth, 372, 406, 458 Lactation, 406, 433 Laminin, 232, 362, 388, 406 Language Development, 315, 406 Language Development Disorders, 406 Language Disorders, 252, 307, 373, 406 Language Therapy, 259, 305, 406 Large Intestine, 380, 404, 406, 438, 445 Larynx, 407, 454, 457 Latency, 216, 407 Latent, 407, 431 Lateral Ventricles, 34, 41, 407, 443, 452 Laterality, 126, 253, 407 Laxative, 353, 407, 446 Least-Squares Analysis, 407, 439 Lens, 220, 358, 391, 407, 459 Lethal, 49, 115, 361, 407 Leucocyte, 407, 410 Leukemia, 159, 189, 211, 232, 252, 293, 295, 321, 352, 381, 392, 407 Leukocytes, 50, 362, 363, 369, 385, 395, 401, 403, 407, 415, 455 Leukopenia, 407, 460 Levodopa, 135, 169, 174, 381, 407 Libido, 355, 407 Library Services, 344, 407 Life Expectancy, 127, 192, 407 Ligament, 407, 434 Ligands, 77, 217, 402, 408 Likelihood Functions, 408, 439 Limbic, 34, 67, 79, 228, 267, 314, 355, 395, 408, 432 Limbic System, 67, 228, 267, 314, 355, 395, 408, 432 Linear Energy Transfer, 235, 408 Linear Models, 408, 439 Linkage, 30, 225, 408 Lipectomy, 57, 408 Lipid, 29, 149, 203, 206, 229, 230, 358, 359, 365, 370, 394, 402, 406, 408, 416, 424 Lipid Peroxidation, 29, 149, 408, 424 Lipophilic, 23, 206, 408 Lipopolysaccharide, 104, 408 Lipoprotein, 46, 81, 408, 409 Liver scan, 408, 441 Lobe, 368, 408, 433 Lobule, 8, 408 Localization, 5, 47, 48, 75, 76, 77, 79, 80, 81, 82, 87, 108, 231, 259, 260, 311, 400, 408, 411
Locomotion, 115, 409, 428 Locomotor, 409, 442 Logistic Models, 409, 439 Longitudinal study, 9, 290, 409 Long-Term Care, 243, 409 Long-Term Potentiation, 13, 409 Loop, 89, 272, 409 Lordosis, 148, 409 Low-density lipoprotein, 408, 409 Lucida, 406, 409 Luciferase, 38, 409 Lumbar, 409, 441, 453 Lumen, 206, 219, 365, 385, 409 Lupus, 160, 162, 330, 409 Lutein Cells, 409, 433 Lymph, 361, 369, 371, 385, 409, 410, 448 Lymph node, 361, 369, 410 Lymphatic, 160, 230, 385, 401, 409, 410, 413, 422, 429, 445, 447, 452 Lymphatic system, 230, 409, 410, 445, 447, 452 Lymphoblastic, 410 Lymphoblasts, 211, 352, 410 Lymphocyte, 215, 351, 357, 410, 412 Lymphocyte Count, 351, 410 Lymphoid, 67, 211, 357, 376, 407, 410 Lymphokines, 215, 410 Lymphoma, 295, 410 Lymphoproliferative, 217, 410 Lymphoproliferative Disorders, 217, 410 Lymphotoxin, 217, 410 M Macroglia, 410, 414 Macrophage, 78, 403, 410 Mafosfamide, 149, 189, 410 Magnetic Resonance Imaging, 4, 7, 8, 30, 34, 37, 41, 48, 97, 99, 117, 240, 314, 410, 441 Magnetic Resonance Spectroscopy, 21, 39, 91, 136, 137, 410 Magnetoencephalography, 46, 410 Malabsorption, 295, 411 Malaria, 86, 411 Malaria, Falciparum, 411 Malaria, Vivax, 411 Malformation, 118, 334, 411 Malignancy, 222, 411 Malignant, 39, 53, 55, 62, 113, 114, 149, 182, 183, 191, 192, 193, 197, 235, 293, 295, 334, 337, 351, 352, 357, 359, 376, 392, 393, 399, 411, 412, 418, 437, 440, 441 Malignant tumor, 411, 440
Index 473
Malnutrition, 354, 360, 411, 416 Malondialdehyde, 29, 411 Mammary, 411, 450 Mania, 411 Manic, 135, 240, 322, 336, 358, 411, 435 Manic-depressive psychosis, 135, 411, 435 Manifest, 11, 66, 361, 411 Maple Syrup Urine Disease, 21, 106, 411 Matrix metalloproteinase, 37, 81, 411 Maximum Tolerated Dose, 196, 382, 411 Measles Virus, 123, 274, 412 Meatus, 412, 456 Medial, 4, 9, 231, 359, 371, 372, 393, 395, 412, 423, 443, 453 Mediate, 17, 76, 126, 372, 381, 412 Mediator, 38, 63, 369, 381, 403, 412, 443 Medical Oncology, 412, 437 Medicament, 237, 412 MEDLINE, 285, 293, 296, 412 Medullary, 412, 436 Medulloblastoma, 55, 184, 187, 191, 195, 196, 412 Megaloblastic, 390, 412 Meiosis, 362, 412, 450 Melanin, 314, 405, 412, 427, 456 Melanocytes, 412, 421 Melanoma, 121, 189, 190, 196, 235, 295, 364, 412 Membrane, 17, 29, 62, 72, 80, 102, 148, 204, 210, 226, 228, 231, 256, 294, 359, 367, 370, 373, 374, 379, 387, 395, 404, 406, 407, 412, 414, 416, 417, 424, 425, 427, 440, 443, 444, 455, 459 Membrane Fusion, 228, 412 Membrane Glycoproteins, 412 Membrane Lipids, 412, 427 Meningeal, 226, 413 Meninges, 368, 376, 382, 413, 448 Meningioma, 182, 183, 188, 189, 195, 413 Meningitis, 122, 160, 413 Meningoencephalitis, 49, 413 Menopause, 160, 413, 431 Menstrual Cycle, 6, 413, 432 Menstruation, 230, 413 Mental Disorders, 41, 61, 124, 200, 399, 406, 413, 435 Mental Retardation, 13, 16, 29, 223, 297, 373, 397, 413 Mercury, 389, 413 Mesenchymal, 386, 413 Metabolic disorder, 41, 322, 413 Metabolite, 21, 43, 362, 386, 413, 428, 432
Metallothionein, 12, 155, 413 Metastasis, 144, 190, 192, 199, 318, 411, 413 Metastatic, 35, 105, 108, 118, 186, 191, 192, 194, 195, 196, 199, 413, 442 Methionine, 154, 175, 414, 433, 449 Methylphenidate, 26, 116, 186, 414 MI, 77, 80, 103, 240, 257, 349, 414 Microbe, 414, 454 Microbiology, 352, 360, 414 Microcirculation, 230, 414, 429 Microdialysis, 24, 26, 414 Microglia, 38, 58, 67, 224, 248, 360, 414, 415 Microorganism, 372, 414, 425, 459 Microscopy, 15, 17, 35, 96, 362, 414 Microspheres, 16, 414 Microtubule-Associated Proteins, 414, 419, 450 Microtubules, 403, 414, 419, 425, 450 Middle Cerebral Artery, 18, 47, 414 Migration, 49, 67, 209, 228, 371, 403, 414 Mitochondria, 70, 351, 414, 417, 424 Mitosis, 358, 415 Mitotic, 387, 415, 458 Mobility, 241, 329, 415 Modeling, 20, 26, 146, 381, 415 Modification, 64, 76, 133, 151, 230, 261, 354, 392, 415, 436, 460 Modulator, 214, 215, 415 Monitor, 7, 41, 44, 53, 55, 63, 202, 207, 236, 415, 421 Monoamine, 10, 75, 379, 415, 456 Monoamine Oxidase, 10, 75, 379, 415, 456 Monoclonal, 35, 62, 73, 187, 195, 199, 209, 213, 214, 405, 415, 437, 460 Monoclonal antibodies, 35, 187, 195, 199, 415 Monocytes, 65, 403, 407, 415, 451 Mononuclear, 25, 415, 455 Morbillivirus, 412, 415 Morphological, 42, 247, 254, 255, 263, 353, 383, 391, 412, 415, 420 Morphology, 24, 133, 253, 415 Motility, 401, 416, 443 Motion Sickness, 160, 416, 417, 442 Motor Skills, 116, 243, 416 Movement Disorders, 207, 358, 382, 416, 451 Mucinous, 391, 416 Mucolytic, 351, 416 Mucosa, 409, 416, 417, 433, 448 Mucositis, 416, 452
474 Brain
Multiple sclerosis, 25, 91, 117, 119, 120, 203, 213, 237, 240, 259, 317, 416 Multivariate Analysis, 220, 416 Muscle Contraction, 329, 416 Muscle Fibers, 416, 417 Muscular Atrophy, 296, 416 Muscular Diseases, 388, 416 Muscular Dystrophies, 382, 416 Music Therapy, 144, 416 Mydriatic, 380, 416, 442 Myelin, 75, 416, 423, 443 Myelin Sheath, 416, 423 Myeloma, 398, 416 Myocardial infarction, 95, 375, 414, 417 Myocardial Reperfusion, 417, 439 Myocardial Reperfusion Injury, 417, 439 Myocardium, 414, 417 Myoglobin, 417, 430 Myopathy, 223, 417 Myosin, 416, 417 Myotonic Dystrophy, 296, 417 N N-acetyl, 62, 91, 150, 351, 417 N-Acetyl, 176 Naive, 22, 136, 417 Narcolepsy, 379, 414, 417 Nasal Cavity, 228, 417 Nasal Mucosa, 211, 212, 417 Nasal Septum, 417 Nausea, 358, 399, 417, 435 Neocortex, 261, 418, 419 Neonatal, 34, 40, 101, 108, 112, 148, 149, 210, 418 Neonatal period, 34, 418 Neoplasia, 295, 418 Neoplasm, 188, 190, 191, 192, 198, 199, 260, 418, 441, 456 Neoplastic, 235, 388, 410, 418, 423 Neostriatum, 367, 376, 418, 436 Nephropathy, 406, 418 Nerve Endings, 222, 418 Nerve Fibers, 232, 372, 418, 453 Nerve Growth Factor, 76, 78, 217, 418 Networks, 30, 34, 48, 332, 418 Neurites, 7, 84, 418 Neuroanatomy, 14, 64, 231, 261, 408, 418 Neurobehavioral Manifestations, 364, 380, 418 Neuroblastoma, 192, 197, 199, 418 Neurodegenerative Diseases, 10, 44, 46, 52, 131, 152, 361, 418 Neuroectodermal tumor, 191, 419, 432
Neuroeffector Junction, 418, 419 Neurofibrillary Tangles, 5, 84, 226, 249, 251, 258, 261, 419, 420, 450 Neurofilaments, 419 Neurogenic, 135, 255, 265, 419 Neuroleptic, 357, 371, 419 Neurologic Manifestations, 267, 419 Neurologist, 11, 419 Neuroma, 260, 263, 310, 419 Neuromuscular, 223, 351, 388, 419 Neuromuscular Junction, 351, 419 Neuronal atrophy, 28, 419 Neuropathy, 223, 295, 355, 419 Neuropeptide, 75, 84, 419 Neurophysiology, 40, 89, 98, 146, 148, 150, 379, 419 Neuropil, 7, 420, 450 Neuropil Threads, 7, 420, 450 Neuropsychological Tests, 4, 5, 9, 30, 420 Neuropsychology, 99, 107, 231, 246, 252, 420 Neurosciences, 47, 93, 113, 116, 122, 137, 420 Neurosecretory Systems, 384, 420 Neurosis, 258, 420 Neurosurgeon, 231, 420 Neurosurgical Procedures, 207, 231, 420 Neurotensin, 77, 420 Neurotic, 420, 457 Neurotoxic, 36, 38, 39, 52, 58, 227, 351, 420 Neurotoxicity, 29, 50, 53, 75, 420 Neurotoxins, 249, 420 Neutron Capture Therapy, 235, 420 Neutrons, 235, 354, 364, 389, 405, 421, 437 Neutrophil, 214, 403, 421 Nevus, 313, 421 Niacin, 138, 139, 421, 455 Nicotine, 26, 50, 66, 87, 421 Nifedipine, 133, 421 Nitric Oxide, 16, 42, 83, 135, 214, 421 Nitrogen, 127, 353, 354, 355, 377, 388, 394, 421, 455 Non-small cell lung cancer, 185, 188, 195, 421 Nonverbal Communication, 373, 421, 435 Norepinephrine, 127, 353, 381, 420, 421 Nuclear, 17, 59, 87, 97, 235, 319, 361, 365, 374, 387, 389, 391, 393, 408, 421, 451, 456 Nuclear Family, 389, 421 Nucleic acid, 215, 221, 225, 387, 392, 398, 401, 421, 432, 436, 448, 460 Nucleic Acid Hybridization, 398, 422
Index 475
Nucleus Accumbens, 93, 422 Nursing Care, 422, 444 Nutritional Support, 213, 422 O Obsessive-Compulsive Disorder, 101, 422 Occipital Lobe, 256, 422, 459 Occult, 137, 422 Ocular, 204, 422 Odds Ratio, 6, 422 Oedema, 99, 422, 432 Olfactory Bulb, 422 Olfactory Nerve, 205, 422 Oligodendroglia, 209, 416, 422 Oligodendroglial, 423 Oligodendroglioma, 191, 195, 423 Oligoelement, 423 Oncogene, 225, 295, 423 Oncogenic, 403, 423, 434 Oncology, 39, 51, 54, 55, 89, 95, 96, 109, 110, 113, 133, 135, 149, 154, 187, 191, 193, 197, 423 Oncolysis, 423 Oncolytic, 95, 423 On-line, 33, 337, 347, 423 Opacity, 379, 423 Opiate, 328, 423 Opioid Peptides, 101, 382, 384, 385, 423 Opium, 423 Opportunistic Infections, 49, 267, 351, 423 Optic Chiasm, 399, 423 Optic Nerve, 423, 424, 435, 440, 442 Optical Illusions, 315, 423 Orbit, 423 Orbital, 7, 423 Organelles, 378, 412, 415, 424 Orgasm, 383, 424 Orofacial, 388, 424 Osmosis, 424 Osmotic, 58, 354, 424, 443 Osteoarthritis, 22, 160, 424 Outpatient, 23, 424 Ovaries, 359, 424, 444 Ovary, 215, 386, 394, 424, 430, 448 Overall survival, 53, 61, 190, 424 Ovum, 393, 424, 432, 433, 459, 460 Oxaliplatin, 39, 424 Oxidation, 218, 263, 351, 357, 362, 377, 394, 396, 408, 424 Oxidative Phosphorylation, 97, 147, 424 Oxidative Stress, 13, 29, 45, 72, 83, 150, 424 Oxygen Consumption, 424, 440 Oxygenation, 399, 424
P Pachymeningitis, 413, 424 Paclitaxel, 65, 424 Palliative, 398, 425, 452 Palsy, 107, 258, 310, 322, 425 Pancreas, 351, 380, 402, 425, 446 Pancreatic, 77, 295, 366, 369, 425 Pancreatic cancer, 295, 425 Papilledema, 399, 425, 435 Paralysis, 348, 358, 388, 396, 425 Parenteral, 24, 131, 213, 270, 425 Parenteral Nutrition, 213, 425 Paresis, 388, 425 Parietal, 8, 256, 261, 267, 313, 425, 427, 429 Parietal Lobe, 256, 425 Parkinsonism, 28, 88, 94, 135, 358, 407, 425 Paroxysmal, 295, 425 Partial remission, 425, 439 Parturition, 425, 433 Passive transport, 23, 230, 425 Patch, 29, 375, 425, 454 Pathogen, 52, 425 Pathogenesis, 25, 39, 50, 52, 72, 244, 248, 249, 251, 254, 258, 425 Pathologic, 203, 257, 358, 362, 364, 375, 399, 425, 431, 435 Pathologic Processes, 257, 358, 425 Pathologies, 109, 244, 426 Pathologist, 243, 247, 426 Pathophysiology, 10, 37, 38, 67, 152, 261, 329, 426 Patient Compliance, 204, 426 Patient Education, 303, 333, 342, 344, 349, 426 Pelvic, 426, 434 Penicillin, 176, 357, 426 Penis, 383, 426 Peptide T, 122, 311, 426 Perception, 4, 22, 26, 47, 60, 237, 240, 291, 314, 374, 395, 396, 426, 441 Percutaneous, 204, 208, 426, 427 Perfusion, 17, 18, 26, 40, 58, 62, 106, 207, 219, 317, 319, 399, 426 Pericytes, 35, 228, 426 Perinatal, 13, 16, 40, 426 Peripheral blood, 154, 191, 403, 426 Peripheral Nervous System, 224, 232, 241, 382, 385, 416, 419, 420, 425, 426, 432, 446, 449 Peripheral stem cell transplantation, 184, 192, 197, 426 Peritoneal, 89, 422, 427
476 Brain
Peritoneal Cavity, 422, 427 Peritoneum, 427 Perivascular, 228, 414, 422, 427 Peroneal Nerve, 427, 441 Petechiae, 395, 427 PH, 11, 22, 319, 329, 427 Phagocytosis, 228, 414, 427 Pharmacokinetic, 427 Pharmacologic, 112, 356, 360, 427, 454 Pharynx, 417, 427, 457 Phenotype, 69, 70, 212, 427 Phenyl, 427 Phenylalanine, 92, 146, 176, 427, 456 Phonophoresis, 205, 405, 427 Phosphodiesterase, 76, 78, 427 Phospholipases, 427, 444 Phospholipids, 62, 151, 198, 389, 402, 408, 412, 427 Phosphorus, 62, 365, 427, 428 Phosphorylated, 372, 420, 427 Phosphorylates, 64, 428 Phosphorylating, 74, 428 Phosphorylation, 10, 64, 428, 434 Photocoagulation, 371, 428 Photodynamic therapy, 187, 235, 428 Photoperiod, 57, 428 Photosensitizer, 235, 428 Photosensitizing Agents, 428, 430 Physiologic, 22, 44, 58, 207, 353, 381, 399, 413, 428, 433, 438, 444, 455 Pigments, 366, 428, 440 Pilot study, 46, 109, 428 Pineal Body, 386, 428 Pineal gland, 216, 428 Pituitary Gland, 132, 133, 389, 390, 428, 433 Placenta, 359, 386, 389, 428, 432, 436, 456 Plant Proteins, 216, 428, 457 Plaque, 28, 38, 84, 94, 203, 208, 226, 356, 428 Plasma, 37, 67, 101, 106, 112, 117, 134, 213, 214, 216, 228, 237, 353, 354, 357, 363, 367, 369, 385, 388, 389, 392, 393, 396, 397, 416, 429, 434, 439, 442, 443, 458 Plasma cells, 357, 416, 429 Plasma protein, 354, 385, 429, 434, 443 Plasmin, 429 Plasminogen, 120, 429 Plasminogen Activators, 429 Plasticity, 13, 47, 254, 429 Platelet Activation, 429, 444 Platelet Aggregation, 355, 390, 421, 429
Platelets, 208, 421, 429, 441, 452 Platinum, 409, 424, 429 Platinum Compounds, 424, 429 Pleomorphic, 422, 429 Pleural, 422, 429 Pleural cavity, 422, 429 Plexus, 429, 441 Pneumonia, 267, 375, 430 Podophyllotoxin, 387, 430 Poisoning, 203, 365, 369, 378, 404, 413, 417, 430, 443 Policy Making, 394, 430 Pollen, 229, 230, 430, 437 Polycystic, 296, 430 Polymerase, 6, 430 Polymerase Chain Reaction, 6, 430 Polymers, 204, 430, 434 Polymorphic, 370, 379, 430 Polysaccharide, 353, 357, 368, 430, 434 Pons, 364, 388, 390, 430 Porfimer sodium, 187, 430 Porphyrins, 235, 430 Port, 207, 219, 220, 430, 431 Port-a-cath, 431 Positron emission tomography scan, 329, 431 Posterior, 10, 19, 252, 256, 355, 359, 360, 368, 370, 381, 386, 393, 405, 422, 425, 428, 431, 442 Postmenopausal, 8, 431 Postnatal, 431, 447 Postoperative, 252, 260, 431 Postoperative Complications, 252, 431 Postsynaptic, 79, 222, 419, 431, 444, 450 Post-traumatic, 364, 416, 431 Postural, 115, 250, 431 Potassium, 35, 66, 75, 149, 214, 215, 229, 272, 431 Potentiates, 29, 403, 431 Potentiation, 29, 370, 409, 431, 444 Practice Guidelines, 292, 317, 431 Precipitating Factors, 367, 431 Preclinical, 51, 196, 431 Predisposition, 223, 431, 451 Preeclampsia, 100, 431 Pre-eclamptic, 382, 431 Prefrontal Cortex, 5, 7, 26, 432 Premedication, 432, 442 Prenatal, 13, 34, 243, 383, 432 Preoperative, 231, 260, 432 Presynaptic, 418, 419, 420, 432, 450 Presynaptic Terminals, 418, 432
Index 477
Prevalence, 30, 31, 36, 37, 56, 79, 106, 124, 125, 267, 312, 317, 334, 422, 432 Primitive neuroectodermal tumors, 184, 412, 432 Prion, 244, 249, 432 Probe, 5, 24, 67, 83, 260, 414, 432 Probenecid, 18, 432 Procaine, 67, 432 Prodrug, 213, 432 Progeny, 209, 374, 432 Progesterone, 177, 432, 433, 447 Progression, 7, 12, 36, 38, 110, 188, 190, 212, 356, 432, 455 Projection, 13, 378, 403, 421, 422, 423, 432, 436, 438 Prolactin, 134, 433 Promoter, 38, 59, 210, 211, 433 Promyelocytic leukemia, 211, 433 Prone, 43, 433 Pro-Opiomelanocortin, 384, 423, 433 Prophase, 362, 433, 450 Prophylaxis, 54, 319, 432, 433 Prosencephalon, 380, 397, 433, 451 Prospective study, 409, 433 Prostaglandin, 29, 38, 74, 78, 295, 433 Prostaglandins A, 52, 401, 433 Prostaglandins D, 433, 434 Prostate, 161, 221, 231, 295, 434 Protease, 434, 441 Protein C, 103, 108, 113, 226, 249, 328, 354, 358, 361, 389, 408, 434, 456 Protein Conformation, 354, 434 Protein S, 64, 125, 223, 250, 296, 297, 362, 392, 434, 440 Protein-Tyrosine Kinase, 392, 434 Proteinuria, 431, 434 Proteoglycans, 362, 388, 434 Proteolytic, 64, 373, 389, 429, 434 Prothrombin, 388, 434, 452 Protocol, 16, 41, 193, 197, 198, 434 Protons, 354, 398, 405, 410, 434, 437 Proto-Oncogene Proteins, 425, 434 Proto-Oncogene Proteins c-mos, 425, 434 Protozoan, 411, 434 Proximal, 381, 406, 417, 432, 435, 443 Pruritus, 435, 442 Pseudotumor Cerebri, 404, 435 Psoriasis, 217, 428, 435 Psychic, 315, 407, 413, 420, 435, 442 Psychoactive, 435, 459 Psychology, 41, 60, 63, 91, 374, 380, 420, 435
Psychometric testing, 252, 435 Psychomotor, 4, 30, 378, 419, 435 Psychoneuroimmunology, 144, 435 Psychophysics, 260, 435 Psychophysiology, 99, 147, 420, 435 Psychosis, 258, 357, 435 Psychotherapy, 128, 243, 435 Puberty, 134, 436 Public Health, 37, 243, 250, 268, 288, 289, 292, 324, 436 Public Policy, 124, 125, 127, 285, 436 Puerperium, 230, 436 Pulmonary, 37, 92, 111, 117, 122, 135, 204, 208, 363, 369, 375, 382, 399, 436, 449, 457 Pulmonary Artery, 111, 363, 382, 436, 458 Pulmonary Edema, 135, 369, 436 Pulmonary Embolism, 92, 122, 208, 436 Pulmonary Gas Exchange, 37, 436 Pulmonary Ventilation, 399, 436 Pulse, 16, 21, 41, 56, 348, 415, 436 Pupil, 375, 380, 416, 436 Pupillary Reflex, 83, 436 Purines, 436, 443 Purpura, 395, 436 Putamen, 16, 45, 65, 361, 376, 418, 436 Pyramidal Cells, 379, 436 Pyridoxal, 394, 436 Pyrimidines, 436, 443 Q Quality of Life, 56, 59, 60, 153, 186, 197, 333, 337, 376, 436, 449 Quaternary, 434, 436, 442 Quercetin, 229, 437 R Race, 381, 414, 437 Radiation Oncology, 39, 55, 437 Radioactive iodine, 187, 195, 437 Radiobiology, 408, 437 Radioimmunotherapy, 437 Radiolabeled, 187, 195, 199, 405, 437, 460 Radiological, 190, 260, 300, 426, 437 Radiology, 21, 33, 39, 43, 46, 55, 71, 86, 113, 115, 136, 145, 231, 300, 318, 437 Radiopharmaceuticals, 319, 437 Radiotherapy, 56, 98, 181, 192, 194, 364, 405, 437, 447, 460 Randomized, 8, 59, 110, 112, 181, 186, 187, 188, 193, 194, 195, 196, 289, 383, 437 Randomized Controlled Trials, 289, 437 Ras gene, 78, 438 Reactive Oxygen Species, 38, 438 Reagent, 204, 369, 387, 409, 438
478 Brain
Reality Testing, 435, 438 Receptors, Serotonin, 438, 443 Recombinant, 29, 59, 113, 217, 278, 438, 457 Recombination, 374, 392, 438 Recovery of Function, 71, 232, 438 Rectal, 314, 438 Rectum, 358, 364, 373, 380, 389, 391, 401, 402, 406, 434, 438, 444 Recurrence, 36, 370, 411, 438 Red Nucleus, 360, 438 Reductase, 359, 438 Reflex, 250, 313, 438 Refraction, 438, 446 Refractory, 55, 96, 183, 184, 187, 189, 191, 196, 225, 383, 438 Regeneration, 233, 389, 438 Regimen, 50, 382, 426, 439, 440 Registries, 334, 439 Regression Analysis, 6, 439 Rehabilitative, 251, 439 Relapse, 62, 67, 439 Relaxant, 390, 439 Remission, 211, 411, 438, 439 Renal failure, 378, 439 Renal tubular, 432, 439 Renin, 86, 92, 356, 439 Renin-Angiotensin System, 86, 92, 439 Reperfusion, 18, 64, 136, 150, 151, 153, 214, 417, 439 Reperfusion Injury, 64, 439 Research Design, 30, 40, 439 Research Support, 56, 439 Resection, 53, 112, 118, 231, 439 Respiration, 41, 313, 366, 415, 439 Respirator, 440, 457 Respiratory failure, 440, 457 Respiratory Physiology, 440, 457 Respite Care, 309, 332, 440 Restitution, 71, 440 Restoration, 417, 439, 440, 459 Retina, 80, 132, 370, 375, 407, 423, 436, 440, 441, 459 Retinal, 83, 374, 399, 423, 440 Retinal Hemorrhage, 399, 440 Retinoblastoma, 192, 295, 440 Retractor, 220, 221, 440 Retreatment, 440 Retroviral vector, 392, 440 Rhabdoid tumor, 188, 440 Rhabdomyosarcoma, 192, 197, 440 Ribose, 352, 440
Ribosome, 440, 455 Rigidity, 404, 425, 428, 440 Risk factor, 7, 10, 11, 34, 50, 70, 105, 202, 236, 248, 262, 367, 409, 433, 440 Rod, 149, 361, 371, 441 Rutin, 437, 441 S Saliva, 441 Salivary, 78, 377, 380, 425, 441, 448 Salivary glands, 377, 380, 441 Saponins, 441, 447 Saquinavir, 65, 441 Sarcoma, 191, 432, 441, 445 Sargramostim, 191, 441 Satellite, 422, 441 Scans, 7, 16, 19, 22, 48, 71, 329, 441 Schizoid, 441, 459 Schizotypal Personality Disorder, 441, 459 Sciatic Nerve, 233, 427, 441, 453 Sclera, 370, 374, 375, 442 Sclerosis, 28, 111, 117, 160, 244, 296, 317, 359, 416, 442 Scopolamine, 150, 442 Scrapie, 75, 84, 442 Screening, 24, 83, 222, 234, 236, 246, 302, 371, 442 Scrotum, 376, 442, 451 Sebaceous, 379, 442, 459 Sebaceous gland, 379, 442, 459 Secondary tumor, 413, 442 Secretion, 67, 177, 225, 228, 370, 386, 402, 403, 406, 414, 442, 454 Secretory, 77, 209, 215, 419, 442, 450 Sedative, 361, 442, 457 Segmentation, 16, 23, 31, 397, 442 Seizures, 20, 36, 44, 47, 89, 186, 207, 245, 251, 307, 378, 393, 397, 399, 425, 442 Selective estrogen receptor modulator, 442, 450 Self Care, 352, 442 Sella, 428, 442 Semantics, 48, 442 Semen, 167, 383, 434, 442 Semisynthetic, 365, 387, 442 Senescence, 222, 244, 443 Senile, 3, 38, 84, 162, 226, 240, 251, 252, 253, 254, 256, 258, 261, 263, 291, 420, 443 Senile Plaques, 226, 252, 258, 261, 420, 443 Senility, 239, 443 Sensor, 220, 443 Sensory loss, 29, 443, 451 Septal, 408, 443
Index 479
Septal Nuclei, 408, 443 Septicemia, 217, 443 Septum, 77, 407, 443 Septum Pellucidum, 407, 443 Sequence Homology, 426, 443 Sequencing, 312, 430, 443 Sequester, 24, 369, 443 Serine, 74, 100, 434, 443 Serologic, 400, 443 Serotonin, 98, 101, 130, 131, 216, 255, 313, 358, 371, 415, 420, 438, 443, 455 Serous, 385, 443 Serum, 21, 59, 74, 104, 116, 354, 355, 373, 394, 409, 443, 455 Serum Albumin, 74, 443 Sex Behavior, 409, 444 Sex Behavior, Animal, 409, 444 Sex Characteristics, 352, 355, 436, 444, 451 Sex Determination, 296, 444 Shivering, 202, 444 Shock, 23, 150, 162, 217, 219, 444, 455 Shunt, 9, 89, 219, 444 Sigmoid, 43, 444 Sigmoid Colon, 444 Signal Transduction, 13, 39, 40, 52, 232, 402, 444 Signs and Symptoms, 333, 419, 439, 444 Silicon, 130, 251, 444 Silicon Dioxide, 444 Skeletal, 84, 294, 355, 370, 371, 416, 444, 446 Skeleton, 352, 406, 433, 444, 445 Skilled Nursing Facilities, 212, 444 Skull, 43, 202, 221, 242, 259, 302, 304, 376, 404, 423, 445, 447, 451 Skull Base, 221, 445 Skull Fracture, Depressed, 445 Skull Fractures, 304, 445 Small cell lung cancer, 185, 445 Small intestine, 370, 382, 398, 400, 404, 445 Smooth muscle, 355, 360, 390, 416, 426, 439, 445, 446, 449 Social Environment, 436, 445 Social Security, 438, 445 Social Support, 288, 290, 445 Sodium, 83, 155, 187, 214, 229, 445, 449 Sodium Channels, 83, 445 Soft tissue, 191, 363, 389, 444, 445 Soft tissue sarcoma, 191, 389, 445 Solid tumor, 181, 193, 197, 198, 199, 356, 381, 385, 445 Solvent, 387, 394, 424, 445, 456
Soma, 436, 445 Somatic, 40, 44, 218, 352, 367, 376, 383, 393, 408, 412, 415, 426, 432, 445, 446, 456 Somatic cells, 367, 412, 415, 446 Somatic mutations, 44, 446 Somatostatin, 76, 82, 446 Sorbitol, 397, 446 Sound wave, 374, 446 Spasm, 358, 446 Spasmodic, 263, 446 Spatial disorientation, 381, 446 Specialist, 338, 380, 446 Specificity, 5, 26, 27, 51, 226, 253, 353, 400, 446 Spectroscopic, 32, 43, 62, 113, 220, 410, 446 Spectrum, 55, 219, 222, 248, 377, 414, 446 Speech Disorders, 265, 446 Speech pathologist, 252, 446 Sperm, 355, 370, 393, 430, 446, 451 Spinal Nerves, 426, 446 Spinous, 386, 447 Spleen, 111, 215, 226, 377, 398, 410, 447 Sporadic, 38, 134, 418, 440, 447 Squamous, 421, 447 Squamous cell carcinoma, 421, 447 Stabilization, 72, 447 Staging, 223, 441, 447 Stasis, 208, 447 Steel, 371, 447 Stem cell transplantation, 40, 184, 192, 197, 447 Stem Cells, 94, 209, 257, 426, 447 Stenosis, 31, 447, 448 Stereotactic, 39, 45, 51, 98, 103, 117, 118, 194, 447 Stereotactic radiosurgery, 117, 118, 194, 447 Steroid, 8, 109, 211, 359, 376, 441, 447 Stimulant, 379, 406, 414, 447 Stimulus, 103, 118, 154, 374, 381, 383, 387, 395, 402, 404, 407, 435, 438, 448, 452 Stomach, 351, 380, 386, 391, 392, 398, 417, 427, 445, 447, 448 Stool, 373, 401, 406, 448 Strand, 223, 430, 448 Stria, 155, 443, 448 Striatum, 25, 418, 422, 448 Stricture, 447, 448 Stringency, 215, 448 Stromal, 15, 69, 102, 448 Stromal Cells, 15, 69, 102, 448 Subacute, 123, 401, 448
480 Brain
Subarachnoid, 93, 137, 203, 390, 396, 448 Subclavian, 219, 361, 364, 406, 448 Subclavian Artery, 448 Subclavian Vein, 219, 361, 364, 406, 448 Subclinical, 401, 442, 448 Subcutaneous, 206, 382, 408, 422, 425, 448 Subiculum, 77, 397, 448 Submaxillary, 386, 448 Subspecies, 79, 82, 446, 448 Substance P, 413, 442, 449 Substrate, 18, 26, 232, 263, 449, 456 Substrate Specificity, 26, 449 Suction, 408, 449 Sudden death, 117, 449 Sulfur, 137, 388, 414, 449 Superior vena cava, 219, 364, 449 Superoxide, 83, 149, 449 Superoxide Dismutase, 83, 149, 449 Supplementation, 13, 155, 216, 218, 449 Support group, 144, 263, 309, 312, 331, 332, 333, 337, 449 Supportive care, 398, 449 Suppression, 64, 449, 460 Suppressive, 62, 449 Supratentorial, 19, 184, 191, 192, 195, 449 Surfactant, 387, 449 Survival Rate, 55, 312, 424, 449 Sweat, 227, 379, 399, 449 Sweat Glands, 379, 449 Sympathetic Nervous System, 57, 361, 420, 449, 450 Sympathomimetic, 379, 381, 386, 421, 450, 456 Symphysis, 369, 434, 450 Symptomatic, 20, 94, 117, 450 Symptomatology, 56, 450 Synapse, 15, 353, 419, 432, 450, 455 Synapsis, 450 Synaptic, 13, 33, 47, 97, 147, 232, 251, 409, 420, 421, 444, 450 Synaptic Transmission, 421, 450 Synergistic, 433, 450 Systemic disease, 194, 443, 450 Systolic, 236, 399, 450 T Tacrolimus, 105, 450 Tamoxifen, 211, 442, 450 Tau Proteins, 420, 450 Taurine, 18, 178, 450 Technetium, 11, 451 Telangiectasia, 296, 451 Telencephalon, 209, 361, 368, 433, 451
Temozolomide, 184, 189, 190, 194, 195, 196, 198, 199, 276, 451 Temperament, 242, 451 Temporal Lobe, 9, 67, 231, 261, 313, 355, 360, 451 Tendon, 391, 451 Terminator, 451, 460 Testicles, 376, 442, 451 Testicular, 359, 376, 451 Testis, 215, 386, 451 Testosterone, 30, 438, 451 Thalamic, 4, 45, 79, 108, 155, 360, 386, 451 Thalamic Diseases, 360, 451 Thalamic Nuclei, 386, 451 Thalamus, 12, 16, 154, 313, 364, 376, 380, 386, 408, 432, 451 Thalidomide, 187, 189, 190, 198, 278, 451 Therapeutics, 51, 191, 194, 277, 307, 415, 452 Thermal, 227, 235, 364, 380, 421, 430, 452 Thermoregulation, 428, 452 Thiotepa, 184, 452 Third Ventricle, 386, 399, 407, 428, 451, 452 Thorax, 351, 409, 449, 452, 457 Threonine, 426, 434, 443, 452 Threshold, 44, 399, 452 Thrombectomy, 383, 452 Thrombin, 388, 389, 429, 434, 452 Thrombocytes, 429, 452 Thromboembolism, 208, 452 Thrombolytic, 429, 452 Thrombomodulin, 434, 452 Thrombophlebitis, 208, 452 Thrombosis, 208, 229, 259, 403, 404, 434, 448, 452 Thrombus, 203, 208, 375, 401, 405, 417, 429, 452 Thymidine, 6, 87, 193, 452 Thymidine Kinase, 6, 87, 193, 452 Thymus, 179, 400, 410, 452 Thyroid, 76, 135, 155, 404, 452, 453, 456 Thyroid Gland, 453 Thyroiditis, 106, 453 Thyroxine, 354, 427, 453 Tibial Nerve, 441, 453 Tidal Volume, 399, 453 Tinnitus, 263, 304, 435, 453, 458 Tissue Culture, 418, 453 Tolerance, 229, 230, 352, 394, 453 Tomography, 5, 7, 11, 20, 32, 71, 97, 99, 240, 256, 261, 300, 374, 410, 441, 453
Index 481
Tone, 115, 453, 457 Tonicity, 382, 453 Tonus, 453 Tooth Preparation, 352, 453 Topical, 309, 359, 387, 398, 453 Topoisomerase inhibitors, 405, 453 Torsion, 328, 401, 453 Toxaemia, 431, 453 Toxicity, 29, 46, 49, 51, 53, 55, 69, 98, 131, 193, 197, 381, 411, 413, 454, 456 Toxicokinetics, 454 Toxicology, 56, 136, 151, 286, 454 Toxin, 65, 67, 103, 270, 385, 453, 454 Toxoplasmosis, 307, 454 Trace element, 130, 363, 444, 454 Trachea, 365, 407, 427, 452, 453, 454 Traction, 371, 454 Tractus, 135, 454 Transcription Factors, 58, 126, 454 Transdermal, 204, 454 Transduction, 41, 68, 205, 209, 444, 454 Transfection, 38, 362, 392, 454 Transforming Growth Factor beta, 68, 454 Transfusion, 454 Transgenes, 209, 225, 454 Transient Ischemic Attacks, 162, 202, 454 Translating, 51, 454 Translation, 64, 250, 354, 455 Translational, 52, 244, 455 Translocation, 232, 455 Transmitter, 29, 222, 351, 360, 381, 387, 404, 412, 421, 455, 456 Transplantation, 69, 105, 112, 119, 184, 207, 209, 210, 370, 400, 426, 455 Trauma Centers, 332, 455 Trees, 428, 455 Tremor, 108, 109, 425, 455 Trigeminal, 388, 455 Trisomy, 226, 455 Trophic, 69, 232, 249, 455 Tropism, 78, 455 Tryptophan, 130, 131, 216, 372, 443, 455 Tubercle, 422, 455 Tuberous Sclerosis, 296, 455 Tumor model, 87, 89, 455 Tumor Necrosis Factor, 79, 111, 217, 410, 451, 455 Tumorigenic, 209, 455 Tumour, 86, 145, 333, 358, 391, 423, 455 Turpentine, 50, 456 Tyramine, 415, 456
Tyrosine, 132, 175, 179, 231, 232, 381, 434, 456 U Ubiquitin, 84, 419, 456 Umbilical Arteries, 456 Umbilical Cord, 215, 456 Unconscious, 356, 378, 400, 456 Unresectable, 185, 456 Uranium, 451, 456 Urea, 220, 449, 456 Urethra, 426, 434, 456 Uricosuric, 179, 432, 456 Urinary, 108, 163, 370, 392, 401, 442, 456 Urine, 21, 182, 183, 363, 386, 397, 401, 411, 434, 456 Urogenital, 392, 456 Uterus, 369, 376, 384, 413, 420, 424, 432, 456 V Vaccine, 80, 191, 221, 222, 257, 272, 274, 275, 277, 352, 434, 456 Vagina, 369, 379, 413, 456 Vagotomy, 135, 456 Vagus Nerve, 52, 456 Valerian, 155, 179, 457 Vascular endothelial growth factor, 15, 68, 457 Vasculitis, 368, 457 Vasoactive, 225, 457 Vasoconstriction, 212, 386, 457 Vasodilator, 364, 381, 417, 421, 457 Vasogenic, 37, 457 Vector, 26, 41, 49, 68, 205, 225, 402, 454, 457 Vegetable Proteins, 428, 457 Vegetative, 45, 88, 301, 380, 457 Vein, 208, 359, 404, 421, 441, 448, 449, 452, 456, 457 Vena, 457 Venoms, 420, 457 Venous, 20, 112, 208, 219, 359, 361, 364, 368, 404, 422, 434, 457 Venous blood, 364, 368, 457 Venter, 457 Ventilation, 37, 457 Ventilator, 306, 440, 457 Ventral, 93, 372, 399, 422, 430, 446, 457 Ventricle, 24, 34, 355, 367, 397, 407, 422, 436, 450, 457, 458 Ventricular, 9, 24, 82, 101, 122, 417, 458 Ventricular Dysfunction, 122, 458 Ventriculostomy, 206, 458
482 Brain
Venules, 363, 365, 385, 414, 458 Vertebrae, 446, 458 Vertigo, 163, 310, 458 Vesicular, 35, 82, 122, 397, 458 Vestibular, 263, 458 Vestibule, 372, 458 Vestibulocochlear Nerve, 360, 372, 453, 458 Vestibulocochlear Nerve Diseases, 453, 458 Veterinary Medicine, 285, 458 Villous, 370, 458 Vinblastine, 18, 458 Vinca Alkaloids, 458 Vinorelbine, 190, 458 Viral, 29, 39, 49, 65, 67, 107, 136, 225, 232, 248, 351, 384, 423, 454, 455, 458, 460 Viral Load, 67, 136, 458 Viral vector, 49, 225, 458 Virulence, 454, 459 Visceral, 163, 314, 361, 376, 393, 408, 427, 456, 459 Visceral Afferents, 361, 393, 456, 459 Viscosity, 351, 459 Visual Cortex, 231, 328, 459 Vitamin A, 132, 402, 459 Vitreous, 220, 407, 440, 459 Vitreous Body, 440, 459 Vitreous Humor, 220, 459
Vitro, 5, 14, 24, 26, 29, 36, 51, 65, 66, 75, 81, 126, 209, 210, 211, 227, 235, 367, 392, 401, 430, 450, 453, 459 Vivo, 9, 12, 17, 21, 24, 26, 29, 34, 36, 43, 46, 51, 62, 66, 67, 68, 72, 125, 126, 137, 150, 205, 209, 210, 211, 216, 225, 227, 234, 253, 367, 392, 401, 414, 450, 459 Volition, 404, 459 Vulgaris, 179, 459 W Wakefulness, 378, 459 Weight Gain, 213, 459 White blood cell, 352, 357, 407, 410, 416, 421, 429, 459 Windpipe, 427, 452, 459 Withdrawal, 6, 12, 23, 66, 207, 378, 459 Womb, 241, 456, 459 Wound Healing, 389, 403, 411, 459 X Xenograft, 356, 455, 459 X-ray therapy, 405, 460 Y Yeasts, 391, 427, 460 Z Zebrafish, 24, 460 Zidovudine, 65, 460 Zygote, 374, 460 Zymogen, 434, 460
Index 483
484 Brain
