Dry Eyes - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

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

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

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Dry Eyes: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00383-X 1. Dry Eyes-Popular works. I. Title.

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

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on dry eyes. 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 DRY EYES .................................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Dry Eyes ....................................................................................... 4 The National Library of Medicine: PubMed .................................................................................. 8 CHAPTER 2. PATENTS ON DRY EYES ............................................................................................... 23 Overview...................................................................................................................................... 23 Patents on Dry Eyes .................................................................................................................... 23 Patent Applications on Dry Eyes................................................................................................. 26 Keeping Current .......................................................................................................................... 29 CHAPTER 3. BOOKS ON DRY EYES................................................................................................... 31 Overview...................................................................................................................................... 31 Book Summaries: Federal Agencies.............................................................................................. 31 CHAPTER 4. PERIODICALS AND NEWS ON DRY EYES ..................................................................... 33 Overview...................................................................................................................................... 33 News Services and Press Releases................................................................................................ 33 Newsletter Articles ...................................................................................................................... 34 Academic Periodicals covering Dry Eyes..................................................................................... 36 CHAPTER 5. RESEARCHING MEDICATIONS .................................................................................... 37 Overview...................................................................................................................................... 37 U.S. Pharmacopeia....................................................................................................................... 37 Commercial Databases ................................................................................................................. 38 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 43 Overview...................................................................................................................................... 43 NIH Guidelines............................................................................................................................ 43 NIH Databases............................................................................................................................. 45 Other Commercial Databases....................................................................................................... 47 APPENDIX B. PATIENT RESOURCES ................................................................................................. 49 Overview...................................................................................................................................... 49 Patient Guideline Sources............................................................................................................ 49 Finding Associations.................................................................................................................... 52 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 55 Overview...................................................................................................................................... 55 Preparation................................................................................................................................... 55 Finding a Local Medical Library.................................................................................................. 55 Medical Libraries in the U.S. and Canada ................................................................................... 55 ONLINE GLOSSARIES.................................................................................................................. 61 Online Dictionary Directories ..................................................................................................... 61 DRY EYES DICTIONARY.............................................................................................................. 63 INDEX ................................................................................................................................................ 91

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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 dry eyes is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about dry eyes, 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 dry eyes, 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 dry eyes. 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 dry eyes, 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 dry eyes. 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 DRY EYES Overview In this chapter, we will show you how to locate peer-reviewed references and studies on dry eyes.

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

Whole Saliva and the Diagnosis of Sjogren's Syndrome: An Evaluation of Patients Who Complain of Dry Mouth and Dry Eyes. Part 1: Screening Tests Source: Gerodontology. 13(1): 35-43. July 1996. Contact: Available from FDI World Dental Press Ltd. 7 Carlisle Street, London W1V 5RG, United Kingdom. Summary: Sjogren's syndrome (SS) is a common autoimmune disorder characterized by generalized desiccation, exocrine hypofunction, and serologic abnormalities. More than 90 percent of SS patients are women. This article reports on a study undertaken to determine if whole saliva can be used to diagnose SS. The study included 49 subjects (48 female, 1 male) with a mean age of 54 years (plus or minus 13 years). In order to be admitted into the study, the subjects had to complain of dry mouth and dry eyes. Whole

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saliva was collected by the spitting method. Tests were used to measure the salivary flow rate, pH, buffer capacity, lactobacillus concentrations, yeast concentrations, and protein, albumin, sodium, and amylase activity. Based on the sialometric (salivary measurements) findings, the patients were divided into 3 groups: group 1 contained those with abnormally low resting (RFR) and stimulated (SFR) flow rates; group 2 contained those with a low RFR but normal SFR; and group 3 contained those with normal salivary flow rates. The group 1 patients were unique: their saliva demonstrated a low pH and buffer capacity, high lactobacillus and yeast concentrations, decreased protein output and amylase activity, and elevated albumin and sodium. Moreover, virtually all of them had abnormally low lacrimal flow rates. The authors conclude that these findings suggest that whole saliva could be used to provisionally diagnose SS. Critical to this diagnosis was an abnormally low stimulated whole saliva flow rate. 6 tables. 26 references. (AA-M). •

Salivary Flow and Its Relationship to Oral Signs and Symptoms in Patients with Dry Eyes Source: Oral Diseases. Volume 10: 75-80. 2004. Summary: This article reports on a study undertaken to investigate oral symptoms and clinical parameters in patients with dry eyes. Subjective reports of the sensation of a dry mouth, salivary flow rates, and clinical parameters of oral disease related to three different types of dry eye patients were examined. There were 224 individuals in the study, including dry eye patients and control subjects. The dry eye patients were classified into three types: patients with Sjogren's syndrome (SS-DE), patients without SS-DE, and patients with Stevens-Johnson syndrome. Results showed that over half of the dry eye patients complained of a dry mouth. The flow rates of their simulated whole saliva and parotid saliva were significantly lower than those of the control groups. The authors conclude that the sensation of a dry mouth and changes in oral soft tissues, dental caries (cavities), and oral Candida frequently occurred in dry eye patients. 2 figures. 7 tables. 24 references.

Federally Funded Research on Dry Eyes The U.S. Government supports a variety of research studies relating to dry eyes. 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 dry eyes. 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

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

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animals or simulated models to explore dry eyes. The following is typical of the type of information found when searching the CRISP database for dry eyes: •

Project Title: CAPILLARY ELECTROPHORESIS PROFILING OF TEARS IN DRY EYE Principal Investigator & Institution: Jacob, Jean T.; Associate Professor; Ophthalmology; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2005 Summary: (Applicant's Abstract) We propose to investigate and develop an inexpensive and reliable method to determine the lipid and protein composition of tears that could be used both in the basic science laboratory and clinically in a diagnostic laboratory setting. Our approach would not only generate the detailed information needed for more precise diagnosis of dry eye conditions, but also provide the basis for development of more specific and effective categories for (and possibly therapies targeted directly to) the individual deficiencies that ' characterize the spectrum of dry eye disorders. More than 12 million people in the United States alone have been clinically diagnosed with some form of keratitis sicca or dry eyes. Although their symptoms are similar, the underlying causes are often unknown and no practical methodology for evaluating the composition of tears from such patients exists. To date, analysis of tear composition has been hampered by the minute sample sizes available and the technical inability to identify and measure the components of such a complex fluid at concentration scales of nanomoles or less. Capillary electrophoresis-electrospray ionization mass spectrometry (CE-ESI/MS) is a sensitive, relatively inexpensive method capable of analyzing samples 2 pl or less in size. Using micellar electrokinetic capillary chromatography techniques coupled with mass spectrometry detection, we plan to design and develop 1) a novel standard separation method for the lipids within tears and 2) a novel standard separation method for the proteins within tears. We will then investigate the use of these methods to develop standard lipid and protein component profiles of normal tears and identify specific component differences in the tears from two different dry eye models. The development of this technology to provide specific information on the complex disorder know as dry eye could provide relief to and enhance the quality of life of millions of patients for whom no reliable long-lasting therapy is currently available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IL-4 SIGNALING PATHWAY REGULATION OF SJOGREN'S SYNDROME Principal Investigator & Institution: Peck, Ammon B.; Professor; Pathology, Immunol & Lab Med; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: Sjogren's syndrome is a human autoimmune disease characterized by exocrine dysfunction resulting from the action of1 a chronic autoimmune attack against the lacrimal and salivary glands. It is one of the leading causes of salivary gland inflammation and dysfunction, leading to severe dryness of the ocular and oral surfaces. Diagnosis of Sjogren's syndrome includes detection of leukocytic infiltrates in the minor salivary glands, the presence of rheumatoid factor, hypergammaglobulinemia, specific anti-nuclear autoantibodies, loss of stimulated fluid secretion, and complaints of dry eyes and/or dry mouth. Over the past several years, the NOD mouse has been shown to exhibit numerous disease manifestations that parallel Sjogren's syndrome, including loss of stimulated fluid secretion concomitant with the appearance of leukocyte infiltrates in

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the lacrimal and salivary glands. Studies of autoimmune exocrinopathy in NOD mice have revealed that the disease can be separated into two phases: Phase 1 is characterized by pathophysiological and biochemical changes in the exude glands whose occurrence are independent of the autoimmune attack. Phase 2 is characterized by the appearance of leukocytic infiltrates in the exocrine glands, proinflammatory responses, autoantibodies to multiple acinar cell components, loss of acinar cell mass, and decline in exocrine function. The use of specific gene knockout mice congenic with the parental NOD mouse strain indicated that loss of exocrine function was dependent, first, on the presence of B cells and, second, expression of the intedeukin-4 (IL-4) cytokine. Subsequent studies suggested that IL-4 exerted its activity by regulating antibody isotypic class switching in B ceils. Nevertheless, IL-4 can activate two distinct signaling pathways in B ceils: the STAT-6 and the IRS pathways. The STAT-6 signaling pathway is involved in antibody class switching, while the IRS pathway is involved in B cell maturation and clonal deletion. Thus, the purpose of the current R21 grant application is to initiate studies examining the mechanism(s) by which IL-4 elicits its effector function in the development of exocrine gland dysfunction and decreased fluid secretion. Specifically, we plan to (t) document the autoimmune phenotype of a newly constructed NOD.B10.H-2b.B/c-STAT6 knockout mouse line and compare this phenotype to NOD.B10.H-2b, NOD.B10.H-2b.lgp KO and NOD.B10.H-2b.IL4 KO mice, and (2) identify if the IL-4 dependent development of exocrine gland dysfunction is due to activation of the STAT-6, IRS or both signal transduction pathway(s). Results from these studies will provide insight into the role of the cytokine, IL-4, and its effector mechanism in regulating development of the pathogenesis of Sj gren's syndrome. Identification of this effector mechanism could be important to the long-term goal of developing targeted preventive or early intervention strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENESIS OF CONJUNCTIVAL SQUAMOUS Principal Investigator & Institution: Pflugfelder, Stephen Carl.; Professor; Ophthalmology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-AUG-1997; Project End 31-MAR-2006 Summary: (provided by applicant): Our research has identified that changes in the ocular surface environment of dry eye, such as a hyperosmolar tear film, stimulate the production of pro-inflammatory cytokines by the ocular surface epithelia. Our preliminary data suggests that these cytokines, particularly interleukin-1 (IL-1) and TNF-alpha, may play a key role in the pathogenesis of the epithelial and immunopathology of keratoconjunctivitis sicca, (KCS) the ocular surface disease of dry eye. Four proposed Specific Aims will test this theory. Aim I will confirm whether experimentally induced dry eye in mice stimulates the production and release of pro-inflammatory cytokines by the ocular surface epithelium that promote ocular surface inflammation and KCS. Aim 2 will determine whether hyperosmolar stress stimulates the production of pro-inflammatory cytokines by the ocular surface epithelium by activating the p38 stress activated protein kinase pathway. Aim 3 will study the expression of IL-1 and TNF-alpha receptors on the ocular surface and determine if there are differences in the expression of these receptors and their soluble antagonists between normal and dry eyes. Aim 4 will investigate the effects of the pro-inflammatory cytokines of dry eye on the expression of matrix metalloproteinase enzymes (MMPs) and mucins on the ocular surface. These factors that have been implicated in the disruption of ocular surface barrier function and homeostasis in KCS. These studies will provide clinically relevant information regarding the role of inflammation and its cytokine mediators on the

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pathogenesis of the ocular surface disease of dry eye, a condition experienced by over 10 percent of the population over the age of 30. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIALOADENITIS IN AG INDUCED AND SPONTANEOUS AUTOIMMUNITY Principal Investigator & Institution: Fu, Shu Man M.; Professor & Chief; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2004 Summary: (adapted from the Investigator's Abstract): This proposal focuses on the pathogenesis of Sjogren's Syndrome (SS), a systematic autoimmune disease largely affecting the exocrine glands. The disease has been defined as the combination of dry eyes and dry mouth due to lymphocytic infiltration of these glands (sialoadenitis). The syndrome is often, if not always, associated with autoantibodies to SSA/Ro and SSB/La. It is a prevalent disorder with considerable ocular and oral morbidity. long term goal of the research program is to elucidate the immunological and genetic factors which are important in the development of sialoadenitis. In this application a murine model of sialoadenitis will be defined. Four specific aims are included.Four specific aims are included. In Specific Aim 1, different strains of mice will be identified which are susceptible to the induction of sialoadenitis by immunization with recombinant Ro60, Ro522 or La. Functional, histochemical and immunocytochemical studies will be done to monitor the development of sialoadenitis. In animals with salivary infiltrates, the involvement of other exocrine glands and tissues will be determined. Further studies will identify Ro60 peptides capable of inducing sialoadenitis. Considerable efforts will be devoted to determining whether salivary gland dysfunction is present in mice which have developed antigen induced sialoadenitis in order to validate this model to studying SS. In Specific Aim 2, T cell lines and clones from infiltrating T cells of disease salivary glands and the draining lymph nodes will be generated after stimulation with mouse salivary gland cellular extract. The responsible antigens will be identified and pathogenic potential of the T cell lines determine by cell transfer experiments. Additionally, the T cell specificities of cell lines derived from these mice will be compared with those derived from NOD mice, a model for spontaneous autoimmunity. In Specific Aim 3, the feasibility of developing an autoantigen-induced sialoadenitis in mice expressing certain HLA-DR and/or HLA-DQ transgenes will be explored. By a rapid breeding scheme, these transgenes will be bred into appropriate background for the development of sialoadenitis as determined in Specific Aim 1. In the fourth specific aim, B-less mice which are congenic with the sialoadenitis susceptible strains will be generated to explore the role of B cells in both the spontaneous and antigen-induced autoimmune model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE CONTACT LENS AND DRY EYE STUDY Principal Investigator & Institution: Nichols, Jason J.; None; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2007 Summary: The primary goal of this K23 proposal is to train the Jason J. Nichols, OD MS is an independent clinician-scientist. To achieve this goal, a five-year training program is proposed which emphasizes mentoring and formal coursework in 1) vision science leading to a PhD from The Ohio State University College of Optometry and in 2)

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biostatistics and epidemiology leading to an MPH degree from The Ohio State University College of Medicine and Public Health. In 1995, the National Eye Institute (NEI) sponsored dry eye workshop report identified contact lens-related dry eye as a major sub-classification of dry eye syndrome. Yet, there has been little clinical research sponsored by the NEI to study the etiology or epidemiology of contact lens-related dry eyes since that time. The proposed training will provide Dr. Nichols with the necessary patient-oriented research skills to conduct an epidemiologic study of contact lens-related dry eye, which has been carefully designed to complement and enhance those skills obtained during the development period. Contact lens-related dry eye may severely impact ocular health by leading to desiccation of the corneal epithelium or an increased incidence of infectious disease. The relation between contact lens dehydration and evaporative changes in the tear film needs to be understood as they may be the primary cause of contact lens-related dry eye. A cross-sectional/nested case-control study will be conducted and the analyses will address risk factors thought to be associated with contact lens-related dry eye. In the cross-sectional phase of the study (Phase I), we will characterize and elucidate the functional significance of the discrepancy between the frequency and severity of dry eye symptoms during contact lens wear. In the nested case-control phase of the study (Phase II), we will test the hypothesis that evaporative factors including contact lens characteristics, tear film changes, Meibomian gland disease, and blanking patterns are associated with an increased risk for contact lensrelated dry eye. The long-term objective of this research is to contribute to a better understanding of the etiology and risk factors for contact lens-related dry eye so that progress can be made toward its prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

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A classification for dry eyes following comparison of tear thinning time with Schirmer tear test. Author(s): Farrell J, Grierson DJ, Patel S, Sturrock RD. Source: Acta Ophthalmol (Copenh). 1992 June; 70(3): 357-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1636398

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A comparative study of polyacrylic acid (Viscotears) liquid gel versus polyvinylalcohol in the treatment of dry eyes. Author(s): Brodwall J, Alme G, Gedde-Dahl S, Smith J, Lilliedahl NP, Kunz PA, Sunderraj P. Source: Acta Ophthalmologica Scandinavica. 1997 August; 75(4): 457-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9374260

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A comparative study to assess the clinical use of Fluorescein Meniscus Time (FMT) with Tear Break up Time (TBUT) and Schirmer's tests (ST) in the diagnosis of dry eyes. Author(s): Kallarackal GU, Ansari EA, Amos N, Martin JC, Lane C, Camilleri JP. Source: Eye (London, England). 2002 September; 16(5): 594-600. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12194075

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A new noninvasive tear stability analysis system for the assessment of dry eyes. Author(s): Kojima T, Ishida R, Dogru M, Goto E, Takano Y, Matsumoto Y, Kaido M, Ohashi Y, Tsubota K. Source: Investigative Ophthalmology & Visual Science. 2004 May; 45(5): 1369-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15111590

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A randomised, crossover, multicentre study to compare the performance of 0.1% (w/v) sodium hyaluronate with 1.4% (w/v) polyvinyl alcohol in the alleviation of symptoms associated with dry eye syndrome. Author(s): McDonald CC, Kaye SB, Figueiredo FC, Macintosh G, Lockett C. Source: Eye (London, England). 2002 September; 16(5): 601-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12194076

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Abnormal protein profiles in tears with dry eye syndrome. Author(s): Ohashi Y, Ishida R, Kojima T, Goto E, Matsumoto Y, Watanabe K, Ishida N, Nakata K, Takeuchi T, Tsubota K. Source: American Journal of Ophthalmology. 2003 August; 136(2): 291-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12888052

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Analysis of tear protein patterns by a neural network as a diagnostical tool for the detection of dry eyes. Author(s): Grus FH, Augustin AJ. Source: Electrophoresis. 1999 April-May; 20(4-5): 875-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10344262

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Analysis of tear-protein patterns as a diagnostic tool for the detection of dry eyes. Author(s): Grus FH, Augustin AJ, Evangelou NG, Toth-Sagi K. Source: Eur J Ophthalmol. 1998 April-June; 8(2): 90-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9673477

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Association of dry eyes and dry mouth with anti-Ro/SS-A and anti-La/SS-B autoantibodies in normal adults. Author(s): Jacobsson L, Hansen BU, Manthorpe R, Hardgrave K, Neas B, Harley JB. Source: Arthritis and Rheumatism. 1992 December; 35(12): 1492-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1472126

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Autologous serum eyedrops for dry eyes and epithelial defects: clinical and in vitro toxicity studies. Author(s): Poon AC, Geerling G, Dart JK, Fraenkel GE, Daniels JT. Source: The British Journal of Ophthalmology. 2001 October; 85(10): 1188-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11567963

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Botox use in prevention of dry eyes. Author(s): Benvenuti D. Source: Plastic and Reconstructive Surgery. 1998 September; 102(3): 918. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9727468

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Cataract surgery in patients with dry eyes. Author(s): Ram J, Sharma A, Pandav SS, Gupta A, Bambery P. Source: Journal of Cataract and Refractive Surgery. 1998 August; 24(8): 1119-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9719973

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Central corneal thickness of patients with dry eyes. Author(s): Pole JJ, Batzer JK. Source: J Am Optom Assoc. 1985 March; 56(3): 220-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3980916

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Changes of the tear film in dry eyes. Author(s): Kilp H, Schmid E, Poss W, Kirchner L. Source: Trans Ophthalmol Soc U K. 1985; 104 ( Pt 4): 450-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3862274

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Chronic blepharitis and dry eyes. Author(s): Bowman RW, Dougherty JM, McCulley JP. Source: International Ophthalmology Clinics. 1987 Spring; 27(1): 27-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3818198

Studies

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Clinical tests for dry eyes. Author(s): Storz DJ, Wolfe CP. Source: J Ophthalmic Nurs Technol. 1984 November-December; 3(6): 252-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6568294

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Comparison of the efficacy and safety of two eye gels in the treatment of dry eyes: Lacrinorm and Viscotears. Author(s): Bron AJ, Daubas P, Siou-Mermet R, Trinquand C. Source: Eye (London, England). 1998; 12 ( Pt 5): 839-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10070521

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Constant perfusion for dry eyes and sockets. Author(s): Ruben M, Trodd C. Source: The British Journal of Ophthalmology. 1978 April; 62(4): 268-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=646987

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Contact lenses in dry eyes. Author(s): Mackie IA. Source: Trans Ophthalmol Soc U K. 1985; 104 ( Pt 4): 477-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3898480

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Corneal epithelial permeability of dry eyes before and after treatment with artificial tears. Author(s): Gobbels M, Spitznas M. Source: Ophthalmology. 1992 June; 99(6): 873-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1630776

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Diagnosis and management of dry eyes. Author(s): Wright P. Source: Trans Ophthalmol Soc U K. 1971; 91: 119-28. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5291517

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Diagnosis and treatment of dry eyes. Author(s): Wright M, Dhillon B. Source: The Practitioner. 1997 April; 241(1573): 210-2, 214, 216. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9206292

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Different concentrations of amino acids in tears of normal and human dry eyes. Author(s): ChenZhuo L, Murube J, Latorre A, del Rio RM. Source: Advances in Experimental Medicine and Biology. 2002; 506(Pt A): 617-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12613969

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Dry eye syndrome in thyroid-associated ophthalmopathy: lacrimal expression of TSH receptor suggests involvement of TSHR-specific autoantibodies. Author(s): Eckstein AK, Finkenrath A, Heiligenhaus A, Renzing-Kohler K, Esser J, Kruger C, Quadbeck B, Steuhl KP, Gieseler RK. Source: Acta Ophthalmologica Scandinavica. 2004 June; 82(3 Pt 1): 291-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15115450

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Dry eyes and dry mouth in patients with generalized nodal osteoarthritis. Author(s): Kassimos DG, Panayl GS, Challacombe S. Source: Archives of Internal Medicine. 2001 February 26; 161(4): 615. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11252129

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Dry eyes and mouth syndrome or sicca, asthenia and polyalgia syndrome? Author(s): Mariette X, Caudmont C, Berge E, Desmoulins F, Pinabel F. Source: Rheumatology (Oxford, England). 2003 July; 42(7): 914-5; Author Reply 913-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12826718

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Dry eyes and mouth syndrome--a subgroup of patients presenting with sicca symptoms. Author(s): Price EJ, Venables PJ. Source: Rheumatology (Oxford, England). 2002 April; 41(4): 416-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11961172

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Dry eyes and refractive surgery. Author(s): Stonecipher KG. Source: Journal of Cataract and Refractive Surgery. 1996 November; 22(9): 1130-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8972357

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Dry eyes and video display terminals. Author(s): Tsubota K, Nakamori K. Source: The New England Journal of Medicine. 1993 February 25; 328(8): 584. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8426634

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Dry eyes in diabetes. Author(s): Jain S. Source: Diabetes Care. 1998 August; 21(8): 1375; Disscusion 1375-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9702459

Studies

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Dry eyes or mouth--an epidemiological study in Swedish adults, with special reference to primary Sjogren's syndrome. Author(s): Jacobsson LT, Axell TE, Hansen BU, Henricsson VJ, Larsson A, Lieberkind K, Lilja B, Manthorpe R. Source: Journal of Autoimmunity. 1989 August; 2(4): 521-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2789654

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Dry eyes revisited. Author(s): Rakow PL. Source: J Ophthalmic Nurs Technol. 1999 March-April; 18(2): 71-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10410001

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Dry eyes. Eye series. 3. Author(s): Hodge C, Sutton G. Source: Aust Fam Physician. 2003 April; 32(4): 265-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12735267

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Dry eyes: a late effect of topical steroids. Author(s): Jain IS, Bansal SL, Gupta A, Vishwanath K. Source: Indian J Ophthalmol. 1985 January-February; 33(1): 33-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4077202

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Dry eyes: autoimmunity and relationship to other systemic disease. Author(s): Maddison PJ. Source: Trans Ophthalmol Soc U K. 1985; 104 ( Pt 4): 458-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3898478

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Dry eyes--a common problem. Author(s): Hunt L. Source: Nasnewsletter. 1991 May; 6(3): 15. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2031164

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Dry eyes--aspects of pathophysiology. Author(s): Dohlman CH. Source: Fortschr Ophthalmol. 1987; 84(5): 443-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3428812

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Effect of artificial tears on corneal surface regularity, contrast sensitivity, and glare disability in dry eyes. Author(s): Huang FC, Tseng SH, Shih MH, Chen FK. Source: Ophthalmology. 2002 October; 109(10): 1934-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12359618

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Effect of sodium hyaluronate (0.1%) on break-up time (NIBUT) in patients with dry eyes. Author(s): Mengher LS, Pandher KS, Bron AJ, Davey CC. Source: The British Journal of Ophthalmology. 1986 June; 70(6): 442-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3718907

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Effects of artificial tears on corneal epithelial permeability in dry eyes. Author(s): Gobbels M, Spitznas M. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 1991; 229(4): 345-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1916322

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Epidemiology of dry eye syndrome. Author(s): Schaumberg DA, Sullivan DA, Dana MR. Source: Advances in Experimental Medicine and Biology. 2002; 506(Pt B): 989-98. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12614022

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Evaluation of the clinical course of dry eye syndrome. Author(s): Horwath-Winter J, Berghold A, Schmut O, Floegel I, Solhdju V, Bodner E, Schwantzer G, Haller-Schober EM. Source: Archives of Ophthalmology. 2003 October; 121(10): 1364-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14557170

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Flow cytometric analysis of inflammatory markers in conjunctival epithelial cells of patients with dry eyes. Author(s): Brignole F, Pisella PJ, Goldschild M, De Saint Jean M, Goguel A, Baudouin C. Source: Investigative Ophthalmology & Visual Science. 2000 May; 41(6): 1356-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10798650

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Flow cytometric analysis of the inflammatory marker HLA DR in dry eye syndrome: results from 12 months of randomized treatment with topical cyclosporin A. Author(s): Baudouin C, Brignole F, Pisella PJ, De Jean MS, Goguel A. Source: Advances in Experimental Medicine and Biology. 2002; 506(Pt B): 761-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12613989

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Gel tears. A new medication for the treatment of dry eyes. Author(s): Leibowitz HM, Chang RK, Mandell AI. Source: Ophthalmology. 1984 October; 91(10): 1199-204. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6392979

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GVHD dry eyes treated with autologous serum tears. Author(s): Rocha EM, Pelegrino FS, de Paiva CS, Vigorito AC, de Souza CA. Source: Bone Marrow Transplantation. 2000 May; 25(10): 1101-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10828873

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Inexpensive punctal plugs for dry eyes. Author(s): Luke C, Kearney J. Source: Australian and New Zealand Journal of Ophthalmology. 1992 May; 20(2): 143. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1389134

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Inflammation: a unifying theory for the origin of dry eye syndrome. Author(s): Wilson SE. Source: Manag Care. 2003 December; 12(12 Suppl): 14-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14723109

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Low spatial-contrast sensitivity in dry eyes. Author(s): Rolando M, Iester M, Macri A, Calabria G. Source: Cornea. 1998 July; 17(4): 376-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9676908

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Lubrithal (Leo viscous eye gel), precorneal residence time in normal and dry eyes. Author(s): al-Mansouri S, Tabbara KF, Rask-Pedersen E. Source: Documenta Ophthalmologica. Advances in Ophthalmology. 1994; 88(2): 187-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7781487

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Lysozyme, alfa-1-antitrypsin and serum albumin in tear fluid of timolol treated glaucoma patients with and without symptoms of dry eyes. Author(s): Nielsen NV, Prause JU, Eriksen JS. Source: Acta Ophthalmol (Copenh). 1981 August; 59(4): 503-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6976056

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Managing dry eyes and dry mouth in Sjogren's syndrome. Author(s): Kassan SS. Source: Am J Manag Care. 2001 September; 7(14 Suppl): S444-50. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11605979

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Marked reduction and distinct patterns of eye blinking in patients with moderately dry eyes during video display terminal use. Author(s): Schlote T, Kadner G, Freudenthaler N. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2004 April; 242(4): 306-12. Epub 2004 January 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14747951

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Medications for dry eye syndrome: a drug-therapy review. Author(s): Perry HD, Donnenfeld ED. Source: Manag Care. 2003 December; 12(12 Suppl): 26-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14723111

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Morphological changes in ocular surface in dry eyes and other disorders by impression cytology. Author(s): Rivas L, Oroza MA, Perez-Esteban A, Murube-del-Castillo J. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 1992; 230(4): 329-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1505763

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Oral disease associated with dry eyes. Author(s): Kurrasch RH, Wu AJ, Fox PC. Source: International Ophthalmology Clinics. 1994 Winter; 34(1): 89-100. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8169075

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Oral pilocarpine for symptomatic relief of dry mouth and dry eyes in patients with Sjogrens syndrome. Author(s): Papas AS, Fernandez MM, Castano RA, Gallagher SC, Trivedi M, Shrotriya RC. Source: Advances in Experimental Medicine and Biology. 1998; 438: 973-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9634997

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Oral pilocarpine improves radiotherapy-induced dry eyes. Author(s): Kumar S, Tyler AB, Phillips S, Burnet NG. Source: Clin Oncol (R Coll Radiol). 1997; 9(1): 62-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9039817

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Other forms of treatment of dry eyes. Author(s): Wright P. Source: Trans Ophthalmol Soc U K. 1985; 104 ( Pt 4): 497-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3862279

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Oxidative reactions in the tear fluid of patients suffering from dry eyes. Author(s): Augustin AJ, Spitznas M, Kaviani N, Meller D, Koch FH, Grus F, Gobbels MJ. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 1995 November; 233(11): 694-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8566825

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Polyacrylic acid gel in patients with dry eyes: a randomised comparison with polyvinyl alcohol. Author(s): Bron AJ, Mangat H, Quinlan M, Foley-Nolan A, Eustace P, Fsadni M, Sunder Raj P. Source: Eur J Ophthalmol. 1998 April-June; 8(2): 81-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9673476

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Potential use of ocular-insert therapy in dry eyes. Author(s): Pavan-Langston D. Source: International Ophthalmology Clinics. 1973 Spring; 13(1): 231-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4724259

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Prevalence and associations of dry eye syndrome in an older population: the Blue Mountains Eye Study. Author(s): Chia EM, Mitchell P, Rochtchina E, Lee AJ, Maroun R, Wang JJ. Source: Clinical & Experimental Ophthalmology. 2003 June; 31(3): 229-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786773

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Prevalence of dry eye syndrome among US women. Author(s): Schaumberg DA, Sullivan DA, Buring JE, Dana MR. Source: American Journal of Ophthalmology. 2003 August; 136(2): 318-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12888056

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Primary amyloidosis with dry eyes and dry mouth--a case report. Author(s): Itoh T, Ohashi S, Tsujino T, Takenaka M, Kodama H, Kishihara M, Inatome T, Inoh T. Source: Jpn J Med. 1991 November-December; 30(6): 597-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1798223

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Rapid development of band keratopathy in dry eyes. Author(s): Lemp MA, Ralph RA. Source: American Journal of Ophthalmology. 1977 May; 83(5): 657-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=868965

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Reduced corneal sensation and severe dry eyes in a child with fetal valproate syndrome. Author(s): Boyle NJ, Clarke MP, Figueiredo F. Source: Eye (London, England). 2001 October; 15(Pt 5): 661-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11702984

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Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. Author(s): Lemp MA. Source: The Clao Journal : Official Publication of the Contact Lens Association of Ophthalmologists, Inc. 1995 October; 21(4): 221-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8565190

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Safety of blepharoplasty in patients with preoperative dry eyes. Author(s): Saadat D, Dresner SC. Source: Archives of Facial Plastic Surgery : Official Publication for the American Academy of Facial Plastic and Reconstructive Surgery, Inc. and the International Federation of Facial Plastic Surgery Societies. 2004 March-April; 6(2): 101-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15023797

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Salivary flow and its relationship to oral signs and symptoms in patients with dry eyes. Author(s): Koseki M, Maki Y, Matsukubo T, Ohashi Y, Tsubota K. Source: Oral Diseases. 2004 March; 10(2): 75-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996276

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Schirmer testing for dry eyes in patients with rosacea. Author(s): Gudmundsen KJ, O'Donnell BF, Powell FC. Source: Journal of the American Academy of Dermatology. 1992 February; 26(2 Pt 1): 211-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1532401

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Scleral gel contact lenses in treatment of dry eyes. Author(s): Krejci L. Source: The British Journal of Ophthalmology. 1972 May; 56(5): 425-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5044104

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Should patients presenting with dry eyes be screened for autoimmune rheumatic disorders? Author(s): Pal B. Source: British Journal of Rheumatology. 1997 February; 36(2): 301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9133958

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Sjogren's syndrome. More than dry eyes and dry mouth. Author(s): Smith DL, Lucas LM. Source: Postgraduate Medicine. 1987 July; 82(1): 123-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3601833

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Slow-release artificial tear inserts in the treatment of dry eyes in patients with rheumatoid arthritis. Author(s): Hill JC. Source: The British Journal of Ophthalmology. 1989 February; 73(2): 151-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2649149

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Slow-release artificial tear inserts in the treatment of dry eyes resulting from the oculomucocutaneous syndrome. Author(s): Wright P, Vogel R. Source: The British Journal of Ophthalmology. 1983 June; 67(6): 393-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6849861

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Sodium hyaluronate eyedrops in the treatment of dry eyes. Author(s): Shimmura S, Ono M, Shinozaki K, Toda I, Takamura E, Mashima Y, Tsubota K. Source: The British Journal of Ophthalmology. 1995 November; 79(11): 1007-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8534643

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Subclinically dry eyes in urban Delhi: an impact of air pollution? Author(s): Gupta SK, Gupta V, Joshi S, Tandon R. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2002 September-October; 216(5): 368-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12424406

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Surgical treatment of dry eye syndrome: conjunctival graft of the minor salivary gland. Author(s): Guerrissi JO, Belmonte J. Source: The Journal of Craniofacial Surgery. 2004 January; 15(1): 6-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14704553

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Systemic linoleic and gamma-linolenic acid therapy in dry eye syndrome with an inflammatory component. Author(s): Barabino S, Rolando M, Camicione P, Ravera G, Zanardi S, Giuffrida S, Calabria G. Source: Cornea. 2003 March; 22(2): 97-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12605039

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Tear film breakup time (B.U.T.) in sub clinical dry eyes. Author(s): Kulshrestha OP, Talwar P, Mathur M. Source: Indian J Ophthalmol. 1984 September-October; 32(5): 454-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6545340

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Tear glycoprotein determinations in the diagnosis and differential diagnosis of dry eyes. Author(s): Berta A, Torok M. Source: Scand J Rheumatol Suppl. 1986; 61: 228-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3296149

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Tear physiology and dry eyes. Author(s): Holly FJ, Lemp MA. Source: Survey of Ophthalmology. 1977 September-October; 22(2): 69-87. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=335548

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Tear secretion in dry eyes as assessed by objective fluorophotometry. Author(s): Gobbels M, Goebels G, Breitbach R, Spitznas M. Source: Ger J Ophthalmol. 1992; 1(5): 350-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1477640

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Tear substitutes in the treatment of dry eyes. Author(s): Lemp MA. Source: International Ophthalmology Clinics. 1973 Winter; 13(4): 145-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4783997

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The challenge of severe dry eyes--not for the fainthearted. Author(s): Olver J. Source: Orbit (Amsterdam, Netherlands). 2003 March; 22(1): 1-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12759861

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The significance of salivary gland ultrasonography in the diagnosis of dry eye syndrome. Author(s): Switka-Wieclawska I, Portacha L, Kecik T, Markiewicz H. Source: Advances in Experimental Medicine and Biology. 2002; 506(Pt B): 1217-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12614055

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The size of corneal epithelial cells collected by contact lens cytology from dry eyes. Author(s): Wilson G, Laurent J. Source: Advances in Experimental Medicine and Biology. 1998; 438: 831-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9634974

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The treatment of dry eyes. Author(s): Whitcher JP. Source: The British Journal of Ophthalmology. 2004 May; 88(5): 603-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15090407

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Timolol transitory manifestations of dry eyes in long term treatment. Author(s): Nielsen NV, Eriksen JS. Source: Acta Ophthalmol (Copenh). 1979 June; 57(3): 418-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=89777

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Topical application of hyaluronic acid and chondroitin sulfate in the treatment of dry eyes. Author(s): Limberg MB, McCaa C, Kissling GE, Kaufman HE. Source: American Journal of Ophthalmology. 1987 February 15; 103(2): 194-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3101502

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Topical therapy for dry eyes. Author(s): Gilbard JP. Source: Trans Ophthalmol Soc U K. 1985; 104 ( Pt 4): 484-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3898481

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Treatment of brittle nails and dry eyes. Author(s): Campbell AJ, McEwan GC. Source: The British Journal of Dermatology. 1981 July; 105(1): 113. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7259976

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Treatment of ocular surface disorders and dry eyes with high gas-permeable scleral lenses. Author(s): Kok JH, Visser R. Source: Cornea. 1992 November; 11(6): 518-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1468214

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Trehalose eye drops in the treatment of dry eye syndrome. Author(s): Matsuo T, Tsuchida Y, Morimoto N. Source: Ophthalmology. 2002 November; 109(11): 2024-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12414409

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Understanding dry eye syndrome. Author(s): Tsubota K. Source: Advances in Experimental Medicine and Biology. 2002; 506(Pt A): 3-16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12613883

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Viscous carbomer eye drops in patients with dry eyes. Efficacy and safety. A randomized, open, cross-over, multicentre study. Author(s): Marner K, Mooller PM, Dillon M, Rask-Pedersen E. Source: Acta Ophthalmologica Scandinavica. 1996 June; 74(3): 249-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8828721

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Weak association between subjective symptoms or and objective testing for dry eyes and dry mouth: results from a population based study. Author(s): Hay EM, Thomas E, Pal B, Hajeer A, Chambers H, Silman AJ. Source: Annals of the Rheumatic Diseases. 1998 January; 57(1): 20-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9536818

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Whole saliva and the diagnosis of Sjogren's syndrome: an evaluation of patients who complain of dry mouth and dry eyes. Part 1: Screening tests. Author(s): Sreebny L, Zhu WX. Source: Gerodontology. 1996 July; 13(1): 35-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9452640

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Whole saliva and the diagnosis of Sjogren's syndrome: an evaluation of patients who complain of dry mouth and dry eyes. Part 2: Immunologic findings. Author(s): Sreebny L, Zhu WX. Source: Gerodontology. 1996 July; 13(1): 44-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9452641

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CHAPTER 2. PATENTS ON DRY EYES 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.4 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 “dry eyes” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on dry eyes, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Dry Eyes By performing a patent search focusing on dry eyes, 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

4Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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will 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 dry eyes: •

Drugs for topical application of sex steroids in the treatment of dry eye syndrome, and methods of preparation and application Inventor(s): Lubkin; Virginia (One Blackstone Pl., New York, NY 10471) Assignee(s): none reported Patent Number: 5,041,434 Date filed: May 7, 1990 Abstract: A topical drug application for the alleviation of keratoconjunctivitis sicca (dry eye syndrome) is comprised of a solution of sex steroids or their derivatives suspended or dissolved in a vehicle, and the method of preparation and application of the same. In the preferred embodiments, the sex steroid consists essentially of conjugated estrogen in a lipid vehicle or a derivative of estrogen known as 17 beta-Estradiol 3-phosphate disodium dissolved in an aqueous vehicle having a pH of between 6 and 8. Excerpt(s): This invention relates to drugs for the topical application of sex steroids in the treatment of human dry eye syndrome (keratoconjunctivitis sicca) and, more specifically, to the preparation and application of estrogen and its derivatives in lipid or aqueous vehicles for the topical treatment of the ocular surface tissues. In the specification and claims hereinafter the term `sex steroids` is defined to include estrogen, progesterone, testosterone, dehydroepiandrosterone and chemical variants and derivatives of the same. The high incidence of keratoconjunctivitis sicca in the population of postmenopausal women is attended by symptoms ranging from mild foreign body sensation to frank pain and visual loss due to ocular surface abnormalities. Web site: http://www.delphion.com/details?pn=US05041434__

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Eye pillow Inventor(s): Igaki; Michihito (Tokyo, JP), Oka; Takeshi (Tokyo, JP), Sato; Shinichi (Tokyo, JP), Tokunaga; Tadayuki (Tokyo, JP) Assignee(s): Kao Corporation (Tokyo, JP) Patent Number: 6,409,746 Date filed: October 6, 2000 Abstract: The eye pillow of the present invention has a steam-generating unit that uses chemical energy. The temperature of steam released from the surface of the eye pillow which is applied to the eyes and the area around the eyes is kept at 50.degree. C. or lower and total weight of the eye pillow is 50 g or more. Preferably, the eye pillow has the steam-generating unit and a cooler which are attached to the eye pillow body removably. Thus, the moisture as with a steamed towel and the cold as with a cold towel can be continuously introduced to the eyes and the area around the eyes easily and safely to relieve the dry eyes, etc., while applying an appropriate pressure to the eyes and the area around the eyes. Excerpt(s): The present invention relates to an eye pillow with which the eyes and the area around the eyes are cooled at a temperature that is not damaging or irritating or warmed at a steam temperature that is not damaging or irritating in order to alleviate

Patents 25

and improve eyestrain, the main cause of which is dry, burning eyes, and thereby provide comfort by relaxing, refreshing, etc., and induce a pleasant sleep. Many people complain of eye fatigue (eyestrain) in today's stressful world flooded with information. Dry eyes as a result of operating a VDT (visual display terminal), such as a computer terminal, driving an automobile, watching television or videos, playing video games, studying, reading, etc., are one of the main causes of eyestrain. As a result of the eyes staring and blinking very few times while operating a VDT, etc., the eyes become bloodshot, the accommodation muscles around the eyes become over-strained, and there is an increase in the amount of evaporation of tears, which are an important protective component of the surface of the eyes, and the eyes thereby become dry. The environment in which a VDT is operated today is generally air-conditioned and in a state of low moisture and therefore, the eyes easily become dry. This probably exacerbates eyestrain due to dry eyes. Furthermore, many people now wear contact lenses that float in tears on the cornea. Therefore, there is a possibility that the cornea will be scratched by a contact lens when the eyes become dry, particularly in persons who secrete few tears. Dry-eyes causes not only eyestrain, but also the other problems. Web site: http://www.delphion.com/details?pn=US06409746__ •

Method for diagnosing dry eyes Inventor(s): Fujishima; Hiroshi (Ichikawa, JP) Assignee(s): Taisho Pharmaceutical Co., Ltd. (Tokyo, JP) Patent Number: 5,884,630 Date filed: December 23, 1996 Abstract: Dry eyes are more objectively and exactly diagnosed on the basis a rate of decrease in corneal surface temperature due to the heat vaporization in tear evaporation as determined by measuring corneal surface temperatures in time course from one blinking to next blinking of eyes of patients by an infrared radiation thermometry. Excerpt(s): The present invention relates to a method for diagnosing dry eyes, and more particularly to a method for diagnosing dry eyes by measuring corneal surface temperatures after one blinking and determining a rate of decrease in the corneal surface temperature due to the heat of vaporization in the tear evaporation of eyes of patients. Dry eyes are a disease occurring as a disorder on the ocular surface, i.e. cornea and conjunctiva surfaces, due to qualitative or quantitative abnormality of tears. With the advent of the current information age office automation is now in rapid progress and consequently the video display terminal work is rapidly growing, resulting in increase in asthenopia or dry eye-complaining patients. It is said that Japan only has a latent dry eye patient population of eight millions. A primary cause of dry eyes has not been clarified yet, but the up-to-date knowledge suggests that the dry eyes are closely related to an abnormal autoimmunity or viruses. Heretofore, diagnosis of dry eyes has been carried out not by a single test procedure, but by a combination of various test procedures. A particularly important test procedure for the diagnosis is an inquiry and most of asthonopia-complaining patients are diagnosed as suffering from dry eyes. Besides the inquiry, vital staining test and quantative determination of tears have been regarded as essential test procedures. In addition, other test procedures, such as quantitative determination of tear evaporation, have been also in practice. Web site: http://www.delphion.com/details?pn=US05884630__

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Patent on use of aloe vera ophthalmic solution for treatment of the dry eye syndrome, inflammations, ulcerations, alkaline or acid burns, infections, and cataracts Inventor(s): de de la Pena; Nuria E. A. C. (1825 I St., NW Suite 400, Washington, DC 20008), Madoz; Silvia Cristina (M.T. de Alvear, 1624 2do., Capital Federal 1060, Buenos Aires, AR) Assignee(s): none reported Patent Number: 6,013,259 Date filed: September 22, 1997 Abstract: This invention relates to a process for obtaining Aloe Vera gel and the ophthalmic use of Aloe Vera gel in the treatment of dry eye syndrome. Excerpt(s): The dry eye syndrome is a very common disorder that affects mainly contact lens users, and post-menopaual women. It is also known as keratoconjuntivitis sicca. This disorder induces a feeling of dryness, burning, redness, and a persistent irritation of the eye. In severe cases it can produce pain, photophobia, corneal ulceration, severe inflammation, loss of vision, and develop of opportunistic infections. The investigation into the use of aloe Vera in ophthalmologic disorders was aimed at examining whether the rapid tissue repairing and anti-inflammatory properties of aloe Vera, which have been successfully demonstrated in the treatment of internal and external wounds, could be applied to disorders of the eye involving inflammation, ulceration and infections. Current available treatments for the dry eye are not fully effective because they do not induce re-epithelization of the cornea and repairing of the physiology of the eye. In this cases is common the use of corticosteroids to decrease inflammation, thus impairing local immunity. This situation facilitates the onset of opportunistic and chronic infections. The persistent irritation caused because the fail in lubrication between the eyes' lid and the eye surface may also trigger Herpes virus (HSV) recurrence. Web site: http://www.delphion.com/details?pn=US06013259__

Patent Applications on Dry Eyes As of December 2000, U.S. patent applications are open to public viewing.5 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 dry eyes: •

Artificial tear formulation Inventor(s): Macey-Dare, Beatrix Valeria; (Oxford, GB), Tiffany, John Michael; (Oxford, GB) Correspondence: Lahive & Cockfield, LLP.; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20040126419 Date filed: April 1, 2003 Abstract: Provided by the present invention are formulations suitable for application to mammalian eyes which contain a lipid binding protein and a polar lipid, present as a soluble complex in an aqueous electrolyte. The formulations described have shear-

5

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

Patents 27

thinning (non-Newtonian viscosity) and surface tension properties to natural tears and are therefore useful as artificial tear substitutes for the treatment of dry eyes (e.g. keratoconjunctivitis sicca) and useful in ophthalmic applications in general. Excerpt(s): Human tears are composed of water, electrolytes, small molecules such as carbohydrates and lipids, and a variety of proteins, several of which have an enzymic function. The principal proteins of tears include lysozyme (an enzyme which attacks bacterial cell walls), lactoferrin (an iron-sequestering and thus bacteriostatic protein with a free-radical scavenging function), secretory IgA antibodies, and lipid binding proteins of the lipocalin family (previously known as tear-specific prealbumin). A wide variety of other enzymes (e.g. glycosidases and lysosomal hydrolases) is also present but in much smaller amounts. Present formulations of artificial tears act by replacing the volume of the tear film, but they can only do this while they remain in contact with the surface of the eye. A simple saline solution would remain in contact with the eye surface for only a few seconds and thus a viscosity improving component is required in the formulation. Such components presently used include hypromellose, hydroxyethylcellulose, carboxymethylcellulose, polyvinyl pyrrolidone, polyvinyl alcohol, polyethylene glycol, dextran, hyaluronic acid, or carbomer 940 (polyacrylic acid). Such compounds act by mimicking the mucus present on the corneal surface and may interact with such mucus already present. The presence of such mucus mimicking (mucomimetic) components can, in some instances, lead to symptoms of blurred vision due to slow mixing with tears, and irritation caused by the crystallisation of said components on lids and lashes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Gene therapy for dry eye syndrome Inventor(s): Chen, Weiliam; (Coram, NY), DeHazya, Philip; (Westbury, NY) Correspondence: Darby & Darby P.C.; P. O. Box 5257; New York; NY; 10150-5257; US Patent Application Number: 20030087850 Date filed: July 10, 2001 Abstract: The present invention provides bioconjugates comprising substances which provide increased safety and bioavailability of nucleic acids when used in gene therapy applications. The dihydrazide derivatized hyaluronic acid/nucleic acid compositions of the present invention include hyaluronic acid which has been derivatized with a dihydrazide, preferably adipic dihydrazide, which is crosslinked to a nucleic acid. These compositions may be included in microsphere, film, wafer, matrix, hydrogel, gel and sol formulations. These bioconjugates are useful in gene therapy applications for the treatment of a variety of medical conditions including dry eye syndrome or other medical conditions wherein an increase in the production of hyaluronic acid in the eye would be therapeutic. Further, there may be other medical conditions which could benefit from increased production of hyaluronan, such as osteoarthritis of the articular joints. In the treatment of dry eye syndrome, the compositions of the invention include a hyaluronan synthase gene. When cells in the eye are transfected with and express hyaluronan synthase, hyaluronic acid production is a result. Hyaluronic acid production in the eye provides a therapeutic effect in the treatment of dry eye syndrome by augmenting production of or composition of the ocular tear film. Production of the compositions of the invention is also possible in a process which is easily modified for production of large quantities of dihydrazide derivatized hyaluronic acid.

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Excerpt(s): The present invention relates to the use of derivatized hyaluronic acid/nucleic acid compositions, preferably dihydrazide derivatized hyaluronic acid/nucleic acid compositions, and microsphere, film, wafer, matrix, gel and sol formulations comprising these compositions. The invention also relates to the use of the compositions of the invention, preferably, wherein the nucleic acid is a hyaluronan synthase (HAS) gene, in gene therapy applications to treat dry eye syndrome(DES). Methods for the production of these compositions are also provided. Dry eye is a chronic condition characterized, simplistically, by a paucity of moisture in the eye. The cause of dry eye can be infectious disease, the aging process, autoimmunity, trauma or other pathological changes. There is no single cause. Symptoms of dry eye include scarcity of moisture and lubrication or tear film, itching, burning, inflammation, erythema, distortion of vision and in severe cases damage to the tissue of the eye leading to blindness. The tear film of the eye protects ocular tissues by providing moisture and lubrication. It is composed of three major components: water (whose primary source is the lachrymal duct), lipid and "mucin", a proteoglycan mixture containing polymeric forms of carbohydrate and protein. The tear film of the eye is compromised in most patients with dry eye, in that the water component is reduced in quantity. The tear volume may be determined by the schirmer test. This is a test using a filter paper strip with graduations. The strip is placed at the lower lid and the tear is allowed to wick into the paper for a set time interval. The more liquid, the farther the liquid edge travels. The distance the tear fluid travels determines whether the person is determined to have dry eye syndrome. These tear film alterations lead to the symptoms observed in DES. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

REMEDY FOR DRY EYE SYNDROME Inventor(s): Schwebel, Mary; (Minneapolis, MN) Correspondence: Patterson, Thuente, Skaar & Christensen, P.A.; 4800 Ids Center; 80 South 8th Street; Minneapolis; MN; 55402-2100; US Patent Application Number: 20030193644 Date filed: April 15, 2002 Abstract: A treatment for dry eye syndrome. An at least partially sealed chamber including a reservoir for moisture for surrounding the eyes is disclosed. The invention may be transparent for use during the day or in association with prescription or nonprescription lenses. The moisture chamber may also be opaque to act as a blackout mask for sleeping. Excerpt(s): The present invention relates to the treatment of dry eye syndrome. More particularly, it relates to altering the local environment to reduce the discomfort of dry eye syndrome. Dry eye syndrome is one of the most commonly treated eye problems in the United States. Dry eye syndrome is also known as keratitis sicca, keratoconjunctivitis sicca (KCS) xerophthalmia, and lacrimal insufficiency. It is estimated that over ten million Americans and 30 million persons worldwide suffer from dry eye syndrome. For a large fraction of dry eye patients, dry eye syndrome creates discomfort or annoyance. For those severely afflicted, dry eye syndrome can be debilitating and, in some circumstances, even sight-threatening. In extremely severe cases, dry eye syndrome can even lead to the loss of an eye. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with dry eyes, 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 “dry eyes” (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 dry eyes. You can also use this procedure to view pending patent applications concerning dry eyes. 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 3. BOOKS ON DRY EYES Overview This chapter provides bibliographic book references relating to dry eyes. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on dry eyes 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 “dry eyes” (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 dry eyes: •

New Sjogren's Syndrome Handbook Source: New York, NY: Oxford University Press. 1998. 230 p. Contact: Available from Sjogren's Syndrome Foundation, Inc. 8120 Woodmont Avenue, Suite 530, Bethesda MD 20814-1437. (301) 718-0300 or (800) 475-6473. Fax (301) 718-0322. Website: www.sjogrens.org. PRICE: $20.00 for members; $25.00 for nonmembers; plus shipping and handling. ISBN: 0195117247. Summary: This book offers a comprehensive guide to Sjogren's syndrome (SS). Designed both for people with Sjogren's and for physicians, the 26 chapters provide readers with both medical and practical information on this disorder. The book describes the symptoms, which can range from dry eyes and dry mouth (xerostomia), to hoarseness and difficulty in eating, to chronic fatigue and joint pain that can seriously impair quality of life. The authors offer complete information about diagnosis and how SS affects the various organ systems of the body, including the kidneys, blood vessels,

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lungs, liver, pancreas, and brain. The book also discusses treatment options and offers tips for daily living. The authors stress that, although there is no cure for SS, many strategies can be used to alleviate the suffering and problems faced by people with SS. The book concludes with a glossary of terms, a reference list, and a subject index. 53 references.

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CHAPTER 4. PERIODICALS AND NEWS ON DRY EYES Overview In this chapter, we suggest a number of news sources and present various periodicals that cover dry eyes.

News Services and Press Releases One of the simplest ways of tracking press releases on dry eyes 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 “dry eyes” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to dry eyes. 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 “dry eyes” (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

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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 “dry eyes” (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 “dry eyes” (or synonyms). If you know the name of a company that is relevant to dry eyes, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “dry eyes” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “dry eyes” (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 dry eyes:

Periodicals and News

•

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Help for Troublesome Bladder Symptoms Source: ICA Update. p. 1-3. January-February 2002. Contact: Available from Interstitial Cystitis Association. 110 North Washington Street, Suite 340, Rockville, MD 20850. (800) HELP-ICA or (301) 610-5300. Website: www.ichelp.org. Summary: For some patients with interstitial cystitis (IC), frequency of urination is the most troubling symptom. Other IC patients experience bladder spasms and resulting pain as a main component of their IC symptoms. For others, occasional urinary tract infections (UTIs) intensify the symptoms of IC. This article reviews the use of some oral medications in IC. While not specifically designed to treat IC, several different types of medications may be helpful in treating these related symptoms. These medications may not work for all IC patients because they can cause urinary retention (difficulty in urinating), which may already be a problem for some IC patients. They can also cause dry eyes and mouth, which can be troublesome for IC patients with co-existing conditions such as Sjogren's syndrome. The author stresses that these medications are for symptom management only and are not disease-specific therapies; patients need to continue with their standard IC therapies while taking these medications as needed. Medications discussed include combination medicines (antispasmodics, pain relievers, antiseptics) and bladder antispasmodics or anticholinergics.

•

Early and Late Side Effects of Radiation Therapy for Head and Neck Cancers Source: News from SPOHNC. News from Support for People with Oral and Head and Neck Cancer, Inc. 10(4): 1-3. Winter 2000. Contact: Available from Support for People with Oral and Head and Neck Cancer, Inc. (SPOHNC). P.O. Box 53, Locust Valley, NY 11560-0053. (516) 759-5333. E-mail: [email protected]. Website: www.spohnc.org. Summary: Radiation therapy plays an important role in the treatment of head and neck cancers. With the new imaging modalities and sophisticated treatment planning and delivery systems, it is possible today to deliver radiation more precisely, but still not without some side effects to the normal tissues in the vicinity of the tumor bearing area. This article briefly discusses the early and late side effects of curative irradiation for head and neck cancers. Early side effects discussed include fatigue, radiation dermatitis (skin changes in the area under treatment, something like sunburn), mucositis (inflammation of the mucous membranes lining the mouth and throat), loss of taste and smell, and impaired hearing. Late side effects (more than 3 months after radiation therapy) discussed include xerostomia (dry mouth), osteoradionecrosis (bone disease, notably necrosis or death of the jawbone), dry eyes, hair loss, laryngeal edema (swelling of the voice box), hypothyroidism, delayed wound healing, stiffness in the muscles that open and close the mouth, and risk of secondary cancers. The authors briefly describe each of these problems, how they may be treated, and what the patient can expect in terms of recovery.

•

Primary Sjogren's Syndrome: Diagnostic Criteria, Clinical Features and Disease Activity Source: Moisture Seekers Newsletter. 15(9): 1,4-6. Winter 1997. Contact: Available from Sjogren's Syndrome Foundation, Inc. 8120 Woodmont Avenue, Suite 530, Bethesda MD 20814-1437. (301) 718-0300 or (800) 475-6473. Fax (301) 718-0322. Website: www.sjogrens.org.

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Dry Eyes

Summary: This newsletter article provides information about the diagnostic criteria, clinical features, and disease activity of primary Sjogren's syndrome (SS). Primary SS is considered the most common disorder among the group of chronic systemic rheumatic diseases. The author begins with a section on terminology and classification; included in this discussion is the European Economic Community (EEC) classification criteria. The article provides the SS wheel to help when describing and classifying the clinical disease manifestations. As patients with SS usually emphasize subjective symptoms, the authors mention a few key features. The four most troublesome symptoms (in order of frequency at the time of diagnosis) are extraordinary tiredness, dry mouth, dry eyes, and pain in the wrist or finger joints. The authors conclude that the routinely used clinical tests for evaluating disease activity probably measure both activity and damage. No immunopathogenic markers have been shown to adequately represent all aspects of disease activity to date. 1 figure. 1 table. 14 references. •

Sjogren's Syndrome: Clinical Picture and Diagnostic Tests Source: Moisture Seekers Newsletter. 13(12): 1,3-6. Winter 1995. Contact: Available from Sjogren's Syndrome Foundation, Inc. 8120 Woodmont Avenue, Suite 530, Bethesda MD 20814-1437. (301) 718-0300 or (800) 475-6473. Fax (301) 718-0322. Website: www.sjogrens.org. Summary: This newsletter article reviews the diagnostic tests used to confirm Sjogren's syndrome (SS). The authors outline the differential diagnosis for this disease and describe the typical clinical presentation of patients with SS. Topics covered include a brief discussion of prevalence of SS, xerostomia and its oral consequences, xerophthalmia (dry eyes), the differential diagnosis of sixxa syndrome, the objective assessment of xerostomia and xerophthalmia, typical laboratory findings in SS, the use of salivary gland biopsy, and atypical presentations of Sjogren's. 3 tables. 14 references.

Academic Periodicals covering Dry Eyes Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to dry eyes. In addition to these sources, you can search for articles covering dry eyes that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

37

CHAPTER 5. 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 dry eyes. 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 dry eyes. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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Dry Eyes

following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to dry eyes: Beta-Carotene •

Systemic - U.S. Brands: Lumitene; Max-Caro http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202623.html

Cyclosporine •

Ophthalmic - U.S. Brands: Restasis http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500453.html

Hydroxypropyl Cellulose •

Ophthalmic - U.S. Brands: Lacrisert http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202289.html

Hydroxypropyl Methylcellulose •

Ophthalmic - U.S. Brands: Artificial Tears; Bion Tears; Gonak; Goniosoft; Goniosol; Isopto Alkaline; Isopto Plain; Isopto Tears; Just Tears; Lacril; Moisture Drops; Nature's Tears; Ocucoat; Ocucoat PF; Tearisol; Tears Naturale; Tears Naturale Free; Tears Naturale II; Tears Renewed; Ultra Tears http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202290.html

Vitamin A •

Systemic - U.S. Brands: Aquasol A http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202595.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.

Researching Medications

39

Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

41

APPENDICES

43

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 Institute6: •

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/

6

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

44

Dry Eyes

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Physician Resources

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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.7 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:8 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

7

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

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Dry Eyes

•

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

•

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

The NLM Gateway9 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.10 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “dry eyes” (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 1853 37 958 5 2957 5810

HSTAT11 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.12 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.13 Simply search by “dry eyes” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

9

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

10

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). 11 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 12 13

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

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

Physician Resources

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Coffee Break: Tutorials for Biologists14 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.15 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.16 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

14 Adapted 15

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

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 16 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.

49

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 dry eyes 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 dry eyes. 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 dry eyes. 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 “dry eyes”:

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Dry Eyes

Eye Diseases http://www.nlm.nih.gov/medlineplus/eyediseases.html Eye Injuries http://www.nlm.nih.gov/medlineplus/eyeinjuries.html Facial Injuries and Disorders http://www.nlm.nih.gov/medlineplus/facialinjuriesanddisorders.html Laser Eye Surgery http://www.nlm.nih.gov/medlineplus/lasereyesurgery.html Macular Degeneration http://www.nlm.nih.gov/medlineplus/maculardegeneration.html Sjogren's Syndrome http://www.nlm.nih.gov/medlineplus/sjogrenssyndrome.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on dry eyes. 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: •

Dry Eyes? Dry Mouth? Rheumatic Disease?: You Need to Know About Sjogren's Syndrome Source: Bethesda, MD: Sjogren's Syndrome Foundation, Inc. 199x. [4 p.]. Contact: Available from Sjogren's Syndrome Foundation, Inc. 8120 Woodmont Avenue, Suite 530, Bethesda MD 20814-1437. (301) 718-0300 or (800) 475-6473. Fax (301) 718-0322. Website: www.sjogrens.org. PRICE: Single copy free. Summary: Sjogren's syndrome (SS) is a chronic, autoimmune disorder in which the body's immune system mistakenly attacks its own moisture-producing glands. The typical symptoms of SS include dry eyes and dry mouth (xerostomia). This brochure familiarizes readers with the symptoms, diagnosis, and treatment of SS. Topics include the classification of SS as primary or secondary, the symptoms, diagnostic tests used to confirm the presence of SS, the importance of early diagnosis and intervention, and the Sjogren's Syndrome Foundation. The brochure notes that saliva substitutes and a prescription medication can ease the symptoms of dry mouth. The brochure includes a list of questions for readers to ask themselves, when determining if SS may be involved in their own symptoms. Also included is a list of tips for daily living, and a glossary of

Patient Resources

51

related terms. The brochure has a tear off form with which readers can join the Sjogren's Syndrome Foundation. 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: •

What is Blepharospasm? Summary: The term blepharospasm can be applied to any abnormal blinking or eyelid tic or twitch resulting from any cause, ranging from dry eyes to Tourette's syndrome to tardive dyskinesia. Source: Benign Essential Blepharospasm Research Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7987 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 dry eyes. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

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Dry Eyes

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

53

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 “dry eyes” (or a synonym) into the search box, and click “Submit Query.”

55

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.17

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

17

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)18: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

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

•

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

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

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

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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/

•

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/

18

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

Finding Medical Libraries

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•

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

•

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

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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

•

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

•

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

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

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

•

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

•

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

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

•

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

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

•

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

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

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

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

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

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

•

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

•

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

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

•

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

•

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

•

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

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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

•

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

•

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

•

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

•

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

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

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

•

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

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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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

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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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

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

•

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

•

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

•

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

•

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

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

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

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

•

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

•

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

•

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

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DRY EYES DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] Accommodation: Adjustment, especially that of the eye for various distances. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] 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] 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] 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] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Aloe: A genus of the family Liliaceae containing anthraquinone glycosides such as aloinemodin or aloe-emodin (emodin). [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

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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] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amylase: An enzyme that helps the body digest starches. [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] 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] 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] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergics: Medicines that calm muscle spasms in the intestine. Examples are

Dictionary 65

dicyclomine (dy-SY-kloh-meen) (Bentyl) and hyoscyamine (HY-oh-SY-uh-meen) (Levsin). [NIH]

Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] 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-inflammatory: Having to do with reducing inflammation. [NIH] Antispasmodics: Medicines that help reduce or stop muscle spasms in the intestines. Examples are dicyclomine (dy-SY-klo-meen) (Bentyl) and atropine (AH-tro-peen) (Donnatal). [NIH] Aqueous: Having to do with water. [NIH] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Asthenia: Clinical sign or symptom manifested as debility, or lack or loss of strength and energy. [NIH] Asthenopia: Term generally used to describe complaints related to refractive error, ocular muscle imbalance, including pain or aching around the eyes, burning and itchiness of the eyelids, ocular fatigue, and headaches. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [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

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bacillary, and spiral or spirochetal. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] 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] Blackout: A condition characterized by failure of vision and momentary unconsciousness, due to diminished circulation to the brain and the retina. [NIH] Bladder: The organ that stores urine. [NIH] Blepharitis: Inflammation of the eyelids. [NIH] Blepharoplasty: Plastic surgery of the eyelid. [NIH] Blepharospasm: Excessive winking; tonic or clonic spasm of the orbicularis oculi muscle. [NIH]

Blinking: Brief closing of the eyelids by involuntary normal periodic closing, as a protective measure, or by voluntary action. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Aqueous Barrier: The selectively permeable barrier between the capillary bed in the ciliary body and the aqueous humor. It consists of two layers of epithelium joined at their apical surfaces by tight junctions. [NIH] Blood-Retinal Barrier: Specialized nonfenestrated tightly-joined endothelial cells that form a transport barrier for certain substances between the retinal capillaries and the retinal tissue. [NIH]

Dictionary 67

Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] 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] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [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] 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] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carboxymethylcellulose: It is used as an emulsifier, thickener, suspending agent, etc., in cosmetics and pharmaceuticals; in research as a culture medium; in chromatography as a stabilizer for reagents; and therapeutically as a bulk laxative with antacid properties. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [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] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH]

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Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in cartilage. [NIH]

Chronic: A disease or condition that persists or progresses over a long period of time. [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] Clonal Deletion: Removal, via cell death, of immature lymphocytes that interact with antigens during maturation. For T-lymphocytes this occurs in the thymus and ensures that mature T-lymphocytes are self tolerant. B-lymphocytes may also undergo clonal deletion. [NIH]

Clonic: Pertaining to or of the nature of clonus. [EU] 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] 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] Colloidal: Of the nature of a colloid. [EU] 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

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that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] 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] Computer Systems: Systems composed of a computer or computers, peripheral equipment, such as disks, printers, and terminals, and telecommunications capabilities. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [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 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] 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] Contrast Sensitivity: The ability to detect sharp boundaries (stimuli) and to detect slight changes in luminance at regions without distinct contours. Psychophysical measurements of this visual function are used to evaluate visual acuity and to detect eye disease. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Ulcer: Loss of epithelial tissue from the surface of the cornea due to progressive erosion and necrosis of the tissue; usually caused by bacterial, fungal, or viral infection. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [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] Curative: Tending to overcome disease and promote recovery. [EU] Cystitis: Inflammation of the urinary bladder. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytotoxic: Cell-killing. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU]

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Dehydration: The condition that results from excessive loss of body water. [NIH] 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] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

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] Dermatitis: Any inflammation of the skin. [NIH] Desiccation: Removal of moisture from a substance (chemical, food, tissue, etc.). [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dicyclomine: A muscarinic antagonist used as an antispasmodic and in urinary incontinence. It has little effect on glandular secretion or the cardiovascular system. It does have some local anesthetic properties and is used in gastrointestinal, biliary, and urinary tract spasms. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] 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] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duct: A tube through which body fluids pass. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU]

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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] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emodin: Purgative anthraquinone found in several plants, especially Rhamnus frangula. It was formerly used as a laxative, but is now used mainly as tool in toxicity studies. [NIH] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [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] Epidemiological: Relating to, or involving epidemiology. [EU] Epigastric: Having to do with the upper middle area of the abdomen. [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] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Estrogen: One of the two female sex hormones. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at

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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] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] 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] Flatus: Gas passed through the rectum. [NIH] Fluorophotometry: Measurement of light given off by fluorescein in order to assess the integrity of various ocular barriers. The method is used to investigate the blood-aqueous barrier, blood-retinal barrier, aqueous flow measurements, corneal endothelial permeability, and tear flow dynamics. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [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] 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] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [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

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action. [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] Genotype: The genetic constitution of the individual; the characterization of the genes. [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] Glare: Scatter from bright light that decreases vision. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Refers to the liver. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hoarseness: An unnaturally deep or rough quality of voice. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH]

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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] 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] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [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] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

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

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [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] 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]

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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] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] 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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [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] Intracellular: Inside a cell. [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] 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]

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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] 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] 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] Keratitis: Inflammation of the cornea. [NIH] Keratoconjunctivitis: Simultaneous inflammation of the cornea and conjunctiva. [NIH] Keratoconjunctivitis Sicca: Drying and inflammation of the conjunctiva as a result of insufficient lacrimal secretion. When found in association with xerostomia and polyarthritis, it is called Sjogren's syndrome. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lacrimal: Pertaining to the tears. [EU] Lactobacillus: A genus of gram-positive, microaerophilic, rod-shaped bacteria occurring widely in nature. Its species are also part of the many normal flora of the mouth, intestinal tract, and vagina of many mammals, including humans. Pathogenicity from this genus is rare. [NIH] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH]

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Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lubricants: Oily or slippery substances. [NIH] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment but it can be used for the application of substances to tissue to reduce friction, such as lotions for skin and vaginal lubricants. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] 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] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

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]

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MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Membrane: A very thin layer of tissue that covers a surface. [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] 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] 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] 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] 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] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Miotic: 1. Pertaining to, characterized by, or producing miosis : contraction of the pupil. 2. An agent that causes the pupil to contract. 3. Meiotic: characterized by cell division. [EU] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] 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] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH]

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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] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oculi: Globe or ball of the eye. [NIH] Oculomucocutaneous: Pertaining to or affecting the mucous membrane and the skin around the eyes. [EU] Office Automation: Use of computers or computer systems for doing routine clerical work, e.g., billing, records pertaining to the administration of the office, etc. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmic: Pertaining to the eye. [EU] Ophthalmologic: Pertaining to ophthalmology (= the branch of medicine dealing with the eye). [EU]

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Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Orbicularis: A thin layer of fibers that originates at the posterior lacrimal crest and passes outward and forward, dividing into two slips which surround the canaliculi. [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] Osteoradionecrosis: Necrosis of bone following radiation injury. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [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] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3. [NIH]

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Photophobia: Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. [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] Pilocarpine: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] 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] Pneumonia: Inflammation of the lungs. [NIH] Polyarthritis: An inflammation of several joints together. [EU] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyvinyl Alcohol: A polymer prepared from polyvinyl acetates by replacement of the acetate groups with hydroxyl groups. It is used as a pharmaceutic aid and ophthalmic lubricant as well as in the manufacture of surface coatings artificial sponges, cosmetics, and other products. [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]

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Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [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] 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] Preoperative: Preceding an operation. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] 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] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein 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] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [NIH]

Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

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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] 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] 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] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] 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] 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] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of

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treatment. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] 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] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] 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] 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] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins

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have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] 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]

Sicca: Failure of lacrimal secretion, keratoconjunctivitis sicca, failure of secretion of the salivary glands and mucous glands of the upper respiratory tract and polyarthritis. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or

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Latinized adjective or noun. [EU] 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] 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] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [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] Strained: A stretched condition of a ligament. [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] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subcutaneous: Beneath the skin. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [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] 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] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and

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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] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] Timolol: A beta-adrenergic antagonist similar in action to propranolol. The levo-isomer is the more active. Timolol has been proposed as an antihypertensive, antiarrhythmic, antiangina, and antiglaucoma agent. It is also used in the treatment of migraine and tremor. [NIH]

Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [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] 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

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no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU]

Dictionary 89

Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] 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] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xerophthalmia: Dryness of the eye surfaces caused by deficiency of tears or conjunctival secretions. It may be associated with vitamin A deficiency, trauma, or any condition in which the eyelids do not close completely. [NIH] Xerostomia: Decreased salivary flow. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

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INDEX A Abdominal, 63, 80 Accommodation, 25, 63 Adrenal Cortex, 63, 69, 82 Adrenal Glands, 63, 64 Adrenergic, 63, 82, 87 Adverse Effect, 63, 85 Affinity, 63, 85 Agonist, 63, 81 Albumin, 4, 63, 81 Algorithms, 63, 66 Alkaline, 26, 38, 63, 67 Aloe, 26, 63 Alpha Particles, 63, 83 Alternative medicine, 34, 64 Amino Acid Sequence, 64, 73 Amino Acids, 11, 64, 73, 80, 82 Amylase, 4, 64 Amyloidosis, 17, 64 Anaesthesia, 64, 75 Anaphylatoxins, 64, 69 Anions, 63, 64, 76, 85 Antiarrhythmic, 64, 87 Antibacterial, 64, 86 Antibiotic, 64, 86 Antibodies, 27, 64, 65, 74, 81, 83 Antibody, 6, 63, 64, 65, 68, 74, 75, 76, 78, 83, 89 Anticholinergics, 35, 64 Anticoagulant, 65, 82 Antigen, 7, 63, 64, 65, 68, 74, 75 Antigen-Antibody Complex, 65, 68 Antihypertensive, 65, 87 Anti-inflammatory, 26, 65 Antispasmodics, 35, 65 Aqueous, 24, 26, 65, 66, 72, 76 Arteries, 65, 66 Arterioles, 65, 66, 67 Artery, 65, 66, 80, 83 Articular, 27, 65, 80 Asthenia, 12, 65 Asthenopia, 25, 65 Atropine, 65 Atypical, 36, 65 Autoantibodies, 5, 7, 10, 12, 65 Autoantigens, 65 Autoimmune disease, 5, 7, 65 Autoimmunity, 7, 13, 25, 28, 65

Autologous, 10, 15, 65 B Bacteria, 64, 65, 66, 70, 71, 73, 76, 78, 86, 87, 88 Bacteriostatic, 27, 66 Base, 66, 73, 76 Benign, 51, 66, 79, 83 Bile, 66, 77, 86 Bilirubin, 63, 66 Bioavailability, 27, 66 Biochemical, 6, 66, 80 Biopsy, 36, 66 Biotechnology, 8, 34, 45, 66 Blackout, 28, 66 Bladder, 35, 66, 69, 79, 88 Blepharitis, 10, 66 Blepharoplasty, 18, 66 Blepharospasm, 51, 66 Blinking, 16, 25, 51, 66 Blood pressure, 65, 66, 78, 85 Blood vessel, 31, 66, 77, 80, 85 Blood-Aqueous Barrier, 66, 72 Blood-Retinal Barrier, 66, 72 Body Fluids, 67, 70, 85 Bone Marrow, 15, 67, 73, 74, 77, 78 Brachytherapy, 67, 75, 76, 83, 89 Breeding, 7, 67 C Calcium, 67, 68, 77, 85 Capillary, 5, 66, 67, 88 Carbohydrate, 28, 67, 73, 81 Carboxymethylcellulose, 27, 67 Carcinogenic, 67, 86 Cardiac, 64, 67, 86 Case report, 17, 67 Cataracts, 26, 67 Cell, 6, 7, 27, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 77, 78, 79, 80, 81, 83, 84, 85, 86, 87, 89 Cell Death, 67, 68, 79 Cell Differentiation, 67, 85 Cell proliferation, 67, 85 Chemotactic Factors, 68, 69 Cholesterol, 66, 68, 86 Chondroitin sulfate, 21, 68 Chronic, 5, 10, 26, 28, 31, 36, 50, 68, 75 Clinical trial, 4, 45, 68, 69, 83 Clonal Deletion, 6, 68

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Clonic, 66, 68 Cloning, 66, 68 Collagen, 68, 72, 77 Colloidal, 63, 68, 71, 85 Complement, 8, 64, 68, 81 Computational Biology, 45, 69 Computer Systems, 69, 79 Concomitant, 5, 69 Congestion, 69, 71 Conjugated, 24, 69 Conjunctiva, 25, 69, 76 Connective Tissue, 67, 68, 69, 77, 82, 84 Contraindications, ii, 69 Contrast Sensitivity, 14, 15, 69 Control group, 4, 69 Cornea, 15, 19, 21, 25, 26, 69, 73, 76, 84 Corneal Ulcer, 26, 69 Corpus, 69, 82, 89 Corpus Luteum, 69, 82 Corticosteroids, 26, 69 Cortisol, 63, 69 Curative, 35, 69, 86 Cystitis, 35, 69 Cytokine, 6, 69 Cytotoxic, 69, 83, 85 D Degenerative, 69, 80 Dehydration, 8, 70 Dehydroepiandrosterone, 24, 70 Deletion, 68, 70 Dental Caries, 4, 70 Depolarization, 70, 85 Dermatitis, 35, 70 Desiccation, 3, 8, 70 Diagnostic procedure, 23, 34, 70 Dicyclomine, 65, 70 Diffusion, 70, 75 Digestion, 66, 70, 75, 77 Digestive system, 70, 79 Direct, iii, 37, 70, 83 Dissociation, 63, 70, 75 Drug Interactions, 38, 70 Duct, 28, 70, 71, 84 Dyskinesia, 51, 70 E Edema, 35, 71 Effector, 6, 68, 71 Efficacy, 11, 22, 71 Electrolyte, 26, 71, 85 Electrons, 66, 71, 75, 76, 83 Electrophoresis, 5, 9, 71 Embryo, 67, 71, 75

Emodin, 63, 71 Enamel, 70, 71 Endotoxic, 71, 77 Endotoxins, 68, 71 Environmental Health, 44, 46, 71 Enzymatic, 67, 68, 70, 71 Enzyme, 27, 64, 71, 73, 81, 82, 85, 86, 89 Epidemiological, 13, 71 Epigastric, 71, 80 Epithelial, 6, 10, 11, 14, 20, 69, 71 Epithelial Cells, 14, 20, 71 Epithelium, 6, 8, 66, 71, 76 Erythema, 28, 71 Estrogen, 24, 71 Exocrine, 3, 5, 7, 71, 80 External-beam radiation, 71, 76, 83, 89 Extracellular, 69, 72, 77, 85 Extracellular Matrix, 69, 72, 77 Extracellular Matrix Proteins, 72, 77 F Facial, 18, 50, 72, 80 Facial Nerve, 72, 80 Family Planning, 45, 72 Fat, 67, 72, 77, 85 Fatigue, 25, 31, 35, 65, 72 Fatty acids, 63, 72 Flatus, 72 Fluorophotometry, 20, 72 Friction, 72, 77 G Gamma Rays, 72, 83 Gas, 21, 70, 72, 74 Gels, 11, 72 Gene, 6, 27, 28, 66, 72, 73, 87 Gene Expression, 72, 73 Gene Therapy, 27, 28, 73 Genetic Code, 73, 79 Genotype, 73, 80 Gland, 5, 7, 8, 19, 20, 36, 63, 73, 77, 80, 84, 87 Glare, 14, 73 Glycoprotein, 20, 73, 86 Glycosaminoglycan, 68, 73 Glycoside, 73, 74, 84 Gonadal, 73, 86 Governing Board, 73, 82 Graft, 19, 73 Gram-positive, 73, 76 Granulocytes, 73, 85, 89 H Hemoglobinopathies, 73 Hemorrhage, 73, 81

93

Hepatic, 63, 73 Heredity, 72, 73 Hoarseness, 31, 73 Homeostasis, 6, 73 Homologous, 73, 74, 86 Hormone, 69, 74, 82, 84, 85, 86, 87 Hydrogel, 27, 74 Hydrogen, 66, 67, 72, 74, 78, 79, 82 Hydrolases, 27, 74, 80 Hydrophilic, 74 Hypersensitivity, 74, 84 I Immune response, 65, 74, 86, 88 Immune Sera, 74 Immune system, 50, 65, 74, 77, 89 Immunity, 26, 74, 87 Immunization, 7, 74 Immunogenic, 74, 77 Immunologic, 22, 68, 74, 83 Immunosuppression, 74, 80 Implant radiation, 74, 75, 76, 83, 89 In vitro, 10, 73, 74 In vivo, 73, 74 Induction, 7, 75 Infection, 68, 69, 74, 75, 77, 80, 84, 89 Infiltration, 7, 75 Inflammation, 5, 6, 15, 26, 28, 35, 63, 65, 66, 69, 70, 75, 76, 78, 81, 84 Inorganic, 75, 79 Insight, 6, 75 Interleukin-1, 6, 75 Interleukin-2, 75 Intermittent, 75 Internal radiation, 75, 76, 83, 89 Interstitial, 35, 67, 75, 76, 89 Intestinal, 75, 76 Intestine, 64, 74, 75, 83 Intracellular, 75, 85 Invasive, 74, 75 Involuntary, 66, 75, 85, 87 Ionization, 5, 75 Ionizing, 64, 75, 83 Ions, 66, 70, 71, 74, 75, 76 Iris, 69, 76, 83 Irradiation, 35, 76, 89 K Kb, 44, 76 Keratitis, 5, 28, 76 Keratoconjunctivitis, 6, 24, 27, 28, 76, 85 Keratoconjunctivitis Sicca, 6, 24, 27, 28, 76, 85 Keratolytic, 70, 76

L Labile, 68, 76 Lacrimal, 4, 5, 12, 28, 72, 76, 80, 85 Lactobacillus, 4, 76 Laryngeal, 35, 76 Larynx, 76, 87 Latent, 25, 76 Laxative, 67, 71, 76 Lens, 8, 18, 20, 25, 26, 67, 76 Lesion, 76, 86, 88 Leukemia, 73, 76 Levo, 76, 87 Ligament, 77, 86 Lipid, 5, 24, 26, 27, 28, 77 Lipid A, 5, 28, 77 Lipopolysaccharides, 77 Liver, 32, 63, 64, 66, 70, 73, 77 Localized, 64, 70, 75, 77, 81, 88 Lubricants, 77 Lubrication, 26, 28, 77 Lymph, 7, 77 Lymph node, 7, 77 Lymphatic, 75, 77, 86 Lymphatic system, 77, 86 Lymphocytes, 65, 68, 74, 75, 77, 86, 89 Lymphocytic, 7, 77 Lymphoid, 64, 69, 77 Lytic, 77, 84 M Macrophage, 75, 77 Malignant, 77, 79, 83 Malnutrition, 63, 77 Matrix metalloproteinase, 6, 77 MEDLINE, 45, 78 Membrane, 68, 69, 70, 72, 76, 78, 79, 80, 84, 85 Meningitis, 78, 81 Menopause, 78, 81, 82 Menstrual Cycle, 78, 82 Mental, iv, 4, 44, 46, 70, 72, 78, 81, 82 Mental Disorders, 78, 81 Metastasis, 77, 78, 79 Microbe, 78, 87 Microbiology, 65, 78 Micro-organism, 70, 78 Miotic, 78, 81 Mitochondrial Swelling, 78, 79 Modification, 78, 83 Molecular, 45, 47, 66, 69, 78 Molecule, 65, 66, 68, 70, 71, 73, 78, 82, 83, 85 Monitor, 7, 78, 79

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Monoclonal, 76, 78, 83, 89 Monocytes, 75, 78 Mucins, 6, 78, 84 Mucositis, 35, 79 Mucus, 27, 78, 79 N Necrosis, 35, 69, 79, 80 Neoplasms, 79, 83 Neural, 9, 79 Neurogenic, 79, 88 Neurotransmitter, 79, 85, 86 Neutrons, 63, 76, 79, 83 Nuclear, 5, 71, 72, 79 Nuclei, 63, 71, 73, 79, 82 Nucleic acid, 27, 28, 73, 79 Nucleotidases, 74, 79 O Ocular, 5, 6, 7, 8, 16, 17, 21, 24, 25, 27, 28, 65, 72, 79 Oculi, 66, 79 Oculomucocutaneous, 19, 79 Office Automation, 25, 79 Opacity, 67, 79 Ophthalmic, 11, 13, 26, 27, 38, 79, 81 Ophthalmologic, 26, 79 Ophthalmology, 5, 6, 9, 10, 11, 14, 15, 16, 17, 18, 19, 20, 21, 79, 80 Opportunistic Infections, 26, 80 Orbicularis, 66, 80 Osmotic, 63, 78, 80, 85 Osteoarthritis, 12, 27, 80 Osteoradionecrosis, 35, 80 Ovum, 69, 80, 82 P Palliative, 80, 86 Pancreas, 32, 63, 70, 80 Parotid, 4, 80 Pathologic, 66, 74, 80 Pathophysiology, 13, 80 Patient Education, 50, 56, 58, 61, 80 Peptide, 74, 80, 82 Peptide Hydrolases, 74, 80 Perfusion, 11, 80 Pharmacologic, 80, 87, 88 Phenotype, 6, 80 Phospholipases, 80, 85 Phosphoric Monoester Hydrolases, 74, 80 Photophobia, 26, 81 Physiologic, 63, 78, 81, 83, 87 Physiology, 20, 26, 81 Pilocarpine, 16, 81 Placenta, 81, 82

Plants, 65, 67, 71, 73, 81, 84, 87 Plasma, 63, 64, 81, 85 Plasma cells, 64, 81 Plasma protein, 63, 81, 85 Platelet Activation, 81, 85 Pneumonia, 69, 81 Polyarthritis, 76, 81, 85 Polyethylene, 27, 81 Polysaccharide, 65, 73, 81, 82 Polyvinyl Alcohol, 9, 17, 27, 81 Posterior, 76, 80, 81, 84 Postmenopausal, 24, 81 Postsynaptic, 82, 85 Potentiates, 75, 82 Potentiation, 82, 85 Practice Guidelines, 46, 82 Precursor, 71, 82 Preoperative, 18, 82 Prevalence, 17, 36, 82 Progesterone, 24, 82, 86 Progressive, 67, 69, 79, 80, 81, 82 Propranolol, 82, 87 Protein C, 5, 63, 64, 82 Protein S, 66, 73, 82 Proteins, 5, 27, 64, 65, 68, 72, 75, 77, 78, 80, 81, 82, 84, 87, 88 Proteoglycan, 28, 82 Proteolytic, 68, 82 Protons, 63, 74, 75, 82, 83 Psychogenic, 82, 88 Public Policy, 45, 83 Pulse, 78, 83 Pupil, 69, 78, 83 Q Quality of Life, 5, 31, 83 R Radiation, 25, 35, 71, 72, 74, 75, 76, 80, 83, 89 Radiation therapy, 35, 71, 75, 76, 83, 89 Radioactive, 74, 75, 76, 79, 83, 89 Radioimmunotherapy, 83 Radiolabeled, 76, 83, 89 Radiotherapy, 16, 67, 76, 83, 89 Randomized, 14, 22, 71, 83 Receptor, 12, 65, 83, 85 Recombinant, 7, 83 Recombination, 73, 83 Rectum, 70, 72, 83 Recurrence, 26, 83 Refer, 1, 68, 77, 79, 83 Refraction, 83, 86 Regimen, 71, 83

95

Remission, 83, 84 Respiration, 78, 84 Retina, 66, 76, 84 Retroviral vector, 73, 84 Rheumatic Diseases, 22, 36, 84 Rheumatoid, 5, 19, 84 Rheumatoid arthritis, 19, 84 Risk factor, 8, 84 Rod, 76, 84 S Saline, 27, 84 Saliva, 3, 4, 22, 50, 84 Salivary, 4, 5, 7, 18, 19, 20, 36, 70, 72, 84, 85, 89 Salivary glands, 5, 7, 70, 72, 84, 85 Saponins, 84, 86 Sclera, 69, 84 Screening, 3, 22, 68, 84 Secretion, 5, 20, 70, 76, 78, 79, 84, 85 Secretory, 27, 84 Serologic, 3, 84 Serum, 10, 15, 63, 64, 68, 74, 84, 85 Serum Albumin, 15, 85 Sex Characteristics, 85, 86 Shock, 85, 87 Sicca, 5, 12, 24, 26, 28, 85 Side effect, 35, 37, 63, 85, 87 Signal Transduction, 6, 85 Signs and Symptoms, 4, 18, 84, 85 Social Environment, 83, 85 Sodium, 4, 9, 14, 19, 85 Soft tissue, 4, 67, 85 Spasm, 66, 85 Specialist, 52, 85 Species, 76, 78, 85, 87, 88 Spectrum, 5, 86 Spleen, 64, 77, 86 Stabilizer, 67, 86 Steroid, 24, 69, 84, 86 Strained, 25, 86 Stress, 6, 32, 69, 84, 86 Subarachnoid, 81, 86 Subcutaneous, 71, 86 Substance P, 84, 86 Substrate, 74, 86 Symptomatic, 16, 86 Synaptic, 79, 85, 86 Synergistic, 86, 87 Systemic, 13, 19, 36, 38, 64, 66, 75, 76, 83, 86, 87, 89 Systemic disease, 13, 86

T Tardive, 51, 86 Testosterone, 24, 86 Therapeutics, 39, 86 Thrombin, 82, 86 Thrombomodulin, 82, 86 Thymus, 68, 74, 77, 86 Thyroid, 12, 87 Thyroxine, 63, 87 Tic, 51, 87 Timolol, 15, 21, 87 Tissue, 26, 28, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 84, 85, 87, 89 Tonic, 66, 87 Topical, 13, 14, 21, 24, 87 Toxic, iv, 65, 74, 87 Toxicity, 10, 70, 71, 87 Toxicology, 46, 87 Toxins, 65, 71, 75, 83, 87 Trachea, 76, 87 Transduction, 85, 87 Transfection, 66, 73, 87 Transfer Factor, 74, 87 Transgenes, 7, 87 Transplantation, 15, 74, 87 Trauma, 28, 79, 87, 89 Tremor, 87 U Ulcer, 88 Ulceration, 26, 88 Ultrasonography, 20, 88 Ureters, 88 Urethra, 88 Urinary, 35, 69, 70, 88 Urinary Retention, 35, 88 Urinary tract, 35, 70, 88 Urinary tract infection, 35, 88 Urinate, 88 Urine, 66, 88 Uterus, 69, 82, 88 V Vaccines, 88 Vagina, 76, 88 Vaginal, 77, 88 Vein, 79, 80, 88 Venules, 66, 67, 88 Veterinary Medicine, 45, 88 Viral, 69, 87, 88 Virulence, 87, 88 Virus, 26, 84, 87, 88 Viscosity, 27, 88

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Visual Acuity, 69, 89 Vitreous, 76, 84, 89 Vitro, 89 W White blood cell, 64, 77, 79, 81, 89 Windpipe, 87, 89 Wound Healing, 35, 77, 89

X Xerophthalmia, 28, 36, 89 Xerostomia, 31, 35, 36, 50, 76, 89 X-ray, 72, 76, 79, 83, 86, 89 X-ray therapy, 76, 89 Y Yeasts, 80, 89 Z Zymogen, 82, 89