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

BRONCHIOLITIS 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., 1960Bronchiolitis: 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: 0-497-00183-7 1. Bronchiolitis-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 bronchiolitis. 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 BRONCHIOLITIS ......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Bronchiolitis.................................................................................. 4 E-Journals: PubMed Central ....................................................................................................... 38 The National Library of Medicine: PubMed ................................................................................ 39 CHAPTER 2. NUTRITION AND BRONCHIOLITIS ............................................................................... 85 Overview...................................................................................................................................... 85 Finding Nutrition Studies on Bronchiolitis................................................................................. 85 Federal Resources on Nutrition ................................................................................................... 87 Additional Web Resources ........................................................................................................... 87 CHAPTER 3. ALTERNATIVE MEDICINE AND BRONCHIOLITIS......................................................... 89 Overview...................................................................................................................................... 89 National Center for Complementary and Alternative Medicine.................................................. 89 Additional Web Resources ........................................................................................................... 91 General References ....................................................................................................................... 92 CHAPTER 4. DISSERTATIONS ON BRONCHIOLITIS........................................................................... 93 Overview...................................................................................................................................... 93 Dissertations on Bronchiolitis...................................................................................................... 93 Keeping Current .......................................................................................................................... 93 CHAPTER 5. PATENTS ON BRONCHIOLITIS ..................................................................................... 95 Overview...................................................................................................................................... 95 Patents on Bronchiolitis............................................................................................................... 95 Patent Applications on Bronchiolitis ........................................................................................... 98 Keeping Current .......................................................................................................................... 99 CHAPTER 6. BOOKS ON BRONCHIOLITIS ....................................................................................... 101 Overview.................................................................................................................................... 101 Book Summaries: Online Booksellers......................................................................................... 101 CHAPTER 7. PERIODICALS AND NEWS ON BRONCHIOLITIS ......................................................... 103 Overview.................................................................................................................................... 103 News Services and Press Releases.............................................................................................. 103 Academic Periodicals covering Bronchiolitis ............................................................................. 105 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 107 Overview.................................................................................................................................... 107 U.S. Pharmacopeia..................................................................................................................... 107 Commercial Databases ............................................................................................................... 108 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 113 Overview.................................................................................................................................... 113 NIH Guidelines.......................................................................................................................... 113 NIH Databases........................................................................................................................... 115 Other Commercial Databases..................................................................................................... 117 APPENDIX B. PATIENT RESOURCES ............................................................................................... 119 Overview.................................................................................................................................... 119 Patient Guideline Sources.......................................................................................................... 119 Finding Associations.................................................................................................................. 122 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 125 Overview.................................................................................................................................... 125 Preparation................................................................................................................................. 125 Finding a Local Medical Library................................................................................................ 125 Medical Libraries in the U.S. and Canada ................................................................................. 125

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ONLINE GLOSSARIES................................................................................................................ 131 Online Dictionary Directories ................................................................................................... 133 BRONCHIOLITIS DICTIONARY.............................................................................................. 135 INDEX .............................................................................................................................................. 191

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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 bronchiolitis 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 bronchiolitis, 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 bronchiolitis, 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 bronchiolitis. 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 bronchiolitis, 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 bronchiolitis. 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 BRONCHIOLITIS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on bronchiolitis.

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

Recognizing the Extra-Articular Manifestations of RA Source: Journal of Musculoskeletal Medicine. 19(8): 307-310,312,314-315. August 2002. Summary: This journal article discusses extra-articular manifestations of rheumatoid arthritis (ExRA). Predictors for ExRA include severe articular disease, a positive antinuclear antibody assay, the presence of IgA rheumatoid factor, increased levels of circulating immune complexes, and the early development of rheumatoid nodules. Rheumatoid nodules, atrophy, erythema nodosum, skin fragility, livedo reticularis, pyoderma gangrenosum, Sweet syndrome, and vasculitis are some cutaneous manifestations of rheumatoid arthritis (RA). The eyes are frequently involved in RA, with manifestations such as episcleritis, scleritis, limbic ulceration, keratoconjunctivitis sicca, and blepharitis. Pulmonary manifestations associated with RA consist of pleuritis, parenchymal lung disease, bronchiectasis, bronchiolitis obliterans with organizing

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pneumonia, Caplan syndrome, pulmonary hypertension, and empyema. Cardiac manifestations include vasculitis, pericarditis, aortitis, myocarditis, and nodular valve disease. Vasculitic manifestations are common in patients with RA and include cutaneous arteriolitis, medium-sized arteritis, and small-vessel vasculitis. Chronic inflammation of the antlantoaxial joint, peripheral neuropathies, and CNS vasculitis are some of the neurologic manifestations of patients with RA. Kidney disease is a less common manifestation of RA. There is an increased incidence of both Hodgkin and nonHodgkin lymphoma and leukenias in patients with RA. The most common hematologic manifestation of RA is hypergammaglobulinemia. Systemic disease may result from adverse effects of treatment with pharmacologic agents. Specific treatment depends on the organ system involved; the overall goal of therapy is control of the underlying rheumatoid process. 27 references, 4 figures, and 2 tables. (AAM).

Federally Funded Research on Bronchiolitis The U.S. Government supports a variety of research studies relating to bronchiolitis. 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 bronchiolitis. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore bronchiolitis. The following is typical of the type of information found when searching the CRISP database for bronchiolitis: •

Project Title: 2-5A ANTISENSE INHIBITION OF RESPIRATORY SYNCTIAL VIRUS Principal Investigator & Institution: Cramer, Hagen; Ridgeway Biosystems, Inc. 9500 Euclid Ave, Nd-50 Cleveland, Oh 44195 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: (Adapted from Applicant's Abstract): Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in infants, young children and the elderly, particularly those that are institutionalized. It is the most common cause of viral bronchiolitis and pneumonia in children, and outbreaks frequently reach epidemic proportions during the winter months, accounting for roughly 90,000 hospitalizations and 4,500 deaths per year. Gemini Technologies, Inc. is developing novel antisense chimeras for use in the treatment of RSV infections. These chimeras are comprised of an antisense component to the targeted viral RNA genome, while the 2-5A portion of the chimera attracts and activates RNase L, an endoribonuclease that can cleave the associated genomic RNA strand. In the phase I studies, we succeeded in synthesizing and testing a second generation anti-RSV chimera that had potent antiviral activity in

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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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cultured cells and in primates. Here we propose to carry this compound through more definitive animal studies, utilizing aerosol delivery to mimic the clinical application of this compound. In addition, we propose medicinal chemistry-based studies aimed at improving chimera synthesis, and preliminary toxicology studies. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AGE-DEPENDENT INCREASES IN AIRWAY RESPONSIVENESS BY RSV Principal Investigator & Institution: Gelfand, Erwin W.; National Jewish Medical & Res Ctr and Research Center Denver, Co 80206 Timing: Fiscal Year 2004; Project Start 01-SEP-1999; Project End 30-APR-2008 Summary: (provided by applicant): Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and lower respiratory tract infection in infants. Acute RSV leads to wheezing, and re-infection, a common event, results in even more severe airway symptoms. The pathogenic basis for the association between RSV and reactive airway disease and the subsequent development of asthma is not clearly elucidated. Nonetheless, RSV bronchiolitis in infancy appears associated with an increased risk for later development of asthma, a risk that may persist for several years. We have demonstrated in a murine model that prior RSV infection enhances the airway response (airway inflammation and hyperresponsiveness) to subsequent allergen exposure. Our hypothesis is that the age at initial RSV infection not only plays an important role in response to the acute infection, but also dictates or shapes the response to subsequent reinfection with RSV or allergen exposure. Both the immune/inflammatory responses and neurogenic control of airway function are age-dependent. We now know that the younger the age at initial encounter with RSV, the more vigorous the inflammatory response and airway responsiveness are, both acutely and subsequently on re-infection or allergen-exposure. Using a model of RSV infection/re-infection/allergen exposure, we will further characterize the immune/inflammatory responses and airway function following RSV infection in < 1, 3 and 8 week old mice. In these responses, we will systematically define the role of RSV structural proteins, cytokine production, neuropeptide levels, the production of RSV-specific antibody, especially IgE, and identify, at the T cell level, how acute RSV at the different ages influences the differentiation of T helper cells. Based on this information, we will then define how these factors direct the subsequent response to re-infection or allergen. The approach proposed is supported by extensive preliminary data, the availability of all of the molecular and cellular techniques, reagents and mutant strains of mice, as well as the ability to monitor infection and lung function in mice less than 1 week of age. The information generated from these studies will delineate the important age-dependent influences on the immune/inflammatory response in the lung and reveal new options for therapeutic intervention to prevent the long-term sequelae of RSV infection in infancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BASIS HYPERPLASIA

OF

LONG-TERM

VIRUS-INDUCED

GOBLET

CELL

Principal Investigator & Institution: Holtzman, Michael J.; Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007

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Summary: (provided by applicant): The long-term goal of this proposal is to understand how respiratory viral infections lead to chronic hypersecretory airway diseases like asthma. The present proposal focuses on new findings related to the role of respiratory viruses in fine development of long-term goblet cell hyperplasia. This focus derives from our studies of mice and mouse tracheal epithelial cells successively defining that paramyxoviral infection produces not only acute bronchiolitis but also triggers a chronic response with airway hyperreactivity and goblet cell hyperplasia lasting at least a year after viral clearance. This chronic response proceeds despite protection from acute airway infammation and hyperreactivity, and in contrast to allergen challenge, the chronic response persists indefinitely and is uninfluenced by IFN-gamma deficiency. Similar to allergen, the chronic response is at least partially prevented by glucocorticoid treatment. The virus-induced chronic response also exhibits genetic susceptibility allowing for the identification of candidate target genes by a combined genetic/microarray strategy. Memory for the chronic response appears to be contained in the adaptive immune system allowing for adoptive transfer in vivo and in vitro. In addition, we find similar phenotypic responses in human subjects with asthma. Thus, we propose that paramyxoviruses cause both acute airway inflammation/hyperreactivity and chronic airway remodeling/hyperreactivity phenotypes (the latter by a hit-and-ran strategy since viral effects persist after clearance). Further, each of these phenols (acute inflammation/hyperreactivity, chronic hyperreactivity, and chronic goblet cell hyperplasia) may be genetically segregated and therefore depend on distinct controls that appear critical for the development of lifelong airway diseases. Accordingly, we have the following specific aims: I. Use a mouse model of bronchiolitis to define how specific candidate genes control longterm virusinduced goblet cell hyperplasia and how immune cells mediate this response. Here, we develop a plan to identify and characterize our first candidate gene, i.e. mouse calciumactivated chloride channel (mCLCA3) as well as a specific immune cell subset, i.e., virus-specific CD8+ memory T cells. II. Use isolated airway epithelial cells to define the molecular basis for how specific candidate genes and immune cells cause goblet cell hyperplasia in coordination with Aim I. III Use healthy and asthmatic subjects in a glucocorticoid treatment-withdrawal model to define the relationship between goblet cell hyperplasia and the status of candidates from Aims I and II. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CD40 AND TGFB IN HUMAN LUNG TRANSPLANT CHRONIC REJECTION Principal Investigator & Institution: Mckee, Charlotte M.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 16-JUL-2001; Project End 01-AUG-2002 Summary: Chronic rejection is the most important clinical problem in human lung transplantation. The underlying causes of this process (which is manifest as obliterative bronchiolitis (OB) in lung transplants) are not completely understood, but host antidonor cellular immunity has been shown to be a key factor. The CD40 costimulatory pathway is critical for optimal cellular immune responses, and evidence suggests that CD40 activity plays a major role in chronic rejection. However, the mechanism(s) by which CD40 facilitates chronic rejection are not known. CD40 signaling can induce the production of TGFbeta, a pro-fibrotic cytokine whose role in chronic rejection and organ fibrosis is well-established, in human B cells. We postulate that CD40-mediated induction of TGFbeta1 by alveolar macrophages (AM), which are important sources of this cytokine in pulmonary fibrosis, represents a mechanistic link between CD40 activity

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and chronic rejection. We therefore propose to study 1) indices of CD40 activity in tissues from lung transplant patients with OB and from patients with acute rejection (who are at increased risk of developing OB) and 2) the ability of CD40 signaling to induce TGFbeta1 in AM from lung transplant patients. The Principal Investigator has an extensive background in basic immunology and clinical lung transplantation. The research project outlined here will train her to integrate these elements of her background and to approach clinical problems such as chronic rejection with the combined tools of basic science and clinical research. This award will provide her with the training, resources and protected time she needs to establish a successful career as an independent investigator in lung transplant immunology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELLULAR TUBERCULOSIS

NECROSIS

INDUCED

BY

MYCOBACTERIUM

Principal Investigator & Institution: King, C Harold.; Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-DEC-2003 Summary: (provided by applicant): A key step in the pathogenesis of M tuberculosis is its ability to cause caseating necrosis, parenchymal lung destruction, and cavity formation, which develop into the characteristic necrotizing bronchointerstitial pneumonia and bronchiolitis of tuberculosis. M tuberculosis is cytotoxic to epithelial cells in vitro, and we have shown that this cytotoxicity is associated with cell membrane permeation to lactose dehydrogenase and is mediated by necrosis of lung epithelial cells after infection with virulent mycobacteria (Dobos, K. M., Quinn, F. D. and King, C. H. 2000, Infect. Immun. 68:6300-6310). Interestingly, the attenuated M bovis BCG does not induce necrosis in this epithelial cell model suggesting that necrosis is related to the virulence of mycobacteria. Our working hypothesis is that M tuberculosis possesses factors that cause necrosis. We intend to identify the genes that encode or synthesize such factors and determine their functions. Towards this goal, we have been successful in isolating two such (necrosis-deficient) mutants with insertions into genes that have no known function by screening a transposon library of the Erdman strain of M tuberculosis (TN5370) for mutants that have lost their ability to cause cell membrane permeation and necrosis. Both nec mutants possess extremely interesting phenotypes when grown in mice. The first mutant (necA) appears to be highly attenuated for growth and virulence in SCID mice. This is an important result as it suggests that we have identified a gene whose product either directly causes necrosis or induces necrosis and thus should enhance our understanding of tuberculosis pathogenesis. Interestingly, the second mutant (necB) appears to kill SCID mice more rapidly than the parental strain. We intend to characterize these mutants, characterize the functions of the gene products, and extend this mutant isolation strategy to identify a large battery of mutants defective for necrosis of host cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMOKINE BIOLOGY IN BRONCHIOLITIS OBLITERANS SYNDROME Principal Investigator & Institution: Belperio, John A.; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 15-MAR-2001; Project End 28-FEB-2006

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Bronchiolitis

Summary: (Adapted from applicant's abstract) Chronic lung allograft rejection, Bronchiolitis Obliterans Syndrome (BOS) is a chronic process that demonstrates features of dysregulated and aberrant repair of airways. This process of fibroproliferation and deposition of extracellular matrix that ultimately leads to fibroobliteration of airways, and impaired lung function. In this proposal, the investigators hypothesize that the persistent expression of monocyte chemoattractant protein-1 (MCP1) during an allogeneic response and recruitment and activation of mononuclear phagocytes expression CC chemokine receptor 2 (CCR2) is a pivotal event that promotes the continuum of acute to chronic lung allograft rejection. Specifically, MCP-1 production, and the recruitment and activation of CCR2 expressing mononuclear phagocytes occurs during acute rejection. Moreover, the persistent presence of MCP-1 in the allograft maintains recruitment and activation of specific populations of mononuclear phagocytes expressing CCR2. These cells have a unique pro- fibrogenic phenotype that promotes fibrogenesis of chronic allograft rejection, BOS. Understanding the interaction between MCP-1 and CCR2 during the continuum of acute to chronic lung allograft rejection, will lead to novel therapies in the treatment and prevention of BOS. This proposal ,will test this hypothesis by performing the following experiments: I) determine the time-course, magnitude of expression, and cellular sources of MCP-1, as correlated to the recruitment of monocular cells expression CCR2 in an orthotopic rat model of acute lung allograft rejection. II) determine the specific contribution of MCP-1 to the pathogenesis of acute lung allograft rejection by a strategy of depletion of MCP-1. III) determine the time-course of MCP-1 expression, as correlated to the recruitment of mononuclear cells expression CCR2 in a murine model of BOS. B) determine the specific contribution of MCP-1/CCR2 biology to the pathogenesis of BOS by using genetic approaches for deletion of the bioactivity of MCP-1 and/or CCR2. IV) determine if CCR2 expression mononuclear phagocytes are phenotypically profibrogenic (i.e., produce higher levels of TGF-beta and PDGF) and promote fibrogenesis during the pathogenesis of BOS. By successfully completing these objectives, the applicants hope to have gained significant insight into the persistence of MCP-1/CCR2 biology that impacts on the continuum and transition of acute lung allograft rejection to BOS. The understanding of this pathobiology will lead to novel therapies in the treatment and prevention of chronic lung allograft rejection, BOS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMOKINES IN LUNG TRANSPLANTATION Principal Investigator & Institution: Medoff, Benjamin D.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 04-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): With the proposed Mentored Clinical Scientist Development Award the applicant will continue his investigations into basic mechanisms of lung inflammation. After two productive years in this laboratory the applicant remains firmly committed to a career in academic pulmonary medicine. The proposed research will allow the applicant to master a broad range of laboratory techniques in immunology, cell, and molecular biology. The research experience will be supplemented by a program of study of immunology and medical science. The project focuses on the development of inflammation and fibrosis following lung transplantation and the role of chemokines in these processes. After a lung is transplanted there may be several types of injury to the graft, including ischemia-reperfusion injury, acute rejection, and chronic rejection. These immune mediated injuries contribute to the development of scarring of the airways, so called bronchiolitis obliterans (BO). Over

Studies

9

50% of all lung transplants will develop BO after transplantation, and this remains the major cause of morbidity and mortality after lung transplantation. Neutrophils have been shown to be a prominent component of ischemia-reperfusion injury while T lymphocytes are the primary mediators of both acute and chronic rejection. The proposed project will determine which chemokines are produced after transplantation and their contribution to the development of graft injury and subsequent BO. Further experiments will manipulate chemokine or chemokine receptor expression in animal models of lung transplantation to investigate their role in the development of graft injury and BO. The applicant specifically proposes to: (1) investigate the expression of chemokines and chemokine receptors in the lung following transplantation in patients with and without acute rejection and BO; (2) investigate the role of chemokines in the development of ischemia-reperfusion injury in the airways using the murine tracheal heterotopic model of lung transplantation; (3) investigate the role of chemokines in the development of acute airway rejection and the development of BO in the murine tracheal heterotopic model of lung transplantation; (4) develop a novel murine model of airway rejection and BO. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMPLEMENT MEDIATED INJURY IN ALLOGRAFT REJECTION Principal Investigator & Institution: Baldwin, William M.; Associate Professor; Pathology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-AUG-1994; Project End 31-MAR-2008 Summary: (provided by applicant): This continuation application is based on our novel finding that a deficiency of C6, which prevents assembly of the membrane attack complex (MAC), can delay acute allograft rejection from 7-10 days to greater than 6 weeks. This finding is of potential importance for 4 reasons. First, it demonstrates that complement (C), which is not suppressed adequately by conventional immunosuppressive agents used clinically, can play a significant role in acute allograft rejection. Second, this does not appear to be a strain-specific or anecdotal effect, because acute rejection is inhibited in all of the high responder strains into which we have now bred the C6 deficiency. Third, the effects C6 deficiency are not limited to one type of vascularized allografts, but affects transplants of both heart and lung. Fourth, C6 deficiency delays both acute rejection and chronic graft vasculopathy. Preliminary data indicate that donor and recipient sources of C6 can contribute to graft injury and rejection. Our hypothesis is that C from donor and recipient sources contribute to early tissue injury initiated by physiological stress as well as antibody deposition. The specific aims are to test mechanisms that control C6 production and activation in allografts. We will use an interrelated series of in vivo experiments that take advantage of congenic C6 deficient rat strains that we have bred to determine: 1) the source of C6 in acute injury cardiac and lung transplants, 2) the source of C6 in chronic vasculopathy and obliterative bronchiolitis, and 3) the role of altered expression of membrane-associated C regulators. The experimental approach will utilize the novel C6 deficient strains of rats that we developed in the first funding period of this project for both in vivo cardiac transplant studies and as sources of C6 deficient cells for in vitro studies. Most importantly, we will use our extensive clinical material to verify the relevance of our experimental findings to humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DENDRITIC CELLS, RSV AND INFLUENZA INFECTION IN CHILDREN Principal Investigator & Institution: Ramilo, Octavio; Associate Professor; Pediatrics; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2004; Project Start 15-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): Respiratory syncytial virus (RSV) is the principal etiologic agent of bronchiolitis and viral pneumonia in infants and young children worldwide. Influenza viruses also contribute to significant number of hospitalizations among children. While the clinical manifestations are similar, there are remarkable differences in terms of their immune responses. In a simplified comparison, RSV does not induce protective immunity, there is no available vaccine, and it is associated with recurrent wheezing. In contrast, influenza does induce a more effective protective immune response, vaccines are quite effective, and it is not associated with long-term wheezing. This provides an ideal setting for a comparative analysis of the immune responses of children with these two viral infections. Dendritic cells (DCs) constitute a complex system of cells with a unique ability to induce primary immune responses. In addition, emerging evidence indicates that DCs control cytokine production by T cells and regulate the Th1/Th2 balance of the immune responses. Numerous studies have demonstrated the importance of the interaction between viruses and different DCs subsets and how that initial interaction influences the development of the subsequent immune responses. Although to date, not much is known about the interaction between DCs and RSV, our preliminary results suggest a direct participation of DCs in the immune response to RSV infection in children. Our hypothesis is that RSV and influenza virus target DC differentially leading to different immune responses, mostly deleterious in case of RSV and protective in case of influenza. We will begin to address this hypothesis in the following specific aims: 1. To determine how RSV and influenza infection affect human DC subsets in vivo, and 2. To determine how RSV and influenza infection affect human DC subsets in vitro, These studies will permit us to define the nature of the DC subset(s) that constitute the target of RSV and influenza infection in children, and begin to identify the mechanisms implicated in the interaction between these respiratory viruses and DCs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DETERMINANTS OF EPITHELIAL SURVIVAL IN AIRWAY ALLOGRAFTS Principal Investigator & Institution: Neuringer, Isabel P.; Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 07-MAY-2001; Project End 30-APR-2006 Summary: (provided by applicant) Lung transplantation has become a viable option for the treatment of end-stage lung disease, as surgical techniques and immunosuppressive therapies have improved. The major cause of late mortality and morbidity posttransplant is obliterative bronchiolitis (0B), characterized by a progressive decline in lung function and small airway fibroobliteration. Recurrent acute rejection predisposes to 0B, but HLA mismatch, ischernic injury, and infection may contribute, resulting in irreversible injury to the airway epithelium. A mouse model of heterotopic airway transplantation reproduces the histopathological lesion of 0B, and has been employed to investigate the pathogenesis of this disorder. In this model, allograft epithelium regenerates and proliferates vigorously, yet undergoes rapid, irreversible injury, through augmented apoptotic pathways, leading to airway denudation and

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fibroobliteration. We hypothesize that the survival of the airway epithelium is critical to preventing the ingrowth of fibroproliferative matrix, and that pro-apoptotic mediators present in the alloirnmune environment alter the normal kinetics of airway epithelial cell cycle-regulated proliferation and repair. The overall objective of this proposal is to determine dominant pathways of airway epithelial death in OB as mediated through cell cycle regulators p2l and p53, and assess the role of TGFB-1, a potent inhibitor of airway epithelial cell growth, in modulating the expression of these proteins. Specifically, we will quantitatively assess epithelial cell proliferation and cell cycle regulatory proteins in heterotopic mouse airway grafts, test the role of TGFB-1 in promoting airway epithelial cell death using in-vitro cell culture and in-vivo animal models, and lastly evaluate the kinetics of airway epithelial cell growth and death in clinical specimens with active OB lesions. This project will involve intensive training in tissue culture of rodent and human airway epithelium, protein chemistry, immunology, molecular biology techniques, and pulmonary pathophysiology and pathology, in a unique environment that will facilitate the development of independent investigation in pulmonary diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF DENERVATION ON THE FUNCTION OF THE AIRWAYS Principal Investigator & Institution: Perez Fontan, J Julio.; Aluni Endowed Professor; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-APR-1997; Project End 31-MAR-2005 Summary: The nervous system modulates the responses of the airways to inflammatory stimuli. The studies described here continue ongoing research into the role of substance P and other preprotachykinin (PPT)-A gene-encoded tachykinins in this modulation. The proposed work applies genetically altered murine systems to: 1. define the topographical organization and hierarchical connectivity of the airway's peptidergic sensory-motor network, 2. identify the cellular origin of the PPT-A tachykinins released in response to inflammatory stimuli and elucidate the contribution of three candidate cell types (sensory neurons, intrinsic ganglia, or hemopoietic cells) to the ensuing injury, and 3. establish whether over-expression of the PPT-A gene can in itself produce an inflammatory injury or requires a separate inflammatory stimulus. Aim 1 will be accomplished by examining the expression of a fluorescent protein (ECFP) placed under the transcriptional control of the PPT-A 5' regulatory region in conjunction with tracking studies using pseudorabies virus as a retrograde trans-synaptic marker. Aim 2 will be approached by a combination of selective chemical ablation of C-fibers by capsaicin and bone marrow reconstitution experiments in wild type mice and mice homozygous for targeted disruptions of the PPT-A and NK-1 receptor genes. The effects of these manipulations will then be compared in intact, inflamed (immune complex, Sendai virus, and stretch-induced), and denervated airways (selective C-fiber ablation and heterotopic tracheal transplantation). Aim 3 will be achieved by analyzing the effects of transgenic manipulations of the PPT-A gene resulting either in ectopic constitutive overexpression of PPT-A in airway epithelial cells or in isotopic inducible overexpression of PPT-A in intact and inflamed airways (see above). Completion of these aims will improve our understanding of airway neurogenic injury and may help to develop therapeutic strategies to minimize tachykinin amplification of immunemediated inflammation of the lungs and airways in disease processes such as bronchiolitis obliterans after lung transplantation or hyperoxic/stretch injury after mechanical ventilation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECTS OF MAJOR BASIC PROTEIN ON HUMAN AIRWAY CELLS Principal Investigator & Institution: Wylam, Mark E.; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002 Description (provided by applicant): Eosinophils are central to the pathogenesis of asthma. Activated eosinophils release several polycationic protein substances, which are associated with an increase in airway smooth muscle (ASM) contractile response. The long-term goal of the proposed studies is to understand the mechanism(s) by which eosinophil-derived proteins alter ASM contractile responses. Deposits of polycationic proteins released from activated eosinophils, including MBP, are found within both airway epithelial and smooth muscle layers of airways of patients dying from status asthmaticus. Recent studies by others indicate that MBP increases force in airways indirectly through an effect on airway epithelium or by inhibiting airway muscarinic M2 receptors. In addition, recent work in our laboratory indicates that MBP and other model polycationic proteins directly elevate intracellular calcium concentration ([Ca2+]i) in cultured ASM cells in a concentration-dependent manner and increase basal force generation in an epithelium-independent manner in ASM strips. It is possible that alteration in both epithelial and myocyte [Ca2+]i mobilization induced by eosinophilderived polycationic proteins may indirectly and/or directly influence clinical disease states of altered airway force, such as asthma and viral bronchiolitis. The overall hypothesis of the proposed studies is that MBP causes an increase in airway cell [Ca2+]i that in airway epithelium elicits epithelial broncho-constrictor release and in ASM elicits smooth muscle contraction. In the proposed studies, human airway epithelium and human airway smooth muscle strips and freshly dissociated human airway myocytes will be used to examine the effects of MBP on epithelial broncho-constrictor release and ASM force generation, [Ca2+]i regulation and Ca2+ sensitivity. Critique: The comments below represent essentially unedited comments from the reviewers of this application. They are included to indicate the range of comments made during the discussion and may not reflect the final thinking of the committee. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPITHELIAL MMPS IN AIRWAY REPAIR Principal Investigator & Institution: Parks, William C.; Professor of Pediatrics, Medicine and Ce; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2009 Summary: (provided by applicant): The accumulative, progressive remodeling of airways seen in many conditions, such as bronchiolitis obliterans, asthma, cystic fibrosis, and more, indicates that normal repair processes have gone awry. To understand the pathogenic mechanisms of destructive diseases, the mechanisms of normal airway repair need to be better understood. Injury sets off a programmed series of interdependent yet separate responses, such as re-epithelialization, inflammation, scarring, and eventually resolution. During each stage in this process, a number of extracellular proteinases are released by all cells. Acting on specific substrates, these enzymes serve numerous and diverse functions, including regulating cell-cell and cellmatrix signaling by both gain and loss-of-function mechanisms. In particular, members of the matrix metalloproteinase (MMP) family can activate the latent forms of a number of proteins involved in cellular communication, among several other functions. The goal of this project is to identify actual, physiologic protein substrates of specific MMPs, to understand the biological consequence of proteolytically processing a given protein, and

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to determine the regulation of MMP activity. Preliminary data with knock-out mice indicate that airway metalloproteinases, specifically, matrilysin (MMP7) and epilysin (MMP28), regulate distinct, non-overlapping processes essential for normal repair. Whereas matrilysin is required for re-epithelialization and neutrophil influx, epilysin seems to serve a more confined role to regulating generalized inflammation. The overall goals of this project are to determine the function of these MMPs in transplanted trachea and lung with and without underlying injury or infection. For Aim 1, both in vivo and cell-based models will be used to assess the expression patterns, source, and function of matrilysin in airway repair and damage. The goal of these studies is to identify the substrate upon which matrilysin acts to facilitate re-epithelialization. For Aim 2, the mechanisms regulating matrilysin's catalytic activity will be assessed, with a focus on the hypothesis that activation of the zymogen and inaction of the active enzyme are controlled by site-specific modifications mediated by neutrophil-generated oxidants, specifically HOCI. For Aim 3, gene targeted mice will be used to test the idea that airway-derived epilysin regulates inflammation by proteolytic processing (i.e., activation) of a latent factor (e.g., a chemokine) or accessory protein (e.g., syndecans). These studies will demonstrate essential functions served by specific MMPs in airway repair. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ETHNOBOTANICAL ANTI-RESPIRATORY SYNCYTIAL VIRUS DRUGS Principal Investigator & Institution: Ojwang, Joshua O.; Zymetx, Inc. 800 Research Pky, Ste 100 Oklahoma City, Ok 73104 Timing: Fiscal Year 2002; Project Start 15-MAY-2000; Project End 28-FEB-2004 Summary: (provided by applicant): Lower respiratory tract infections such as bronchiolitis and pneumonia in pediatrics and some adults are caused by respiratory syncytial virus. The therapies include the controversial ribavirin for treatment or humanized RSV monoclonal antibodies (Synagis) for prevention. The cost per season for Synagis prophylaxis is about US$ 5,000. In the absence of an effective vaccine, RSV remains a serious health threat and effort must be mounted to find effective and more economical therapies. An innovative approach of treating RSV infection with ethnobotanical (EB) preparations was identified in Phase I of this project and this concept has the potential of reducing the current treatment cost. In Phase I, the feasibility of the concept was proved by the significant in vitro and in vivo anti-RSV activity, which was better or comparable to ribavirin. This approach of using EB preparations with historical use as a treatment to target diseases was developed in enough detail to provide a basis for further development of active ingredients as antiRSV agents. In Phase II, the active compounds in these EB fractions will be chemically purified, characterized and developed to the level of readiness required to launch clinical evaluation of these compounds as therapeutic agents against RSV infections. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC DETERMINANTS OF RSV SUSCEPTIBILITY IN MICE Principal Investigator & Institution: Stark, James M.; Assistant Professor; Molecular Microbiol and Immun; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-MAY-2003

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Summary: (provided by applicant): Respiratory syncytial virus (RSV) is the most common cause of lower respiratory infection and hospitalization for airway obstruction in young children in the U.S. (about 90,000 admissions annually). While every child is "susceptible" to RSV infection (will be infected by age 2 years), the developmental, environmental or genetic factors that predispose children for acute and chronic airway obstruction following RSV infection remain unclear. However, epidemiologic studies demonstrate a clear role for familial predisposition in RSV related disease (infants with a family history of atopy and asthma are more likely to develop bronchiolitis and require hospitalization). The reason why some individuals develop severe disease following RSV infection is unknown, but is likely to involve mechanisms that control the initial infection, viral replication and resolution of infection. Recent data demonstrate that strains of inbred mice vary in RSV susceptibility. This trait was transmitted to offspring, suggesting that factors controlling viral processing are inherited. The studies outlined in this grant application propose to use these mouse strains to further delineate the mode of inheritance and the mouse chromosomal regions that encode the major determinants of RSV susceptibility. The quantitative trait loci (QTL) identified in the mouse can then be used to identify candidate genes controlling RSV susceptibility, and by comparative mapping, candidate genes in the human. Therefore, this application tests the hypothesis that susceptibility to RSV infection is a complex genetic trait and the chromosomal regions containing major determinants for susceptibility to RSV can be identified and mapped, and candidate genes for RSV susceptibility can be identified. To test this hypothesis, three Specific Aims are proposed. Aim 1 proposes to perform trait segregation analysis to estimate the number of genes involved in the RSV susceptibility phenotype, the mode of inheritance of these gene(s), and the potential effects of sex linkage and parental imprinting on the RSV susceptibility phenotype. Aims 2 and 3 propose to identify chromosomal regions with linkage to RSV susceptibility by phenotyping and performing linkage analysis on Recombinant Inbred (RI) mouse strains (Aim 2) and by performing Quantitative Trait Locus (QTL) analysis of F2 and offspring derived from the F1 backcrossed with the susceptible AKR strain (Aim 3). The overall goal of the studies proposed is to estimate the number of genes associated with the RSV susceptibility/ resistance in genetically-defined inbred mouse strains, allowing us to focus on these regions for potential candidate genes regulating RSV responses. Future studies will focus on further characterization of the candidate genes located in the DNA segments identified in this grant application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC EPIDEMIOLOGY OF RSV BRONCHIOLITIS AND ASTHMA Principal Investigator & Institution: Randolph, Adrienne G.; Director; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: This proposal is designed to provide an opportunity for the Principal Investigator (PI) to gain knowledge and skills in designing and conducting genetic epidemiology research under the supervision of an advisory committee comprised of highly qualified sponsors and co-investigators. This K23 award in combination with the PI's background in pediatrics, critical care, outcomes research, clinical epidemiology and medical informatics, provides excellent potential for development of a successful independent research career focused on patient-oriented research in the genetic epidemiology of complex inflammatory lung diseases. The overall scientific goal of this proposal is to determine the genetic association between severe bronchiolitis in

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previously healthy infants caused by respiratory syncytial virus (RSV) and the later development of childhood asthma. Using a prospective cohort design, we propose to follow the large population of patients who were hospitalized for confirmed RSV bronchiolitis during infancy at Children's Hospital, Boston from 1990 to 2000 when they reach 3 to 13 years of age to identify those with persistent or new onset wheezing. Using an interviewer-administered questionnaire, we will assess asthma and atopy diagnoses and symptoms and environmental exposures in both biological parents and the index child. Parents will be surveyed every three months over a 2 to 5 year period to assess the persistence of wheezing in their child. Questionnaire findings will be incorporated into a multiple logistic regression model to predict the development of childhood asthma after RSV bronchiolitis in infancy. Blood will be drawn from both parents and the index child for DNA analysis to test for transmission disequilibrium in the distribution of alleles of nitric oxide synthase genes. We hypothesize that genetic mechanisms confer susceptibility to persistent wheezing after RSV bronchiolitis in infancy and that this susceptibility is found in genes regulating nitric oxide synthase. This proposal is vital to the care of the greater than 6 million childhood asthmatics in the United States. Identifying the genes associated with the onset of childhood asthma could lead to targeted interventions aimed at prevention and treatment of this disorder that is increasing at a rate of 5 percent per year. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC RISK FACTORS FOR AIRFLOW OBSTRUCTION AFTER HSCT Principal Investigator & Institution: Clark, Joan G.; Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 16-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Bronchiolitis obliterans syndrome (BOS), a clinical syndrome of irreversible, progressive airway disease causing obstructive lung disease (OLD), is a serious complication of hematopoietic stem cell transplant (HSCT). Research investigating the pathogenesis of BOS suggests that this form of OLD is immune mediated and consistent with pulmonary graft versus host disease (GVHD). Since proinflammatory and anti-inflammatory cytokines play a significant role in the pathophysiology of GVHD and the production of these cytokines is influenced by environmental and genetic factors, we believe there are genetic determinants other than histocompatibility disparity that influence the risk of developing OLD after HSCT. This project will develop a new collaborative effort between investigators in lung medicine and immunology and genetic epidemiologists to utilize an existing source of stored DNA and a novel haplotypic approach in exploring the hypothesis that allelic haplotypes of genes in the lipopoly-saccharide (LPS) inflammatory pathway influence the risk of developing OLD after HSCT. Aim 1 will assess for the association of susceptibility as well as protective allelic haplotypes of genes in the LPS inflammatory pathway in both diseased as well as hypernormal individuals. The allelic haplotypes will be generated using the Phase program developed at the University of Washington. These haplotypes are generated by selecting for single nucleotide polymorphisms (SNPs) with an allele frequency ?10% that exist in significant linkage disequilibrium with each other. When multiple such haplotypes are considered for each gene, a nonbiased analysis of nearly the entire gene can be performed for association with a complex disease. Aim 2 will confirm the association and linkage of certain allelic haplotypes of the genes in the LPS inflammatory pathway with OLD using an established family-based study design, the transmission disequilibrium test. Father,

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mother, and proband offspring trios will be identified in our DNA resource for genotyping to determine if haplotypes found to be significantly associated with OLD in aim 1 are indeed genetically linked and associated with disease in a family based analysis. Use of allelic haplotypes will provide an unbiased look for association with disease throughout the entire gene and an opportunity to perform rigorous fine genetic mapping and gene discovery. Ultimately, this insight can be applied to understand inflammation and how it causes more common lung diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC, BIOLOGIC, & IMMUNOLOGIC DETERMINANTS OF ASTHMA Principal Investigator & Institution: Castro, Mario; Associate Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-AUG-2006 Summary: (provided by applicant): The overall goal of this application is to determine how specific genetic, biologic, and immunologic characteristics interact to predispose individuals to develop asthma. In that context, over the last three years, we have developed a carefully selected cohort of 206 infants with respiratory syncytial virus (RSV) bronchiolitis (the RBEL (RSV Bronchiolitis in Early Life) cohort) who are at substantial risk of developing asthma. Surprisingly, physicians have already diagnosed asthma in 40 percent of the children in the RBEL cohort. The children have had at least one year of follow-up. This project builds upon our previous work establishing the largest prospective U.S. study children with RSV bronchiolitis severe enough to require hospitalization and proposes that this study should be continued for an additional five years in order to more definitively establish the diagnosis of asthma in this cohort. The interaction of RSV with the host epithelial-immune system and underlying genetic background is unclear. Accordingly, Aim I proposes to evaluate the association between genotypes associated with atopy, the IL-4 receptor a and IL- 13 single nucleotide polymorphisms, and the development of an asthmatic phenotype in the RBEL cohort of children. Given the appropriate risk factors, RSV elicits an immune response characterized by inflammatory cell influx, especially T cells, into the airway. Accordingly, Aim II proposes to evaluate the effect of airway epithelial inflammation, demonstrated by persistent RANTES (Regulated upon Activation, Normal T-cell Expressed) expression in airway epithelial cells, on the development of an asthmatic phenotype in the RBEL cohort of children. This possibility is supported by evidence of increased RANTES expression (by mRNA stabilization) in human tracheal epithelial cells infected with RSV in vitro and in upper airway epithelial cells from RBEL infants with RSV bronchiolitis. The T cell immune response following viral infection appears to be primarily Th1-type; however, in the setting of RSV infection, there actually may be a skewing of the immune response to a Th2 phenotype early in life. Accordingly, Aim III proposes to evaluate prospectively the T cell profile, Th1 vs. Th2 phenotype, as defined by cytokine expression and other phenotypic markers, in the RBEL cohort of children who are at risk of developing an asthmatic phenotype. Therefore, this application will lead to a better understanding of the interaction of genetic, biologic, and immunologic factors following serious RSV infection which lead to the development of asthma in early life. Furthermore, we propose to develop an asthma predictive index for children with serious RSV infection based upon the findings of the studies outlined in this application. Such an index would be extremely valuable to clinicians taking care of children following a severe RSV infection to provide prognostic information and to

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identify children at highest risk for the development of asthma who may benefit from an early intervention or treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOST VIRUS INTERACTION AND GENE EXPRESSION Principal Investigator & Institution: Banerjee, Amiya K.; Chairman; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 01-FEB-1992; Project End 31-MAY-2007 Summary: (provided by applicant): The long term goal of this renewal grant application is to understand the molecular mechanism of host-virus interactions and gene expression of human parainfluenza virus, type 3 (HPIV3), an important human pathogen which targets lung epithelial cells of the respiratory tract of infants and children leading to acute bronchiolitis, pneumonia and croup. Effective vaccines or antivirals to combat HPIV3 infection are currently unavailable. Our primary goal is to gain insight into some specific host-virus interactive processes which include, (b) identification and characterization of the cell surface receptors of epithelial cells (a) the role of actin binding protein, beta catenin in the transcription ability of HPIV3 ribonucleoprotein (RNP) complex and (c) regulation of expression of major histocompatibility complex II induced by HPIV3 which may play an important role in cellular immunity leading to infection-related damage to lung epithelium. We also propose to continue our studies in understanding the structure and function of the RNA polymerase, L and P proteins, of HPIV3, especially with regard to the role of phosphorylation of P protein and identification and characterization of the functional domains of L and P proteins. Finally, we wish to exploit reverse genetics using the infectious cDNA of HPIV3 constructed in our laboratory to study phenotypic characteristics of some distinctive cis-regulatory mutants. The studies proposed in this application have the potential to gain deeper insight to various host-virus interactive pathways, which may eventually lead to rational designing of antivirals, vaccines, and expression vectors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMEDIATE-EARLY CYTOMEGALOVIRUS

REGULATORY

GENES

OF

Principal Investigator & Institution: Hayward, Gary S.; Professor; Pharmacol & Molecular Sciences; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-APR-1987; Project End 30-NOV-2007 Summary: (provided by applicant): Persistent but benign infection with cytomegalovirus (CMV) is a nearly ubiquitous occurrence in most human populations. However, primary infection during pregnancy can lead to serious CNS disease in the developing fetus or newborn infant and reactivated disseminated infection causes retinitis in AIDS patients and life-threatening pneumonitis, or hepatitis and allograft rejection in immunosuppressed bone marrow and heart, lung, kidney, liver and pancreas transplant patients. CMV is also suspected of contributing to chronic vascular disease and obliterative bronchiolitis in transplant patients and possibly also to restenosis and atherosclerosis. Acute disseminated infection can be reduced but not eliminated by Ganciclovir treatment and resistant strains develop. HCMV is one of the largest and most complex of mammalian viruses and despite much progress in the molecular biology and identifying important genes of the virus in recent years, a great deal more basic research is needed to understand its cell biology and pathogenesis. In

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this project, we have undertaken a detailed analysis of the major immediate-early (MIE) genes of HCMV whose two principal gene products IE1 (IE72, UL123) and IE2(IE86, UL122) function to switch the cell into and out of latency and to prepare the cell for efficient productive lytic cycle infection. The focus of these studies encompasses control of MIE gene expression via the MIE enhancer domain, the role of IE1 in dispersing PML from its associated intra-nuclear bodies, called PML-oncogenic domains (PODs or ND10) and the pleotrophic roles of IE2 in positive and negative transcriptional control, post-translation regulation of cell cycle events and the switch from cellular to viral DNA replication. Specific projects in the present 5-year proposal include: (I) Analysis of the functional consequences of post-transcriptional interactions of IE2 with four potential cell cycle regulatory proteins p21, JAB1, APC2 and MAD2; (II) continued exploration of the role of PML, DAXX, SUMO and the PODs at very early times in the nucleus, including how IE1 and IE2 target to the PODS and the role of IE1 in removing SUMO from PML, in PML and SP100 repression, and in facilitating proper IE2 intranuclear localization; and (III) Evaluation of the viral and cellular protein components, functions and temporal interrelationships between four distinct subnuclear domains containing the IE2 protein, including three that are presumed to be MIE enhancer or Ori-Lyt associated forming "IE transcription sites", pre-replication foci" (pre-RF) and mature viral DNA replication compartments (RC). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNE REGULATION IN LUNG TRANSPLANTATION Principal Investigator & Institution: Burlingham, William J.; Associate Professor; Surgery; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 30-JUN-2004 Summary: Adapted from Investigator's abstract): Rapamycin inhibits obliterative fibrosis in a rat tracheal transplant model and promotes tolerance induction in mouse heart transplant models. Because it can spare the use of calcineurin inhibitors, rapamycin also promises to help eliminate the numerous side effects of cyclosporine and FK506. An ongoing multi-center, prospective, randomized, double-blinded clinical trial including patients from the UW-Madison is underway to see if a form of rapamycin (RAD) can prevent bronchiolitis obliterans syndrome (BOS) while improving long-term outcome in lung transplants. The clinical trial sponsored by Novartis relies on biopsy histology and pulmonary function tests to determine the primary endpoints; no immune function tests are funded. This proposal addresses not only surrogate markers of disease and therapeutic effects, but also aims, for the first time, to provide useful surrogate markers for the dynamic process of development and maintenance of allograft tolerance. We believe that such markers are essential for rational adjustment of maintenance immune suppressive therapy in a given patient. We also believe that tolerance is the best solution to the long-term problem of allograft obliterative airway disease, a problem that currently affects virtually all lung transplants. Specifically we will: 1) monitor the development of both systemic and local immune regulation of delayed type hypersensitivity (DTH) responses in all UW/Madison lung transplant recipients, including those receiving RAD-based vs. conventional IS therapy; 2) monitor the systemic and local release of soluble forms of donor HLA antigen in lung transplant patients, determine which soluble donor HLA antigens can trigger regulation of DTH, and analyze the role of metalloproteinase therein; and 3) monitor the persistence of donor T cells (including CMV-specific CD8+ cells), and alveolar macrophages, using flow cytometry of BAL cells. This research project will be conducted in conjunction with the current clinical trial, but will not exclude any lung transplant patients not enrolled in

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the trial. Our study has a high likelihood of providing clinical correlation of outcomes (acute & chronic rejection, infection) with surrogate markers of tolerance, alloreactivity and pathogen reactivity. We will determine how the sensitivity, specificity, and predictive value of each test would be clinically useful in the management of lung transplant patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPACT TRANSPLANTATION

OF

AEROSOL

CYCLOSPORINE

IN

LUNG

Principal Investigator & Institution: Zeevi, Adriana V.; Professor; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: Our clinical program has recently been awarded a 4-year RO1 NIH grant HL59490: "Aerosol Cyclosporine for Prevention of Lung Rejection". The project deals with a prospective double-blind randomized clinical trial to evaluate the effectiveness of aerosol CsA (versus placebo) combined with standard immunosuppression given for prevention of acute rejection early after lung transplantation. The clinical grant relies on biopsy histology and pulmonary function test to determine the primary end-points; no immune function tests are funded. This research proposal deals with immune correlates of rejection in this cohort of lung transplant recipients. The human lung allograft presents a unique clinical model where we can directly measure the effect of local drug delivery on the immune intragraft events associated with rejection. This proposal addresses not only "surrogate markers of disease and therapeutic effects" but will also permit us to draw important inferences regarding the "mechanism of the allograft response" to the human lung transplant. 1) We will extend our understanding of the patterns of intragraft cytokines and other effector molecules (competitive RT-PCR) and their origins (intracellular cytokine staining) following lung transplantation. Their measurements will be evaluated in stable and rejecting allografts and quantitation will be interpreted not only in lieu of systemic (oral) vs. regional (aerosol) immunosuppression but also in consideration of cytokine gene polymorphism. 2) We will study humoral allo-immunization in lung transplant recipients by following serum antibody levels against donor HLA class I and II antigens using a direct and an antihuman globulin-augmented lymphocytotoxicity assays and by an HLA-specific ELISA assay. HLA class I and II alloantibodies will be followed sequentially and related to systemic vs. regional immunosuppression. 3) We will study indirect allo-presentation by following BAL and plasma soluble donor HLA (by ELISA) in attempt to better understand its relationship to acute and chronic obliterative bronchiolitis in lung transplant recipients. The impact of aerosol CsA on the persistence of donor-specific macrophages (by flow-cytometry) will be also determined. This research project will be conducted in conjunction with the clinical trial. The project considers both cellular and humoral immune responses and has a high likelihood of providing clinical correlation of potential surrogate markers of alloreactivity. We will correlate the clinical end-points for acute rejection, chronic rejection and infection with the above laboratory parameters and determined how the sensitivity, specificity and predictive value of each assay would be clinical useful in management of lung transplant recipients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INNATE BRONCHIOLITIS

IMMUNE

RESPONSES

IN

OBLITERATIVE

Principal Investigator & Institution: Palmer, Scott M.; Medicine; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Dr. Scott M. Palmer, currently on faculty in the Duke University Pulmonary Division as an Associate in Medicine, proposes a structured five-year career development plan in order to develop into an independent investigator in pulmonary medicine. The proposal involves rigorous research training under an experienced physician scientist mentor, Dr. David Schwartz, who has expertise in the immunogenetics of innate immunity. Further research training is proposed under the guidance of a co-mentor with expertise in statistical genetics, a collaborator with expertise in transplant immunology, and complemented by didactic graduate coursework. The overall goal of the proposed research is to understand how innate immune responses contribute to the development of posttransplant bronchiolitis obliterans syndrome (BOS). We hypothesize that genetic, physiological or biological differences in innate immune responsiveness will significantly alter the risk for the development of BOS after lung transplant. This novel hypothesis is clinically relevant based on the high rate of posttransplant death due to BOS, scientifically relevant because of the incomplete understanding of the pathophysiology of BOS, and supported by several basic and clinical observations. We and others have recently demonstrated that significant polymorphisms exist in innate immune receptor genes, and that these differences significantly alter subsequent inflammatory and immune responses. In order to test our hypothesis, we will characterize polymorphisms in donor and recipient tolllike receptor-2 (TLR2), TLR4, and CD14 genes, and phenotypically characterize the airway physiological and biological response to endotoxin in a cohort of 120 lung transplant recipients. We will prospectively capture clinical information on the cohort and determine the predictive importance of innate genetic, physiological, or biological factors on the development or progression of BOS in a multivariate model. At the conclusion of the career development award, Dr. Palmer will have gained considerable expertise in study design, basic genetic analyses, transplant immunology, and statistical analyses. He will apply these skills to direct future investigations of patient oriented research problems in pulmonary medicine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERFERON-ALPHA/BETA PATHOGENESIS

IN

RESPIRATORY

VIRUS

Principal Investigator & Institution: Durbin, Joan E.; Associate Professor of Pediatrics; Children's Research Institute 700 Children's Dr Columbus, Oh 432052664 Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 28-FEB-2005 Summary: Respiratory syncytial virus (RSV) is a major cause of lower respiratory infections in infants and the elderly. Bronchiolitis and pneumonia caused by RSV are the primary reasons for the hospitalization of infants under 6 months of age. The initial infection often occurs in the presence of maternal antibodies and reinfections occur throughout life. To date, efforts to develop a safe and effective vaccine have failed. Progress in RSV vaccine development has been hampered by the legacy of enhanced, even fatal, illness in vaccinated children during trials of a formalin- inactivated, alumprecipitated whole virus vaccine in the mid 1960s. The lack of a clear understanding of vaccine-augmented RSV disease still stands in the way of clinical trials of new vaccines

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in RSV naive infants. Our laboratory has demonstrated enhanced RSV and influenza disease in strains of knockout mice that are unable to respond to IFN-alpha/beta (IFNalpha/beta Receptor-/-) or IFN-alpha/beta and IFN-gamma (Stat1-/- ). The pathology of primary virus infection in these mutant animals resembles that seen following RSV challenge of mice previously immunized with the formalin-inactivated whole virus vaccine (FI-RSV) with exacerbated, eosinophilic inflammation and a Th-2-like cytokine pattern. In this proposal we will test our hypothesis: that poor IFN- alpha/beta induction by RSV may help to explain the induction of Th-2 biased immunity by the FIRSV vaccine preparation. The specific aims of this proposal are: 1) Characterization of exacerbated disease in response to RSV infection in Stat1-/- mice. 2) Analysis of T cell lines derived from RSV immune WT and mutant animals. 3) Alteration of RSV pathology by priming in the presence of IFN- alpha/beta. 4) Development of a vaccine strategy promoting strong induction of IFN- alpha/beta. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LUNG FIBROSIS: TREATMENT AND MYOFIBROBLAST CONTROL Principal Investigator & Institution: Schwarz, Marvin I.; Professor of Medicine; National Jewish Medical & Res Ctr and Research Center Denver, Co 80206 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: (Applicant's Abstract) In Project 5 we propose to define the role of the fibroblastic foci and myofibroblast presence in IPF/UIP pathogenesis, to test an antiproliferative therapy for this disorder, and develop surrogate markers which predict outcome. Because of its antiproliferative properties and antagonism of transforming growth factor-beta-1 (TGF-b1) functions in vitro, as well as TGFb-1 driven myofibroblast generation, we propose to study the efficacy of interferon gamma (IFN) (subcutaneous and inhaled) in idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP). In the recently initiated phase III trial, we will define surrogate markers of outcome; to include dyspnea scores, physiologic tests, quantitative image analysis of the high resolution computed tomographic images, and fibroproliferative biomarkers. Recently, we were instrumental in organizing an NHLBI workshop which proposed systematic evaluation of several available novel therapeutic agents that could abrogate the fibroproliferative response. Myofibroblast apoptosis, proliferation, clonality and structure of fibroblastic foci will be compared to bronchiolitis obliterans organizing pneumonia (BOOP), a disease whose positive outcome exceeds IPF/UIP. Gene expression patterns of whole IPF[UIP lung will be analyzed by microarray and compared to normals and BOOP to determine differences and characteristic patterns. Microdissection of fibroblastic foci in IPF1UIP and Masson's bodies of BOOP will be performed. Based on this and utilizing laser capture microdissection BOOP will be performed to determine diagnostic patterns. The goal is to determine gene expression patterns of IPF/UIP and BOOP, which predict clinical behavior and are typical for that particular disease. We will also determine within the IPFIUIP group which genes reflect a bad vs. improved prognosis and the differential gene expression pattern between Fibroblastic foci (IPF/IJIP) and Masson's bodies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MBRS SCORE PROGRAM AT ALABAMA STATE UNIVERSITY Principal Investigator & Institution: Gunn, Karyn S.; Biological Sciences; Alabama State University Box 271, 915 S Jackson St Montgomery, Al 361045714 Timing: Fiscal Year 2004; Project Start 01-AUG-1997; Project End 31-JUL-2008

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Bronchiolitis

Summary: (provided by applicant): Alabama State University (ASU) seeks to support its commitment to research excellence by applying for continuation of its successful Minority Biomedical Research Support (MBRS)-Support of Continuous Research Excellence (SCORE) Program. Funding is requested for four (4) years (2004-2008) from the National Institute of General Medical Sciences (NIGMS)/National Institutes of Health (NIH). The overall Goal of the proposed ASU MBRS-SCORE Program is to advance the vision and mission of the MBRS-SCORE Program to develop biomedical research faculty at minority-serving institutions who are committed to improving competitive research programs and increasing the number of underrepresented minorities professionally engaged in biomedical research. The proposed ASU MBRSSCORE Program features two (2) research projects in the disciplines of sensory physiology, molecular virology and environmental bioremediation, respectively. The first subproject will study the molecular mechanisms of signal transduction in the mammalian vomeronasal organ, a chemosensory organ that mediates the perception of pheromones affecting reproductive behavior and physiology. The second subproject will assess the immunoprotective effects of a DNA vaccine against respiratory syncytial virus (RSV), one of the most common viral causes of upper and lower respiratory tract disease leading to bronchiolitis and pneumonia. An administrative component aims to facilitate coordinated operation of the Program's research and programmatic activities, assure unified, synergistic interface of the Program with the goals, objectives and activities of the University's highly successful existing Biomedical Research and Training Programs, and evaluate the progress of the individual subprojects and overall Program toward attainment of its proposed aims. The proposed ASU MBRS-SCORE Program will ultimately contribute to enhancing the biomedical research capability of Alabama State University by providing expanded opportunities for underrepresented minorities to engage in biomedical research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS IN THE REMODELING OF LUNG STRUCTURE Principal Investigator & Institution: Senior, Robert M.; Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-SEP-1983; Project End 31-AUG-2008 Summary: This multidisciplinary program, comprised of five projects and three cores, will apply the concepts and techniques of cell and molecular biology to study lung structure and cellular function in response to injury due to inflammation. The focal points of the studies proposed are airway and alveolar epithelial cells, extracellular matrix, neutrophil-derived proteinases, matrix metalloproteinases (MMPs), and surfactant associatedprotein D (SP-D). The following hypotheses will be tested: (1) laminin-5 has in important role in lung development and the response to alveolar injury via its effects on alveolar epithelial cell migration; (2) neutrophil-derived proteinases degrade SP-D and contribute to enhanced clearance of SP-D in alveolar injury; (3) matrilysin cleaves the ectodomain of syndecan-1 and that cleavage is required for airway epithelial cell migration and repair; (4) collagen turnover in COPD is complex with divergent changes in airway and alveolar collagen and with divergent effects of MMPs on airway and alveolar collagen, and (5) remodeling of airway epithelial structure after experimental viral bronchiolitis involves prolonged epithelial cell survival. The proposed studies encompass murine lung cells and embryonic lungs in culture, transgenic and gene targeted mice, and murine models of airway and alveolar injury induced by paramyxovirus, lipopolysaccharide (LPS), Pseudomonas aeruginosa, bleomycin and cigarette smoke. A Morphology Core for assistance with diverse

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morphologic procedures, and a Mouse Core for production of transgenic and gene targeted mice and for implementing the model of cigarette smoke-induced emphysema, will provide specialized centers for correlative interactions among the investigators in their complementary, yet independent, studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS ALLOGRAFTS

OF

MAST

CELL

APOPTOSIS

IN

LUNG

Principal Investigator & Institution: Fang, Kenneth C.; Cardiovascular Research Inst; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: Mast cells and their mediators play critical roles in homeostatic wound healing pathways. Therefore, the premature demise of the mast cell population via programmed cell death or apoptosis may permit uncontrolled tissue remodeling which progresses to fibrosis. Metalloproteinases and their inhibitors exert diverse influences on cellular functions by processing matrix proteins and by regulating the dynamic display of membrane- anchored receptors, adhesion molecules and growth factors at the cell surface. The overall hypothesis of this proposal is that metalloproteinase-dependent mechanisms regulate mast cell apoptosis during fibrinogenesis. Binding of c-kit ligand (stem cell factor) to kit receptor tyrosine kinase regulates mast cell proliferation and apoptosis, and also induces receptor down-regulation via an uncharacterized metalloproteinase-dependent cleavage of Kit's extracellular domain. The experimental design employs complementary approaches using a rat model of lung transplantassociated airway fibrosis to study the role of metalloproteinases in mast cell apoptosis in vivo, and cultured mast cells to investigate the role of metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs) in molecular mechanisms which regulate proteolytic shedding of the Kit ectodomain. Consistent features of mast cells in fibrotic lung disorders, including transplant-associated obliterative bronchiolitis are fluctuations in the size of their population and persistent degranulation of stored mediators. To address the overall hypothesis, the proposed studies will investigate metalloproteinase- dependent induction of mast cell apoptosis and the role of mast cell mediators in regulating proteolytic processing of Kt receptor. Aim 1 will identify the role of metalloproteinases and mast cell apoptosis during the development of obliterative bronchiolitis in a rat lung allograft model. Aim 2 will clarify the metalloproteinase-dependent Kit receptor shedding mechanism by investigating mast cell expression of metalloproteinases such as tumor necrosis. Factor-alpha converting enzyme (TACE), and by identifying the proteases and peptide sites cleaved in Kit ectodomain processing. Aim 3 will determine the role of mast cell proteases and oxygen radicals in proteolytic and non-proteolytic processing of TIMPs which not only inhibit metalloproteolytic sheddases, but also regulate apoptosis. These studies should provide valuable insights into the role of mast cells in the pathogenesis of fibrotic lung disorders and also clarify mechanisms responsible for the development of obliterative bronchiolitis, the major obstacle to improved outcome and survival in lung transplant patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BASIS FOR PARAINFLUENZA 3 INFECTION Principal Investigator & Institution: Moscona, Anne; Professor of Pediatrics; Pediatrics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029

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Bronchiolitis

Timing: Fiscal Year 2002; Project Start 01-APR-1992; Project End 30-JUN-2003 Summary: Human parainfluenza virus type 3 (HPF3), a member of the paramyxovirus family of non-segmented negative-strand RNA viruses, is an important agent of lower respiratory tract disease in children and causes several of the most significant childhood viral diseases (croup, bronchiolitis and pneumonia). The recognition of infections caused by HPF3 is increasing in the U.S. due to the increasing numbers of individuals with underlying immune deficiencies, and serious HPF3 disease is re-emerging. There are currently no treatments or vaccines available to combat this serious pediatric pathogen, and there remain gaps in the knowledge of fundamental processes leading to growth of the virus. Dr. Moscona's studies have provided an understanding of some factors controlling virus-host cell interactions for HPF3, including the role of HN in the virus-induced fusion process. The overall goal of the current proposal is to expand the investigation of the molecular pathogenesis of HPF3. The central hypothesis is that the envelope glycoprotein hemagglutinin-neuraminidase (HN)-receptor interaction is critical for several essential components of the viral life cycle -- entry, fusion and release -- and that this interaction regulates pathogenicity in vitro and in vivo. The specific objectives of the current proposal are: (1) To elucidate both the viral HN and cellular receptor components of the virus-host interaction, specifically by (A) evaluating the role of HN in viral entry, fusion and release using HPF3 HN variants that are altered in receptor binding or fusion promotion and (B) identifying functional cellular receptor molecules for HN. (2) To evaluate strategies for interfering with HN-receptor interaction and thus test the hypothesis about the functions of HN in the viral life cycle, using (A) sialic acid analogs that mimic the sugar moiety of the HN receptor as decoys to interfere with viral attachment and (B) HN expression on the surface of uninfected cells to mimic viral interference and thus prevent viral entry. (3) To analyze the contribution of the HN-receptor interaction to pathogenesis in vivo by extending the studies to HPF3 infection in the cotton rat, a model that mimics HPF3 lower respiratory tract infection in man. She will test the hypotheses that (A) avidity of virus-receptor interaction is a determinant of pathogenesis in the lung and (B) neuraminidase determines the outcome of infection in the lung as it does in cell culture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUTANT F. TULARENSIS INTERACTIONS WITH MACROPHAGES Principal Investigator & Institution: Banas, Jeffrey A.; Associate Professor; Albany Medical Center Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Inhalation of as few as 10-50 F. tularensis organisms can lead to glandular tularemia as well as to acute and severe bronchiolitis, pneumonitis or pleuropneumonia. This extreme infectivity of F. tularensis, and the significant morbidity and mortality that can result in the absence of prompt antibiotic treatment, are reasons why F. tularensis has traditionally been considered to have potential as an agent of biological warfare. Little is known about the pathogenic mechanisms of F. tularensis, including the basis for its extraordinary infectivity. This infectivity may be at least partially explained by efficient uptake, survival and growth within host macrophages. The ability of F. tularensis to propagate intracellularly is enhanced by failure of lysosomes to fuse with the phagosome and the lack of stimulation of a respiratory burst. However, little has been described pertaining to the initial uptake of F. tularensis by macrophages early in infection. In general, macrophages can recognize intact bacteria via several different receptors; whether or not a respiratory burst is stimulated depends on which receptor(s) mediates uptake. We hypothesize that specific components on the

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surface of F. tularensis facilitate uptake by macrophages and that the identification of these interactions will lead to an understanding of why macrophages fail to undergo a respiratory burst. We further postulate that the identification of these surface components will suggest targets for modulating the immune response. In order to test this hypothesis we propose the following specific aims: 1) Generate and screen mutants of F. tularensis that are deficient in being taken up by macrophages, 2) Generate and screen mutants of F. tularensis that become capable of stimulating the production of a respiratory burst or alter cytokine secretion in unstimulated macrophages, 3) Examine the mutants identified in Aims 1 and 2 in an animal model of infection noting changes in virulence, pathology, and immunity. The completion of these Aims will directly support at least two other subprojects, including the testing of vaccine candidates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NA+ TRANSPORT INHIBITION BY RESPIRATORY SYNCYTIAL VIRUS Principal Investigator & Institution: Davis, Ian C.; Anesthesiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: CANDIDATE: I graduated from the University of Bristol in 1992, with Honours in Anatomical Science and Veterinary Science. At UAB I received training in laboratory animal medicine, laboratory animal pathology, and viral pathogenesis in animal models (Ph.D. February 2000; mentor Dr. Patricia Fultz). Subsequently, I elected to join Dr. Matalon's research group, where I might build on my knowledge of viral pathogenesis by cross-mining in electrophysiology, and apply these techniques to study the pathogenesis of human respiratory viral pneumonitides. RESEARCH: Respiratory syncytial virus (RSV) is commonest cause of lower respiratory tract disease in children worldwide. Pathogenesis of RSV-induced bronchiolitis is poorly understood, and effects of RSV infection on ion transport (a seminal function of respiratory epithelial cells) have not been investigated. I hypothesize that RSV infection of respiratory epithelial cells reduces their Na ? transport capacity. Preliminary studies have demonstrated that this hypothesis is correct, both in vitro and in RSV-infeeted BALB/c mice. My aims for years 01- 03 are to: (1) quantify alterations in Na + transport across airway and alveolar epithelia in vivo and ex vivo, after infection of BALB/c mice with RSV; (2) define changes in Na + currents and amiloride-sensitive channel activity after RSV infection of murine epithelial cells in vitro; and (3) correlate alterations in Na + transport induced by RSV in vitro and in vivo with alterations in ENaC expression by marine respiratory epithelia. My plan for years 04-05 is to determine the role of the ubiquitin/proteasome pathway in mediating reduced Na+ transport after RSV infection of respiratory epithelia, and to identify the role of the RSV small hydrophobic (SH) gene product in modulation of Na + transport. I will use a combined electrophysiologic and biochemical approach to investigate effects of RSV on Na + transport at all levels, from the single cell to the whole animal, and to correlate these effects to Na + channel expression and degradation. My project will emphasize cross-training in diverse techniques, including short-circuit measurements across monolayers, radioisotopic ion flux studies, whole cell and single channel patch-clamp, and measurement of alveolar fluid clearance and nasal potential difference in mice. ENVIRONMENT: This SERCA, with Dr. Matalon (lung physiology) as mentor and Dr. Sullender (respiratory syncytial virus) as co-mentor, will provide the training and setting I require for my maturation into an independent scientist focused on comparative pathophysiologic effects of respiratory viruses on normal epithelial cell function.

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

Project Title: NITRATION IMMUNOLOGY Principal Investigator & Institution: Hunt, John F.; Pediatrics; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 28-FEB-2006 Summary: (provided by applicant): Nitration of tyrosine residues on proteins in the respiratory tract has been shown to occur during inflammatory lung diseases including asthma, chronic obstructive pulmonary disease, cystic fibrosis, and bronchiolitis obliterans. Formation of nitrotyrosine occurs inorganically, but also is catalyzed by enzymes of polymorphonuclear leukocytes including eosinophil peroxidase and neutrophil myeloperoxidase. Nitrotyrosine bears pronounced structural and chemical similarity to many well-described haptens--low molecular weight compounds that when covalently bound to proteins incite immune responses. We hypothesize that nitrotyrosine--formed during nitration of proteins early during innate immune processes--functions as a hapten and is a key factor initiating acquired immune responses against the protein in which it is bound. We plan initially to evaluate this hypothesis with respect to nitration of inhaled allergens. We will determine optimum chemical conditions for nitration of natural and recombinant dust mite proteins, and compare these conditions to those found in the airways during inflammation such as occurs with the common cold. Expanding upon supportive preliminary data, we will concurrently investigate the potential of nitrated allergen to augment immune responses by evaluating in vitro the proliferative responses of human peripheral blood mononuclear cells upon exposure to nitrated allergen in comparison to non-nitrated allergen. Further, we will seek immune responses to nitrated allergen in humans by assaying for specific antibody to nitrated proteins with skin testing and serum assays. We anticipate that, consistent with preliminary data, nitration of proteins will initiate and augment immune responses. The pro-inflammatory signals should then be eliminated as nitrated proteins are removed from the tissue. This novel project may serve to elucidate an important link between innate and acquired immunity--identifying a highly novel mechanism for both inciting and regulating immune responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OXIDATIVE DEVELOPMENT

STRESS

AND

FUNCTIONAL

LYMPHOCYTE

Principal Investigator & Institution: Karp, David R.; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The prevalence of childhood asthma is increasing dramatically in industrialized societies. The reasons for this are not completely understood, although persistent indoor aeroallergen challenge, exposure to industrial pollutants and tobacco smoke, and infant bronchiolitis have all been implicated. From these studies, the concept emerges that asthma is the result of a preponderance of accumulated risk factors occurring in a critical sequence, at a critical time in development. Primary prevention of asthma will result from elimination or interruption of any of these risks. One such risk may be the balance between oxidative stress and antioxidants, particularly in the lung. Recent evidence has suggested that oxidative stress may influence the polarization of T cell responses in mice. The effects of oxidative stress on the development of Th2 responses in humans are unknown, as are the effects

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of antioxidants. The Specific Aims of this Project are: 1. To determine how exposure to oxidative and nitrosative stress affects the function of various antigen presenting cells. 2. To test whether oxidative stress alters the Th1/Th2 balance of a T cell response to antigen. 3. To determine whether antioxidant treatment of antigen presenting cells, and/or T cells, will alter the type of T cell response to antigen. Different types of antigen presenting cells, including monocytic cell lines and primary cells (e.g., dendritic cells) will be subjected to relevant stressors and tested for their ability to modulate the expression of co-stimulatory molecules, cytokines, and chemokines. The APC that are generated under different conditions of oxidative stress will then be tested for the ability to support or modulate the polarization of T cell responses to Th1 or Th2. Finally, the ability of thiol and non-thiol antioxidants to modulate the induction of Th1 or Th2 responses will be determined. These experiments will both answer fundamental questions about the development of immune responses, but also provide a framework for rational clinical trials of specific antioxidants used at critical times for the primary prevention of asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENESIS AND THERAPY OF CHRONIC LUNG REJECTION Principal Investigator & Institution: Hertz, Marshall I.; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): More than 10,000 lung and heart-lung transplants have been performed worldwide. These procedures have proven to be highly effective for many recipients; however, long-term survival rates for lung recipients are considerably lower than those observed in kidney, heart, and liver recipients. This is due, in large part, to the development of chronic lung rejection, manifested histologically as OB, and clinically as bronchiolitis obliterans syndrome (BOS). The goal of this proposal is to improve understanding of the immunopathogenesis, molecular diagnosis, and therapy of CR after lung transplantation. To accomplish this, we have assembled a multidisciplinary team of experienced investigators at one of the world?s most experienced and respected lung transplant centers. The proposed Program consists of four research projects which apply innovative experimental approaches and state-of the-art technologies to address three major gaps in knowledge: First, while an alloimmune reaction is generally accepted to be central to the pathogenesis of CR, the molecular mechanisms by which this reaction occurs remain obscure. Projects 1 and 2 address the immunopathogenesis of CR use T-cell receptor Tg mice in which the location and activity of graft-specific T-cells can be identified. A second major problem has been the inability to identify a specific group of at-risk recipients as potential candidates for augmented immune suppression or novel therapeutics. Project 3 addresses this problem by using large-scale gene expression microarray (>10,000 genes) technology to identify sensitive and specific gene expression patterns associated with CR. Finally, current therapeutic approaches, based primarily on augmenting immune suppressive therapy, are ineffective in reversing the course of chronic lung rejection in most affected individuals. Project 4 seeks to explore a novel therapeutic direction: triggering apoptosis in airway fibroblasts by transfection with gene constructs, which sensitize them to HMG-CoA reductase inhibitors. The projects in this proposal will be supported by two cores: 1) An Administrative Core will coordinate administrative, educational, and biostatistical functions of the Program; and 2) a Murine Tracheal Transplant Core will concentrate expertise related to performing, harvesting, and processing the heterotopic mouse tracheal transplants used in Projects 1, 2, and 4.

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

Project Title: PATHOGENESIS OBLITERANS

OF

POST-TRANSPLANT

BRONCHIOLITIS

Principal Investigator & Institution: Mohanakumar, Thalachallour; Professor; Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 10-DEC-2000; Project End 30-NOV-2004 Summary: Lung transplantation (LTx) is a common treatment option in a variety of endstage pulmonary Parenchymal and vas diseases. Improvements in recipient selection, surgical techniques, and immunosuppressive regimens have all increased survival following LTx. However, the long term survival of the lung allograft are limited by the development of bronchiolitis obliterans syndrome (BOS) an unexplained and irreversible condition unresponsive to therapy and in most cases fatal. Although much has been written on the possible etiological factors and pathogenesis of BOS, no definite answers exist to explain the basic mechanism by which BOS develops. A growing body of evidence suggests that BOS is caused by immunological-mediated injury directed against epithelial cells of the lung allograft. Using a unique murine model of heterotopic transplantation of HLA-A2 transgenic tracheal grafts into CD8 T cell-knockout (KO) as well as CD4 T cell-KO C57BL/6 mice, we have obtained compelling evidence for a seminal role for indirect antigen presentation of the mismatched HLA-A2 molecule in the pathogenesis of obliterative airway disease (OAD). Specific goals of this project are: 1) To define the role of CD4 T cells, CD8 T cells, and NK cells in the development of OAD in this model where there is only a single MHC difference between donor and recipient. This will be accomplished by HLA-A2 tracheal transplantation into CD4-KO or CD8-KO animals as well as administration of anti-CD4 or anti-CD8 antibodies to abrogate the pathology. In addition, the role of interleukin-2 in the immunopathogenesis of OAD will be investigated. 2) To determine the mechanism of OAD development following HLA-A2 tracheal transplantation into syngeneic CD8-KO recipients. We will test the ability of spleen cells from animals with OAD to respond to HLA-A2 and their peptides. Requirement for processing of HLA-A2 molecules as well as production of antibodies specific for HLA-A2 will be investigated. 3) To determine the dominant HLA-A2 epitopes to which immune response takes place leading to OAD. Towards this, proliferation assays at different time points following transplantation will be done using peptides covering the alpha1, 2 and 3 domains of HLA-A2 molecule. 4) To determine the role of CD4 TH1 and TH2 cells against the HLA-A2 peptides in the development of OAD. Passive transfer of in vitro generated HLA-A2 specific CD4 TH1 or TH2 cells and its consequences on OAD will be investigated, and 5) To define the role of antibodies specific for HLA-A2 in the development and/or perpetuation of OAD in the HLA-A2 tracheal grafts. This will b accomplished by using Immunoglobulin-KO recipients and by passive administration of HLA-A2 antibodies following transplantation. Production of growth factors by epithelial cells and their effect on fibroblasts and smooth muscle cells will also be investigated to define the mechanism of OAD development. The overall goal of this proposal is to employ this unique murine preclinical model of OAD in order to define the cellular and molecular mechanism leading to BOS following clinical lung transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHOGENESIS OF VIRAL PROLIFERATIVE BRONCHIOLITIS Principal Investigator & Institution: London, Lucille; Associate Professor; Microbiology and Immunology; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-MAR-2004 Summary: (Adapted from the applicant's abstract): Bronchiolitis obliterans with organizing pneumonia (BOOP) is a term for a long observed, but unclassified pattern of acute lung injury. In humans, BOOP is characterized by fibrosis of small airways with fibrous extension into the alveolar spaces with preservation of alveolar ducts and walls. It is frequently associated with a peribronchiolar organizing pneumonia. The lesions may also be accompanied by lipid-laden foamy alveolar macrophages trapped in the air spaces by the fibrosis and by a T cell rich lymphocytic interstitial infiltrate in the regions of the lung directly affected by the lesion. Also, necrosis and sloughing of epithelial cells has been observed and is thought to result in the partial alveolar collapse seen in human BOOP. While BOOP can be associated with documented viral and bacterial infections, many cases are not associated with known causes and are thus classified as idiopathic. Little is known concerning the pathogenesis and treatment of BOOP since no animal models were available for this disorder. The investigators are the first to establish an experimental animal model for this disease. In this model, CBA/J mice infected with reovirus serotype 1/strain Lang develop BOOP lesions which closely resemble the histopathological picture of human BOOP. In addition, the development of BOOP lesions in CBA/J mice is virus strain specific. The central hypothesis of this proposal is that "Disruption of the epithelial basement membrane determines the susceptibility to fibrosis". The investigators propose to characterize the host and/or viral factors (both immune and non-immune cellular populations) that result in initiation of damage to the basement membrane and relate these finding to the development of fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PEDIATRIC EBM-GETTING EVIDENCE USED AT THE POINT OF CARE Principal Investigator & Institution: Davis, Robert L.; Associate Professor; Pediatrics; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: The applicant plans to study the provision of evidence at the point of pediatric care, in order to increase the application of evidence- based medicine, change physician behavior, and expedite the translation of research into clinical practice. There will be two main questions. First, that use of an evidence-based decision support system at the point of care will improve antibiotic use in specific index pediatric outpatient diseases, and will (i) reduce frequency and duration of antibiotic therapy for otitis media, (ii) reduce duration of therapy for acute sinusitis, (iii) reduce use of bronchodialators in outpatient treatment of bronchiolitis, and (iv) increase use of intranasal steroids for allergic rhinitis. Second, that individualized physician feedback will provide additional benefit, when used in conjunction with the support system. This study will be carried out through a series of randomized controlled trials, implemented at three sites, including academic pediatric and family medicine health care centers, rural and suburban pediatric clinics, and a regional pediatric emergency department. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POINT OF CARE INSTRUMENT FOR VIRAL RESPIRATORY DIAGNOSIS Principal Investigator & Institution: Ives, Jeffrey T.; Director; Xtrana, Inc. 717 Yosemite Cir Denver, Co 80220 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): The common respiratory viruses (influenza, parainfluenza, respiratory syncytial virus or RSV, and rhinovirus) cause millions of cases of upper and lower respiratory tract disease every year. The spectrum of illness induced directly by the viruses is very broad, ranging from mild colds and simple ear infections to more serious and sometimes life-threatening diseases such as bronchiolitis, pneumonia, and asthma. In spite of the importance of diagnosing and treating these viral infections, current diagnostic methods of physical exam or rapid immunoassays or culture in reference laboratories do not provide the accuracy, sensitivity, or timely information that the primary care physician needs for treatment. Antiviral therapeutics are becoming increasingly viable, but they require accurate identification of the infectious virus(es). While sensitive, newer assays and instrumentation based on nucleic acid technologies are not cost effective or practical for point of care in a physician's office. To provide a cost effective, point of care system for diagnosing respiratory viruses, this application describes an integrated and unique device that will begin with a nasal wash sample and use nucleic acid-based technologies to accurately identify eight respiratory viruses: RSV A and B; parainfluenza 1, 2, and 3; influenza A and B; and rhinovirus. After loading the sample, proprietary steps of sample preparation, RNA extraction, multiplexed amplification, and detection by lateral flow strips will be automatically performed. These processing steps will be directed on a disposable, microfluidic card that both minimizes the reagent costs and provides an enclosed container for convenient, biosafe disposal. To develop this diagnostic device, a series of technical milestones will be accomplished. First, a novel method of multiplexed target amplification will be optimized on respiratory viral targets. Second, nasal wash samples will be directly prepared for multiplexed amplification by flow through extraction and unique solid phase analysis. Sample preparation and amplification will be managed by developing disposable, laminated microfluidics cards with channels, reagents, and valves. Using a protoype workstation, the described system will be tested with patient samples and spiked samples to verify the utility, specificity, sensitivity, and reproducibility of the system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POSTTRANSPLANT IMMUNE PARAMETERS AND DECREASED IMMUNOSUPPRESSION Principal Investigator & Institution: Matas, Arthur J.; Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002 Summary: The long-term objective of our Project is to determine whether posttransplant immune parameters can predict which solid organ transplant recipients will tolerate decreased immunosuppression. The specific aims for recipients developing donor antigen-specific hyporesponsiveness. 1. To determine, in a prospective randomized trial, whether kidney transplant recipients can be tapered off steroids without an increased incidence of late acute rejection or of chronic rejection. 2. To determine whether heart transplant recipients can be tapered off steroids without an increased incidence of acute rejection and without an increased risk of allograft vasculopathy. 3. To determine

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whether lung transplant recipients can be converted from oral to inhaled steroids without an increased incidence of acute rejection episodes and without an increased risk of obliterative bronchiolitis. It is well-recognized that posttransplant immunosuppression is associated with morbidity. And many immunosuppressive care protocols attempt to lower or withdraw some immunosuppressive agents. However, trials of immunosuppression drug withdrawal or dosage lowering, based on clinical criteria alone, have not been routinely successful. We have previously shown that patients who develop donor antigen-specific hyporesponsiveness have decreased incidence of late acute rejection episodes, decreased chronic rejections (biopsy proven in kidney transplant recipients, coronary artery disease on angiogram in heart transplant recipients, and of obliterative bronchiolitis in lung transplant recipients), and improved long term graft survival. The goal of the current study is to determine whether those who have developed donor antigen-specific hyporesponsiveness can have the same excellent long-term outcome after prednisone withdrawal ( in kidneys and heart recipients) or conversion to nebulized prednisone (in lung transplant recipients). Identification of a subpopulation of patients who can safely tolerate prednisone (in long transplant recipients). Identification of a subpopulation of patient who can safely tolerate prednisone withdrawal will allow potential for decreased morbidity for these, while simultaneously not withdrawing prednisone from those who would be at risk for rejection episodes, will similarly help preserve graft function and decrease morbidity (due to the antirejection treatment). Finally, for lung transplant recipients who remain responsive to donor antigens, we will also determine if the addition of inhaled steroids to their oral steroid regimen will decrease the risk of bronciolitis obliterans. Thus, this study has the potential for allowing selective immunosuppression for transplant recipients after the first year. The selective immunosuppression will help improve graft survival while potential decreasing posttransplant morbidity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREVENTION OF LUNG REJECTION BY AEROSOL CYCLOSPORINE Principal Investigator & Institution: Iacono, Aldo; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002 Summary: This proposal describes a prospective double blind randomized trial to evaluate the effectiveness of aerosolized cyclosporine (ACsA) as prevention of acute rejection after lung transplantation. Patients with recurrent acute rejection commonly develop chronic rejection characterized histologically by obliterative bronchiolitis and an inexorable decline in lung function. Cyclosporine targeted directly into the lung allograft by aerosol inhalation may offer important advantages over systemic immunosuppressive therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PULMOZYME IN BRONCHIOLITIS NEEDING MECHANICAL VENTILATION Principal Investigator & Institution: Nasr, Samya Z.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RAS POLARIZATION

AND

CHEMOKINE

STIMULATED

NEUTROPHIL

Principal Investigator & Institution: Knall, Cindy M.; Lovelace Biomedical & Environmental Res Albuquerque, Nm 87108 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Polymorphonuclear leukocytes, neutrophils, are the most abundant leukocytes in peripheral blood. They play a major role in innate immunity and may contribute to the development of the adaptive immune response. The early and selective recruitment of neutrophils into inflamed tissues is thought to be a major factor in the tissue damage/destruction seen in a number of disease states. The chemokines Interleukin-8 (IL8) and Growth-Regulated Oncogene alpha (GROalpha) control much of the normal function of neutrophils. These chemokines are also implicated in the diseases associated with neutrophil dysfunction. Research is beginning to investigate the specific signal transduction pathways activated by these chemokines to regulate neutrophil functions. Our long-range goal is to define the signal transduction mechanisms used by chemokines to activate neutrophils in order to develop effective therapeutic strategies to regulate this activation. Polarization is the first step in the process of neutrophil migration into sites of inflammation. However, the signal transduction pathways that regulate chemokine stimulated neutrophil polarization remain undefined. The objective of this proposal is to determine the mechanisms that induce chemokine stimulated neutrophil polarization. The central hypothesis of this proposal is that IL8, in contrast to GROalpha regulates neutrophil polarization independent of phosphatidylinositol-3 (PI3) kinase because IL8 stimulates a more robust activation of several different signal transduction molecules. This hypothesis is based on strong preliminary data that suggest that efficient activation of Ras by IL8, in contrast to GROalpha allows for PI3 kinase independent regulation of neutrophil polarization, because IL8 binds to both CXCR1 and CXCR2. The rationale for the proposed research is that once the mechanisms controlling neutrophil polarization are defined, effective therapies can be developed to control this process. The central hypothesis will be tested and the objective accomplished through two specific aims: 1) identify the signal transduction molecule that allows IL8 to by-pass PI3 kinase in the regulation of neutrophil polarization; 2) determine the extent to which the chemokine receptors CXCR1 and CXCR2 contribute to PI3 kinase independent neutrophil polarization. The proposed work is innovative because it utilizes a technique, recently developed by the applicant, to transfect primary human neutrophils. Our expectation is that this approach establish how IL8 and GROalpha regulate neutrophil polarization using two different mechanisms. This outcome is significant because it will suggest new targets for prevention and treatment strategies to control neutrophil recruitment in a variety of inflammatory diseases such as obliterative bronchiolitis, the most significant long-term complication in lung transplant patients. The proposed study fulfills the scope of the NIAID small research grants program as a small, self-contained research project requiring minimal funding for a limited time. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESPIRATORY SYNCYTIAL VIRUS GENE PRODUCTS Principal Investigator & Institution: Wertz, Gail W.; Professor; Microbiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-FEB-1987; Project End 31-JAN-2004

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Summary: The pneumovirus respiratory syncytial (RS) virus is the major viral cause of bronchiolitis and pneumonia in infants and children and no effective vaccine is available. Maternal antibody does not confer solid immunity on neonates and natural infection provides only partial protection against frequent repeat infections. To address this major public health problem, this research program has focused on the molecular biology of RS virus, characterizing the viral genes and gene products and examining the immune response to individual gene products. Until recently it has not been possible to address the relationship between the distinctive genomic regions and gene products of RS virus and the unusual pathogenesis of disease because it was not possible to engineer specific alterations into the genomes of these viruses and recover replicable, infectious RNA and virus. Recent technical advances have overcome this problem and opened the way to genetic analysis of every aspect of replication, both the unique cis-acting genetic elements and trans-acting protein factors in control of viral replication and in the pathogenesis of disease. The experiments in this proposal apply this technology to investigate previously inaccessible questions concerning the role of the unique RS virus gene products in the life cycle of the virus and in the progression of the virus to severe respiratory disease. The specific aims are 1) To determine the mechanism of action of the RS virus M2 ORF1 protein as a transcription antiterminator; 2) To analyze the role of the M2 protein conserved Cys3His1 motif in transcription antitermination, N protein binding and binding of zinc; 3) To analyze the role of the M2 protein in the virus life cycle; 4) To investigate the role of the NS1 and NS2 proteins in infection; 5) To investigate the role of the glycoprotein G in the infection process; 6) To analyze the role of G and the secreted form of G in viral pathogenesis and spread; 7) To investigate the potential of gene rearrangement to alter the vral phenotype beneficially. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF EOSINOPHILS IN AIRWAY INFLAMMATION Principal Investigator & Institution: Lemanske, Robert F.; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 05-JAN-2002; Project End 30-NOV-2006 Summary: (Applicant's Abstract) Viral respiratory infections early in life may represent a significant risk factor for the development of asthma and for sensitization to common allergens during childhood. The mechanisms by which viral infections may render airways vulnerable to subsequent allergen exposure and the potential role of eosinophils in these processes are incompletely understood. In Brown Norway rats, viral bronchiolitis during a critical developmental period (3-4 weeks of life) induces a heightened state of airway vulnerability to the pathophysiological consequences of allergen sensitization and airway allergen exposure. These observations provide a rationale for using this rat model to test the hypothesis that the interaction of eosinophils with the post-viral airway environment may result in alterations in pulmonary function. There are at least two mechanisms, which are not mutually exclusive, that could account for an enhanced vulnerability of post-viral airways to eosinophil-dependent effects. First, eosinophils may experience changes in their phenotypic characteristics arising from migration into, and interactions with, the altered post-viral airways. Second, structural changes in the post-viral airway environment may increase the likelihood that eosinophils will migrate into and remain in the airway walls. Therefore, studies will be performed to track the migration of labeled eosinophils (which are either instilled into the airspace of the lung or infused intravenously) into normal and post-viral airways. The physiological consequences that occur as a result of the presence of these eosinophils in the airway walls will be determined using

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pulmonary function measurements and lung imaging techniques. The effect of IL-5 priming of these eosinophils, with or without activation by a secondary stimulus, on migration, granular protein release, and pulmonary physiology will be determined. These studies should provide important insights into mechanisms by which airway injury early in life may enhance the susceptibility of children to morbidity from aeroallergen sensitization and exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RSV INDUCED PATTERN OF CYTOKINE EXPRESSION AND DISEASE Principal Investigator & Institution: Tang, Yi-Wei; Associate Professor of Medicine & Pathol; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-FEB-1994; Project End 29-FEB-2004 Summary: Respiratory Syncytial Virus (RSV) is the most important cause of severe lower respiratory tract disease in infants, rivaling influenza as a cause of excess mortality and morbidity in the elderly, and causing epidemics in bone marrow transplant units with fatality in the majority of cases. Adequate therapy and vaccines are not available, in part because of the unique immunologic features of RSV-induced disease. Formalin-inactivated whole virus vaccine (FI-RSV) did not protect against Infection and was associated with enhanced disease. Data from murine models and evidence from human studies suggest that selective induction of CD4+ T lymphocytes with a Type 2 cytokine expression pattern (dominant IL-4 production) by the FI-RSV vaccine is the basis for vaccine-enhanced illness. Severe RSV bronchiolitis in infants is also associated with Type 2 immune responses. The primary objective of this proposal is to define the mechanisms by which RSV promotes immune responses associated with Type 2 pattern of cytokine production. The specific alms are to: 1) Define the mechanisms by which the RSV G glycoprotein promotes eosinophilia, Th2-like immune responses, and enhanced illness, and 2) Define the mechanisms by which IL-4 delays virus clearance, inhibits CD8+ CTL induction, and promotes enhanced RSV-induced illness. The unique antigenic properties of RSV G will be studied using recombinant vaccinia viruses that express membrane-anchored G, secreted G, or produce both in equal amounts. We will define the role of G structure and antigen processing events on the IL-4 independent induction of IL-5 and eosinophils recently discovered in our laboratory. The mechanism of IL-4 inhibition of CD8+ CTL induction will be defined using recombinant vaccinia viruses constructed in our laboratory that co-express the RSV M2 protein and individual cytokines. The proposed studies will define viral and host factors responsible for patterns of immune response and disease expression after RSV infection. They will improve our basic understanding of how viruses cause disease, and how vaccine-induced immune responses are regulated, will have direct impact on new strategies for development of preventive vaccines and immunotherapeutics for RSV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE ENDOTHELIUM IN ORGAN SPECIFIC CD8 T CELL RECRUITMENT Principal Investigator & Institution: Lichtman, Andrew H.; Assoiate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2004; Project Start 15-APR-2004; Project End 31-MAR-2008

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Summary: (provided by applicant): CD8+ T cells specific for antigens expressed only in particular tissues are important in the pathogenesis of organ-specific autoimmune diseases and allograft rejection, but the mechanisms of recruitment of T cells in these settings are poorly understood. There are likely to be unique aspects of recruitment of tissue antigen-specific T cells, due to the abundance of the tissue antigens, the absence of infection, and the particular characteristics of each organ's vascular bed. This project will focus on endothelial-dependent recruitment mechanisms of pathogenic tissue antigenspecific CD8 + T cells. The approach will rely on transgenic mouse models in which well-defined populations of TCR-transgenic T cells specific for a defined antigen are introduced into mice that express transgene-encoded antigen in an organ specific manner. In Specific Aim #1, the role of selectins in tissue antigen-specific CD8* recruitment will be examined. This Aim will test the hypothesis that selectin-dependent adhesion to endothelium is a key step in the recruitment of these CD8* T cells. The studies will examine different subsets of CD8* T cells, and different tissues. The experiments will involve transgenic models of CD8* T cell-mediated autoimmune myocarditis, pancreatic islet inflammation, nephritis, and bronchiolitis. The recruitment and pathogenicity of CD8- T cells with altered selectin-ligand expression will be quantitatively compared with control T cells. Specific Aim #2 will focus on how chemokines influence recruitment of tissue antigen-specific CD8+ T cells. The underlying hypothesis is that chemokines expressed in tissues will differentially effect the recruitment of CD8+ T cells, depending on the vascular bed and the subsetphenotype of the T cells. The emphasis will be on CXCR and CCR5 binding chemokines. The experimental approach will rely on the same transgenic models of autoreactive T cell recruitment used in Aim 1, in combination with pharmacologic chemokine receptor blockade, and chemokine or chemokine receptor gene knock-out mice. In Specific Aim #3, the role of endothelial antigen-presentation in direct T cell recruitment will be studied. The experiments will directly examine antigen-specific interactions of CD8+ T cells and endothelium in vivo, using sensitive techniques including intravital microscopy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF TLR4 AND RSV F PROTEIN IN IMMUNITY TO RSV Principal Investigator & Institution: Blanco, Jorge C.; Scientific Director; Virion Systems, Inc. 9610 Medical Center Dr, Ste 100 Rockville, Md 20850 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): The respiratory tract is a major portal for pathogens. The bronchoalveolar macrophage, positioned at the mucosal surface, recognizes "pathogen associated molecular patterns (PAMPs)" through structures called "pattern recognition receptors (PRRs)." A family of closely related mammalian PRRs, the "Tolllike receptors (TLRs)," are transmembrane signaling molecules that respond to diverse PAMPs. The lipopolysaccharide (LPS) of Gram negative bacteria stimulates macrophages through TLR4 to elicit a pattern of gene expression that is strongly proinflammatory, e.g., TNF-a, IL-1a, IL-12, and IFN-? resulting in a "Th1-type" cytokine milieu. Respiratory syncytial virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants and young children worldwide, and has recently been attributed to increased morbidity and mortality in the elderly and immunosuppressed. In a failed clinical trial, a formalin-inactivated RSV (FI-RSV) vaccine led to exacerbated RSV disease. Vaccine-enhanced RSV disease, demonstrated by histopathology and airway hyperreactivity, are faithfully recapitulated in the cotton rat (S. hispidus), and is associated with a Th2-type pattern of cytokine gene expression. Vaccination with FI-RSV

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and a TLR4 agonist mitigates enhanced disease. Recently, the RSV fusion (F) protein was shown to be a TLR4 agonist. In vitro, cotton rat macrophages respond to LPS and F protein to elicit the same spectrum of inflammatory genes, although the F protein is less potent. The overall hypothesis to be tested is that the interaction of F protein with TLR4 is essential for establishment of a Thl-type milieu and that formalin fixation of RSV destroys the capacity of F to interact with TLR4, resulting in a Th2-type response. This proposal details novel experimental approaches: (i) to evaluate the contribution and regulation of F protein signaling through TLR4 to the development of a Th1-type cytokine profile, (ii) to determine the role of TLR4 in the development of RSV-mediated disease in vivo, and (iii) to determine if polymorphic forms of TLR4 previously associated with airway hyporesponsiveness to LPS exhibit diminished sensitivity to F protein and if they are overrepresented in a population at high risk for RSV. It is expected that at the completion of this grant, we will have determined the molecular basis for primary and vaccine-enhanced RSV disease, and have identified strategies for the development of a human RSV vaccine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TYPE V COLLAGEN PREVENTS LUNG ALLOGRAFT REJECTION Principal Investigator & Institution: Wilkes, David S.; Associate Professor; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-MAY-2001; Project End 30-APR-2006 Summary: (Applicant's abstract): Lung transplantation is a commonly utilized modality for the treatment of end stage pulmonary diseases. However, the lung is rejected more commonly than other solid organ allografts. Repeated acute rejection episodes result in chronic rejection known as bronchiolitis obliterans, the leading cause of death in lung allograft recipients. Presentation of donor major histocompatibility complex (MHC) antigens by antigen presenting cells, such as macrophages and dendritic cells, to recipient lymphocytes is the stimulus for rejection episodes. Conversely, allograft acceptance may be induced by immunizing the recipient, orally, with donor-derived MHC proteins/peptides or MHC-"like" proteins prior to transplantation. This phenomenon, known as oral tolerance, has been shown to prevent rejection in allografts other than the lung, but has not been examined in lung allograft rejection. Although donor MHC-antigens are the stimulus and target of the rejection response, we have reported recently that type V collagen (col(V)), which may be MHC-"like," is also recognized as an antigen during lung allograft rejection in humans, and the local immune response to lung alloantigens in mice. Also, immunizing mice with col(V) induces immunological tolerance to lung alloantigens. However, the ability of col(V) to induce oral tolerance and prevent the immunology and pathology of lung allograft rejection is unknown. Our laboratory is one of the few that developed the rat model of lung allograft rejection in which F344 rat lungs (RT1lv1) are transplanted orthotopically into WKY (RT1I) recipients. Utilizing this model, the current proposal tests the hypothesis that oral tolerance induction by col(V) prevents the immunology and pathology of lung allograft rejection by examining the following specific aims: Aim 1: To determine if oral immunization with col(V) induces oral tolerance to alloantigens and prevents the development of rejection pathology in lung allografts, rats will be fed col(V) followed by an assessment of delayed type hypersensitivity (DTH) responses to donor alloantigens, and onset of acute rejection and bronchiolitis obliterans (BO) in allograft lungs. Aim 2: To determine the cell types responsible for oral tolerance induced by col(V), the role of specific lymphocyte subsets and APC's in down regulating the

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immunology and pathology of lung allograft rejection will be investigated. Aim 3. To determine the peptides of col(V) that induce oral tolerance to lung allografts, peptides of specific alpha-chains of col(V) will be produced by cyanogen bromide digestion followed by an assessment of these peptides to induce oral tolerance and prevent the immunology and pathology of the rejection response. Aim 4. To determine the role of soluble mediators in oral tolerance induced by col(V), tolerized lung allograft recipients will be treated with antagonists and neutralizing antibodies to cytokines and other mediators believed to have key roles in oral tolerance followed by an assessment of the immunology and pathology of the rejection response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UVA ASTHMA AND ALLERGIC DISEASES CENTER Principal Investigator & Institution: Platts-Mills, Thomas A.; Professor; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 24-SEP-2001; Project End 30-JUN-2005 Summary: OVERALL (provided by applicant: The primary objective of research at the University of Virginia has been to understand the role of foreign antigens or allergens in causing and maintaining the chronic inflammation of asthma. However, it has become clear that many factors contribute to the severity of the disease, including: viral infections, chronic hyperplastic sinusitis, the nature of the immune response to allergens and the biochemistry of the lung response, including the recently recognized fall in pH. The current application will focus on four different aspects of this interaction. Project 1 will investigate the mechanisms that control the pH of lung lining fluid, including decreased glutaminase with the resulting fall in ammonia. The hypothesis is that glutaminase can be downregulated by interferon-gamma (IFN-gamma) from T cells responding to rhinovirus (RV), and that the pH fall acts on already inflamed lung to exacerbate attacks of asthma. Project 2 focuses on the relationship between chronic sinusitis and asthma using prospective studies, analysis of the response to allergen or viral challenge, and detailed investigation of the relevance of the leukotriene receptors, CysLTR1 and CysLTR2, to inflammation of the sinuses. Project 3 continues studies on the role of viral infections in asthma by studying infants and children hospitalized for asthma/bronchiolitis and by defining the role of pre-existing inflammation and IgE antibody (Ab) in the response to rhinoviral challenge. These studies will play an important role in interacting with each of the other projects. Project 4 will investigate the recent finding that exposure to high levels of the cat allergen, Fel d 1, can induce a "modified T helper (Th)2" response with IgG Ab and IgG4 Ab but without IgE Ab. These studies will examine the relevance of this response to symptoms, asthma and the response to other allergens in ongoing prospective studies in children. The mechanisms controlling the form of immunological tolerance will be investigated by studying the specificity and cytokine response of Fel d 1-specific T cells in vitro. Overall, the studies are designed to understand: 1) the immunological and biochemical events that underlie acute episodes of asthma; 2) the relationship between responses of the nose and sinuses to allergen or viral exposure and subsequent events in the lungs; and 3) the aspects of the immune response to allergens that explain why so many allergic patients are being treated for asthma and admitted to hospital with asthma. Understanding the mechanisms involved is essential for defining new approaches to treatment and prevention and also for explaining the increasing prevalence of asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: V & Q DISTURBANCES IN OBLITERATIVE BRONCHIOLITIS Principal Investigator & Institution: Lipson, David A.; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 06-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Candidate?s Plans/Training: The candidate plans a career as an independent clinical investigator focusing on patient oriented research related to advanced lung disease and lung transplantation. Training will include formal epidemiological course work in patient oriented research, a mentored laboratory experience, and closely mentored completion of the research protocol. Environment: The University of Pennsylvania is a uniquely suited environment for this training award. The Center for Clinical Epidemiology and Biostatistics will provide formal didactic training. The Metabolic Magnetic Resonance Research and Computing Center will provide a mentored laboratory experience. Research: Obliterative Bronchiolitis (OB) is recognized as a form of chronic allograft rejection and affects as many as 60 to 80% of lung transplant recipients between 5 and 10 years after transplantation. Diagnosis of OB is difficult to make, yet detection of the disease is important because patients who have OB detected early may have improved survival. Current techniques in detection include lung biopsy, which is insensitive and morbid, and spirometry, which detects disease after it has progressed. Recently, non-invasive functional MRI methods using hyperpolarized, non-radioactive 3He gas and magnetic labeling of blood, termed "Arterial Spin-Tagging" (AST) have been developed which detect ventilation and perfusion (V & Q) disturbances in patients with airway obstruction, such as in OB. The overall hypothesis of the proposal is that a predictive model combining clinical risk factors for OB with the detection of airspace and perfusion disturbances using 3He and AST MR imaging will identify OB earlier than conventional techniques. The study has three specific aims: (1) a retrospective cohort study to examine the relationship between clinical parameters and the incidence of OB; (2) a prospective cohort study to test the hypothesis that V & Q imaging using hyperpolarized 3He and AST MRI can differentiate between normal subjects and patients with varying degrees of airway obstruction and (3) a prospective cohort study to test the hypothesis that V & Q as visualized by 3He and AST MRI following lung transplant predicts patients who will develop OB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

3 4

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

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

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full-text articles. The following is a sample of items found for bronchiolitis in the PubMed Central database: •

Comparison of Corticosteroids for Treatment of Respiratory Syncytial Virus Bronchiolitis and Pneumonia in Cotton Rats. by Ottolini MG, Curtis SJ, Porter DD, Mathews A, Richardson JY, Hemming VG, Prince GA.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127305

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Critical role for the chemokine MCP-1/CCR2 in the pathogenesis of bronchiolitis obliterans syndrome. by Belperio JA, Keane MP, Burdick MD, Lynch JP III, Xue YY, Berlin A, Ross DJ, Kunkel SL, Charo IF, Strieter RM.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=209398

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Inflammatory myopathy, bronchiolitis obliterans/organizing pneumonia, and anti-Jo1 antibodies--an interesting association. by Kalenian M, Zweiman B.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170510

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Lack of Protection in Mice and Necrotizing Bronchointerstitial Pneumonia with Bronchiolitis in Guinea Pigs Immunized with Vaccines Directed against the hsp60 Molecule of Mycobacterium tuberculosis. by Turner OC, Roberts AD, Frank AA, Phalen SW, McMurray DM, Content J, Denis O, D'Souza S, Tanghe A, Huygen K, Orme IM.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97658

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Obliterative bronchiolitis after lung transplantation: a fibroproliferative disorder associated with platelet-derived growth factor. by Hertz MI, Henke CA, Nakhleh RE, Harmon KR, Marinelli WA, Fox JM, Kubo SH, Shumway SJ, Bolman RM 3rd, Bitterman PB.; 1992 Nov 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50343

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Pilot study of recombinant interferon alpha-2a for treatment of infants with bronchiolitis induced by respiratory syncytial virus. by Portnoy J, Hicks R, Pacheco F, Olson L.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172227

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Tidal breathing flow-volume loops in bronchiolitis in infancy: the effect of albuterol [ISRCTN47364493]. by Totapally BR, Demerci C, Zureikat G, Nolan B.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111183

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to 6

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

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

A cohort of children hospitalised with acute RSV bronchiolitis: impact on later respiratory disease. Author(s): Sigurs N. Source: Paediatric Respiratory Reviews. 2002 September; 3(3): 177-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12376053

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A hypothesis: antenatal sensitisation to respiratory syncytial virus in viral bronchiolitis. Author(s): Legg JP, Jones CA, Warner JA, Johnston SL, Warner JO. Source: Archives of Disease in Childhood. 2002 June; 86(6): 431-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12023178

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A limited form of Wegener's granulomatosis with bronchiolitis obliterans organizing pneumonitis-like variant in an ulcerative colitis patient. Author(s): Yano S, Kobayashi K, Kato K, Nishimura K. Source: Intern Med. 2002 November; 41(11): 1013-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12487180

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A meta-analysis of randomized controlled trials evaluating the efficacy of epinephrine for the treatment of acute viral bronchiolitis. Author(s): Hartling L, Wiebe N, Russell K, Patel H, Klassen TP. Source: Archives of Pediatrics & Adolescent Medicine. 2003 October; 157(10): 957-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14557155

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A multicenter, randomized, double-blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis. Author(s): Wainwright C, Altamirano L, Cheney M, Cheney J, Barber S, Price D, Moloney S, Kimberley A, Woolfield N, Cadzow S, Fiumara F, Wilson P, Mego S, VandeVelde D, Sanders S, O'Rourke P, Francis P. Source: The New England Journal of Medicine. 2003 July 3; 349(1): 27-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12840089

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A randomized, controlled trial of the effectiveness of nebulized therapy with epinephrine compared with albuterol and saline in infants hospitalized for acute viral bronchiolitis. Author(s): Patel H, Platt RW, Pekeles GS, Ducharme FM. Source: The Journal of Pediatrics. 2002 December; 141(6): 818-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12461499

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A rare cause of chronic cough: bronchiolitis obliterans caused by microcarcinoids. Case report. Author(s): Zompatori M, Poletti V, Battista G, Bini A, Consorti N. Source: Radiol Med (Torino). 2002 April; 103(4): 424-7. English, Italian. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12107395

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A role for indirect allorecognition in lung transplant recipients with obliterative bronchiolitis. Author(s): Stanford RE, Ahmed S, Hodson M, Banner NR, Rose ML. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2003 June; 3(6): 736-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12780566

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Acute and chronic onset of bronchiolitis obliterans syndrome (BOS): are they different entities? Author(s): Jackson CH, Sharples LD, McNeil K, Stewart S, Wallwork J. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 June; 21(6): 658-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12057699

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Acute viral bronchiolitis and its sequelae in developing countries. Author(s): Fischer GB, Teper A, Colom AJ. Source: Paediatric Respiratory Reviews. 2002 December; 3(4): 298-302. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12457599

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Administration of anti-interleukin-2Ralpha monoclonal antibody in bronchiolitis obliterans syndrome after lung transplantation. Author(s): Ding IB, Baumgartner RA, Schwaiblmair M, Behr J. Source: Transplantation. 2003 May 27; 75(10): 1767-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12777880

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Admission to the intensive care unit for respiratory syncytial virus bronchiolitis: a national survey before palivizumab use. Author(s): Prais D, Schonfeld T, Amir J; Israeli Respiratory Syncytial Virus Monitoring Group. Source: Pediatrics. 2003 September; 112(3 Pt 1): 548-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12949282

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Alarming hypoxemia during one-lung ventilation in a patient with respiratory bronchiolitis-associated interstitial lung disease. Author(s): Baraka AS, Taha SK, Yaacoub CI. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2003 April; 50(4): 411-4. English, French. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12670821

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Alveolar neutrophilia is a predictor for the bronchiolitis obliterans syndrome, and increases with degree of severity. Author(s): Devouassoux G, Drouet C, Pin I, Brambilla C, Brambilla E, Colle PE, Pison C; Grenoble Lung Transplant Group. Source: Transplant Immunology. 2002 November; 10(4): 303-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12507402

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An evidence-based clinical pathway for bronchiolitis safely reduces antibiotic overuse. Author(s): Wilson SD, Dahl BB, Wells RD. Source: American Journal of Medical Quality : the Official Journal of the American College of Medical Quality. 2002 September-October; 17(5): 195-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12412948

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Another face of bronchiolitis obliterans organizing pneumonia. Author(s): Turner MO. Source: Can Respir J. 2003 July-August; 10(5): 278-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12945005

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Anti-HLA class I antibody binding to airway epithelial cells induces production of fibrogenic growth factors and apoptotic cell death: a possible mechanism for bronchiolitis obliterans syndrome. Author(s): Jaramillo A, Smith CR, Maruyama T, Zhang L, Patterson GA, Mohanakumar T. Source: Human Immunology. 2003 May; 64(5): 521-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12691702

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Association between acute and chronic graft-versus-host disease and bronchiolitis obliterans organizing pneumonia in recipients of hematopoietic stem cell transplants. Author(s): Freudenberger TD, Madtes DK, Curtis JR, Cummings P, Storer BE, Hackman RC. Source: Blood. 2003 November 15; 102(10): 3822-8. Epub 2003 July 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869516

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Association of rhinovirus infection with increased disease severity in acute bronchiolitis. Author(s): Papadopoulos NG, Moustaki M, Tsolia M, Bossios A, Astra E, Prezerakou A, Gourgiotis D, Kafetzis D. Source: American Journal of Respiratory and Critical Care Medicine. 2002 May 1; 165(9): 1285-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11991880

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Association of severe respiratory syncytial virus bronchiolitis with interleukin-4 and interleukin-4 receptor alpha polymorphisms. Author(s): Hoebee B, Rietveld E, Bont L, Oosten M, Hodemaekers HM, Nagelkerke NJ, Neijens HJ, Kimpen JL, Kimman TG. Source: The Journal of Infectious Diseases. 2003 January 1; 187(1): 2-11. Epub 2002 December 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12508140

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Bronchiolitis drugs lack convincing evidence of efficacy. Author(s): Nelson R. Source: Lancet. 2003 March 15; 361(9361): 939. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12648980

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Bronchiolitis in popcorn-factory workers. Author(s): Parmet AJ. Source: The New England Journal of Medicine. 2002 December 12; 347(24): 1980-2; Author Reply 1980-2; Discussion 1980-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12479196

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Bronchiolitis in popcorn-factory workers. Author(s): Taubert D, Lazar A, Schomig E. Source: The New England Journal of Medicine. 2002 December 12; 347(24): 1980-2; Author Reply 1980-2; Discussion 1980-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12479195

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Bronchiolitis in popcorn-factory workers. Author(s): Ezrailson EG. Source: The New England Journal of Medicine. 2002 December 12; 347(24): 1980-2; Author Reply 1980-2; Discussion 1980-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12477954

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Bronchiolitis management by the Belgian paediatrician: discrepancies between evidence-based medicine and practice. Author(s): de Bilderling G, Bodart E. Source: Acta Clin Belg. 2003 March-April; 58(2): 98-105. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12836492

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Bronchiolitis management preferences and the influence of pulse oximetry and respiratory rate on the decision to admit. Author(s): Mallory MD, Shay DK, Garrett J, Bordley WC. Source: Pediatrics. 2003 January; 111(1): E45-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12509594

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Bronchiolitis obliterans and lung transplantation: evidence for an infectious etiology. Author(s): Husain S, Singh N. Source: Seminars in Respiratory Infections. 2002 December; 17(4): 310-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12497548

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Bronchiolitis obliterans and organising pneumonia caused by carbamazepine and mimicking community acquired pneumonia. Author(s): Banka R, Ward MJ. Source: Postgraduate Medical Journal. 2002 October; 78(924): 621-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12415089

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Bronchiolitis obliterans in a survivor of a chemical weapons attack. Author(s): Thomason JW, Rice TW, Milstone AP. Source: Jama : the Journal of the American Medical Association. 2003 August 6; 290(5): 598-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12902361

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Bronchiolitis obliterans organising pneumonia in pregnancy. Author(s): Futagami M, Sakamoto T, Sakamoto A, Shigetou T, Taniguchi R, Fukuhara R. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 May; 23(3): 309. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12918462

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Bronchiolitis obliterans syndrome and early human cytomegalovirus DNAaemia dynamics after lung transplantation. Author(s): Westall GP, Michaelides A, Williams TJ, Snell GI, Kotsimbos TC. Source: Transplantation. 2003 June 27; 75(12): 2064-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12829913

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Bronchiolitis obliterans syndrome in lung transplant recipients: correlation of computed tomography findings with bronchiolitis obliterans syndrome stage. Author(s): Choi YW, Rossi SE, Palmer SM, DeLong D, Erasmus JJ, McAdams HP. Source: Journal of Thoracic Imaging. 2003 April; 18(2): 72-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12700480

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Bronchiolitis obliterans syndrome in lung transplant recipients: use of spirometrically gated CT. Author(s): Knollmann FD, Ewert R, Wundrich T, Hetzer R, Felix R. Source: Radiology. 2002 December; 225(3): 655-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12461243

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Bronchiolitis obliterans syndrome: utility of the new guidelines in single lung transplant recipients. Author(s): Nathan SD, Barnett SD, Wohlrab J, Burton N. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 April; 22(4): 427-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12681420

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Bronchiolitis obliterans. Organizing pneumonia. Author(s): Popper HH. Source: Verh Dtsch Ges Pathol. 2002; 86: 101-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12647357

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Bronchiolitis obliterans: the Achilles heel of lung transplantation. Author(s): Frost AE. Source: Verh K Acad Geneeskd Belg. 2002; 64(5): 303-19; Discussion 319-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12647579

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Bronchiolitis, respiratory syncytial virus, and recurrent wheezing: what is the relationship? Author(s): Fonseca Cde B, Grisi S. Source: Revista Do Hospital Das Clinicas. 2003 January-February; 58(1): 39-48. Epub 2003 April 30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12754590

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Bronchiolitis-associated outpatient visits and hospitalizations among American Indian and Alaska Native children--United States, 1990-2000. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2003 August 1; 52(30): 707-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12894058

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Bronchoalveolar lavage cellularity in infants with severe respiratory syncytial virus bronchiolitis. Author(s): McNamara PS, Ritson P, Selby A, Hart CA, Smyth RL. Source: Archives of Disease in Childhood. 2003 October; 88(10): 922-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14500316

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Bronchoalveolar lavage cytokine profiles in acute asthma and acute bronchiolitis. Author(s): Kim CK, Kim SW, Park CS, Kim BI, Kang H, Koh YY. Source: The Journal of Allergy and Clinical Immunology. 2003 July; 112(1): 64-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12847481

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Can surfactant cure babies with severe bronchiolitis? Author(s): Haroon M. Source: Archives of Disease in Childhood. 2003 September; 88(9): 834-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12937117

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Case report: bronchiolitis obliterans organizing pneumonia in a spice process technician. Author(s): Alleman T, Darcey DJ. Source: Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. 2002 March; 44(3): 215-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11911018

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CD8+ T lymphocytes in bronchiolitis obliterans, paraneoplastic pemphigus, and solitary Castleman's disease. Author(s): Hoffman MA, Qiao X, Anhalt GJ. Source: The New England Journal of Medicine. 2003 July 24; 349(4): 407-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12878753

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Chemokines and inflammation in the nasal passages of infants with respiratory syncytial virus bronchiolitis. Author(s): Noah TL, Ivins SS, Murphy P, Kazachkova I, Moats-Staats B, Henderson FW. Source: Clinical Immunology (Orlando, Fla.). 2002 July; 104(1): 86-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12139952

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Chronic bronchiolitis with associated eosinophilic lung disease (eosinophilic bronchiolitis). Author(s): Takayanagi N, Kanazawa M, Kawabata Y, Colby TV. Source: Respiration; International Review of Thoracic Diseases. 2001; 68(3): 319-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11416256

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Circumstances of bronchiolitis obliterans development after lung transplantation: analysis of risk factors. Author(s): Pereszlenyi A Jr, Harustiak S, Klepetko W. Source: Bratisl Lek Listy. 2000; 101(12): 633-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11723655

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Classification of bronchiolitis obliterans syndrome-taxonomic realism or skepticism. Author(s): McGiffin DC. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 September; 21(9): 941-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12231364

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Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant. Author(s): Kreiss K, Gomaa A, Kullman G, Fedan K, Simoes EJ, Enright PL. Source: The New England Journal of Medicine. 2002 August 1; 347(5): 330-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12151470

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Clinical effectiveness of an integrated care pathway for infants with bronchiolitis. Author(s): Peter S, Fazakerley M. Source: Paediatric Nursing. 2004 February; 16(1): 30-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15000038

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Clinical similarities and differences between human T-cell lymphotropic virus type 1-associated bronchiolitis and diffuse panbronchiolitis. Author(s): Kadota J, Mukae H, Fujii T, Seki M, Tomono K, Kohno S. Source: Chest. 2004 April; 125(4): 1239-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15078730

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Complications in infants hospitalized for bronchiolitis or respiratory syncytial virus pneumonia. Author(s): Willson DF, Landrigan CP, Horn SD, Smout RJ. Source: The Journal of Pediatrics. 2003 November; 143(5 Suppl): S142-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14615713

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Concomitant allorecognition of mismatched donor HLA class I- and class II-derived peptides in pediatric lung transplant recipients with bronchiolitis obliterans syndrome. Author(s): Lu KC, Jaramillo A, Mendeloff EN, Huddleston CB, Sweet SC, Patterson GA, Mohanakumar T. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 January; 22(1): 35-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12531411

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Constrictive bronchiolitis obliterans. Characterisation of fibrogenesis and lysyl oxidase expression patterns. Author(s): Streichenberger N, Peyrol S, Philit F, Loire R, Sommer P, Cordier JF. Source: Virchows Archiv : an International Journal of Pathology. 2001 July; 439(1): 78-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11499844

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Contribution of RSV to bronchiolitis and pneumonia-associated hospitalizations in English children, April 1995-March 1998. Author(s): Muller-Pebody B, Edmunds WJ, Zambon MC, Gay NJ, Crowcroft NS. Source: Epidemiology and Infection. 2002 August; 129(1): 99-106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12211603

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Critical role for CXCR3 chemokine biology in the pathogenesis of bronchiolitis obliterans syndrome. Author(s): Belperio JA, Keane MP, Burdick MD, Lynch JP 3rd, Xue YY, Li K, Ross DJ, Strieter RM. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 July 15; 169(2): 1037-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12097412

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Critical role for the chemokine MCP-1/CCR2 in the pathogenesis of bronchiolitis obliterans syndrome. Author(s): Belperio JA, Keane MP, Burdick MD, Lynch JP 3rd, Xue YY, Berlin A, Ross DJ, Kunkel SL, Charo IF, Strieter RM. Source: The Journal of Clinical Investigation. 2001 August; 108(4): 547-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11518728

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Current management of acute bronchiolitis in Switzerland. Author(s): Barben J, Hammer J. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2003 January 11; 133(1-2): 9-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12596090

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Current treatment for acute viral bronchiolitis in infants. Author(s): Martinon-Torres F. Source: Expert Opinion on Pharmacotherapy. 2003 August; 4(8): 1355-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12877643

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Cytokines in severe respiratory syncytial virus bronchiolitis. Author(s): Mobbs KJ, Smyth RL, O'Hea U, Ashby D, Ritson P, Hart CA. Source: Pediatric Pulmonology. 2002 June; 33(6): 449-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12001278

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Cytomegalovirus antibody status of donor/recipient does not influence the incidence of bronchiolitis obliterans syndrome in lung transplantation. Author(s): Luckraz H, Sharples L, McNeil K, Wreghitt T, Wallwork J. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 March; 22(3): 287-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12633696

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Decreased serum and bronchoalveolar lavage levels of Clara cell secretory protein (CC16) is associated with bronchiolitis obliterans syndrome and airway neutrophilia in lung transplant recipients. Author(s): Nord M, Schubert K, Cassel TN, Andersson O, Riise GC. Source: Transplantation. 2002 April 27; 73(8): 1264-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11981419

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Detection of bronchiolitis obliterans syndrome (BOS) in single lung transplant recipients. Author(s): Hadjiliadis D, Hutcheon MA. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 July; 22(7): 829-30; Author Reply 830-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873556

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Detection of obliterative bronchiolitis after lung transplantation by indexes of ventilation distribution. Author(s): Estenne M, Van Muylem A, Knoop C, Antoine M. Source: American Journal of Respiratory and Critical Care Medicine. 2000 September; 162(3 Pt 1): 1047-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10988128

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Development of an antibody specific to major histocompatibility antigens detectable by flow cytometry after lung transplant is associated with bronchiolitis obliterans syndrome. Author(s): Palmer SM, Davis RD, Hadjiliadis D, Hertz MI, Howell DN, Ward FE, Savik K, Reinsmoen NL. Source: Transplantation. 2002 September 27; 74(6): 799-804. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12364858

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Dexamethasone and bronchiolitis: a new look at an old therapy? Author(s): McBride JT. Source: The Journal of Pediatrics. 2002 January; 140(1): 8-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11815756

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Diagnosis and testing in bronchiolitis: a systematic review. Author(s): Bordley WC, Viswanathan M, King VJ, Sutton SF, Jackman AM, Sterling L, Lohr KN. Source: Archives of Pediatrics & Adolescent Medicine. 2004 February; 158(2): 119-26. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14757603

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Diagnosis of bronchiolitis obliterans in heart-lung transplantation patients: importance of bronchial dilatation on CT. Author(s): Lentz D, Bergin CJ, Berry GJ, Stoehr C, Theodore J. Source: Ajr. American Journal of Roentgenology. 1992 September; 159(3): 463-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1503006

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Differences in admission rates of children with bronchiolitis by pediatric and general emergency departments. Author(s): Johnson DW, Adair C, Brant R, Holmwood J, Mitchell I. Source: Pediatrics. 2002 October; 110(4): E49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12359822

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Differential detection of rhinoviruses and enteroviruses RNA sequences associated with classical immunofluorescence assay detection of respiratory virus antigens in nasopharyngeal swabs from infants with bronchiolitis. Author(s): Andreoletti L, Lesay M, Deschildre A, Lambert V, Dewilde A, Wattre P. Source: Journal of Medical Virology. 2000 July; 61(3): 341-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10861643

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Differential diagnosis of bronchiolitis obliterans organizing pneumonia. Author(s): Kitaichi M. Source: Chest. 1992 July; 102(1 Suppl): 44S-49S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1623810

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Differential role for T cells in the development of fibrotic lesions associated with reovirus 1/L-induced bronchiolitis obliterans organizing pneumonia versus Acute Respiratory Distress Syndrome. Author(s): Majeski EI, Harley RA, Bellum SC, London SD, London L. Source: American Journal of Respiratory Cell and Molecular Biology. 2003 February; 28(2): 208-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12540488

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Diffuse aspiration bronchiolitis due to achalasia. Author(s): Teramoto S, Yamamoto H, Yamaguchi Y, Tmoita T, Ouchi Y. Source: Chest. 2004 January; 125(1): 349-50; Author Reply 350. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718468

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Discharge criteria for bronchiolitis patients. Author(s): Weiss J, Annamalai VR. Source: Pediatrics. 2003 February; 111(2): 445; Author Reply 445. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12563079

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DNase treatment for atelectasis in infants with severe respiratory syncytial virus bronchiolitis. Author(s): Merkus PJ, de Hoog M, van Gent R, de Jongste JC. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2001 October; 18(4): 734-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11716180

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Do bronchodilators have an effect on bronchiolitis? Author(s): Schindler M. Source: Critical Care (London, England). 2002 April; 6(2): 111-2. Epub 2002 March 11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11983033

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Does histologic acute rejection in lung allografts predict the development of bronchiolitis obliterans? Author(s): Yousem SA, Dauber JA, Keenan R, Paradis IL, Zeevi A, Griffith BP. Source: Transplantation. 1991 August; 52(2): 306-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1871804

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Does nebulised adrenaline (epinephrine) reduce admission rate in bronchiolitis? Author(s): Meates M. Source: Archives of Disease in Childhood. 2002 December; 87(6): 548-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12456566

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Does nebulised adrenaline reduce admission rate in bronchiolitis? Author(s): Meates M. Source: Archives of Disease in Childhood. 2001 September; 85(3): 254-255. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12035815

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Does respiratory syncytial viral-induced bronchiolitis result from helper T cell type 1/type 2 cytokine imbalance? Author(s): Lemanske RF Jr. Source: American Journal of Respiratory and Critical Care Medicine. 2003 September 15; 168(6): 625-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12963579

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Duration of illness in ambulatory children diagnosed with bronchiolitis. Author(s): Swingler GH, Hussey GD, Zwarenstein M. Source: Archives of Pediatrics & Adolescent Medicine. 2000 October; 154(10): 997-1000. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11030851

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Early infections and bronchiolitis obliterans-organizing pneumonia in single lung transplant recipients. Author(s): Barberis M, Bauer D, Harari S, Belloni PA, Masini T, Baisi A. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1992 September-October; 11(5): 1012-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1420231

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Early ribavarin treatment of bronchiolitis: effect on long-term respiratory morbidity. Author(s): Clin Evid. 2002 Dec;(8):291-303 Source: Chest. 2002 September; 122(3): 935-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12603884

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Effect of interventions during acute respiratory syncytial virus bronchiolitis on subsequent long term respiratory morbidity. Author(s): Khoshoo V, Ross G, Edell D. Source: The Pediatric Infectious Disease Journal. 2002 May; 21(5): 468-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12150194

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Effect of RSV bronchiolitis practice guidelines on resource utilization. Author(s): Harrison AM, Boeing NM, Domachowske JB, Piedmonte MR, Kanter RK. Source: Clinical Pediatrics. 2001 September; 40(9): 489-95. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11583047

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Effect of salbutamol on oxygen saturation in bronchiolitis. Author(s): Ho L, Collis G, Landau LI, Le Souef PN. Source: Archives of Disease in Childhood. 1991 September; 66(9): 1061-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1929514

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Efficacy of nebulized budesonide in hospitalized infants and children younger than 24 months with bronchiolitis. Author(s): Chao LC, Lin YZ, Wu WF, Huang FY. Source: Acta Paediatr Taiwan. 2003 November-December; 44(6): 332-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14983653

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Efficacy of oral dexamethasone in outpatients with acute bronchiolitis. Author(s): Schuh S, Coates AL, Binnie R, Allin T, Goia C, Corey M, Dick PT. Source: The Journal of Pediatrics. 2002 January; 140(1): 27-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11815760

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Efficacy of recombinant human deoxyribonuclease I in the hospital management of respiratory syncytial virus bronchiolitis. Author(s): Nasr SZ, Strouse PJ, Soskolne E, Maxvold NJ, Garver KA, Rubin BK, Moler FW. Source: Chest. 2001 July; 120(1): 203-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11451839

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Encephalopathy associated with respiratory syncytial virus bronchiolitis. Author(s): Ng YT, Cox C, Atkins J, Butler IJ. Source: Journal of Child Neurology. 2001 February; 16(2): 105-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11292214

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Enhanced IL-4 responses in children with a history of respiratory syncytial virus bronchiolitis in infancy. Author(s): Pala P, Bjarnason R, Sigurbergsson F, Metcalfe C, Sigurs N, Openshaw PJ. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 August; 20(2): 376-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12212970

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Eosinophil cationic protein in infants with respiratory syncytial virus bronchiolitis: predictive value for subsequent development of persistent wheezing. Author(s): Pifferi M, Ragazzo V, Caramella D, Baldini G. Source: Pediatric Pulmonology. 2001 June; 31(6): 419-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11389573

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Epidemic of bronchiolitis in infants. Author(s): Doyle E, Britto J, Best C. Source: Bmj (Clinical Research Ed.). 1992 March 7; 304(6827): 638. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1559099

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Epidemic of bronchiolitis in infants. Author(s): Gibbs T, Harper JR. Source: Bmj (Clinical Research Ed.). 1992 February 15; 304(6824): 444. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1547398

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Epidemiology and aetiology of acute bronchiolitis in Hong Kong infants. Author(s): Sung RY, Chan RC, Tam JS, Cheng AF, Murray HG. Source: Epidemiology and Infection. 1992 February; 108(1): 147-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1312477

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Epidemiology of respiratory syncytial virus bronchiolitis in hospitalized infants in Greece. Author(s): Tsolia MN, Kafetzis D, Danelatou K, Astral H, Kallergi K, Spyridis P, Karpathios TE. Source: European Journal of Epidemiology. 2003; 18(1): 55-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12705624

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Epinephrine is efficacious for outpatient treatment of bronchiolitis. Author(s): Saseen JJ. Source: The Journal of Family Practice. 2004 March; 53(3): 175-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15000916

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Erythromycin reduces neutrophils and neutrophil-derived elastolytic-like activity in the lower respiratory tract of bronchiolitis patients. Author(s): Ichikawa Y, Ninomiya H, Koga H, Tanaka M, Kinoshita M, Tokunaga N, Yano T, Oizumi K. Source: Am Rev Respir Dis. 1992 July; 146(1): 196-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1626803

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Erythropoietin therapy in children with bronchiolitis and anemia. Author(s): Jacobs BR, Lyons K, Brilli RJ. Source: Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2003 January; 4(1): 44-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12656541

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Estimation of the dose of fluticasone propionate inhaled by infants after bronchiolitis: Effect on urinary cortisol excretion. Author(s): Wong J, Davies T, O'Callaghan C. Source: The Journal of Allergy and Clinical Immunology. 2002 November; 110(5): 721-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12417880

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Evaluation of hospitalized infants and young children with bronchiolitis - a multi centre study. Author(s): Kabir ML, Haq N, Hoque M, Ahmed F, Amin R, Hossain A, Khatoon S, Akhter S, Shilpi T, Haq R, Anisuzzaman S, Khan MH, Ahamed S, Khashru A. Source: Mymensingh Med J. 2003 July; 12(2): 128-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12894048

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Factors related to the relapse of bronchiolitis obliterans organizing pneumonia. Author(s): Watanabe K, Senju S, Wen FQ, Shirakusa T, Maeda F, Yoshida M. Source: Chest. 1998 December; 114(6): 1599-606. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9872195

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Failure of oxygen saturation and clinical assessment to predict which patients with bronchiolitis discharged from the emergency department will return requiring admission. Author(s): Roback MG, Baskin MN. Source: Pediatric Emergency Care. 1997 February; 13(1): 9-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9061726

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Failure of thalidomide to control bronchiolitis obliterans post bone marrow transplant. Author(s): Heaton DC. Source: Bone Marrow Transplantation. 1989 September; 4(5): 598. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2790340

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Fatal bronchiolitis obliterans in a patient with juvenile rheumatoid arthritis receiving chrysotherapy. Author(s): Pegg SJ, Lang BA, Mikhail EL, Hughes DM. Source: The Journal of Rheumatology. 1994 March; 21(3): 549-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8006901

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Fatal cytomegalovirus bronchiolitis in a patient with Nezelof's syndrome. Author(s): Tanner DD, Buckley PJ, Hong R, Shearer WT. Source: Pediatrics. 1980 January; 65(1): 98-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6243769

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Fatal pneumothorax complicating BAL in a bone marrow transplant recipient with bronchiolitis obliterans. Author(s): Cazzadori A, Di Perri G, Bonora S, Lanzafame M, Allegranzi B, Concia E. Source: Chest. 1997 May; 111(5): 1468-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9149624

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Feeding efficiency and respiratory integration in infants with acute viral bronchiolitis. Author(s): Pinnington LL, Smith CM, Ellis RE, Morton RE. Source: The Journal of Pediatrics. 2000 October; 137(4): 523-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11035832

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Filgrastim treatment of acute myelogenous leukemia (M7) relapse after allogeneic peripheral stem cell transplantation resulting in both graft-versus-leukemia effect with cytogenetic remission and chronic graft-versus-host disease manifesting as polyserositis and subsequent bronchiolitis obliterans with organizing pneumonia. Author(s): Law L, Tuscano J, Wun T, Ahlberg K, Richman C. Source: International Journal of Hematology. 2002 November; 76(4): 360-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12463601

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FK 506 'rescue' immunosuppression for obliterative bronchiolitis after lung transplantation. Author(s): Ross DJ, Lewis MI, Kramer M, Vo A, Kass RM. Source: Chest. 1997 November 5; 112(5): 1175-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9367453

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Follicular bronchiolitis (FBB) associated with Legionella pneumophilia infection. Author(s): Masuda T, Ishikawa Y, Akasaka Y, Ishii T, Tateda K, Ishii Y, Yamaguchi K, Kiguchi H. Source: Pediatric Pathology & Molecular Medicine. 2002 November-December; 21(6): 517-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12537768

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Follicular bronchiolitis associated with Legionella pneumophilia infection. Author(s): Masuda T, Ishikawa Y, Akasaka Y, Ishii T, Tateda K, Ishii Y, Yamaguchi K, Kiguchi H. Source: Pediatric Pathology & Molecular Medicine. 2002 January-February; 21(1): 41-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11842978

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Follicular bronchiolitis associated with rheumatoid arthritis. Author(s): Kinoshita M, Higashi T, Tanaka C, Tokunaga N, Ichikawa Y, Oizumi K. Source: Intern Med. 1992 May; 31(5): 674-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1504435

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Follicular bronchiolitis: clinical and pathologic findings in six patients. Author(s): Romero S, Barroso E, Gil J, Aranda I, Alonso S, Garcia-Pachon E. Source: Lung. 2003 November-December; 181(6): 309-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749935

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Follicular bronchiolitis: thin-section CT and histologic findings. Author(s): Howling SJ, Hansell DM, Wells AU, Nicholson AG, Flint JD, Muller NL. Source: Radiology. 1999 September; 212(3): 637-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10478225

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Follicular bronchitis/bronchiolitis. Author(s): Yousem SA, Colby TV, Carrington CB. Source: Human Pathology. 1985 July; 16(7): 700-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4007845

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Follow-up of children with respiratory syncytial virus bronchiolitis in 1986 and 1987: potential effect of ribavirin on long term pulmonary function. The Bronchiolitis Study Group. Author(s): Krilov LR, Mandel FS, Barone SR, Fagin JC. Source: The Pediatric Infectious Disease Journal. 1997 March; 16(3): 273-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9076814

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Four cases of bronchiolitis obliterans organizing pneumonia associated with thyroid disease. Author(s): Watanabe K, Senju S, Maeda F, Yshida M. Source: Respiration; International Review of Thoracic Diseases. 2000; 67(5): 572-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11070466

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Free-base cocaine use associated with bronchiolitis obliterans organizing pneumonia. Author(s): Patel RC, Dutta D, Schonfeld SA. Source: Annals of Internal Medicine. 1987 August; 107(2): 186-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3605899

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Fulminant respiratory failure and death in a patient with idiopathic bronchiolitis obliterans. Author(s): Iannuzzi MC, Farhi DC, Bostrom PD, Petty TL, Fisher JH. Source: Archives of Internal Medicine. 1985 April; 145(4): 733-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3985736

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Further studies on the natural history of obliterative bronchiolitis following heartlung transplantation. Author(s): Scott JP, Sharples L, Mullins P, Aravot DJ, Stewart S, Otulana BA, Higenbottam TW, Wallwork J. Source: Transplantation Proceedings. 1991 February; 23(1 Pt 2): 1201-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1989185

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Gastro-esophageal reflux as cause of obliterative bronchiolitis: a case report. Author(s): Rinaldi M, Martinelli L, Volpato G, Pederzolli C, Silvestri M, Pederzolli N, Arbustini E, Vigano M. Source: Transplantation Proceedings. 1995 June; 27(3): 2006-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7792868

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Gene expression of profibrotic mediators in bronchiolitis obliterans syndrome after lung transplantation. Author(s): Bergmann M, Tiroke A, Schafer H, Barth J, Haverich A. Source: Scandinavian Cardiovascular Journal : Scj. 1998; 32(2): 97-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9636965

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General case of the day. Bronchiolitis obliterans with organizing pneumonia. Author(s): Snyder BJ, Abbott GF, Tung GA. Source: Radiographics : a Review Publication of the Radiological Society of North America, Inc. 1996 March; 16(2): 456-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8966304

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Graft vessel disease and obliterative bronchiolitis after heart/lung transplantation in children. Author(s): Radley-Smith RC, Burke M, Pomerance A, Yacoub MH. Source: Transplantation Proceedings. 1995 June; 27(3): 2017-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7792871

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Granulomatous bronchiolitis associated with Crohn's disease. Author(s): Vandenplas O, Casel S, Delos M, Trigaux JP, Melange M, Marchand E. Source: American Journal of Respiratory and Critical Care Medicine. 1998 November; 158(5 Pt 1): 1676-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9817724

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Guidelines on pediatric bronchiolitis length of stay and actual practice don't match, study says. Author(s): Levenson D. Source: Rep Med Guidel Outcomes Res. 2002 February 22; 13(4): 9-10, 12. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12434777

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Haplotype mapping of the bronchiolitis susceptibility locus near IL8. Author(s): Hull J, Rowlands K, Lockhart E, Sharland M, Moore C, Hanchard N, Kwiatkowski DP. Source: Human Genetics. 2004 February; 114(3): 272-9. Epub 2003 November 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605870

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Harmful effects of aerosolised bronchodilator therapy in bronchiolitis. Author(s): Nagabhushana S. Source: Indian Pediatrics. 2000 June; 37(6): 684-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10869163

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Harmful effects of aerosolized bronchodilator therapy in bronchiolitis. Author(s): Bharti S, Bharti B, Goraya JS, Poddar B, Parmar VR. Source: Indian Pediatrics. 1999 October; 36(10): 1052-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10745319

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Heliox therapy in infants with acute bronchiolitis. Author(s): Martinon-Torres F, Rodriguez-Nunez A, Martinon-Sanchez JM. Source: Pediatrics. 2002 January; 109(1): 68-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11773543

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Helium-oxygen improves Clinical Asthma Scores in children with acute bronchiolitis. Author(s): Hollman G, Shen G, Zeng L, Yngsdal-Krenz R, Perloff W, Zimmerman J, Strauss R. Source: Critical Care Medicine. 1998 October; 26(10): 1731-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9781732

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Helium-oxygen mixture does not improve gas exchange in mechanically ventilated children with bronchiolitis. Author(s): Gross MF, Spear RM, Peterson BM. Source: Critical Care (London, England). 2000; 4(3): 188-92. Epub 2000 April 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11056751

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Heterogeneity of bronchiolitis obliterans organizing pneumonia. Author(s): Epler GR. Source: Current Opinion in Pulmonary Medicine. 1998 March; 4(2): 93-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9612671

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Hidden Markov models for the onset and progression of bronchiolitis obliterans syndrome in lung transplant recipients. Author(s): Jackson CH, Sharples LD. Source: Statistics in Medicine. 2002 January 15; 21(1): 113-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11782054

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High altitude as an explanation for bronchiolitis-associated hospitalizations. Author(s): D'Angio CT. Source: The Pediatric Infectious Disease Journal. 2000 May; 19(5): 492. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10819360

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High rate of indigenous bronchiolitis and palivuzumab. Author(s): Whitehall JS, Bolisetty S, Whitehall JP, Francis F, Norton R, Patole SK. Source: Journal of Paediatrics and Child Health. 2001 August; 37(4): 416-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11547779

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High rates of hospitalisation for bronchiolitis in Inuit children on Baffin Island. Author(s): Banerji A. Source: Int J Circumpolar Health. 2001 August; 60(3): 375-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11590877

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High-frequency oscillatory ventilation in RSV bronchiolitis patients. Author(s): Duval EL, Leroy PL, Gemke RJ, van Vught AJ. Source: Respiratory Medicine. 1999 June; 93(6): 435-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10464828

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High-resolution computed tomographic features of bronchiolitis obliterans organizing pneumonia. Author(s): Nishimura K, Itoh H. Source: Chest. 1992 July; 102(1 Suppl): 26S-31S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1623807

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High-resolution computed tomography in pediatric patients with postinfectious bronchiolitis obliterans. Author(s): Zhang L, Irion K, da Silva Porto N, Abreu e Silva F. Source: Journal of Thoracic Imaging. 1999 April; 14(2): 85-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10210478

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High-resolution computed tomography of bronchiolitis obliterans syndrome after bone marrow transplantation. Author(s): Ooi GC, Peh WC, Ip M. Source: Respiration; International Review of Thoracic Diseases. 1998; 65(3): 187-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9670299

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High-resolution CT features of severe asthma and bronchiolitis obliterans. Author(s): Jensen SP, Lynch DA, Brown KK, Wenzel SE, Newell JD. Source: Clinical Radiology. 2002 December; 57(12): 1078-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12475532

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Histology of childhood bronchiolitis obliterans. Author(s): Mauad T, Dolhnikoff M; Sao Paulo Bronchiolitis Obliterans Study Group. Source: Pediatric Pulmonology. 2002 June; 33(6): 466-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12001281

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HRCT of obliterative bronchiolitis and other small airways diseases. Author(s): Hansell DM. Source: Semin Roentgenol. 2001 January; 36(1): 51-65. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11204759

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Human leukocyte antigen mismatches predispose to the severity of bronchiolitis obliterans syndrome after lung transplantation. Author(s): Chalermskulrat W, Neuringer IP, Schmitz JL, Catellier DJ, Gurka MJ, Randell SH, Aris RM. Source: Chest. 2003 June; 123(6): 1825-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12796156

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Human metapneumovirus in severe respiratory syncytial virus bronchiolitis. Author(s): Greensill J, McNamara PS, Dove W, Flanagan B, Smyth RL, Hart CA. Source: Emerging Infectious Diseases. 2003 March; 9(3): 372-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12643835

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Idiopathic bronchiolitis mimicking diffuse panbronchiolitis. Author(s): Poletti V, Chilosi M, Trisolini R, Cancellieri A, Zompatori M, Agli LL, Boaron M, Schulte W, Theegarten D, Guzman J, Costabel U. Source: Sarcoidosis Vasc Diffuse Lung Dis. 2003 March; 20(1): 62-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12737282

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IL-16 in the airways of lung allograft recipients with acute rejection or obliterative bronchiolitis. Author(s): Laan M, Linden A, Riise GC. Source: Clinical and Experimental Immunology. 2003 August; 133(2): 290-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869037

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Illness severity, viral shedding, and antibody responses in infants hospitalized with bronchiolitis caused by respiratory syncytial virus. Author(s): Wright PF, Gruber WC, Peters M, Reed G, Zhu Y, Robinson F, ColemanDockery S, Graham BS. Source: The Journal of Infectious Diseases. 2002 April 15; 185(8): 1011-8. Epub 2002 Apr 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11930309

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Immunological mechanisms of severe respiratory syncytial virus bronchiolitis. Author(s): Bont L, Kimpen JL. Source: Intensive Care Medicine. 2002 May; 28(5): 616-21. Epub 2002 March 26. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12029411

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Impact of a bronchiolitis guideline: a multisite demonstration project. Author(s): Kotagal UR, Robbins JM, Kini NM, Schoettker PJ, Atherton HD, Kirschbaum MS. Source: Chest. 2002 June; 121(6): 1789-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12065340

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Incidence of hyponatraemia and hyponatraemic seizures in severe respiratory syncytial virus bronchiolitis. Author(s): Hanna S, Tibby SM, Durward A, Murdoch IA. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 April; 92(4): 430-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12801108

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Increased exhaled nitric oxide in bronchiolitis obliterans organizing pneumonia after allogeneic bone marrow transplantation. Author(s): Kanamori H, Fujisawa S, Tsuburai T, Yamaji S, Tomita N, Fujimaki K, Miyashita A, Suzuki S, Ishigatsubo Y. Source: Transplantation. 2002 November 15; 74(9): 1356-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12451281

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Increased macrophage inflammatory protein-1alpha and -1beta in BAL fluid of bronchiolitis obliterans organizing pneumonia. Author(s): Asano T, Ogushi F, Tani K, Tamiya H, Nishioka Y, Sone S. Source: Respirology (Carlton, Vic.). 2003 December; 8(4): 461-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14629649

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Increased Toll-like receptor 4 expression in infants with respiratory syncytial virus bronchiolitis. Author(s): Gagro A, Tominac M, Krsulovic-Hresic V, Bace A, Matic M, Drazenovic V, Mlinaric-Galinovic G, Kosor E, Gotovac K, Bolanca I, Batinica S, Rabatic S. Source: Clinical and Experimental Immunology. 2004 February; 135(2): 267-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738455

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Increasing incidence of hospitalization for bronchiolitis among Canadian children, 1980-2000. Author(s): Langley JM, LeBlanc JC, Smith B, Wang EE. Source: The Journal of Infectious Diseases. 2003 December 1; 188(11): 1764-7. Epub 2003 November 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639549

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Indirect allorecognition of mismatched donor HLA class II peptides in lung transplant recipients with bronchiolitis obliterans syndrome. Author(s): Reznik SI, Jaramillo A, SivaSai KS, Womer KL, Sayegh MH, Trulock EP, Patterson GA, Mohanakumar T. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2001 September; 1(3): 228-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12102256

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Infectious etiology of bronchiolitis obliterans: the respiratory viruses connection myth or reality? Author(s): Vilchez RA, Dauber J, Kusne S. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2003 March; 3(3): 245-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12614277

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Influence of promoter variants of interleukin-10, interleukin-9, and tumor necrosis factor-alpha genes on respiratory syncytial virus bronchiolitis. Author(s): Hoebee B, Bont L, Rietveld E, van Oosten M, Hodemaekers HM, Nagelkerke NJ, Neijens HJ, Kimpen JL, Kimman TG. Source: The Journal of Infectious Diseases. 2004 January 15; 189(2): 239-47. Epub 2004 Jan 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14722888

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Interleukin 9 production in the lungs of infants with severe respiratory syncytial virus bronchiolitis. Author(s): McNamara PS, Flanagan BF, Baldwin LM, Newland P, Hart CA, Smyth RL. Source: Lancet. 2004 March 27; 363(9414): 1031-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15051283

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Interleukin-1 receptor antagonist as a biomarker for bronchiolitis obliterans syndrome in lung transplant recipients. Author(s): Belperio JA, DiGiovine B, Keane MP, Burdick MD, Ying Xue Y, Ross DJ, Lynch JP 3rd, Kunkel SL, Strieter RM. Source: Transplantation. 2002 February 27; 73(4): 591-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11889437

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Interleukin-17 stimulates release of interleukin-8 by human airway smooth muscle cells in vitro: a potential role for interleukin-17 and airway smooth muscle cells in bronchiolitis obliterans syndrome. Author(s): Vanaudenaerde BM, Wuyts WA, Dupont LJ, Van Raemdonck DE, Demedts MM, Verleden GM. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 November; 22(11): 1280-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14585390

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Interleukin-6 and interferon-gamma gene polymorphisms in the development of bronchiolitis obliterans syndrome after lung transplantation. Author(s): Lu KC, Jaramillo A, Lecha RL, Schuessler RB, Aloush A, Trulock EP, Mendeloff EN, Huddleston CB, Alexander Patterson G, Mohanakumar T. Source: Transplantation. 2002 November 15; 74(9): 1297-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12451269

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Is epinephrine efficacious in the treatment of bronchiolitis? Author(s): King TM, Alperovitz-Bichell K, Rowe PC, Lehmann HP. Source: Archives of Pediatrics & Adolescent Medicine. 2003 October; 157(10): 965-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14557156

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Is transplant operation important in determining posttransplant risk of bronchiolitis obliterans syndrome in lung transplant recipients? Author(s): Hadjiliadis D, Davis RD, Palmer SM. Source: Chest. 2002 October; 122(4): 1168-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12377838

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Ischemia-reperfusion injury after lung transplantation increases risk of late bronchiolitis obliterans syndrome. Author(s): Fiser SM, Tribble CG, Long SM, Kaza AK, Kern JA, Jones DR, Robbins MK, Kron IL. Source: The Annals of Thoracic Surgery. 2002 April; 73(4): 1041-7; Discussion 1047-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11996238

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Leucocyte populations in respiratory syncytial virus-induced bronchiolitis. Author(s): Smith PK, Wang SZ, Dowling KD, Forsyth KD. Source: Journal of Paediatrics and Child Health. 2001 April; 37(2): 146-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11328469

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Levitating lung lesions due to bronchiolitis obliterans organizing pneumonia. Author(s): Reich J, Scott D. Source: Chest. 1993 February; 103(2): 623-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8432169

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Linear opacities on HRCT in bronchiolitis obliterans organising pneumonia. Author(s): Murphy JM, Schnyder P, Verschakelen J, Leuenberger P, Flower CD. Source: European Radiology. 1999; 9(9): 1813-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10602956

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Links between respiratory syncytial virus bronchiolitis and childhood asthma: clinical and research approaches. Author(s): Openshaw PJ, Dean GS, Culley FJ. Source: The Pediatric Infectious Disease Journal. 2003 February; 22(2 Suppl): S58-64; Discussion S64-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12671454

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Living-donor lobar lung transplantation for bronchiolitis obliterans after StevensJohnson syndrome. Author(s): Date H, Sano Y, Aoe M, Goto K, Tedoriya T, Sano S, Andou A, Shimizu N. Source: The Journal of Thoracic and Cardiovascular Surgery. 2002 February; 123(2): 38991. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11828317

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Long and short-term effect of prednisolone in hospitalized infants with acute bronchiolitis. Author(s): Zhang L, Ferruzzi E, Bonfanti T, Auler MI, D'avila NE, Faria CS, Costa MM. Source: Journal of Paediatrics and Child Health. 2003 September-October; 39(7): 548-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969212

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Long-term course of bronchiectasis and bronchiolitis obliterans as late complication of smoke inhalation. Author(s): Tasaka S, Kanazawa M, Mori M, Fujishima S, Ishizaka A, Yamasawa F, Kawashiro T. Source: Respiration; International Review of Thoracic Diseases. 1995; 62(1): 40-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7716354

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Long-term effects of prednisolone in the acute phase of bronchiolitis caused by respiratory syncytial virus. Author(s): van Woensel JB, Kimpen JL, Sprikkelman AB, Ouwehand A, van Aalderen WM. Source: Pediatric Pulmonology. 2000 August; 30(2): 92-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10922130

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Long-term effects of respiratory syncytial virus (RSV) bronchiolitis in infants and young children: a quantitative review. Author(s): Kneyber MCJ, Steyerberg EW, de Groot R, Moll HA. Source: Acta Paediatrica (Oslo, Norway : 1992). 2000 June; 89(6): 654-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10914957

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Lucid and comprehensive review of the approach to acute bronchiolitis in Israel. Author(s): Paret G, Barzilay Z. Source: Isr Med Assoc J. 2000 April; 2(4): 334. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10804920

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Lung function, airway responsiveness, and respiratory symptoms before and after bronchiolitis. Author(s): Young S, O'Keeffe PT, Arnott J, Landau LI. Source: Archives of Disease in Childhood. 1995 January; 72(1): 16-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7717730

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Lung retransplantation for bronchiolitis obliterans syndrome: long-term follow-up in a series of 15 recipients. Author(s): Brugiere O, Thabut G, Castier Y, Mal H, Dauriat G, Marceau A, Leseche G. Source: Chest. 2003 June; 123(6): 1832-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12796157

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Lung transplant rejection: obliterative bronchiolitis. Author(s): Spector NM, Connolly MA, Garrity ER Jr. Source: American Journal of Critical Care : an Official Publication, American Association of Critical-Care Nurses. 1996 September; 5(5): 366-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8870860

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Lung transplantation and bronchiolitis obliterans syndrome: are two lungs better than one? Author(s): Levine SM. Source: Chest. 2002 October; 122(4): 1112-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12377826

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Lung transplantation and bronchiolitis obliterans: an evolution in understanding. Author(s): McKane BW, Trulock EP, Patterson GA, Mohanakumar T. Source: Immunologic Research. 2001; 24(2): 177-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11594455

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Lung transplantation for patients with end-stage Sauropus androgynus-induced bronchiolitis obliterans (SABO) syndrome. Author(s): Luh SP, Lee YC, Chang YL, Wu HD, Kuo SH, Chu SH. Source: Clinical Transplantation. 1999 December; 13(6): 496-503. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10617240

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Lung transplantation in bronchiolitis obliterans associated with vegetable consumption. Author(s): Lai RS, Wang JS, Wu MT, Hsu HK. Source: Lancet. 1998 July 11; 352(9122): 117-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9672286

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Lung transplantation. Bronchiolitis obliterans syndrome. Author(s): Corris PA. Source: Chest Surg Clin N Am. 2003 August; 13(3): 543-57. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13678312

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Lymphocytic bronchitis/bronchiolitis in a patient with primary biliary cirrhosis. Author(s): Chatte G, Streichenberger N, Boillot O, Gille D, Loire R, Cordier JF. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1995 January; 8(1): 176-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7744186

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Lymphocytic bronchitis/bronchiolitis in lung allograft recipients. Author(s): Yousem SA. Source: The American Journal of Surgical Pathology. 1993 May; 17(5): 491-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8470763

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Macrophage inflammatory protein-1alpha (not T helper type 2 cytokines) is associated with severe forms of respiratory syncytial virus bronchiolitis. Author(s): Garofalo RP, Patti J, Hintz KA, Hill V, Ogra PL, Welliver RC. Source: The Journal of Infectious Diseases. 2001 August 15; 184(4): 393-9. Epub 2001 July 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11471095

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Maintenance azithromycin therapy for bronchiolitis obliterans syndrome: results of a pilot study. Author(s): Gerhardt SG, McDyer JF, Girgis RE, Conte JV, Yang SC, Orens JB. Source: American Journal of Respiratory and Critical Care Medicine. 2003 July 1; 168(1): 121-5. Epub 2003 April 02. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12672648

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Malaria infection does not appear to modify the risk of bronchiolitis early in life. Author(s): Menendez C, Sunyer J, Ventura PJ, Aponte JJ, Acosta CJ, Schellenberg D, Kahigwa E, Anto JM, Alonso PL. Source: The Pediatric Infectious Disease Journal. 2002 March; 21(3): 249-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12005090

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Management and prevention strategies for respiratory syncytial virus (RSV) bronchiolitis in infants and young children: a review of evidence-based practice interventions. Author(s): Cooper AC, Banasiak NC, Allen PJ. Source: Pediatric Nursing. 2003 November-December; 29(6): 452-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14743842

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Management of bronchiolitis: current practices in Ireland. Author(s): Cahill P, Finan E, Loftus BG. Source: Ir Med J. 2002 June; 95(6): 167-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12171262

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Management of severe bronchiolitis: indications for ventilator support. Author(s): Gavin R, Anderson B, Percival T. Source: N Z Med J. 1996 April 26; 109(1020): 137-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8649668

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Managing bronchiolitis and respiratory syncytial virus: finding the yellow brick road. Author(s): Hall CB. Source: Archives of Pediatrics & Adolescent Medicine. 2004 February; 158(2): 111-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14757601

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Mast cells in bronchiolitis obliterans organizing pneumonia. Mast cell hyperplasia and evidence for extracellular release of tryptase. Author(s): Pesci A, Majori M, Piccoli ML, Casalini A, Curti A, Franchini D, Gabrielli M. Source: Chest. 1996 August; 110(2): 383-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8697838

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Measurement of fibroblast proliferative activity in bronchoalveolar lavage fluid in the analysis of obliterative bronchiolitis among lung transplant recipients. Author(s): Jonosono M, Fang KC, Keith FM, Turck CW, Blanc PD, Hall TS, Fukano AK, Rifkin CJ, Gold WM, Webb WR, Edinburgh KJ, Finkbeiner WE, Golden JA. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1999 October; 18(10): 972-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10561108

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Meningococcal disease presenting as bronchiolitis. Author(s): Hameed R, Riordan FA. Source: The Journal of Infection. 2002 February; 44(2): 94-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12076069

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Methotrexate can halt the progression of bronchiolitis obliterans syndrome in lung transplant recipients. Author(s): Dusmet M, Maurer J, Winton T, Kesten S. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1996 September; 15(9): 948-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8889991

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Migratory bronchiolitis obliterans organizing pneumonia after unilateral radiation therapy for breast carcinoma. Author(s): Crestani B, Kambouchner M, Soler P, Crequit J, Brauner M, Battesti JP, Valeyre D. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1995 February; 8(2): 318-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7758569

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Misuse of antimicrobials in children with asthma and bronchiolitis: a review. Author(s): Henderson M, Rubin E. Source: The Pediatric Infectious Disease Journal. 2001 February; 20(2): 214-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11224845

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Monocyte IL-10 production during respiratory syncytial virus bronchiolitis is associated with recurrent wheezing in a one-year follow-up study. Author(s): Bont L, Heijnen CJ, Kavelaars A, van Aalderen WM, Brus F, Draaisma JT, Geelen SM, Kimpen JL. Source: American Journal of Respiratory and Critical Care Medicine. 2000 May; 161(5): 1518-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10806148

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Monocyte interleukin-12 production is inversely related to duration of respiratory failure in respiratory syncytial virus bronchiolitis. Author(s): Bont L, Kavelaars A, Heijnen CJ, van Vught AJ, Kimpen JL. Source: The Journal of Infectious Diseases. 2000 May; 181(5): 1772-5. Epub 2000 May 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10823782

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Montelukast for respiratory syncytial virus bronchiolitis: significant effect or provocative findings? Author(s): Szefler SJ, Simoes EA. Source: American Journal of Respiratory and Critical Care Medicine. 2003 February 1; 167(3): 290-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12554617

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Montelukast in RSV-bronchiolitis. Author(s): Bisgaard H. Source: American Journal of Respiratory and Critical Care Medicine. 2004 February 15; 169(4): 542-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14766663

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More about heliox and bronchiolitis. Author(s): Ganeshananthan M. Source: Pediatrics. 2002 July; 110(1 Pt 1): 198-9; Author Reply 198-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12093979

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Morphologic changes leading to bronchiolitis obliterans in a patient with delayed non-infectious lung disease after allogeneic bone marrow transplantation. Author(s): Trisolini R, Bandini G, Stanzani M, Chilosi M, Cancellieri A, Boaron M, Poletti V. Source: Bone Marrow Transplantation. 2001 December; 28(12): 1167-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11803362

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71

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Mycoplasma pneumoniae-associated bronchiolitis causing severe restrictive lung disease in adults: report of three cases and literature review. Author(s): Chan ED, Kalayanamit T, Lynch DA, Tuder R, Arndt P, Winn R, Schwarz MI. Source: Chest. 1999 April; 115(4): 1188-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10208228

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Nasogastric rehydration does have a role in acute paediatric bronchiolitis. Author(s): Sammartino L, James D, Goutzamanis J, Lines D. Source: Journal of Paediatrics and Child Health. 2002 June; 38(3): 321-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12047708

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Nebulised racemic adrenaline in the treatment of acute bronchiolitis in infants and toddlers. Author(s): Kristjansson S, Lodrup Carlsen KC, Wennergren G, Strannegard IL, Carlsen KH. Source: Archives of Disease in Childhood. 1993 December; 69(6): 650-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8285776

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Nebulized 3% hypertonic saline solution treatment in ambulatory children with viral bronchiolitis decreases symptoms. Author(s): Sarrell EM, Tal G, Witzling M, Someck E, Houri S, Cohen HA, Mandelberg A. Source: Chest. 2002 December; 122(6): 2015-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12475841

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Nebulized 3% hypertonic saline solution treatment in hospitalized infants with viral bronchiolitis. Author(s): Mandelberg A, Tal G, Witzling M, Someck E, Houri S, Balin A, Priel IE. Source: Chest. 2003 February; 123(2): 481-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12576370

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Nebulized salbutamol versus racemic epinephrine in the treatment of infants with bronchiolitis. Author(s): Carter ER, Moffitt DR. Source: The Journal of Pediatrics. 1993 September; 123(3): 491-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8355133

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Neuroendocrine cell hyperplasia and obliterative bronchiolitis in patients with peripheral carcinoid tumors. Author(s): Miller RR, Muller NL. Source: The American Journal of Surgical Pathology. 1995 June; 19(6): 653-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7755151

72

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Neutrophil elastase and obliterative bronchiolitis. Author(s): Scott JP, Holt DW, Wallwork J. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1994; 7 Suppl 1: S402-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11271264

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Neutrophil survival is prolonged in the airways of healthy infants and infants with RSV bronchiolitis. Author(s): Jones A, Qui JM, Bataki E, Elphick H, Ritson S, Evans GS, Everard ML. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 September; 20(3): 651-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12358343

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New approaches to respiratory infections in children. Bronchiolitis and croup. Author(s): Wright RB, Pomerantz WJ, Luria JW. Source: Emergency Medicine Clinics of North America. 2002 February; 20(1): 93-114. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11826639

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No effect of cromoglycate treatment in hospitalized infants with respiratory syncytial virus bronchiolitis. Author(s): Troe JW, Versteegh FG, Mooi-Kokenberg EA, Van den Broeck J. Source: Pediatric Pulmonology. 2003 November; 36(5): 455. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520733

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No effect of cromoglycate treatment in hospitalized infants with respiratory syncytial virus bronchiolitis. Author(s): Troe JW, Versteegh FG, Mooi-Kokenberg EA, Van den Broeck J. Source: Pediatric Pulmonology. 2003 August; 36(2): 170. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12833498

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No objective benefit from steroids inhaled via a spacer in infants recovering from bronchiolitis. Author(s): Wong JY, Moon S, Beardsmore C, O'Callaghan C, Simpson H. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2000 February; 15(2): 388-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10706509

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Nomina sunt consequentia rerum: time for a change in the definition of bronchiolitis? Author(s): Barbi E, Neri E, Ventura A. Source: Archives of Pediatrics & Adolescent Medicine. 2004 April; 158(4): 403; Author Reply 403. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15066885

Studies

73

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Non-fatal bronchiolitis obliterans possibly associated with tiopronin. A case report with long-term follow-up. Author(s): Demaziere A, Maugars Y, Chollet S, Prost A. Source: British Journal of Rheumatology. 1993 February; 32(2): 172-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8428237

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Non-immune acute graft injury after lung transplantation and the risk of subsequent bronchiolitis obliterans syndrome (BOS). Author(s): Fisher AJ, Wardle J, Dark JH, Corris PA. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 November; 21(11): 1206-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12431494

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Nonspecific refractoriness to adenylyl cyclase stimulation in alveolar macrophages from infants with recurrent bronchiolitis. Author(s): Galoppin L, de Blic J, Azevedo I, Scheinmann P, Vargaftig BB, Bachelet M. Source: The Journal of Allergy and Clinical Immunology. 1994 May; 93(5): 885-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8182232

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Obliterative bronchiolitis after lung transplantation. Author(s): Boehler A, Estenne M. Source: Current Opinion in Pulmonary Medicine. 2000 March; 6(2): 133-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10741773

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Obliterative bronchiolitis in juvenile chronic arthritis. Author(s): Porter DR, Stevenson RD, Sturrock RD. Source: The Journal of Rheumatology. 1992 March; 19(3): 476-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1578465

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Obliterative bronchiolitis: prevention. Author(s): Kallio EA, Koskinen PK, Tikkanen JM, Lemstrom KB. Source: Transplantation Proceedings. 2001 February-March; 33(1-2): 1617-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11267443

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Obliterative bronchiolitis: the Achilles heel of lung transplantation. Author(s): Thistlethwaite PA, Jamieson SW. Source: Transplantation. 1999 October 15; 68(7): 923-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10532527

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Bronchiolitis

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Obliterative bronchiolitis: varying presentations and clinicopathological correlation. Author(s): Markopoulo KD, Cool CD, Elliot TL, Lync DA, Newell JD Jr, Hale VA, Brown KK, Schwarz MI, Tuder RM. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 January; 19(1): 20-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11843321

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Observer variation in detecting the radiologic features associated with bronchiolitis. Author(s): Janower ML. Source: Investigative Radiology. 1991 October; 26(10): 917. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1960036

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Obstructive granulomatous bronchiolitis due to Mycobacterium avium complex in an immunocompetent man. Author(s): Grimes MM, Cole TJ, Fowler AA 3rd. Source: Respiration; International Review of Thoracic Diseases. 2001; 68(4): 411-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11464091

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Oligoclonal CD4(+) T cell expansions in lung transplant recipients with obliterative bronchiolitis. Author(s): Duncan SR, Leonard C, Theodore J, Lega M, Girgis RE, Rosen GD, Theofilopoulos AN. Source: American Journal of Respiratory and Critical Care Medicine. 2002 May 15; 165(10): 1439-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12016109

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On interleukin-8, neutrophil activation, and bronchiolitis obliterans syndrome in lung transplantation. Author(s): Riise GC. Source: Transplantation. 2000 July 27; 70(2): 265-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10933146

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Other option in bronchiolitis. Author(s): Anklecha MU. Source: Indian Pediatrics. 2002 February; 39(2): 212. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11867862

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Paraneoplastic pemphigus associated with Castleman's disease and asymptomatic bronchiolitis obliterans. Author(s): Fujimoto W, Kanehiro A, Kuwamoto-Hara K, Saitoh M, Nakakita T, Amagai M, Arata J, Iwatsuki K. Source: European Journal of Dermatology : Ejd. 2002 July-August; 12(4): 355-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12095881

Studies

75

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Paraneoplastic pemphigus with bronchiolitis obliterans in a child. Author(s): Mar WA, Glaesser R, Struble K, Stephens-Groff S, Bangert J, Hansen RC. Source: Pediatric Dermatology. 2003 May-June; 20(3): 238-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12787274

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Perfusion and ventilation isotope lung scans in constrictive bronchiolitis obliterans. A series of three cases. Author(s): Hasegawa Y, Imaizumi K, Sekido Y, Iinuma Y, Kawabe T, Hashimoto N, Shimokata K. Source: Respiration; International Review of Thoracic Diseases. 2002; 69(6): 550-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12457011

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Plasma endothelin-1 in infants and young children with acute bronchiolitis and viral pneumonia. Author(s): Samransamruajkit R, Moonviriyakit K, Vanapongtipagorn P, Prapphal N, Deerojanawong J, Poovorawan Y. Source: Asian Pac J Allergy Immunol. 2002 December; 20(4): 229-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12744623

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Pneumocystis carinii detection using nested-PCR in nasopharyngeal aspirates of immunocompetent infants with bronchiolitis. Author(s): Nevez G, Totet A, Pautard JC, Raccurt C. Source: The Journal of Eukaryotic Microbiology. 2001; Suppl: 122S-123S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11906020

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Postinfectious bronchiolitis obliterans in children: clinical and radiological profile and prognostic factors. Author(s): Yalcin E, Dogru D, Haliloglu M, Ozcelik U, Kiper N, Gocmen A. Source: Respiration; International Review of Thoracic Diseases. 2003 July-August; 70(4): 371-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14512672

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Post-Infectious Bronchiolitis Obliterans. Author(s): Jones MH, Pitrez PM, Stein RT. Source: Pediatr Pulmonol Suppl. 2004; 26: 64-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15029600

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Preliminary results of rescue therapy with tacrolimus and mycophenolate mofetil in lung transplanted patients with bronchiolitis obliterans. Author(s): Roman A, Bravo C, Monforte V, Reyes L, Canela M, Morell F. Source: Transplantation Proceedings. 2002 February; 34(1): 146-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11959227

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Presence of the new human metapneumovirus in French children with bronchiolitis. Author(s): Freymouth F, Vabret A, Legrand L, Eterradossi N, Lafay-Delaire F, Brouard J, Guillois B. Source: The Pediatric Infectious Disease Journal. 2003 January; 22(1): 92-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12553303

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Procalcitonin, interleukin-6, C-reactive protein and leukocyte counts in infants with bronchiolitis. Author(s): Resch B, Gusenleitner W, Muller W. Source: The Pediatric Infectious Disease Journal. 2003 May; 22(5): 475-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12792393

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Quantifying pulmonary hypertension in ventilated infants with bronchiolitis: a pilot study. Author(s): Fitzgerald D, Davis GM, Rohlicek C, Gottesman R. Source: Journal of Paediatrics and Child Health. 2001 February; 37(1): 64-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11168873

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Question from the clinician: racemic epinephrine for bronchiolitis. Author(s): Guill MF. Source: Pediatrics in Review / American Academy of Pediatrics. 2003 August; 24(8): 284. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12897269

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Quiz case 6. Bronchiolitis obliterans organizing pneumonia (BOOP). Author(s): Edinburgh KJ, Levin DL, Hatabu H. Source: European Journal of Radiology. 1999 April; 30(1): 39-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10389011

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Randomized controlled trial of nebulized adrenaline in acute bronchiolitis. Author(s): Hariprakash S, Alexander J, Carroll W, Ramesh P, Randell T, Turnbull F, Lenney W. Source: Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology. 2003 April; 14(2): 134-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12675760

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Randomized, double-blind, placebo-controlled trial of oral albuterol in infants with mild-to-moderate acute viral bronchiolitis. Author(s): Patel H, Gouin S, Platt RW. Source: The Journal of Pediatrics. 2003 May; 142(5): 509-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12756382

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77

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Respiratory reovirus 1/L induction of intraluminal fibrosis, a model of bronchiolitis obliterans organizing pneumonia, is dependent on T lymphocytes. Author(s): Majeski EI, Paintlia MK, Lopez AD, Harley RA, London SD, London L. Source: American Journal of Pathology. 2003 October; 163(4): 1467-79. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14507654

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Respiratory syncytial virus bronchiolitis and the pathogenesis of childhood asthma. Author(s): Martinez FD. Source: The Pediatric Infectious Disease Journal. 2003 February; 22(2 Suppl): S76-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12671456

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Respiratory syncytial virus bronchiolitis: supportive care and therapies designed to overcome airway obstruction. Author(s): Panitch HB. Source: The Pediatric Infectious Disease Journal. 2003 February; 22(2 Suppl): S83-7; Discussion S87-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12671457

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Risk factors for admission and the role of respiratory syncytial virus-specific cytotoxic T-lymphocyte responses in children with acute bronchiolitis. Author(s): Jeena PM, Ayannusi OE, Annamalai K, Naidoo P, Coovadia HM, Guldner P. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2003 April; 93(4): 291-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12806723

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Risk factors for bronchiolitis-associated deaths among infants in the United States. Author(s): Holman RC, Shay DK, Curns AT, Lingappa JR, Anderson LJ. Source: The Pediatric Infectious Disease Journal. 2003 June; 22(6): 483-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12799502

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Risk factors for hypoxemia and respiratory failure in respiratory syncytial virus bronchiolitis. Author(s): Chan PW, Lok FY, Khatijah SB. Source: Southeast Asian J Trop Med Public Health. 2002 December; 33(4): 806-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12757230

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Risk factors for recurrent wheezing following acute bronchiolitis: a 12-month followup. Author(s): Cifuentes L, Caussade S, Villagran C, Darrigrande P, Bedregal P, Valdivia G, Sanchez I. Source: Pediatric Pulmonology. 2003 October; 36(4): 316-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950045

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RSV-induced bronchiolitis but not upper respiratory tract infection is accompanied by an increased nasal IL-18 response. Author(s): van Benten IJ, van Drunen CM, Koopman LP, KleinJan A, van Middelkoop BC, de Waal L, Osterhaus AD, Neijens HJ, Fokkens WJ. Source: Journal of Medical Virology. 2003 October; 71(2): 290-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12938205

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Sarcoidosis-associated bronchiolitis obliterans organizing pneumonia. Author(s): Rodriguez E, Lopez D, Buges J, Torres M. Source: Archives of Internal Medicine. 2001 September 24; 161(17): 2148-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11570948

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Severe bronchiolitis in acute Mycoplasma pneumoniae infection. Author(s): Ebnother M, Schoenenberger RA, Perruchoud AP, Soler M, Gudat F, Dalquen P. Source: Virchows Archiv : an International Journal of Pathology. 2001 December; 439(6): 818-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11787856

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Short term effects of adrenaline in bronchiolitis: a randomised controlled trial. Author(s): Abul-Ainine A, Luyt D. Source: Archives of Disease in Childhood. 2002 April; 86(4): 276-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11919104

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Simultaneous viral infection and childhood bronchiolitis obliterans. Author(s): Hirschheimer M, Silva PS, Giudici R, Carrilho M, Mauad T, Ishida M. Source: The Brazilian Journal of Infectious Diseases : an Official Publication of the Brazilian Society of Infectious Diseases. 2002 June; 6(3): 146-8. Epub 2003 March 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12144753

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Smoking in parents of children with asthma and bronchiolitis in a pediatric emergency department. Author(s): Mahabee-Gittens M. Source: Pediatric Emergency Care. 2002 February; 18(1): 4-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11862128

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Socioeconomic environmental factors and hospitalization for acute bronchiolitis during infancy. Author(s): Jansson L, Nilsson P, Olsson M. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(3): 335-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12022309

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Some clinico-epidemiological aspect of bronchiolitis among infants and young children--a hospital based study. Author(s): Das PK, Saha JB, Basu K, Lahiri S, Sarkar GN. Source: Indian J Public Health. 2003 April-June; 47(2): 66-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15129856

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Successful lung volume reduction surgery in a child with severe airflow obstruction and hyperinflation due to constrictive bronchiolitis. Author(s): Bloch KE, Weder W, Boehler A, Zalunardo MP, Russi EW. Source: Chest. 2002 August; 122(2): 747-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12171863

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Successful treatment of a case with rapidly progressive Bronchiolitis obliterans organizing pneumonia (BOOP) using cyclosporin A and corticosteroid. Author(s): Koinuma D, Miki M, Ebina M, Tahara M, Hagiwara K, Kondo T, Taguchi Y, Nukiwa T. Source: Intern Med. 2002 January; 41(1): 26-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11838586

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Surfactant use in severe bronchiolitis. Author(s): Marraro GA. Source: Biology of the Neonate. 2002; 81 Suppl 1: 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12011564

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The overlap between respiratory bronchiolitis and desquamative interstitial pneumonia in pulmonary Langerhans cell histiocytosis: high-resolution CT, histologic, and functional correlations. Author(s): Vassallo R, Jensen EA, Colby TV, Ryu JH, Douglas WW, Hartman TE, Limper AH. Source: Chest. 2003 October; 124(4): 1199-205. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14555547

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The value of switching from cyclosporine to tacrolimus in the treatment of refractory acute rejection and obliterative bronchiolitis after lung transplantation. Author(s): Sarahrudi K, Carretta A, Wisser W, Senbaklavaci O, Ploner M, Neuhauser P, Dobrovits M, Miwai Marta G, Papp A, Klepetko W. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 2002 January; 15(1): 24-8. Epub 2002 January 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11875609

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Time-related changes in pulmonary function after conversion to tacrolimus in bronchiolitis obliterans syndrome. Author(s): Cairn J, Yek T, Banner NR, Khaghani A, Hodson ME, Yacoub M. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 January; 22(1): 50-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12531413

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Transplant bronchiolitis obliterans: Deja vu. Author(s): Anthonisen NR. Source: Can Respir J. 2003 March; 10(2): 66-8. English, French. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12687024

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Treating acute bronchiolitis associated with RSV. Author(s): Steiner RW. Source: American Family Physician. 2004 January 15; 69(2): 325-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14765771

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Treatment of acute bronchiolitis. Author(s): Wohl ME, Chernick V. Source: The New England Journal of Medicine. 2003 July 3; 349(1): 82-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12840097

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Treatment of bronchiolitis. Author(s): Zwerdling RG, O'Sullivan BP. Source: The New England Journal of Medicine. 2003 October 2; 349(14): 1384-5; Author Reply 1384-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14523149

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Type 1 and type 2 cytokine imbalance in acute respiratory syncytial virus bronchiolitis. Author(s): Legg JP, Hussain IR, Warner JA, Johnston SL, Warner JO. Source: American Journal of Respiratory and Critical Care Medicine. 2003 September 15; 168(6): 633-9. Epub 2003 May 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12773328

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Type 2 cytokines in respiratory syncytial virus bronchiolitis. Author(s): Dheda K, Huggett JF, Kim LU, Zumla A. Source: American Journal of Respiratory and Critical Care Medicine. 2004 May 15; 169(10): 1167-8; Author Reply 1168. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15132965

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Typing of Pneumocystis carinii f.sp. hominis isolates from nasopharyngeal aspirates of immunocompetent infants with bronchiolitis by dihydropteroate synthase gene analysis. Author(s): Totet A, Latouche S, Lacube P, Bolognini J, Raccurt C, Nevez G, Roux P. Source: The Journal of Eukaryotic Microbiology. 2001; Suppl: 121S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11906019

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Ulcerative colitis presenting with bronchiolitis obliterans organizing pneumonia in a pediatric patient. Author(s): Mahajan L, Kay M, Wyllie R, Steffen R, Goldfarb J. Source: The American Journal of Gastroenterology. 1997 November; 92(11): 2123-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9362212

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Ultrastructural evidence of alveolar epithelial injury in idiopathic bronchiolitis obliterans-organizing pneumonia. Author(s): Myers JL, Katzenstein AL. Source: American Journal of Pathology. 1988 July; 132(1): 102-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3394793

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Unilateral bronchiolitis obliterans organizing pneumonia and bronchoalveolar lavage neutrophilia in a patient with parainfluenza 3 virus infection. Author(s): Peramaki E, Salmi I, Kava T, Romppanen T, Hakkarainen T. Source: Respiratory Medicine. 1991 March; 85(2): 159-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1653446

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Unilateral bronchiolitis obliterans: a case report. Author(s): Dosanjh A. Source: Clinical Pediatrics. 1992 May; 31(5): 319-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1582105

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Update on cryptogenic organising pneumonia (idiopathic bronchiolitis obliterans organising pneumonia). Author(s): Cordier JF. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2002 November 23; 132(41-42): 588-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12571758

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Use of a large national database for comparative evaluation of the effect of a bronchiolitis/viral pneumonia clinical care guideline on patient outcome and resource utilization. Author(s): Todd J, Bertoch D, Dolan S. Source: Archives of Pediatrics & Adolescent Medicine. 2002 November; 156(11): 1086-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12413334

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Use of extracorporeal membrane oxygenation in the treatment of respiratory syncytial virus bronchiolitis: the national experience, 1983 to 1988. Author(s): Steinhorn RH, Green TP. Source: The Journal of Pediatrics. 1990 March; 116(3): 338-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2308023

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Use of simple clinical parameters to assess severity of bronchiolitis. Author(s): Mai TV, Selby AM, Simpson JM, Isaacs D. Source: Journal of Paediatrics and Child Health. 1995 October; 31(5): 465-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8554871

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Utility of high resolution computed tomography in predicting bronchiolitis obliterans syndrome following lung transplantation: preliminary findings. Author(s): Miller WT Jr, Kotloff RM, Blumenthal NP, Aronchick JM, Gefter WB, Miller WT. Source: Journal of Thoracic Imaging. 2001 April; 16(2): 76-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11292208

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Utility of sepsis evaluation in infants 90 days of age or younger with fever and clinical bronchiolitis. Author(s): Melendez E, Harper MB. Source: The Pediatric Infectious Disease Journal. 2003 December; 22(12): 1053-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14688564

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Value of high-resolution computed tomography in routine evaluation of lung transplantation recipients during development of bronchiolitis obliterans syndrome. Author(s): Ikonen T, Kivisaari L, Harjula AL, Lehtola A, Heikkila L, Kinnula VL, Kyosola K, Savola J, Sipponen J, Verkkala K, Mattila SP. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1996 June; 15(6): 587-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8803756

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Variants of the chemokine receptor CCR5 are associated with severe bronchiolitis caused by respiratory syncytial virus. Author(s): Hull J, Rowlands K, Lockhart E, Moore C, Sharland M, Kwiatkowski D. Source: The Journal of Infectious Diseases. 2003 September 15; 188(6): 904-7. Epub 2003 Sep 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12964123

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Variations in bronchiolitis management between five New Zealand hospitals: can we do better? Author(s): Vogel AM, Lennon DR, Harding JE, Pinnock RE, Graham DA, Grimwood K, Pattemore PK. Source: Journal of Paediatrics and Child Health. 2003 January-February; 39(1): 40-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12542811

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VEGF and bFGF are highly expressed in intraluminal fibromyxoid lesions in bronchiolitis obliterans organizing pneumonia. Author(s): Lappi-Blanco E, Soini Y, Kinnula V, Paakko P. Source: The Journal of Pathology. 2002 February; 196(2): 220-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11793374

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Ventilation-perfusion inequalities in a patient with obliterative bronchiolitis after single-lung transplantation for primary pulmonary hypertension. Author(s): Mannes GP, de Boer WJ, Meuzelaar JJ, Meinesz AF. Source: Chest. 1993 April; 103(4): 1311. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8131508

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Ventilatory assistance in infants with bronchiolitis. Author(s): Wren WS, Moore KP, Cahill J. Source: Ir Med J. 1982 December; 75(12): 461-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7161025

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Viral bronchiolitis. Comments. Author(s): Eller JJ. Source: Pediatric Research. 1977 March; 11(3 Pt 2): 247-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=403501

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Water electrolyte homeostasis in acute bronchiolitis. Author(s): Poddar U, Singhi S, Ganguli NK, Sialy R. Source: Indian Pediatrics. 1995 January; 32(1): 59-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8617536

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Water, electrolyte, and endocrine homeostasis in infants with bronchiolitis. Author(s): Gozal D, Colin AA, Jaffe M, Hochberg Z. Source: Pediatric Research. 1990 February; 27(2): 204-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2179835

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What are bronchiolitis obliterans organizing pneumonia (BOOP) and cryptogenic organizing pneumonia (COP)? Author(s): Hansell DM. Source: Clinical Radiology. 1992 June; 45(6): 369-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1606792

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What are the best pulmonary function test parameters for early detection of post-lung transplant bronchiolitis obliterans syndrome in children? Author(s): Sritippayawan S, Keens TG, Horn MV, Starnes VA, Woo MS. Source: Pediatric Transplantation. 2003 June; 7(3): 200-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12756044

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What is the best treatment for bronchiolitis? Author(s): Purdon M, Dodson S. Source: The Journal of Family Practice. 2003 January; 52(1): 69-70; Discussion 70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12540317

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Wheezing at 8 and 13 years: changing importance of bronchiolitis and passive smoking. Author(s): McConnochie KM, Roghmann KJ. Source: Pediatric Pulmonology. 1989; 6(3): 138-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2717240

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Widespread occurrence of diffuse aspiration bronchiolitis in patients with dysphagia, irrespective of age. Author(s): Matsuse T, Teramoto S, Matsui H, Ouchi Y, Fukuchi Y. Source: Chest. 1998 July; 114(1): 350-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9674505

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Work of breathing, intra-thoracic pressure and clinical findings in a group of babies with bronchiolitis. Author(s): Stokes GM, Milner AD, Groggins RC. Source: Acta Paediatr Scand. 1981 September; 70(5): 689-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7324919

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CHAPTER 2. NUTRITION AND BRONCHIOLITIS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and bronchiolitis.

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

7

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

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

Airway obstruction and bronchiolitis obliterans after lung transplantation. Author(s): Division of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pennsylvania. Source: Paradis, I Yousem, S Griffith, B Clin-Chest-Med. 1993 December; 14(4): 751-63 0272-5231

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Clinical relevance summary: Collagen vs elastin in pathogenesis of emphysema; cellular origin of elastases; bronchiolitis vs emphysema as a cause of airflow obstruction. Author(s): Boston Veterans Affairs Medical Center, Boston, MA 02130, USA. Source: Snider, G L Chest. 2000 May; 117(5 Suppl 1): 244S-6S 0012-3692

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Cryptogenic organizing pneumonitis. Bronchiolitis obliterans organizing pneumonia. Author(s): Department of Pulmonary Medicine, Hopital Cardiovasculaire et Pneumologique Louis Pradel, Universite Claude Bernard, Lyon, France. Source: Cordier, J F Clin-Chest-Med. 1993 December; 14(4): 677-92 0272-5231

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Evidence for oxidative stress in bronchiolitis obliterans syndrome after lung and heart-lung transplantation. The Munich Lung Transplant Group. Author(s): Department of Internal Medicine I, Klinikum Grosshadern, LudwigMaximilians-University of Munich, Germany. Source: Behr, J Maier, K Braun, B Schwaiblmair, M Vogelmeier, C Transplantation. 2000 May 15; 69(9): 1856-60 0041-1337

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Idiopathic bronchiolitis obliterans organizing pneumonia/cryptogenic organizing pneumonia with unfavorable outcome: pathologic predictors. Author(s): Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania, USA. Source: Yousem, S A Lohr, R H Colby, T V Mod-Pathol. 1997 September; 10(9): 864-71 0893-3952

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Inflammatory responses and mucus secretion in rats with acute bronchiolitis induced by nickel chloride. Author(s): Department of Hygiene and Public Health (I), School of Medicine, Tokyo Women's Medical University, Tokyo, Japan. [email protected] Source: Ishihara, Yoko Kyono, Hiroko Serita, Fumio Toya, Tadao Kawashima, Hiroto Miyasaka, Masayuki Inhal-Toxicol. 2002 April; 14(4): 417-30 0895-8378

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Intravenous cyclophosphamide and methylprednisolone for the treatment of bronchiolitis obliterans and interstitial fibrosis associated with crysotherapy. Author(s): Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107. Source: Fort, J G Scovern, H Abruzzo, J L J-Rheumatol. 1988; 15(5): 850-4 0315-162X

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Nitric oxide in the development of obliterative bronchiolitis in a heterotopic pig model. Author(s): Tissue Engineering Centre, Imperial College School of Medicine, Chelsea and Westminster Hospital, London, UK. Source: Salminen, Ulla Stina Maasilta, Paula K Harjula, Ari L J Romanska, Hanna M Bishop, Anne E Polak, Julia M Transplantation. 2002 June 15; 73(11): 1724-9 0041-1337

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Recent advances in the treatment of bronchiolitis and laryngitis. Author(s): Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Canada. Source: Klassen, T P Pediatr-Clin-North-Am. 1997 February; 44(1): 249-61 0031-3955

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Tacrolimus for treatment of bronchiolitis obliterans syndrome after unilateral and bilateral lung transplantation. Author(s): Division of Thoracic and Cardiovascular Surgery, University Hospital, D-60 590 Frankfurt, Germany. Source: Fieguth, H G Krueger, S Wiedenmann, D E Otterbach, I Wagner, T O Transplant-Proc. 2002 August; 34(5): 1884 0041-1345

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Ultrastructural morphogenesis of 4-ipomeanol-induced bronchiolitis and interstitial pneumonia in calves. Author(s): Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison. Source: Li, X Castleman, W L Vet-Pathol. 1990 May; 27(3): 141-9 0300-9858

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 3. BRONCHIOLITIS

ALTERNATIVE

MEDICINE

AND

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

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

A pediatrician and his mothers and infants. Author(s): Gracey M. Source: Turk J Pediatr. 1997 January-March; 39(1): 1-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10868186

•

Bronchiolitis obliterans following the ingestion of an Asian shrub leaf. Author(s): Higenbottam TW. Source: Thorax. 1997 August; 52 Suppl 3: S68-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9381431

•

Bronchiolitis: a pilot study of osteopathic manipulative treatment, bronchodilators, and other therapy. Author(s): Belcastro MR, Backes CR, Chila AG.

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Source: J Am Osteopath Assoc. 1984 May; 83(9): 672-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6725033 •

Clinical trial of vitamin A as adjuvant treatment for lower respiratory tract infections. Author(s): Kjolhede CL, Chew FJ, Gadomski AM, Marroquin DP. Source: The Journal of Pediatrics. 1995 May; 126(5 Pt 1): 807-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7752011

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Hypersensitivity pneumonitis associated with Mycobacterium avium complex and hot tub use. Author(s): Rickman OB, Ryu JH, Fidler ME, Kalra S. Source: Mayo Clinic Proceedings. 2002 November; 77(11): 1233-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12440560

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Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: a report from the Intergroup Rhabdomyosarcoma Study Group. Author(s): Breitfeld PP, Lyden E, Raney RB, Teot LA, Wharam M, Lobe T, Crist WM, Maurer HM, Donaldson SS, Ruymann FB. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2001 May; 23(4): 225-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11846301

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Management of mycotic rupture of the ascending aorta after heart-lung transplantation. Author(s): Albes J, Haverich A, Freihorst J, von der Hardt H, Manthey-Stiers F. Source: The Annals of Thoracic Surgery. 1990 December; 50(6): 982-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2146932

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Psyllium aspiration causing bronchiolitis: radiographic, high-resolution CT, and pathologic findings. Author(s): Janoski MM, Raymond GS, Puttagunta L, Man GC, Barrie JR. Source: Ajr. American Journal of Roentgenology. 2000 March; 174(3): 799-801. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10701628

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Segmental necrosis of small bronchi after prolonged intakes of Sauropus androgynus in Taiwan. Author(s): Chang YL, Yao YT, Wang NS, Lee YC. Source: American Journal of Respiratory and Critical Care Medicine. 1998 February; 157(2): 594-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9476878

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•

The effect of large-dose prednisolone on patients with obstructive lung disease associated with consuming sauropus androgynus. Author(s): Wu CL, Hsu WH, Chiang CD. Source: Zhonghua Yi Xue Za Zhi (Taipei). 1998 January; 61(1): 34-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9509690

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Treatment of acute bronchiolitis with Chinese herbs. Author(s): Kong XT, Fang HT, Jiang GQ, Zhai SZ, O'Connell DL, Brewster DR. Source: Archives of Disease in Childhood. 1993 April; 68(4): 468-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8503668

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Use of complementary treatment by those hospitalised with acute illness. Author(s): Armishaw J, Grant CC. Source: Archives of Disease in Childhood. 1999 August; 81(2): 133-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10490520

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Use of soy-protein formulas and soyfood for feeding infants and children in Asia. Author(s): Quak SH, Tan SP. Source: The American Journal of Clinical Nutrition. 1998 December; 68(6 Suppl): 1444S1446S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9848514

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 4. DISSERTATIONS ON BRONCHIOLITIS Overview In this chapter, we will give you a bibliography on recent dissertations relating to bronchiolitis. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “bronchiolitis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on bronchiolitis, we have not necessarily excluded nonmedical dissertations in this bibliography.

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

Predicting long-term airflow obstruction and obliterative bronchiolitis after allogeneic marrow transplantation by Marras, Theodore Konstantine; MSc from University of Toronto (Canada), 2003, 134 pages http://wwwlib.umi.com/dissertations/fullcit/MQ78197

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

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CHAPTER 5. PATENTS ON BRONCHIOLITIS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “bronchiolitis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on bronchiolitis, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Bronchiolitis By performing a patent search focusing on bronchiolitis, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted

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

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

Immunogenic compositions comprising cold-adapted attenuated respiratory syncytial virus mutants Inventor(s): Chanock; Robert M. (Bethesda, MD), Connors; Mark (Chevy Chase, MD), Crowe, Jr.; James E. (Chevy Chase, MD), Davis; Alan R. (Wayne, PA), Hsu; Kuo-Hom Lee (Fort Washington, PA), Lubeck; Michael D. (Glenmoore, PA), Murphy; Brian R. (Bethesda, MD), Selling; Bernard H. (Bryn Mawr, PA) Assignee(s): The United States of America as represented by the Department of Health and (Washington, DC) Patent Number: 6,284,254 Date filed: May 30, 1995 Abstract: The respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in infants and children throughout the world. RSV is a major cause of pneumonia and bronchiolitis in infants under one year of age, and is a major cause of fatal respiratory tract disease in these infants. The treatment and prevention of RSV infection has been problematic. However, the present invention addresses some of these concerns by providing attenuated RSV strains that are suitable for inclusion in immunizing compositions. Specifically, the present invention is directed toward the introduction of growth restriction mutations into incompletely attenuated host rangerestricted cold-passaged respiratory syncytial virus (cpRSV) strains by further passage of the strains at increasingly reduced temperatures to produce derivative strains which are more satisfactorily attenuated. These cold-adaptation (ca) approaches were used to introduce further attenuation in the parental RSV virus cpRSV-3131, which is incompletely attenuated in seronegative children. Mutants of the parental strain were obtained by selecting for large plaque production at reduced temperatures. An RSV cp3131 derivative, designated D1, was isolated that produces large plaques at 25.degree. C. Biologically cloned virus D1 produces distinctly and uniformly larger plaques at 25.degree. C. as compared to the parental attenuated strain cpRSV-3131 or wild-type strain A2. Thus, D1 is an attenuated cold-adapted, but not temperature-sensitive, RSV mutant. The invention also provides methods for stimulating RSV-specific immune responses in an individual through the administration of said mutants. Excerpt(s): Respiratory syncytial (RS) virus infection of humans ranges from asymptomatic to severe respiratory tract disease. In infants and children, RS virus (RSV) is regarded as one of the most important causes of lower respiratory tract disease in all geographic areas of the world. RS virus outranks all other microbial pathogens as a cause of pneumonia and bronchiolitis in infants under one year of age, and is a major cause of fatal respiratory tract disease in these infants. Virtually all children are infected by two years of age. Reinfection occurs with appreciable frequency in older children and young adults. (Chanock et al., in Viral Infections of Humans, 3rd ed., A. S. Evans, ed., Plenum Press, N.Y. (1989)). Although most healthy adults do not have serious disease due to RS virus infection, elderly patients and immunocompromised individuals are more likely to have severe and possibly life-threatening infections. Treatment of RSV infection has been problematic. Small infants have diminished serum and secretory antibody responses to RSV antigens and thus suffer more severe infections, whereas cumulative immunity appears to protect older children and adults against more serious forms of the infection. One antiviral compound, ribavirin, has shown promise in the treatment of severely infected infants, although there is no indication that it shortens the

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duration of hospitalization or diminishes the infant's need for supportive therapy. The mechanisms of immunity in RSV infection have recently come into focus. Secretory antibodies appear to be most important in protecting the upper respiratory tract, whereas high levels of serum antibodies are thought to have a major role in resistance to RSV infection in the lower respiratory tract. Purified human immunoglobulin containing a high titer of neutralizing antibodies to RSV may prove useful in immunotherapeutic approaches for serious lower respiratory tract disease in infants and young children. Immune globulin preparations, however, suffer from several disadvantages, such as the possibility of transmitting blood-bome viruses and difficulty and expense in preparation and storage. Web site: http://www.delphion.com/details?pn=US06284254__ •

Therapeutic agents for respiratory diseases Inventor(s): Hiki; Masato (Osaka, JP), Tanaka; Masaya (Kobe, JP) Assignee(s): Medion Research Laboratories (Hyogo, JP) Patent Number: 6,309,674 Date filed: November 19, 1999 Abstract: Prophylactic or therapeutic agents for respiratory diseases, allergic diseases, keratosis, and carcinomatous pain, containing Smilax china or a plant analogous thereto as the active ingredient. These agents can improve the condition and predisposition of acute and chronic respiratory diseases, such as acute bronchitis, bronchial asthma, asthmatic bronchitis, chronic bronchitis, pan bronchiolitis and bronchiectasis, allergic diseases, such as atopic dermatitis, pollinosis, allergic rhinitis and allergic conjunctivitis, and keratosis, such as psoriasis, lichen, ichthyosis, furfur, and palmoplantar keratosis without side effects and at the same time can lower serum IgE level on an abnormally high level in a short period of time. After the symptom and predisposition have been improved, these agents can, even after suspension of administration, persistently lower the serum IgE level and in addition can inhibit the recurrence of the symptom. Excerpt(s): This application is a 371 of PCT/JP98/02237, filed May 21, 1998. The therapeutic agent for respiratory disease according to this invention relates to a prophylactic or therapeutic drug for respiratory diseases, a prophylactic or therapeutic drug for allergic diseases, a prophylactic or therapeutic drug for keratosis, a prophylactic or therapeutic drug for carcinomatous pain, a health food, a performance food, a cosmetic additive and a cosmetic product, which are capable of improving the symptom of, and the predisposition to, acute and chronic respiratory diseases, such as acute bronchitis, bronchial asthma, asthmatic bronchitis, chronic bronchitis, pan bronchiolitis and bronchiectasis, allergic diseases, such as atopic dermatitis, pollinosis, allergic rhinitis and allergic conjunctivitis, and keratosis, such as psoriasis, lichen, ichthyosis, furfur, and palmoplantar keratosis without side effects and at the same time capable of lowering serum IgE level on an abnormally high level in a short period of time. After the symptom and predisposition have been improved, these agents can, even after suspension of administration, persistently lower the serum IgE level if it is still abnormally high and in addition can inhibit the recurrence of the symptom. Acute and chronic respiratory diseases such as acute bronchitis, bronchial asthma, asthmatic bronchitis, chronic bronchitis, diffuse ordinary bronchiolitis and bronchiectasis are intractable diseases. The therapy of these diseases is generally a symptomatic treatment centered around temporary control of coughing with an antitussive or, in case respiratory distress intervenes, assisted respiration with a bronchodilator, although the

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treatment is not rewarding in cases of severe coughing. Moreover, bronchial asthma can be regarded as allergy and anti-allergics are also used for its prevention or therapy but the efficacy of such medication is not always reliable but even in patients with remission of the symptom, suspension of the administration results in recurrence of the symptoms. Adrenocortical hormones are administered in severe cases but, despite a certain rewarding effect they provide, sometimes cause intense side effects. Moreover, those, too, are symptomatic remedies. Thus, no drug is known of which recurrence of the symptom does not occur after suspension of administration. Health foods, for instance, are also available with claims to the effect that their intake leads to improvements in the patient's predisposition and a cure of diseases or control of symptoms but their efficacy is either not steadfast or has not been medically proven. Web site: http://www.delphion.com/details?pn=US06309674__

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

Use of TGF-beta antagonists to treat or to prevent chronic transplant rejection Inventor(s): George, Judith A. St.; (Hudson, MA), Keshavjee, Shaf; (Toronto, CA), Liu, Mingyao; (Richmond Hill, CA) Correspondence: Leon R. Yankwich, ESQ.; Yankwich & Associates; 201 Broadway; Cambridge; MA; 02139; US Patent Application Number: 20030180301 Date filed: January 21, 2003 Abstract: Effective use of a TGF-.beta. antagonist to treat or to prevent loss of transplant function is described herein. Use of a TGF-.beta. antagonist is demonstrated to effectively prevent loss of organ function in a host due to chronic rejection in which TGF-.beta.-mediated fibroproliferation is a characteristic. Expression in situ of a TGF.beta. antagonist in the form of a recombinant receptor, i.e., TGF-.beta. type III receptor (TGFBIIIR) showed prevention of bronchiolitis obliterans in comparison to untreated controls in a rat lung transplant model. This provides an effective method for preventing or inhibiting chronic rejection of transplant organs such as lung, kidney, liver and heart in vertebrate hosts including human hosts. Excerpt(s): This application claims priority under 35 U.S.C.sctn.119(e) to U.S. provisional application serial No. 60/350,529, filed Jan. 22, 2002. The present invention is in the fields of molecular biology and organ transplantation. The present invention is directed to novel methods for treating or preventing rejection of transplanted organs or tissues by the use of an effective inhibitor of TGF-.beta. Organ transplantation has become an important therapy for patients facing loss of organ function due to disease or injury. In the United States, for example, for the period from January 1997 through December 1998 (i.e., the most recent period with complete 3-year follow-up statistics), more than 1600 lung transplants, more than 4000 heart transplants, more than 7000 liver transplants,

9

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

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more than 400 pancreas transplants, and more than 22,000 kidney transplants were performed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with bronchiolitis, 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 “bronchiolitis” (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 bronchiolitis. You can also use this procedure to view pending patent applications concerning bronchiolitis. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON BRONCHIOLITIS Overview This chapter provides bibliographic book references relating to bronchiolitis. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on bronchiolitis 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: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “bronchiolitis” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “bronchiolitis” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “bronchiolitis” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Management of Bronchiolitis in Infants and Children (Evidence Report/Technology Assessment) by Meera Viswanathan (Other Contributor); ISBN: 158763130X; http://www.amazon.com/exec/obidos/ASIN/158763130X/icongroupinterna

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CHAPTER 7. PERIODICALS AND NEWS ON BRONCHIOLITIS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover bronchiolitis.

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

Lung retransplantation for bronchiolitis obliterans a viable option in some cases Source: Reuters Medical News Date: June 23, 2003

•

Evidence lacking to support common bronchiolitis therapies Source: Reuters Industry Breifing Date: March 07, 2003

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•

Higher risk of bronchiolitis obliterans seen in flavor manufacturing workers Source: Reuters Medical News Date: April 25, 2002

•

Heliox therapy safe and effective for acute viral bronchiolitis in infants Source: Reuters Industry Breifing Date: January 08, 2002

•

Bronchoalveolar lavage analysis predicts obliterative bronchiolitis posttransplant Source: Reuters Medical News Date: January 30, 2001

•

Resolution of symptoms of bronchiolitis in ambulatory children may take weeks Source: Reuters Medical News Date: October 20, 2000

•

CF may be complicated by bronchiolitis obliterans organizing pneumonia Source: Reuters Medical News Date: July 13, 2000

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RSV bronchiolitis in infancy strongly linked to childhood asthma Source: Reuters Medical News Date: June 15, 2000

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Asthma-associated symptoms linked to bronchiolitis in infancy Source: Reuters Medical News Date: March 17, 2000

•

Early bronchiolitis and eosinophilia point to asthma in later childhood Source: Reuters Medical News Date: January 11, 2000

•

High hospitalization rates for childhood RSV-associated bronchiolitis reported Source: Reuters Medical News Date: October 20, 1999

•

Prognosis For Lung Function After Acute Bronchiolitis In Infancy Considered Good Source: Reuters Medical News Date: April 11, 1997 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name.

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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 “bronchiolitis” (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 “bronchiolitis” (or synonyms). If you know the name of a company that is relevant to bronchiolitis, 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 “bronchiolitis” (or synonyms).

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

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CHAPTER 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for bronchiolitis. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with bronchiolitis. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to bronchiolitis: Corticosteroids •

Dental - U.S. Brands: Kenalog in Orabase; Orabase-HCA; Oracort; Oralone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202010.html

•

Inhalation - U.S. Brands: AeroBid; AeroBid-M; Azmacort; Beclovent; Pulmicort Respules; Pulmicort Turbuhaler; Qvar; Vanceril; Vanceril 84 mcg Double Strength http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202011.html

•

Nasal - U.S. Brands: Beconase; Beconase AQ; Dexacort Turbinaire; Flonase; Nasacort; Nasacort AQ; Nasalide; Nasarel; Nasonex; Rhinocort; Vancenase; Vancenase AQ 84 mcg; Vancenase pockethaler http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202012.html

•

Ophthalmic - U.S. Brands: AK-Dex; AK-Pred; AK-Tate; Baldex; Decadron; Dexair; Dexotic; Econopred; Econopred Plus; Eflone; Flarex; Fluor-Op; FML Forte; FML Liquifilm; FML S.O.P.; HMS Liquifilm; Inflamase Forte; Inflamase Mild; I-Pred; Lite Pred; Maxidex; Ocu-Dex; Ocu-Pred; Ocu-Pred Forte; Ocu-PredA; Pred Forte; Pred Mild; Predair; Predair A; Predair Forte; Storz-Dexa; Ultra Pred http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202013.html

•

Otic - U.S. Brands: Decadron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202014.html

•

Rectal - U.S. Brands: Anucort-HC; Anu-Med HC; Anuprep HC; Anusol-HC; Anutone-HC; Anuzone-HC; Cort-Dome; Cortenema; Cortifoam; Hemorrhoidal HC; Hemril-HC Uniserts; Proctocort; Proctosol-HC; Rectasol-HC http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203366.html

Influenza Virus Vaccine •

Systemic - U.S. Brands: FluMist; FluShield; Fluvirin; Fluzone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202297.html

Respiratory Syncytial Virus Immune Globulin Intravenous •

Systemic - U.S. Brands: RespiGam http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203069.html

Ribavirin •

Systemic - U.S. Brands: Copegus; Rebetol; Virazole http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202509.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.

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Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

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

•

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

•

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

•

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

•

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

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

•

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

10

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

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•

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

•

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

•

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

•

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

•

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

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

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

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

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

•

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

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

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

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

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

•

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

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

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

11

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.

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•

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

•

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

The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “bronchiolitis” (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 5639 38 31 57 36 5801

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “bronchiolitis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

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

14

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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

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

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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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

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

•

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

18 Adapted 19

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

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on bronchiolitis 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 bronchiolitis. 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 bronchiolitis. 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 “bronchiolitis”:

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Bronchitis http://www.nlm.nih.gov/medlineplus/bronchitis.html COPD http://www.nlm.nih.gov/medlineplus/copdchronicobstructivepulmonarydisease.t ml Pneumonia http://www.nlm.nih.gov/medlineplus/pneumonia.html Respiratory Diseases http://www.nlm.nih.gov/medlineplus/respiratorydiseases.html Respiratory Syncytial Virus Infections http://www.nlm.nih.gov/medlineplus/respiratorysyncytialvirusinfections.html

Within the health topic page dedicated to bronchiolitis, the following was listed: •

General/Overviews Acute Bronchitis Source: American Academy of Family Physicians http://familydoctor.org/677.xml Bronchitis Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00031 Chronic Bronchitis Source: American Lung Association http://www.lungusa.org/site/pp.asp?c=dvLUK9O0E&b=35019

•

Diagnosis/Symptoms Blood Gas Tests Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/blood_gases/test.html Understanding PFT's (Pulmonary Function Testing) Source: Alpha 1 Association http://www.alpha1.org/what/lunginfo_pfts.htm

•

Specific Conditions/Aspects Bronchiolitis Obliterans with Organizing Pneumonia (BOOP) Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00307

•

Children Bronchiolitis and Your Child Source: American Academy of Family Physicians http://familydoctor.org/020.xml

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•

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From the National Institutes of Health Lungs in Health and Disease Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/health/public/lung/other/lungs_hd.pdf

•

Organizations American Lung Association http://www.lungusa.org/ National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/

•

Research AHRQ Report Says Doctors Commonly Treat Bronchiolitis with Medicines that May Be Ineffective Source: Agency for Healthcare Research and Quality http://www.ahrq.gov/news/press/pr2003/bronchpr.htm

•

Statistics FASTATS: Bronchitis Source: National Center for Health Statistics http://www.cdc.gov/nchs/fastats/brnchtis.htm

•

Teenagers Bronchitis Source: Nemours Foundation http://kidshealth.org/teen/infections/common/bronchitis.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 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 bronchiolitis. 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.

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Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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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 “bronchiolitis”. 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 “bronchiolitis” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “bronchiolitis” (or a synonym) into the search box, and click “Submit Query.”

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

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

21

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

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

22

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Basic Guidelines for Bronchiolitis Bronchiolitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000975.htm Respiratory syncytial virus (RSV) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001564.htm RSV Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001564.htm

•

Signs & Symptoms for Bronchiolitis Apnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003069.htm Bluish color Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003215.htm

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Bluish skin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003215.htm Breath sounds Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003323.htm Cough Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm Cyanosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003215.htm Difficulty breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Intercostal retractions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003322.htm Irritability Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003214.htm Lethargic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Rapid breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003071.htm Rapid, shallow breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Shortness of breath Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Tachycardia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003077.htm Tachypnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003071.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Wheezing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003070.htm •

Diagnostics and Tests for Bronchiolitis Blood gases Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003855.htm

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Chest X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003804.htm Pulmonary function Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003443.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •

Background Topics for Bronchiolitis Auscultation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002226.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm

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

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

•

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

•

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

•

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

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BRONCHIOLITIS 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] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually

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referred to as adolescence lie between 13 and 18 years of age. [NIH] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenaline: A hormone. Also called epinephrine. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Aetiology: Study of the causes of disease. [EU] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Aggravation: An increasing in seriousness or severity; an act or circumstance that intensifies, or makes worse. [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] Albuterol: A racemic mixture with a 1:1 ratio of the r-isomer, levalbuterol, and s-albuterol. It is a short-acting beta 2-adrenergic agonist with its main clinical use in asthma. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU]

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Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allo: A female hormone. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alum: A type of immune adjuvant (a substance used to help boost the immune response to a vaccine). Also called aluminum sulfate. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] 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] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH]

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Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angiogram: An x-ray of blood vessels; the person receives an injection of dye to outline the vessels on the x-ray. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antiallergic: Counteracting allergy or allergic conditions. [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

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binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Aortitis: Inflammation of the wall of the aorta. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH]

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Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atelectasis: Incomplete expansion of the lung. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Avidity: The strength of the interaction of an antiserum with a multivalent antigen. [NIH] Azithromycin: A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders.

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Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Factors: Compounds made by living organisms that contribute to or influence a phenomenon or process. They have biological or physiological activities. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Warfare: Warfare involving the use of living organisms or their products as disease etiologic agents against people, animals, or plants. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] 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] Bladder: The organ that stores urine. [NIH] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] Blepharitis: Inflammation of the eyelids. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [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] Body Fluids: Liquid components of living organisms. [NIH]

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Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiectasis: Persistent abnormal dilatation of the bronchi. [NIH] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchiolitis: Inflammation of the bronchioles. [NIH] Bronchiolitis Obliterans: Inflammation of the bronchioles with obstruction by fibrous granulation tissue or bronchial exudate. It may follow inhalation of irritating gases or foreign bodies and it complicates pneumonia. [NIH] Bronchiolitis Obliterans Organizing Pneumonia: Inflammation of the bronchioles. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Bronchoalveolar Lavage Fluid: Fluid obtained by washout of the alveolar compartment of the lung. It is used to assess biochemical and inflammatory changes in and effects of therapy on the interstitial lung tissue. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Budesonide: A glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis. [NIH] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of

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cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoid: A type of tumor usually found in the gastrointestinal system (most often in the appendix), and sometimes in the lungs or other sites. Carcinoid tumors are usually benign. [NIH]

Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] 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] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH]

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Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Chimera: An individual that contains cell populations derived from different zygotes. [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] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH]

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Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] C-kit receptor: A protein on the surface of some cells that binds to stem cell factor (a substance that causes certain types of cells to grow). Altered forms of this receptor may be associated with some types of cancer. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH]

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Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH]

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Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] 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] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU]

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Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH] Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Croup: A condition characterized by resonant barking cough, hoarseness and persistant stridor and caused by allergy, foreign body, infection, or neoplasm. It occurs chiefly in infants and children. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanogen Bromide: Cyanogen bromide (CNBr). A compound used in molecular biology to digest some proteins and as a coupling reagent for phosphoroamidate or pyrophosphate internucleotide bonds in DNA duplexes. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH]

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Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [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] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH]

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Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diagnostic procedure: A method used to identify a disease. [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] Dihydropteroate Synthase: An enzyme that catalyzes the formation of dihydropteroate from p-aminobenzoic acid and dihydropteridine-hydroxymethyl-pyrophosphate. EC 2.5.1.15. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Dysphagia: Difficulty in swallowing. [EU] Dyspnea: Difficult or labored breathing. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH]

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Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [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] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empyema: Presence of pus in a hollow organ or body cavity. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH]

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Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Episcleritis: Inflammation of the episclera and/or the outer layers of the sclera itself. [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] Erythema Nodosum: An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring or atrophy. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH]

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Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extracorporeal Membrane Oxygenation: Application of a life support system that circulates

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the blood through an oxygenating system, which may consist of a pump, a membrane oxygenator, and a heat exchanger. Examples of its use are to assist victims of smoke inhalation injury, respiratory failure, and cardiac failure. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] 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] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds

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with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] 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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] 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] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Gonadal: Pertaining to a gonad. [EU]

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Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Granulation Tissue: A vascular connective tissue formed on the surface of a healing wound, ulcer, or inflamed tissue. It consists of new capillaries and an infiltrate containing lymphoid cells, macrophages, and plasma cells. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granulomatous Disease, Chronic: A recessive X-linked defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Hay Fever: A seasonal variety of allergic rhinitis, marked by acute conjunctivitis with lacrimation and itching, regarded as an allergic condition triggered by specific allergens. [NIH]

Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart-Lung Transplantation: The simultaneous, or near simultaneous, transference of heart and lungs from one human or animal to another. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level

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may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Histiocytosis: General term for the abnormal appearance of histiocytes in the blood. Based on the pathological features of the cells involved rather than on clinical findings, the histiocytic diseases are subdivided into three groups: Langerhans cell histiocytosis, nonLangerhans cell histiocytosis, and malignant histiocytic disorders. [NIH] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Histocompatibility Antigens: A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] 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] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or

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bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoxemia: Deficient oxygenation of the blood; hypoxia. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Ichthyosis: Any of several generalized skin disorders characterized by dryness, roughness, and scaliness, due to hypertrophy of the stratum corneum epidermis. Most are genetic, but some are acquired, developing in association with other systemic disease or genetic syndrome. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Immune adjuvant: A drug that stimulates the immune system to respond to disease. [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

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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] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenetics: A branch of genetics which deals with the genetic basis of the immune response. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunologic Factors: Biologically active substances whose activities affect or play a role in the functioning of the immune system. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [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] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] 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 situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a

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specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Information Science: The field of knowledge, theory, and technology dealing with the collection of facts and figures, and the processes and methods involved in their manipulation, storage, dissemination, publication, and retrieval. It includes the fields of communication, publishing, library science and informatics. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] 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] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the

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laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-10: Factor that is a coregulator of mast cell growth. It is produced by T-cells and B-cells and shows extensive homology with the Epstein-Barr virus BCRFI gene. [NIH] Interleukin-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-17: Proinflammatory cytokine produced primarily by T-lymphocytes or their precursors. IL-17 is homologous to an open reading frame found in Herpesvirus saimiri. [NIH]

Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Interleukin-9: Factor that is thought to be a regulator of hematopoiesis. It has been shown to enhance the growth of human mast cells and megakaryoblastic leukemic cells as well as murine helper t-cell clones. IL-9 is a glycoprotein with a molecular weight of 32-39 that is derived from T-cells, and maps to human chromosome 5. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] 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] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

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Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] 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] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [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] Keratosis: Any horny growth such as a wart or callus. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lacrimal: Pertaining to the tears. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Laryngitis: Inflammation of the larynx. This condition presents itself with dryness and soreness of the throat, difficulty in swallowing, cough, and hoarseness. [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]

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Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Length of Stay: The period of confinement of a patient to a hospital or other health facility. [NIH]

Lesion: An area of abnormal tissue change. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukemia: Cancer of blood-forming tissue. [NIH] Leukocyte Count: A count of the number of white blood cells per unit volume in venous blood. A differential leukocyte count measures the relative numbers of the different types of white cells. [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] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Livedo: A discoloured spot or patch on the skin, commonly due to passive congestion; commonly used alone to refer to l. reticularis. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view

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and on which the outline of the object may be traced. [NIH] Lung Transplantation: The transference of either one or both of the lungs from one human or animal to another. [NIH] Lung volume: The amount of air the lungs hold. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [NIH] Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells. [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] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [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] Macrophage Inflammatory Protein-1: A chemokine that is chemotactic for neutrophils and monocytes, stimulates macrophages, and may play a role in regulating hematopoiesis. Its two variants, MIP-1alpha and MIP-1beta, are 60% homologous to each other. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH]

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Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Matrilysin: The smallest member of the matrix metalloproteinases. It plays a role in tumor progression. EC 3.4.24.23. [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] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Informatics: The field of information science concerned with the analysis and dissemination of medical data through the application of computers to various aspects of health care and medicine. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be

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absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methylprednisolone: (6 alpha,11 beta)-11,17,21-Trihydroxy-6-methylpregna-1,4-diene-3,2dione. A prednisolone derivative which has pharmacological actions similar to prednisolone. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Minor Histocompatibility Antigens: Allelic alloantigens often responsible for weak graft rejection in cases when (major) histocompatibility has been established by standard tests. In the mouse they are coded by more than 500 genes at up to 30 minor histocompatibility loci. The most well-known minor histocompatibility antigen in mammals is the H-Y antigen. [NIH]

Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA,

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can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocular: Diplopia identified with one eye only; it may be induced with a double prism, or it may occur either as a result of double imagery due to an optical defect in the eye, or as a result of simultaneous use of normal and anomalous retinal correspondence. [NIH] Monocyte: A type of white blood cell. [NIH] Monocyte Chemoattractant Protein-1: A chemokine that is a chemoattractant for human monocytes and may also cause cellular activation of specific functions related to host defense. It is produced by leukocytes of both monocyte and lymphocyte lineage and by fibroblasts during tissue injury. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Mycosis: Any disease caused by a fungus. [EU] Mycotic: Pertaining to a mycosis; caused by fungi. [EU] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further

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damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]

Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasal Septum: The partition separating the two nasal cavities in the midplane, composed of cartilaginous, membranous and bony parts. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] 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] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992) EC 3.2.1.18. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the

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bladder. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurologic Manifestations: Clinical signs and symptoms caused by nervous system injury or dysfunction. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [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] Neutrophil: A type of white blood cell. [NIH] Neutrophil Activation: The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cellsurface receptors on the neutrophil. [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] 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] 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

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next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Olfactory Bulb: Ovoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the vomeronasal organ via the vomeronasal nerve, is also included here. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] 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] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

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Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oximetry: The determination of oxygen-hemoglobin saturation of blood either by withdrawing a sample and passing it through a classical photoelectric oximeter or by electrodes attached to some translucent part of the body like finger, earlobe, or skin fold. It includes non-invasive oxygen monitoring by pulse oximetry. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] 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] Pancreas Transplant: A surgical procedure that involves replacing the pancreas of a person who has diabetes with a healthy pancreas that can make insulin. The healthy pancreas comes from a donor who has just died or from a living relative. A person can donate half a pancreas and still live normally. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Paramyxovirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have both hemagglutinin and neuraminidase activities and encode a C protein. Human parainfluenza virus 1 is the type species. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] 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

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and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericarditis: Inflammation of the pericardium. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral stem cell transplantation: A method of replacing blood-forming cells destroyed by cancer treatment. Immature blood cells (stem cells) in the circulating blood that are similar to those in the bone marrow are given after treatment to help the bone marrow recover and continue producing healthy blood cells. Transplantation may be autologous (an individual's own blood cells saved earlier), allogeneic (blood cells donated by someone else), or syngeneic (blood cells donated by an identical twin). Also called peripheral stem cell support. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor

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of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Pheromones: Chemical substances which, when secreted by an individual into the environment, cause specific reactions in other individuals, usually of the same species. The substances relate only to multicellular organisms. This includes kairomones. Allomones are repellent pheromones. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] 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] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together

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can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]

Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Pneumothorax: Accumulation of air or gas in the space between the lung and chest wall, resulting in partial or complete collapse of the lung. [NIH] Pneumovirus: A genus of the familyParamyxoviridae (subfamily Pneumovirinae) where the human and bovine virions have neither hemagglutinin nor neuraminidase activity. Pneumonia virus of mice has hemagglutinin activity. Human respiratory syncytial virus is the type species. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Polyarthritis: An inflammation of several joints together. [EU] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] 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] 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

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the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [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] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the

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nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [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] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Pseudorabies: A highly contagious herpesvirus infection affecting the central nervous system of swine, cattle, dogs, cats, rats, and other animals. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH]

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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] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyoderma: Any purulent skin disease (Dorland, 27th ed). [NIH] Pyoderma Gangrenosum: An idiopathic, rapidly evolving, and severely debilitating disease occurring most commonly in association with chronic ulcerative colitis. It is characterized by the presence of boggy, purplish ulcers with undermined borders, appearing mostly on the legs. The majority of cases are in people between 40 and 60 years old. Its etiology is unknown. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] 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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays,

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gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] 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] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [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] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for

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treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory Burst: A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (granulomatous disease, chronic) often die as a result of recurrent bacterial infections. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Respiratory syncytial virus: RSV. A virus that causes respiratory infections with cold-like symptoms. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Rhabdomyosarcoma: A malignant tumor of muscle tissue. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH]

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Rheumatoid Nodule: Subcutaneous nodules seen in 20-30% of rheumatoid arthritis patients. They may arise anywhere on the body, but are most frequently found over the bony prominences. The nodules are characterized histologically by dense areas of fibrinoid necrosis with basophilic streaks and granules, surrounded by a palisade of cells, mainly fibroblasts and histiocytes. [NIH] Rhinovirus: A genus of Picornaviridae inhabiting primarily the respiratory tract of mammalian hosts. It includes the human strains associated with common colds. [NIH] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] 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] Saimiri: A genus of the family Cebidae consisting of four species: S. boliviensis, S. orstedii (red-backed squirrel monkey), S. sciureus (common squirrel monkey), and S. ustus. They inhabit tropical rain forests in Central and South America. S. sciureus is used extensively in research studies. [NIH] Saline: A solution of salt and water. [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] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior five-

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sixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Scleritis: Refers to any inflammation of the sclera including episcleritis, a benign condition affecting only the episclera, which is generally short-lived and easily treated. Classic scleritis, on the other hand, affects deeper tissue and is characterized by higher rates of visual acuity loss and even mortality, particularly in necrotizing form. Its characteristic symptom is severe and general head pain. Scleritis has also been associated with systemic collagen disease. Etiology is unknown but is thought to involve a local immune response. Treatment is difficult and includes administration of anti-inflammatory and immunosuppressive agents such as corticosteroids. Inflammation of the sclera may also be secondary to inflammation of adjacent tissues, such as the conjunctiva. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sepsis: The presence of bacteria in the bloodstream. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] 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]

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Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin test: A test for an immune response to a compound by placing it on or under the skin. [NIH]

Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smoke Inhalation Injury: Pulmonary injury following the breathing in of toxic smoke from burning materials such as plastics, synthetics, building materials, etc. This injury is the most frequent cause of death in burn patients. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Behavior: Any behavior caused by or affecting another individual, usually of the same species. [NIH] Social Security: Government sponsored social insurance programs. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spirometry: Measurement of volume of air inhaled or exhaled by the lung. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes,

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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] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Status Asthmaticus: A sudden intense and continuous aggravation of a state of asthma, marked by dyspnea to the point of exhaustion and collapse and not responding to the usual therapeutic efforts. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cell Factor: Hematopoietic growth factor and the ligand of the c-kit receptor CD117 (proto-oncogene protein C-kit). It is expressed during embryogenesis and provides a key signal in multiple aspects of mast-cell differentiation and function. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] 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] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stridor: The loud, harsh, vibrating sound produced by partial obstruction of the larynx or trachea. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions

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of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] 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] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been

Dictionary 185

reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thoracic: Having to do with the chest. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [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] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU]

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Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]

Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] 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] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tularemia: A plague-like disease of rodents, transmissible to man. It is caused by Francisella tularensis and is characterized by fever, chills, headache, backache, and weakness. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] 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] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This

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condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Urease: An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. EC 3.5.1.5. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH]

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Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Interference: A phenomenon in which infection by a first virus results in resistance of cells or tissues to infection by a second, unrelated virus. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vomeronasal Organ: A specialized part of the olfactory system located anteriorly in the nasal cavity within the nasal septum. Chemosensitive cells of the vomeronasal organ project via the vomeronasal nerve to the accessory olfactory bulb. The primary function of this organ appears to be in sensing pheromones which regulate reproductive and other social behaviors. While the structure has been thought absent in higher primate adults, data now suggests it may be present in adult humans. [NIH] Wart: A raised growth on the surface of the skin or other organ. [NIH] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] 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]

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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, 135, 171, 187 Abdominal Pain, 135, 187 Aberrant, 8, 135 Ablation, 11, 135 Acantholysis, 135, 172 Acetylcholine, 135, 169 Actin, 17, 135, 167, 168 Acute myelogenous leukemia, 56, 135 Acute myeloid leukemia, 135 Acute nonlymphocytic leukemia, 135 Adaptability, 135, 144 Adaptation, 96, 135 Adjustment, 18, 135 Adjuvant, 90, 135 Adolescence, 135, 172 Adoptive Transfer, 6, 136 Adrenal Cortex, 136, 148, 175 Adrenal Medulla, 136, 152 Adrenaline, 51, 52, 71, 76, 78, 136 Adrenergic, 136, 150, 152, 184 Adverse Effect, 4, 136, 173, 181 Aerosol, 5, 19, 31, 136 Aetiology, 54, 136 Affinity, 136 Agar, 136, 173 Aggravation, 136, 183 Agonist, 36, 136, 150 Airway, 5, 6, 9, 10, 11, 12, 14, 15, 16, 18, 20, 22, 23, 25, 27, 28, 33, 35, 38, 42, 49, 64, 66, 77, 86, 136, 142, 188 Airway Obstruction, 14, 38, 77, 136 Albuterol, 39, 41, 76, 136 Algorithms, 136, 141 Alkaline, 136, 137, 143 Alkaloid, 137, 143, 145 Alleles, 15, 137, 163 Allergen, 5, 6, 26, 33, 37, 137, 149, 181 Allergic Rhinitis, 29, 97, 137, 142, 156 Allo, 19, 137 Allogeneic, 8, 56, 62, 70, 93, 137, 172 Allogeneic bone marrow transplantation, 62, 70, 137 Allograft, 8, 9, 10, 17, 18, 19, 23, 28, 30, 31, 35, 36, 38, 62, 67, 137, 157 Alopecia, 137, 148 Alpha Particles, 137, 177 Alternative medicine, 105, 137

Alum, 20, 137, 145 Aluminum, 137 Alveoli, 137, 187 Amino Acid Sequence, 137, 138, 155 Amino Acids, 137, 153, 155, 169, 172, 174, 176, 180, 186 Ammonia, 37, 137, 187 Amphetamines, 137, 145 Amplification, 11, 30, 137 Anaesthesia, 42, 138, 160 Anal, 138, 152, 154 Analogous, 97, 138, 186 Analytes, 120, 138 Anaphylatoxins, 138, 146 Androgens, 136, 138, 148 Anemia, 54, 138 Anesthesia, 136, 138 Anesthetics, 138, 140, 152 Angiogram, 31, 138 Animal model, 9, 11, 25, 29, 138 Antagonism, 21, 138 Antiallergic, 138, 148 Antibacterial, 138, 182 Antibiotic, 24, 29, 42, 138, 140, 153, 172, 182 Antibodies, 20, 28, 37, 39, 97, 138, 139, 156, 158, 167, 173 Anticoagulant, 139, 176 Anticonvulsant, 139, 143, 173 Antigen-Antibody Complex, 139, 146 Antigen-presenting cell, 139, 149 Anti-inflammatory, 15, 139, 148, 150, 155, 175, 181 Anti-Inflammatory Agents, 139, 148 Antimetabolite, 139, 180 Antineoplastic, 139, 141, 148, 165, 174, 188 Antioxidant, 27, 139, 170, 171 Antiproliferative, 21, 139 Antiserum, 139, 140 Antitussive, 97, 139 Antiviral, 4, 30, 96, 139, 161, 180 Aorta, 90, 139, 187 Aortitis, 4, 139 Apoptosis, 21, 23, 27, 139 Aqueous, 139, 140, 149, 151 Arginine, 138, 139, 157, 169, 186 Arterial, 38, 140, 158, 176 Arteries, 139, 140, 141, 147, 177

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Arteritis, 4, 140 Artery, 31, 140, 141, 167, 177, 178, 187 Articular, 3, 140, 163 Aspiration, 51, 84, 90, 140 Assay, 3, 19, 50, 140 Asymptomatic, 74, 96, 140 Atelectasis, 51, 140 Atopic, 97, 140 Atrophy, 3, 135, 140, 152 Attenuated, 7, 96, 140 Attenuation, 96, 140 Autoimmune disease, 35, 140 Autologous, 140, 172 Avidity, 24, 140 Azithromycin, 68, 140 B Bacteria, 24, 35, 138, 139, 140, 151, 156, 166, 181, 182, 185, 186, 187 Bacterial Infections, 29, 140, 156, 179 Bacterial Physiology, 135, 140 Barbiturate, 140, 184 Base, 57, 140, 155, 162, 184 Basement Membrane, 29, 140, 153, 162 Benign, 17, 140, 143, 156, 168, 177, 181 Beta-Thromboglobulin, 140, 161 Bilateral, 87, 141, 152, 179 Bile, 141, 158, 163, 175, 183 Bile duct, 141, 175 Biochemical, 25, 37, 137, 139, 141, 142, 154 Biological Factors, 20, 141 Biological response modifier, 141, 160 Biological therapy, 141, 156 Biological Warfare, 24, 141 Biomarkers, 21, 141 Biopsy, 18, 19, 31, 38, 141 Biotechnology, 38, 39, 105, 115, 141 Bladder, 141, 168, 176, 187 Bleomycin, 22, 141 Blepharitis, 3, 141 Blister, 141, 172 Blood Coagulation, 141, 143, 185 Blood pressure, 141, 158, 167, 177 Blood vessel, 138, 141, 142, 151, 154, 155, 162, 163, 164, 172, 182, 185, 187 Body Fluids, 141, 186 Bone Marrow, 11, 17, 34, 55, 56, 61, 70, 135, 142, 148, 156, 159, 164, 165, 167, 172, 182 Bone Marrow Transplantation, 55, 61, 70, 142 Bone scan, 142, 180 Bowel, 138, 142, 187

Brachytherapy, 142, 161, 162, 177, 189 Bradykinin, 142, 169 Bronchi, 90, 142, 152, 186 Bronchial, 50, 97, 142 Bronchiectasis, 3, 66, 97, 142 Bronchioles, 137, 142 Bronchiolitis Obliterans Organizing Pneumonia, 21, 42, 43, 46, 50, 51, 55, 57, 59, 60, 62, 65, 69, 77, 78, 81, 83, 84, 86, 104, 142 Bronchitis, 57, 67, 97, 120, 121, 142, 145 Bronchoalveolar Lavage, 49, 69, 81, 142 Bronchoalveolar Lavage Fluid, 69, 142 Bronchodilator, 59, 97, 142 Budesonide, 53, 142 C Calcineurin, 18, 142 Calcium, 6, 12, 142, 143, 146, 165, 168, 181 Callus, 143, 151, 162 Calmodulin, 142, 143 Capsaicin, 11, 143 Carbamazepine, 44, 143 Carbohydrate, 143, 148, 174 Carbon Dioxide, 143, 154, 155, 179, 187 Carcinogen, 143, 165 Carcinogenic, 143, 160, 170, 175, 183 Carcinoid, 71, 143 Carcinoma, 69, 143 Cardiac, 4, 9, 143, 152, 154, 168, 183 Case report, 41, 46, 58, 73, 81, 143 Causal, 143, 152 Cause of Death, 36, 143, 182 Cell Cycle, 11, 18, 143, 153 Cell Death, 11, 23, 42, 139, 144, 153, 168 Cell Differentiation, 144, 181, 183 Cell Division, 140, 143, 144, 153, 156, 165, 166, 173, 175, 181 Cell membrane, 7, 144, 149, 162 Cell proliferation, 11, 23, 144, 161, 181 Cell Respiration, 144, 179 Cell Size, 144, 154 Cell Survival, 22, 144, 156 Cell Transplantation, 144 Central Nervous System, 135, 137, 142, 144, 145, 155, 156, 170, 176 Cerebral, 144, 152, 153 Chemokines, 8, 27, 32, 35, 46, 144 Chemotactic Factors, 144, 146, 169 Chemotherapy, 144 Chest wall, 144, 174 Chimera, 4, 144 Cholesterol, 141, 144, 183

193

Chorioretinitis, 144, 179 Choroid, 144, 179 Chromatin, 139, 144, 164 Chromosomal, 14, 137, 144, 145, 157 Chromosome, 145, 161, 163, 181 Chronic Obstructive Pulmonary Disease, 26, 145 Cirrhosis, 145, 175 CIS, 17, 33, 145, 179 C-kit receptor, 145, 183 Clamp, 25, 145 Cleave, 4, 145 Clinical trial, 4, 18, 19, 20, 27, 35, 90, 115, 145, 147, 148, 150, 176, 178 Cloning, 141, 145 Coca, 145 Cocaine, 57, 145 Cofactor, 145, 169, 176, 185 Cohort Studies, 145, 152 Colitis, 145 Collagen, 22, 36, 86, 140, 145, 146, 153, 154, 165, 174, 175, 181 Collagen disease, 146, 181 Collapse, 29, 146, 174, 183 Colon, 145, 146, 186 Combination chemotherapy, 90, 146 Complement, 9, 138, 146, 164, 181 Complementary and alternative medicine, 89, 92, 146 Complementary medicine, 89, 146 Complete remission, 146, 178 Computational Biology, 115, 146 Computed tomography, 45, 60, 61, 82, 147, 180 Computerized axial tomography, 147, 180 Computerized tomography, 147 Conception, 147, 154, 183 Congestion, 147, 152, 163 Conjunctiva, 147, 160, 162, 181 Conjunctivitis, 97, 147, 156 Connective Tissue, 142, 145, 146, 147, 154, 155, 156 Constitutional, 147, 179 Constriction, 147, 162, 187, 188 Contamination, 147, 157 Continuum, 8, 147 Contraindications, ii, 147 Control group, 147, 175 Coordination, 6, 147 Cornea, 147, 162, 181 Corneum, 147, 152, 158 Coronary, 31, 147

Cortical, 147, 181 Corticosteroid, 79, 148, 175 Cortisol, 55, 148 Cortisone, 148, 150, 175 Cowpox, 148, 187 Cowpox Virus, 148, 187 Critical Care, 14, 43, 49, 51, 52, 54, 58, 59, 66, 68, 70, 74, 80, 90, 148 Cross-Sectional Studies, 148, 152 Croup, 17, 24, 72, 148 Cryptosporidiosis, 140, 148 Cultured cells, 5, 148 Curative, 148, 185 Cutaneous, 3, 148, 187 Cyanogen Bromide, 37, 148 Cyclic, 143, 148, 156, 169 Cyclophosphamide, 86, 148 Cyclosporine, 18, 19, 31, 79, 148 Cysteine, 144, 149 Cytochrome, 149, 179 Cytochrome b, 149, 179 Cytokine, 5, 6, 10, 16, 19, 21, 25, 34, 35, 37, 46, 52, 80, 149, 161, 185 Cytomegalovirus, 17, 45, 49, 55, 149 Cytoplasm, 139, 144, 149, 152, 156, 164, 180 Cytotoxic, 7, 77, 143, 149, 159, 178, 181 Cytotoxicity, 7, 149 D Degenerative, 149, 157 Deletion, 8, 139, 149 Dendrites, 149, 169, 170 Dendritic, 10, 27, 36, 149 Dendritic cell, 10, 27, 36, 149 Depolarization, 149, 181 Dermatitis, 97, 149 Desensitization, 149, 159 Developing Countries, 41, 149 Dexamethasone, 50, 53, 150 Diagnostic procedure, 95, 105, 150 Diffusion, 150, 162 Digestion, 37, 141, 142, 150, 163, 183 Dihydropteroate Synthase, 81, 150 Dihydrotestosterone, 150, 178 Direct, iii, 5, 10, 19, 20, 34, 35, 107, 150, 163, 178, 184 Disparity, 15, 150 Dopamine, 145, 150, 169, 173 Double-blind, 18, 19, 40, 76, 150 Double-blinded, 18, 150 Drive, ii, vi, 10, 36, 85, 150, 162 Drug Interactions, 109, 150

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Drug Tolerance, 150, 185 Dysphagia, 84, 150 Dyspnea, 21, 150, 177, 183 E Ectopic, 11, 150 Effector, 19, 135, 146, 150 Efficacy, 21, 40, 43, 53, 98, 150 Elastic, 151, 184 Elastin, 86, 145, 151, 153 Electrolyte, 83, 84, 148, 151, 166 Electrons, 139, 140, 151, 162, 170, 177, 178 Embryo, 144, 151, 160 Embryogenesis, 151, 183 Emphysema, 23, 86, 145, 151 Empyema, 4, 151 Emulsion, 151, 154 Endocrine Glands, 151 Endogenous, 150, 151, 170, 176 Endothelial cell, 151, 161, 185 Endothelium, 35, 151, 169 Endothelium, Lymphatic, 151 Endothelium, Vascular, 151 Endothelium-derived, 151, 169 Endotoxin, 20, 151, 186 Enhancer, 18, 151 Environmental Exposure, 15, 152, 170 Environmental Health, 114, 116, 152 Enzymatic, 143, 146, 152, 179 Enzyme, 13, 23, 150, 152, 156, 168, 169, 172, 174, 176, 178, 181, 184, 185, 187, 188, 189 Eosinophil, 12, 26, 33, 53, 152 Eosinophilia, 34, 104, 152 Eosinophilic, 21, 47, 152 Epidemic, 4, 54, 152 Epidemiologic Studies, 14, 152 Epidemiological, 38, 79, 152 Epidermis, 135, 141, 147, 152, 158, 162, 172 Epigastric, 152, 171 Epinephrine, 40, 41, 51, 54, 64, 71, 76, 136, 150, 152, 169, 186 Episcleritis, 3, 152, 181 Epithelial, 6, 7, 11, 12, 16, 17, 22, 25, 28, 29, 42, 81, 152, 157, 162 Epithelial Cells, 6, 7, 11, 16, 17, 22, 25, 28, 29, 42, 152, 157, 162 Epithelium, 10, 12, 17, 140, 151, 152 Erythema, 3, 152 Erythema Nodosum, 3, 152 Erythrocytes, 138, 142, 152, 181 Erythromycin, 54, 140, 153 Esophageal, 58, 153

Esophagus, 153, 172, 178, 183 Etoposide, 90, 153 Eukaryotic Cells, 153, 186 Evoke, 153, 183 Excitation, 137, 153, 154, 169 Exhaustion, 138, 153, 183 Exocrine, 153, 171 Exogenous, 151, 153, 176 Expiration, 153, 179 Extensor, 153, 176 External-beam radiation, 153, 162, 177, 189 Extracellular, 8, 12, 22, 23, 69, 147, 153, 154, 165 Extracellular Matrix, 8, 22, 147, 153, 154, 165 Extracellular Matrix Proteins, 153, 165 Extracellular Space, 153 Extracorporeal, 82, 153 Extracorporeal Membrane Oxygenation, 82, 153 Extraction, 30, 154 Exudate, 142, 144, 154 F Family Planning, 115, 154 Fat, 142, 148, 154, 163, 182, 184 Fetus, 17, 154 Fibroblasts, 27, 28, 154, 161, 167, 180 Fibrosis, 6, 8, 12, 18, 23, 26, 29, 77, 86, 154, 177 Fixation, 36, 154, 181 Flatus, 154, 155 Flow Cytometry, 18, 50, 154 Fluorescence, 154 Fluorescent Dyes, 154 Fold, 155, 171 Fovea, 154, 155 Free Radicals, 139, 155, 168 G Gamma Rays, 155, 177, 178 Ganglia, 11, 135, 155, 168 Gas, 38, 59, 120, 137, 143, 150, 154, 155, 158, 169, 174, 179, 187 Gas exchange, 59, 155, 179, 187 Gastrointestinal, 142, 143, 152, 155, 184, 186 Gene Expression, 17, 18, 21, 27, 35, 155 Gene Rearrangement, 33, 155 Genetic Code, 155, 169 Genetics, 17, 20, 59, 155, 159 Genotype, 155, 172

195

Gland, 136, 148, 155, 171, 173, 176, 181, 183, 185 Glomerulus, 155, 168 Glucocorticoid, 6, 142, 150, 155, 175 Glycoprotein, 24, 33, 34, 155, 161, 162, 167, 185, 186 Glycosidic, 155, 168, 170 Gonadal, 155, 183 Governing Board, 156, 175 Graft, 8, 9, 15, 27, 31, 43, 56, 58, 73, 156, 159, 166, 167 Graft Survival, 31, 156 Graft-versus-host disease, 43, 56, 156, 167 Granulation Tissue, 142, 156 Granulocytes, 156, 163, 181, 188 Granulomatous Disease, Chronic, 156, 179 Growth factors, 23, 28, 42, 156 Guanylate Cyclase, 156, 169 H Haplotypes, 15, 156 Haptens, 26, 136, 156 Hay Fever, 137, 156 Headache, 156, 160, 186 Heart failure, 156, 177 Heart-Lung Transplantation, 50, 58, 86, 90, 156 Hematopoiesis, 156, 161, 164 Hemoglobin, 138, 152, 156, 171 Hepatitis, 17, 157 Hepatitis A, 17, 157 Hepatocytes, 157 Hepatovirus, 157 Hereditary, 157, 172 Heredity, 155, 157 Histiocytosis, 79, 157 Histocompatibility, 15, 50, 157, 166 Histocompatibility Antigens, 50, 157 Histology, 18, 19, 61, 157 Histones, 142, 144, 157 Hoarseness, 148, 157, 162 Homeostasis, 83, 84, 157 Homogeneous, 147, 157 Homologous, 137, 157, 161, 164, 167, 181, 184 Hormonal, 140, 148, 157 Hormone, 136, 137, 148, 152, 157, 160, 174, 175, 179, 181, 184, 185 Humoral, 19, 157 Humour, 157 Hybridomas, 158, 161 Hydrogen, 140, 143, 153, 158, 163, 166, 169, 170, 176

Hydrolysis, 158, 162, 168, 173, 174, 176, 186 Hydrophobic, 25, 158 Hydroxylysine, 145, 158 Hydroxyproline, 145, 158 Hyperaemia, 147, 158 Hyperplasia, 6, 69, 71, 158 Hypersensitivity, 18, 36, 90, 137, 149, 152, 158, 179, 181 Hypertension, 156, 158, 185 Hypertrophy, 158 Hypnotic, 140, 158, 184 Hypoxemia, 42, 77, 158 Hypoxia, 158 I Ichthyosis, 97, 158 Idiopathic, 21, 29, 57, 61, 81, 86, 158, 177 Immune adjuvant, 137, 158 Immune Sera, 158, 159 Immune system, 6, 16, 139, 141, 158, 159, 164, 172, 187, 188 Immunity, 6, 10, 17, 20, 21, 25, 26, 32, 33, 96, 159, 161, 186 Immunization, 19, 36, 136, 159, 175, 181 Immunocompromised, 96, 159 Immunofluorescence, 50, 159 Immunogenetics, 20, 159 Immunologic, 16, 34, 67, 136, 144, 159, 178 Immunologic Factors, 16, 159 Immunology, 7, 8, 11, 15, 20, 29, 36, 42, 46, 48, 55, 62, 63, 73, 76, 135, 136, 155, 159 Immunophilin, 143, 159 Immunosuppression, 19, 30, 56, 159, 164 Immunosuppressive, 9, 10, 28, 31, 143, 148, 155, 159, 181, 184 Immunosuppressive Agents, 9, 31, 159, 181 Immunosuppressive therapy, 31, 159 Immunotherapy, 136, 141, 149, 159 Implant radiation, 159, 161, 162, 177, 189 In situ, 98, 159 In vitro, 6, 7, 9, 10, 13, 16, 21, 24, 25, 26, 28, 36, 37, 64, 159, 184, 185 In vivo, 6, 9, 10, 13, 23, 24, 25, 35, 36, 159, 164, 170, 184 Incision, 159, 161 Induction, 6, 18, 21, 23, 27, 34, 36, 77, 138, 159 Infancy, 5, 15, 39, 53, 78, 104, 160 Infarction, 140, 160, 179 Influenza, 10, 21, 30, 34, 108, 160 Information Science, 160, 165

196

Bronchiolitis

Ingestion, 89, 160 Inhalation, 24, 31, 66, 108, 136, 142, 160 Initiation, 29, 160 Initiator, 160, 161 Inorganic, 160, 167 Insight, 8, 16, 17, 160 Insulin, 160, 171 Intensive Care, 42, 62, 160 Interferon, 21, 37, 39, 64, 160, 161 Interferon-alpha, 160, 161 Interleukin-1, 63, 64, 70, 161 Interleukin-10, 63, 161 Interleukin-12, 70, 161 Interleukin-17, 64, 161 Interleukin-2, 28, 41, 161 Interleukin-6, 64, 76, 161 Interleukin-8, 32, 64, 74, 161 Interleukin-9, 63, 161 Interleukins, 159, 161 Internal radiation, 161, 162, 177, 189 Interstitial, 21, 29, 42, 79, 86, 87, 142, 153, 161, 162, 168, 189 Intoxication, 161, 188 Intracellular, 12, 19, 160, 161, 169, 181 Intrinsic, 11, 136, 140, 161 Invasive, 38, 159, 161, 164, 171 Ion Transport, 25, 162, 166 Ionizing, 137, 152, 162, 177 Ions, 140, 143, 151, 158, 162 Irradiation, 90, 162, 189 Ischemia, 8, 65, 140, 162, 167, 179 K Kb, 114, 162 Keratinocytes, 161, 162 Keratoconjunctivitis, 3, 162 Keratoconjunctivitis Sicca, 3, 162 Keratosis, 97, 135, 162 Kinetics, 11, 162 L Labile, 146, 162 Lacrimal, 162 Laminin, 22, 140, 153, 162 Laryngitis, 86, 162 Larynx, 162, 183, 186 Latency, 18, 163 Latent, 12, 163, 175 Length of Stay, 58, 163 Lesion, 10, 29, 163, 186 Leucocyte, 65, 152, 163 Leukemia, 56, 163 Leukocyte Count, 76, 163 Levo, 163, 165

Life cycle, 24, 33, 163 Ligaments, 147, 163 Limbic, 3, 163 Linkage, 14, 15, 163 Linkage Disequilibrium, 15, 163 Lipid, 29, 160, 163, 171 Lipid Peroxidation, 163, 171 Lipopolysaccharide, 22, 35, 163 Livedo, 3, 163 Liver, 17, 27, 98, 135, 141, 145, 148, 149, 151, 157, 163, 175, 180 Liver scan, 163, 180 Localization, 18, 163 Localized, 154, 160, 162, 163, 173, 186 Lucida, 162, 163 Lung volume, 79, 164 Lymph, 151, 157, 164 Lymphatic, 151, 160, 164, 182, 185 Lymphatic system, 164, 182, 185 Lymphocyte Depletion, 159, 164 Lymphocyte Subsets, 36, 164 Lymphocytes, 9, 34, 36, 46, 77, 139, 143, 149, 158, 159, 161, 163, 164, 168, 182, 184, 185, 188 Lymphocytic, 29, 67, 164 Lymphoid, 138, 156, 163, 164 Lymphoma, 4, 164 Lytic, 18, 164, 188 M Macrophage, 35, 62, 68, 161, 164 Macrophage Inflammatory Protein-1, 62, 164 Magnetic Resonance Imaging, 164, 180 Major Histocompatibility Complex, 17, 36, 156, 157, 164 Malignant, 139, 157, 164, 168, 177, 179 Malignant tumor, 164, 179 Malnutrition, 140, 165 Manifest, 6, 165 Matrilysin, 13, 22, 165 Matrix metalloproteinase, 12, 22, 165 Mechanical ventilation, 11, 165 Mediate, 6, 150, 165 Mediator, 161, 165, 174 Medical Informatics, 14, 165 Medical Staff, 150, 165 MEDLINE, 115, 165 Meiosis, 165, 167, 184 Melanin, 165, 173, 186 Melphalan, 90, 165 Memory, 6, 165 Mental, iv, 4, 114, 116, 165, 175, 176, 180

197

Mental Disorders, 165, 175, 176 Mental Health, iv, 4, 114, 116, 165, 175, 176 Mercury, 154, 165 Meta-Analysis, 40, 166 Metastasis, 165, 166 Metastatic, 90, 166 Methylprednisolone, 86, 166 Microbiology, 29, 32, 75, 81, 135, 166 Microorganism, 145, 166, 171, 188 Microscopy, 35, 140, 166 Migration, 22, 32, 33, 166 Mineralocorticoids, 136, 148, 166 Minor Histocompatibility Antigens, 157, 166 Mitochondrial Swelling, 166, 168 Mitosis, 139, 166 Mitotic, 153, 166 Mobilization, 12, 166 Molecule, 28, 32, 39, 139, 140, 146, 150, 151, 153, 155, 158, 166, 170, 171, 174, 178, 181, 187 Monitor, 5, 18, 167, 169 Monoclonal, 13, 41, 158, 162, 167, 177, 189 Monoclonal antibodies, 13, 167 Monocular, 8, 167 Monocyte, 8, 70, 167 Monocyte Chemoattractant Protein-1, 8, 167 Mononuclear, 8, 26, 167, 186 Morphogenesis, 87, 167 Mucociliary, 167, 182 Mucolytic, 142, 167 Mucus, 86, 167, 187 Multivalent, 140, 167 Muscle Contraction, 12, 167 Myalgia, 160, 167 Mycophenolate mofetil, 75, 167 Mycosis, 167 Mycotic, 90, 167 Myelogenous, 167 Myocardial Reperfusion, 167, 168, 179 Myocardial Reperfusion Injury, 168, 179 Myocarditis, 4, 35, 168 Myocardium, 168 Myopathy, 39, 168 Myosin, 142, 167, 168 N Nasal Cavity, 168, 171, 188 Nasal Mucosa, 160, 168 Nasal Septum, 168, 188 Natural killer cells, 161, 168

NCI, 1, 113, 145, 168 Necrosis, 7, 23, 29, 90, 139, 160, 168, 179, 180 Neoplasm, 148, 168 Nephritis, 35, 168 Nervous System, 11, 144, 165, 168, 169, 183, 184 Neural, 157, 168 Neuraminidase, 24, 168, 171, 174 Neurogenic, 5, 11, 168 Neurologic, 4, 169 Neurologic Manifestations, 4, 169 Neurons, 11, 145, 149, 155, 169, 184 Neuropeptide, 5, 169 Neuroretinitis, 169, 179 Neurotransmitter, 135, 142, 150, 169, 181, 183 Neutrons, 137, 162, 169, 177 Neutrophil, 13, 22, 26, 32, 54, 72, 74, 169 Neutrophil Activation, 74, 169 Nickel, 86, 169 Nitric Oxide, 15, 62, 169 Nitrogen, 137, 138, 148, 153, 154, 165, 169, 186 Nuclear, 18, 151, 153, 155, 168, 169 Nucleic acid, 30, 155, 169, 180 Nucleus, 18, 139, 144, 148, 149, 153, 155, 164, 165, 167, 169, 170, 176, 183 O Olfactory Bulb, 170, 188 Oligosaccharides, 168, 170 Oncogene, 32, 170, 183 Oncogenic, 18, 170 Ophthalmology, 154, 170 Optic Nerve, 169, 170, 179, 181 Organ Culture, 170, 185 Organ Transplantation, 72, 79, 98, 170 Otitis, 29, 170 Otitis Media, 29, 170 Outpatient, 29, 46, 54, 170 Ovum, 163, 170, 175 Oxidants, 13, 170 Oxidation, 139, 149, 163, 170, 171 Oxidation-Reduction, 170, 171 Oxidative Stress, 26, 86, 171 Oximetry, 44, 171 Oxygen Consumption, 171, 179 Oxygenation, 158, 171 Oxygenator, 154, 171 P Paediatric, 40, 41, 47, 71, 171 Palliative, 171, 185

198

Bronchiolitis

Pancreas, 17, 99, 135, 141, 160, 171, 186 Pancreas Transplant, 17, 99, 171 Pancreatic, 35, 171 Paramyxovirus, 22, 24, 171 Paranasal Sinuses, 171, 182 Partial remission, 171, 178 Particle, 171, 186 Patch, 25, 163, 171 Pathogen, 17, 19, 24, 35, 171 Pathologic, 57, 86, 90, 139, 141, 147, 158, 171, 172, 176, 187 Pathologic Processes, 139, 172 Pathophysiology, 11, 15, 20, 172 Pemphigus, 46, 74, 75, 135, 172 Penicillin, 138, 172 Peptide, 23, 172, 174, 176 Perception, 22, 172, 180 Perfusion, 38, 75, 158, 172 Pericarditis, 4, 172 Pericardium, 172 Peripheral blood, 26, 32, 161, 172 Peripheral stem cell transplantation, 56, 172 Peripheral stem cells, 156, 172 Peroxidase, 26, 163, 172 Peroxide, 163, 172 Phagocyte, 170, 172 Phallic, 154, 172 Pharmacologic, 4, 35, 138, 172, 185 Pharynx, 160, 168, 172 Phenotype, 8, 14, 16, 33, 35, 172 Phenylalanine, 172, 186 Phenytoin, 143, 173 Pheromones, 22, 173, 188 Phospholipases, 173, 181 Phosphorus, 143, 173 Phosphorylation, 17, 173 Physiologic, 12, 21, 136, 173, 178 Physiology, 22, 25, 34, 173 Pilot study, 39, 68, 76, 89, 173 Pituitary Gland, 148, 173 Plague, 173, 186 Plants, 137, 141, 143, 145, 173, 180, 185 Plaque, 96, 173 Plasma, 19, 75, 138, 140, 144, 151, 156, 166, 173 Plasma cells, 138, 156, 173 Platelet Activation, 173, 181 Platelet Aggregation, 138, 169, 173, 174 Platelet Factor 4, 161, 174 Platelet-Derived Growth Factor, 39, 174 Platelets, 140, 169, 173, 174

Pneumonitis, 17, 24, 40, 86, 90, 174 Pneumothorax, 56, 174 Pneumovirus, 33, 174 Podophyllotoxin, 153, 174 Polyarthritis, 162, 174 Polymerase, 17, 174 Polymorphic, 36, 174 Polymorphism, 19, 174 Polypeptide, 137, 145, 174, 189 Polysaccharide, 139, 174, 176 Posterior, 138, 144, 171, 174, 180 Postsynaptic, 174, 181 Potentiates, 161, 174 Potentiation, 174, 181 Practice Guidelines, 52, 116, 175 Preclinical, 28, 175 Precursor, 148, 150, 152, 172, 175, 186 Predisposition, 14, 97, 175 Prednisolone, 65, 66, 91, 166, 175 Prednisone, 31, 175 Prevalence, 26, 37, 175 Primary Biliary Cirrhosis, 67, 175 Primary endpoint, 18, 175 Primary Prevention, 27, 175 Progesterone, 175, 183 Prognostic factor, 75, 175 Progression, 20, 33, 60, 69, 138, 165, 175 Progressive, 10, 12, 15, 79, 144, 145, 150, 168, 173, 175, 177 Proline, 145, 158, 175 Promoter, 63, 175 Prophase, 167, 175, 184 Prophylaxis, 13, 176, 187 Prospective Studies, 37, 176 Prostate, 141, 176, 186 Protein Binding, 33, 176 Protein C, 11, 18, 33, 137, 176 Protein S, 12, 36, 141, 153, 155, 176, 180 Proteoglycans, 140, 153, 176 Proteolytic, 13, 23, 146, 176 Protocol, 38, 176 Protons, 137, 158, 162, 176, 177 Pseudorabies, 11, 176 Psoriasis, 97, 176 Psychiatry, 154, 176, 187 Psychic, 165, 176, 181 Psychoactive, 176, 188 Public Health, 33, 77, 79, 86, 116, 176 Public Policy, 115, 177 Publishing, 38, 160, 177 Pulmonary, 3, 6, 8, 11, 15, 18, 19, 20, 21, 28, 33, 36, 57, 59, 73, 76, 79, 80, 83, 84,

199

86, 120, 133, 141, 142, 152, 177, 182, 184, 187 Pulmonary Fibrosis, 6, 21, 177 Pulmonary hypertension, 4, 76, 83, 177 Pulse, 44, 167, 171, 177 Purulent, 177 Pyoderma, 3, 177 Pyoderma Gangrenosum, 3, 177 Q Quality of Life, 177, 184 R Race, 71, 76, 136, 165, 166, 177 Racemic, 71, 76, 136, 165, 177 Radiation, 69, 152, 153, 154, 155, 159, 161, 162, 177, 180, 188, 189 Radiation therapy, 69, 153, 161, 162, 177, 189 Radioactive, 38, 142, 158, 159, 161, 162, 163, 167, 169, 170, 177, 180, 189 Radiolabeled, 162, 177, 189 Radiological, 58, 75, 177 Radiology, 45, 57, 61, 65, 74, 76, 84, 177 Radiotherapy, 142, 162, 177, 189 Randomized, 18, 19, 29, 30, 31, 40, 41, 76, 150, 178 Randomized clinical trial, 19, 178 Randomized Controlled Trials, 29, 40, 178 Reagent, 30, 148, 178 Receptor, 8, 9, 11, 16, 20, 21, 23, 24, 27, 35, 43, 63, 64, 83, 98, 135, 139, 145, 150, 178, 181 Recombinant, 14, 26, 34, 39, 53, 98, 178, 187 Recombination, 155, 178 Rectum, 146, 154, 155, 176, 178 Recurrence, 97, 178 Reductase, 27, 178 Refer, 1, 146, 154, 163, 169, 178, 185 Reflux, 58, 178 Refraction, 178, 182 Refractory, 79, 178 Regimen, 31, 150, 178 Relapse, 55, 56, 178 Remission, 56, 98, 178 Reperfusion, 8, 65, 167, 168, 178, 179 Reperfusion Injury, 8, 65, 179 Respiration, 47, 57, 61, 66, 74, 75, 97, 143, 167, 179 Respirator, 165, 179 Respiratory Burst, 24, 179 Respiratory failure, 57, 70, 77, 154, 179

Respiratory Physiology, 51, 53, 67, 69, 72, 74, 179, 187 Retina, 144, 169, 170, 179, 180 Retinal, 150, 167, 170, 179, 188 Retinitis, 17, 179 Retrograde, 11, 179 Retrospective, 38, 179 Rhabdomyosarcoma, 90, 179 Rheumatoid, 3, 55, 56, 146, 170, 179, 180 Rheumatoid arthritis, 3, 55, 56, 146, 179, 180 Rheumatoid Nodule, 3, 180 Rhinovirus, 30, 37, 43, 180 Ribavirin, 13, 57, 96, 108, 180 Ribosome, 180, 186 Risk factor, 16, 26, 33, 38, 47, 77, 152, 180 Rod, 145, 180 S Saimiri, 161, 180 Saline, 41, 71, 142, 180 Salivary, 149, 180, 188 Salivary glands, 149, 180 Saponins, 180, 183 Scans, 75, 180 Schizoid, 180, 188 Schizophrenia, 180, 188 Schizotypal Personality Disorder, 180, 188 Sclera, 144, 147, 152, 180, 181 Scleritis, 3, 181 Screening, 7, 145, 181 Secretion, 25, 86, 148, 158, 161, 162, 166, 167, 181 Secretory, 49, 96, 181 Segregation, 14, 178, 181 Seizures, 62, 143, 173, 181 Semisynthetic, 153, 181 Sensitization, 33, 181 Sepsis, 82, 181 Serous, 151, 181 Serum, 19, 26, 49, 96, 97, 136, 138, 139, 146, 158, 164, 166, 181, 186 Side effect, 18, 97, 107, 136, 141, 148, 181, 184, 185 Signal Transduction, 22, 32, 143, 181 Signs and Symptoms, 169, 178, 182 Sinusitis, 29, 37, 182 Skeletal, 138, 145, 182 Skeleton, 135, 182 Skin test, 26, 182 Skull, 182, 184 Smallpox, 182, 187 Smoke Inhalation Injury, 154, 182

200

Bronchiolitis

Smooth muscle, 12, 28, 64, 137, 138, 142, 182, 184 Social Behavior, 182, 188 Social Security, 178, 182 Soft tissue, 142, 182 Solid tumor, 141, 182 Somatic, 135, 151, 157, 165, 166, 182 Specialist, 122, 182 Specificity, 19, 30, 37, 136, 182 Spectrum, 30, 36, 182 Spinal cord, 144, 168, 182 Spirometry, 38, 182 Spleen, 28, 149, 164, 182 Stabilization, 16, 173, 183 Staging, 180, 183 Status Asthmaticus, 12, 183 Steel, 145, 183 Stem Cell Factor, 23, 145, 183 Stem Cells, 137, 172, 183 Sterility, 148, 183 Steroid, 31, 148, 180, 183 Stimulus, 11, 34, 36, 150, 153, 161, 163, 183 Stomach, 135, 153, 155, 157, 172, 178, 183 Strand, 4, 24, 174, 183 Stress, 9, 26, 148, 171, 175, 179, 183 Stridor, 148, 183 Subacute, 160, 182, 183 Subclinical, 160, 181, 183 Subcutaneous, 21, 180, 183 Subspecies, 182, 183, 187 Substance P, 153, 181, 183 Substrate, 13, 168, 184 Superoxide, 179, 184 Supportive care, 77, 184 Suppression, 27, 148, 184 Suppressive, 18, 27, 184 Surfactant, 22, 46, 79, 184 Survival Rate, 27, 184 Sympathomimetic, 150, 152, 184 Symptomatic, 97, 184 Symptomatic treatment, 97, 184 Synapse, 136, 184 Synapsis, 184 Synaptic, 11, 169, 181, 184 Synergistic, 22, 184 Systemic disease, 4, 158, 184 T Tacrolimus, 75, 79, 80, 87, 184 Temporal, 18, 184 Testosterone, 178, 184 Thalidomide, 55, 184 Therapeutics, 27, 30, 109, 185

Thoracic, 45, 47, 57, 60, 61, 65, 66, 74, 75, 82, 84, 87, 90, 164, 185, 188 Thrombin, 174, 176, 185 Thrombomodulin, 176, 185 Thrombosis, 140, 176, 185 Thymus, 159, 164, 185 Thyroid, 57, 185, 186 Tinnitus, 170, 185 Tissue Culture, 11, 185 Tolerance, 18, 36, 37, 135, 185 Tomography, 185 Tooth Preparation, 135, 185 Toxic, iv, 149, 152, 159, 165, 174, 182, 185 Toxicity, 150, 166, 185 Toxicology, 5, 116, 185 Toxin, 151, 185 Toxoplasmosis, 140, 186 Trace element, 169, 186 Trachea, 13, 142, 162, 172, 183, 185, 186 Traction, 145, 186 Transduction, 32, 181, 186 Transfection, 27, 141, 186 Transfer Factor, 159, 186 Translation, 18, 29, 153, 186 Trauma, 156, 168, 185, 186 Trypsin, 186, 189 Tryptophan, 145, 186 Tuberculosis, 7, 39, 186 Tularemia, 24, 186 Tumor marker, 141, 186 Tumor Necrosis Factor, 63, 185, 186 Tyrosine, 23, 26, 150, 186 U Ubiquitin, 25, 186 Ulcer, 156, 186 Ulceration, 3, 186 Ulcerative colitis, 40, 81, 177, 186 Urease, 169, 187 Urinary, 55, 187 Urine, 141, 187 V Vaccination, 35, 187 Vaccine, 10, 13, 20, 22, 25, 33, 34, 35, 108, 135, 137, 176, 187 Vaccinia, 34, 187 Vaccinia Virus, 34, 187 Valves, 30, 187 Variola, 187 Vascular, 17, 35, 144, 151, 156, 160, 169, 187 Vasculitis, 3, 187 Vasoconstriction, 152, 187

201

Vasodilators, 169, 187 Vector, 186, 187 Vein, 169, 187 Venous, 140, 163, 176, 187 Venous blood, 163, 187 Ventilation, 38, 42, 49, 60, 75, 83, 187 Ventricle, 177, 187 Vertigo, 170, 187 Veterinary Medicine, 87, 115, 187 Vinca Alkaloids, 188 Vincristine, 90, 188 Viral Interference, 24, 188 Virulence, 7, 25, 140, 185, 188 Virulent, 7, 188 Visual Acuity, 181, 188 Vitro, 11, 25, 188 Vivo, 9, 11, 24, 25, 164, 188 Vomeronasal Organ, 22, 170, 188

W Wart, 162, 188 Wheezing, 5, 10, 15, 45, 53, 70, 77, 84, 132, 188 White blood cell, 138, 163, 164, 167, 168, 169, 173, 188 Windpipe, 172, 185, 188 Withdrawal, 6, 31, 188 Wound Healing, 23, 165, 188 X Xenograft, 138, 188 Xerostomia, 162, 188 X-ray, 133, 138, 147, 154, 155, 162, 169, 177, 180, 188, 189 X-ray therapy, 162, 189 Y Yeasts, 172, 189 Z Zymogen, 13, 176, 189

202

Bronchiolitis

203

204

Bronchiolitis